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A Facile Synthesis of 1‐Substituted 3‐Alkoxy‐1 H ‐isoindoles Based on the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Nitriles, Followed by Acid‐Catalyzed Cyclization
Author(s) -
Kuroda Minami,
Kobayashi Kazuhiro
Publication year - 2015
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201400333
Subject(s) - chemistry , phenyllithium , alkoxy group , catalysis , aryl , medicinal chemistry , organic chemistry , alkyl
A two‐step synthesis of 1‐substituted 3‐alkoxy‐1 H ‐isoindoles 4 has been developed. Thus, the reaction of 2‐(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li exchange between 1‐bromo‐2‐(dialkoxymethyl)benzenes 1 and BuLi in THF at −78°, with nitriles afforded [2‐(dialkoxymethyl)phenyl]methanimines 2 , which were treated with a catalytic amount of TsOH⋅H 2 O in refluxing CHCl 3 to give the desired products in reasonable yields. Similarly, 3‐aryl‐1‐ethoxy‐1‐methyl‐1 H ‐isoindoles 7 have been prepared starting from 1‐bromo‐2‐(1,1‐diethoxyethyl)benzenes 5 .