Patent GB-625442-A (GB)
Title: Process for the manufacture of 2-aminoalkyl-glyoxalines
IPC: C07D233/64
Filed: 1946-09-12
Abstract: Aminoalkyl glyoxaline derivatives of the general formula <FORM:0625442/IV (b)/1> wherein n is an integer, R1 and R2 are hydrogen, or alkyl, aryl or aralkyl groups, R3 is hydrogen or an alkyl, aryl or aralkyl group and R6 is the acyl residue of an organic carboxylic or sulphonic acid, or R3 and R6 are both alkyl, aryl or aralkyl groups, or R3 and R6 together consist in the acyl residue of an organic dicarboxylic acid, are prepared by reacting an aminoalkyl imino ether of the general formula <FORM:0625442/IV (b)/2> wherein n, R3 and R6 have the above significance and R5 is an alkyl or aralkyl group with an a -amino carbonyl compound which in one tautomeric form has the general formula HO.CR1=CR2.NH2, wherein R1 and R2 have the above significance, or an acetal thereof, or an O-alkyl ether of the enol form thereof.  The a -amino carbonyl compound or its acetal or O-alkyl ether may be added portionwise to the aminoalkyl imino ether. Suitable a -amino carbonyl compounds are aminoacetone, amino-acetaldehyde, o -aminoacetophenone, and a -aminopropiophenone. The reaction may be effected in solution or in partial solution in an alkanol having not more than eight carbon atoms in the molecule, and the iminoether may be dissolved in the alkanol in the form of its hydrochloride and the free iminoether released with an equivalent amount of an alkali metal alkoxide such as sodium ethoxide.  The group R6 may be an alkyl, aryl, aralkyl or heterocyclic carboxylic or sulphonic acid residue, e.g. it may be an acetyl, propionyl, n-butyryl, benzoyl, substituted benzoyl such as p-acylamidobenzoyl, toluoyl, phenylacetyl, picolinyl, nicotinyl or isonicotinyl residue or an ethane, n-butane, benzene, naphthalene, toluene or phenylethane sulphonyl residue.  The groups R3 and R6 together may represent the residue of succinic or phthalic acid.  The acylamidoalkyl iminoether employed may have as the acyl group a benzenesulphonyl group which contains as a substituent in the para-position to the sulphonyl group an amino group, a protected amino group, a substituted amino group, or a group which is readily convertible to an amino group. Benzenesulphonamidoalkyl imino ethers other than those containing an amino group, a protected amino group or a group readily convertible to an amino group may also be employed, e.g. those containing alkyl, hydroxyl and alkoxyl substituents which may be present in the para or any other position, and they may contain two substituents in the benzene ring.  There may also be employed the N-substituted amino alkyl iminoethers in which the substituents carried by the disubstituted nitrogen atom of the amino group are alkyl, aryl or aralkyl groups and these may be like or unlike in character.  When a carboxylic acylamidoalkyl iminoether is employed in the reaction, the resulting 2-(carboxylic acylamidoalkyl) glyoxaline may be hydrolysed to yield the free 2-(aminoalkyl)-glyoxaline, e.g. by reaction with aqueous mineral acid.  When a p-acylaminobenzene sulphonamidoalkylimino-ether is employed in the reaction, the resulting 2 - (p - acylamidobenzenesulphonamidoalkyl) - glyoxaline may be hydrolysed to remove the acyl radical to form the corresponding compound containing a free amino group in the para-position of the benzene ring.  In examples: (1) benzamidoacetimino ethyl ether is reacted with aminoacetone to yield 2 - (benzamidomethyl)-4-methyl glyoxaline which is hydrolysed with hydrochloric acid to aminomethyl-4-methyl glyoxaline; similarly, by employing o -aminoacetophenone, 2 - (benzamidomethyl) - 4 - phenyl glyoxaline and 2-aminomethyl-4-phenyl glyoxaline are prepared; (2) b -phthalimido propionimino ethyl ether is reacted with aminoacetone to yield 2 - (b  - phthalimido - ethyl) - 4 - methyl glyoxaline; (3) b -benzamido-propioniminoethyl ether is reacted with aminoacetone to yield 2 - (b  - benzamido - ethyl) - 4 - methyliminazole which is hydrolysed to 2-(b -aminoethyl)-4-methyliminazole.  Aminoalkyl imino ethers of the general formula <FORM:0625442/IV (b)/3> wherein n, R3 and R6 have the above significance, are prepared by treating a cyanide of the general formula <FORM:0625442/IV (b)/4> with a hydrogen halide in the presence of an alkanol, e.g. ethanol or an aralkanol, e.g. benzyl alcohol as described, for example, in Specification 605,952.  In examples: (2) b -phthalimido propion imino ether is prepared by the action of hydrogen chloride and ethyl alcohol on b -phthalimido propionitrile; (3) similarly b -benzamidopropioniminoethyl ether is prepared from b -benzamidopropionitrile.