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

Malcolm D'Souza,Dennis Kevill

doi:10.3390/ijms151018310

Abstract

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. The phenyl chlorothioformate (PhSCOCl) and phenyl chlorothionoformate (PhOCSCl) react at remarkably similar rates in a given solvent and there is a dichotomy of behavior with the A-E pathway favored in solvents such as ethanol-water and the ionization mechanism favored in aqueous solvents rich in fluoroalcohol. Alkyl esters behave similarly but with increased tendency to ionization as the alkyl group goes from 1° to 2° to 3°. N,N-Disubstituted carbamoyl halides favor the ionization pathway as do also the considerably faster reacting thiocarbamoyl chlorides. The tendency towards ionization increases as, within the three contributing structures of the resonance hybrid for the formed cation, the atoms carrying positive charge (other than the central carbon) change from oxygen to sulfur to nitrogen, consistent with the relative stabilities of species with positive charge on these atoms.

Highlights

Compounds of the type RO(C=O)Cl can be considered as derived from formate esters by replacement of the carbonyl-attached hydrogen by chlorine, leading to the naming as chloroformates, or as derived from half-esters of carbonic acid by replacing the hydroxyl group by chlorine, leading to naming as chlorocarbonates [1]
Reactions involving a rate-determining addition at an unsaturated carbon atom, such as the carbonyl carbon of chloroformate esters, will show a high sensitivity to changes in solvent nucleophilicity and a reduced sensitivity to changes in solvent ionizing power, governed primarily by the solvation of the negative charge developing on the carbonyl oxygen
A steady increase was observed from methyl to primary to secondary structures, with the continuation to the tertiary alkyl structure leading to a specific rate too large to measure by the conductometric technique employed

Summary

Introduction

Compounds of the type RO(C=O)Cl can be considered as derived from formate esters by replacement of the carbonyl-attached hydrogen by chlorine, leading to the naming as chloroformates, or as derived from half-esters of carbonic acid by replacing the hydroxyl group by chlorine, leading to naming as chlorocarbonates [1]. An alternative approach to naming involves a consideration of replacing one of the chlorines of carbonyl chloride (phosgene, COCl2) with an alkoxy or aroxy group, to give alkoxycarbonyl or aroxycarbonyl chloride This system of naming is the most convenient to use when these compounds are being used as reagents for the introduction of protecting groups (substituents) during peptide synthesis [2,3,4]. Reactions involving a rate-determining addition at an unsaturated carbon atom, such as the carbonyl carbon of chloroformate esters, will show a high sensitivity to changes in solvent nucleophilicity and a reduced sensitivity to changes in solvent ionizing power, governed primarily by the solvation of the negative charge developing on the carbonyl oxygen. N,N-disubstituted thiocarbamoyl halides have been summarized [39]

Chlorothioformates

Chlorothionoformates

Chlorodithioformates

Carbamoyl and Thiocarbamoyl Halides

Conclusions