The Synthetic Processing Of 5-Hydroxymethylthiazole

5-Hydroxymethylthiazole is one of the most important medication and pesticide intermediates and a fine solvent. It is widely used in medicine, pesticide, electronic, et al. The synthetic processes of 5-hydroxymethylthiazole are studied by many scientists. 5-Hydroxymethylthiazole was synthesized by four processes of ethanol esterification method, aqueous solution esterification method, "one pot" method and resin catalytic hydrolysis method from 2-chloro-5-chloromethylthiazole for reducing cost. The optimum process was determined by univariate experiments and intuitionistic analysises. The results showed that:1. For 1 mol 2-chloro-5-chloromethylthiazole in the ethanol esterification method, the total yield of 5-hydroxymethylthiazole was 76.23%(w(5-hydroxymethylthiazole) >99%, GC peak area normalization method) under optimum conditions.5-Hydroxy-methylthiazole was synthesized by esterification in 80%-90% ethanol refluxing for 5 h-6 h with the materials ratio of n(2-chloro-5-chloromethylthiazole):n(sodium acetate trihydrate) =1:2; reduction dechlorination on zinc/glacial acetic acid for 1 h with the materials ratio of n(2-chloro-5-chloromethylthiazole):n(Zn)=1:3; hydrolysis in 25% sodium hydroxide solution at 70℃-75℃for 2 h.2. For 0.05 mol 2-chloro-5-chloromethylthiazole in the aqueous solution esterification method, the total yield of 5-hydroxymethylthiazole was 68.30%(w(5-hydroxymethyl-thiazole)>99%, GC peak area normalization method) under optimum conditions. 5-Hydroxymethylthiazole was synthesized by esterification in 33% sodium acetate solution at 85℃for 3 h; reduction dechlorination on zinc/glacial acetic acid for 1 h with the materials ratio of n(2-chloro-5-chloromethylthiazole): n(Zn)=1:3; hydrolysis in 25% sodium hydroxide solution at 70℃-75℃for 2 h.3. For 0.25 mol 2-chloro-5-chloromethylthiazole in the "one pot" method, the total yield of 5-hydroxymethylthiazole was 68.20%(w(5-hydroxymethylthiazole)>99%, GC peak area normalization method) under optimum conditions.5-Hydroxymethyl-thiazole was synthesized by esterification in glacial acetic acid at 120℃for 3 h with the materials ratio of n(2-chloro-5-chloromethylthiazole):n(sodium acetate trihydrate)=1: 2; reduction dechlorination on zinc/glacial acetic acid for 1 h with the materials ratio of n(2-chloro-5-chloromethylthiazole): n(Zn)=1 :3; hydrolysis in 25% sodium hydroxide solution at 70℃-75℃for 2 h.4. For 0.05 mol 2-chloro-5-chloromethylthiazole in the resin catalytic hydrolysis method, the total yield of 5-hydroxymethylthiazole was 72.65%(w(5-hydroxymethyl-thiazole)>99%, GC peak area normalization method) under optimum conditions. 5-Hydroxymethylthiazole was synthesized by hydrolysis in 80 mL aqueous solution at 75℃for 3 h with 57.3 g resin; reduction dechlorination on 2.0 g 10% Pd/C as catalyst with the materials ratio of n(2-chloro-5-chloromethylthiazole):n(hydrazine hydrate) =1:3 for 1 h. The resin was used repeatedly by 6 times and the Pd/C was re-used 4 times.5. Ethanol esterification method was the optimum synthetic process of 5-hydroxy-methylthiazole, which was determined by raw materials cost calculations. The yield of 5-hydroxy-methylthiazole was up to 81.00% with the raw materials cost decreased 10% after amplification experiment by 20 L reaction vessel.6. The structures of intermediates were confirmed by IR, LC-MS and 1H-NMR. The structure of 5-hydroxymethylthiazole was confirmed by element analysis, IR, LC-MS, 1 H-NMR and 13C-NMR.