Patent GB-908786-A (GB)
Title: New 10,11-dihydrodibenzazepines and processes for their production
Filed: 1960-07-21
Abstract: The invention comprises 3-alkanoyl-10,11-dihydrodibenzoazepine compounds of general formula <FORM:0908786/IV (b)/1> wherein R1 represents an alkyl radical (1 to 4 carbon atoms), X is a straight or branched chain alkylene radical having 2-6 carbon atoms, R2 represents an alkyl or alkenyl radical, R3 represents hydrogen or an alkyl or alkenyl radical (each up to 4 carbon atoms), and wherein the radical R2 may be bound to the alkylene radical X, or if R2 and R3 represent alkyl radicals, both can be bound to each other directly or by way of an oxygen atom, an imino, alkylimino (1 to 4 carbon atoms), hydroxyalkylimino (1 to 4 carbon atoms) or alkanoyloxyalkylimino group (the alkanoyl and alkyl moieties of which each have 1 to 4 carbon atoms), and salts thereof with inorganic or organic acids, and the preparation thereof (1) by reacting a 10,11-dihydrodibenzoazepine of the general formula <FORM:0908786/IV (b)/2> or a functional derivative of that general formula with regard to the oxo group, in the presence of an alkaline condensing agent or after conversion into its alkali metal compound, with a reactive ester of an alcohol of general formula <FORM:0908786/IV (b)/3> wherein R13 represents an alkyl, alkenyl or alkanoyl radical, and if necessary hydrolysing any reaction product containing a functionally converted oxo group; (2) by reacting a reactive ester of a hydroxyl compound of the general formula <FORM:0908786/IV (b)/4> or a functional derivative thereof with regard to the oxo group, with an amine of the general formula <FORM:0908786/IV (b)/5> wherein R2 and R3 have the above significance except that R2 cannot be bound to X, and if necessary hydrolysing any reaction product containing a functionally converted oxo group; and (3) by reacting a 10,11-dihydrodibenzoazepine of the second general formula above, or a functional derivative thereof with regard to the oxo group with phosgene and reacting the N - chlorocarbonyl-10,11-dihydrodibenzoazepine compound with an alcohol of general formula <FORM:0908786/IV (b)/6> and heating the resulting N-carboxylic acid ester of the general formula <FORM:0908786/IV (b)/7> to split out carbon dioxide and, if necessary, then hydrolysing the reaction product to liberate the oxo group and/or removing the alkanoyl radical.  The functionally converted oxo group may be a cyclic ketal group such as an ethylenedioxy group, or a ketimine group such as a phenylimino group.  The products are useful for the treatment of mental disorders.  3-Alkanoyliminodibenzyls of general formula II are obtained by condensation of 5-acetyliminodibenzyl with acetic anhydride or alkanoyl chlorides in the presence of aluminium chloride, and hydrolysis of the resulting 3-alkanoyl-5-acetyliminodibenzyl to remove the 5-acetyl group. Reactive esters of hydroxy compounds of general formula IV, or their functional derivatives with respect to the oxo group, are obtained by treatment of the hydroxy compound with appropriate acid halides, the hydroxy compounds themselves being obtained by reaction of the alkali metal derivatives of function derivatives with regard to the oxo group of compounds of general formula II with alkylene oxides.  5-(g -Chloropropyl)-3-(a ,a -ethylenedioxyethyl)-iminodibenzyl is obtained by reaction of the sodium derivative of 3-(a ,a -ethylenedioxyethyl)-iminodibenzyl with g -bromopropyl chloride.  3 - (a ,a  - Ethylenedioxyethyl) - iminodibenzyl is obtained by reaction of 3-acetyl-iminodibenzyl with ethylene glycol in the presence of toluene-p-sulphonic acid, and is converted into the sodium derivative by treatment with sodium amide.  3 - Alkanoyl-5-chlorocarbonyliminodibenzyls are obtained by reaction of phosgene with compounds of general formula II, and are converted into esters of general formula VI by reaction with alcohols of general formula III.  Compounds related to general formula I but in which the keto group is protected, the carbon atom thereof occupying the 2-position of a dioxolane ring, are obtained by the methods given above for compounds of general formula I, and are converted thereinto by acid hydrolysis.  3 - (a ,a  - ethylenedioxyethyl)-5-[g -(41-formylpiperazinyl-11) propyl]iminodibenzyl is obtained by reaction of 3-(a ,a -ethylenedioxyethyl)-5-sodioiminodibenzyl with 1-formyl-4-(g -chloropropyl)piperazine, and is converted by acid hydrolysis into 3-acetyl-5-[g -(41-formylpiperazinyl-11) propyl]iminodibenzyl.