vxEPA
United States
Environmental Protection
Agency
Estimation of Hydrolysis Rate
Constants of Carboxylic Acid
Ester and Phosphate Ester
Compounds in Aqueous
Systems from Molecular
Structure by SPARC
RESEARCH AND DEVELOPMENT
-------
EPA/600/R-06/105
September 2006
Estimation of Hydrolysis Rate Constants of
Carboxylic Acid Ester and Phosphate Ester
Compounds in Aqueous Systems from
Molecular Structure by SPARC
By
S. H. Hilal
Ecosystems Research Division
National Exposure Research Laboratory
Athens, Georgia
U.S. Environmental Protection Agency
Office of Research and Development
Washington, DC 20460
-------
NOTICE
The information in this document has been funded by the United States Environmental
Protection Agency. It has been subjected to the Agency's peer and administrative review, and
has been approved for publication. Mention of trade names of commercial products does not
constitute endorsement or recommendation for use.
-------
ABSTRACT
SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity
models were extended to calculate hydrolysis rate constants for carboxylic acid ester and
phosphate ester compounds in aqueous non- aqueous and systems strictly from molecular
structure. The energy differences between the initial state and the transition state for a molecule
of interest are factored into internal and external mechanistic perturbation components. The
internal perturbations quantify the interactions of the appended perturber (P) with the reaction
center (C). These internal perturbations are factored into SPARC's mechanistic components of
electrostatic and resonance effects. External perturbations quantify the solute-solvent
interactions (solvation energy) and are factored into H-bonding, field stabilization and steric
effects. These models have been tested using 1471 reliable measured base, acid and general
base-catalyzed carboxylic acid ester hydrolysis rate constants in water and in mixed solvent
systems at different temperatures. In addition, they were tested on 397 reliably measured second
order base, acid and general base-catalyzed phosphate ester hydrolysis rate constants over a
range of temperatures. The RMS deviation error between predicted and measured values for
carboxylic acid ester and phosphate ester compounds was close to the intralaboratory
experimental error.
in
-------
EXECUTIVE SUMMARY
This report is in partial fulfillment of the National Exposure Research Laboratory Task
number 16386, "Developing Computational Tools for Predicting Chemical Fate, Metabolism,
and Markers of Exposure", (Goal 4 and GPRA Sub-objective 4.5.2.) under subtask title
"Development of computational tools and databases for screening-level modeling of the
environmental fate of toxic organic chemicals". The primary goal of this subtask is to develop
computational tools to predict the identity of chemical species to which vulnerable organisms are
likely to be exposed. This screening-level model will require a chemical structure as input, and
will generate a set of daughter products that can form when the chemical is released into the
environment.
The subtask is broadly divided into five research areas. The first area focuses on
speciation of organic chemicals in aquatic systems. The second area focuses on the abiotic
transformation processes hydrolysis and reduction. The third is concerned with identifying and
characterizing the state variables that control the rate and extent of transformation processes in
the environment. The fourth focuses on the refinement and extension of SPARC models. The
area integrates 'omic tools' into environmental fate research.
The primary goal of the second research area of this subtask (this project) is to develop
and implement mathematical models to estimate hydrolysis rate constants of carboxylic acid
esters and organophosphate ester using SPARC. This report describes the SPARC
computational modeling approach to estimate hydrolysis rate constants that are necessary to
predict the environmental fate of carboxylic acid ester and organophosphate ester compounds in
water. The SPARC chemical reactivity models were extended to calculate hydrolysis rate
constants for the aforementioned compounds in aqueous and in non-aqueous systems as a
iv
-------
function of temperature in basic, acidic and neutral solution media strictly from molecular
structure. The output from the hydrolysis rate constants models will inform chemists,
environmentalists and toxicologists as to the chemical forms (parent or transformation products)
that may be present in an ecosystem and their rates of hydrolysis transformation. The ultimate
goal of this research project is to extend the SPARC solution-phase hydrolysis model to estimate
the transformation rates of other chemical compounds classes of concern that may hydrolyze
under environmental conditions, and to predict all possible hydrolysis pathways in aqueous and
non-aqueous systems.
The SPARC chemical hydrolysis models will meet some of the needs of EPA's long term
research task agenda under chemical toxicology initiative that emphasizes that EPA will have to
rely heavily on predictive modeling to carry out the increasingly complex array of exposure and
risk assessments necessary to develop scientifically defensible regulations. Ultimately, SPARC
chemical reactivity models (ionization pKa, speciation, tautomerization, chemical hydration and
chemical hydrolysis) will be integrated with the metabolic simulator TIMES (Tissue
MEtabolism Simulator) and CATABOL to provide a highly reliable simulator of metabolic
activity for direct application to the computational toxicology initiative.
-------
TABLE OF CONTENTS
ABSTRACT iii
EXECUTIVE SUMMARY iv
LIST OF FIGURES viii
LIST OF TABLES ix
1. GENERAL INTRODUCTION 1
2. QUANTITATIVE CHEMICAL THEORY 2
3. SPARC COMPUTATIONAL PROCEDURE 3
4. CHEMICAL HYDROLYSIS 4
4.1. Carboxylic acid Esters and Organophosphorus Hydrolysis
Mechanisms and Reactions Pathway 5
4.1.1 Carboxylic Acid Esters 7
4.1.1.1. Base Catalyzed Hydrolysis 7
4.1.1.2. Acid Catalyzed Hydrolysis 8
4.1.1.3. General Base Catalyzed Hydrolysis 9
4.1.2. Phosphate ester (Organophosphorus) 9
4.1.2.1. Base Catalyzed Hydrolysis 10
4.1.2.2. Acid Catalyzed Hydrolysis 11
4.1.2.3. General Base Catalyzed Hydrolysis 12
5. HYDROLYSIS MODELING APPROACH 14
5.1. Reference Rate Model 16
5.2. Internal Perturbation Models 16
5.2.1. Electrostatic Effect 17
5.2.1.1. Direct Field Effect 18
5.2.1.2. Mesomeric Field Effect 20
5.2.1.3. Sigma Induction Effect 22
5.2.1.4. RTI effect 23
5.2.2. Resonance Effect 24
5.3. External Perturbation (Solvation Effect) Models 25
5.3.1. Hydrogen Bonding Effect 26
5.3.2. Field Stabilization Effect 27
5.3.3. Steric Effect 28
5.4. Temperature Effect 30
VI
-------
6. RESULTS AND DISCUSSIONS 31
7. MODELS VERIFICATION AND VALIDATION 37
8. TRAINING AND MODEL PARAMETER INPUT 39
9. CONCLUSION 95
10. REFERENCES 97
APPENDIX 101
vn
-------
LIST OF FIGURES
Figure 1. The effect of solvent alpha sites on the initial and
the transition states on hydrolysis rate constants 27
Figure 2. Log hydrolysis rate constants vs temperature for alkaline hydrolysis
of carboxylic acid esters 30
Figure 3. SPARC-calculated versus observed log hydrolysis rate constants
for alkaline hydrolysis of carboxylic acid esters 34
Figure 4. SPARC-calculated versus observed log hydrolysis rate constants
for acid hydrolysis of carboxylic acid esters 35
Figure 5. SPARC-calculated versus observed log hydrolysis rate constants for
general alkaline base hydrolysis of carboxylic acid esters 35
Figure 6. Sample calculation of the log hydrolysis rate constant in acidic media
for p-nitrophenyl acetate in water at 25° C 102
Vlll
-------
LIST OF TABLES
Tablel A. Statistical comparison of SPARC-calculated to observrecf values of
log hydrolysis rate constants of carboxylic acid in water and in mixed
solvent systems 36
TablelB. Statistical comparison of SPARC-calculated to observed values of log
hydrolysis rate constants of organophosphorus in water 36
Table 2. SPARC-calculated vs. observed log base catalyzed hydrolysis rate
constants for carboxylic acid esters in water 40
Table 3. SPARC-calculated vs. observed log base catalyzed hydrolysis rate
constants for carboxylic acid esters in water-acetone mixtures 44
Table 4. SPARC-calculated vs. observed log base catalyzed hydrolysis rate
constants for carboxylic acid esters in ethanol-water mixtures 48
Table 5. SPARC-calculated vs. observed log base catalyzed hydrolysis rate constants
for carboxylic acid esters in methanol-water mixtures 51
Table 6. SPARC-calculated vs. observed log base catalyzed hydrolysis rate constants
for carboxylic acid esters in dioxane-water mixtures 55
Table 7. SPARC-calculated vs. observed log base catalyzed hydrolysis rate constants
for carboxylic acid esters in acetonitrile-water mixtures 58
Table 8. SPARC-calculated vs. observed log acid catalyzed hydrolysis rate constants
for carboxylic acid esters in water 59
Table 9. SPARC-calculated vs. observed log acid catalyzed hydrolysis rate
constants for carboxylic acid esters in water-acetone mixtures 69
Table 10. SPARC-calculated vs. observed log acid catalyzed hydrolysis rate constants
for carboxylic acid esters in water-methanol mixtures 74
Table 11. SPARC-calculated vs. observed log acid catalyzed hydrolysis rate constants
for carboxylic acid esters in water-ethanol mixtures 75
Table 12. SPARC-calculated vs. observed log acid catalyzed hydrolysis rate constants
for carboxylic acid esters in water-dioxane mixtures 76
Table 13. SPARC-calculated vs. observed log neutral hydrolysis rate constants for
carboxylic acid esters in water 77
IX
-------
Table 14. SP ARC-calculated vs. observed log neutral hydrolysis rate constants
for carboxylic acid esters in water-acetone mixtures 79
Table 15. SPARC-calculated vs. observed log neutral hydrolysis rate constants for
carboxylic acid esters in water-ethanol mixtures 82
Table 16. SPARC-calculated vs. observed log neutral hydrolysis rate constants
for carboxylic acid esters in water-dioxane mixtures 83
Table 17. SPARC-calculated vs. observed log hydrolysis rate constants for
organophosphorus in water in basic media 84
Table 18. SPARC-calculated vs. observed log acid hydrolysis rate constants for
organophosphorus in water 91
Table 19. SPARC-calculated vs. observed log neutral hydrolysis rate constants
For organophosphorus in water 93
-------
1. GENERAL INTRODUCTION
The major differences among the behavior profiles of organic compounds in the
environment are attributable to their physicochemical properties. The key properties are believed to
be vapor pressure, solubility, Henry's constant in water, octanol/water distribution coefficient and
transportation processes rates/equilibrium constants. Although considerable progress has been
made in transportation process elucidation and modeling for chemical and physical processes,
determination of the complete set of values for the fundamental thermodynamic and physicochemi-
cal properties have been achieved for only a small number of molecular structures. For most
chemicals, only fragmentary knowledge exists about those properties that determine their fate in the
environment. A big gap still exists between the available information and what is needed.
In fact, physical and chemical properties have only actually been measured for about 1
percent of the approximately 70,000 industrial chemicals listed by the U.S. Environmental
Protection Agency's Office of Prevention, Pesticides and Toxic Substances (OPPTS) [1], with
approximately 1000 new chemicals being added each year. These properties, in most instances,
must be obtained from measurements or from the judgment of expert chemists. Reliable estimation
techniques for these properties are therefore very cost-effective. In any case, trained technicians and
adequate facilities would not be available for measurement efforts involving thousands of
chemicals.
Mathematical models for predicting the fate of pollutants in the environment require
reactivity parameter values—that is, the physical and chemical constants that govern reactivity.
Although empirical structure-activity relationships (SAR) have been developed that allow
estimation of some constants, such relationships generally hold only within limited families of
chemicals. Computer programs have been under development for several years that predict
1
-------
chemical reactivity parameters such as ionization pKa, electron affinity and numerous physical
properties strictly from molecular structure for a broad range of molecular structures [2-14]. The
prototype computer program called SPARC uses computational algorithms based on fundamental
chemical structure theory to estimate a variety of reactivity parameters. This capability crosses
chemical family boundaries to cover a broad range of organic compounds. SPARC costs the user
minimal computer time and will provide greater accuracy and a boarder scope of predicted physical
and chemical parameters than is possible with other conventional estimation techniques.
2. QUANTITATIVE CHEMICAL THEORY
Chemical properties describe molecules in transition, that is, the conversion of a reactant
molecule to a different state or structure. For a given chemical property, the transition of interest
may involve electron redistribution within a single molecule or a bimolecular union to form a
transition state or distinct new product. The behavior of chemicals depends on the differences in
electronic properties of the initial state of the system and the state of interest. For example,
chemical equilibrium - thus ionization chemical equilibrium constants - depends on the energy
differences between the protonated state and unprotonated state. Electron affinity depends on the
energy differences between the LUMO (Lowest Unoccupied Molecular Orbital) state and the
HOMO (Highest Unoccupied Molecular Orbital) state of the molecule. Hydrolysis reaction rates,
on the other hand, depend on the energies of the transition states relative to the reactant (initial)
states.
In every case, these differences are usually small compared to the overall energy. The ab
initio methods that calculate absolute energies have a difficult time in predicting the small energy
differences between the chemical states of interest. Estimation approaches based on LFER (Linear
2
-------
Free Energy Relationships), QSAR (Quantitative Structure Activity Relationship) and QSP
(Quantitative Structure Property) have proven to offer good prediction for a limited number of
molecules and those within a particular class of molecules, but have failed to predict either chemical
or physical properties for a board range of molecular structures. In most cases, the number of data
points/values does not exceed the number of the trainable parameters needed to estimate a property
of interest by large amount as would be desired.
Perturbation methods, however, can be used to accurately compute the small differences in
energy leading to differences in reactivity. These methods treat the final state as a perturbed initial
state and the energy differences then are determined by quantifying the perturbation. These
perturbation methods are ideally suited for expert system application due to their extreme flexibility
and computational simplicity. The requisite conditions for applicability, as well as the selection of
appropriate reference structures or reactions, can be easily built into the computation control portion
of the expert system.
3. SPARC COMPUTATIONAL PROCEDURE
SPARC does not do "first principles" computation, but seeks to analyze chemical structure
relative to a specific reactivity query in much the same manner as an expert chemist would do. For
chemical properties, reaction centers with known intrinsic reactivity are identified and the impact on
the reactivity of appended molecular structure (termed perturber) is quantified using mechanistic
perturbation models. For physical properties, molecular structures are broken at each essential
single bond and a molecular descriptor is expressed as a linear combination of fragment
contributions of the property of interest. SPARC calculates the molecular descriptors and inserts
them in to the physical process models developed from intermolecular interaction models to
calculate a chemical and/or physical property of interest.
3
-------
The computational approaches in SPARC are a blending of conventional LFER [15-17],
Structure Activity Relations (SAR) [18, 19] and Perturbed Molecular Orbital (PMO) theory [20,
21]. In general, SPARC utilizes a classification scheme that defines the role of structural
constituents in effecting or modifying reactivity, and quantifies the various "mechanistic"
descriptions commonly utilized in physical analysis, such as resonance, electrostatic, induction
and dipole effects, etc. SPARC uses LFER to compute thermodynamic or thermal properties and
PMO theory to describe quantum effects such as delocalization energies or polarizabilities of n
electrons. In reality, every chemical property involves both quantum and thermal contributions
and necessarily requires the use of both perturbation methods for prediction.
A "toolbox" of mechanistic perturbation models has been developed that can be
implemented where needed for a specific reactivity query. Resonance models were developed
and calibrated on light absorption spectra [1, 22],- whereas electrostatic models were developed
and calibrated on ionization equilibrium constants [3, 4, 7-9]. Solvation models (e.g., dispersion,
induction, H-bonding, deipole-dipole) have been developed and calibrated on physical properties
such as vapor pressure, solubility, distribution coefficient Henry's law constant and gas
chromatographic retention time [4, 5, 11, 12].
4. CHEMICAL HYDROLYSIS
Hydrolysis is a chemical transformation process in which an organic compound, RX,
reacts with water, forming a new carbon-oxygen bond and the cleaving of the carbon-X bond in
the original molecule. The net reaction is most commonly a direct displacement of X by OH or:
R-X - ^ R-OH + X' + H
4
-------
Hydrolysis is likely to be the most important reaction of organic molecules with water in
aqueous environments and is a significant environmental fate process for many organic
chemicals. Hydrolysis under environmental conditions is actually not one reaction as shown in
equation (1), but a family of reactions involving compound types as diverse as alkyl halides,
carboxylic acid esters, phosphate esters, carbamates, epoxides, nitriles, amides, amines, etc [23].
However, many organic compounds have functional groups that are relatively inert with respect
to chemical hydrolysis, such as alkanes, ethers, aromatic nitro compounds, etc.
The object of this study is to extend the SPARC chemical reactivity models to estimate
hydrolysis rate constants for carboxylic acid esters and organophosphorus compounds from
molecular structure. Based on these models, the chemical forms or species that may be present
in the ecosystem can be identified (parent compounds such as carboxylic acid
esters/organophosphorus or hydrolyzed products such as organic acid and alcohol). This report
describes the process models and rate constants that are necessary to predict the environmental
fate of these chemicals in the aqueous phase as a function of temperature in basic, acidic and
neutral (general base) solution media strictly from molecular structure.
4.1. Carboxylic acid Esters and Organophosphorus Hydrolysis Mechanisms
and Reactions Pathway
When an organic molecule undergoes hydrolysis, a nucleophile (H2O, OH ") attacks an
electrophile (carbon or phosphorus atom) and displaces a leaving group such as phenoxide. For
a long time, it has been was recognized that nucleophilic displacement reactions usually fit one
of two distinct substitution processes: SN! (Substitution, Nucleophilic, Unimolecular) and SN2
(Substitution, Nucleophilic, Bimolecular) [24]. Kinetically, the SN! process is characterized by
-------
A rate independent of the concentration and nature of the nucleophile, the formation of racemic
products from optically active parent chemicals, and enhancement of the rate due to an electron-
donating substituent on the central atom. The rate determining step is the ionization of the RX to
yield a planar carbonium ion (equation 2a), that then undergoes a relatively rapid nucleophilic
attack as shown in equation 2b.
slow (2 a)
RX - ^ R+ + x-
R+ + H0 _ _ ^ ROH + H+
In an SN2 process, on the other hand, the rate depends on the concentration and type of the
nucleophile, and an optically active starting material yields gives a product of inverted
configuration. This is a one-step bimolecular process involving nucleophilic attack on the
central atom at the side opposite the leaving group:
H20 + R - X - *- [ H20 -R--X] - ^ H+ + H0 - R + x-
Generally, the hydrolysis of carboxylic acid esters and organophosphorus compounds involves
bimolecular nucleophilic attack analogous to the SN2 (rather than SN!) mechanism on the
saturated carbon. Organophosphate and carboxylic acid esters, depending on the substituents
and the local environmental conditions, can undergo acid catalyzed hydrolysis, second-order
alkaline hydrolysis, and neutral hydrolysis (general base). The alkaline and neutral hydrolysis
pathways may not give the same products depending on the structure of the ester groups [25].
This is because hydroxide is about 108 times better as a nucleophile than water towards the
phosphorous atom but only 104 times better as a nucleophile towards saturated carbon [25].
-------
4.1.1. Carboxylic Acid Esters
Ester functions are among the most common acid derivatives present in natural as well as
man-made chemicals (e.g., lipids, plasticizers, pesticides). An ester bond is defined as
ROC(=O)-, where R is a carbon-centered substituent. The general structure of carboxylic acid
esters is represented by RiC(=O)OR2, where RI and R2 are appended perturber structures. These
perturbers can be alkyl chains, phenyl groups or heteroatoms. Carboxylic acid esters are used
industrially to make flavors, soaps, herbicides and so on. Generally hydrolysis of an ester bond
yields the corresponding acid and alcohols. Carboxylic acid esters undergo hydrolysis through
three different mechanisms: base, acid and general base-catalyzed (neutral) hydrolysis.
4.1.1.1. Base Catalyzed Hydrolysis
The base-catalyzed or alkaline hydrolysis of esters generally takes place via a BAC2
mechanism as shown in the following equation [26, 27]. BAc2 stands for base-catalyzed, acyl-
oxygen fission, bimolecular reaction. It is similar to the SN2 reaction, occurring when the
hydroxide ion attacks the carbonyl carbon of an ester to yield a carboxylic acid and an alcohol.
Alkaline hydrolysis of esters also occurs through other mechanisms, e.g., BACI (base-catalyzed,
acyl-oxygen fission, unimolecular), BALI (base-catalyzed, alkyloxygen fission, unimolecular) and
BAL2 (base-catalyzed, alkyl-oxygen fission, bimolecular). However, BAC2 is the most common
mechanism, and usually masks all other possible mechanisms.
-------
I /o-
\ / H0
r - C//,O •« C.H »- R,COOH + R2OH+OJT
'U- / "-OR, /'
SOR2
OH" ' . OR2
4.1.1.2. Acid Catalyzed Hydrolysis
Acid catalyzed hydrolysis of esters takes place via an AAc2 mechanism as shown in the
following equation [26, 27]. AAc2 stands for acid-catalyzed, acyl-oxygen fission, bimolecular
reaction. It is similar to the SN2 reaction, occurring when a positive hydrogen ion catalyzes the
ester and a water molecule attacks the carbonyl carbon of the ester to produce a carboxylic acid
and an alcohol. Acid-catalyzed hydrolysis of esters also takes place by other mechanisms, such
as AACI (acid-catalyzed, acyl-oxygen fission, unimolecular), AALI (acid-catalyzed, alkyl-oxygen
fission, unimolecular) and AAL2 (acid-catalyzed, alkyl-oxygen fission, bimolecular) [26, 27].
However, AAc2 is the general mechanism for acid-catalyzed hydrolysis of esters, and usually
masks all other possible mechanisms.
RjCOOH + R2OH
-------
4.1.1.3. General Base Catalyzed Hydrolysis
The general base-catalyzed hydrolysis of esters takes place via a BAC2 mechanism illustrated
in the following reaction [26, 27]:
0
P
BH
R,COOH + R2OH
^OR2 ' - ~
OH
RI
As before, BAC2 stands for base-catalyzed, acyl-oxygen fission, bimolecular reaction. It is also
similar to the 8^2 reaction, occurring when a base (B:) present extracts a hydrogen atom from a
water molecule, releasing the hydroxide ion, that eventually attacks the carbonyl carbon of the ester
to yield a carboxylic acid and an alcohol. The base, B: stands for any base, such as ammonia,
acetate ion, pyridine, imidazole and so on. In the case of neutral hydrolysis, B: represents the water
molecule.
4.1.2. Phosphate ester (Organophosphorus)
Organophosphorus compounds are of interest to many groups of chemists. Biochemists
study their relationship to cholinesterase inhibition [28] ; organic chemists investigate the
reaction mechanisms to improve synthetic routes to these chemicals [29]; environmental
chemists are interested in these compounds for their role a pesticides, as well as their persistence
and overall toxicity in the environment [25]. These compounds are widely used as insecticides
for different types of cultivation and for elimination of crustaceans and mosquitoes [30]. Also,
they are widely used in heavy industries as hydraulic fluid additives, and in the petrochemical
-------
industry as plasticizers [31]. Despite the extensive production and resultant widespread exposure
of environmental compartments to various amounts of these compounds, surprisingly few
quantitative data on their hydrolytic reactivity are reported in the open literature. This lack of
information is particularly surprising because hydrolytic transformation is proposed as an
important pathway for the degradation of these compounds in aquatic ecosystems [32].
Organophosphorus or phosphate esters can be represented as RiOP(=O)(R2)(R3), where
the oxygen of ORi is bonded to a sp2 or sp3 carbon (Ri). R2 and RS represent additional leaving
groups or substituents of the perturber structure, P. Depending on the local environment, these
compounds hydrolyze via three distinct mechanisms: acid, base and neutral hydrolysis [25, 29].
4.1.2.1. Base Catalyzed Hydrolysis
The base-catalyzed (alkaline) hydrolysis of phosphate esters follows the same general
mechanism as carboxylic acid ester base hydrolysis, see section 4.1.1.1. This mechanism is
depicted in the following [14, 29]. BP2 stands for base-catalyzed, phosphoyl-oxygen fission,
bimolecular reaction, and is similar to the SN2 reaction that occurs when a hydroxide ion attacks
the carbonyl carbon of an ester to yield a carboxylic acid and an alcohol.
H0
o
HO— --R--— OR2
/ \
H?O
R2OH + OH'
OH
10
-------
The hydroxide ion attacks the phosphorus atom in the rate-controlling step of the
sequence [29]. Formation of an intermediate addition product of hydroxide ion and the ester that
is in equilibrium with the reactants and decomposes to give the products is excluded by the
failure of the phosphorus group to exchange oxygen with the solvent prior to chemical
hydrolysis. Therefore, the reaction cannot, proceed by an addition-elimination sequence
analogous to that believed to represent the course of hydrolysis of carboxylic acid esters, but
must consist either of a one-step process in which the leaving group is being expelled at the same
time the substituent group is entering (see the above mechanism), or a two step process in which
the intermediate decomposes so very rapidly that it cannot equilibrate with the solvent [33, 34].
