GB1048043A - Benzodioxole derivatives and methods of preparing the same - Google Patents

Abstract

Novel compounds of the formulae <FORM:1048043/C2/1> wherein R1 is NH2, N-(R1)2, N-+(R1)3 (in combination with a pharmaceutically acceptable anion), NH-NH2, NH-CONH2, NH-CO-R1, NH-C(= NH)NH2, piperidino, piperazine or morpholino; R2 is hydrogen or C1- 5 alkyl; R3 is hydrogen or C1- 5 alkyl; R4 is NH-NH2, NH-CO-NH2, NHR1, N(R1)2, piperidino, piperazine or morpholino; and R5, R6, R7 and R8 are hydrogen, halogen, nitro, C1- 5 alkyl, C1- 5 alkoxy or C2- 5 carbalkoxy; R1 being C1- 3 alkyl and each R1 being the same or different in each compound; with the provisos that when in Formula (I) R1 is dimethylamino, diethylamino or piperidino and R2 and R5-R8 are all hydrogen then R3 is not methyl, and when in Formula (II) R3 and R5-R8 are all hydrogen, R4 is not NH-NH2, and acid-addition salts thereof are prepared (1) for the amino compounds, from an appropriate 2-halo-alkyl - 1,3 - benzodioxole and the amine R1H and, if required, quaternizing the product, or reacting it or a salt thereof with a metal cyanate to give the urea compound, or with the anhydride or halide of an acid to give the acylamino compound, or with cyanamide and water to give the guanidino compound; or (2) for the amide compounds, from an appropriate 2 - alkoxycarbonyl - 1,3 - benzodioxole and the amine R,H and, if required, reducing the product to the amines wherein R2 is H; or (3) for the compounds (I), by reacting an appropriate catechol with a compound R3COCH(R2).X wherein X is halogen and replacing the halogen in the product by the basic R1 group; or (4) for the compounds (II), by reacting an appropriate 2 - halocarbonyl - 1,3 - benzodioxole with the compound R4H, or (except when R4 is NHCONH2) reacting the esters used in (3) with the compound R4H. Esters of the formula <FORM:1048043/C2/2> wherein R is C1- 5 alkyl) are prepared from the appropriate catechol and the compound R3CX2.COOR and are converted into 2-halomethyl-1,3-benzodioxoles by reduction to 2 - hydroxymethyl-1,3-benzodioxoles and reaction of these with halogenating agents; and into 2-halocarbonyl-1,3-benzodioxoles by hydrolysis to 2-carboxy-1,3-benzodioxoles and reaction of these with halogenating agents. The benzodioxoles of the invention, which are stated to show antihistaminic, hypotensive, adrenergic nerve and ganglion blocking, adrenolytic, sedative, tranquillizing, anticonvulsant and spasmolytic activity, may be made up into pharmaceutical compositions for oral or parenteral administration.