Reaction Safety: A Critical Parameter in the Development of a Scaleable Synthesis of 2,3-Bis-chloromethylpyridine Hydrochloride

详细信息    查看全文

• 作者：J. S. Grimm ; C. A. Maryanoff ; M. Patel ; D. C. Palmer ; K. L. Sorgi ; S. Stefanick ; R. R. H. Webster ; and X. Zhang
• 刊名：Organic Process Research & Development
• 出版年：2002
• 出版时间：November 2002
• 年：2002
• 卷：6
• 期：6
• 页码：938 - 942
• 全文大小：275K
• 年卷期：v.6,no.6(November 2002)
• ISSN：1520-586X

文摘

This report describes the development of a scaleable processto prepare 2,3-bis(chloromethyl)pyridine hydrochloride, 2, thatis safe, economical, and environmentally acceptable. On a smallscale this material is prepared using thionyl chloride as thesolvent. However, this reaction is not readily scaleable becauseof environmental and disposal issues. Reaction calorimetry isused to evaluate a number of potentially viable chlorinationprocedures. In the course of this investigation potentiallyhazardous reagent/solvent incompatibilities were identified. Theuse of thionyl chloride in MTBE is particularly hazardous owingto solvent decomposition in the presence of HCl and subsequentoutgassing of large amounts of isobutylene. Reaction conditionsemploying thionyl chloride and 1% v/v DMF in toluene werefound to be safe for scale-up. As a result, an environmentallyacceptable, safe process has been developed and scaled toproduce multikilogram amounts of material.