Alkaline hydrolysis of phosphate esters also occurs through other mechanisms, such as:
BP1 (base-catalyzed, phosphoryl-oxygen fission, unimolecular), BALI (base-catalyzed, alkyl-
oxygen fission, unimolecular), and BAL2 (base-catalyzed, alkyl-oxygen fission, bimolecular).
However, the BP2 mechanism usually dominates and these other mechanisms are masked. In
certain circumstances, such as when carbonyl or glycerol groups are attached to the molecule,
there is no dominant pathway; this situation makes it difficult to accurately assess the rate of
hydrolysis [35, 36]. Since the SPARC model was not designed to model these later situations,
molecules with these types of mechanisms have not been investigated.
4.1.2.2. Acid Catalyzed Hydrolysis
Acid-catalyzed hydrolysis of phosphoric acid esters can occur by direct nucleophilic
attack at the phosphorus atom without the formation of a pentavalent intermediate. The reaction
takes place via an AAC2 mechanism as shown in the following equation. AAC2 stands for acid-
catalyzed, acyl-oxygen fission, bimolecular reaction. It is similar to the SN2 reaction, occurring
11
-------
when a positive hydrogen ion catalyzes the ester and a water molecule attacks the carbonyl
carbon of the ester to produce a carboxylic acid and an alcohol. Acid-catalyzed hydrolysis of
esters also takes place by other mechanisms such as phosphoryl-oxygen or alkyl-oxygen fission
unimolecular and alkyl-oxygen fission bimolecular [26, 27]. However, AAC2 is the general
mechanism for acid-catalyzed hydrolysis of esters and usually masks all other possible
mechanisms.
R3\\tt»lllllt
O
OH
o:
°o
4.1.2.3. General Base Catalyzed (Neutral) Hydrolysis
Neutral hydrolysis of phosphoric acid esters occurs by direct nucleophilic substitution
of water at the carbon atom, causing C-O cleavage,, as is the case for trialkyl phosphates such as
trimethyl phosphate:
12
-------
CJ. — I
R1CH20-^ ^^0J^CH2R3 R^O^N^ © + HOCH2R3 + H+
RoCHoO \ LI /
\ / R2CH20
)o
H
This reaction is analogous to the base catalyzed 8^2 reaction; however neutral and base
hydrolysis may not yield the same products. This difference in products is primarily because
toward phosphorous, OH" is a better nucleophile than H2O by about a factor of 108 [37]. This
usually causes the base catalyzed reaction to occur at the phosphorous atom with the hydroxide
causing the best leaving group to dissociate (P-O cleavage). However, depending on the leaving
groups present, the neutral (general base) reaction may occur where water acts as the
nucleophilic substituent at the carbon atom (C-O cleavage). If a good leaving group is present,
the reaction may proceed simultaneously by both neutral and base hydrolysis reaction
mechanisms with C-O and P-O cleavage. Multiple researchers [38] have found higher
temperatures cause the proportion of C-O to P-O cleavage to be greater; while at lower
temperatures, P-O cleavage dominates. For example, at 70°C and pH = 5.9 parathion reacted
90% by C-O cleavage, while at a lower temperature, higher proportion of the neutral reaction
occurred by P-O cleavage [39]. This observation is explained because the reaction involving C-
O cleavage requires a greater activation energy than that involving P-O cleavage [40]. Even this
simple thermal case demonstrates the complexity of the mechanisms involved when dealing with
phosphoric acid derivatives.
13
-------
5. HYDROLYSIS MODELING APPROACH
Hydrolysis reaction kinetics have been quantitatively modeled within the chemical
equilibrium framework described in previous publications for ionization pKa in water [3, 6-9].
For this, it was assumed that a reaction rate constant could be described in terms of a pseudo
equilibrium constant between the reactant (initial) and transition (final) states of the molecule
undergoing hydrolysis. This reaction rate constant is expressed in the appropriate second order
form inclusive of catalytic effects. For molecules susceptible to hydrolysis, reaction centers with
known intrinsic reactivity were identified and the reaction rate constants expressed (energy
terms) by perturbation theory as:
logkHH1. = logk + Aplogk (4)
D Hydrolysis D c '—»P D c
where log knydroiysis is the log hydrolysis rate constant of interest and log kc is the log of the
intrinsic rate constant of the reaction center. A given reaction center may have two or more
appendages or perturbing units. For example, a carboxylic acid ester reaction center has two
appendages and a phosphate ester has three. The log kc for the reaction center can be either
measured directly (if the reaction center exists as a distinct molecule) or determined via data-fit.
The Ap log kc term denotes the perturbations of the intrinsic rate constant of the reaction center
due to the appended structures, P, and to solvation effects. The perturbations associated with
appendages to the reaction center are factored into the mechanistic components of resonance and
electrostatic effects. Likewise, the perturbations associated with the solvent are factored into
steric, H-bonding, and field stabilization effects. The solvent dependence of log kc is expressed
as a linear function of solvent properties (alpha/beta H-bonding and dipole; calculated as
described later) with data-fitted coefficients. For mixed solvents, solvent descriptors that are site
interactions, such as H- bonding, are the mole-fraction-weighted average when used in the
14
-------
interaction models, and the interactions are summed over all solvent components [11]. Solvent
properties that are essentially bulk in nature, such as the dielectricity, volume, and polarizability,
are volume-fraction-averaged [11]. With the exception of steric effects, all the perturbations of
the reaction center are modeled independently and simply summed.
The SPARC computational model for the hydrolysis rate constant is divided into three
sub-models: reference rate, internal perturbation, and external perturbation. The reference rate
sub-model calculates the hydrolysis rate constant for the smallest ester compound substructure
that excludes internal perturbation and steric effects. The internal perturbation model calculates
the perturbation of the reference hydrolysis rate constant due to the internal perturbation
interactions between the reaction center and its appended perturber. Finally, the external
perturbation model calculates the solvation contributions to changes in the hydrolysis rate
constant due to solute-solvent interactions. The hydrolysis rate constant contributions from these
three sub-models are then summed to give the total calculated hydrolysis rate constant for the
compound under investigation according to equation:
logkHH, = logk + 5IPlogk + 5Fplogk (5)
O Hydrolysis O c ^^ O c EP O c
where log kc describes the hydrolysis behavior of the reaction center (reference structure), i.e.,
the "reference rate", in this study the hydrolysis rate constant for the smallest ester compound
structure that resemble the structure of the reaction center C(=O)OCH3 or P(=O)OCH3. The
term, 5n> log kc is the change in hydrolysis behavior of the reaction center brought about by
internal interactions due to the perturber structure, P. SPARC computes the various internal
reactivity perturbations, 5n> log kc, used to "correct" the hydrolysis behavior of the reaction center
(reference structure) for the compound in question in terms of all the potential "mechanisms" for
the interaction of the perturber structure, P, of the compound and its reaction center (reference
15
-------
structure), C [3, 4, 6-9]. The last term in equation 5 describes the external perturbation of the
hydrolysis rate due to the effect of the solvent on both the initial (reactant) and the final
(transition) state. Specifically, SEP log kc describes the change in the solvation of the initial state
versus the transition state due to steric, H-bond, and field stabilization effects of the solvent.
5.1. Reference Rate Model
As stated earlier, the reference rate, log kc, is the hydrolysis rate constant for the smallest
ester compound that resembles the structure of reaction center C(=O)OR or P(=O)OR (in this
study). The reference rate is free of any internal perturbation interactions, such as resonance,
electrostatic and steric effects. However, it is dependent upon the temperature. As the
temperature increases, the reference hydrolysis rate increases. SPARC expresses the reference
rate, log kc, as a function of the temperature and enthalpic and entropic contributions as
log kc = A + logTk + Refi + Ref2/Tk (6)
where A is the log of the Arrhenius equation pre-exponential factor, Tk is the temperature in
degrees Kelvin, Refi is the entropic contribution to the rate, and Refz is the enthalpic
contribution. A, Refi, and Refz are all data-fitted parameters that are the same for all molecules,
solvents, and temperatures.
5.2. Internal Perturbation Models
The internal perturbation of the hydrolysis rate constant of the reaction center (reference
structure) in equation (5) for a molecule of interest can be expressed in terms of mechanistic
perturbations as:
16
-------
5IPlogk = 5 logk + 5, logk (7)
vyip O c res O c elec O c
where the 5res logkc and 5eiec logkc describe the change in the hydrolysis rate due to the difference
in the resonance and electrostatic interactions of P with the initial state versus the transition state
(activation energy) of C, respectively. Electrostatic interactions are derived from local dipoles or
charges in P interacting with charges or dipoles in C. The term, 5res logkc describes the effect on
the rate due to a change in the delocalization of ^-electrons of the two states due to P. The
delocalization of TT electrons can be into or out of the reaction center.
The modeling of the perturber effects on chemical reactivity relates to the structural
representation S-R-C, where S-R is the perturber structure, P, appended to the reaction center, C.
S denotes a substituent group that "instigates" the perturbation. For electrostatic effects, S
contains (or can induce) electric fields; for resonance, S donates/receives electrons to/from the
reaction center. R links the substituent and reaction center and serves as a conductor of the
perturbation (e.g., "conducts" resonant TI electrons or electric fields) [2-4, 7].
5.2.1. Electrostatic Effect
Electrostatic effects on reactivity derive from charges or electric dipoles in the appended
perturber structure, P, interacting through space with charges or dipoles in the reaction center, C.
Direct electrostatic interaction effects (field effects) are manifested by a fixed charge or dipole in
a substituent interacting through the intervening molecular cavity with a charge or dipole in the
reaction center. The substituent can also "induce" electric fields in R that can interact
electrostatically with C. This indirect interaction is called the "mesomeric field effect". In
addition, electrostatic effects derived from electronegativity differences between the reaction
center and the substituent are termed sigma induction (or Rn if 7r-electrons involves). These
17
-------
effects are transmitted progressively through a chain of a-bonds (or ii) bonds between atoms.
For compounds containing multiple substituents, electrostatic perturbations are computed for
each singly and summed to produce the total effect.
5.2.1.1. Direct Field Effect
For a given dipolar or charged substituent interacting with the change in the charge at the
reaction center, the direct field effect is expressed as a multipole expansion
5Vc
held r/ j^ r 2 j^ r D r3 D
where qs is the charge on the substituent, approximated as a point charge located at point, s7; |j,s is
the substituent dipole located at point s (this dipole includes any polarization of the anchor atom i
effected by S); qc (5|j,c) is the change in charge (dipole moment) of the reaction center
accompanying the reaction, both presumed to be located at point c; 9 gives the orientation of the
substituent dipole relative to the reaction center; De is the effective dielectric constant for the
medium; and rcs (rcs) is the distance from the substituent dipole (charge) center to the reaction
center.
In modeling electrostatic effects, only those terms containing the "leading" nonzero
electric field change in the reaction center are retained. For example, acid-base ionization is a
monopole reaction that is described by the first two terms of the preceding equation; electron
affinity is described by only the second term, whereas the dipole change in hydrolysis rate
constant or H-bond formation is described by the third and fourth terms.
18
-------
In order to provide parameter "portability" and, hence, effects-model portability to other
structures and to other types of chemical reactivity, the contribution of each structural component
is quantified independently:
o 1 1 T^ PelecFsCOSUcs (Q\
5fieldlogk = pelecap = PelecacsFs = 3 (9)
Ics LJe
where ap characterizes the field strength that the perturber exerts on the reaction center and has
been previously calculated for estimation of ionization pKa [2-4, 7]. peie is the susceptibility of a
given reaction center to electric field effects that describes the electrostatic change
accompanying the hydrolysis rate constant reaction. peie is presumed to be independent of the
perturber. The perturber potential, op, is further factored into a field strength parameter, F
(characterizing the magnitude of the field component, charge or dipole, on the substituent), and a
conduction descriptor, acs, of the intervening molecular network for electrostatic interactions.
This structure-function specification and subsequent parameterization of individual component
contributions enables one to analyze a given molecular structure (containing an arbitrary
assemblage of functional elements) and to "piece together" the appropriate component
contributions to give the resultant reactivity effect.
The electrostatic susceptibility, peie, is a data-fitted parameter inferred directly from
measured hydrolysis rate constants. This parameter is determined once for each reaction center
and stored in the SPARC database. With regard to the substituent parameters, each uncharged
substituent has one field strength parameter, F^, characterizing the dipole field strength; whereas,
a charged substituent has two, Fq and F^. Fq characterizes the effective charge on the substituent
and F^ describes the effective substituent dipole inclusive of the anchor atom i, assumed to be a
19
-------
carbon atom. If the anchor atom i, is a noncarbon atom, then F^ is adjusted based on the
electronegativity of the anchor atom relative to carbon. The effective dielectric constant, De, for
the molecular cavity, any polarization of the anchor atom i affected by S, and any unit
conversion factors for charges, angles, distances, etc. are included in the F's.
Since the transition states for both base and general base-catalyzed hydrolysis of the
reaction center are negatively charged, the substituent dipole will increase the hydrolysis rate
constant of these reactions. In contrast, the transition state for acid hydrolysis of carboxylic acid
esters and organophosphorus is positively charged, and the substituent dipole will decrease the
hydrolysis rate constant. For example, the direct field contribution is 0.32 and -0.042 log-units
for base and acid catalyzed hydrolysis of ethyl p-nitrobenzoate respectively, while it is 0.346 log-
unit for general base catalyzed hydrolysis of p-nitrophenyl acetate. Since the transition states of
the base and general base catalyzed hydrolysis of esters are negative, the field always contributes
positively to the internal perturbations causing the hydrolysis rate constant to increase. In
contrast, the field contributes negatively to the internal perturbations for acid catalyzed
hydrolysis because of the positive transition state that occurs during the hydrolysis reaction
causing the hydrolysis rate constant to decrease.
5.2.1.2. Mesomeric Field Effect
A mesomeric field, MF, (K-induction or indirect field) is generated when either an
electron withdrawing or electron donating substituent induces electric fields or charges on the
molecular conductor R that can interact electrostatically with the reaction center, C. An electron-
withdrawing substituent creates positive charges on the conductor, while an electron-donating
substituent creates negative charges. Since the transition states in both base and general base-
20
-------
catalyzed hydrolysis of carboxylic acid and phosphate esters are negatively charged, the
electron-withdrawing substituents will increase the hydrolysis rate constant because the induced
positive charges on the molecular conductor will stabilize the negative charges of the reaction
center. However, electron-donating substituents induce negative charges on the molecular
conductor and have an opposite effect on the hydrolysis rate constant.
In SPARC, this mesomeric field effect (ft-induction or indirect field) is treated as a
collection of discrete charges, QR, with the contribution of each described by the following
equation. The MF effect on the log of the hydrolysis rate constant due to either the electron-
withdrawing or electron-donating substituents is given as
5MFlogk = PelecMFsZ% AMF (10)
k T,
1 kc
where as before, peiec is the intrinsic susceptibility of the reference reaction center to electrostatic
effects independent of the substituent; MFs is the mesomeric field constant of the substituent that
describes its ability to induce charges on the molecular conductor, R, and generate the
mesomeric field. MFs gauges the ability or strength of a given S to induce a field in Rn. It
describes the TT-induction ability of a particular substituent relative to the CH2". AMp is a data-
fitted parameter and has the same value for all molecules in this study. Substituent MFS values
have been calculated and presented in previous work [4]; q;k is the charge induced at atom k in R
calculated using PMO (Perturbed Molecular Orbital) theory [4, 20, 21] ;and rkc is the through-
cavity distance between the charge on atom k and C.
21
-------
An electron-withdrawing substituent creates positive charges on the conductor, while an
electron-donating substituent creates negative charges. Since the transition states in both base
and general base-catalyzed hydrolysis of carboxylic acid and phosphate esters are negatively
charged, the electron-withdrawing substituents will increase the hydrolysis rate constant because
the induced positive charges on the molecular conductor will stabilize the negative charges of the
reaction center. However, electron-donating substituents induce negative charges on the
molecular conductor and have an opposite effect on the hydrolysis rate constant. For example,
the mesomeric field (MF) contribution is 0.65 and 0.147 log-units for hydrolysis of ethyl p-
nitrobenzoate in base and acid catalyzed media respectively and it is 0.513 log unit for hydrolysis
of p-nitrophenyl acetate in general base catalyzed medium. The MF contributions are positive in
all three catalyzed media and increase the hydrolysis rate constant because the induced positive
charges on the phenyl ring stabilize the charged transition states. In addition, we see large
positive values for the base and general base catalyzed hydrolysis because of the negative
transition states that occur during the hydrolysis reactions for these mechanisms. The induced
positive charges on the phenyl ring enhance the stabilization of the negative transition states
more. In contrast, the small positive value for acid catalyzed hydrolysis is due to the positive
transition state that occurs during the hydrolysis reaction and diminishing stabilization of it.
5.2.1.3. Sigma Induction Effect
Sigma induction occurs due to the difference in electronegativity between C and S. For
base and general base-catalyzed hydrolysis of carboxylic acid and phosphate esters, the reaction
center has a large electronegativity. Therefore, methyl substituents, for example, will move
charge or electrons into the reaction center and decrease the hydrolysis rate constant. The acid
22
-------
hydrolysis reaction center is less electronegative and the substituent-induced perturbations are
always quite small. Sigma induction is a short range effect. Calculated effects due to
substituents beyond two atoms from C were considered negligible. The sigma induction effects
are given as:
8 losk = o y (Y — Y ) 1STR (11)
Usigma J-wfc>rvc yeiec/-l VA/c A/s/ iNJJ
where Xc and x§ are the electronegativities of the reaction center and the appended substituent,
respectively, and NB is a data-fitted parameter that depends on the number of appended
substituents. Values of x§ and NB have been calculated using ionization pKadata [4, 7].
5.2.1.4. R, effect
The Rn effect is similar to sigma induction, except that it involves 7r-electrons instead of
a-electrons. The magnitude of the reactivity perturbation, 5,ilog kc, depends upon the difference
in the electronegativity of the substituent atom :r group and that of the reaction center to which it
is attached. Since the differential induction capability of carboxylic acid and phosphate esters is
highly correlated with peiec, SPARC uses a simple model, requiring a minimum of computation
and only one extra parameter to estimate the Rn effect on the hydrolysis rate constant as follows:
SJogk = pelec p]C ^ (12>
where Pjc = cos2@jc, 0 jc is the dihedral angle of C and R-TT unit (describing the TT orbital
alignment), and is set to 1 for this study. an is a data-fitted parameter; currently anis 0.008 and
0.1 for aromatic and ethylenic R-TT units, respectively. When an R-TT unit is attached to a
carbonyl carbon or P=O (electron withdrawing group), the Rn effect contributes negatively or
23
-------
lowers the hydrolysis rate constant. In contrast, when the TT-system is attached to an acyl oxygen
(electron donating group), the Rn effect increases the hydrolysis rate constant.
5.2.2. Resonance Effect
Resonance is a phenomenon of TT-electrons moving in or out of the reaction center.
Resonance stabilization energy in SPARC is a differential quantity, related directly to the extent
of electron delocalization in the initial state versus the transition state of the reaction center. The
TT-electron source, or sink, in P may be either from a substituent, S, or R-TT units contiguous to the
reaction center. Substituents that withdraw electrons from a reference point, CH2", are
designated S+ and those that donate electrons are designated S-. The R-TT units can either
withdraw or donate electrons or may serve as "conductors" of ^-electrons between resonance
units. Reaction centers are likewise classified as C+ (C=O or P=O) and C- (alkyl oxygen),
denoting the withdrawing and donating of electrons, respectively. The distribution of NBMO
(Non-Bonded Molecular Orbital) charge from the surrogate donor, CH2", is used to quantify the
acceptor potential for P, the perturber structure [4, 20, 21]. The resonance reactivity perturbation
is given by:
5rjogkc =PresAqc + presAq; (13)
where pres and p res are the susceptibilities of the alkyloxygen (donating electrons) and C=O/P=O
(withdrawing electrons), respectively, of the ester to resonance interactions. pres (p res) quantifies
the differential "donor" ability of the initial and transition states of the alkyl oxygen (C=O and
P=O) of the reaction center relative to CH2". Aqc (Aq c) is the fraction loss of NBMO charge from
the alkyl oxygen (C=O or P=O) surrogate reaction center calculated based on PMO theory [4,
24
-------
21]. Resonance plays different roles in carboxylic acid ester and organophosphorus hydrolysis.
The major impact is that of resonance stabilization of the leaving group. Thus, the R-TT unit
attached to the oxygen of the ester (alkyl oxygen) reaction center has a pronounced effect, greatly
increasing the hydrolysis rate constant. Conversely, the R-TT unit attached to the C=O or P=O
(electron-withdrawing group) tends to destabilize the leaving group, thereby decreasing the
hydrolysis rate constant.
5.3. External Perturbation (Solvation Effect) Model
Hydrolysis reactions (involve reactants, intermediates and/or products), are affected by
changes in the solvating power of the reaction medium. The presence of organic solvents can
affect the solvating power and thus alter the hydrolysis rate. The presence of water as solvent
influences the rate and mechanism of hydrolysis reactions in a number of ways; as a nucleophilic
reagent, as a high dielectric-constant continuum in which reaction takes place; and as a specific
solvating agent for organic reactants and products (leaving group).
The external reactivity perturbation (solvation effects) model, i.e., for SEP log kc,
describes the hydrogen bonding, dielectric field stabilization and steric effects of the solvent on
the transition (final) state versus the reactant (initial) state of the molecule. The hydrogen
bonding calculation gauges both the hydrogen acceptor effect (alpha) and hydrogen donor effect
(beta) of the esters, while the field stabilization calculation describes the effect of dielectric
constant of the solvent on the ester hydrolysis rate constant.
25
-------
5.3.1. Hydrogen Bonding Effect
The hydrogen bonding interaction is a direct, site-coupling of a proton-donating site of
one molecule with a proton-accepting site of another molecule. The total H-bonding energy is
resolved into a proton-donating site, a, and proton-accepting site, |3 that in the SPARC models
are presumed to be independently quantifiable [4, 6-9]. If the transition state of the ester is
better solvated or stabilized by the H-bonding than the initial state, the hydrolysis rate constant
increases. The negatively charged transition states of base and general base-catalyzed ester
hydrolysis are strongly stabilized by solvent alpha sites, while the solvent beta sites play a minor
role. Thus, it might appear that a the sites of the solvent should increase carboxylic acid and
phosphate esters hydrolysis rate constants. However, the a sites do not only solvate the
transition states, but also the attacking hydroxide ion. The latter tends to stabilize the initial state
more than the transition state as shown in Figure 1 . The net effect is that the solvent a sites tend
to decrease the carboxylic acid and phosphate esters hydrolysis rate constants. On the other
hand, the P site of the solvent can interact with an a site, freeing-up hydroxide ions to react with
an ester thereby tending to increase the base and neutral hydrolysis rate constant. For acid-
catalyzed carboxylic acid and phosphate esters hydrolysis, both the a and the P sites of the
solvent stabilize the initial state more than the transition state. Therefore, both solvent site types
decrease the acid-catalyzed hydrolysis rate constant. SPARC expresses the alpha and beta site
H-bond contribution as:
alpha = A_ beta= - (14)
Tk Tk
where alpha (beta) is the hydrogen accepter (donor) effect of the solute ester and a (P) is the
hydrogen donating (accepting) value of the solvent. PA and PB are data-fitted parameters
26
-------
quantifying the susceptibility of the a and |3 values of the solvent, respectively. Tk is the
temperature in degrees Kelvin. Both a and |3 of the solvent are calculated as pseudo pKa's, with the
electrostatic component treated as a dipole transition [4, 7, 11, 12].
Transition, state
Initial state
Reaction coordinate
Figure 1. The effect of solvent alpha sites on the initial and transition states in carboxylic acid ester or
phosphate ester hydrolysis rate. The alpha sites solvate the hydroxide ion and stabilize the initial state more
than the transition state. As a result, the alphas decrease the hydrolysis rate constant during ester hydrolysis.
5.3.2. Field Stabilization Effect
The field stabilization effect describes the perturbation of the log of the hydrolysis rate
constant by dielectric stabilization of the transition state by the solvent. It is expressed as a
function of both the temperature of reaction and the dielectric constant of the solvent:
FS =
PFS
TkD
(15)
-------
where De is the nonlinear temperature dielectric constant of the solvent, and PFS is the intrinsic
susceptibility of the hydrolysis rate constant to the solvation effect due to the dielectric properties
of the solvent, and is a data-fitted parameter. It describes the susceptibility of the transition state
to dielectric stabilization. Equation 15 quantifies the differential solvation of initial (reactant)
versus the transition states of the reactants in the hydrolysis reaction due to the dielectric
constant of the solvent. The dielectric constant of solvents solvates or stabilizes the initial state
of ester hydrolysis reactants more than the transition states. Thus, the field stabilization effect
always decreases the hydrolysis rate constant. Comparing the dielectric effect on the ester
hydrolysis rate constant in various mixed solvents, we observe that the decrease in the rate
constant is less in pure water than in mixed aqueous-organic solvents. This is because to the
higher dielectric of pure water compared to the organic solvent component of the mixed solvent
relatively enhances the stability of the transition state. Thus, the hydrolysis rate constant
reduction is greater in mixed aqueous-organic solvents.
