Issue in Honor of Prof. Rudolph Abramovitch ARKIVOC 2001 (vi) 94-99
1,3-Dichloropropenes – in the preparation of thiazole derivatives – 2-chloro-5-chloromethylthiazole and 5-hydroxymethylthiazole
Gregory F. Hillstrom, Michelle A. Hockman, Ramiah Murugan*, Eric F.V. Scriven, James
R. Stout, and Jason Yang Reilly Industries, Inc., 1500 South Tibbs Ave., Indianapolis, IN 46242-0912 E-mail:
[email protected]
Dedicated to Professor Rudy Abramovitch on the occasion of his 70th birthday (received 21 Jun 01; accepted 11 Oct 01; published on the web 19 Oct 01)
Abstract
1,3-Dichloropropene (a mixture of cis and trans isomers) has been used to synthesize thiazole derivatives by starting its reaction with sodium thiocyanate to give 3-chloro-2propenylthiocyanate. This thiocyanate on heating undergoes thermal [3,3]-sigmatropic rearrangement to give the isothiocyanate derivative, 3-chloro-1-propenylisothiocyanate. This mixture of cis and trans isomers of isothiocyanate on chlorination gave 2-chloro-5chloromethylthiazole. 5-Hydroxymethylthiazole is made from 2-chloro-5-chloromethyl thiazole in two steps, first by displacement of the aliphatic halogen with formate anion followed by hydrolysis of the formate ester and hydrodehalogenation of the aromatic halogen using hydrogen and palladium on carbon catalyst.
Keywords: 1,3-Dichloropropene, 2-chloro-5-chloromethylthiazole, 5-hydroxymethylthiazole, thiocyanate, isothiocyanate, chlorination
Introduction
Heterocycles based on thiazole ring systems are biologically active. Hence, thiazole ring systems containing molecules are known in pharmaceuticals as well as in agrochemical products.1-6 For example, ritonavir an anti-HIV drug contains a 5-substituted oxymethylthiazole moiety, and an isostere of the important insecticide, imidacloprid has 2-chloro-5-substituted methylthiazole as part of the molecule (Figure 1).
ISSN 1424-6376 Page 94 ©ARKAT USA, Inc
