Patent GB-804193-A (GB)
Title: Improvements in or relating to iminodibenzyl compounds
IPC: C07D473/08
Filed: 1956-09-18
Abstract: The invention comprises iminodibenzyl compounds of the general formula <FORM:0804193/IV (b)/1> wherein A represents a saturated straight or branched divalent hydrocarbon group containing from 1 to 6 carbon atoms, R represents hydrogen or an alkyl (not more than 6 carbon atoms), aryl or araliphatic group, Y and Y1 are the same or different and represent hydrogen, or alkyl (not more than 6 carbon atoms) groups and one or more carbon atoms of the piperazine ring may carry a methyl substituent, and the acid addition and quaternary ammonium salts thereof, and the 8-halogenoxanthine salts and theophylline acetates thereof, and the preparation thereof by any of the following methods:  (1) An iminodibenzyl of the general formula <FORM:0804193/IV (b)/2> is reacted with a halogenoalkylpiperazine of the general formula <FORM:0804193/IV (b)/3> wherein Y, Y1, A, R and the carbon atoms of the piperazine ring have the above significance and X represents a halogen.  This process may be carried out in the presence or absence of an organic solvent and, if desired, in the presence of an alkali metal or an alkali metal derivative such as an hydride, hydroxide, amide or alcoholate or an organo-alkali metal derivative.  The halogenoalkylpiperazine may be used in the form of a salt in which case a greater proportion of the condensing agent is used to neutralize the acid of the salt.  (2) An iminodibenzyl of the general formula <FORM:0804193/IV (b)/4> is reacted with a piperazine derivative of the general formula <FORM:0804193/IV (b)/5> wherein T represents the acid residue of a reactive ester, e.g. a halogen atom or the residue of a sulphuric or sulphonic ester, and Y, Y1, A, R and the carbon atoms of the piperazine ring have the above significance. (3) An iminodibenzyl of the general formula <FORM:0804193/IV (b)/6> is reacted with an amine of the general formula RNH2 wherein Y, Y1, A, R and T have the above significance.  (This method forms iminodibenzyl compounds of the above general formula in which the carbon atoms of the piperazine ring are not substituted by methyl groups.)  (4) An iminodibenzyl compound corresponding to the general formula of the desired iminodibenzyl compound above except that group A is replaced by a group -A1-CO-and/or the group R ix replaced by the group -CO-R, and the groups A1 and R1 are similar to the groups A and R respectively but contain one carbon atom less, is reduced.  (5) An iminodibenzyl compound of the general formula <FORM:0804193/IV (b)/7> is hydrogenated, Y, Y1, A1 and the carbon atoms of the piperazine ring having the above significance and Z representing an aldehyde (CHO) or nitrile (CN) group.  (6) An iminodibenzyl compound corresponding to the general formula of the desired iminodibenzyl compound above except that R represents -COOR2 or -CON(R2)2, and R2 is a hydrocarbon group, is hydrolysed.  (This method forms iminodibenzyl compounds of the above general formula in which Rrepresents hydrogen.)  (7) An iminodibenzyl compound of the general formula <FORM:0804193/IV (b)/8> is heated to effect decarboxylation, wherein Y, Y1, A and the carbon atoms of the piperazine ring have the above significance.  The above processes may be modified in that iminodibenzyl compounds prepared in which R represents hydrogen may be alkylated as required, in which R represents a phenyl group may be converted into iminodibenzyl compounds in which R represents hydrogen by nitrosation and fission, and in which R represents a benzyl group may be converted to iminodibenzyl compounds in which R represents hydrogen by reduction.  In the example the following compounds are prepared: 5-(3-41-methyl-11-piperazinylpropyl-, 5 - (2 - 41 - ethyl - 11 - piperazinylethyl) -, 5 - (3 - 41 - ethyl - 11 - piperazinyl-propyl) - and 5 - (2 - methyl - 3 - 41 - methyl-11 - piperazinylpropyl - iminodibenzyl and the dihydrochlorides thereof.