For example, The field stabilization effects are -2.843 and -0.297 log-units for
hydrolysis of ethyl p-nitrobenzoate in base and acid media respectively, while it is -4.530 log-
units for hydrolysis of p-nitrophenyl acetate in general base catalyzed medium. The field
stabilization effect involves the dielectric constant of the solvent and in general it rises
the energy of the transition state more than the initial state. As a result, it lowers the
hydrolysis rate constant [41].
5.3.3. Steric Effect
The normal trend for a steric effect is as the bulkiness of the substituent increases, the steric
effect also increases. Thus, the steric effect always decreases the hydrolysis rate constant.
28
-------
Comparing the relative steric effect on carboxylic acid ester or phosphate ester hydrolysis rate
constant for various solvents, we observe there is much less steric effect in pure water than in
mixed solvents. The reason for this is that pure water more efficiently solvates the solute
molecule and aligns the structure of the solute ester for the attacking hydroxide ion or water
molecule. Conversely, the mixed-organic aqueous solvents only partially solvate the solute
molecule and deform the ester structure, creating a hindrance to attack from the hydroxide ion or
water molecule. Thus, the reaction does not proceed as rapidly as it does in pure water, and the
hydrolysis rate constant decreases. Steric effects include both steric blockage of reaction site
access and strain in achieving the transition state. SPARC expresses the steric effect on the log
hydrolysis rate constant as:
Steric
(16)
TkD.
where: Vs is the sum of the appended substituent sizes, Vthresh is a threshold size for onset of
steric effects; Vex is the excluded (cavity) volume between pairs of appended substituents; psteric
is the intrinsic steric susceptibility, and De is the dielectric constant of the solvent.
For example, The steric effects are -1.29 and -1.5 log-units for hydrolysis of ethyl
pnitrobenzoate in base and acid media respectively and it is -0.781 log-unit for neutral hydrolysis
of p-nitrophenyl acetate. The normal trend of steric effect is that bulkier the substituents lower
the hydrolysis rate constants. Since both ethyl p-nitrobenzoate and p-nitrophenyl acetate have
bulky phenyl rings, the steric effects display huge negative values [41].
29
-------
5.4. Temperature Effect
The quantitative relationship between the rate constant and temperature is frequently
expressed by the Arrhenius equation as:
' E
A
e i
(17)
where k is the hydrolysis rate constant, A is the pre-exponential or frequency factor, Ea is the
activation energy (the minimum energy required to form a product from the reactants), R, is the
gas constant, and T is the absolute temperature in degrees Kelvin. This temperature dependence
relationship is incorporated in the reference rate model, the field stabilization effect, the
alpha/beta H-bond effect, and the steric effect.
The observed rates of hydrolysis of organic compounds, including the carboxylic acid
phosphate esters, increases with temperature (see Figure 2). Figure 2 also illustrates the
predictive power of the SPARC model versus measured values for three esters undergoing
alkaline hydrolysis in three different solvents.
0 n
I
o
O
ro
ce
o
;R
D)
-1.5 -
-2 -
-3 J
0
methyl benzoate
cyclohexyl acetate
10
20 30 40
temperature (degree Celsius)
50
60
Figure 2. Log hydrolysis rate constants vs temperature for alkaline hydrolysis of methyl benzoate in 80%
methanol-water (circles), cyclopropyl acetate in pure water (triangles), and cyclohexyl acetate in 70%
acetone (diamonds). Solid symbols are observed values, empty symbols represent calculated values.
30
-------
6. RESULTS AND DISCUSSIONS
SPARC's computational methodology is based on structure query and analysis. This
involves combining the perturbation potentials of perturber units with the susceptibilities of the
reaction center. The reaction parameters that describe a given reaction center are constant,
regardless of the appended molecular structure. The same is true of substituents; the parameters
that describe their mechanistic contributions are independent of the rest of the molecule. This
structure factorization and mechanistic specification enables the construction of virtually any
molecule and computation of its properties.
Thus, in the estimation of any molecular property via SPARC, the contributions of the
structural components C, S, and R are quantified independently. For example, the strength of a
substituent, S, in creating an electrostatic field effect depends only on the substituent, regardless
of the reaction center, C, the appended molecular conductor, R, or the property of interest.
Likewise, R is modeled so as to be independent of the identities of S, C, or the property being
estimated. Hence, S and R parameters for hydrolysis rate are the same as those for pKaor
electron affinity. The susceptibility of a C to an electrostatic effect quantifies only the
differential interaction of the initial state versus the final state with the electrostatic fields. The
susceptibility gauges only the reaction Cmitiai - C transition state, and is completely independent of R
or S. Thus, no modifications in any of the previously developed pKa models in SPARC or any
extra parameterization for either S or R, were needed to calculate the hydrolysis rate constant
using the pKa models, other than inferring the electronegativity and the susceptibilities of
carboxylic acid ester and phosphate ester hydrolysis rate constants to electrostatic, resonance,
steric and solvation effects.
31
-------
Table 1 displays the aggregate statistical performance of the SP ARC-calculated versus
observed hydrolysis rate constants for all tests of the hydrolysis rate models to date. Figures 3-5
present observed versus SP ARC-calculated values of carboxylic acid ester hydrolysis rate
constants undergoing base, acid and general base catalyzed hydrolysis, respectively. These
carboxylic acid ester test sets represent 321, 416 and 50 unique esters undergoing base, acid and
general-base catalyzed hydrolysis, respectively. Because several of the esters were measured
under different conditions (solvents, temperatures, etc) there were 654, 667 and 150 base, acid
and general base-catalyzed calculations performed. The RMS deviations between the SPARC-
calculated and observed values for each of these reaction mechanisms were 0.37, 0.37 and 0.39
log M'V1, respectively. A sample calculation of the acid hydrolysis rate constant for p-
nitrophenyl acetate is shown in the appendix.
The same chemical hydrolysis models were used to estimate base, acid and neutral
organophosphorus hydrolysis rate constants in water as a function of temperature from molecular
structure. Results were tested against 225 base, 83 acid and 89 neutral measured
organophosphorus hydrolysis rate constants. The RMS deviation error between the observed and
SPARC-calculated values were 0.40, 41 and 1.08 log M'V1 for the base, acid and neutral
hydrolysis organophosphate ester rate constants, respectively also as is reported in Table IB.
We discovered that to expand our model to fluorine leaving groups on organophosphate
esters base hydrolysis, all that was required was a single addition to the reference rate model.
This addition took the form of redefining the Refi constant. The remaining portions of the model
use the parameters of the group that will hydrolyze after the fluorine-containing group. For
example, if the compound has two additional leaving groups and one is an aromatic group and
32
-------
the other is aliphatic, then the aromatic parameters will be used. This resulted in a fluorine-
containing organophosphate esters hydrolysis model with a RMS of 0.268 log M'V1.
The organophosphate ester base-catalyzed hydrolysis calculator was initially trained on
15 compounds (29 data points), chosen by visual inspection to span all hydrolysis mechanisms.
This training set had a RMS deviation of 0.403 log M-V1 and a R2 value of 0.97. The calculator
was then tested on 78 other compounds (196 data points) with a RMS deviation of 0.50 log
M-V1 and a R2 value of 0.95.
Acid catalyzed and neutral hydrolysis rate constants have been measured by many groups
[37, 42-47]. Unfortunately, the interlab agreement between measurements of the same
compounds is low. This experimental data varies by a much greater amount than that reported
for base catalyzed hydrolysis. The variance is partially due to the slow hydrolysis rate of acid
and neutral solutions as compared to alkaline hydrolysis. Slow hydrolysis rates (hundreds of
years) require sensitive instruments to detect any change in the composition of the solution.
Also, these compounds are usually synthesized as inorganic species or complexes and accurate
measurements depend on being able to measure the transformation of a single species. Acid
catalyzed hydrolysis doesn't really begin to occur until a pH of 2 or lower is reached and for
many compounds, it doesn't begin until the solution is at a negative pH. Further complicating
matters is the ionization or multiple ionization of the compound that occurs. This can lead to
different concentrations of various species, obscuring the overall hydrolysis rate. In neutral
hydrolysis, much of the same is true, with the pH range being from 2-8. For most components in
this range, the hydrolysis rate is only approximately constant. This is due to competing
mechanisms which occur at the same time. A complete listing of the compounds used to develop
these models can be found in Tables 18 and 19. These compounds represent the best
33
-------
experimentally measured data available for these types of phosphate ester hydrolysis. SPARC's
acid catalyzed hydrolysis model is robust and accurately represents the mechanisms influencing
the hydrolysis rate constant. In order to determine the parameters for the mechanisms that
describe acid catalyzed hydrolysis, the model was trained on all the data found in the literature:
28 compounds, at a variety of temperatures (83 data points). The neutral model is not as
accurate as most SPARC models, however, as the disparity of measurements as reported in the
literature preclude a more accurate model. The same procedure was repeated for neutral
hydrolysis model as for acid: 36 compounds (89 data points) were found in the literature and
used to train the parameters.
o>
•4-1
JS
3
<1
re
O
6
Q.
CO
-6
-6
-2
O b se rve d
Figure 3. SPARC-calculated vs. observed log hydrolysis rate constants for alkaline hydrolysis of
carboxylic acid esters in six different solvents. The RMS deviation error of the log values is
0.37 A/TV1 and R2is 0.97. See Tables 2-7.
34
-------
d>
+rf
_re
3
_0
re
O
6
Q.
V>
0
-2
-4
-6
-8
-1 0
-10
-8
-6 -4
O bserved
-2
0
Figure 4. SPARC-calculated vs. observed log hydrolysis rate constants for acid hydrolysis of carboxylic
acid esters in five solvents and at different temperatures. The RMS deviation error of the log values is
0.37 M-Vand R2is 0.97. See Tables 8-12.
5 -2
re
9
O
OL
0.
(O
-7
-12
-1 2
-7
-2
O bse rve d
Figure 5. SPARC-calculated vs. observed log hydrolysis rate constants for general alkaline base
hydrolysis of carboxylic acid esters in four different solvents and at different temperatures. The RMS
deviation error of the log values is 0.39 M'V'and R2is 0.97. See Tables 13-16.
35
-------
Tablel A. Statistical comparison of SPARC-calculated to observed21 values of log hydrolysis rate
constants of carboxylic acid ester in water and in mixed solvent systems
Training Set
All Mechanisms
(Base, Acid,
Neutral)
No RMS R2
705 0.33 0.98
Test Sets
Solvent
Water
Acetone
/Water
Ethanol
/Water
Methanol
/Water
Dioxnae/
Water
Aceteonitrile
/Water
Total
Total.
Comp
576
424
153
172
122
24
1471
Base
Catalyzed
No
142
143
105
150
90
24
654
RMS R2
0.39 0.98
0.34 0.83
0.29 0.83
0.36 0.78
0.47 0.75
0.3 0.97
0.37 0.96
Acid
Catalyzed
No
383
208
39
22
15
N/A
667
RMS R2
0.36 0.98
0.33 0.96
0.17 0.98
0.22 0 .95
0.16 0.87
N/A N/A
0.37 0.97
Neutral
Catalyzed
No
51
73
9
N/A
17
N/A
150
RMS R2
0.34 0.98
0.36 0.96
0.1 0.99
N/A N/A
0.47 0.67
N/A N/A
0.39 0.97
a: Observed values are from many sources, see Tables 2-16. Units are (L/mole) s"
TablelB. Statistical comparison of SPARC-calculated to observed21 values of log hydrolysis
rate constants of organophosphorus in water
Training Set
All Mechanisms
(Base, Acid, Neutral)
No
278b
RMS R2
0.38 0.94
Test Sets
Total.
Comp
397
Base -Catalyzed
No
225
RMS R2
0.40 0.93
Acid-Catalyzed
No
83
RMS R2
0.41 0.81
Neutral -Catalyzed
No
89
RMS R2
1.08 0.51
a: Observed values are from many sources, see Tables 17-19. Units are (L/mole) s"
b: The training set include all acid, neutral and 197 base hydrolysis data points
36
-------
7. MODELS VERIFICATION AND VALIDATION
In chemistry, as with all physical sciences, one can never determine the "validity" of
any predictive model with absolute certainty. This is a direct consequence of the empirical
nature of science. Because SPARC is expected to predict reaction parameters for processes
for which little data exists, "validity" must drive the efficiency of the model constructs in
"capturing" or reflecting the existing knowledge base of chemical reactivity. In every
aspect of SPARC development, from choosing the programming environment to building
model algorithms or rule bases, system validation and verification were important criteria.
The basic mechanistic models in SPARC were designed and parameterized to be portable to
any type of chemistry or organic chemical structure. This extrapolatability impacts system
validation and verification in several ways. First, as the diversity of structures and the
chemistry that is addressable increases, so does the opportunity for error. More importantly,
however, in verifying against the theoretical knowledge of reactivity, specific situations can
be chosen that offer specific challenges. This is important when verifying or validating
performance in areas where existing data are limited or where additional data collection may
be required. Finally, this expanded prediction capability allows one to choose, for
exhaustive validating, the reaction parameters for which large and reliable data sets do exist
to validate against.
In SPARC, the experimental data for physicochemical properties (such as hydrolysis
rate constant, or ionization pKa) are not used to develop (or directly impact) the model that
calculates that particular property. Instead, physicochemical properties are predicted using a
few models that quantify the underlying phenomena that drive all types of chemical
behavior (e.g., resonance, electrostatic, induction, dispersion, H-bonding interactions, etc.).
37
-------
These mechanistic models were parameterized using a very limited set of experimental data,
but not data for the end-use properties that will subsequently be predicted. After
verification, the mechanistic models were used in (or ported to) the various software
modules that calculate the various end-use properties (such as chemical reduction or
hydrolysis rate constant). It is critical to recognize that the same mechanistic model (e.g.,
H-bonding model) will appear in all of the software modules that predict the various end-use
properties (e.g., chemical hydrolysis rate constant or ionization pKa) for which that
phenomenon is important. Thus, any comparison of SPARC-calculated physicochemical
properties to an adequate experimental data set is a true model validation test - there is no
training (or calibration) data set in the traditional sense for that particular property. The
SPARC physical properties and chemical reactivity parameters models have been tested and
validated on more than 10,000 data points [48].
A quality assurance (QA) plan was developed to recalculate all the hydrolysis rate
constants reported in Tables 2-19 and compare each calculation to an originally-calculated-value
stored in the SPARC databases. Under this plan, every quarter, two batch files that contain all the
hydrolysis rate constants data recalculate various hydrolysis rate constants. The QA software
compares every single "new" output to the SPARC originally-calculated-value in earlier date
(stored in SPARC database). In this way, we ensure that existing parameter models still work
correctly after new capabilities and improvements are added to SPARC. This also ensures that
the computer code for hydrolysis rate constants and other mechanistic models are fully
operational.
38
-------
8. TRAINING AND MODEL PARAMETER INPUT
All quantitative chemical models require, at some point, calibration or parameterization.
The quality of computational output necessarily reflects the quality of the calibration parameters
For this reason, a self-training complement (TRAIN) to SPARC was developed. Although a
detailed description of TRAIN will not be given at this time, the following is a general review.
For a given set of targeted model parameters, the program takes initial "guesstimates" (and the
appropriate boundary constraints) together with a set of designated training data and provides an
optimized set of model parameters. TRAIN cycles once or iteratively through Jacobian
optimization procedure that is basically a non-linear, least square matrix method. TRAIN sets-
up and executes the optimization specifics according to user prescription.
39
-------
Table 2. SPARC-calculated vs. observed log base-catalyzed hydrolysis rate
constants for carboxylic acid esters in water as a function of temperature in M'V
Num
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Methyl formate
Ethyl formate
Propyl formate
Butyl formate
Methyl dichloroacetate
Ethyl difluoroacetate
Ethyl methyl sulfoxide acetate
Ethyl methyl sulfone acetate
Methyl acetate
Ethyl acetate
Propyl acetate
Butyl acetate
Isopropyl acetate
Cyclopropyl acetate
Cyclopentyl acetate
b-Methoxyethyl acetate
b-Chloroethyl acetate
Chloromethyl acetate
Dichloromethyl acetate
Trichloromethyl acetate
Bromomethyl acetae
Dimethyl-amino-ethyl acetate
Ethyl propionate
Ethyl butyrate
Ethyl sec-butyrate
Ethyl neopentate
Ethyl fluoroacetate
Ethyl chloroacetate
Methyl chloroacetate
Ethyl dichloroacetate
Ethyl tri chloroacetate
Isopropyl tri chloroacetate
Ethyl bromoacetate
Methyl bromoacetate
Ethyl dibromoacetate
Ethyl bromopropionate
Ethyl iodoacetate
Ethyl methoxyacetate
Ethyl oxyacetate
Ethyl methyl thioacetate
Obs
1.4
1.4
1.2
1.3
3.2
3.7
0.6
1.1
-0.7
-1
-1.1
-1.1
-1.5
-0.6
-1.4
-0.7
-0.4
1.8
3.2
4.1
2
-1
-1
-1.3
-1.5
-2.8
1.1
1.5
1.8
2.8
3.4
2.6
1.7
2
2.3
1
1.2
0.1
0
0
Calc
1.1
1.1
1.1
1.1
3.1
3.8
0.5
2.2
-0.4
-0.6
-0.7
-0.7
-0.9
-0.5
-0.9
-0.4
-0.2
1.8
3.4
3.9
1.7
-0.4
-1
-1.2
-1.4
-2
1.9
1.5
1.6
3
3.5
3.2
1.3
1.5
2.4
0.8
1.1
0.2
-0.1
0.2
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref
[49]
[49]
[49]
[49]
[49]
[49]
[49]
[49]
[50]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
40
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Ethyl aminoacetate
Acetic acid, 1-Pentene, 3 -methyl- ester
Vinyl acetate
Ethyl aery late
2-Butenoic acid, ethyl ester
Ethyl 2-butynoate
Ethyl propiolate
p-Nitrophenyl chloroacetate
Phenyl di chloroacetate
Ethyl benzoate
Ethyl p-aminobenzoate
Ethyl p-nitrobenzoate
Ethyl p-fluorobenzoate
Ethyl m-aminobenzoate
Methyl benzoate
Isopropyl benzoate
p-Tolyl benzoate
m-cyanophenyl benzoate
p-Nitrophenyl benzoate
2,4-dinitrophenyl benzoate
Phenyl acetate
Phenyl propionate
Phenyl butyrate
Phenyl sec-butyrate
Phenyl pentate
Phenyl sec-pentate
Phenyl neopentate
Phenyl (t-butyl)acetate
p-Methoxyphenyl acetate
p-Methoxyphenyl propionate
p-Methoxyphenyl butyrate
p-Methoxyphenyl sec-butyrate
p-Methoxyphenyl pentate
p-Methoxyphenyl sec-pentate
p-Methoxyphenyl neopentate
o-Nitrophenyl acetate
p-Nitrophenyl acetate
p-Nitrophenyl propionate
p-Nitrophenyl butyrate
p-Nitrophenyl sec-butyrate
p-Nitrophenyl pentate
p-Nitrophenyl sec-pentate
Obs
-0.2
-2.4
0.6
-1.1
-1.9
-0.3
0.7
3.8
4.1
-1.5
-2.6
-0.1
-1.4
-1.6
-1.1
-2.2
-0.5
0.3
0.4
1.2
-0.3
0.1
-0.1
-0.2
-0.2
-0.6
-0.9
-0.3
0
-0.1
-0.1
-0.3
-0.2
-0.6
-0.9
1.3
1.5
0.9
0.8
0.7
0.7
0.5
Calc
-0.3
-1.1
1
-0.7
-2.1
-1.2
0.6
3.2
4
-1.3
-2.8
-0.3
-1.3
-1.8
-1.1
-1.5
-0.3
0.4
0.5
1.7
0.5
0
-0.1
-0.4
-0.2
-0.9
-1
-0.9
0.2
-0.2
-0.4
-0.6
-0.4
-1.1
-1.2
1.1
1.2
0.7
0.5
0.3
0.5
-0.2
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[51]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
41
-------
Num
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
Esters
p-Nitrophenyl neopentate
o-Fluorophenyl acetate
o-Chlorophenyl acetate
o-Bromophenyl acetate
o-Iodophenyl acetate
o-Methylphenyl acetate
o-Ethylphenyl acetate
o-Isopropylphenyl acetate
o-(t-Butyl)phenyl acetate
o-Methoxyphenyl acetate
o-Nitrophenyl acetate
o-Cyanophenyl acetate
m-Fluorophenyl acetate
m-Bromophenyl acetate
m-Methylphenyl acetate
m-Ethylphenyl acetate
m-Methoxyphenyl acetate
m-Nitrophenyl acetate
m-Cyanophenyl acetate
p-Fluorophenyl acetate
p-Chlorophenyl acetate
p-Bromophenyl acetate
p-Ethylphenyl acetate
p-(t-Butyl)phenyl acetate
p-Cyanophenyl acetate
(p-Ethanal)phenyl acetate
Isopropyl acetate
Cyclopropyl acetate
Vinylic acetate
Vinylic acetate
Isopropenyl acetate
Isopropenyl acetate
Cyclopentenyl acetate
Cyclopentenyl acetate
Cyclohexyl acetate
Cyclohexyl acetate
Cyclopentyl acetate
Cyclopentyl acetate
Butyl acetate
Ethyl chloroacetate
Ethyl chloroacetate
Ethyl di chloroacetate
Obs
0.1
0.9
0.7
0.8
0.7
0.1
0.1
0
-0.3
0.3
1.3
1.5
0.9
0.9
0.4
0.4
0.6
1
1.2
0.6
0.8
0.7
0.3
0.3
1.3
1
-0.8
-0.1
-0.2
0.5
-1.2
-0.5
-0.1
0.4
-0.8
-0.3
-1.6
-1
-1.2
1.3
1.7
2.7
Calc
-0.3
0.9
1
0.9
0.9
0
-0.2
-0.5
-0.8
0.3
1.6
1.6
0.7
0.8
0.4
0.4
0.5
1.1
1
0.6
0.6
0.6
0.3
0.3
1.1
0.7
-0.6
-0.2
0.5
0.9
0.3
0.6
0
0.3
-1.2
-0.8
-1.1
-0.7
-0.8
1.4
1.6
2.9
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
20
40
0.2
20
0.2
20
0.2
20
20
40
20
40
20
15
35
15
Ref
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[50]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[52]
[53]
[53]
[53]
42
-------
Num
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
Esters
Ethyl dichloroacetate
Ethyl trichloroacetate
Ethyl trichloroacetate
Ethyl bromoacetate
Ethyl bromoacetate
Ethyl iodoacetate
Ethyl iodoacetate
Ethyl dibromoacetate
Methyl chloroacetate
Methyl chloroacetate
Mehtyl bromoacetate
Mehtyl bromoacetate
Methyl dichloroacetate
Methyl dichloroacetate
Ethyl trifluoroacetate
Isopropyl trichloroacetate
Chloromethyl acetate
Ethyl 2-pyridine-carboxylate
Obs
o
o o
J.J
3.5
1.5
1.8
1.1
1.4
2.5
1.5
2
1.8
2.2
3
o o
J.J
5.2
2.7
0.8
-0.3
Calc
3
3.5
3.5
1.2
1.4
1
1.2
2.4
1.5
1.8
1.3
1.6
3.1
3.2
4.7
3.3
1.7
0.3
Temp
35
15
35
15
35
15
35
35
15
35
15
35
15
35
15
35
15
25
Ref
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[49]
43
-------
Table 3. SPARC-calculated vs. observed log base-catalyzed hydrolysis rate constants
for carboxylic acid esters in water-acetone mixture as a function of temperature in M'1'
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
Esters
Methyl formate
Ethyl formate
Propyl formate
Isopropyl formate
Butyl formate
sec-Butyl formate
Isobutyl formate
Pentyl formate
Isopentyl formate
Methyl acetate
Methyl propionate
Methyl butyrate
Methyl isobutyrate
Ethyl acetate
propyl acetate
Butyl acetate
sec-Butyl acetate
Isobutyl acetate
Pentyl acetate
Isopentyl acetate
Hexyl acetate
Ethyl propionate
Ethyl butyrate
Methyl acetate
Ethyl acetate
propyl acetate
Isopropyl acetate
sec-Butyl acetate
Butyl acetate
sec-Butyl acetate
t-Butyl acetate
Cyclohexyl acetate
Methyl propionate
Ethyl propionate
Isopropyl propionate
Butyl propionate
Benzyl benzoate
p-Methylbenzyl benzoate
m-Methylbenzyl benzoate
Obs.
1.2
1
0.9
0.5
0.8
0.3
0.8
0.7
0.7
-0.8
-1
-1.3
-1.4
-1.2
-1.3
-1.4
-2.2
-1.5
-1.5
-1.5
-1.5
-1.3
-1.7
-1
-1.3
-1.6
-2.2
-1.7
-1.6
-2.5
-3.6
-2.3
-1.2
-1.7
-2.5
-2
-2.2
-2.3
-2.2
Calc.
