Issue in Honor of Prof. Otto Meth-Cohn ARKIVOC 2000 (v) 832-839
Synthesis of 8-bromoisoquinolines and a crystal structure of an acyclic
secondary amine-borane
Montserrat Armengol, Madeleine Helliwell# , and John A. Joule*
Chemistry Department, The University of Manchester, Manchester M13 9PL, U.K. phone: 44 (0) 161 275 4633; fax: 44 (0) 161 275 4598 *E-mail:
[email protected] **E-mail:
[email protected]
Dedicated to Professor Otto Meth-Cohn on the occasion of his 65th birthday (received 12 Sep 00; accepted 03 Oct 00; published on the web 11 Oct 00)
Abstract
8-Bromo-7-methoxyisoquinoline was produced by Jackson’s modification of the Pomeranz-Fritsch ring synthesis accompanied by 8-bromo-3-(8-bromo-7-methoxyisoquinolin-4-yl)-1,2,3,4tetrahydro- 7-methoxy-2-(4-methylphenylsulfonyl)isoquinoline. A mechanism for the formation of the latter is suggested. The ready formation of secondary amine-BH3 complexes was noted and the X-ray crystal structure of N-(2-bromo-3-methoxybenzyl)aminoacetaldehyde dimethyl acetal boranedetailed.
Keywords: 8-Bromoisoquinolines, dimerisation during Pomeranz-Fritsch synthesis, X-ray crystal structure of a secondary amine borane complex
Introduction
Our interest in the fusion of a third ring to an isoquinoline framework, across the 8- and 1-positions, led to a requirement for 8-bromoisoquinoline or a derivative, so that a chain could be attached at the 8-position via a coupling procedure. 8-Bromoisoquinoline appears in the literature three times: it was prepared1 from isoquinoline by nitration, reduction, diazotisation and Sandmeyer reaction, it was used2 to prepare 8,8’-biisoquinoline without mention of its method of synthesis, and it was prepared in 31% yield by ring synthesis;3 we chose to follow the ring synthesis route.
Results and Discussion
Reaction of 2-bromobenzaldehyde with 2,2-dimethoxyethanamine gave the Schiff base 1, borohydride reduction of which produced the 2-bromobenzylamine-acetal 2 (see later for further discussion of this reduction). Conversion to a tosylamide 3 so that Jackson’s modification4 of the Pomeranz-Fritsch
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