GB638695A - Manufacture of biguanide derivatives - Google Patents

Abstract

Biguanide derivatives, useful as therapeutic agents, especially in the treatment of malaria, and of the general formula <FORM:0638695/IV (b)/1> (wherein R represents hydrogen or an alkyl radical of 1-3 carbon atoms, R1 represents hydrogen or a lower alkyl radical and R11 a lower alkyl or cycloalkyl radical such that R1 and R11 together contain more than one and fewer than 8 carbon atoms, A and B represent hydrogen, or one but not both of them may represent an alkyl radical of 1-3 carbon atoms, X represents halogen, Y hydrogen, halogen or an alkyl or alkoxy radical of 1-3 carbon atoms and Z hydrogen or halogen), are manufactured by reacting a substituted aminomagnesium halide of the formula <FORM:0638695/IV (b)/2> with a substituted dicyandiamide, respectively of the formula <FORM:0638695/IV (b)/3> preferably in a liquid medium (e.g. anisole or diethyl ether), with or without heating, and treating the product with acid or an acidreacting salt (e.g. a mineral acid, such as hydrochloric acid, or a salt thereof with a weak base, such as ammonium chloride). The aminomagnesium halides may be prepared (preferably immediately before use) by treating the appropriate amine, e.g. in ethereal solution or suspension, with an alkylmagnesium halide, preferably so chosen that the by-product is gaseous (e.g. an ethylmagnesium halide, which yields the aminomagnesium halide and ethane). Examples describe the preparation (and isolation in the form of their hydrochlorides) of: (1) N1-p-chlorophenyl - N5 - isopropylbiguanide from isopropylaminomagnesium iodide and p-chlorophenyldicyandiamide; (2) N1 - p - chlorophenyl-N5-methyl-N5-isopropylbiguanide similarly from methylisopropylaminomagnesium iodide; (3) N1-3 : 4-dichlorophenyl-N5-isopropylbiguanide from 3 : 4 - dichlorophenylaminomagnesium bromide and isopropyldicyandiamide. A list of further products is given. Specification 577,843 is referred to.