Thioamides from ammonia

Thioketenes (34) are highly electrophilic and give a smooth reaction with ammonia or amines. In fact, addition of a secondary amine offers the best way to scavenge a suspected thioketene. But the approach also deserves interest from the point of view of thioamide synthesis as it allows very mild and nonreducing conditions, tolerating the presence of sensitive additional functional groups such as cyano, nitro, or sulfonyl residues (equation... 

Tetrakis(dimethylamino)titanium is a useful reagent for preparing amidines from secondary amides. From A X-thionyldiimidazole and secondary amides of boA aromatic and aliphatic carboxylic acids amidines (313 Scheme 50) are formed under mild conditions in moderate to good yields. N-Tosyl-amidines (314) can be obtained by reacting secondary thioamides (aliphatic and aromatic) with tosyl azide. Thiobenzamides have been condensed with anilines to afford amidines (315). Thioamides can be converted to amidines, e.g. (316), by treatment with ammonia in the presence of mercury acetate. ... 

Synthesis of Isothiazoles from Aqueous Ammonia and Thioamide Vinylogues (Type H). Aqueous ammonia transaminates the thioamide vinylogues. In addition, the 3-amino-l-arylpropenethiones, in the presence of elemental sulphur, undergo ring-closure to give 65-95% of 5-arylisothiazoles (9) (Scheme 2). 

Aqueous ammonia reacts in the cold with PSCI3 to produce a mixture of NH4 POS(NH2)2 and (NH4)2P02S(NH2). The proportion of diamidate in the product increases with the concentration of ammonia used. Various thioamides, ammonium salts and so forth, can be obtained from direct reactions between ammonia and amides with the phosphorus sulphides (Chapter 4.3). 

The Hantzsch synthesis has been used to generate pyrroles, thiazoles and dihydropyridine derivatives. Pyrroles (3) are generated from the reaction of P-ketoesters with ammonia, ammonia derivatives or primary amines, and a-haloketones (path A). Thiazoles (5) are generated from the reaction between a-haloketones and thiourea or thioamide derivatives (path B). Dihydropyridines (7) are generated from the reaction of aldehydes with p-ketoesters and ammonia or ammonia derivatives, or enamines derived from the reaction of ketones or P-ketoesters with amines (path C). Dihydropyridines can be readily converted to the corresponding pyridine derivatives and so this reaction is often termed the Hantzsch pyridine synthesis. 

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... 

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