Abstract
In the course of our work on infectious diseases, we were led
to prepare 6-bromo-2-chloro-4-methylquinoline as a starting material.
Since surprisingly little has been reported in the literature, the
two synthetic steps to this compound were investigated. The synthesis
involves a condensation between β-keto esters and 4-bromoaniline
and the cyclization of the resulting anilides into 6-bromoquinolin-2(1H )-one, otherwise known as the Knorr
reaction. The ¹ H NMR monitoring of the first
step allowed us to optimize the conditions leading specifically
to the anilide without the occurrence of the alternative crotonate.
To illustrate the scope of our finding, few additional anilides
featuring electron-attracting groups were prepared. The study of
their cyclization revealed some unsuspected steric effect governing
this second step. Aside from rectifying a few claims in this chemistry,
this study led to a three-step preparation of 6-bromo-2-chloro-4-methylquinoline
in 48% overall yield from 4-bromoaniline.
Key words
acylation - cyclization - heterocycles - quinolines - carbocation
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