A comparative study of the rearrangement of some 6- and 7-halo-substituted 3-amino-3,4-dihydro-l-hydroxycarbostyrils in concentrated hydrohalic acids

Autor: J. Mark Winter and, Alvie L. Davis, Charles P. Crawford, James A. Rabon, Tommy J. McCord, Larry D. Gage
Rok vydání: 1982
Předmět:
Zdroj: Journal of Heterocyclic Chemistry. 19:401-406
ISSN: 1943-5193
0022-152X
DOI: 10.1002/jhet.5570190237
Popis: The 6-bromo (16), 6-fluoro (17), 7-bromo (14), and 7-fluoro (15) substituted 3-amino-3,4-dihydro-l-hydroxycarbostyrils were treated with concentrated hydrochloric and hydrobromic acids under reflux conditions. The 7-halogenated N-hydroxycarbostyrils (14,15) gave the normal rearrangement products, the 6,7-dihalolactams (18–21). The 6-halogenated compounds (16,17) yielded the corresponding 6,8-dihalolactams (22–24) under the same experimental conditions, with the exception of the hydrobromic acid reaction of the 6-fluoro derivative 17 which yielded a mixture of products. Based on the comparison of the nmr spectrum of the product mixture with those of two authentic compounds, the mixture was identified as consisting of the normal rearrangement product, the 8-bromo-6-fluorolactam (27) and the straightforward reduction product, the 6-fluorolactam (26) in a ratio of about 2:1. The latter compounds were prepared by an independent method of synthesis in which 2-amino-5-fluorophenylalanine (25) was acidified to yield the corresponding lactam 26, followed by bromination to afford the 8-bromo-6-fluorolactam 27. A mechanism is proposed to interpret the experimental results of nucleophilic substitution with rearrangement and reduction which occur with the 6-fluoro compound 17 when exposed to bromide ions in strongly acidic solution.
Databáze: OpenAIRE
Externí odkaz: