Patent GB-1095052-A (GB)
Title: 4,5-dihalo-1,2-dihydro-pyridazine diones
IPC: C07D453/02
Filed: 1965-05-11
Abstract: Novel 4,5 - dihalo - 1,2 - dihydropyridazine dione compounds of the general formula <FORM:1095052/C2/1> wherein X and Y each represent a halogen and each of R and R1 represent the same or dissimilar substituants and each can be (1) an unsubstituted or substituted aliphatic hydrocarbon being saturated or unsaturated and having a straight, branched or cyclic structure or having a combination of a cyclic structure with a straight and/or branched chain aliphatic hydrocarbon structure, (2) an unsubstituted or substituted carbocyclic aryl which can be monocyclic or bicyclic but preferably a monocarbocyclic aryl, or (3) an unsubstituted or substituted saturated, or mono- or poly-unsubstituted heterocyclic group either monocyclic or bicyclic or tricyclic but preferably at monocyclic heterocycle having a 5-membered or 6-membered ring possessing one or more sulphur, oxygen or nitrogen atoms or combinations, an exhaustive list of substituents for R and R1 is given thereof.  The bicyclic and tricyclic heterocycle groups can be composed of fused heterocyclic rings or fused heterocyclic and saturated or unsaturated carbocyclic rings, and the preparation thereof by reacting the required dihalogenated maleic acid or anhydride thereof with the required hydrazine or a mono- or di-acyl derivative thereof, or an acid addition salt thereof, with or without isolation of the intermediate dihalo maleamic acid.  The above compounds may also be prepared by reacting the corresponding compound in which R1 and R2 represent hydrogen with an alkylating agent, reacting the above compounds with a hydrohalide or a metal halide to exchange the halogen atoms, or esterifying or acylating substituants contained in R and R1. Hydrazines of the general formula RNHNHR1 where R and R1 have the above significance are prepared (a) by reacting hydrazines of the formula RNHNH2 with an acylating agent such as an acid chloride or anhydride-particularly benzoyl chloride, benzyloxycarbonyl chloride or formic acid to form 1-R-1,2-dibenzoylcarbonyl hydrazine or a 1-R-1,2-diacyl hydrazine, reacting this compound with R1-Halogen or (R1)2-sulphate in the presence of sodium hydride to form 1 - R - 2 - R1 - 1,2 - dibenzoyloxycarbonyl-hydrazine or the corresponding 1,2-diacyl compound and treating this compound with HBr or HCl; (b) by reducing the corresponding 1-R-2-organo-ylidene hydrazine (obtained by reacting a 1-R-hydrazine with an aldehyde or ketone) with hydrogen or LiAlH4.  This process may be modified by acylating the organo-ylidene compound, reducing the resulting 1-R-1-acyl-2-organo-ylidene compound as before and treating the resulting 1-R-1-acyl-2-R1-hydrazine with HCl.  4 - (N,N - Dimethylaminomethyl) phenylhydrazine is prepared by reducing the diazo compound formed from 4-(N,N-dimethylaminomethyl) aniline with stannous chloride.  Pharmaceutical compositions having the effect of inhibiting gastric acid secretion and which may be administered orally in the form of tablets, capsules, suspensions or other liquid form contain compounds of the general formula above as the active ingredient, R and R1 being as hereinbefore defined.