Synthesis and reactions of 2‐(alkylthio)‐4,4‐dimenthyl‐1,3‐thiazole‐5(4H)‐thiones

Abstract

Dedicated to Prof. Heinr G. Viehe on the occasion of his 65th birthday (2.1X.94) Six 2-(alkylthio)-substituted 4,4-dimethyl-l,3-thiazole-5(4H)-thiones were synthesized according to a new method. The reactions of these compounds with allyl-and benzyllithium reagents, 1,3-dipoles, and dimethyl acetylenedicarboxylate proceeded in a similar manner to 2-alkyl-substituted analogues, while methyllithium reacted in a different way yielding trithio-orthoester derivatives.1. Introduction. -A few years ago, due to the lack of appropriate synthetic methods, 1,3-thiazole-5(4H)-thiones were only scarcely known five-membered heterocycles. In 1986, a convenient synthesis of 4,4-disubstituted 1,3-thiazole-5(4H)-thiones was developed by our group [l] [2]. It is based on a reaction involving reactive three-membered rings, the 3-amino-2H-azirines [3] : the addition reaction of thiocarboxylic acids and 3-amino-2H-azirines yielded thiodiamides. On heating with Lawesson reagent [4-61, cyclization of the thioamides afforded 2-substituted 1,3-thiazole-5(4H)-thiones in very good yields [2].Another approach to 1,3-thiazole-5(4H)-thiones is the reaction of carboxylic acids with 3-amino-2H-azirines affording diamides; after thionation of the latter with Heimgartner reagent [7], 2-substituted 1,3-thiazole-5(4H)-thiones were obtained in fair-togood yields [7].However, 1,3-thiazole-5(4H)-thiones with substituents other than alkyl or aryl at C(2) are not accessible by these methods. Since 2-seleno-and 2-thio-substituted 4,5-dihydro-1,3-thiazoles could be useful intermediates in penam syntheses [8] [9], new approaches for the preparation of differently substituted 1,3-thiazole-5(4H)-thiones are still needed. In this paper, a new approach for the synthesis of 2-(alky1thio)-substituted 1,3-thiazole-5(4H)-thiones is described, and some reactions of these compounds with organolithium reagents, 1,3-dipoles, acetylenes, and reducing agents are reported and compared with the 2-alkyl-substituted analogues.

Intramolecular fixation of t-butyl groups in thiolactim ethers influencing molecular conformation and the packing behavior

“…That is, involvement of the t-butyl group at both ends of the molecule in the formation of inversely bifurcated hydrogen bond type interactions to one of the pyrimidine nitrogens each has been observed. Aside from related behavior found for a few thiourea derivatives [5][6][7][8], this kind of intramolecular bonding motif has not yet been observed for respectively substituted azines such as in the present case. The question arises whether the particular conformation of the molecule is only a consequence of packing effects in the crystalline state or reversely an attractive C-H···N interaction restricting conformational flexibility of the molecule which exercises an influence on the packing.…”

New Addition Reactions of Organometal Compounds with 4,4‐Dimethyl‐1,3‐thiazole‐5(4H)‐thiones

“…This is obvious for the formation of trithioorthoesters from 2-(alkylthio)-4,4-dimethyl-l,3-thiazole-5(4H)-thiones and MeLi [64]. On the basis of our experiments and the results reported in the literature, we propose the radical mechanisms formulated 'in Scheme 5 for the reaction of the thiocarbonyl group of 1 with alkyl(ary1)metals ( A ) and allylmetals (B), rlespectively.…”

Synthesis of Endothiopeptides and Their Cyclization to 1,3-Thiazol-5(4H)-imines

“…However, as a result of the steric interactions with the geminal Me groups at C(4) of the thiazole ring, it can be assumed that the (Z)-configuration is preferred, as shown for simpler but comparable 1,3-thiazol-5(4H )-imines (cf. [30] [31]).…”