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
-0.8
-1.3
-1.5
-1.5
-1
-1
-1.1
-1.9
-1.1
-1.1
-1.6
-1.1
-1.5
-1.7
-1.1
-1.3
-1.4
-1.8
-1.5
-1.5
-2.6
-2.7
-2.1
-1.7
-2
-2.4
-2.1
-1.9
-2
-2
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent.
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
37% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
Ref.
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[54]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
44
-------
Num
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
Esters
p-Ethylbenzyl benzoate
p-Isopropylbenzyl benzoate
p-(t-Butyl)benzyl benzoate
p-Methoxylbenzyl benzoate
p-Phenoxybenzyl benzoate
(p-Methiol)benzyl benzoate
(m-Methiol)benzyl benzoate
p-Phenylbenzyl benzoate
2-Naphthylcarbinyl benzoate
p-Fluorobenzyl benzoate
p-Chlorobenzyl benzoate
m-Chlorobenzyl benzoate
p-Bromobenzyl benzoate
m-Bromobenzyl benzoate
p-Nitrobenzyl benzoate
m-Nitrobenzyl benzoate
p-Cyanobenzyl benzoate
m-Cyanobenzyl benzoate
p-methylsulfoxide benzyl benzoate
p-m ethyl sulfone benzyl benzoate
m-methylsulfone benzyl benzoate
2-Fluorenylcarbinyl benzoate
1-Naphthylcarbinyl benzoate
2-Phenanthrylcabinyl benzoate
3-Phenanthrylcarbinyl benzoate
9-Phenanthrylcarbinyl benzoate
9-Anthrylcarbinyl benzoate
Ethyl phenyl acetate
Ethyl o-fluorophenyl acetate
Ethyl o-chlorophenyl acetate
Ethyl o-bromophenylacetate
Ethyl o-iodophenyl acetate
Ethyl m-iodophenyl acetate
Ethyl o-methylphenylacetate
Ethyl o-butylphenylacetate
Ethyl 1,6-dichlorophenylacetate
Ethyl p-(t-butyl)phenylacetate
Ethyl p-dimethylaminophenylacetate
Ethyl o-nitrophenylacetate
Ethyl p-aminophenylacetate
Ethyl m-methoxyphenylacetate
Obs.
-2.3
-2.3
-2.3
-2.3
-2.1
-2.1
-2
-2.1
-2.1
-2
-1.9
-1.8
-1.9
-1.8
-1.4
-1.5
-1.5
-1.5
-1.6
-1.4
-1.5
-2.2
-2.1
-2
-2.1
-2
-2.2
-1.4
-1.5
-1.8
-1.9
-1.9
-1.1
-2
-2.8
-2.9
-1.7
-1.6
-1.6
-1.5
-1.3
Calc.
-2
-2
-2
-2.1
-1.9
-1.9
-1.8
-1.8
-1.8
-1.8
-1.7
-1.6
-1.7
-1.6
-1.2
-1.3
-1.2
-1.3
-1.4
-1.3
-1.3
-1
-1.9
-1.8
-1.7
-1.9
-1.7
-1.4
-1.8
-1.9
-2
-2.1
-1.3
-2.1
-2.5
-2.4
-1.6
-1.9
-2
-1.9
-1.5
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
Ref.
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[57]
[57]
[57]
[57]
[57]
45
-------
Num
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
Esters
Ethyl (3,4-biphenyl)phenylacetate
Ethyl (p-phenyl)phenylacetate
Ethyl p-iodophenylacetate
Ethyl m-chlorophenylacetate
Ethyl m-fluorophenylacetate
Ethyl p-cyanophenylacetate
Ethyl p-nitrophenylacetate
Ethyl m-nitrophenyl acetate
Ethyl p-bromophenylacetate
Ethyl p-chlorophenylacetate
Ethyl p-fluorophenylacetate
Ethyl p-methoxyphenylacetate
Ethyl p-methylphenylacetate
Methyl phenyl acetate
Methyl 9-anthrylacetate
Methyl 9-phenanthrylacetate
Methyl 1-naphthylacetate
Methyl p-methylbenzoate
Methyl 2-naphthylacetate
Methyl 4-biphenylacetate
Methyl 2-anthrylacetate
Methyl 3 -phenanthryl acetate
Methyl 2-phenanthrylacetate
Methyl acetate
Ethyl acetate
Ethyl acetate
Ethyl acetate
Propyl acetate
Propyl acetate
Propyl acetate
Isopropyl acetate
Isopropyl acetate
Isopropyl acetate
Isobutyl acetate
Isobutyl acetate
Isobutyl acetate
n-Butyl acetate
n-Butyl acetate
n-Butyl acetate
sec-Butyl acetate
sec-Butyl acetate
sec-Butyl acetate
Obs.
-1.3
-1.5
-1.2
-1
-1
-0.7
-0.6
-0.8
-1
-1
-1.2
-1.4
-1.6
-0.9
-1.8
-1.4
-1.3
-1
-0.8
-0.8
-0.8
-0.8
-0.8
-1
-1.5
-1.3
-0.9
-1.7
-1.3
-1
-2.3
-1.9
-1.6
-1.9
-1.4
-1.2
-1.8
-1.6
-1.1
-2.6
-2.2
-1.9
Calc.
-1.4
-1.4
-1.3
-1.4
-1.4
-1.1
-1.1
-1.2
-1.4
-1.4
-1.4
-1.7
-1.6
-1.5
-2.3
-1.7
-1.7
-1.7
-1.4
-1.4
-1.4
-1.4
-1.5
-1.2
-1.4
-1.1
-0.9
-1.5
-1.2
-1
-1.9
-1.6
-1.4
-1.6
-1.3
-1.1
-1.6
-1.3
-1.1
-2.7
-2.3
-2.2
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
20
20
35
44.7
20
35
44.7
20
35
44.7
20
35
44.7
20
35
44.7
20
35
44.7
Solvent
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
60% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
75% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[57]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
46
-------
Num
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
Esters
t-Butyl acetate
t-Butyl acetate
Cyclohexyl acetate
Cyclohexyl acetate
Methyl propionate
Methyl propionate
Methyl propionate
Ethyl propionate
Ethyl propionate
Ethyl propionate
Isopropyl propionate
Isopropyl propionate
Isopropyl propionate
n-Butyl propionate
n-Butyl propionate
n-Butyl propionate
Ethyl picolinate
Ethyl isonicotinate
Ethyl nicotinate
Obs.
-3.2
-3
-2
-1.8
-1.3
-1
-0.8
-1.8
-1.4
-1.2
-2.7
-2.2
-1.9
-2.1
-1.7
-1.5
-0.7
-0.2
-0.9
Calc.
-2.5
-2.3
-1.9
-1.7
-1.8
-1.5
-1.3
-2.1
-1.8
-1.6
-2.6
-2.2
-2
-2.2
-1.9
-1.7
-0.9
-1.1
-1.2
Temp
35
44.7
35
44.7
20
35
44.7
20
35
44.7
20
35
44.7
20
35
44.7
25
25
25
Solvent
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
70% Acetone
60% acetone
60% acetone
60% acetone
Ref.
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[55]
[59]
[59]
[59]
47
-------
Table 4. SPARC-calculated vs. observed log base-
carboxylic acid esters in ethanol-water mixtures as
catalyzed hydrolysis rate constants of
a function of temperature in M'V1
Num
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Ethyl 1-naphthoate
Ethyl 3-chloro-l-napthoate
Ethyl 3 -bromo- 1-naphthoate
Ethyl 4-bromo- 1-naphthoate
Ethyl 5 -bromo- 1 -naphthoate
Ethyl 4'-methoxy-p-biphenyl carboxylate
Ethyl 4'-methyl-p-biphenyl carboxylate
Ethyl p-biphenyl carboxylate
Ethyl 4'-chloro-p-biphenyl carboxylate
Ethyl 4'-bromo-p-biphenyl carboxylate
Ethyl 3'-bromo-p-biphenyl carboxylate
Ethyl 4'-nitro-p-biphenyl carboxylate
Ethyl benzoate
Ethyl phenyl acetate
Ethyl o-iodophenyl acetate
Ethyl p-iodophenylacetate
Ethyl p-nitrophenylacetate
Ethyl o-methylphenylacetate
Ethyl p-methylphenylacetate
Ethyl phenyl acetate
Ethyl o-iodophenylacetate
Ethyl p-iodophenylacetate
Ethyl p-nitrophenylacetate
Ethyl o-methylphenylacetate
Ethyl p-methylphenylacetate
Ethyl phenyl acetate
Ethyl o-chlorophenyl acetate
Ethyl o-chlorophenyl acetate
Ethyl o-bromophenylacetate
Ethyl o-iodophenylacetate
Ethyl p-iodophenylacetate
Ethyl o-nitrophenyl acetate
Ethyl m-nitrophenyl acetate
Ethyl p-nitrophenylacetate
Ethyl o-methylphenylacetate
Ethyl p-methylphenylacetate
Ethyl p-(t-butyl)phenylacetate
Ethyl phenyl acetate
Ethyl o-fluorophenyl acetate
Ethyl p-fluorophenylacetate
Obs
-3.6
-2.7
-2.7
-3
-3
-3.5
-3.4
-3.3
-3.1
-3.1
-3
-2.8
-3
-1.9
-2.3
-1.5
-1
-2.4
-2
-1.8
-2.2
-1.4
-0.9
-2.3
-1.9
-1.7
-2.1
-1.3
-2.1
-2.2
-1.3
-1.9
-0.9
-0.8
-2.2
-1.8
-1.8
-2
-2.1
-1.8
Calc
-3
-2.7
-2.7
-2.9
-2.9
-2.9
-2.8
-2.7
-2.7
-2.7
-2.7
-2.5
-2.5
-1.7
-2.5
-1.6
-1.3
-2.5
-1.8
-1.6
-2.3
-1.4
-1.2
-2.3
-1.7
-1.4
-1.8
-1.3
-2
-2
-1.3
-1.9
-1.1
-1
-2.1
-1.5
-1.5
-1.7
-2.2
-1.7
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
75% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
65% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
Ref
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
48
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Ethyl o-chlorophenyl acetate
Ethyl m-chlorophenylacetate
Ethyl p-chlorophenylacetate
Ethyl o-bromophenylacetate
Ethyl p-bromophenylacetate
Ethyl o-iodophenylacetate
Ethyl m-iodophenylacetate
Ethyl p-iodophenylacetate
Ethyl o-nitrophenyl acetate
Ethyl m-nitrophenyl acetate
Ethyl p-nitrophenylacetate
Ethyl o-methylphenylacetate
Ethyl p-methylphenylacetate
Ethyl o-(t-butyl)phenyl acetate
Ethyl p-(t-butyl)phenylacetate
Ethyl o-methoxyphenylacetate
Ethyl m-methoxyphenylacetate
Ethyl p-methoxyphenylacetate
Ethyl p-nitrophenylacetate
Ethyl 1,6-dichlorophenylacetate
Ethyl 3,4-dimethoxyphenylacetate
Ethyl 1-naphthoate
Ethyl 1-naphthoate
Ethyl 1-naphthoate
Ethyl 1-naphthoate
Ethyl 3 -chloro- 1-naphthoate
Ethyl 3 -chloro- 1-naphthoate
Ethyl 3 -chloro- 1-naphthoate
Ethyl 4-chloro- 1-naphthoate
Ethyl 4-chloro- 1-naphthoate
Ethyl 4-chloro- 1-naphthoate
Ethyl 4-chloro- 1-naphthoate
Ethyl 3 -bromo- 1-naphthoate
Ethyl 3 -bromo- 1-naphthoate
Ethyl 4-bromo- 1-naphthoate
Ethyl 4-bromo- 1-naphthoate
Ethyl 4-bromo- 1-naphthoate
Ethyl 5 -bromo- 1-naphthoate
Ethyl 5 -bromo- 1-naphthoate
Ethyl 5 -bromo- 1-naphthoate
Ethyl 4-m ethyl- 1-naphthoate
Ethyl 4-m ethyl- 1-naphthoate
Obs.
-2.3
-1.6
-1.6
-2.4
-1.6
-2.4
-1.6
-1.6
-2.1
-1.1
-1.1
-2.5
-2.1
-3.3
-2.1
-2.8
-2
-2.1
-2.3
-3.4
-2
-3.1
-2.8
-2.5
-2.1
-2.7
-2
-1.6
-2.6
-2.2
-1.9
-2.5
-2
-1.3
-2.6
-1.9
-1.5
-2.3
-1.9
-1.6
-3.1
-2.8
Calc.
-2.3
-1.6
-1.6
-2.4
-1.6
-2.5
-1.6
-1.6
-2.4
-1.4
-1.3
-2.5
-1.9
-3.4
-1.9
-2.8
-1.8
-2
-2.1
-2.9
-2.1
-2.8
-2.6
-2.4
-2.3
-2.5
-2.3
-2.2
-2.8
-2.6
-2.4
-2.2
-2.3
-2
-2.7
-2.4
-2.2
-2.5
-2.3
-2.1
-3.2
-3
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
35
45
55
65
35
45
55
35
45
55
65
45
65
35
55
65
45
55
65
45
55
Solvent.
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
90% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
Ref.
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[56]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
[60]
49
-------
Num
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
Esters
Ethyl 4-m ethyl- 1-naphthoate
Ethyl 4-m ethyl- 1-naphthoate
Ethyl 3 -methyl- 1-naphthoate
Ethyl 3 -methyl- 1-naphthoate
Ethyl 3 -methyl- 1-naphthoate
Ethyl 3 -methyl- 1-naphthoate
Ethyl 4'-methoxy-p-biphenyl carboxylate
Ethyl 4'-methyl-p-biphenyl carboxylate
Ethyl p-biphenyl carboxylate
Ethyl 4'-chloro-p-biphenyl carboxylate
Ethyl 4'-bromo-p-biphenyl carboxylate
Ethyl 3'-bromo-p-biphenyl carboxylate
Ethyl 3'-nitro-p-biphenyl carboxylate
Ethyl 4'-nitro-p-biphenyl carboxylate
Ethyl picolinate
Ethyl nicotinate
Ethyl isonicotinate
Ethyl picolinate
Ethyl nicotinate
Ethyl isonicotinate
Ethyl picolinate
Ethyl nicotinate
Ethyl isonicotinate
Obs.
-2.4
-2
-2.9
-2.6
-2.2
-1.9
-2.8
-2.7
-2.6
-2.5
-2.5
-2.4
-2.2
-2.2
-1.5
-1.7
-0.9
-1.2
-1.4
-0.7
-0.9
-1.1
-0.4
Calc.
-2.8
-2.6
-2.7
-2.5
-2.4
-2.2
-2.6
-2.5
-2.4
-2.4
-2.4
-2.4
-2.3
-2.2
-1.1
-1.5
-1.4
-1
-1.3
-1.2
-0.8
-1.1
-1
Temp
65
75
45
55
65
75
40
40
40
40
40
40
40
40
17
17
17
25
25
25
35
35
35
Solv.
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
85% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
91% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
75% Ethanol
Ref.
[60]
[60]
[60]
[60]
[60]
[60]
[61]
[61]
[61]
[61]
[61]
[61]
[61]
[61]
[62]
[62]
[62]
[62]
[62]
[62]
[62]
[62]
[62]
50
-------
Table 5. SPARC-calculated vs. observed log base-catalyzed hydrolysis rate constants
for carboxylic acid esters in methanol-water mixtures as a function of temperature in M'
Num
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Methyl o-fluorobenzoate
Methyl m-nitrobenzoate
Methyl m-chlorobenzoate
Methyl benzoate
Methyl p-bromobenzoate
Methyl p-nitrobenzoate
Methyl m-bromobenzoate
Methyl m-nitrobenzoate
Methyl 9-anthrylacetate
Methyl 6-chryslacetate
Methyl 9-phenanthrylacetate
Methyl 1-naphthylacetate
Methyl 1-pyrenyl acetate
Methyl p-methylphenylacetate
Methyl 2-fluorenylacetate
Methyl phenyl acetate
Methyl 2-naphthylacetate
Methyl 4-biphenylacetate
Methyl 2-anthrylacetate
Methyl 3 -phenanthryl acetate
Methyl 2-phenanthrylacetate
Methyl benzoate
Mehtyl p-nitrobenzoate
Methyl m-nitrobenzoate
Methyl m-bromobenzoate
Methyl p-bromobenzoate
Methyl m-methoxybenzoate
Methyl benzoate
Methyl m-methylbenzoate
Methyl m-dimethylaminobenzoate
Methyl p-methylbenzoate
Methyl p-methoxybenzoate
Methyl benzoate
Methyl benzoate
Methyl benzoate
Methyl benzoate
Methyl o-methylbenzoate
Methyl o-methylbenzoate
Methyl o-methylbenzoate
Methyl o-methylbenzoate
Obs.
-2.6
-1.6
-2.4
-2.7
-2.3
-1.1
-2
-1.3
-3.3
-2.9
-2.9
-2.9
-2.7
-2.6
-2.6
-2.5
-2.4
-2.4
-2.4
-2.4
-2.4
-2.3
-1.9
-2.1
-2.9
-3.2
-3.6
-3.7
-3.9
-4
-4
-4.3
-2.8
-2.4
-2.3
-2
-3.7
o o
-J.J
-2.9
-2.3
Calc
-2.7
-2.2
-2.7
-2.2
-2.2
-1.4
-2
-1.6
-2.9
-2.4
-2.4
-2.4
-2.3
-2.3
-1.7
-2.1
-2.1
-2.1
-2
-2.4
-2.1
-2.1
-2.3
-2.5
-2.9
-3.1
-3.5
-3.2
-3.5
-3.7
-3.8
-4.3
-2.7
-2.5
-2.4
-2.3
-3.5
-3.3
-3.1
-2.8
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
34.8
44.8
49.8
55.2
35
45
55
70.2
Solvent
80% Methanol
80% Methanol
80% Methanol
60% Methanol
60% Methanol
60% Methanol
60% Methanol
60% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
50% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
Ref.
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[64]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
51
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Methyl o-ethylbenzoate
Methyl o-ethylbenzoate
Methyl o-ethylbenzoate
Methyl o-ethylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Methyl o-fluorobenzoate
Methyl o-fluorobenzoate
Methyl o-fluorobenzoate
Methyl o-chlorobenzoate
Methyl o-chlorobenzoate
Methyl o-chlorobenzoate
Methyl o-chlorobenzoate
Methyl o-bromobenzoate
Methyl o-bromobenzoate
Methyl o-bromobenzoate
Methyl o-bromobenzoate
Methyl o-iodobenzoate
Methyl o-iodobenzoate
Methyl o-iodobenzoate
Methyl o-iodobenzoate
Methyl m-nitrobenzoate
Methyl m-nitrobenzoate
Methyl m-nitrobenzoate
Methyl m-chlorobenzoate
Methyl m-chlorobenzoate
Methyl m-chlorobenzoate
Methyl m-methylbenzoate
Methyl m-methylbenzoate
Methyl m-methylbenzoate
Methyl m-methylbenzoate
Methyl 9-anthrylacetate
Methyl 9-phenanthrylacetate
Methyl 1-naphthylacetate
Methyl 6-chrysylacetate
Methyl p-methylphenylacetate
Obs.
-3.6
-3.2
-2.5
-2.1
-2.6
-2.4
-2
-1.7
-3.5
-3.2
O
-1.8
-3
-2.2
-1.8
-2.5
-2.2
-2
-1.8
-2.7
-2.3
-2.1
-2
-2.9
-2.5
-2.3
-2.1
-2.6
-2.1
-1.3
-2.9
-2
-1.6
-3.1
-2.7
-2.3
-2
-2.9
-2.6
-2.6
-2.4
-2.3
Calc.
-3.5
-3.3
-3
-2.9
-3.1
-3
-2.8
-2.6
-2.4
-2.2
-2.2
-2.1
-2.9
-2.5
-2.3
-2.4
-2.2
-2.1
-2
-2.5
-2.3
-2.2
-2.1
-2.5
-2.3
-2.2
-2.1
-2.6
-2.4
-2
-2.9
-2.5
-2.3
-3.1
-2.8
-2.6
-2.4
-2.8
-2.2
-2.2
-2.2
-2.2
Temp
45
55
70.2
80.4
71.6
78.4
89.9
100.2
119.8
129.8
134
140
15.4
35
44.8
35
44.8
50
55
35
45
50
55
34.8
44.8
49
54.9
4.6
15
34.5
15
34.5
45.2
30.1
40.7
50
59.8
32.5
32.5
32.5
32.5
32.5
Solvent
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
80% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
Ref.
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[58]
[58]
[58]
[58]
[58]
52
-------
Num
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
Esters
2-Fluorenyl phenylacetate
Methyl phenylacetate
Methyl 2-naphthylacetate
Methyl p-biphenylacetate
Methyl 3 -phenanthryl acetate
Methyl 2-phenanthrylacetate
Methyl phenylacetate
Methyl 2-naphthylacetate
Methyl p-biphenylacetate
Methyl 2-phenanthrylacetate
Methyl 9-anthrylacetate
Methyl 9-phenanthrylacetate
Methyl 1-naphthylacetate
Methyl 6-chrysylacetate
Methyl p-methylphenylacetate
2-Fluorenyl phenylacetate
Methyl phenylacetate
Methyl 2-naphthylacetate
Methyl p-biphenylacetate
Methyl 3 -phenanthryl acetate
Methyl 2-phenanthrylacetate
Methyl 9-anthrylacetate
Methyl 9-phenanthrylacetate
Methyl 2-naphthylacetate
Methyl 6-chrysylacetate
Methyl p-methylphenylacetate
2-Fluorenyl phenylacetate
Methyl 3 -phenanthryl acetate
2-Carbomethoxyquinoline
Methyl 2-nitropicolinate
Methyl 2-bromopicolinate
Methyl 2-methylpicolinates
Methyl 2-dimethylnitropicolinate
Methyl nicotinate
Methyl picolinate
Methyl isonicotinate
Methyl 5-nitropicolinate
Methyl 5-bromopicolinate
Methyl picolinate
Methyl 5-methylpicolinate
Methyl 5-methoxylpicolinate
Methyl 5-dimethylnitropicolinate
Obs.
-2.2
-2.2
-2.1
-2.1
-2
-2.1
-2
-1.9
-1.9
-1.8
-2.3
-2
-2
-1.8
-1.7
-1.6
-1.6
-1.5
-1.5
-1.5
-1.5
-1.9
-1.6
-1.6
-1.4
-1.4
-1.3
-1.1
-0.5
-0.6
-1.5
-2.3
-2.9
-1.4
-1.2
-0.7
-0.4
-1.5
-2
-2.4
-2.8
-3.7
Calc.
-1.6
-2
-1.9
-1.9
-1.9
-1.9
-1.9
-1.8
-1.8
-1.8
-2.4
-1.9
-1.9
-1.9
-1.8
-1.3
-1.7
-1.6
-1.6
-1.6
-1.6
-2.2
-1.7
-1.7
-1.7
-1.6
-1.2
-1.4
-0.6
-1
-1.5
-2
-2.3
-1.2
-0.9
-1.1
-0.8
-1.7
-1.8
-2.3
-2.8
-3.3
Temp
32.5
32.5
32.5
32.5
32.5
32.5
40
40
40
40
50
50
50
50
50
50
50
50
50
50
50
60.2
60.2
60.2
60.2
60.2
60.2
60.2
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
85% Methanol
50% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
Ref.
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[58]
[64]
[65]
[65]
[65]
[65]
[49]
[49]
[49]
[65]
[65]
[65]
[65]
[65]
[65]
53
-------
Num
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
Esters
Methyl 4-nitropicolinate
Methyl 4-bromopicolinate
Methyl 4-methylpicolinate
Methyl 4-methoxylpicolinate
Methyl 5-bromonicotinate
Methyl nicotinate
Methyl 5-methylnicotinate
Methyl 5-methoxynicotinate
Methyl 5-dimethylnitronicotinate
Methyl 2-bromonicotinate
Methyl 2-methylnicotinate
Methyl 2-methoxynicotinate
Methyl 2-dimethylnitronicotinate
Methyl 2-nitroisonicotinate
Methyl 2-bromoisonicotinate
Methyl isonicotinate
Methyl 2-methylisonicotinate
Methyl 2-methoxyisonicotinate
Methyl 2-dimethylnitroisonicotinate
3-Carbomethoxyquinoline
4-Carbomethoxyquinoline
5-Carbomethoxyquinoline
6-Carbomethoxyquinoline
7-Carbomethoxyquinoline
8-Carbomethoxyquinoline
Obs.
-0.7
-1.3
-2.2
-2
-1.5
-2.3
-2.3
-2.1
-2.7
-1.8
-2.6
-3.2
-4.3
0.2
-0.9
-1.5
-1.7
-1.8
-2.3
-1.1
-0.8
-1.7
-1.6
-1.5
-2.4
Calc.
-1
-1.5
-2
-2.1
-1.8
-2.1
-2.3
-2.4
-2.6
-2
-2.7
-3.2
-3.8
-1.2
-1.7
-2
-2.2
-2.2
-2.5
-0.9
-1.1
-1.4
-1.2
-1.2
-1.4
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
88% Methanol
50% Methanol
50% Methanol
50% Methanol
50% Methanol
50% Methanol
50% Methanol
Ref.
