Grunwald Winstein Research Articles

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides.

There have been several studies on the solvolysis mechanisms for alkanesulfonyl chlorides (RSO2Cl) and arenesulfonyl chlorides (ArSO2Cl). The earlier of these studies were reviewed a little over thirty years ago by Gordon, Maskill and Ruasse (Chem. Soc. Rev. 1989, 18, 123–151) in a contribution entitled “Sulfonyl Transfer Reactions”. The present review will emphasize more recent contributions and, in particular, the application of the extended Grunwald–Winstein equation and kinetic solvent isotope effects to the solvolysis reactions. There is also an appreciable number of reports concerning the corresponding anhydrides with the chloride leaving group replaced by the appropriate sulfonate leaving group, concerning sulfamoyl chlorides (ZZ'NSO2Cl) with Z and Z' being alkyl or aryl and concerning the solvolysis of chlorosulfate esters (alkoxy- or aryloxysulfonyl chlorides), with the structures ROSO2Cl or ArOSO2Cl. The solvolyses of these additional types of sulfur(VI) substrates will be the topics of a future review.

Rate and Product Studies with 1-Adamantyl Chlorothioformate under Solvolytic Conditions.

A study was carried out on the solvolysis of 1-adamantyl chlorothioformate (1-AdSCOCl, 1) in hydroxylic solvents. The rate constants of the solvolysis of 1 were well correlated using the Grunwald–Winstein equation in all of the 20 solvents (R = 0.985). The solvolyses of 1 were analyzed as the following two competing reactions: the solvolysis ionization pathway through the intermediate (1-AdSCO)+ (carboxylium ion) stabilized by the loss of chloride ions due to nucleophilic solvation and the solvolysis–decomposition pathway through the intermediate 1-Ad+Cl− ion pairs (carbocation) with the loss of carbonyl sulfide. In addition, the rate constants (kexp) for the solvolysis of 1 were separated into k1-Ad+Cl− and k1-AdSCO+Cl− through a product study and applied to the Grunwald–Winstein equation to obtain the sensitivity (m-value) to change in solvent ionizing power. For binary hydroxylic solvents, the selectivities (S) for the formation of solvolysis products were very similar to those of the 1-adamantyl derivatives discussed previously. The kinetic solvent isotope effects (KSIEs), salt effects and activation parameters for the solvolyses of 1 were also determined. These observations are compared with those previously reported for the solvolyses of 1-adamantyl chloroformate (1-AdOCOCl, 2). The reasons for change in reaction channels are discussed in terms of the gas-phase stabilities of acylium ions calculated using Gaussian 03.

Better late than never! Transition state character involved in the neutral solvolysis of an oxalic ester determined by the ionizing power of ethanol/water and methanol/water mixtures

Solvation effects and solvolysis extent are major aspects of the decomposition of esters, particularly in polar protic media. Among the many different ester derivatives, oxalic esters are substances that have two ester groups in the same molecular framework, but with potentially different reactivities. Aryl oxalic esters are commonly used in efficient organic chemiluminescent reactions, leading to important analytical and biological applications. We studied the decomposition of bis(2,4,6-trichlorophenyl) oxalate (TCPO) in 100, 98, 95, 90, 80, 70, 60, and 50% ethanol/water (EtOH/W) and 100, 90, 80, and 70% methanol/water (MeOH/W) mixtures (% in v/v). In these media, one phenolic residue is generated in a fast addition–elimination (step 1), followed by a second slower addition–elimination (step 2), thus, two rate constants are observed. Using a Grunwald–Winstein (G–W) relationship between these rate constants and the solvent ionizing power (Υ), we determined the sensibility (m) to solvation effects and charge development associated with the transition state (TS) of the rate-determining step (rds). We also determined the Gibbs free energy of activation (∆‡G, at 25 °C) associated with each step, and used it to rationalize the TS character of the rds, considering that in both steps a zwitterionic intermediate is generated and that the addition step is rate limiting. In EtOH/W binary mixtures a non-linear G–W plot was observed, and for 100–95% EtOH/W mixtures the sensibility was m = 1.0 (step 1, ∆‡G = 21.6 to 20.6 kcal mol−1) and 1.1 (step 2, ∆‡G = 23.9 to 23.0 kcal mol−1), indicating full ionization in the TS of the addition step. Smaller Y values in 90–50% EtOH/W reflect a more symmetrical TS, with not as many charges being generated (step 1, m = 0.196, ∆‡G = 20.3 to 19.4 kcal mol−1; step 2, m = 0.30, ∆‡G = 22.6 to 21.7 kcal mol−1). In 100%–70% MeOH/W binary mixtures, with Y values similar to those for 90–50% EtOH/W, m = 0.52 (step 1, ∆‡G = 20.3 to 18.8 kcal mol−1) and 0.27 (step 2, ∆‡G = 21.5 to 20.9 kcal mol−1) were observed. Particularly for step 1 in MeOH/W, the observation of a solvent kinetic isotope effect that varies from inverse (0.63 ± 0.09 in pure MeOH) to normal (1.9 ± 0.3 in 70% MeOH/W) is consistent with the significant participation of the solvent in TS stabilization, resembling general acid catalysis.

