Application of Continuous Flow-Flash Chemistry to Scale-up Synthesis of 5-Cyano-2-formylbenzoic Acid

Autor:	Koichiro Fukuda, Shinichi Masada, David G. Cork, Masaki Seto, Hirotsugu Usutani, Tetsuji Kawamoto
Rok vydání:	2019
Předmět:	010405 organic chemistry Chemistry Organic Chemistry 010402 general chemistry 01 natural sciences 0104 chemical sciences Formylation Column chromatography Group (periodic table) SCALE-UP Electrophile Batch processing Organic chemistry Physical and Theoretical Chemistry Microreactor Isopropyl
Zdroj:	Organic Process Research & Development. 23:1420-1428
ISSN:	1520-586X 1083-6160
DOI:	10.1021/acs.oprd.9b00180
Popis:	Efficient scale-up synthesis of 5-cyano-2-formylbenzoic acid or its cyclic isomer 6-cyano-3-hydroxy-2-benzofuran-1(3H)-one (1) as a key intermediate for various biologically important compounds has been achieved from isopropyl 2-bromo-5-cyanobenzoate (8c) by means of continuous flow-flash chemistry using flow microreactors. It was found that Br/Li exchange reaction of 8c, bearing both a carboisopropoxy group and a cyano group, with BuLi took place within 0.1 s at −50 °C, and the resulting highly reactive aryllithium intermediate underwent formylation with DMF to afford 1, which is extremely difficult to achieve by a conventional batch process. Optimization of the continuous flow-flash reaction conditions and modification of the reaction system brought about the production of 237 g of 1 from 897 g of 8c in 270 min, without purification by column chromatography. The results suggest that phthalaldehydic acid derivatives bearing electrophilic group(s) can be synthesized conveniently from the corresponding 2-b...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::72454ea0f4681285c6fb791ee7666b16 https://doi.org/10.1021/acs.oprd.9b00180 Zobrazit plný text záznamu