The Pharmaceutical Intermediates Synthesis Of Thiadiazole

1,3,4,-thiadiazoles derivatives are a series of compounds which are widely investigated and applied to industry,agriculture,medicine and so on,especially they have achieved great progress in the synthesis of anticancer medicine.In this paper,2-amino-5-mercapto-1, 3,4-thiadiazole was used as the material to decorate the 2-amino and 5-metcapto.New compounds were obtained and their corresponding synthetical methods were formed.The new compounds were expected to provide the basis for the synthesis and drug screening.The main content was described from three aspects as follows:1.Forming a new synthesis methods of 2-amino-5-carboxymethylmethylthio-1,3,4-thiadiazoleThe new compounds:2-amino-5-mercapto-1,3,4-thiadiazole and methyl chloroacetate was taken as the reagent to obtain 2-amino-5-carboxymethylmethylthio-1,3,4-thiadiazole.The experimental results of new route shows that under room temperature in water and while the mole ratio was n(2-amino-5-mercapto-1,3,4-thiadiazole):n(methyl chloroacetate):n(NaOH)= 1:1.4:1.05,the product yield was near 90%,and the purity was more than 99%.2.With 2-amino-5-mercapto-1,3,4-thiadiazole as the reagent,two new compounds were synthesized by aminoacylase,mercapto-sulfonyl chlorination,sulfonation reaction.And the synthetical conditions were optimized.â‘ Aminoacylase:the product can be obtained in 12ml acetic acid at 70℃when the mole ratio is n(2-(?)amino-5-mercapto-1,3,4-thiadiazole):n(acetic anhydride)=1:1.25. And the product yield was more than 88%.â‘¡Mercapto-sulfonyl chlorination:2-acetylamino-5-mercapto-1,3,4-thiadiazole was Oxidized by chlorine at 0-4℃in the 33%acetic acid solution.The yield of 2-acetylamino-1, 3,4-thiadiazole-5-sulfonyl chloride was more than 85%.â‘¢sulfonation reaction:5-acetylamino-1,3,4-thiadiazole-(2-N-methyl piperazine) sulfonylanilin and 5-acetylamino-1,3,4-thiadiazole-(2-sulfonyl)-aniline have been synthesized in ethanol solution with the mole ratio of n(2-acetylamino-1,3,4 -thiadiazole-5-sulfonyl chloride):n(secondary amine)=1:2.The yield was 94%and 97% respectively.The purity was 97.8%and 97.3%.Their structures were confirmed by IR,¹H NMR and MS. 3.2-amino-5-(β-nitriethylsulfhydryl)-1,3,4-thiadiazole was synthesized by a new method under N₂ atmosphere at 40℃in methanol with triethylamine as the catalyst while the mole ratio of 2-amino-5-mercapto-1,3,4-thiadiazole and ccrylonitrileis was 1:2.The product yield was 52%and the purity was 99.7%.And another new compound of 2-amino-5-(β-methoxy methacyl ethylsulfhydryl)-1,3,4-thiadiazole was synthesized.The product yield was 45.7%and purity was 98.3%.