R. Issac, J. Tierney
1996
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Heterocyclic Communications
Abstract
The reaction of chloral with substituted anilines resulted in formation of the respective 2,2,2-trichloroethylidene anilines. Subsequent treatment of these imines in situ with thioglycolic acid produced a series of substituted 2trichloromethyl-3-phenyl-1,3-thiazolidin-4-ones. This synthetic route was interesting in light of several other possible intermediates which can be formed on reaction of chloral with amines. High resolution (300 MHz) H and C magnetic resonance spectra and ab initio calculations gave insight into the conformation of the observed products. Introduction. Review of the literature shows that the reaction of chloral with amines yields a variety of products depending on amine type and choice of reaction conditions. Chloral reacts exclusively with aliphatic amines to produce Nformyl compounds (1-4). Reaction of equimolar or excess substituted anilines with chloral in benzene gives Ν,Ν'-β,β,βtrichloroethylidene-fc/s-substituted anilines, CI3CCH(NH-C6H4X)2 (5). However, in polar solvents, i.e. aqueous acetic acid, these same two substrates yield N-arylaminoalcohols, CI3CCH(OH)NHC6H4X (6). Reaction of chloral with anthranilic acid results in formation of the imine Cl3CCH=NC6H4COOH (7). It would therefore appear that any primary amine, aliphatic or aromatic, reacts with chloral to initially form an aminoalcohol (8). The kinetics (3,4) of the reaction between chloral and some aliphatic cyclic amines, [C6H4(CH2)3NH], to give formamides (1,2) have been investigated. The reaction is second order overall, first order in each reactant. Unreacted aliphatic amine acts as a strong base which subsequently reacts with the intermediate N-alkylaminoalcohol. Since aliphatic amines are 1x10 more basic than their aromatic counterparts (9), the alcohol proton is removed from the Nalkylaminoalcohol and the trichloromethyl group leaves in a manner similar to the final stage of the iodoform reaction (10). In the case of the reaction of chloral with aromatic amines the outcome is less clear. The alcohol proton of the Narylaminoalcohol intermediate is not as labile because of the lower basicity of the aromatic amine. The N-arylaminoalcohol can now be attacked either by the amine acting as a nucleophile to yield the N,N'-ß,ß,ß-trichloroethylidene-b/'ssubstituted anilines, CI3CCH(NH-C6H4X)2, or undergo condensation to the imine. There is some evidence that condensation to the imine can be effected upon heating; however, the imines are generally unstable on attempted isolation (11).