卤代硝基苯酚中间体的应用与关键合成技术

Application and Crucial Synthetic Progress of Halogenated Nitrophenol Intermediates

卤代硝基苯酚中间体(含氟、氯或溴等)普遍表现出较强的药理和毒理活性,其应用已从过去的染料、农药逐渐过渡到高附加值医药产品。该文对国内外卤代硝基苯酚中间体的应用及合成工艺进行了总结和分析,其关键的合成工艺主要分为水解、卤化和硝化3种。水解工艺多用强碱和高温,条件相对较为苛刻,卤化工艺的局限性在于卤化试剂的安全性风险不可忽视,而传统的硝化工艺多在强酸环境下进行,但近年来提出的非酸体系和光催化硝化较符合绿色化学标准。同时结合已有文献的环境毒理数据,发现水解工艺前驱体的毒性显著高于卤化和硝化工艺的前驱体。综合评价得出,采用硝化工艺可能使企业在成本、能耗、环保和安全等方面承受的压力较小。

Halogenated nitrophenol intermediates(containing fluorine,chlorine or bromine,etc.)generally show strong pharmacological and toxicological activities.They are previously applied in the synthesis of dyes and pesticides and now frequently use as the high valued pharmaceuticals.This article reviews the application and synthetic process of halogenated nitrophenol intermediates in recent years.The crucial processes are mainly divided into three ones,namely hydrolysis,halogenation and nitration.Among them,the hydrolysis process mostly utilizes strong alkalis and high temperature that might be relatively harsh conditions.The limitation of halogenation process is that the safety risk of halogenated reagents is unignorable.The traditional nitration process is mostly carried out in a strong acidic environment and yet recently the non-acid system and photocatalytic nitration are proposed in line with the green chemistry standards.In view of the toxicological data in the existing literature,it is found that the toxicities of the precursors in hydrolysis process are significantly higher than those in the halogenation and nitration processes.Through all-round comprehensive evaluation,it can be concluded that adopting a nitrification process may minimize the pressure of chemical enterprises in terms of cost,energy consumption,environmental protection and safety.