Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides.

There have been several studies on the solvolysis mechanisms for alkanesulfonyl chlorides (RSOCl) and arenesulfonyl chlorides (ArSOCl). The earlier of these studies were reviewed a little over thirty years ago by Gordon, Maskill and Ruasse ( , , 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.

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, ) in hydroxylic solvents. The rate constants of the solvolysis of were well correlated using the Grunwald-Winstein equation in all of the 20 solvents (R = 0.985).

The Influence of a Terminal Chlorine Substituent on the Kinetics and the Mechanism of the Solvolyses of -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 Nitro Group in the Solvolysis of Benzyl and Benzoyl Halides.

A kinetic study was carried out on the solvolysis of -nitrobenzyl bromide (-isomer, ) and -nitrobenzyl bromide (-isomer, ), and -nitrobenzoyl chloride (-isomer, ) in a wide range of solvents under various temperatures. In all of the solvents without aqueous fluoroalcohol, the reactions of were solvolyzed at a similar rate to those observed for , and the reaction rates of were about ten times slower than those of the previously studied -nitrobenzoyl chloride (-isomer, ). For solvolysis in aqueous fluoroalcohol, the reactivity of was kinetically more reactive than .

Classical tosylate/chloride leaving group approach supports a tetrahedral transition state for additions to trigonal carbon.

The experimentally measured rates of solvolysis of 2-chloroethoxycarbonyl chloride (2-chloroethyl chloroformate, , 2-chloroethoxycarbonyl -toluenesufonate , and phenoxycarbonyl -toluenesulfonate () were followed at 25.0 °C in various pure and binary aqueous-organic solvents with varying degrees of polarity. An analysis of the rate constants for , and , was carried out using the two-term extended Grunwald-Winstein equation and comparisons are made to the previously published results for ethyl and phenyl chloroformate esters.

Correlation of the rates of solvolysis of α-bromoisobutyrophenone using both simple and extended forms of the Grunwald-Winstein equation and the application of correlation analysis to related studies.

A Grunwald-Winstein treatment of the specific rates of solvolysis of α-bromoisobutyrophenone in 100% methanol and in several aqueous ethanol, methanol, acetone, 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) mixtures gives a good logarithmic correlation against a linear combination of (solvent nucleophilicity) and (solvent ionizing power) values. The and sensitivity values are compared to those previously reported for α-bromoacetophenone and to those obtained from parallel treatments of literature specific rate values for the solvolyses of several tertiary mesylates containing a C(=O)R group attached at the α-carbon. Kinetic data obtained earlier by Pasto and Sevenair for the solvolyses of the same substrate in 75% aqueous ethanol (by weight) in the presence of silver perchlorate and perchloric acid are analyzed using multiple regression analysis.

Correlation analysis of the rates of solvolysis of 4-bromopiperidine: a reaction following a Grob fragmentation pathway.

A Grunwald-Winstein treatment of the specific rates of solvolysis of 4-bromopiperidine gives for aqueous ethanol, methanol, acetone, and dioxane a very good logarithmic correlation against the solvent ionizing power values with a slope ( value) of 0.46±0.02, consistent with the operation of a synchronous Grob fragmentation mechanism.

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.

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.

Influence of sulfur for oxygen substitution in the solvolytic reactions of chloroformate esters and related compounds.

The replacement of oxygen within a chloroformate ester (ROCOCl) by sulfur can lead to a chlorothioformate (RSCOCl), a chlorothionoformate (ROCSCl), or a chlorodithioformate (RSCSCl). Phenyl chloroformate (PhOCOCl) reacts over the full range of solvents usually included in Grunwald-Winstein equation studies of solvolysis by an addition-elimination (A-E) pathway. At the other extreme, phenyl chlorodithioformate (PhSCSCl) reacts across the range by an ionization pathway.

LFER Studies Evaluating Solvent Effects on an α-Chloro-and two β,β,β-Trichloro-Ethyl Chloroformate Esters.

To provide insight and to identify the occurrence of mechanistic changes in relation to variance in solvent-type, the solvent effects on the rates of solvolysis of three substrates, 2,2,2-trichloro-1,1-dimethylethyl chloroformate, 2,2,2-trichloroethyl chloroformate, and 1-chloroethyl chloroformate, are analyzed using linear free energy relationships (LFERs) such as the extended Grunwald-Winstein equation, and a similarity-based LFER model approach that is based on the solvolysis of phenyl chloroformate. At 25.0 °C, in four common solvents, the α-chloroethyl chloroformate was found to react considerably faster than the two β,β,β-trichloro-substituted analogs.

Kinetic studies that evaluate the solvolytic mechanisms of allyl and vinyl chloroformate esters.

At 25.0 °C the specific rates of solvolysis for allyl and vinyl chloroformates have been determined in a wide mix of pure and aqueous organic mixtures. In all the solvents studied, vinyl chloroformate was found to react significantly faster than allyl chloroformate.

Correlation of the rates of solvolysis of -butyl chlorothioformate and observations concerning the reaction mechanism.

