Synthesis of symmetrical 2,2',4,4'-tetrasubstituted [4,4'-bithiazole]-5,5'(4H,4'H)-diones and their reactions with some nucleophiles.

Symmetrical ,2′,4,4′-tetrasubstituted-[4,4′-bithiazole]-5,5′(4H, 4′H)-diones were obtained in high yields by oxidation of 5(4H)-thiazolones by KMnO₄ in acetic acid. In some cases, the isomeric 2,4′- and 2,2′-bithiazolones were also formed. Results from two crossover reactions were consistent with a free radical mechanism. Four series of thiazolones were prepared, each based on a different substituent at the 2-position; i.e., phenyl, ethoxy, ethyl and ethylthio. The effects of substituents on the isomer distributions of the dehydrodimers indicated that electronic factors were less important than steric factors. X-Ray crystallography established the structure of the dehydrodimer (4R*,4′R^*)-2,2′-diethoxy-4,4′-dibenzyl-[4,4′ -bithiazole]-5,5′(4H,4′H)-dione. One stereoisomer of 2,2′-diphenyl-4,4′-dimethyl-[4,4′-bithiazole]-5,5′(4H, 4′H)-dione and a mixture of the stereoisomers of 2,2′ -diphenyl-4,4′-dibenzyl-[4,4′-bithiazole]-5,5′(4H,4′H)- dione were treated with nucleophiles. The former gave imide derivatives of ́,́′-dehydrodimeric amino acids when the nucleophile was L-alanine ethyl ester or 1-butylamine. The structure of one of the reaction products, (4R*,5R*)-2,5-diphenyl-2-thiazoline-4-carboxylic acid piperidylamide, was established by X-ray crystallography. Treatment of stereoisomeric mixtures of 2,2′-diethoxy-4,4′-bithiazolones with HCl in benzene gave the corresponding racemic and meso bis-(N-carboxythioanhydride)s. A stereoisomeric mixture of the bis(N-carboxythioanhydride)s of leucine treated with glycine ethyl ester gave a bicyclic derivative of the ́,́′-dehydrodimeric amino acid.