Structural problems posed by reactions of thiocyanates with malonyl chloride.

Malonyl Chloride reacts with alkyl and aryl thiocyanates yielding 2-alkyl- (or aryl) thio-7-chloro-4-5-dioxopyrano[3,4-e]-3-oxazines (I). These react stepwise with amines, undergoing replacement of the thio group and then of the chloro substituent. Next, the pyrone ring is opened and finally the oxazine ring, to yield N-substituted beta-aminoglutacondiamides having an alpha-carboxyureido side chain. The intermediate 2-7-diamino-4,5-dioxopyrano[3,4-e]I,3-oxazines (some of which are tautomeric) suffer oxazine ring scission with amine hydrochloride and yield substituted 4,6-diaminopyran-2-one-3-carboxyureides. The parent product (I) with amine hydrochloride retains the sulphur group and yields 4,6-diaminopyrone-3-carboxythiourethanes. However, the reactions of the parent product (I) with water and alcohol gave several quite unexpected products. From the reaction of compounds (I) with water (1 mol.) at 80°C the 6-Amino-3-thioester-2 pyrones (2) were obtained. Whilst in the presence of hydrogen chloride, 4-chloro-6-N-(substituted) thiocarboxyamido 2-pyrones resulted. Boiling water (2 mols) with compounds (I) gave 4-chloro-2,6-dihydroxypyridins, also obtained similarly from the compounds (2). 4-Chloro-2,6-dihydroxypyridine-3carboxylic esters arose when compounds (I) or (2) were refluxed with alcohols. With alcohols at ambient temperature the compounds (I) underwent replacement of the S-alkyl group by alkoxyl, but under reflux with I mol of alcohol two isomers C[7]H[2]C1NO[4](SR)OR[I] were formed. The structures of these and other products were elucidated by chemical and physical means, especially [1]H and [13]C NMR and mass spectrometry. Possible reaction mechanisms are discussed and some use has been made of specific carbon-13 labelling