Patent GB-577606-A (GB)
Title: Improvements in or relating to alkaloid derivatives
Filed: 1944-03-04
Abstract: Aminoderivatives of colchicine, regarded as R=CH.OCH3, wherein R represents the residue of the colchicine molecule, and having the general formula <FORM:0577606/IV/1> wherein R has the significance defined, and R1 and R2 may be the same or different, and either both represent substituted or unsubstituted alkyl or alkenyl radicals or R1 represents hydrogen and R2 represents a substituted or unsubstituted alkyl or alkenyl radical, are obtained by the reaction of colchicine with a substituted or unsubstituted alkylamine (including a dialkylamine), an alkenylamine or an alkylenediamine by heating colchicine with the particular amine in a solvent such as ethanol.  Specified amines are methylamine, ethylamine, dimethylamine, isopropylamine and allylamine; ethylenediamine; ethanolamine and b -ethoxyethylamine, n-propylamine, n- and iso-butylamines, a -phenylethylamine and b -phenylethylamine.  In examples: (1) colchicine and 9 per cent alcoholic methylamine are heated on a steam bath for 4 hours and the crude product is precipitated by ether; (2) colchicine and 4 per cent alcoholic ethylamine are heated as in (1), and the residue, in chloroform-benzene, is chromatographed through alumina previously saturated with chloroform, the product being diluted with chloroform-benzene (1 : 1); (3) colchicine and 3 per cent methyl alcoholic isopropylamine are heated as in (1) for 16 hours, and the product is isolated as in (2); (4) colchicine, 45 per cent allylamine in methyl alcohol and methyl alcohol are heated as in (1) for 5 hours, and the product is isolated as in (2); (5) colchicine and 15 per cent dimethylamine in methyl alcohol are heated as in (3) and the product is isolated as in (2); (6) colchicine, ethylenediamine and alcohol are heated as in (4) and the product is isolated as in (1); (7) colchicine, ethanolamine and alcohol as in (1) after removal of solvent and the crude product is isolated as in (1); (8) colchicine, b -ethoxyethylamine and alcohol are processed as in (7).  According to the first Provisional Specification: colchicine, ethanol and aqueous diethylamine (ca. 30 per cent) are heated together in a sealed tube on a steam bath for 4 hours, the residue being evaporated to dryness in vacuo over sulphuric acid to isolate the product. According to the second Provisional Specification: (1) colchicine, n-propylamine and ethanol are heated in a sealed tube at 100 DEG  C. for 4 hours, and the residue is purified by a chromatographic treatment; (2) colchicine and 3 per cent methanolic isopropylamine are heated as in (1) for 16 hours and the product is purified as in (1); (3) n-butylamine; and (4) isobutylamine are heated as in (1) for 24 and 16 hours, respectively, the products being purified as in (1); (5) colchicine and piperidine are heated at 110 DEG  C. for 1 hour and the product is isolated by crystallisation; (6) colchicine, a -phenylethylamine and ethanol are heated in a sealed tube at 100 DEG C. for 4 hours, and the residue is triturated with ether to isolate the product; (7) colchicine, aminodiethylacetal (b b -diethoxyethylamine) and ethanol are heated as in (6) and the product is isolated by crystallisation; (8) colchicine, glycine ester hydrochloride and pyridine are heated as in (6) for 12 hours and the residue is purified by a chromatographic treatment.