Efficient and Eco-Friendly Preparation of 4-Methyl-5-formyl-thiazole.docVIP

Molecules 2008, 13, 943-947 molecules ISSN 1420-3049 ? 2008 by MDPI /molecules Communication Efficient and Eco-Friendly Preparation of 4-Methyl-5-formyl-thiazole Nan Bai, Yaowu Sha* and Ge Meng The Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China * Author to whom correspondence should be addressed; E-mail: shayw@ Received: 6 April 2008; in revised form: 17 April 2008 / Accepted: 17 April 2008 / Published: 21 April 2008 Abstract: 4-Methyl-5-formylthiazole, an intermediate for synthesizing cefditoren pivoxil, was prepared in good yield by Pd/BaSO4 catalyzed hydrogenation of 4-methylthiazole-5- carboxylic acid chloride. Detailed reaction conditions have been studied. Keywords: 4-Methyl-5-formylthiazole, Pd/BaSO4 catalyzed hydrogenation. Introduction Cefditoren pivoxil (a, Figure 1) is a third-generation cephalosporin antibacterial with broad- spectrum and enhanced stability against many common β-lactamases. It has been approved in many countries for the treatment of adults and adolescents with acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), streptococcal pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections [1]. 4-Methyl-5-formylthiazole (b, Figure 1) is a key intermediate for the synthesis of cefditoren pivoxil [2], which was first synthesized in 1939 [3]. The formation of the aldehyde group in this substance has been the focus of much research. Recently developed methods include the oxidation of 4-methyl-5-(2- hydroxyethyl)thiazole or 4-methyl-5-(hydroxymethyl)thiazole with MnO2, CrO3, or NaOCl [4-7] and the reduction of carboxylic ester with LiAlH4, NaBH4, or Red-Al [4,8-10]. However, these methods are eco-unfriendly and too expensive for industrial production. One reported better method is Cr-ZrO2 catalyzed the gas phase hydrogenation