Patent GB-573514-A (GB)
Title: Process for separating and purifying the alkaloids of ergot
IPC: C07D519/02
Filed: 1943-09-15
Abstract: Derivatives of lysergic and isolysergic acids of the formula C15H15N2COR, wherein R represents a peptide-like radical formed from two amino acids and an a -keto-acid amide, or represents an alcohol, amino alcohol or hydrazine radical, are obtained in a pure state by treatment to convert them into their salts or complexes with di-acylated tartaric acids of the general formula HOOC.CHOX.CHOX.COOH, in which X denotes an aroyl residue, e.g. by reaction of the alkaloid derivative with the acid in methanol, ethanol or acetone, or by employing a double decomposition of two suitable salts, such as the barium salt of the acylated tartaric acid with the sulphate of the alkaloid derivative, separating such salts or complexes by fractional crystallization and reconverting each into the lysergic or isolysergic acid derivative by treatment with an alkaline compound.  Specified aroyl residues are benzoyl, p-toluyl, anisoyl, a -methoxybenzoyl, veratroyl and a -naphthoyl.  In examples: (1) a mixture of d-isolysergic acid-d-isopropanol-amide (ergobasinine) and l-isolysergic acid-d-isopropanol amid<\>pe, prepared by the reaction of d, l-isolysergic acid hydrazide with d-2-amino propanol, is treated with d-dibenzoyl-tartaric acid in boiling methanol; on cooling the ergo basinine salt crystallises first and is separated and treated in aqueous suspension with excess of sodium bicarbonate solution to liberate the free base which is extracted with ether; the l-isolysergic acid-(+)-isopropanolamide salt in the mother liquor is decomposed to yield the free base which is recrystallised from acetone; (2) d-l-isolysergic acid hydrazide is treated with d - di - (p - toluyl) - tartaric acid in boiling methanol; on cooling, the l-isolysergic acid-hydrazide salt crystallises first and is separated and treated with sodium bicarbonate to liberate the free hydrazide which is extracted with ethyl acetate and recrystallised from methanol; the d-isolysergic hydrazide salt crystallises later, but the pure salt is obtained advantageously by resolving the original d-l-lysergic acid hydrazide with l-di-(p-toluyl)-tartaric acid, whereby the d - isolysergic acid - hydrazide l - di - p - toluyl - tartrate crystallises first and is further treated similarly to obtain the free base; (3) ergotoxine is mixed with l-di-(p-toluyl)-tartaric acid in alcohol and water added slowly to cause crystallisation of a mass which is extracted with alcohol and recrystallised into three fractions (the second and third being obtained from methanol solutions), viz. the l-di-p-toluyl-bitartrate salts of ergocristine, an alkaloid to be called ergocryptine, and one to be called ergocornine; the free ergocristine and ergocryptine may be obtained by treating the respective salts in aqueous suspension with sodium bicarbonate and extracting with chloroform; the free ergocornine may be obtained by dissolving the third fraction in methanol, allowing a further quantity of ergocryptine to crystallise out, treating the mother liquor with sufficient water to lower the content of methyl alcohol to 80 per cent to obtain crystals of the ergocornine-l-di-(p-toluyl)-bitartrate, purifying this by repeated recrystallisation from methanol and liberating the free base with sodium bicarbonate and extracting it with chloroform; the ergocryptine and ergocornine may be converted into their dentro-rotatory isomers to be called ergocyptinine and ergocorninine respectively, by boiling with methanol and by the action of alcoholic caustic potash respectively.  Specifications 463,936 and 480,822 are referred to.  Di-aroylated tartaric acids are prepared by melting tartaric acid with the aroyl carboxylic acid chlorides.