Verfahren zur Herstellung von chemischen Verbindungen

摘要

The invention comprises (a) quaternary compounds having cations of the skeletal formula wherein R1 and R2 are aliphatic, araliphatic or aryl groups, R3 is H or OH, R4 is H, or R3 and R4 together form a carbon-carbon bond and R5 is a group COR1 or CH2R1, R4 being hydroge when R5 is COR1, with one or more anions; (b) a process for the preparation of compounds of the above formula by reacting a compound of the formula with a compound R2X, wherein X is an anion-forming atom or group, such as sulphate or p-toluenesulphonate and (c) a process for the preparation of compounds of the formula by decomposing I to remove the 3-oxo-alkyl group from the 21-position, e.g. by treatment with acids or bases or by heating, preferably in a solvent. Suitably the group R1 may be alkyl, e.g. methyl, phenyl or benzyl and R2 may be arylmethyl, alkyl, hydroxyalkyl or alkenyl, and the benzene rings may carry benzyloxy, phenoxy or alkoxy substituents, e.g. methoxy groups in the 61, 71, 9 and 10 positions or methylenedioxy substituents. If the group R2 is an arylmethyl group, it may be removed by hydrogenolysis. An alkenyl group R2, e.g. allyl, may be reduced to the corresponding saturated group. If R5 is a group COR1, it may be converted to a group CH2R1 by reduction. In examples, 2-hydroxy-3-acetyl-21-(3-oxo - n - butyl) - 61,71,9,10 - tetramethoxy - 2 - isoquinolylmethyl-benzoquinolizine is treated with benzyl bromide to give the bromide of a 61,71,9,10-tetramethoxy derivative of I, R1= CH3, R2=benzyl, R3=OH, R4=H, R5=CH3CO. This is decomposed to give the corresponding tertiary base III, R2=benzyl, and dehydrated to give the corresponding unsaturated compound, the 61,71,9,10 - tetramethoxy derivative of III, R2=benzyl, R3 and R4 form a carbon-carbon bond and R5=CH3CO, this is treated with ethane dithiol to form the cyclic ketal of the keto group R5, which is reduced (sodium in liquid ammonia) to give N-benzyl-2,3-dehydroemetine, R5=C2H5, followed by removal of the 21-benzyl group to give 2,3-dehydroemetine. Similarly the same starting material is quaternated with methyl iodide and with allyl bromide and the product is converted to the corresponding tertiary compound III and, in the case of the allyl derivative, reduced.