The "parent" tertiary alkyl chloroformate, -butyl chloroformate, is unstable, but the -butyl chlorothioformate () is of increased stability and a kinetic investigation of the solvolyses is presented. Analyses in terms of the simple and extended Grunwald-Winstein equations are carried out. The original one-term equation satisfactorily correlates the data with a sensitivity towards changes in solvent ionizing power of 0.

Application of the Grunwald-Winstein Equations to Studies of Solvolytic Reactions of Chloroformate and Fluoroformate Esters.

Chloroformates are important laboratory and industrial chemicals with almost one hundred listed in the catalogs of leading suppliers. They are, for example, of prime importance as protecting groups in peptide synthesis. In some instances, the more stable fluoroformate is preferred.

Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations.

The specific rates of solvolysis of chloromethyl phenyl sulfide [(phenylthio)methyl chloride] and its p-chloro-derivative have been determined at 0.0 °C in a wide range of hydroxylic solvents, including several containing a fluroalcohol. Treatment in terms of a two-term Grunwald-Winstein equation, incorporating terms based on solvent ionizing power (Y(Cl)) and solvent nucleophilicity (N(T)) suggest a mechanism similar to that for the solvolyses of tert-butyl chloride, involving in the rate-determining step a nucleophilic solvation of the incipient carbocation in an ionization process.

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).

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 N(T) solvent nucleophilicity scale and the Y(Cl) solvent ionizing power scale.

Understanding Solvent Effects in the Solvolyses of 4-Fluorophenyl Chlorothionoformate.

The solvolyses of 4-fluorophenyl chlorothionoformate (1) are studied in fifteen binary aqueous organic mixtures of widely varying nucleophilicity and ionizing power values. The specific rates of solvolyses of 1 are plotted against the specific rates of solvolysis observed for phenyl chloroformate (2) and deviations from the line-of-best-fit are observed in some of the highly ionizing aqueous fluoroalcohol mixtures. An analysis of the solvolytic data accumulated using the extended (two-term) Grunwald-Winstein equation confirms this deviant behavior and shows that dual bimolecular addition-elimination and unimolecular ionization channels occur in the solvolyses of 1.

Detailed Analysis for the Solvolysis of Isopropenyl Chloroformate.

The specific rates of solvolysis (including those obtained from the literature) of isopropenyl chloroformate (1) are analyzed using the extended Grunwald-Winstein equation, involving the N(T) scale of solvent nucleophilicity (S-methyldibenzothiophenium ion) combined with a Y(Cl) scale based on 1-adamantyl chloride solvolysis. A similarity model approach, using phenyl chloroformate solvolyses for comparison, indicated a dominant bimolecular carbonyl-addition mechanism for the solvolyses of 1 in all solvents except 97% 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). An extensive evaluation of the outcomes acquired through the application of the extended Grunwald-Winstein equation resulted in the proposal of an addition-elimination mechanism dominating in most of the solvents, but in 97-70% HFIP, and 97% 2,2,2-trifluoroethanol (TFE), it is proposed that a superimposed unimolecular (S(N)1) type ionization is making a significant contribution.

A Study of Solvent Effects in the Solvolysis of Propargyl Chloroformate.

The specific rates of solvolysis of propargyl chloroformate (1) are analyzed in 22 solvents of widely varying nucleophilicity and ionizing power values at 25.0 °C using the extended Grunwald-Winstein equation. Sensitivities to solvent nucleophilicity (l) of 1.

Kinetic evaluation of the solvolysis of isobutyl chloro- and chlorothioformate esters.

The specific rates of solvolysis of isobutyl chloroformate (1) are reported at 40.0 °C and those for isobutyl chlorothioformate (2) are reported at 25.0 °C, in a variety of pure and binary aqueous organic mixtures with wide ranging nucleophilicity and ionizing power.

Correlation of the rates of solvolysis of neopentyl chloroformate-a recommended protecting agent.

The specific rates of solvolysis of neopentyl chloroformate (1) have been determined in 21 pure and binary solvents at 45.0 °C. In most solvents the values are essentially identical to those for ethyl and n-propyl chloroformates.

Use of the Simple and Extended Grunwald-Winstein Equations in the Correlation of the Rates of Solvolysis of Highly Hindered Tertiary Alkyl Derivatives.

The original Grunwald-Winstein equation (1948) involved the development of a scale of solvent ionizing power (Y). Subsequent work has refined this scale and involved the development of scales of solvent nucleophilicity (N) and a term to correct for deviations when aromatic rings are present, governed by the aromatic ring parameter (I). These three scales, and the sensitivities towards each, can be related to specific rates of solvolysis through linear free energy relationships (LFERs).

Analysis of the nucleophilic solvation effects in isopropyl chlorothioformate solvolysis.

Correlation of the solvent effects through application of the extended Grunwald-Winstein equation to the solvolysis of isopropyl chlorothioformate results in a sensitivity value of 0.38 towards changes in solvent nucleophilicity (l) and a sensitivity value of 0.72 towards changes in solvent ionizing power (m).