Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile.
Addition of organometallics to N-(alpha-haloacyl)-o-aminobenzonitrile resulted in the formation of 2,5-disubstituted 1,4-benzodiazepin-3-ones, whereas N-(beta-haloacyl)-o-aminobenzonitrile gave 2,6-disubstituted 1,5-benzodiazocin-4-ones under similar conditions. Initial cylization of N-(beta-haloacyl)-o-aminobenzonitrile to obtain the corresponding lactam (e.g.alpha,alpha-dimethyl-N-(2-cyanophenyl)-beta-lactam) increased the yield of 1,5-benzodiazocin-4-ones significantly. Somewhat surprisingly, addition of lithium reagents to N-(beta-haloacyl)-o-aminobenzonitrile gave 4,4-disubstituted quinazolines via Grob fragmentation.
Pettersson
Birgitta
B
Karolinska Institute, Department of Biosciences at Novum, Unit of Organic Chemistry, SE-141 57, Huddinge, Sweden.
Rydbeck
Anna
A
Bergman
Jan
J
D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D001570:Benzodiazepinones; D009570:Nitriles; D009942:Organometallic Compounds; C540240:o-aminobenzonitrile