制备异亚硝基丙二酸二乙酯的反应热安全分析和机理研究

本研究在丙二酸二乙酯和亚硝酸钠反应制备法匹拉韦中间体异亚硝基丙二酸二乙酯过程中,发现存在二次放热现象,并且亚硝酸钠的用量远超理论量.通过在线红外检测和反应热力学数据等对其反应过程进行了研究,探讨了二次放热原因,并解释了该反应机制,辨识出风险关键点,为该类亚硝化反应的研究提供了有力的安全数据支撑.

Thermal Safety Analysis and Mechanism Explanation of Preparation of Diethyl Isonitrosomalonate

In this paper,secondary exothermic phenomena was found in the preparation of diethyl isonitrosomalonate from diethyl malonate and sodium nitrite,the intermediate of favipiravir.And the dosage of sodium nitrite was far higher than the theoretical amount.The reaction process was studied by on-line infrared and thermodynamic data,the causes of secondary exothermic phenomena were discussed,and the possible reaction mechanism was explained,and the key risk points were identified,which could provide a strong support for the safety research of this nitrosation reaction.