The Influence of a Terminal Chlorine Substituent on the Kinetics and the Mechanism of the Solvolyses of n-Alkyl Chloroformates in Hydroxylic Solvents.

A previous study of the effect of a 2-chloro substituent on the rates and the mechanisms of the solvolysis of ethyl chloroformate is extended to the effect of a 3-chloro substituent on the previously studied solvolysis of propyl chloroformate and to the effect of a 4-chloro substituent on the here reported rates of solvolysis of butyl chloroformate. In each comparison, the influence of the chloro substituent is shown to be nicely consistent with the proposal, largely based on the application of the extended Grunwald–Winstein equation, of an addition-elimination mechanism for solvolysis in the solvents of only modest solvent ionizing power, which changes over to an ionization mechanism for solvents of relatively high ionizing power and low nucleophilicity, such as aqueous fluoroalcohols with an appreciable fluoroalcohol content.

The Effect of the ortho Nitro Group in the Solvolysis of Benzyl and Benzoyl Halides.

A kinetic study was carried out on the solvolysis of o-nitrobenzyl bromide (o-isomer, 1) and p-nitrobenzyl bromide (p-isomer, 3), and o-nitrobenzoyl chloride (o-isomer, 2) in a wide range of solvents under various temperatures. In all of the solvents without aqueous fluoroalcohol, the reactions of 1 were solvolyzed at a similar rate to those observed for 3, and the reaction rates of 2 were about ten times slower than those of the previously studied p-nitrobenzoyl chloride (p-isomer, 4). For solvolysis in aqueous fluoroalcohol, the reactivity of 2 was kinetically more reactive than 4. The l/m values of the extended Grunwald–Winstein (G–W) equation for solvolysis of 1 and 2 in solvents without fluoroalcohol content are all significantly larger than unity while those in all the fluoroalcohol solvents are less than unity. The role of the ortho-nitro group as an intramolecular nucleophilic assistant (internal nucleophile) in the solvolytic reaction of 1 and 2 was discussed. The results are also compared with those reported earlier for o-carbomethoxybenzyl bromide (5) and o-nitrobenzyl p-toluenesulfonate (7). From the product studies and the activation parameters for solvolyses of 1 and 2 in several organic hydroxylic solvents, mechanistic conclusions are drawn.

Kinetic Study on Solvolysis of 2‐Methylfuran‐3‐carbonyl Chloride in Binary Solvent Mixtures

Rate constants for solvolysis of 2‐methylfuran‐3‐carbonyl chloride (1) in ethanol, methanol, and aqueous binary mixtures incorporating ethanol, methanol, acetone, 2,2,2‐trifluoroethanol, and 1,1,1,3,3,3‐hexafluoro‐2‐propanol are reported. The 34 solvents give an extended Grunwald–Winstein correlation with l = 0.26 ± 0.05, m = 0.71 ± 0.04, and correlation coefficient R2 = 0.963. Activation parameters calculated from the rate constants measured at three different temperatures in five different solvents are presented. In the deuterated methanol, a solvent kinetic isotope effect of 1.15 was observed at 0°C. The kinetic features observed indicate that the reaction proceeds through an SN1 mechanism with a little SN2 character. The reactivity–selectivity principle is also followed in alcohol‐water mixtures.

