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Synthesis of 3‐alkyl‐8‐substituted‐ and 4‐hydroxy‐8‐substituted‐2,3,4,5‐tetrahydro‐1 H ‐2‐benzazepines
Author(s) -
Grunewald Gary L.,
Dahanukar Vilas H.
Publication year - 1994
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570310656
Subject(s) - benzazepines , chemistry , alkyl , stereochemistry , medicinal chemistry , bicyclic molecule , organic chemistry
Based on the Schmidt reaction and an iodolactone ring expansion reaction, two different synthetic routes to substituted 2,3,4,5‐tetrahydro‐1 H ‐2‐benzazepines were developed. The Schmidt reaction on 2,3‐dihydro‐2 H ‐1‐naphthalenone ( 1 ) gave 3 , the product resulting from the alkyl group migration, as the major product instead of the tetrazole 2. This prompted the investigation of the Schmidt reaction on aromatic ketones 8 and 12. The product 9 due to alkyl group migration was the major product of the Schmidt reaction on 2‐methyl‐3,4‐dihydro‐2 H ‐1‐naphthalenone ( 8 ). The β‐keto diester 12 gave a mixture of decarb‐oxylated lactams after the Schmidt reaction. In this case, the lactam 13 resulting from the migration of the aromatic ring dominated over the other lactam 14. When lactam 14 was subjected to nitration, a single regioisomer was produced and transformed to the bromo alcohol 19. The other approach was based on the single pot ring expansion of the iodolactone 22 to the lactam 23 in the presence of methanolic ammonia. The iodolactone 22 was readily prepared from 2‐allylbenzoic acid.