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

Kenneth K. Andersen, Diana D. Bray, Anders Kjær, Yuhui Lin, Massud Shoja

    Research output: Contribution to journalJournal articleResearchpeer-review


    Symmetrical 2,2',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 effect 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*,4R'*)-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 2,2'-diphenyl-4,4'-dibenzyl-[4,4'-bithiazole]-5,5'(4H,4'H)-dione were treated with nocleophiles. The former gave imide derivatives of alfa,alfa-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 and 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 alfa,alfa-dehydrodimeric amino acid.
    Original languageEnglish
    JournalActa Chemica Scandinavica
    Pages (from-to)1000-1015
    Publication statusPublished - 1997

    Cite this