Positioning solvolyses within the SN2‐SN1 and SN3‐SN2 spectrum of reaction mechanisms

A simple linear regression (Q equation) is devised to position solvolyses within the established SN2‐SN1 spectrum of solvolysis mechanisms. Using 2‐adamantyl tosylate as the SN1 model and methyl tosylate as the SN2 model, the equation is applied to solvolyses of ethyl, allyl, secondary alkyl and a range of substituted benzyl and benzoyl tosylates. Using 1‐adamantyl chloride as the SN1 model and methyl tosylate as the SN2 model, the equation is applied to solvolyses of substituted benzoyl chlorides in weakly nucleophilic media. In some instances, direct correlations with methyl tosylate were employed. Grunwald–Winstein l values and kinetic solvent isotope effects are also used to locate solvolyses within the spectrum of mechanisms. Product selectivities (S) for solvolyses at 50 °C of p‐nitrobenzyl tosylate in binary mixtures of alcohol–water and of alcohol–ethanol for five alcohols (methanol, ethanol, 1‐propanol and 2‐propanol and t‐butanol) are reported and show the expected order of solvent nucleophilicity (RCH2OH > R2CHOH > R3COH). The data support the original assignments establishing the NOTs scale of solvent nucleophilicity. Copyright © 2016 John Wiley & Sons, Ltd.

Mechanistic Analysis of 4‐Methylthiobenzoyl Chloride in Solvolysis

The solvolysis mechanism of 4‐methylthiobenzoyl chloride (1) was studied by kinetic methods, and these results were compared with 4‐methoxy (2) and 3,4,5‐trimethoxybenzoyl chlorides (3) reported previously. The analysis of kinetic data was carried out using both the simple and extended Grunwald–Winstein (G–W) equations, thermodynamic parameters, and kinetic solvent isotope effects (KSIE). In fact, 4‐methylthiobenzoyl chloride (1) has a sulfur atom which is bigger in size and has more electrons than oxygen in the para‐position. The results were obtained and showed typical dispersed plots from the simple (R = 0.939) and extended G–W equations (l/m = 0.33, R = 0.952) for all data, and when the data from some of the most dispersed points were removed, the correlation coefficients were improved remarkably. Thermodynamic parameters revealed that the change of enthalpies were 16.2 ~ 17.6 kJ/mol and the change of entropies were −16.5 ~ −8.6 J/K‐mol. The KSIE of MeOH/MeOD was 1.42. The above results for 4‐methylthiobenzoyl chloride supported a unimolecular pathway, or more precisely, a dissociated SN2 mechanism classified by l/m ratio.

Mechanistic Studies of the Solvolyses of Carbamoyl Chlorides and Related Reactions.

Carbamoyl chlorides are important intermediates, both in the research laboratory and in industrial scale syntheses. The most studied and used are the disubstituted derivatives, incorporating either aryl or alkyl groups (Ar2NCOCl or R2NCOCl). Sometimes, the groups are tied back to give a ring and piperidino- and morpholino-derivatives are commonly encountered. Some studies have been made with two different groups attached. Solvolyses tend to occur at the carbonyl carbon, with replacement of the chloride ion. Studies of both rate and products are reviewed and the solvolysis reactions are usually SN1, although addition of an amine leads to a superimposable bimolecular component. Many of the studies under solvolytic conditions include the application of the extended Grunwald–Winstein equation. The monosubstituted derivatives (ArNHCOCl or RNHCOCl) are less studied. They are readily prepared by the addition of HCl to an isocyanate. In acetonitrile, they decompose to set up and reach equilibrium with the isocyanate (ArNCO or RNCO) and HCl. Considering that the structurally related formyl chloride (HOCOCl) is highly unstable (with formation of HCl + CO2), the unsubstituted carbamoyl chloride (H2NCOCl) is remarkably stable. Recommended synthetic procedures require it to survive reaction temperatures in the 300–400 °C range. There has been very little study of its reactions.

