Patent GB-926816-A (GB)
Title: Improvements in and relating to n-heterocyclic compounds
Filed: 1960-05-30
Abstract: The invention comprises iminodibenzyl (10,11-dihydro-5H-dibenzo [b.f.] azepine) derivatives of the general formula <FORM:0926816/IV(a)/1> (wherein R represents a hydrogen atom, a C1-4 alkyl radical or an aralkyl radical, X represents an alkylene radical having 2-6 carbon atoms in a straight or branched chain, and Am represents a C1-4 alkylamino group, or a C2-8 dialkylamino group in which one alkyl radical may be bound direct to X or both alkyl radicals may be bound together direct or through an oxygen atom or an alkylimino, hydroxyalkylimino or alkanoyloxyalkylimino group, each alkyl or alkanoyl radical having at most 4 carbon atoms) and their salts with organic or inorganic acids, and the preparation thereof by reacting a compound of the general formula <FORM:0926816/IV(a)/2> (wherein R1 represents a C1-4 alkyl radical or an aralkyl, a -alkoxyalkyl or tetrahydropyranyl radical) with a reactive ester of an alcohol of the general formula HO-X-Am1 (III) (wherein Am1 has the meanings given for Am other than monoalkylamino, or represents an N - arylmethyl - alkylamino or N - acyl - alkylamino group) in the presence of an alkaline condensing agent, or reacting a reactive ester of a compound of the general formula <FORM:0926816/IV(a)/3> with a compound of the general formula Am-H (VI) or Am1-H (VII) in the presence of an acid binding agent, or (in certain cases) treating a compound of the general formula <FORM:0926816/IV(a)/4> (wherein Am11 represents an amino or C1-4 alkylamino group) with an appropriate alkylating agent, or reducing a compound of the general formula <FORM:0926816/IV(a)/5> (wherein X1 and Am111 have the meanings given for X and Am except that in at least one of them a methylene group attached to a nitrogen atom is replaced by a carbonyl group) by means of an alkali metal-earth metal hydride, and, in any of the foregoing cases where necessary, subjecting the product to acid hydrolysis, transacetalization or hydrogenolysis, or, when -OR is a hydroxy group in the 2-position, by oxidizing a compound of the general formula <FORM:0926816/IV(a)/6> with oxygen or hydrogen peroxide in a neutral to weakly acid aqueous solution in the presence of a compound containing the grouping - CO - C(OH) = C(OH) - or -CO-CO-CO and of iron, nickel, cobalt or manganese ions and, if desired, a complex former.  Ethers of the general formula (II) above are prepared by diazotizing an amine of the general formula <FORM:0926816/IV(a)/7> (wherein Y represents an acyl radical easily split off), decomposing the diazonium salt, by heating with water or aqueous acid, to form a hydroxy compound of the general formula <FORM:0926816/IV(a)/8> and reacting this with an alkylating agent, an aralkyl halide, or an a -halo dialkyl ether, in the presence of an acid-binding agent, or with dihydropyran or a vinyl alkyl ether, before or after removal of the acyl radical Y by hydrolysis. Compounds (XII) in which Y is benzoyl or acetyl and the hydroxy group is in the 4-position are also obtainable by treating iminodibenzyl with an equimolecular proportion of benzoyl or acetyl peroxide. 2-Hydroxyiminodibenzyl is obtainable by hydrolysing corresponding compounds (XII) or by subjecting iminodibenzyl to oxidation with a solution of potassium nitrosodisulphonate and reducing the resulting 2-oxoderivative.  Amines of the general formula (XI) are obtainable by subjecting corresponding compounds containing an acetyl group in place of the amino group to Schmidt reaction conditions and then partially hydrolysing the resulting acetamido compounds.  Reactive esters of compounds of the general formula (V) above are prepared by reacting alkali metal compounds of OR1- substituted iminodibenzyls with preferably mixed diesters (e.g. dihalides or halide-sulphonates) of alkylene glycols, or with alkylene oxides followed by treatment of the hydroxyalkyl compounds (V) so obtained with inorganic acid halides, arylsulphonic acid chlorides or methane sulphochloride. Amides of the general formula (IX) above are prepared as follows: when there is a carbonyl group in X1 only, adjacent to Am11 by reacting compounds (II) with bromoalkanecarboxylic acid dialkylamides, pyrrolidides, piperidides, morpholides or 4-alkylpiperazides; when there is a carbonyl group in X1 only, adjacent to the iminodibenzyl nucleus, by reacting alkali metal derivatives of compounds (II) with haloalkanecarboxylic acid halides and reacting the resulting 5-haloalkanoyl compounds with alkylamines, dialkylamines or piperidine; when there are one or two carbonyl groups in Am111 only, by reacting reactive esters of compounds (V) with alkali metal compounds of, for example, alkanecarboxylic amides or N-alkylamides, di(alkanecarboxylic)amides, d -valerolactam, e -caprolactam, succinimide or glutarimide, or by acylating compounds (VIII).  Aminoalkyl-iminodibenzyls of the general formula (X) above are prepared by reacting iminodibenzyl with a dialkylaminoalkyl halide, or a 5-haloalkyliminodibenzyl with an amine (VI). Pharmaceutical compositions.-The compounds of general formula (I) above may be administered orally, in the form of aqueous solutions of their non-toxic acid addition salts, or parenterally, as antiallergic, sedative, serotonin-antagonistic, antipyretic or thymoleptic agents.