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Synthesis of the 3‐methyl and 4‐methyl derivatives of 3‐amino‐3,4‐dihydro‐1‐hydroxycarbostyril and related compounds
Author(s) -
Davis Alvie L.,
Tabb David L.,
Swan Janet K.,
Mccord Tommy J.
Publication year - 1980
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.5570170711
Subject(s) - chemistry , hydantoin , hydrolysis , amino acid , yield (engineering) , potassium cyanide , potassium carbonate , butyric acid , alanine , ammonium carbonate , organic chemistry , catalysis , medicinal chemistry , cyanide , nuclear chemistry , biochemistry , materials science , metallurgy
The 3‐methyl and 4‐methyl derivatives of 3‐amino‐3,4‐dihydro‐1‐hydroxycarbostyril were synthesized by the reductive cyclization of α‐methyl‐β‐( o ‐nitrophenyl)alanine and α‐amino‐β‐( o ‐nitrophenyl)butyric acid hydrohalides, respectively, under conditions of catalytic hydrogenation in acidic solution. The free bases of the latter two o ‐nitroaromatic amino acids were also catalytically hydrogenated under neutral conditions to yield the respective α‐methyl‐β‐( o ‐aminophenyl)alanine and α‐amino‐β‐( o ‐aminophenyl)butyric acid which were converted to the corresponding lactams, 3‐methyl‐ and 4‐methyl‐3‐amino‐3,4‐dihydrocarbostyrils. α‐Methyl‐β‐( o ‐nitrophenyl)alanine was obtained by acid hydrolysis of 5‐methy)‐5‐( o ‐nitrobenzyl)hydantoin which was prepared by treatment of o ‐nitrophenylacetone with potassium cyanide and ammonium carbonate. α‐Amino‐β‐( o ‐nitrophenyl)butyric acid was synthesized by condensation of α‐bromo‐ o ‐nitroethylbenzene with diethyl acetamidomalonate, followed by acid hydrolysis of the condensation product. The 4‐methylated compounds were obtained as synthetic mixtures of two diasteromeric racemates in nearly the same amounts as shown by nmr spectral analysis. Unlike the demethylated parent compound, 3‐amino‐3,4‐dihydro‐1‐hydroxycarbostyril, neither the 3‐methyl nor 4‐methyl analog was found to possess any antibacterial activity.