Studies of Solvolyses of 1,4‐Benzodioxan‐6‐Sulfonyl Chloride by Extended Grunwald–Winstein Equation

The rate constants of solvolysis of 1,4‐benzodioxan‐6‐sulfonyl chloride (C8H7ClO4Cl, 1) were determined by a conductivity technique. These rate constants of 1 in 28 different solvents correlated well with the extended Grunwald–Winstein equation. The l (1.00) and m (0.59) values support an SN2 reaction pathway having a similar transition state structure to that of the benzenesulfonyl chloride (2, l = 1.10, m = 0.61) reaction. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH ≠ (8.9 to 15.5 kcal/mol) and large negative ΔS ≠ (−27.3 to −49.2 cal/mol/K) values, and the solvent kinetic isotope effect (1.62). The Kivinen's n values (n = 0.03 in methanol, 0.04 in ethanol) obtained in binary solvents were consistent with the proposed bimolecular reaction mechanism.

Correlation of the Rates of Solvolysis of 2,1-Benzoxathiol-3-One-1, 1-dioxide (2-Sulfobenzoic Acid Cyclic Anhydride)

Solvolysis of acyclic mixed carboxylic–sulfonic anhydrides in hydroxylic solvents is known to involve displacement at the carbonyl carbon to produce a carboxylic acid (water as the nucleophile) and/or an ester (alcohol as the nucleophile) plus the anion of the sulfonic acid. Parallel solvolyses of the cyclic mixed anhydride 2-sulfobenzoic anhydride (structurally similar to phthalic anhydride but with one carbonyl group replaced by a sulfonyl group) involve expulsion from the carbonyl carbon of a sulfonate anion that remains attached as an ortho-substituent in the benzoic acid and/or benzoate ester produced. This complicates the choice of a solvent-ionising-power scale for use in an extended Grunwald–Winstein equation treatment. The YOTs scale, previously recommended as a good general purpose scale, is chosen and used in conjunction with the NT solvent nucleophilicity scale. An acceptable correlation is obtained, which is improved when the two solvents rich in the highly ionising 1,1,1,3,3,3-hexafluoro-2-propanol are excluded. As the solvent is varied, the sensitivities to the changes induced in the two scales are low, consistent with an early transition state, but their ratio has a value which is typical for a pathway involving addition–elimination, with addition rate-determining. Earlier reports, supporting aspects of the proposed mechanism, are reviewed.

Correlation of Rates of Solvolysis of Diphenylacetyl Chloride Using Extended Grunwald–Winstein Equation

Rate constants for solvolysis involving the displacement of chloride from the carbonyl carbon of diphenylacetyl chloride ((C6H5)2CHCOCl, 1) in ethanol, methanol, aqueous binary mixtures incorporating ethanol, methanol, acetone, 2,2,2‐trifluoroethanol (TFE), and 1,1,1,3,3,3‐hexafluoro‐2‐propanol, and binary mixtures of TFE with ethanol are reported. The kinetic data obtained from the reactions in 34 different solvents and solvent mixtures gave an extended Grunwald–Winstein correlation with the l value of 0.76 ± 0.06, the m value of 0.34 ± 0.04, and the correlation coefficient (R2) of 0.932. The appreciable values for both l and m suggest that the bond formation is ahead of the bond breaking with an SN2 mechanism, and the l/m ratio of 2.2 is also in the range of values found for SN2 reaction. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH≠ (7.7–16.3 kcal/mol) values and large negative ΔS≠ (−24.6 to −53.4 cal/mol/K) values, and the solvent kinetic isotope effect (1.62).

Statistical Methods for the Investigation of Solvolysis Mechanisms Illustrated by the Chlorides of the Carbomethoxy Protecting Groups NVOC and FMOC.

The solvolysis of 4,5-dimethoxy-2-nitrobenzyl chloroformate (NVOC-Cl, 1) is followed at 25.0°C in twenty hydroxylic solvents. A comparison with previously published rates for benzyl chloroformate and p-nitrobenzyl chloroformate indicates that the inductive effect of the nitro and the two methoxy groups strongly influences the rate of reaction. For 1, the specific rates of solvolysis are correlated using an extended Grunwald-Winstein (G-W) treatment. A direct comparison with the data for phenyl chloroformate (PhOCOCl) in identical solvents strongly suggests that the addition step within an addition-elimination mechanism is rate-determining for both substrates. A reevaluation of the kinetic data for 9-fluorenylmethyl chloroformate (FMOC-Cl, 2) involves a correlation of log⁡(k/k o)2 versus log⁡(k/k o)PhOCOCl. In this plot, deviations were observed in solvents rich in a hydrogen-bonding fluoroalcohol component. Omitting the aqueous fluoroalcohol rate measurements for 2 in an analysis using the extended G-W equation suggested the occurrence of dual pathways differing in the dependences upon the ionizing power and nucleophilicity of the solvent. In addition, the fluorenyl ring is rotated out of the plane containing the ether oxygen and, as a result, PhOCOCl is found to solvolyze 20 times faster than 2 in ethanol and methanol.

Extent of Nucleophilic Participation in the Solvolyses of an Aryl Chloromethyl Ether, α,p-Dichloroanisole

The specific rates of solvolysis of α, p-dichloroanisole (chloromethyl p-chlorophenyl ether, 1) have been measured conductimetrically in a variety of hydroxylic solvents. In three typical solvents, at 25.0 °C, the rate is 20–45 times greater than for the corresponding sulfide. In a comparison with the solvolysis of a substrate with an alkyl group replacing the aryl group, chloromethyl ethyl ether (2), at −10.0 °C in four typical solvents, 1 reacted considerably more slowly than 2, by a little over four orders of magnitude. An extended Grunwald–Winstein equation treatment of the specific rates of solvolyses in 24 solvents at 25.0 °C leads to an l value of 0.68 ± 0.04 and an m value of 0.59 ± 0.03 ( l/ m = 1.15). Appreciable nucleophilic assistance in the progress to the transition state is indicated and either nucleophilic solvation to an ionisation process or a loose SN2 transition state with extensive bond-breaking accompanied by a smaller degree of bond-making lead to an appropriate transition state.

Correlation of the rates of solvolysis of acetic p‐toluenesulfonic anhydride (acetyl p‐toluenesulfonate) and a comparison with acetyl halides

The specific rates of solvolysis of acetyl p‐toluenesulfonate have been measured by a rapid‐response conductivity technique at temperatures in the temperature range of −10 to −55 °C. For 13 solvents at −39.6 °C, an extended Grunwald–Winstein equation correlation led to sensitivities to changes in solvent nucleophilicity of 0.56 and to changes in solvent ionizing power of 0.61. In 89.1% acetone at −20 °C, the comparison with acetyl bromide solvolysis led to a kOTs/kBr ratio of 1.4. In methanol and methanol‐d at −39.6 °C, the solvent deuterium isotope effect kMeOH/kMeOD is 0.99. These results are consistent with an SNl reaction with appreciable nucleophilic solvation or an SN2 reaction with a loose transition state. These two approaches lead to similar structures for the transition state. A solution of the acetyl p‐toluenesulfonate was conveniently prepared by the rapid reaction of acetyl chloride with silver p‐toluenesulfonate in acetonitrile. Copyright © 2013 John Wiley & Sons, Ltd.

Rate and Product Studies of 1-Adamantylmethyl Haloformates Under Solvolytic Conditions

Reactions of 1-adamantylmethyl chloroformate (, 1) and 1-adamantylmethyl fluoroformate (, 2) in hydroxylic solvents have been studied. Application of the extended Grunwald-Winstein (G-W) equation to solvolyses of 1 in a variety of pure and binary solvents indicates an addition-elimination pathway in the majority of the solvents except an ionization pathway in the solvents of relatively low nucleophilcity and high ionizing power. The solvolyses of 2 show an addition-elimination pathway in all of the mixed solvents. The leaving group effects (), the kinetic solvent isotope effects (KSIEs, ), and the enthalpy and entropy of activation for the solvolyses of 1 and 2 were also calculated. The selectivity values (S) for each solvent composition are reported and discussed. These observations are compared with those previously reported for other alkyl haloformate esters.

