Patent GB-605952-A (GB)
Title: Process for the production of imino ethers and amidines
Filed: 1945-07-11
Abstract: Iminoether hydrohalides of the general formula <FORM:0605952/IV(b)/1> (wherein n is an integer, R represents hydrogen and X the residue of an organic carboxylic acid or X and R together represent the residue of an organic dicarboxylic acid, and R1 represents an alkyl group) and the corresponding amidines (also in the form of their hydrohalides, from which the free bases may be liberated by neutralization) are manufactured by treating an acylamidoalkyl or -imidoalkyl cyanide X.NR.CnH2n.CN with a hydrogen halide in the presence of an alkanol R1OH, and, if desired, treating the resulting imino ether hydrohalide with ammonia or a primary or secondary amine. Suitable acylamidoalkyl cyanides (in which the acylamido group may be in any position in an alkylene chain of any desired length, as, for instance, in an acylamidoacetonitrile, an a - or b -acylamidopropionitrile, an a -, b - or g -acylamido-n-butyronitrile, an e -acylamidocapronitrile or an acylamidoundecanonitrile) are obtainable by treating the corresponding aminoalkyl cyanides with an organic (straight or branched chain alkyl, unsubstituted or substituted mono- or poly-nuclear aryl, aralkyl or heterocyclic) carboxylic acid halide or anhydride, e.g. acetyl chloride or bromide, propionyl chloride, n- or iso-butyryl chloride, benzoyl halides or their derivatives substituted in the nucleus by a substituted amino group or a group or atom readily convertible to or replaceable by an amino group, such as an acylamido, dialkylamino, nitro, nitroso, azo or hydrazo group or a halogen atom (especially p-acylamido- or p-nitro-benzoyl halides), or by other substituents such as alkyl, hydroxy or alkoxy groups (e.g. a toluoyl chloride), naphthoyl halides, phenacetyl chloride or picolinyl, nicotinyl or isonicotinyl chlorides.  When the cyanide is soluble in the alkanol (which is preferably a lower alkanol, e.g. ethanol, a propanol or a butanol), the conversion into the imino ether hydrohalide may be effected by dissolving the cyanide in the alkanol before or after passing a hydrogen halide through it; alternatively, the cyanide may be dissolved suspended in an inert solvent (e.g. a cyclic ether, such as dioxane, an ether, such as diethyl ether, or a halogenated hydrocarbon, such as chloroform) containing the alkanol into which the hydrogen halide has already been passed or through which it is then passed.  When the production of the amidine is effected by means of a primary or secondary amine, this may be an alkylamine, a dialkylamine, an arylamine, an alkylarylamine, a cycloalkylamine, a heterocyclic amine or a substituted amine, e.g. methylamine, ethylamine, n-propylamine, n-butylamine, diethylamine, aniline, N-methylaniline, cyclohexylamine, piperidine or b -dimethyl- or -diethyl-aminoethylamine.  The amidines are useful as pharmacological materials and as intermediates for heterocyclic compounds containing a 2-o -amino- or -substituted aminoalkyl group.  In examples: (1) a suspension of benzamidoacetonitrile in chloroform and ethanol is treated with dry hydrogen chloride to produce benzamidoacetimino ethyl ether hydrochloride, which is converted on standing in saturated alcoholic ammonia into benzamidoacetamidine hydrochloride; (2) b -benzamidopropionitrile similarly yields the hydrochlorides of b -benzamidopropionimino ethyl ether and b -benzamidopropionamidine; (3) g -phthalimidobutyronitrile similarly gives g -phthalimidobutyramidine hydrochloride (without isolating the imino ether hydrochloride in a pure state); (4) e -benzamidocapronitrile similarly yields e -benzamidocapramidine hydrochloride; (5) acetamidoacetonitrile (obtainable by the action of acetic anhydride on aminoacetonitrile sulphate in aqueous sodium carbonate solution) is treated as in (1) to form acetamidoacetimino ethyl ether hydrochloride; (6) a -acetamidopropionitrile (obtainable by the action of acetic anhydride on a -aminopropionitrile in ether) is dissolved in ether and ethanol and treated with dry hydrogen chloride to produce a -acetamidopropionimino ethyl ether hydrochloride.