6-allyl-6,7-dihydro-5H-dibenz[c,e]azepine

Originator

Ilidar,Roche,US,1954

Definition

ChEBI: Azapetine is a benzazepine.

Manufacturing Process

29 grams of diphenic acid were stirred in 900 cc of acetic anhydride at 120°C for one hour, The cooled mixture was filtered and washed with acetic acid to give diphenic anhydride, colorless crystals, MP about 222-226°C.
24.11 grams of diphenic anhydride were mixed with 50 cc of concentrated ammonia. The mixture warmed up and cooling was applied, after which the mixture was stirred until a clear solution formed and for 1? hours afterward. The mixture was acidified and allowed to stand overnight. Water was added, initiating precipitation. The mixture was chilled and filtered to yield diphenamic acid, a colorless solid, MP about 191-193°C.
23.5 grams of diphenamic acid were heated at 200°C in an oil bath, first for about 20 hours at atmospheric pressure and then for about 10 hours at about 20 mm.
Melting points were taken at intervals in order to gain an idea of the extent of reaction. The final residue was boiled with alcohol but since the solid exhibited insufficient solubility in the hot solvent, the mixture was filtered. The residue consisted of tan crystals, MP about 220-221°C, and the filtrate on cooling gave an additional crop of tan crystals, MP about 219-221°C. The two materials were identical and consisted of diphenimide.
5.58 g of diphenimide were placed in a Soxhlet thimble and extracted for about 3 days with a boiling mixture of 9.0 g of lithium aluminum hydride in 600 cc of sodium-dried ether. Excess lithium aluminum hydride was then decomposed cautiously with water and the mixture was filtered through a filter aid by suction. The filtrate consisted of two layers. The ether layer was separated and dried with anhydrous potassium carbonate and acidified with alcoholic hydrochloric acid to give 6,7-dihydro-5H-dibenz[c,e]azephine hydrochloride, MP about 287-289°C.
One gram of 6,7-dihydro-5H-dibenz[c,e]azepine hydrochloride was dissolved in water, made alkaline with concentrated ammonia, and the resultant base extracted twice with benzene, The benzene layers were combined, dried with anhydrous potassium carbonate, and mixed with 0.261 g of allyl bromide at 25-30°C. The reaction solution became turbid within a few minutes and showed a considerable crystalline deposit after standing 3? days. The mixture was warmed 1 3/4 hours on the steam bath in a loosely-stoppered flask, then cooled and filtered. The filtrate was washed twice with water and the benzene layer evaporated at diminished pressure. The liquid residue was dissolved in alcohol, shaken with charcoal and filtered. Addition to the filtrate of 0.3 gram of 85% phosphoric acid in alcohol gave a clear solution which, when seeded and rubbed, yielded 6-allyl-6,7-dihydro-5H-dibenz[c,e]azepine phosphate, MP about 211-215°C with decomposition.

Therapeutic Function

Adrenergic blocker

Safety Profile

Poison by intraperitoneal andintravenous routes. Moderately toxic by ingestion,subcutaneous, and intramuscular routes. When heated todecomposition it emits toxic fumes of NOx.