Extent of Nucleophilic Participation in the Solvolyses of Alkyl Chloromethyl Ethers and Sulfides

The specific rates of solvolysis have been determined for chloromethyl ethyl ether (3) and chloromethyl octyl ether (4) at −10.0 °C and for chloromethyl methyl sulfide (5) at 25.0 °C in a variety of pure and binary solvents. These values were used for a correlation analysis treatment using the extended Grunwald–Winstein equation incorporating literature values for solvent nucleophilicity ( NT) and solvent ionising power ( YCl). Appreciable values were found for the sensitivities towards changes in both NT and YCl values. Using a literature specific rate of hydrolysis at 25.0 °C for fluoromethyl methyl ether (2), the required value for chloromethyl methyl ether (1) was obtained from use of NT and YCl values and the sensitivities for 3 to changes in their values, to adjust an experimental specific rate value for 1 in 100% ethanol to the corresponding value in 100% water. In this way, an estimated kCl/ kF of 1.2 × 105 was obtained, essentially identical to values for the solvolyses of tert-butyl halides. A unimolecular mechanism for the solvolyses, with appreciable nucleophilic solvation of the developing carbocation, is proposed. Electronic supplementary information provides, for several solvents, specific rates of solvolysis for 3, 4, and 5 at additional temperatures and the calculated activation parameters.

ChemInform Abstract: Use of Linear Free Energy Relationships (LFERs) to Elucidate the Mechanisms of Reaction of a γ‐Methyl‐β‐alkynyl and an ortho‐Substituted Aryl Chloroformate Ester

AbstractReview: 76 refs.

Use of Linear Free Energy Relationships (LFERs) to Elucidate the Mechanisms of Reaction of a γ-Methyl-β-alkynyl and an ortho-Substituted Aryl Chloroformate Ester

The specific rates of solvolysis of 2-butyn-1-yl-chloroformate (1) and 2-methoxyphenyl chloroformate (2) are studied at 25.0 °C in a series of binary aqueousorganic mixtures. The rates of reaction obtained are then analyzed using the extended Grunwald-Winstein (G-W) equation and the results are compared to previously published G-W analyses for phenyl chloroformate (3), propargyl chloroformate (4), p-methoxyphenyl choroformate (5), and p-nitrophenyl chloroformate (6). For 1, the results indicate that dual side-by-side addition-elimination and ionization pathways are occurring in some highly ionizing solvents due to the presence of the electron-donating γ-methyl group. For 2, the analyses indicate that the dominant mechanism is a bimolecular one where the formation of a tetrahedral intermediate is rate-determining.

Correlation of the rates of solvolysis of i-butyl fluoroformate and a consideration of leaving-group effects.

The specific rates of solvolysis of isobutyl fluoroformate (1) have been measured at 40.0 °C in 22 pure and binary solvents. These results correlated well with the extended Grunwald-Winstein (G-W) equation, which incorporated the NT solvent nucleophilicity scale and the YCl solvent ionizing power scale. The sensitivities (l and m-values) to changes in solvent nucleophilicity and solvent ionizing power, and the kF/kCl values are very similar to those observed previously for solvolyses of n-octyl fluoroformate, consistent with the additional step of an addition-elimination pathway being rate-determining. The solvent deuterium isotope effect value (kMeOH/kMeOD) for methanolysis of 1 was determined, and for solvolyses in ethanol, methanol, 80% ethanol, and 70% TFE, the values of the enthalpy and the entropy of activation for the solvolysis of 1 were also determined. The results are compared with those reported earlier for isobutyl chloroformate (2) and other alkyl haloformate esters and mechanistic conclusions are drawn.