2,6-二氨基吡嗪-1-氧化物的合成优化

以亚胺基二乙腈为起始原料,经过亚硝化、环化两步反应得到2,6-二氨基吡嗪-1-氧化物(DAPO),总产率为66.6%。采用1 H NMR、IR、MS对其结构进行了表征。研究了环化反应的催化剂、氢氧化钠用量、反应起始温度等因素对DAPO总收率的影响。将传统合成方法中的催化剂三乙胺用氢氧化钠代替,确定了环化反应制备DAPO的最佳工艺条件为:N-亚硝基亚氨基二乙腈、盐酸羟胺、氢氧化钠质量比为1.0∶0.6∶1.0,初始温度5~10℃,反应时间30min,随后反应温度20℃,反应时间2h。结果表明,与传统三乙胺作催化剂的合成方法相比,以氢氧化钠作环化反应催化剂合成DAPO的收率由57.0%提高至78.7%。结合DAPO的合成过程,提出了2,6-二氨基吡嗪-1-氧化物(DAPO)的成环机理为:羟胺亲核加成N-亚硝基亚氨基二乙腈的氰基,生成N-亚硝基亚氨基二乙腈单缩合产物,在碱作用下与羟胺缩合成环,得到最终产物DAPO。

Optimization of Synthetic Method of 2,6-Diamino-pyrazine-1-oxide

2,6-Diamino-pyrazine-1-oxide(DAPO) was synthesized by two-step reactions of nitrosylation and cyclization, using iminodiacetonitrile as starting material.The total yield of DAPO was 66.6%.Its structure was characterized by 1H NMR,IR and MS.The effects of catalyst, dosage of sodium hydroxide and initial temperature etc factors for cyclization reaction on the total yield of DAPO were investigated.Triethylamine used in traditional synthesis method was replaced by sodium hydroxide as the catalyst.The optimum process conditions of preparing DAPO via cyclization reaction were determined as∶ONN(CH2CN)2∶NH2OH·HCl∶NaOH=10∶06∶10 (mass ratio),the initial temperature was 5-10℃,the reaction time was 30min,then,the reaction temperature was 20℃, the reaction time was 2h.The results show that compared with the method of triethylamine as catalyst, the yield of synthesizing DAPO by cyclization reaction is significantly increased from 57.0% to 787% with sodium hydroxide as catalyst.According to the synthetic process of DAPO,the cyclization mechanism of DAPO is proposed: nucleophilic addition occurs between hydroxylamine and N-nitrosobis(cyanomethyl)amine, generating the condensation product of N-nitroso-bis(cyanomethyl)amine, this compound cyclizes with hydroxylamine under the effect of alkali,and the final product DAPO is obtained.