5-羟甲基噻唑的合成工艺

Synthetic process of 5-Hydroxymethylthiazole

5-羟甲基噻唑是一种重要的医药和农药中间体,可用于合成第二代抗AIDS药物利托那韦。研究了以2-氯-5-氯甲基噻唑为原料,经过水解、还原脱氯合成5-羟甲基噻唑的工艺。适宜的工艺条件为:水解时,在75℃下,0.05 mol 2-氯-5-氯甲基噻唑,50 mL蒸馏水和22.4 g活化的强碱型阴离子交换树脂,反应3.5 h,树脂可重复使用2次;还原脱氯时,物料比n(2-氯-5-氯甲基噻唑)?n(水合肼)=1?3,10%Pd/C用量为2.0g,反应时间为1 h,Pd/C可重复使用4次。5-羟甲基噻唑总产率为70.44%,w(5-羟甲基噻唑)≥99%(GC,峰面积归一法)。5-羟甲基噻唑结构经元素分析、IR、LC-MS、1H-NMR和13C-NMR确证。

As an important medicine and pesticide intermediate,5-Hydroxymethylthiazole can be furthermore used in the synthesis of the second generation of anti-AIDS drugs Ritonavir.After studying,we obtained an improved process which synthesized 5-hydroxymethylthiazole by taking 2-chloro-5-chloromethylthiazole as raw material and through hydrolysis and reductive de-chlorination.The optimum process conditions were as follows： first,at 75 ℃,2-chloro-5-chloro-methylthiazole（0.05 mol） was hydrolyzed with activated strong alkali anion exchange resin（22.4 g） and 50 mL aqueous solution,the react time was 3.5 hours,and the resins could be repeatedly used twice;second,the obtained 2-Chloro-5-Hydroxymethylthiazole was dechlorinated with hydrazine hydrate and 10% Pd/C of 2.0 g as catalyst,mole ratio of reactants of 2-Chloro-5-Hydroxymethylthiazole and hydrazine hydrate was 1︰3,the Pd/C could be re-used 4 times,the reaction time was 1 hour.The results show that the total yield rate of 5-Hydroxymethylthiazole was 70.44%,w（5-Hydroxymethylthiazole）≥99%（GC,peak area normalization method）.The structure of 5-Hydroxymethylthiazole was confirmed by element analysis,IR,LC-MS,1H-NMR and 13C-NMR.