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[64]
[64]
[64]
[64]
[64]
[64]
54
-------
Table 6. SP ARC-calculated vs. observed log base-catalyzed hydrolysis rate constants
for carboxylic acid esters in dioxane-water mixtures as a function of temperature in M'V
-i.-i
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Ethyl benzoate
p-Nitrobenzyl benzoate
p-Chlorobenzyl benzoate
p-Chlorobenzyl benzoate
Benzyl benzoate
p-Methoxybenzyl benzoate
Methyl benzoate
Methyl p-aminobenzoate
Methyl p-methylbenzoate
Methyl p-chlorobenzoate
Methyl p-nitrobenzoate
Methyl acetate
Methyl propionate
Methyl isobutyrate
Methyl n-butyrate
Mehtyl n-pentate
Methyl isopentate
Methyl sec-pentate
Methyl neopentate
Methyl phenylacetate
Methyl benzoate
Methyl p-methylbenzoate
Methyl m-methylbenzoate
Methyl p-methoxybenzoate
Methyl p-aminobenzoate
Methyl p-bromobenzoate
Methyl m-iodobenzoate
Methyl m-chlorobenzoate
Methyl m-bromobenzoate
Methyl m-nitrobenzoate
Methyl p-nitrobenzoate
Ethyl benzoate
Propyl benzoate
Propyl p-chlorobenzoate
Isopropyl benzoate
Isopropyl p-methoxybenzoate
Isopropyl p-nitrobenzoate
Butyl benzoate
Butyl p-aminobenzoate
Isobutyl benzoate
Obs
-2.1
-1.5
-2
-1.7
-2.3
-2.4
-1.6
-2.9
-2
-1.2
-0.2
-0.5
-0.6
-1.1
-0.9
-1
-1.5
-1.6
-2
-0.4
-1.5
-1.9
-1.8
-2.2
O
-1
-0.9
-0.8
-0.8
0
0.2
-2
-2.2
-1.6
-2.8
-3.4
-0.9
-2.3
-3.8
-2.4
Calc
-1.6
-1.2
-1.4
-1
-1.5
-1.5
-1.5
-3
-2
-1.4
-0.5
-0.3
-0.9
-1.1
-1.1
-1.2
-1.2
-2.1
-1.4
-0.4
-1.7
-2.2
-1.9
-2.7
-3.2
-1.6
-1.3
-1.4
-1.4
-0.9
-0.7
-1.9
-2
-2
-2.4
-3.4
-1.5
-2.1
-3.6
-2.1
Temp.
30
25
25
25
25
25
25
25
25
25
25
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
Solvent
33% dioxane
67% dioxane
67% dioxane
67% dioxane
67% dioxane
67% dioxane
33% dioxane
33% dioxane
33% dioxane
33% dioxane
33% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
40% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
Ref.
[49]
[66]
[67]
[67]
[67]
[67]
[67]
[67]
[67]
[67]
[67]
[68]
[68]
[68]
[68]
[68]
[68]
[68]
[68]
[68]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
55
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Isobutyl p-aminobenzoate
sec-Butyl benzoate
sec-Butyl m-methylbenzoate
Isopentyl benzoate
Isopentyl p-chlorobenzoate
Benzyl benzoate
Benzyl p-methylbenzoate
1-Phenyl -ethyl benzoate
1 , 1 -Biphenyl-methyl benzoate
Ethyl p-methoxybenzoate
Ethyl p-fluorobenzoate
Ethyl m-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl 3,4-dinitrobenzoate
Ethyl p-aminobenzoate
Methyl benzoate
Methyl m-bromobenzoate
Methyl p-bromobenzoate
Methyl p-methoxybenzoate
Methyl m-methoxybenzoate
Methyl p-methylbenzoate
Methyl m-methylbenzoate
Methyl p-nitrobenzoate
Methyl m-nitrobenzoate
Methyl p-trifluoromethylbenzoate
Methyl benzoate
Methyl benzoate
Methyl o-methylbenzoate
Methyl o-methylbenzoate
Methyl o-methylbenzoate
Methyl o-ethylbenzoate
Methyl o-ethylbenzoate
Methyl o-ethylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-isopropylbenzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Methyl o-(t-butyl)benzoate
Ethyl benzoate
Obs.
-3.8
-3.1
-3.3
-2.4
-1.8
-1.8
-2.2
-2.1
-3.6
-2.7
-1.8
-0.5
-0.3
-1.2
-3.5
-2.4
-1.7
-1.8
-3.1
-2.3
-2.8
-2.6
-0.5
-0.8
-1.2
-2.5
-1.9
-2.8
-2.3
-2
-3.1
-2.7
-2.4
-2.9
-2.5
-2.3
-2
-3.1
-2.7
-2.5
-2.2
-2
Calc.
-3.6
-3.2
-3.4
-1.8
-1.7
-1.1
-1.7
-2.8
-4.7
-2.9
-1.9
-1.2
-1
-0.4
-3.5
-2.4
-2.1
-2.3
-3.5
-2.7
O
-2.7
-1.4
-1.6
-2.7
-2.2
-1.9
-2.8
-2.5
-2.3
-2.9
-2.7
-2.5
-2.8
-2.6
-2.4
-2.3
-1.7
-1.6
-1.5
-1.4
-1.7
Temp
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
10
10
10
10
10
10
10
10
10
10
10
25
25
40.2
50.4
30
40
50
40.9
49.9
60
70
114.6
124.1
133.7
144.3
30
Solvent
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
60% dioxane
Ref.
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[69]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[59]
56
-------
Num
83
84
85
86
87
88
89
90
Esters
Ethyl benzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Benzyl benzoate
Benzyl benzoate
Methyl nicotinate
Methyl picolinate
Methyl isonicotinate
Obs.
-2.3
-1.2
-1.3
-1.9
-2.1
-0.9
-0.7
-0.1
Calc.
-2.2
-1.1
-1.2
-1
-1.5
-1
-0.7
-0.9
Temp
30
30
30
30
30
10
10
10
Solvent
70% dioxane
60% dioxane
70% dioxane
50% dioxane
70% dioxane
65% dioxane
65% dioxane
65% dioxane
Ref.
[59]
[59]
[59]
[59]
[59]
[59]
[59]
[59]
57
-------
Table 7. SPARC-calculated vs. observed log base-catalyzed hydrolysis rate constants
for carboxylic acid esters in acetonitrile-water mixtures as a function of temperature in M'V
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Esters
p-Tolyl p-dimethylaminobenzoate
p-Tolyl p-methylbenzoate
p-Tolyl benzoate
p-Tolyl p-chlorobenzoate
p-Tolyl p-nitrobenzoate
Phenyl p-dimethylaminobenzoate
Phenyl p-methylbenzoate
Phenyl benzoate
Phenyl p-chlorobenzoate
Phenyl p-nitrobenzoate
p-Chlorophenyl p-methylbenzoate
p-Chlorophenyl benzoate
p-Chlorophenyl p-chlorobenzoate
p-Chlorophenyl p-nitrobenzoate
m-Nitrophenyl p-dimethylaminobenzoate
m-Nitrophenyl p-methylbenzoate
m-Nitrophenyl benzoate
m-Nitrophenyl p-chlorobenzoate
m-Nitrophenyl p-nitrobenzoate
p-Nitrophenyl p-dimethylaminobenzoate
p-Nitrophenyl p-methylbenzoate
p-Nitrophenyl benzoate
p-Nitrophenyl p-chlorobenzoate
p-Nitrophenyl p-nitrobenzoate
Obs.
-3.1
-1.9
-1.5
-1
0.2
-2.9
-1.6
-1.3
-0.8
0.3
-1.3
-0.9
-0.5
0.7
-2.1
-0.7
-0.3
0.1
1.2
-1.8
-0.5
-0.1
0.3
1.4
Calc.
-2.6
-1.6
-1
-1
-0.1
-2.5
-1.5
-0.9
-0.8
0.1
-1.3
-0.8
-0.7
0.2
-1.9
-0.9
-0.3
-0.2
0.7
-1.8
-0.8
-0.2
-0.1
0.8
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Solvent
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
33% Acetonitrile
Ref.
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
[70]
58
-------
Table 8. SPARC-calculated vs. observed log acid-catalyzed hydrolysis rate constants
for carboxylic acid esters in water as a function of temperature in M'V
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Ethyl acetate
Ethyl propionate
Ethyl cyclo-butyl carboxylate
Ethyl butyrate
Ethyl pentate
Ethyl hexanoate
Ethyl iso-hexanoate
Ethyl (heptyl)acetate
Ethyl (t-butyl)propionate
Ethyl sec-butyrate
Ethyl cyclopentate
Ethyl cyclohexanoate
Ethyl iso-pentate
Ethyl cyclohexyl-acetate
Ethyl sec-pentate
Ethyl cycloheptyl-carboxylate
Ethyl neopentate
Ethyl (t-butyl) acetate
Ethyl (t-butyl)-sec-butyrate
Ethyl (2-ethyl)butyrate
Ethyl (2-propyl)pentate
Ethyl (2-isobutyl-4-methyl)pentate
Ethyl (t-butyl)neopentate
Ethyl (2-neopentyl-4,4-dimethyl)pentate
Ethyl (t-butyl)isopropionate
Ethyl (t-butyl)t-butyrate
Ethyl (2,2-diethyl)butyrate
Ethyl (methyl )(neopentyl) (t-butyl) acetate
Isopropyl formate
Isopropyl acetate
Isopropyl propionate
Isopropyl chloroacetate
Isopropyl butyrate
Isopropyl pentate
Isopropyl hexanoate
Isopropyl iso-hexanoate
Isopropyl phenylacetate
Isopropyl phenylpropionate
Isopropyl phenylbutyrate
Isopropyl isobutyrate
Obs.
-4
-4
-4
-4.3
-4.4
-4.4
-4.3
-4.3
-4.3
-4.4
-4.5
-4.8
-4.9
-4.9
-5.1
-5
-5.5
-5.7
-5.8
-5.9
-6.1
-6.4
-6.5
-7.2
-7.3
-7.9
-7.8
-8
O
-4.2
-4.3
-4.4
-4.6
-4.6
-4.6
-4.6
-4.6
-4.6
-4.7
-4.7
Calc.
-3.9
-4.3
-4.7
-4.4
-4.5
-4.5
-4.4
-4.5
-4.9
-4.6
-5
-5.1
-4.6
-4.8
-5.1
-5.1
-5.2
-5.4
-5.7
-5.9
-6.2
-6.7
-6.5
-7.1
-6.6
-7.1
-6.8
-8.4
-3.5
-4.2
-4.5
-4.8
-4.7
-4.7
-4.8
-4.7
-4.8
-4.8
-4.7
-4.9
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
59
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Isopropyl cyclohexyl-carboxylate
Isopropyl isopentate
Isopropyl cyclohexylacetate
Isopropyl (2-ethyl) propionate
Isopropyl (2,2-methyl-phenyl) acetate
Isopropyl (2,2-ethyl-phenyl) acetate
Isopropyl neopentate
Isopropyl (2,2-diphenyl) acetate
Isopropyl (2-ethyl) butyrate
Isopropyl (3-phenyl)-2-propenoate
Isopropyl trichloroacetate
Isopropyl benzoate
Isopropyl cyclobutyl-carboxylate
Isopropyl methoxyacetate
Isopropyl bromoacetate
Isopropyl thiolpropionate
Isopropyl iodoacetate
Isopropyl nonoate
Isopropyl (4,4-dimethyl)pentate
Isopropyl phenoxy-acetate
Isopropyl cyclopentyl-carboxylate
Isopropyl difluoroacetate
Isopropyl methoxy propionate
Isopropyl chloropropionate
Isopropyl trifluoroacetate
Isopropyl cycloheptyl-carboxylate
Isopropyl dichloracetate
Isopropyl neopentate
Isopropyl (2-neopentyl)propionate
Isopropyl dibromoacetate
Isopropyl (2-propyl)pentate
Isopropyl tribromoacetate
Isopropyl (3,3-methyl-neopentyl)acetate
Isopropyl (3-neopentyl-4,4-dimethyl)pentate
Isopropyl (2-t-butyl)propionate
Isopropyl (2,2-methyl-t-butyl)propionate
Isopropyl (2,2-diethyl)butyrate
Isopropyl (methyl) (neopentyl) (t-butyl)acetate
n-Butyl formate
n-Butyl acetate
n-Butyl propionate
n-Butyl chloroacetate
Obs.
-5
-5.1
-5.2
-5.3
-5.4
-5.7
-5.8
-6
-6.2
-6.2
-6.3
-6.8
-4.3
-4.4
-4.5
-4.6
-4.6
-4.5
-4.6
-4.5
-4.7
-4.9
-5
-5.1
-5.4
-5.3
-5.8
-5.9
-6.1
-6.1
-6.3
-6.6
-6.8
-7.4
-7.5
-8.1
-8
-8.2
-2.8
-4
-4.1
-4.2
Calc.
-5.3
-4.9
-5
-5.4
-5.6
-6.1
-5.4
-6.7
-6.1
-5.9
-5.8
-6.2
-5
-4.9
-4.9
-4.9
-4.9
-4.8
-5.1
-4.9
-5.2
-5.1
-4.8
-4.7
-5.6
-5.3
-5.2
-5.4
-5.9
-5.6
-6.5
-6.4
-6.7
-7.4
-6.8
-7.4
-7.1
-8.6
-3.5
-4
-4.3
-4.6
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
60
-------
Num
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
Esters
n-Butyl butyrate
n-Butyl pentate
n-Butyl hexanoate
n-Butyl iso-hexanoate
n-Butyl phenylacetate
n-Butyl phenylpropionate
n-Butyl phenylbutyrate
n-Butyl isobutyrate
n-Butyl cyclohexyl-carboxylate
n-Butyl isopentate
n-Butyl cyclohexylacetate
n-Butyl (2-ethyl)propionate
n-Butyl (2,2-methyl-phenyl)acetate
n-Butyl (2,2-ethyl-phenyl)acetate
n-Butyl neopentate
n-Butyl (2,2-diphenyl)acetate
n-Butyl (2-ethyl)butyrate
n-Butyl (3-phenyl)2-propenoate
n-Butyl trichloroacetate
n-Butyl benzoate
n-Butyl cyclobutyl-carboxylate
n-Butyl methoxyacetate
n-Butyl bromoacetate
n-Butyl thiolpropionate
n-Butyl iodoacetate
n-Butyl nonoate
n-Butyl (4,4-dimethyl) pentate
n-Butyl phenoxy-acetate
n-Butyl cyclopentyl-carboxylate
n-Butyl difluoroacetate
n-Butyl methoxypropionate
n-Butyl chloropropionate
n-Butyl trifluoroacetate
n-Butyl cycloheptyl-carboxylate
n-Butyl dichloracetate
n-Butyl neopentate
n-Butyl (2-neopentyl)propionate
n-Butyl dibromoacetate
n-Butyl (2-propyl) pentate
n-Butyl tribromoacetate
n-Butyl (3,3-methyl-neopentyl)acetate
n-Butyl (3-neopentyl-4,4-dimethyl)pentate
Obs.
-4.4
-4.4
-4.4
-4.4
-4.4
-4.5
-4.5
-4.5
-4.8
-5
-5
-5.2
-5.2
-5.5
-5.6
-5.8
-6
-6
-6.1
-6.6
-4.1
-4.2
-4.3
-4.4
-4.4
-4.4
-4.4
-4.4
-4.5
-4.7
-4.8
-4.9
-5.2
-5.1
-5.6
-5.8
-5.9
-5.9
-6.1
-6.5
-6.6
-7.2
Calc.
-4.5
-4.5
-4.6
-4.5
-4.6
-4.6
-4.5
-4.7
-5.1
-4.7
-4.8
-5.2
-5.4
-5.9
-5.2
-6.5
-5.9
-5.7
-5.6
-6
-4.8
-4.7
-4.7
-4.7
-4.7
-4.6
-5
-4.7
-5
-4.9
-4.6
-4.5
-5.4
-5.1
-5
-5.2
-5.7
-5.4
-6.3
-6.2
-6.5
-7.2
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
61
-------
Num
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
Esters
n-Butyl (2-t-butyl) propionate
n-Butyl (2,2-methyl-t-butyl) propionate
n-Butyl (2,2-diethyl) butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OCCCC
Propyl formate
Propyl acetate
Propyl propionate
Propyl chloroacetate
Propyl butyrate
Propyl pentate
Propyl hexanoate
Propyl iso-hexanoate
Propyl phenyl acetate
Propyl phenylpropionate
Propyl phenylbutyrate
Propyl isobutyrate
Propyl cyclohexyl-carboxylate
Propyl isopentate
Propyl cyclohexylacetate
Propyl (2-ethyl)propionate
Propyl (2,2-methyl-phenyl)acetate
Propyl (2,2-ethyl-phenyl)acetate
Propyl neopentate
Propyl (2,2-diphenyl)acetate
Propyl (2-ethyl)butyrate
Propyl (3-phenyl)2-propenoate
Propyl tri chloroacetate
Propyl benzoate
Propyl cyclobutyl-carboxylate
Propyl methoxyacetate
Propyl bromoacetate
Propyl thiolpropionate
Propyl iodoacetate
CCCCCCCCC(=O)OCCC
Propyl (4,4-dimethyl)pentate
Propyl phenoxy-acetate
Propyl cyclopentyl-carboxylate
Propyl difluoroacetate
Propyl methoxypropionate
Propyl chloropropionate
Propyl trifluoroacetate
Propyl cycloheptyl-carboxylate
Obs.
-7.4
-7.9
-7.8
-8
-2.8
-4
-4.1
-4.2
-4.4
-4.4
-4.4
-4.4
-4.4
-4.5
-4.5
-4.5
-4.8
-5
-5
-5.2
-5.2
-5.5
-5.6
-5.8
-6
-6
-6.1
-6.6
-4.1
-4.2
-4.3
-4.4
-4.4
-4.4
-4.4
-4.4
-4.5
-4.7
-4.8
-4.9
-5.2
-5.1
Calc.
-6.7
-7.2
-6.9
-8.4
-3.5
-4
-4.3
-4.6
-4.5
-4.5
-4.5
-4.5
-4.6
-4.6
-4.5
-4.7
-5.1
-4.7
-4.8
-5.2
-5.4
-5.9
-5.2
-6.5
-5.9
-5.7
-5.6
-6
-4.8
-4.7
-4.7
-4.7
-4.7
-4.6
-4.9
-4.7
-5
-4.9
-4.6
-4.5
-5.4
-5.1
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
62
-------
Num
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
Esters
Propyl dichloracetate
Propyl neopentate
Propyl (2-neopentyl)propionate
Propyl dibromoacetate
Propyl (2-propyl)pentate
Propyl tribromoacetate
Propyl (3,3-methyl-neopentyl)acetate
Propyl (3-neopentyl-4,4-dimethyl)pentate
Propyl (2-t-butyl)propionate
Propyl (2,2-methyl-t-butyl)propionate
Propyl (2,2-diethyl)butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OCCC
Methyl formate
Methyl acetate
Methyl propionate
Methyl chloroacetate
Methyl butyrate
Methyl pentate
Methyl hexanoate
Methyl iso-hexanoate
Methyl phenyl acetate
Methyl phenylpropionate
Methyl phenylbutyrate
Methyl isobutyrate
Methyl cyclohexyl-carboxylate
Methyl isopentate
Methyl cyclohexylacetate
Methyl (2-ethyl)propionate
Methyl (2,2-methyl-phenyl)acetate
Methyl (2,2-ethyl-phenyl)acetate
Methyl neopentate
Methyl (2,2-diphenyl)acetate
Methyl (2-ethyl)butyrate
Methyl (3-phenyl)2-propenoate
Methyl tri chloroacetate
Methyl benzoate
Methyl cyclobutyl-carboxylate
Methyl methoxyacetate
Methyl bromoacetate
Methyl thiolpropionate
Methyl iodoacetate
CCCCCCCCC(=O)OC
Obs.
-5.6
-5.8
-5.9
-5.9
-6.1
-6.5
-6.6
-7.2
-7.4
-7.9
-7.8
-8
-2.7
-4
-4
-4.2
-4.3
-4.3
-4.4
-4.3
-4.3
-4.4
-4.4
-4.4
-4.8
-4.9
-4.9
-5.1
-5.2
-5.5
-5.5
-5.7
-5.9
-5.9
-6
-6.5
-4
-4.2
-4.2
-4.3
-4.3
-4.3
Calc.
-5
-5.2
-5.7
-5.4
-6.3
-6.2
-6.5
-7.2
-6.6
-7.2
-6.9
-8.4
-3.5
-3.8
-4.1
-4.4
-4.3
-4.3
-4.4
-4.3
-4.4
-4.4
-4.3
-4.5
-4.9
-4.5
-4.6
-5
-5.2
-5.7
-5
-6.3
-5.7
-5.5
-5.4
-5.8
-4.6
-4.5
-4.5
-4.5
-4.5
-4.4
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
63
-------
Num
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
Esters
Methyl (4,4-dimethyl)pentate
Methyl phenoxy-acetate
Methyl cyclopentyl-carboxylate
Methyl difluoroacetate
Methyl methoxypropionate
Methyl chloropropionate
Methyl trifluoroacetate
Methyl cycloheptyl-carboxylate
Methyl dichloracetate
Methyl neopentate
Methyl (2-neopentyl)propionate
Methyl dibromoacetate
Methyl (2-propyl)pentate
Methyl tribromoacetate
Methyl (3,3-methyl-neopentyl)acetate
Methyl (3-neopentyl-4,4-dimethyl)pentate
Methyl (2-t-butyl)propionate
Methyl (2,2-methyl-t-butyl)propionate
Methyl (2,2-diethyl)butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OC
Chloroethyl formate
Chloroethyl acetate
Chloroethyl propionate
Chloroethyl chloroacetate
Chloroethyl butyrate
Chloroethyl pentate
Chloroethyl hexanoate
Chloroethyl iso-hexanoate
Chloroethyl phenyl acetate
Chloroethyl phenylpropionate
Chloroethyl phenylbutyrate
Chloroethyl isobutyrate
Chi oroethy 1 cy cl ohexy 1 -carb oxy 1 ate
Chloroethyl isopentate
Chloroethyl cyclohexylacetate
Chloroethyl (2-ethyl)propionate
Chloroethyl (2,2-methyl-phenyl)acetate
Chloroethyl (2,2-ethyl-phenyl)acetate
Chloroethyl neopentate
Chloroethyl (2,2-diphenyl)acetate
Chloroethyl (2-ethyl)butyrate
Chloroethyl (3-phenyl)2-propenoate
Obs.
-4.3
-4.3
-4.5
-4.6
-4.7
-4.9
-5.1
-5.1
-5.5
-5.7
-5.8
-5.8
-6.1
-6.4
-6.5
-7.1
-7.3
-7.9
-7.8
-8
-2.8
-4.1
-4.2
-4.3
-4.4
-4.5
-4.5
-4.4
-4.5
-4.5
-4.5
-4.6
-4.9
-5
-5.1
-5.2
-5.3
-5.6
-5.6
-5.8
-6.1
-6.1
Calc.
-4.7
-4.5
-5
-4.7
-4.4
-4.3
-5.2
-4.9
-4.8
-5
-5.5
-5.2
-6.1
-6
-6.3
-7
-6.4
-7
-6.7
-8.2
-3.6
-4.1
-4.5
-4.7
-4.6
-4.7
-4.7
-4.6
-4.7
-4.7
-4.6
-4.8
-5.3
-4.8
-4.9
-5.3
-5.5
-6
-5.4
-6.6
-6
-5.8
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
64
-------
Num
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
Esters
Chloroethyl trichloroacetate
Chloroethyl benzoate
Chi oroethy 1 cy cl obuty 1 -carb oxy 1 ate
Chloroethyl methoxyacetate
Chloroethyl bromoacetate
Chloroethyl thiolpropionate
Chloroethyl iodoacetate
Chloroethyl nonatae
Chloroethyl (4,4-dimethyl)pentate
Chloroethyl phenoxy-acetate
Chloroethyl cyclopentyl-carboxylate
Chloroethyl difluoroacetate
Chloroethyl methoxypropionate
Chloroethyl chloropropionate
Chloroethyl trifluoroacetate
Chi oroethy 1 cy cl ohepty 1 -carb oxy 1 ate
Chloroethyl dichloracetate
Chloroethyl neopentate
Chloroethyl (2-neopentyl)propionate
Chloroethyl dibromoacetate
Chloroethyl (2-propyl)pentate
Chloroethyl tribromoacetate
Chloroethyl (3,3-methyl-neopentyl) acetate
Chloroethyl (3-neopentyl-4,4-dimethyl) pentate
Chloroethyl (2-t-butyl)propionate
Chloroethyl (2,2-methyl-t-butyl)propionate
Chloroethyl (2,2-diethyl)butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OCCCl
Methoxymethyl formate
Methoxymethyl acetate
Methoxymethyl propionate
Methoxymethyl chloroacetate
Methoxymethyl butyrate
Methoxymethyl pentate
Methoxymethyl hexanoate
Methoxymethyl iso-hexanoate
Methoxymethyl phenylacetate
Methoxymethyl phenylpropionate
Methoxymethyl phenylbutyrate
Methoxymethyl isobutyrate
Methoxymethyl cyclohexyl-carboxylate
Methoxymethyl isopentate
Obs.
