GB663369A - Manufacture of substituted coumarans, coumarones and chromones - Google Patents

Abstract

A ketone of the general formula (II) is prepared from a 6-hydroxycoumaran of the formula (I) by (a) dissolving it in ether and passing in hydrogen chloride in the presence of zinc chloride and acetonitrile, or (b) reacting with an acetylating agent in the presence of a condensing agent, or from a 6-acetoxycoumaran of the formula (Ia) by reaction with aluminium chloride in nitrobenzene. In the formul R1 and R2 are hydrogen or alkoxy, and R3 is hydrogen, alkyl or aralkyl. The ketone (II) is then converted to a b -diketone (III) by reaction with an ester of a carboxylic acid of the formula R3COOH under the condition of the Claisen reaction, and this is submitted to cyclo-dehydration by means of an acid to give a dihydrofurochromone (IV). Finally, the dihydrofurochromone (IV) is dehydrogenated to yield the furochromone (V). The same product may also be obtained by dehydrogenating the 6-hydroxy-5-acetylcoumaran (II) to give a 6-hydroxy-5-acetylcoumarone (VI) which is reacted with an ester of a carboxylic acid R3COOH under the conditions of the Claisen reaction to give a 6-hydroxy-5-o -acylacetylcoumarone (VII) and then cyclodehydrated by treatment with an acid to yield the furochromone (V). Examples given describe the preparation of 6-hydroxy-4,7-dimethoxy-5-acetylcoumaran from 6-hydroxy-4,7-dimethoxycoumaran by treatment with zinc chloride and acetonitrile followed by hydrolysis of the intermediate imino compound which is formed; 1,4-dimethoxy-2,6-dibenzyloxybenzene and the corresponding diethoxy compound by the action of dimethyl (or diethyl) sulphate on 1,4-dihydroxy-2,6-dibenzyloxybenzene in presence of sodium ethoxide; 2,4 - dihydroxy - 3,6 - dimethoxybenzaldehyde from 1,4 - dimethoxy - 2,6 - dibenzyloxybenzene by the action of zinc cyanide and hydrogen chloride; 2 - hydroxy - 3,6 - dimethoxy - 4-benzyloxy-benzaldehyde from 2,4-dihydroxy-3,6-dimethoxybenzaldehyde by treatment with benzyl bromide; 3,6-dimethoxy-5-benzyloxy-2-formylphenoxyacetic acid from 2-hydroxy-3,6 - dimethoxy - 4 - benzyloxybenzaldehyde by treatment with methyl bromoacetate; 4,7-dimethoxy-6-benzyloxycoumarone from 3,6-dimethoxy - 5 - benzyloxy - 2 - formylphenoxyacetic acid by treatment with acetic anhydride and sodium acetate; 6-hydroxy-4,7-dimethoxycoumaran by hydrogenation of 4,7-dimethoxy-6-benzyloxycoumarone in presence of palladiumcharcoal catalyst; 6-hydroxy-4,7-dimethoxy-5-b -ketobutyrylcoumaran by the action of sodium and ethyl acetate on 6-hydroxy-4,7-dimethoxy - 5 - acetylcoumaran; 6 - hydroxy-5-formylacetylcoumaran by the action of sodium and ethyl formate on 5-acetyl-6-hydroxycoumaran; 6 - hydroxy - 5 - b - ketobutyrylcoumarone by action of sodium and ethyl acetate on 6-hydroxy-5-acetylcoumarone; 6 - hydroxy - 5 - b - ketophenylbutyrylcoumarone by action of sodamide and ethyl phenyl acetate on 5-acetyl-6-hydroxycoumaran; 5,8-dimethoxy - 2 - methyl - 21,31 - dihydrofuro(41,51,6,7) chromone by the action of hydrogen chloride on 6-hydroxy-4,7-dimethoxy-5-b -ketobutyrylcoumaran; 2 - methylfuro -(41,51,6,71) chromone by the action of ethanolic sulphuric acid on 6-hydroxy-5-b -ketoburyrylcoumarone; 21,31 - dihydrofuro - (41,51,6,7) chromone by the action of hydrochloric acid in acetic acid on 6 - hydroxy - 5 - formylacetylcoumaran; 2 - benzyl - 21,31 - dihydrofuro - (41,51,6,7) chromone by heating 6 - hydroxy - 5 - b -ketophenylbutyrylcoumaran with hydrochloric acid and acetic acid; 6-hydroxy-4,7-dimethoxy-5-acetylcoumarone-(khellinone) by the dehydrogenation of 6-hydroxy-4,7-dimethoxy-5-acetylcoumaran using a palladium catalyst; 6-hydroxy - 5 - acetylcoumarone by dehydro <FORM:0663369/IV (b)/1> genation of 6-hydroxy-5-acetylcoumaran; 2-methylfuro - (41,51,6,7) chromone by dehydrogenation of 2 - methyl - 21,31 - dihydrofuro-(41,51,6,7) chromone; and 5,8-dimethoxy-2-methylfuro - (41,51,6,7) chromone - (khellin) by dehydrogenation of 5,8-dimethoxy-2-methyl-21,31 - dihydrofuro - (41,51,6,7) chromone. Specification 663,418 is referred to.