Thioamides from aromatic compounds

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

The Willgerodt reaction is useful in the preparation of arylacetic acids and amides from substituted methyl aryl ketones or vinyl aromatic compounds. The aliphatics and acetylenes give lower yields. The conversion is effected by heating aromatic compounds at 160°-200°C in an aqueous solution under pressure using ammonium polysulfide. In the Kindler modification, the ketone or styrene is refluxed with a mixture of sulfur and an amine, usually morpholine, to give a thioamide, ArCHjCSNRj. 

Oxidation of sulfur compounds. Aromatic amides are obtained from thio-amides on treatment with the H2O2-C0CI2 system. Aliphatic thioamides do not behave in the same way. 

Also, carbanions derived from esters, Al,Al-disubstituted amides, thioamides, imides, and 0-cyanocarbonyl and 0-dicarboxylic compounds have been successfully used as nucleophiles to form new C—C bonds with aromatic substrates [9]. 

That a carbonamide rather than a thioamide is isolated in the Willgerodt reaction with aqueous ammonia does not constitute an argument against the above scheme, for hot aqueous ammonia is known to convert thioamides to carbonamides. The isomerization of straight-chain acetylenic compounds (with and without aromatic substituents) to products having the acetylene function in the terminal position is known to take place in the presence of sodium amide. The assumption that such unsaturated substances are intermediates in the Willgerodt reaction offers an explanation of the appearance of certain by-products. Tetra-hydronaphthoic acid, isolated in small amounts from the reaction of ethyl 6-tetralyl ketone with morpholine and sulfur, may arise from an oxidative attack by sulfur on an unsaturated intermediate. The presence of traces of thiophenes in the reaction mixtures is explicable when it... 

Aromatic thioamides react with MeC(0)CHClC(0)C02Et to give a 3 1 ratio of ethyl 5-acetyl-2-aryl-thiazole-4-carboxylates and the isomeric products (2). Modifications of the Hantzsch synthesis continue to appear. Thus, 2-aryl-5-aroyl-thiazoles may be prepared from the JV -thioaroyl-iViV-dimethyl-formamidines ArC(S)N=CHNMea and a-bromo-ketones [strictly speaking, this is a Type F (C—N—C—S + C) synthesis], whilst 5-amino-2-phenyl-l,2,3-thiadiazolium salts [e.g. (3)] and compounds with the general structure RCHgCN (e.g. R = CN or COaEt) yield 4-amino-thiazoles. ... 

Some of the most common nucleophiles through which a new CC bond can be formed are carbanions from hydrocarbons, nitriles, ketones, esters, N,N-dialkyl acetamides and thioamides, and mono- and dianions from 3-dicarbonyl compounds. The synthesis of indoles, isocarbostyrils, isoquinolines, benza-zepines, binaphthyls, etc. and an important number of natural products has been achieved by ring closure reactions of carbanions with suitable substrates through the Sgj.jl mechanism. Several reviews have been published in relation to aromatic Sgj,l reactions and to the synthetic applications of the process. - ... 

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