-6.1
-6.6
-4.1
-4.3
-4.3
-4.4
-4.4
-4.4
-4.4
-4.4
-4.6
-4.8
-4.8
-5
-5.2
-5.2
-5.6
-5.8
-5.9
-5.9
-6.2
-6.5
-6.7
-7.3
-7.4
-8
-7.9
-8.1
-3.2
-4.5
-4.5
-4.7
-4.8
-4.9
-4.9
-4.8
-4.8
-4.9
-4.9
-4.9
-5.3
-5.4
Calc.
-5.7
-6.1
-4.9
-4.8
-4.8
-4.8
-4.8
-4.7
-5.1
-4.8
-5.1
-5
-4.7
-4.7
-5.5
-5.3
-5.1
-5.4
-5.9
-5.5
-6.4
-6.3
-6.6
-7.3
-6.8
-7.3
-7
-8.6
-3.8
-4.3
-4.6
-4.9
-4.8
-4.8
-4.8
-4.8
-4.9
-4.9
-4.7
-5
-5.4
-4.9
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
65
-------
Num
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
Esters
Methoxymethyl cyclohexylacetate
Methoxymethyl (2-ethyl)propionate
Methoxymethyl (2,2-methyl-phenyl)acetate
Methoxymethyl (2,2-ethyl-phenyl)acetate
Methoxymethyl neopentate
Methoxymethyl (2,2-diphenyl)acetate
Methoxymethyl (2-ethyl)butyrate
Methoxymethyl (3 -phenyl)2-propenoate
Methoxymethyl trichloroacetate
Methoxymethyl benzoate
Methoxymethyl cyclobutyl-carboxylate *
Methoxymethyl methoxyacetate
Methoxymethyl bromoacetate
Methoxymethyl thiolpropionate
Methoxymethyl iodoacetate
CCCCCCCCC(=O)OCOC
Methoxymethyl (4,4-dimethyl)pentate
Methoxymethyl phenoxy-acetate
Methoxymethyl cyclopentyl-carboxylate
Methoxymethyl difluoroacetate
Methoxymethyl methoxypropionate
Methoxymethyl chloropropionate
Methoxymethyl trifluoroacetate
Methoxymethyl cycloheptyl-carboxylate
Methoxymethyl dichloracetate
Methoxymethyl neopentate
Methoxymethyl (2-neopentyl)propionate
Methoxymethyl dibromoacetate
Methoxymethyl (2-propyl)pentate
Methoxymethyl tribromoacetate
Methoxymethyl (3,3-methyl-neopentyl)acetate
CC(C)(C)CC(CC(C)(C)C)C(=O)OCOC
Methoxymethyl (2-t-butyl)propionate
Methoxymethyl (2,2-methyl-t-butyl)propionate
Methoxymethyl (2,2-diethyl)butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OCOC
Chloromethyl formate
Chloromethyl acetate
Chloromethyl propionate
Chloromethyl chloroacetate
Chloromethyl butyrate
Chloromethyl pentate
Obs.
-5.4
-5.6
-5.7
-6
-6
-6.2
-6.4
-6.5
-6.5
-7
-4.5
-4.7
-4.7
-4.8
-4.8
-4.8
-4.8
-4.8
-5
-5.1
-5.2
-5.4
-5.6
-5.6
-6
-6.2
-6.3
-6.3
-6.6
-6.9
-7
-7.7
-7.8
-8.4
-8.3
-8.4
-3.2
-4.4
-4.5
-4.6
-4.8
-4.8
Calc.
-5.1
-5.5
-5.7
-6.2
-5.5
-6.8
-6.2
-6
-5.9
-6.3
-5.1
-5
-5
-4.9
-5
-4.9
-5.2
-5
-5.3
-5.2
-4.9
-4.8
-5.7
-5.4
-5.3
-5.5
-6
-5.7
-6.6
-6.4
-6.8
-7.5
-6.9
-7.5
-7.2
-8.9
-4
-4.4
-4.8
-5.1
-4.9
-5
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
-------
Num
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
Esters
Chloromethyl hexanoate
Chloromethyl iso-hexanoate
Chloromethyl phenylacetate
Chloromethyl phenylpropionate
Chloromethyl phenylbutyrate
Chloromethyl isobutyrate
Chloromethyl cyclohexyl-carboxylate
Chloromethyl isopentate
Chloromethyl cyclohexylacetate
Chloromethyl (2-ethyl)propionate
Chloromethyl (2,2-methyl-phenyl)acetate
Chloromethyl (2,2-ethyl-phenyl)acetate
Chloromethyl neopentate
Chloromethyl (2,2-diphenyl)acetate
Chloromethyl (2-ethyl)butyrate
Chloromethyl (3-phenyl)2-propenoate
Chloromethyl trichloroacetate
Chloromethyl benzoate
Chloromethyl cyclobutyl-carboxylate*
Chloromethyl methoxyacetate
Chloromethyl bromoacetate
Chloromethyl thiolpropionate
Chloromethyl iodoacetate
Chloromethyl nonatae
Chloromethyl (4,4-dimethyl) pentate
Chloromethyl phenoxy-acetate
Chloromethyl cyclopentyl-carboxylate
Chloromethyl difluoroacetate
Chloromethyl methoxypropionate
Chloromethyl chloropropionate
Chloromethyl trifluoroacetate
Chloromethyl cycloheptyl-carboxylate
Chloromethyl dichloracetate
Chloromethyl neopentate
Chloromethyl (2-neopentyl)propionate
Chloromethyl dibromoacetate
Chloromethyl (2-propyl)pentate
Chloromethyl tribromoacetate
Chloromethyl (3,3-methyl-neopentyl)acetate
Chloromethyl (3-neopentyl-4,4-dimethyl)pentate
Chloromethyl (2-t-butyl)propionate
Chloromethyl (2,2-methyl-t-butyl)propionate
Obs.
-4.8
-4.8
-4.8
-4.9
-4.9
-4.9
-5.2
-5.4
-5.4
-5.6
-5.6
-5.9
-6
-6.2
-6.4
-6.4
-6.5
-7
-4.5
-4.6
-4.7
-4.8
-4.8
-4.8
-4.8
-4.8
-5
-5.1
-5.2
-5.3
-5.6
-5.6
-6
-6.2
-6.3
-6.3
-6.6
-6.9
-7
-7.6
-7.8
-8.4
Calc.
-5
-4.9
-5.1
-5.1
-4.9
-5.2
-5.6
-5.1
-5.3
-5.6
-5.8
-6.4
-5.7
-6.9
-6.4
-6.2
-6
-6.4
-5.2
-5.1
-5.1
-5.1
-5.2
-5
-5.4
-5.1
-5.5
-5.3
-5
-5
-5.9
-5.6
-5.5
-5.7
-6.2
-5.9
-6.8
-6.6
-7
-7.6
-7.1
-7.6
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref.
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
[27, 71]
67
-------
Num
377
378
379
380
381
382
383
Esters
Chloromethyl (2,2-diethyl)butyrate
(methyl) (neopentyl) (t-butyl)CC(=O)OCCl
p-Nitrophenyl acetate
p-Nitrophenyl propionate
p-Nitrophenyl butyrate
p-Nitrophenyl isobutyrate
p-Nitrophenyl 3 ,3 -dimethylbutyrate
Obs.
-8.3
-8.4
-3.9
-3.9
-4.1
-4.1
-4.8
Calc.
-7.3
-8.9
-3.9
-4.3
-4.4
-4.6
-5.4
Temp.
25
25
30
30
30
30
30
Ref.
[27, 71]
[27, 71]
[72]
[72]
[72]
[72]
[72]
-------
Table 9. SPARC-calculated vs. observed log acid-catalyzed hydrolysis rate constants
for carboxylic acid esters in water-acetone mixtures as a function of temperature in M'V
-i.-i
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Ethyl m-nitrobenzoate
Ethyl benzoate
Ethyl dichloroacetate
Ethyl iso-butyrate
Ethyl chloroacetate
Methyl acetate
Ethyl phenyl acetate
Ethyl phenylpropionate
Ethyl phenylbutyrate
Ethyl phenylpentate
Ethyl phenylisopropionate
Ethyl (2-ethyl)phenylacetate
Ethyl (2,2-diphenyl)acetate
Ethyl cyclohexylacetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl propionate
Chloromethyl butyrate
Ethyl acetate
Ethyl propionate
Ethyl butyrate
Ethyl pentate
Ethyl hexanoate
Ethyl heptanoate
Ethyl octanoate
Ethyl isobutyrate
Ethyl isopentate
Ethyl hexanoate
Ethyl sec-hexanoate
Ethyl neopentate
Ethyl (2-ethyl)butyrate
Ethyl fluoroacetate
Ethyl fluoroacetate
Ethyl fluoroacetate
Ethyl difluoroacetate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Obs
-7
-6.9
-4.9
-4.7
-4.4
-4.3
-4.8
-4.9
-4.9
-4.8
-6.6
-6.9
-7.3
-5.3
-4.5
-4.6
-4.7
-4.7
-5
-4.3
-4.4
-4.7
-4.7
-4.8
-4.8
-4.8
-4.9
-5.2
-4.8
-5.4
-5.9
-5.9
-4.6
-4.1
-3.6
-4
-5.7
-4.9
-4.2
-3.6
Calc
-6.4
-6.3
-5.2
-4.9
-4.7
-3.7
-5
-4.9
-4.6
-4.7
-6.3
-7.1
-8
-5.2
-4.4
-4.4
-4.4
-4.9
-5.1
-3.8
-4.4
-4.7
-4.8
-4.8
-4.8
-4.8
-5
-4.9
-4.7
-6
-5.9
-6.8
-4.7
-4.3
-3.8
-5
-5.3
-4.7
-4.2
-3.6
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
35
50
25
60
80.2
99.2
119.9
Solvent
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
60% acetone
60% acetone
60% acetone
60% acetone
Ref.
[73]
[73]
[73]
[73]
[73]
[73]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[75]
[75]
[75]
[75]
69
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
Esters
Ethyl p-methoxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl butyrate
Ethyl butyrate
Ethyl butyrate
Ethyl butyrate
Ethyl pentate
Ethyl pentate
Obs.
-3
-5
-4.3
-3.7
-3.2
-4.8
-4.1
-3.5
-3
-4.7
-4
-3.4
-2.9
-4.7
-4.1
-3.4
-2.9
-5.5
-4.7
-4.1
-3.5
-3
-5.3
-4.6
-4
-3.4
-2.8
-5.4
-4.7
-4.1
-3.4
-2.9
-5.8
-5.2
-4.5
-4
-4.9
-4.5
-4.2
-3.8
-4.9
-4.6
Calc.
-3.2
-4.7
-4.1
-3.6
-3.2
-4.5
-4
-3.5
-3
-4.4
-3.9
-3.4
-2.9
-4.5
-3.9
-3.4
O
-5.1
-4.5
-4
-3.5
-3
-5
-4.3
-3.8
-3.3
-2.9
-5.1
-4.4
-3.9
-3.4
-3
-5.2
-4.6
-4.1
-3.7
-4.9
-4.5
-4.1
-3.8
-4.9
-4.6
Temp
138.5
80.2
99.8
120.2
138.9
80.3
100.05
120.5
138.9
80.3
100.2
120.9
139.3
80.3
99.85
120.2
139.4
60.05
80.2
100.15
120.2
139.2
60
80.2
99.4
120
138.5
60
80.2
99.9
120.4
139
80.3
99.85
120.7
139.2
20
30
40
50
20
30
Solvent
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
Ref.
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[74]
[74]
[74]
[74]
[74]
[74]
70
-------
Num
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
Esters
Ethyl pentate
Ethyl pentate
Ethyl isobutyrate
Ethyl isobutyrate
Ethyl isobutyrate
Ethyl isobutyrate
Ethyl sec-hexanoate
Ethyl sec-hexanoate
Ethyl sec-hexanoate
Ethyl sec-hexanoate
Ethyl iso-hexanoate
Ethyl iso-hexanoate
Ethyl iso-hexanoate
Ethyl iso-hexanoate
Ethyl cyclohexyl-carboxylate
Ethyl cyclohexyl-carboxylate
Ethyl cyclohexyl-carboxylate
Ethyl cyclohexyl-carboxylate
Ethyl acetate
Ethyl propionate
Ethyl butyrate
Ethyl pentate
Ethyl hexanoate
Ethyl isobutyrate
Ethyl isopentate
Ethyl t-butyrate
Ethyl phenyl acetate
Ethyl acetate
Ethyl propionate
Ethyl butyrate
Ethyl pentate
Ethyl hexanoate
Ethyl isobutyrate
Ethyl isopentate
Ethyl t-butyrate
Ethyl phenyl acetate
Ethyl phenyl acetate
Ethyl phenylpropionate
Ethyl phenylbutyrate
Ethyl phenylpentate
Ethyl phenylisopropionate
Ethyl 2-ethyl-2-phenylacetate
Obs.
-4.2
-3.8
-5.1
-4.7
-4.3
-3.9
-5.6
-5.2
-4.8
-4.4
-5
-4.6
-4.2
-3.8
-5.3
-4.9
-4.6
-4.2
-3.6
-3.7
-4
-4
-4
-4.1
-4.5
-4.9
-4
-4
-4
-4.3
-4.3
-4.4
-4.5
-4.8
-5.4
-4.1
-5
-5.1
-5.1
-5.1
-6.8
-7.2
Calc.
-4.2
-3.9
-5.2
-4.8
-4.5
-4.1
-6.2
-5.8
-5.5
-5.1
-4.9
-4.5
-4.2
-3.8
-5.7
-5.4
-5
-4.7
-3.2
-3.7
-4
-4.1
-4.1
-4.3
-4.3
-5.1
-4.4
-3.5
-4.1
-4.3
-4.4
-4.4
-4.6
-4.6
-5.5
-4.7
-5.2
-5.1
-4.8
-4.9
-6.5
-7.3
Temp
40
50
20
30
40
50
20
30
40
50
20
30
40
50
20
30
40
50
44.7
44.7
44.7
44.7
44.7
44.7
44.7
44.7
44.7
35
35
35
35
35
35
35
35
35
20
20
20
20
20
20
Solvent
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
Ref.
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
71
-------
Num
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
Esters
Ethyl 2,2-diphenylacetate
Ethyl cyclohexylacetate
Ethyl phenyl acetate
Ethyl phenylpropionate
Ethyl phenylbutyrate
Ethyl phenylpentate
Ethyl phenylisopropionate
Ethyl 2-ethyl-2-phenylacetate
Ethyl 2,2-diphenylacetate
Ethyl cyclohexylacetate
Ethyl phenyl acetate
Ethyl phenylpropionate
Ethyl phenylbutyrate
Ethyl phenylpentate
Ethyl phenylisopropionate
Ethyl 2-ethyl-2-phenylacetate
Ethyl 2,2-diphenylacetate
Ethyl cyclohexylacetate
Ethyl phenyl acetate
Ethyl phenylpropionate
Ethyl phenylbutyrate
Ethyl phenylpentate
Ethyl phenylisopropionate
Ethyl 2-ethyl-2-phenylacetate
Ethyl 2,2-diphenylacetate
Ethyl cyclohexyl-acetate
Benzyl acetate
Benzyl acetate
Benzyl acetate
Benzyl acetate
Benzyl acetate
m-Methylbenzyl acetate
m-Methylbenzyl acetate
m-Methylbenzyl acetate
m-Methylbenzyl acetate
m-Methylbenzyl acetate
p-Methylbenzyl acetate
p-Methylbenzyl acetate
p-Methylbenzyl acetate
p-Methylbenzyl acetate
m-Nitrobenzyl acetate
m-Nitrobenzyl acetate
Obs.
-7.5
-5.5
-4.6
-4.7
-4.7
-4.6
-6.3
-6.7
-7.1
-5.1
-4.3
-4.3
-4.3
-4.3
-6
-6.4
-6.7
-4.7
-4.2
-3.9
-4
-3.9
-5.6
-6
-6.3
-4.3
-4.9
-4.5
-3.9
-3.2
-2.6
-5
-4.5
-4
-3.3
-2.7
-4.5
-3.9
-3.2
-2.6
-5
-4.6
Calc.
-8.2
-5.4
-4.8
-4.8
-4.5
-4.5
-6.1
-6.9
-7.8
-5
-4.5
-4.4
-4.1
-4.1
-5.7
-6.6
-7.5
-4.7
-4.2
-4.1
-3.8
-3.8
-5.4
-6.2
-7.1
-4.3
-4.4
-4
-3.5
-2.9
-2.3
-4.4
-4
-3.5
-2.9
-2.3
-4
-3.5
-2.9
-2.4
-4.4
-4
Temp
20
20
30
30
30
30
30
30
30
30
40
40
40
40
40
40
40
40
50
50
50
50
50
50
50
50
15
25
40
60
80
15
25
40
60
80
25
40
60
80
15
25
Solvent
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
Ref.
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[74]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
-------
Num
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
Esters
m-Nitrobenzyl acetate
m-Nitrobenzyl acetate
m-Nitrobenzyl acetate
p-Nitrobenzyl acetate
p-Nitrobenzyl acetate
p-Nitrobenzyl acetate
p-Nitrobenzyl acetate
p-Nitrobenzyl acetate
Phenyl acetate
Phenyl acetate
Phenyl acetate
Phenyl acetate
Phenyl acetate
m-Methylphenyl acetate
m-Methylphenyl acetate
m-Methylphenyl acetate
m-Methylphenyl acetate
m-Methylphenyl acetate
p-Methylphenyl acetate
p-Methylphenyl acetate
p-Methylphenyl acetate
p-Methylphenyl acetate
m-Nitrophenyl acetate
m-Nitrophenyl acetate
m-Nitrophenyl acetate
m-Nitrophenyl acetate
m-Nitrophenyl acetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Obs.
-4
-3.3
-2.7
-5
-4.6
-4
-3.3
-2.7
-5
-4.6
-3.9
-3.2
-2.6
-5
-4.6
-4
-3.2
-2.6
-4.5
-3.9
-3.2
-2.5
-5.2
-4.7
-4.1
-3.4
-2.8
-4.7
-4.8
-4.9
-5.1
-5.3
-4.3
-4.4
-4.6
-4.7
-4.9
-4.1
-4.2
-4.3
-4.2
-4.6
Calc.
-3.5
-2.9
-2.4
-4.4
-4
-3.5
-2.9
-2.4
-4.6
-4.3
-3.8
-3.1
-2.6
-4.7
-4.3
-3.8
-3.2
-2.6
-4.3
-3.8
-3.2
-2.6
-4.8
-4.4
-3.9
-3.2
-2.7
-5.2
-5.2
-5.3
-5.4
-5.6
-4.8
-4.9
-4.9
-5
-5.2
-4.6
-4.7
-4.7
-4.8
-5
Temp
40
60
80
15
25
40
60
80
15
25
40
60
80
15
25
40
60
80
25
40
60
80
15
25
40
60
80
35
35
35
35
35
45
45
45
45
45
55
55
55
55
55
Solvent
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
60% acetone
35% acetone
44% acetone
51.5% acetone
62% acetone
82.5% acetone
35% acetone
42.5% acetone
52% acetone
62% acetone
82% acetone
35% acetone
42.5% acetone
52% acetone
62% acetone
81.5% acetone
Ref.
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[76]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
73
-------
Table 10. SPARC-calculated vs. observed log acid-catalyzed hydrolysis rate constants
for carboxylic acid esters in water-methanol mixtures as a function of temperature in M'V
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Ester
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Methyl benzoate
Methyl o-methylbenzoate
Methyl o-ethylbenzoate
Methyl o-fluorobenzoate
Methyl o-chlorobenzoate
Methyl o-bromobenzoate
Methyl o-iodobenzoate
Methyl m-methylbenzoate
Methyl m-chlorobenzoate
Methyl m-nitrobenzoate
Obs
-4
-3.4
-3
-2.6
-3.8
-3.3
-2.8
-2.5
-3.8
-3.2
-2.8
-2.5
-3.7
-4.4
-4.7
-3.7
-4.2
-4.3
-4.6
-3.8
-3.8
-3.9
Calc
-4.2
-3.6
-3.2
-2.9
-3.9
-3.4
-3
-2.6
-3.8
-3.3
-2.9
-2.6
-3.9
-4.5
-4.6
-4.4
-4.5
-4.6
-4.7
-3.9
-3.9
-3.9
Temp.
99.85
120.45
138.5
153.9
100.2
121.2
139.2
153.9
100.12
120.75
138.4
153
100.8
100.8
100.8
100.8
100.8
100.8
100.8
100.8
100.8
100.8
Solvent
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
60% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
80% methanol
Ref.
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
[63]
74
-------
Table 11. SPARC-calculated vs. observed log acid-catalyzed hydrolysis rate constants
for carboxylic acid esters in water-ethanol mixtures as a function of temperature in M'V
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
Esters
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-methoxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-hydroxybenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl p-methylbenzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl benzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-bromobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl p-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl m-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Ethyl o-nitrobenzoate
Obs
-5.7
-4.8
-4.2
-3.6
-3.1
-5
-4.4
-3.7
-3.2
-5.5
-4.8
-4.1
-3.5
-3
-5.4
-4.7
-4.1
-3.5
-2.9
-4.7
-4.1
-3.5
-3.1
-4.7
-4.1
-3.5
-3
-4.5
-4
-3.5
-3
-4.7
-4.1
-3.5
-3
-5.8
-5.2
-4.6
-4.1
Calc
-5.5
-4.8
-4.3
-3.7
-3.3
-4.8
-4.3
-3.7
-3.3
-5.3
-4.7
-4.1
-3.6
-3.1
-5.2
-4.5
-4
-3.5
-3.1
-4.6
-4.1
-3.5
-3.1
-4.6
-4.1
-3.6
-3.1
-4.5
-3.9
-3.4
-3
-4.6
-4
-3.5
-3.1
-5.3
-4.7
-4.2
-3.8
Temp
60
80.2
99.4
119.9
138.1
80.2
99.5
120
138.5
60.05
80.25
99.9
120.3
139.7
60
80.2
99.6
120.2
138.6
80.3
100
120.6
139.3
80.2
100
120.2
139.4
80.2
98.9
119.3
138
80.2
99.45
119.9
138.3
80.3
100
120.6
138.9
Solvent
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
60% ethanol
Ref
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
[75]
75
-------
Table 12. SPARC-calculated vs. observed log acid-catalyzed hydrolysis rate constants
for carboxylic acid esters in water-dioxane mixtures as a function of temperature in M'l s"1
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
Esters
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Chloromethyl acetate
Methyl benzoate
Methyl o-methylbenzoate
Methyl o-ethylbenzoate
Obs
-4.4
-4
-3.6
-4.5
-4.1
-3.7
-4.7
-4.3
-3.9
-4.9
-4.5
-4.1
-3.8
-4.4
-4.7
Calc
-4.4
-4.1
-3.7
-4.5
-4.1
-3.8
-4.6
-4.2
-3.9
-4.8
-4.5
-4.1
-4.1
-4.8
-5
Temp
25
35
45
25
35
45
25
35
45
25
35
45
100
100
100
Solvent
10% dioxane
10% dioxane
10% dioxane
25% dioxane
25% dioxane
25% dioxane
50% dioxane
50% dioxane
50% dioxane
75% dioxane
75% dioxane
75% dioxane
60% dioxane
60% dioxane
60% dioxane
Ref.
