Patent GB-890725-A (GB)
Title: Improvements in or relating to azetidine derivatives
IPC: C07D403/12
Filed: 1958-06-03
Abstract: The invention comprises compounds of the general formula <FORM:0890725/IV (b)/1> and acid addition salts thereof, wherein each of R1 and R2 represents an alkyl group containing at most 4 carbon atoms, a phenyl or a benzyl group, with the proviso that R1 and R2 need not be dissimilar; either R3 represents a hydrogen atom an acyl group containing at most 14 carbon atoms and R4 represents a phenyl group, an alkyl group containing at most 4 carbon atoms, an N-alkyl-piperidyl group containing at most 9 carbon atoms or an acyl group containing up to 14 carbon atoms or each of R3 and R4 represents a hydrogen atom, a phenyl or a benzyl group with the proviso that R3 and R4 need not be dissimilar; or R3 and R4 together form one alkylidene group containing at most 4 carbon atoms or a group <FORM:0890725/IV (b)/2> containing at most 9 carbon atoms or the grouping <FORM:0890725/IV (b)/3> represents a saturated or unsaturated heterocyclic system containing 5 or 6 ring members which heterocyclic system may have aromatic groups fused on to it or may contain a second N atom and the preparation thereof by reacting a hydrazine derivative of the general formula <FORM:0890725/IV (b)/4> which the radicals R13 and R14 have the same significance as R3 and R4 with the proviso that one of them must be other than a hydrogen atom with a reactive derivative of malonic acid of the general formula <FORM:0890725/IV (b)/5> in which each of X and Y denotes a chlorine atom, a bromine atom, the azide group N3, an alkoxy group containing at most 4 carbon atoms or a primary amino group and, when it is desired to produce a compound wherein R3 and R4 are H, then splitting off any acyl or alkylidene groups which may be present, or (when R3 is an H atom or an acyl group and R4 is an N-alkyl-piperidyl group) by condensing a compound (I) wherein both R3 and R4 are H atoms with an N-alkyl piperidone in an inert organic solvent and then reducing the resulting hydrazone to the corresponding hydrazine by catalytically activated hydrogen and, if desired, acylating the secondary amino group.  Acyl groups may include acetyl, propionyl, butyryl pivaloyl, caproyl, carbamoyl, thiocarbamoyl benzoyl carbophenoxy and benzylsalicoyl.  Diphenyl and diethyl-malonic acid bis-(diphenyl hydrazide and diethylmalonic acid bis-(phenyl hydrazide) are formed as by-products in the reaction of diphenyl and diethylmalonyl dichlorides with the substituted hydrazine.  1-Amino pyrrolidine is prepared by reacting pyrrolidine with nitrous acid to form 1-nitrosopyrrolidine which is reduced.ALSO:Pharmaceutical compositions having analgesic and antiphlogistic activity comprise a carrier and azetidine derivatives of the general formula <FORM:0890725/VI/1> or their acid addition salts, wherein each of R1 and R2 denotes an alkyl group of at most 4 carbon atoms, a phenyl group or a benzyl group, with the proviso that R1 and R2 need not be dissimilar, either R3 denotes a hydrogen atom or an acyl group containing at most 14 carbon atoms, and R4 denotes a phenyl group, an alkyl group containing at most 4 carbon atoms, an acyl group containing at most 14 carbon atoms or an N-alkyl-piperidyl group containing at most 9 carbon atoms; or each of R3 and R4 denotes a hydrogen atom, a phenyl or a benzyl group, with the proviso that R3 and R4 need not be dissimilar; or R3 and R4 together form one alkylidene group containing at most 4 carbon atoms or a group <FORM:0890725/VI/2> containing at most 9 carbon atoms or the grouping NR3R4 denotes a saturated or unsaturated heterocyclic system containing 5 or 6 ring members which heterocyclic system may have aromatic groups fused on to it or may contain a second N atom, in addition to an inert carrier.  Acid addition salts include hydrohalic, hydrobromic, sulphuric, tartaric, citric and maleic acid salts.  Acyl groups include acetyl, propionyl, butyryl, pivaloyl, caproyl, carbamoyl, thiocarbamoyl, benzoyl, carbophenoxy, and benzylsalicoyl groups.