Patent GB-778808-A (GB)
Title: Azacyclic compounds and process for making them
IPC: C07D223/16
Filed: 1954-04-22
Abstract: The invention comprises heterocyclic compounds with 6 or 7 atoms in the heterocyclic ring, an oxo group ortho to a ring-nitrogen atom and a tertiary amino-alkyl substituent ortho to the nitrogen atom on the other side.  These are made by treating with hydrazoic acid the corresponding 5- or 6-membered carbocyclic ring compounds whereby -NH- is inserted in the ring. The hydrazoic acid may be formed in situ from an azide such as sodium azide in the presence of highly concentrated sulphuric acid.  Alternatively the hydrazoic acid may be added as a solution in an organic solvent.  The products form salts with acids such as hydrohalic, sulphuric, nitric, phosphoric, thiocyanic, acetic, propionic, oxalic, malonic, succinic, malic, isethionic and other sulphonic acids; they may also be quaternated with higher alkyl derivatives such as dodecyl chloride.  Examples show the preparation of the following: (1) 3-piperidinomethyl - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline and hydrochloride from 2-piperidinomethyl - indan - 1 - one; (2) 2 - piperidinomethyl - 7 - oxo - 1:2:3:4 - tetrahydro - 5:6-benzazepine and hydrochloride from 2-piperidinomethyl - 1 - tetralone; (3) 3 - (b  - piperidinoethyl) - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2-(b -piperidinoethyl)-indan-1-one; (4) 2 - (b  - piperidinoethyl) - 7 - oxo-1:2:3:4 - tetrahydro - 5:6 - benzazepine from 2 - (b  - piperidinoethyl) - 1 - tetralone; (5) 3-diethylaminomethyl - 1 - oxo - 1:2:3:4-tetrahydroisoquinoline from 2-diethylaminomethyl - indan - 1 - one; the dimethylaminomethyl compound is made similarly; (6) 2-piperidinomethyl - 7 - oxo - azepidine and hydrochloride from 2 - piperidinomethylcyclohexanone; (7) 3 - (b  - piperidinoethyl)-6:7 - dimethoxy - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2 - (b - piperidinoethyl) - 5:6 - dimethoxy - indan - 1 - one; (8) 3 - piperidinomethyl - 4 - phenyl - 1 - oxo-1:2:3:4 - tetrahydro - isoquinoline from 2-piperidinomethyl - 3 - phenyl - indan - 1 - one; (9) 2 - piperidinomethyl - 4 - phenyl - 7 - oxo-1:2:3:4 - tetrahydro - 5:6 - benzazepine from 2 - piperidinomethyl - 4 - phenyl - 1 - tetralone; (10) 3 - (b  - dimethylamino - propyl) - 6:7 - dimethoxy - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2 - (b  - dimethylamino - propyl)-5:6-dimethoxy-indan-1-one.  2 - Piperidinomethyl - 3 - phenyl - indan - 1-one and 2 - piperidinomethyl - 4 - phenyl - 1-tetralone are obtained as hydrochlorides by condensing piperidine and paraformaldehyde with 3 - phenyl - indan - 1 - one and 4 - phenyl - 1-tetralone respectively. 2 - (b  - Piperidinoethyl) - indan - 1 - one, 2-(b  - piperidinoethyl) - 5:6 - dimethoxy - indan - 1-one and 2 - (b  - dimethylaminopropyl) - 5:6 - dimethoxy - indan - 1 - one are made by ring closure of diethyl benzyl - (b  - piperidinoethyl)-malonate, diethyl 3:4 - dimethoxybenzyl - (b  - piperidinoethyl) - malonate and diethyl 3 : 4 - dimethoxybenzyl - (b  - dimethylaminopropyl)-malonate respectively.  The third product is obtained as hydrochloride.  2 - (b  - Piperidinoethyl) - 1 - tetralone is obtained by condensing N-(b -chloroethyl)-piperidine with di-(tetrahydropyranyl) b -phenethylmalonate and ring closing the product.