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[78]
[79]
[79]
[79]
76
-------
Table 13. SPARC-calculated vs. observed log neutral hydrolysis rate constants
for carboxylic acid esters in water as a function of temperature using different catalysts in M'V
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Ethyl acetate
Vinyl acetate
Chloromethyl formate
Methyl chloroacetate
Methyl dichloroacetate
Ethyl dichloroacetate
Chloroethyl dichloroacetate
Methoxyethyl dichloroacetate
Methyl trichloroacetate
Methoxyethyl trichloroacetate
Ethyl difluoroacetate
Methyl trifluoroacetate
Ethyl trifluoroacetate
Isopropyl trifluoroacetate
t-Butyl trifluoroacetate
Chloromethyl chloroacetate
Phenyl acetate
p-Methylphenyl acetate
p-Chlorophenyl acetate
p-Nitrophenyl acetate
3,4-Dinitrophenyl acetate
2,4-Dinitrophenyl acetate
2,6-Dinitrophenyl acetate
p-Nitrophenyl chloroacetate
Phenyl dichloroacetate
Ethyl trifluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl dichloroacetate
Ethyl chloroacetate
Ethyl chloroacetate
Ethyl trichloroacetate
p-Nitrophenyl chloroacetate
Obs
-11.3
-8.7
-5.8
-8.4
-6.6
-7
-6.2
-6.7
-4.8
-5
-6
-4.2
-4.3
-4.2
-4.6
-5.7
-9
-9.1
-8.9
-7.8
-7.1
-6.7
-6.6
-5.2
-4.5
-4.6
-3.8
-3.2
-2
-4.5
-4.8
-3.7
-3.5
-4.3
-3.6
-2.9
-6.1
-4.4
-2.8
-1.9
Calc
-12.1
-9
-6.5
-8.5
-6.9
-7
-6.4
-6.7
-5.5
-5.3
-5.9
-4.1
-4.2
-4.2
-4.4
-5.6
-9.1
-9.4
-8.9
-8.2
-7.5
-6.5
-5.8
-4.7
-4
-4.4
-3.5
-3
-2
-4.5
-4.6
-3.9
-3.5
-4.1
-3.7
-3.1
-5.7
-4.7
-2.3
-1.6
Catalyst
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
aniline
acetate
imidazole
formate
aniline
pyridine
picoline4
acetate
succinate
imidazole
acetate
imidazole
aniline
pyridine
Temp
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
10
25
25
25
25
25
25
25
25
25
25
25
25
25
25
Ref
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[49]
[49]
[49]
[49]
[49]
[53]
[53]
[49]
[49]
[49]
[49]
[80]
[49]
[80]
[80]
[49]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[80]
[80]
77
-------
Num
41
43
44
45
46
47
48
49
50
51
Esters
p-Nitrophenyl chloroacetate
2,6-dinitrophenyl acetate
2,4-dinitrophenyl acetate
2,3-dinitrophenyl acetate
3,4-dinitrophenyl acetate
p-Nitrophenyl acetate
o-Nitrophenyl acetate
m-Nitrophenyl acetate
p-Chlorophenyl acetate
p-Methylphenyl acetate
Obs
0.2
-2.9
-3.3
-3.6
-4
-5.2
-5.3
-5.5
-6
-6.6
Calc
-0.1
-2.9
-3.6
-3.8
-4.6
-5.3
-4.5
-5.4
-6.1
-6.6
Catalyst
imidazole
acetate
acetate
acetate
acetate
acetate
acetate
acetate
acetate
acetate
Temp
25
25
25
25
25
25
25
25
25
25
Ref
[80]
[82]
[82]
[82]
[82]
[82]
[82]
[82]
[82]
[82]
78
-------
Table 14. SPARC-calculated vs. observed log neutral hydrolysis rate constants for carboxylic acid
esters in water-acetone mixtures as a function of temperature using different catalysts in M'V
Num
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Chloromethyl chloroacetate
Chloromethyl di chloroacetate
Methyl trifluoroacetate
Ethyl trifluoroacetate
Propyl trifluoroacetate
Butyl trifluoroacetate
Pentyl trifluoroacetate
Hexyl trifluoroacetate
Isopropyl trifluoroacetate
sec-Butyl trifluoroacetate
sec-Pentyl trifluoroacetate
sec-Hexyl trifluoroacetate
Phenyl trifluoroacetate
m-Methyl trifluoroacetate
p-Methyl trifluoroacetate
o-Methyl trifluoroacetate
Ethyl pentafluoroacetate
Ethyl heptafluoropropionate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Chloromethyl di chloroacetate
Ethyl trifluoroacetate
Isopropyl trifluoroacetate
Isopropyl trifluoroacetate
sec-Butyl trifluoroacetate
sec-Butyl trifluoroacetate
sec-Pentyl trifluoroacetate
sec-Pentyl trifluoroacetate
sec-Hexyl trifluoroacetate
sec-Hexyl trifluoroacetate
Phenyl trifluoroacetate
Phenyl trifluoroacetate
m-Methylphenyl trifluoroacetate
m-Methylphenyl trifluoroacetate
p-Methylphenyl trifluoroacetate
p-Methylphenyl trifluoroacetate
Obs
-7.2
-5.3
-5.6
-6.1
-6.3
-6.4
-6.4
-6.5
-7
-7.2
-7.3
-7.3
-3.5
-3.7
-3.8
-4.1
-7.3
-7.6
-6.3
-6.1
-5.9
-5.7
-5.5
-5
-4.8
-4.6
-6.7
-6.5
-6.9
-6.7
-7.1
-6.9
-7.1
-6.8
o o
-J.J
-3.2
-3.6
-3.4
-3.7
-3.5
Calc
-7
-5.4
-6.4
-6.5
-6.5
-6.5
-6.5
-6.5
-6.6
-6.8
-6.9
-7
-3.6
-3.7
-3.9
-3.7
-8
-8.3
-6
-5.9
-5.8
-5.7
-5.5
-5.3
-5.1
-4.4
-6.4
-6.2
-6.6
-6.5
-6.7
-6.5
-6.8
-6.6
-3.5
-3.4
-3.6
-3.6
-3.8
-3.7
Catalysts
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
Water
Water
Water
Water
Water
Water
Water
water
water
water
water
water
water
water
water
Temp.
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
-6.23
0
5
12
18
35
45
10
35
45
35
45
35
45
35
45
35
45
35
45
35
45
Solvent
50% acetone
50% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
50% acetone
50% acetone
50% acetone
50% acetone
50% acetone
50% acetone
50% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
Ref.
[53]
[80]
[83]
[83]
[83]
[83]
[83]
[83]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[65]
[83]
[83]
[80]
[80]
[80]
[80]
[80]
[80]
[80]
[83]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
79
-------
Num
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
Esters
o-Methylphenyl trifluoroacetate
o-Methylphenyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Ethyl trifluoroacetate
Ethyl trifluoroacetate
Propyl trifluoroacetate
Propyl trifluoroacetate
Butyl trifluoroacetate
Butyl trifluoroacetate
Pentyl trifluoroacetate
Pentyl trifluoroacetate
Hexyl trifluoroacetate
Hexyl trifluoroacetate
Ethyl pentafluoroacetate
Ethyl pentafluoroacetate
Ethyl heptafluoroacetate
Ethyl heptafluoroacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Ethyl dibromoacetate
Obs
-3.9
-3.7
-5.4
-5.3
-6
-5.8
-6.1
-5.9
-6.2
-6
-6.3
-6
-6.3
-6.1
-7.1
-6.8
-7.4
-7.1
-8.4
-8.8
-9.1
-10.5
-9.6
-8.2
-8.6
-8.9
-9.2
-10.2
-8.1
-8.4
-8.7
-9.1
-10
Calc
-3.7
-3.6
-6.2
-6
-6.3
-6.1
-6.3
-6.1
-6.3
-6.1
-6.3
-6.1
-6.3
-6.1
-7.8
-7.6
-8.1
-7.9
-8
-8.3
-8.7
-10
-9.1
-7.8
-8.1
-8.4
-8.8
-9.7
-7.7
-7.9
-8.3
-8.6
-9.5
Catalysts
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
Temp.
35
45
35
45
35
45
35
45
35
45
35
45
35
45
35
45
35
45
35
35
35
35
35
45
45
45
45
45
51
51
51
51
51
Solvent
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
70% acetone
36% acetone
44% acetone
53% acetone
83% acetone
63% acetone
36% acetone
44% acetone
53% acetone
63% acetone
83% acetone
36% acetone
44% acetone
53% acetone
63% acetone
83% acetone
Ref.
[84]
[84]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[83]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
[77]
80
-------
Table 15. SPARC-calculated vs. observed log neutral hydrolysis rate constants for carboxylic
acid esters in water-ethanol mixtures using different catalysts in M'V
No
1
2
O
4
5
6
7
8
9
Esters
Ethyl trichloroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl difluoroacetate
Ethyl trichloroacetate
Obs
-6.3
-5.8
-5.9
-6
-6.3
-6.4
-6.8
-7.1
-3.7
Calc
-6.3
-5.9
-6
-6.1
-6.2
-6.4
-6.8
-7.1
-3.4
Catalysts
water
water
water
water
water
water
water
water
acetate
Temp.
25
25
25
25
25
25
25
25
25
Solvent
40% ethanol
3% ethanol
7 % ethanol
12% ethanol
22% ethanol
32% ethanol
52% ethanol
72% ethanol
40% ethanol
Ref.
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
[81]
81
-------
Table 16. SPARC-calculated vs. observed log neutral hydrolysis rate constants for carboxylic acid
esters in water-dioxane mixtures as a function of temperature using different catalysts in M'V1
No
1
2
O
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Esters
Methyl trichloroacetate
Trichloroethyl dichloroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Ethyl trichloroacetate
Propyl trichloroacetate
Butyl trichloroacetate
Isopropyl trichloroacetate
Chloroethyl trichloroacetate
Methoxyethyl trichloroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Methyl trifluoroacetate
Obs
-6.3
-6.3
-5.3
-5.7
-7
-7.2
-7.2
-7.8
-6.1
-6.6
-5.3
-5.7
-6.5
-5.4
-6
-5.1
-4.9
Calc
-7.7
-6.6
-5.5
-5.8
-6.7
-6.7
-6.8
-6.9
-6.2
-6.4
-5.5
-5.8
-6.2
-5.4
-5.9
-5.3
-5.2
Catalysts
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
water
Temp.
25
25
25
10
25
25
25
25
25
25
25
25
0
44.6
0
34.8
44.6
Solv
50% dioxane
50% dioxane
60% dioxane
70% dioxane
50% dioxane
50% dioxane
50% dioxane
50% dioxane
50% dioxane
50% dioxane
60% dioxane
70% dioxane
70% dioxane
70% dioxane
60% dioxane
60% dioxane
60% dioxane
Ref.
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[53]
[85]
[85]
[85]
[85]
[85]
82
-------
Table 17. SPARC-calculated vs. observed log hydrolysis rate constants for organophosphorus in
water in basic media in M'V1
No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
Ester
Methyl-o-isopropylphosphonofluoridate
Phosphonofluoridic acid, methyl-, methyl ester
Phosphonofluoridic acid, methyl-, 3,3-dimethylbutyl ester
Phosphonofluoridic acid, (1-methylethyl)-, 1-methylethyl ester
Phosphonofluoridic acid, methyl-, ethyl ester
Phosphonofluoridic acid, methyl-, 2-bromoethyl ester
Phosphonofluoridic acid, methyl-, propyl ester
Phosphonofluoridic acid, ethyl-, 1-methylethyl ester
Diethyl ethylphosphonate
Phosphoric acid, diethyl 4-nitrophenyl ester
Phosphoric acid, trimethyl ester
Obs
1.35
1.412
1.56
1.627
2.025
2.274
1.693
1.979
0.307
0.525
1.783
2.049
2.21
2.479
1.732
1.979
0.971
1.225
-4.691
-4.36
-4.065
-3.05
-2.941
-2.675
-2.51
-1.96
-1.787
-1.574
-1.336
-3.951
-3.603
-3.162
-2.952
-2.798
-2.706
Calc
1.018
1.146
1.271
1.393
2.501
2.722
1.574
1.807
0.731
0.959
1.84
2.076
1.98
2.21
1.791
2.026
0.949
1.187
-4.59
-4.29
-4.01
-3.5
-3.39
-3.13
-2.97
-2.01
-1.91
-1.79
-1.64
-3.64
-3.37
-2.97
-2.83
-2.74
-2.65
Temp
20
25
30
35
25
35
25
35
25
35
25
35
25
35
25
35
25
35
30
40
50
69.5
73.9
84.7
91.3
25
30
37
45
35
44.7
60
65.5
69.3
73
Ref.
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[87]
[87]
[87]
[87]
[45]
[45]
[45]
[45]
[45]
[45]
83
-------
No
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
Ester
Diethyl methylphosphonate
Phosphonic acid, methyl-, dimethyl ester
Phosphoric acid, ethyl bis(4-nitrophenyl) ester
Phosphoric acid, dimethyl 4-nitrophenyl ester
Phosphoric acid, di ethyl 6-methyl-2-(l-methylethyl)-4-
pyrimidinyl ester
Phosphoric acid, 4-nitrophenyl dipropyl ester
Phosphinic acid, dibutyl-, 4-nitrophenyl ester
Diisopropyl methylphosphonate
Phosphonic acid, phenyl-, diethyl ester
Obs
-3.796
-3.483
-3.194
-2.886
-2.717
-2.484
-2.249
-2.136
-1.906
-1.65
-1.363
-1.446
-1.706
-1.409
-1.244
-1.039
-0.845
-1.45
-1.12
-0.607
0.039
-2.526
-2.342
-2.176
-1.911
-0.119
0
0.149
-4.116
-3.941
-2.651
-2.499
-2.298
-2.201
-2.038
-1.99
Calc
-4.31
-4.01
-3.72
-3.44
-3.18
-2.92
-2.68
-2.99
-2.71
-2.46
-2.21
-1.75
-1.99
-1.78
-1.69
-1.55
-1.41
-1.55
-1.38
-1.05
-0.75
-2.08
-1.99
-1.86
-1.72
-0.56
-0.49
-0.43
-3.71
-3.47
-2.58
-2.46
-2.29
-2.21
-2.11
-2.03
Temp
30
40
50
60
70
80
90
49.8
60
70
79.8
25
15
25
30
37
45
10
20
40
60
25
30
37
45
15
20
25
80
90
59.8
65.7
74.9
79.4
84.8
89.1
Ref.
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[88]
[88]
[88]
[88]
[88]
[89]
[89]
[89]
[89]
[88]
[88]
[88]
[88]
[90]
[90]
[90]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
[45]
84
-------
Num
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
Ester
Phosphonic acid, propyl-, dipropyl ester
Phosphoric acid, dibutyl 4-nitrophenyl ester
Phosphonic acid, butyl-, diethyl ester
O,O-Diethyl-O-phenylphosphate
Phosphoric acid, diethyl 4-(methylthio) phenyl ester
Phosphonic acid, (chloromethyl)-, diethyl ester
Bis(l-methylethyl)phosphoric acid 4-nitrophenyl ester
Phosphonic acid, methyl-, 1 -methyl ethyl 4-nitrophenyl ester
Phosphonic acid, methyl-, ethyl 4-nitrophenyl ester
Phosphoric acid, diethyl 2-nitrophenyl ester
Phosphoric acid, diethyl 3-nitrophenyl ester
Phosphinic acid, diethyl-, ethyl ester
Phosphoric acid, 4-chlorophenyl diethyl ester
Phosphoric acid, diethyl 4-methoxyphenyl ester
Phosphoric acid, 4-cyanophenyl diethyl ester
Phosphoric acid, bis(2-methylpropyl) 4-nitrophenyl ester
Obs
-3.747
-2.559
-2.342
-2.156
-1.933
-3.434
-3.233
-3.018
-2.735
-3.51
-3.306
-2.901
-2.604
-2.313
-3.177
-2.978
-2.767
-2.505
-0.714
-0.577
-0.367
-0.164
-2.222
-1.741
-1.398
-1.654
-2.195
O
-2.824
-2.67
-2.535
-2.939
-3.553
-2.196
-2.204
-2.036
-1.825
Calc
-3.15
-2.11
-2.02
-1.89
-1.75
-3.34
-3.09
-2.92
-2.9
-2.96
-2.94
-2.55
-2.32
-2.09
-2.27
-2.18
-2.06
-1.92
-1.42
-1.33
-1.2
-1.06
-1.82
-1.5
-1.31
-2.48
-2.75
-2.27
-2.05
-1.84
-1.68
-2.9
-2.98
-2.12
-1.98
-1.88
-1.76
Temp
95
25
30
37
45
80.3
91.2
99
100
25
25
20
30
40
25
30
37
45
24.9
29.9
37
45
0
15
25
25
25
70
80
90
98
25
25
25
25
30
37
Ref.
[45]
[88]
[88]
[88]
[88]
[45]
[45]
[45]
[45]
[91]
[91]
[90]
[90]
[90]
[88]
[88]
[88]
[88]
[86]
[86]
[86]
[86]
[45]
[45]
[45]
[91]
[91]
[92]
[92]
[92]
[92]
[91]
[91]
[91]
[88]
[88]
[88]
85
-------
No
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
Ester
Phosphoric acid, bis(l-methylpropyl) 4-nitrophenyl ester
Phosphonic acid, ethyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, propyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, isopropyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, butyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, isobutyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, sec-butyl-, isopropyl p-nitrophenyl ester
Phosphonic acid, pentyl-, isopropyl p-nitrophenyl ester
Phosphinic acid, dipropyl-, 4-nitrophenyl ester
Phosphinic acid, diisopropyl-, p-nitrophenyl ester
Obs
-1.591
-3.317
-3.137
-2.914
-2.651
-1.432
-1.28
-1.069
-0.867
-1.479
-1.345
-1.155
-0.954
-2.654
-2.504
-2.278
-2.05
-1.502
-1.384
-1.19
-0.957
-1.706
-1.569
-1.375
-1.175
-2.741
-2.596
-2.377
-2.147
-1.54
-1.393
-1.198
-0.979
-0.004
0.059
0.192
-0.944
Calc
-1.62
-3.27
-3.19
-3.07
-2.94
-1.68
-1.59
-1.47
-1.34
-1.82
-1.74
-1.62
-1.49
-1.95
-1.87
-1.75
-1.63
-1.87
-1.79
-1.67
-1.54
-1.99
-1.9
-1.79
-1.66
-2.36
-2.27
-2.16
-2.04
-1.89
-1.81
-1.69
-1.56
-0.46
-0.39
-0.32
-0.38
Temp
45
25
30
37
45
24.9
29.9
37
45
24.9
29.9
37
45
24.9
29.9
37
45
24.9
29.9
37
45
24.9
29.9
37
45
24.9
29.9
37
45
24.9
29.9
37
45
15
20
25
25
Ref.
[88]
[88]
[88]
[88]
[88]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
-------
No
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
Ester
Phosphinic acid, diisobutyl-, p-nitrophenyl ester
Phosphinic acid, dipentyl-, 4-nitrophenyl ester
Phosphinic acid, di-sec-butyl-, p-nitrophenyl ester
Phosphonic acid, methyl-, diphenyl ester
Phosphinic acid, diethyl-, 4-nitrophenyl ester
Phosphinic acid, dimethyl-, 4-nitrophenyl ester
Phosphinic acid, methylpropyl-, 4-nitrophenyl ester
Phosphinic acid, isopropylmethyl-, p-nitrophenyl ester
Phosphinic acid, butylmethyl-, p-nitrophenyl ester
Phosphinic acid, isobutylmethyl-, p-nitrophenyl ester
Obs
-0.774
-0.548
-0.322
-0.452
-0.329
-0.206
-0.167
-0.058
0.031
-1.19
-1.025
-0.8
-0.574
-2.475
-1.927
-1.771
0.13
0.189
0.329
-0.244
-0.087
0.059
-0.548
-0.394
-0.26
-0.106
-0.714
-0.577
-0.367
-0.164
-0.555
-0.402
-0.269
-0.144
-0.62
-0.473
-0.331
Calc
-0.32
-0.24
-0.15
-0.79
-0.72
-0.66
-0.6
-0.53
-0.46
-1.26
-1.2
-1.13
-1.06
-2.68
-2.35
-2.22
-0.18
-0.1
-0.04
0.111
0.194
0.275
-0.18
-0.11
-0.03
0.043
-0.07
-0
0.09
0.195
-0.23
-0.16
-0.08
-0.01
-0.35
-0.27
-0.2
Temp
30
37
45
15
20
25
15
20
25
25
30
37
45
0.1
15
21.5
15
20
25
15
20
25
15
20
25
30
25
30
37
45
15
20
25
30
15
20
25
Ref.
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[45]
[45]
[45]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
87
-------
No
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
Ester
Phosphinic acid, sec-butylmethyl-, p-nitrophenyl ester
Phosphoric acid, di ethyl 3-methoxyphenyl ester
Phosphoric acid, di ethyl 3-methylphenyl ester
Phosphinic acid, ethylmethyl-, 4-nitrophenyl ester
Phosphinic acid, methylpentyl-, p-nitrophenyl ester
Phosphoric acid, 4-aminophenyl diethyl ester
Phosphoric acid, diethyl 4-ethylphenyl ester
Phosphoric acid, diethyl 4-(l-methylethyl)phenyl ester
Phosphoric acid, diethyl 4-iodophenyl ester
Phosphoric acid, 3-bromophenyl diethyl ester
Phosphoric acid, o-(dimethylamino)phenyl diethyl ester
Phosphoric acid, diethyl o-ethylphenyl ester
Phosphoric acid, diethyl 2-iodophenyl ester
Phosphoric acid, 2-bromophenyl diethyl ester
Phosphoric acid, 2-chlorophenyl diethyl ester
Phosphoric acid, diethyl 2-methoxyphenyl ester
Phosphoric acid, 4-(dimethylamino)phenyl diethyl ester
Phosphoric acid, 4-bromophenyl diethyl ester
Phosphoric acid, diethyl 2-(l-methylethyl)phenyl ester
Phosphoric acid, 4-acetylphenyl diethyl ester
Phosphonic acid, methyl-, mono(4-nitrophenyl) ester, ion(l-)
Phosphonic acid, methyl-, monophenyl ester, ion(l-)
Obs
-0.173
-1.037
-0.901
-0.753
-0.571
-3.206
-3.452
-0.424
-0.278
-0.15
-0.031
-0.591
-0.396
-0.26
-0.112
-3.614
-3.488
-3.473
-2.889
-2.781
-3.829
-3.717
-2.717
-2.623
-2.585
-3.436
-3.555
-2.899
-3.765
-2.49
-4.632
-4.206
-3.848
-3.495
-5.745
-4.9
-4.533
Calc
-0.13
-0.58
-0.51
-0.45
-0.36
-2.9
-2.98
-0.04
0.038
0.114
0.188
-0.25
-0.17
-0.1
-0.03
-3.08
-2.93
-2.96
-2.9
-2.83
-3.39
-3.3
-2.92
-2.89
-2.83
-3.13
-3.07
-2.9
-3.45
-2.9
-4.68
-4.38
-4.05
-3.76
-5.3
-4.65
-4.35
Temp
30
20
25
30
37
25
25
15
20
25
30
15
20
25
30
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
30
39.4
50
60
39
58.8
68.5
Ref.
[86]
[86]
[86]
[86]
[86]
[91]
[91]
[86]
[86]
[86]
[86]
[86]
[86]
[86]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[91]
[93]
[93]
[93]
[93]
[93]
[93]
[93]
-------
No
220
221
222
223
224
225
Ester
Phosphoric acid, 3-chlorophenyl di ethyl ester
Phosphoric acid, diphenyl ester, ion(l-)
Phosphonic acid, methyl-, bis(2,2-dimethylpropyl) ester
Benzoic acid, monoanhydride with phosphoric acid, ion(2-)
Benzoic acid, dianhydride with phosphoric acid, ion(l-)
Obs
-4.206
-2.806
-5.456
-4.319
-2.141
0.404
Calc
-4.07
-2.84
-4.23
-3.69
-1.71
1.073
Temp
78
25
75
88
37
37
Ref.
[93]
[91]
[93]
[45]
[94]
[94]
89
-------
Table 18. SPARC-calculated vs. observed log acid hydrolysis rate constants of organophosphorus
in water in M'V1
No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
Esters
Phosphoric acid, diethyl 1-phenylethenyl ester
Phosphoric acid, diethyl l-(4-methoxyphenyl)ethenyl ester
Phosphoric acid, diethyl l-(4-methylphenyl)ethenyl ester
Phosphoric acid, diethyl l-(4-bromophenyl)ethenyl ester
Phosphoric acid, diethyl l-(4-nitrophenyl)ethenyl ester
Phosphoric acid, diethyl l-(3-nitrophenyl)ethenyl ester
Phosphonic acid, (1,1-dimethylethyl)-, dimethyl ester
Phosphonic acid, methyl-, bis(2,2-dimethylpropyl) ester
Phosphonic acid, butyl-, bis(l-methylethyl) ester
Phosphonic acid, (1,1-dimethylethyl)-, bis(l-methylethyl) ester
Phosphonic acid, methyl-, ethyl 4-nitrophenyl ester
Phosphonic acid, propyl-, bis(l-methylethyl) ester
Phosphonic acid, butyl-, diethyl ester
Phosphonic acid, phenyl-, diethyl ester
Temp.
25
41.5
54.7
70.2
25
41.4
54.4
25
41.5
54.7
70.2
25
41.5
54.2
54.7
70.2
69.8
84.9
99
69.8
85
99
120
103
120
96
101
114.7
115.2
110.4
96
101
107.3
114
114.7
110
119.5
105.2
110.2
114.7
120.3
122.6
Obs.
-4.68
-4.05
-3.50
-2.73
-3.24
-2.46
-2.02
-4.03
-3.18
-2.83
-2.26
-5.03
-4.30
-3.72
-3.60
-3.21
-4.45
-3.80
-3.19
-4.16
-3.50
-2.92
-3.95
-4.33
-3.66
-3.79
-3.68
-3.07
-2.79
-4.12
-3.77
-3.56
-3.33
-3.04
-3.06
-4.58
-4.17
-4.61
-4.45
-4.18
-3.98
-3.96
Calc.
