甲酰胺法合成鸟嘌呤工艺

doi:10.16085/j.issn.1000-6613.2023-2002

摘要/Abstract

摘要：

由2,4-二氨基-5-亚硝基-6-羟基嘧啶（DAHNP）还原为2,4,5-三氨基-6-羟基嘧啶（TAHP）并形成TAHP硫酸盐步骤烦琐，且会带入大量无机盐，对鸟嘌呤（GA）粗品纯化造成困难，直接从DAHNP出发合成GA不仅能够解决这一问题，而且还能缩短反应流程，提高反应效能，为此本文设计了一种甲酰胺法合成GA的绿色路线。本研究以氰乙酸甲酯（MC）和盐酸胍（GH）为原料，经环合、亚硝化一锅法得到DAHNP，分离得到的DAHNP经亚硫酸氢钠还原，与甲酰胺脱水闭环一锅反应得到GA。系统考察了反应原料的摩尔比、亚硝酸钠投料量、甲醇钠甲醇溶液质量分数等对DAHNP收率的影响；研究了不同还原剂种类、投料量以及甲酰胺溶液的质量分数等因素对GA收率的影响。以亚硫酸氢钠为还原剂，n（MC）∶n（GH）∶n（CH₃ONa）∶n（NaNO₂）=1∶1.14∶1.6∶1.2，m（NaHSO₃）=3.5g，80%甲酰胺溶液，20%甲醇钠甲醇溶液时，GA收率可达80.7%，纯度≥99.0%。本合成工艺操作简便，流程简单，实现了甲酰胺溶剂的回收利用，适于工业化生产。

关键词: 鸟嘌呤, 甲酰胺, 氰乙酸甲酯, 盐酸胍, 一锅法

Abstract:

The reduction of 2,4-diamino-5-nitroso-6-hydroxy-pyrimidine (DAHNP) to 2,4,5-triamino-6-hydroxy-pyrimidine (TAHP) and the formation of TAHP sulfate is complicated and involves a large amount of inorganic salts, making it difficult to purify crude guanine (GA). Directly synthesizing GA from DAHNP can not only solve this problem, but also shorten the reaction process and improve the reaction efficiency. Therefore, this article designed a green route for the synthesis of GA by formamide method. This study used methyl cyanoacetate (MC) and guanidine hydrochloride (GH) as raw materials to obtain DAHNP through cyclization and nitrification in one-pot method. The separated DAHNP was then reduced by sodium bisulfite and reacted with formamide dehydration in a closed loop in one-pot to obtain GA. The effects of molar ratio of raw material, dosage of sodium nitrite and mass fraction of sodium methanolate solution on the yield of DAHNP were systemically investigated. The effects of types of reducing agent, dosage and mass fraction of formamide solution on GA yield were studied. When using sodium bisulfite as reducing agent, n(MC)∶n(GH)∶n(CH₃ONa)∶n(NaNO₂)=1∶1.14∶1.6∶1.2, m(NaHSO₃)=3.5g, 80% formamide solution and 20% sodium methanolate methanol solution, GA yield could reach 80.7% with purity ≥99.0%. The synthesis process was easy to operate and had a simple process, achieving the recovery and utilization of formamide solvent, which was suitable for industrial production.

Key words: guanine, formamide, methyl cyanoacetate, guanidine hydrochloride, one-pot method

中图分类号:

TQ612.6

李彬, 刘飞, 张天永, 姜爽. 甲酰胺法合成鸟嘌呤工艺[J]. 化工进展, 2024, 43(12): 6905-6912.

LI Bin, LIU Fei, ZHANG Tianyong, JIANG Shuang. Guanine synthesis process using formamide method[J]. Chemical Industry and Engineering Progress, 2024, 43(12): 6905-6912.

图/表 15

图1 化学法合成GA的路线

图2 甲酰胺法合成GA的路线

图3 GA的FTIR测试结果

图4 GA的13C NMR测试结果

图5 m（GH）∶m（MC）对DAHNP收率的影响

图6 MC与GH环合反应机理

图7 甲醇钠与MC摩尔比对DAHNP收率的影响

图8 甲醇钠甲醇溶液质量分数对DAHNP收率的影响

图9 NaNO2与MC摩尔比对DAHNP收率的影响

表1 酸的种类对DAHNP收率的影响

酸的种类	DAHNP/g	收率/%	纯度/%
HCl	8.8	94.0	99.1
H₂SO₄	7.3	78.0	97.6
H₃PO₄	7.9	84.0	98.5
HCOOH	8.2	87.0	98.6

表2 不同还原剂对GA收率的影响

还原剂种类	还原剂/g	GA/g	收率/%	纯度/%
NaHSO₃	2.1	5.2	85.2	99.2
Na₂S₂O₄	3.5	5.0	82.3	99.1
Na₂S₂O₅	3.8	4.9	81.2	99.2

图10 甲酰胺水溶液质量分数对GA收率的影响

图11 NaHSO3投料量对GA收率的影响

图12 反应时间和温度对GA收率的影响

图13 回收套用甲酰胺对GA收率的影响

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