-4.66
-4.13
-3.74
-3.32
-3.24
-2.79
-2.46
-4.05
-3.56
-3.19
-2.79
-4.36
-3.85
-3.49
-3.47
-3.06
-3.81
-3.41
-3.06
-3.56
-3.16
-2.83
-2.98
-3.83
-3.40
-3.81
-3.68
-3.34
-2.28
-4.56
-3.81
-3.68
-3.52
-3.36
-3.34
-3.45
-3.22
-4.49
-4.35
-4.23
-4.09
-4.03
Ref
[44]
[44]
[44]
[44]
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[441
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
90
-------
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
Diisopropyl methylphosphonate
Phosphonic acid, ethyl-, bis(l-methylethyl) ester
Phosphonic acid, methyl-, dimethyl ester
Diethyl methylphosphonate
Diphosphoric acid
Triphosphoric acid
Phosphoric acid, monophenyl ester
Phosphoric acid, mono(4-methylphenyl) ester
Phosphoric acid, diethyl 4-nitrophenyl ester
Phosphoric acid, diethyl 4-(methylsulfonyl)phenyl ester
1,2,3-Propanetriol, l-(dihydrogen phosphate)
1,2-Propanediol, l-(dihydrogen phosphate)
1,2,3-propanetriol, 2-(dihydrogen phosphate)
D-Glucose, 2-(dihydrogen phosphate)
93.6
100.6
109.9
110
115
92.5
101
105.3
110.4
114.7
99.8
104.4
110
114.3
119.6
101
108.8
109.9
115.3
116.9
119.5
39.8
42.07
44.79
49.77
39.59
42.04
44.71
48.95
100
100
70
70
72.3
85.5
100
72
87.7
100
100
100
-3.49
-3.20
-2.93
-2.85
-2.69
-3.80
-3.40
-3.31
-3.11
-2.88
-4.72
-4.52
-4.29
-3.94
-3.77
-4.75
-4.46
-4.25
-4.21
-4.10
-3.96
-4.93
-4.81
-4.67
-4.44
-4.43
-4.29
-4.20
-3.98
-5.42
-5.22
-3.98
-4.01
-6.81
-6.28
-5.70
-6.82
-6.11
-5.37
-5.70
-3.38
-4.07
-3.88
-3.64
-3.64
-3.52
-3.91
-3.69
-3.58
-3.45
-3.35
-4.59
-4.47
-4.32
-4.20
-4.07
-4.21
-4.00
-3.97
-3.84
-3.80
-3.73
-4.94
-4.86
-4.77
-4.61
-4.36
-4.29
-4.21
-4.08
-5.95
-5.15
-4.58
-3.48
-6.41
-5.96
-5.50
-6.75
-6.21
-5.81
-4.90
-3.95
[451
[45]
[45]
[45]
[45]
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[451
[461
[461
[461
[461
[461
[461
[461
[461
[421
[421
[951
[951
[961
[961
[961
[961
[961
[961
[961
[971
91
-------
Table 19. SPARC-calculated vs. observed log neutral hydrolysis rate constants of organophosphorus
in water in M'V1
No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Esters
Triethyl phosphate
Phosphoramidic acid, (1-methylethyl)-, ethyl 3 -methyl -4-
(methylthio)phenyl ester
Serine dihydrogen phosphate (ester)
Benzoic acid, 4-methoxy-, monoanhydride with phosphoric acid
Benzoic acid, 3,5-dinitro-, anhydride with H3PO4
Phosphoric acid, mono(4-methylphenyl) ester
Phosphoric acid, monophenyl ester
Phosphoric acid, trimethyl ester
Phosphoric acid, mono (4-nitrophenyl) ester
Phosphoric acid, mono(2-nitrophenyl) ester
Phosphoric acid, mono (3-nitrophenyl) ester
Temp.
79.6
101
5
22
32
50
80
90
100
39
39
39
39
39
73
80
89
100
39
39
73
75.6
80
89
100
44.7
65.5
73
80
100.1
39
25
39
73
25
73
100
25
39
73
Obs.
0.63
1.45
-3.96
-3.33
-2.10
-1.66
-1.46
-0.97
-0.37
2.68
-1.20
-0.65
2.84
-1.12
-0.82
-0.49
0.01
0.50
2.91
-1.09
-0.71
-0.49
-0.39
0.09
0.58
-0.27
0.72
1.04
1.34
2.09
3.87
-2.94
-0.97
-0.20
-3.30
-0.43
2.53
-2.80
-0.96
-0.50
Calc.
-0.15
0.34
-2.66
-2.03
-1.68
-1.10
-1.12
-0.90
-0.70
1.73
-0.15
-2.63
1.54
-0.34
0.38
0.52
0.68
0.88
0.83
-1.05
-0.26
-0.20
-0.11
0.07
0.28
-0.61
-0.12
0.04
0.19
0.59
2.42
0.25
0.54
1.17
-1.38
-0.14
0.44
-2.24
-1.84
-0.97
Ref
[981
[981
[991
[991
[991
[991
[1001
[1001
[1001
[1011
[1011
[1011
[1011
[1011
[421
[421
[421
[421
[1011
[1011
[421
[1021
[421
[421
[421
[371
[371
[371
[371
[371
[1011
[1031
[1011
[1031
[1031
[1031
[1031
[1031
[1011
[1031
92
-------
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
Phenol, 2-(l,l-dimethylethyl)-, dihydrogen phosphate
Phenol, 2,6-dimethyl-, dihydrogen phosphate
Phenol, 2,6-bis(l,l-dimethylethyl)-4-methyl-, dihydrogen
phosphate
Phosphoric acid, mono (4-chlorophenyl) ester
Phenol, 4-(l,l-dimethylethyl)-, dihydrogen phosphate
Phosphoric acid, mono (2-chlorophenyl) ester
a-D-Glucopyranose, 1 -(dihydrogen phosphate)
Phosphoric acid, monomethyl ester
2-(Phosphonooxy) benzoic acid
Phosphoric acid, diethyl 6-methyl-2-(l-methylethyl)-4-pyrimidinyl
ester
Diisopropyl methylphosphonate
Phosphoric acid, monoethyl ester
Phosphoric acid, diethyl 4-nitrophenyl ester
Phosphoric acid, diethyl 4-(methylsulfonyl)phenyl ester
Dimethyl-2,2-dichlorovinyl phosphate
Trichlorfon
Phosphoric acid, dimethyl 4-nitrophenyl ester
Phosphoric acid, mono(l-methylethyl) ester
1,2-Propanediol, 1 -(dihydrogen phosphate)
Phenol, 2,4-dinitro-, dihydrogen phosphate (ester)
1-Naphthalenol, dihydrogen phosphate
100
100
73
100
100
39
39
100
100
73
100
82
100.1
82
100.1
80
89
100.1
109.7
117.2
25
37.2
42
47.4
20
70
81
90
98
100
20
70
70
70
70
24
32
40
72.2
84.6
100
100
25
39
80
0.76
-0.30
-1.06
0.31
-0.38
3.24
-1.13
0.58
0.35
-0.78
0.46
0.94
1.92
-1.21
-0.29
-1.97
-1.50
-0.92
-0.43
-0.09
2.36
0.88
1.13
1.48
0.84
-0.17
0.38
0.79
1.12
-2.12
0.15
1.03
1.10
-0.20
3.14
0.74
0.92
1.90
-2.39
-1.58
-0.77
-0.66
1.92
0.70
-1.01
-0.38
-1.13
-0.56
0.10
0.97
0.73
-1.14
0.20
0.68
-1.01
-0.38
-0.22
0.14
-1.84
-1.40
-0.15
0.01
0.20
-0.62
0.47
2.23
-0.16
-0.04
0.09
1.02
1.37
1.58
1.74
1.88
-0.55
0.43
1.61
1.30
-0.36
2.78
0.15
0.35
0.55
-1.63
-1.34
-1.00
-0.62
1.72
-1.08
-0.24
[1031
[1031
[1031
[1031
[103]
[1011
[1011
[1031
[1031
[1031
[1031
[1041
[1041
[1041
[1041
[1051
[1051
[1051
[1051
[1051
[431
[1061
[1061
[1061
[321
[471
[471
[471
[471
[1071
[321
[951
[951
[951
[951
[1081
[1081
[1081
[1091
[1091
[1091
[961
[1031
[HOI
[1061
93
-------
86
87
88
89
2-Naphthalenol, dihydrogen phosphate
Benzoic acid, 3-(phosphonooxy)-
Benzoic acid, 4-(phosphonooxy)-
1-Naphthoic acid, 8-hydroxy-, phosphate
80.6
80
80
80
-0.57
0.33
1.09
-2.39
0.91
-0.14
1.38
-0.42
[1061
[1061
[1061
[1061
94
-------
9. CONCLUSION
SPARC's chemical reactivity models, which are used to calculate both ionization pKa (in
water, non-aqueous liquid and gases) and electron affinity, have been extended to calculate
hydrolysis rate constants for carboxylic acid and organophosphate esters. These reactivity
models have been tested to the maximum extent possible in a single and in a mixed solvent
(organophosphorus only in water) as a function of temperature using all the reliable data found in
the literature.
The strength of the SPARC calculator is its ability to estimate the hydrolysis rate constants
(as well many other properties) of interest for almost any molecular structure within an acceptable
error, especially for molecules that are difficult to measure. However, the real test of SPARC does
not lie in testing the predictive capability for hydrolysis rate constants, pKa's, or activity
coefficient, but is determined by its extrapolatability to other types of chemistry. Further extension
of the SPARC chemical reactivity models will be under development soon to calculate
hydrolysis rate constants for other classes of organic compounds as a function of solvent and
temperature.
Finally, SPARC is an important tool in designing chemicals for specific properties, for
use in preliminary evaluation of the risks associated with chemical release into the environment,
and in chemical fate-modeling applications in the absence of experimentally measured values.
The development of the SPARC chemical hydrolysis models (as well as its other physical and
chemical properties estimation) directly address the EPA Office of Research and Development
(ORD) long term research agenda for the agency's Chemical Toxicology Initiative that
emphasizes that EPA will rely heavily on predictive modeling to carry out the increasingly
95
-------
complex array of exposure and risk assessments necessary to develop scientifically defensible
regulations.
SPARC is online and can be used at http://ibmlc2.chem.uga.edu/sparc
96
-------
10. REFERENCES
1. Karickhoff, S.W.C., L. A. Melton, C. McDaniel, V. K. Vellino, A. N.and Nute, D. E.,
Computer Prediction of Chemical Reactivity—The Ultimate SAR. 1989, U.S.
Environmental Protection Agency: Athens, GA. EPA-600/M-89-017
2. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W.;Melton, C.M., Quant. Struct.-Act. Relat.,
1993. 12(4): 389.
3. Hilal, S.H.;Carreira, L.A.;Baughman, G.L.;Karickhoff, S.W.;Melton, C.M., J. Phy. Org.
Chem., 1994. 7: 122.
4. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W., Estimation of Chemical Reactivity
Parameters and Physical Properties of Organic Molecules using SP'ARC, in Quantitative
Treatments of Solute/Solvent Interactions, P. Politzer and Murray, J.S., Editors. 1994,
Elsevier: Amsterdam, p. 291.
5. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W.;Melton, C.M., J.Chromatogr., 1994. 662:
269.
6. Hilal, S.H.;Brewer, J.M.;Lebioda, L.;Carreira, L.A., Biochem Biophys Res Commun,
1995. 211(2): 607.
7. Hilal, S.H.;Karickhoff, S.W.;Carreira, L.A., Quant. Struct.-Act. Relat., 1995. 14: 348.
8. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W., Talanta, 1996. 43: 607.
9. Hilal, S.H.;Karickhoff, S.W.;Carreira, L.A., Talanta, 1999. 50: 827.
10. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W., QSAR Comb. Sci, 2003. 22(9-10): 917.
11. Hilal, S.H.;Carreira, L.A.;Karickhoff, S.W., QSAR Comb. Sci, 2003. 23: 709.
12. Hilal, S.H.;Karickhoff, S.W.;Carreira, L.A., QSAR Comb. Sci, 2003. 22: 565.
13. Hilal, S.H., Bornander.L.L. and Carreira, L.A, QSAR Comb. Sci. , 2005. 24: 631.
14. Whiteside, T.S., Hilal, S. H., and Carreira, L.A, QSAR Comb. Sci. , 2006. 25: 123 - 133.
15. Hammett, L.P., Chemical Reviews, 1935. 17: 125.
16. Leffler, J.E.;Grunwald, E., Rates and Equilibria of Organic Reactions. 1963, New York:
John Wiley & Sons.
17. Lowry, T.H.;Richardson, K.S., Mechanism and Theory in Organic Chemistry. 3 ed. 1987,
New York, NY: Harper & Row.
18. Hammett, L.P., Physical Organic Chemistry. 1970, New York, NY: McGraw Hill.
19. Taft, R.W., Progress in Organic Chemistry. Vol. 16. 1987, New York, NY,: John Wiley
& Sons.
20. Dewar, M.J.S., The Molecular Orbital Theory of Organic Chemistry. 1969, New York,
NY: McGraw Hill.
21. Dewar, M.J.S.;Dougherty, R.C., The PMO Theory of Organic Chemistry. 1975, New
York, NY: Plenum Press.
22. Karickhoff, S.W.;McDaniel, V.K.;Melton, C.;Vellino, A.N.;Nute, D.E.;Carreira, L.A.,
Environmental Toxicology and Chemistry, 1991. 10: 1405.
23. Lyman, W. J., ed. Handbook of Chemical Property Estimation Methods. 1990.
24. Hughes, E.D.;Ingold, C.K.;Patel, J.C., J. Chem. Soc. B., 1963: 526.
25. Wolfe, N.L., Chemosphere, 1980. 9: 571 - 579.
26. Ingold, C.K., Structure and Mechanism in Organic Chemistry. 1953: Cornell University
Press.
27. Patai, S., The Chemistry of Carboxylic Acids and Esters. 1969, NY: John Wiley and Sons
Ltd.
97
-------
28. Murakami, Y.;Sunamoto, 1, J. Chem. Soc. Perk. T2, 1973. 9: 1235.
29. Cox, J.R.;Ramsay, O.B., Chem. Rev., 1964. 64: 317.
30. Lacorte, S.;Lartiges, S.B.;Garrigues, P.;Barcel6, D., Environ.Sci. Technol, 1995. 29(2):
431.
31. Melnikov, N.N., Chemistry of Pesticides. 1971, New York, NY,: Springer-Verlag,.
32. Faust, S.D.;Gomaa, H.M., 1972. 3: 171.
33. Ramires, F.;Ramanathan, N.;Desai, N.B., J. Am. Chem. Soc., 1963. 85(1963): 3465.
34. Ramires, F.;Hansen, B.;Desai, N.B., J. Am. Chem. Soc., 1963. 85: 3252.
35. Brown, D.;Usher, D., J. Chem. Soc. B., 1965: 6559.
36. Brown, D.;Hall, G.;Higson, H., J. Chem. Soc. B., 1958: 1360.
37. Barnard, P.W.C.;Bunton, C.A.;Llewellyn, D.R.;Vernon, C.A.;Welch, V.A., J. Chem.
Soc., 1961:2670-2676.
38. Heath, F.F., J. Chem. Soc., 1956: 3796.
39. Weber, K., Water Res., 1976. 10: 237.
40. Schwarzenbach, R.P.;Gschwend, P.M.;Imboden, D.M., Environmental Organic
Chemistry. First ed. 1993, New York: John Wiley & Sons, Inc.
41. Shrestha, B.P., Ph.D Thesis. 2001, University of Georgia: Athens, A.
42. Barnard, P.W.C.;Bunton, C.A.;Kellerman, D.;Mhala, M.M.;Silver, B.;Vernon,
C.A.;Welch, V.A., J. Chem. Soc. B: Phy. Org. , 1966. 3: 227-235.
43. Bender, M.L.;Lawlor, J.M., J. Am. Chem. Soc, 1963. 85: 3010.
44. Frampton, R.D.;Tidwell, T.T.;Young, V.A., J. Am. Chem. Soc., 1972. 94: 1271.
45. Hudson, R.F.;Keay, L., J. Chem. Soc., 1956: 2463.
46. Friess, S.L., J. Am. Chem. Soc., 1952. 74: 4027-4029.
47. Sega, G.A.;Tomkins, B.A.;Griest, W.H.;Bayne, C.K., J. Environ. Sci. Health, 1998: 213.
48. Hilal, S.H., Verification and Validation of the SPARC Model. 2003, U.S. Environmental
Protection Agency: Athens, GA. EPA/600/R-03/033
49. Mill, T.;Mabey, W., J. Phys. Chem. Ref. Data, 1978. 7: 383.
50. Nishioka, T.;Toshio Fujita, K.;Nakajima, M., J. Org. Chem., 1975. 40: 2520
51. Mill, T., Chromophore, 1988. 17 1509.
52. DePuy, C.H.;Mahoney, L.R., J. Am. Chem. Soc., , 1964. 86: 2653
53. Euranto, E.K.;Moisio, A.-L., Suomen Kemistilehti, 1962. 35B: 18.
54. Sun, S.;Connors, K.A., J. Pharm. Sci. , 1961. 58: 1150.
55. Jones, R.W.A.;Thomas, J.D.R., J. Chem. Soc. (B), 1966: 661
56. J. G Watkinson, J.G;Watson, W.;Yates, B.L., J. Chem. Soc., 1966: 5437.
57. Norman, R.O.C.;Ralph, P.O., J. Chem. Soc., 1966: 5431.
58. Acton, N.;Berlinger, E., J. Am. Chem. Soc, 1964. 64: 3312.
59. Mill, T.;Mabey, W., J. Phys. Chem. Ref. Data, 1978. 7: 383.
60. Fischer, A.;Mitchell, W.J.;Ogilvie, G.S.;Packer, J.;Packer, J.E.;Vaughan, J., J. Chem.
Soc., 1958: 1426.
61. Berlinger, E.;Liang Huang Liu, J. Am. Chem. Soc., 953. 75: 2417
62. Falkner, P., R.,;D. Harrison, D., J. Chem. Soc., 1960: 1171.
63. Chapman, N.B.;Shorter, J.;Utley, J.H.P., J. Chem. Soc., , 1963: 1291.
64. Elderfield, R.C.;Siegel, M., J. Am. Chem. Soc., 1951. 73: 5622
65. Deady, L.W.;Shanks, R.A., Aust. J. Chem., , 1972. 25: 2363.
66. Bender, M.L.;Thomas, R.J., J. Am. Chem. Soc., 1961. 83: 4193.
67. Bender, M.L.;Thomas, R.J., J. Am. Chem. Soc., 1961. 83: 4189.
98
-------
68. Rapoport, M.;Hancock, C.K.;Meyers, E.A., J. Am. Chem. Soc., , 1961. 83: 4211.
69. Hancock, C.K.;Falls, C.P., J. Am. Chem. Soc., , 1961. 83: 4214.
70. Kirsch, J.F.;et al., J. Org. Chem.,, 1968. 33: 127.
71. Taft, R.W., J. Am. Chem. Soc., 1952. 74: 2729.
72. Fife, T.H.;McMahon, D.N., J. Am. Chem. Soc., 1969. 91: 7481.
73. Newling, W.B.S.;Hinselwood, C.N., J. Chem. Soc., 1936: 1357
74. Charton, M., J. Am. Chem. Soc., , 1975. 97: 1554
75. Timm, E.;Hinselwood, C.N., J. Chem. Soc., , 1938: 862.
76. E. Tomilla;Hinselwood, C.N., J. Chem. Soc., 1938: 1801.
77. Hornyak, F.N.;S. Amis, E.S., J. Am. Chem. Soc., 1957. 79: 2079
78. Cabani, S.;Gianni, P.;Matteoli, E., J. Phys. Chem. , 1972. 76: 2959.
79. McCelland, R.A.;et al., Can. J. Chem., , 1994. 72: 2333.
80. Cleve, NJ.;Euranto, E.K., Suomen Chemistilehti, 1964. 37: 126.
81. Jencks, W.P.;Carriuolo, I, J. Am. Chem. Soc., 1961. 83: 1743
82. Gold, V., J. Chem. Soc. (B), 1968: 515.
83. Moffat, A.;Hunt, H., J. Am. Chem. Soc., 1957. 79: 54.
84. Moffat, A.;Hunt, H., J. Am. Chem. Soc., 1958. 81: 2082.
85. Bunton, C.A.;Hadwick, T., J. Chem. Soc., 1958: 3248.
86. Larsson, L.,Acta Chemica Scandinavica, 1958. 12: 783.
87. Aldridge, W.;Davison, A., Biochem. J., 1952. 52: 663 - 671.
88. Ginjaar, L.;Vel, S., Recueil travaux chim. Pays-Bas, 1958. 77: 956.
89. Gomaa, H.;Suffet, I.;Faust, S., Residue Rev, 1969. 29: 171 -190.
90. Ginjaar, L.;Vel, S., Recueil travaux chim. Pays-Bas, 1966. 85: 694.
91. Van Hooidonk, C.;Ginjaar, L., Recueildes travaux chimiques desPays-Bas, 1967: 449-
457.
92. Cook, R.D., J. Am. Chem. Soc., 1973. 95: 8088 - 8096.
93. Behrman, E.;Biallas, MJ.;Brass, HJ.;Edwards, J.O.;Isaks, M., J. Org. Chem. , 1970. 35:
3063-3069.
94. Koefoed, J.;Jensen, A.H., Acta Chem. Scand, 1951. 5: 23-30.
95. M'uhlmann, V.R.;Schrader, G., ZeitschriftfuerNaturforsch 1057. 12b: 196.
96. Kugel, L.;Halmann, M., J. Am. Chem. Soc., 1966. 88: 3566-3572.
97. Farrar, K.R., J. Am. Chem. Soc., 1949: 3131.
98. Lyznicki, J., E. P.; ;Kiyotaka, O.;Tidwell, T.T., Can. J. Chem., 1974. 52: 1066.
99. Ramesh, A.;Balasubramanian, M., J. Agr. Food Chem., 1999. 47(8): 3367.
100. Samuel, D.;Silver, B.L., J.Chem. Soc., 1963: 289.
101. Sabato, GD.;Jencks, W.P., J.Am. Chem. Soc., 1961. 83: 4400.
102. Takamuku, T.;Tabata, M.;Yamaguchi, A.;Nishimoto, J.;Kumamoto, M.;Wakita,
H.;Yamaguchi, T.,J. Phys. Chem. B, 1998. 102(44): 8880.
103. Bunton, C.A.;Fendler, EJ.;Fendler, J.H., J. Am. Chem. Soc., 1967. 89: 1221-1230.
104. Bunton, C.A.;Llewellyn, D.R.;Oldham, K.G;Vernon, C.A., J. Chem. Soc., 1958: 3588-
3594.
105. Bunton, C.A.;Llewellyn, D.R.;Oldham, K.G;Vernon, C.A., J. Chem. Soc., 1958: 3574-
3587.
106. Chanley, J.D.;Gindler, E.M.;Sobotka, H., J. Am. Chem. Soc, 1952. 74: 4347.
107. Desjobert, A., Bulletin de la Societe Chimique de France, 1947: 809-812.
108. Noblet, J.A.;Smith, L. A.;Suffet, I.H., Journal ofAgric. Food Chem., 1996. 44(11): 3685.
99
-------
109. Kugel, L.;Halmann, M., J. Org. Chem., 1967. 32: 642-647.
110. Kirby, AJ.;Varvoglis, A.G., J. Am. Chem. Soc., 1967. 89: 415-423.
100
-------
APPENDIX
Figure 6. Sample calculations of log hydrolysis rate constant in acid catalyzed media for p-nitrophenyl
acetate in water at 25° C. Only the reaction center parameters are trained on hydrolysis rate
constant (at the top). The substituent, molecular conductor parameters and distances (r's)
between the various components are the same as of ionization pKa
101
-------
Carboxylic Acid Ester Hydrolysis Rate Constant Reaction Center Characteristic Parameters
a b
Reaction Center pde pares pres & A MF Refi Ref2 PFS Pstenc Pa Pp on° a
Acid Hydrolysis 0 8? -0.4 1.11 1.80 $.67 ^.36 3.886 -3070.8 -3.0 * 105 -310935 -1821 944.6 0.008 0.1
Base Hydrolysis "' 3.90 2.55 -0.67 3.36 -3.522 .14434 * 107 -328642 -4205 2119 0.008 0.1
GBase Hydrolysis^ 7 _n 8-0.6 2.59 2.65 -0.67 3.36 -5.249 -3479.7 ^ 15 * 107 -114969 -373 5598 0.008 ni
logkc= 3.36 log (298.15) + 3.886 + (-3070.8/298.15) = -0.59
5IPdlogk = pe]
k-x.)
Fscos0
cs
+ MFs AMF Z^
8,P1ogko= -°-87
).65(2.3-U
7.746x1
(1.3 + 2 + 1)3
-0.67)1 2x0.078 +q078_3x 0.078
(1.73 + 1.3) 1.32 (1.3 + 2)'
0.28 x 1.11= -0.07
jc 14 (p-benzene) r is
M3 (m-benzene)
PPS
-D.
PA CC
Tk
Tk
-3xl05
298.15x78.54
-310935x0.0687
298.15x78.54
-1821x0.384
298.15
944.6x0.382
298.15
= -3.333
Log k Hydrolysis = -0.59+ (-0.075) + (.3 33) =.3995 (Observed is 3.9)
a: for carbonyl of C, b: for the oxygen of C, c: for aromatic R-TI unit, d: for ethylenic R-TI unit.
102
------- |