FORFARANDE FOR FRAMSTELLNING AV KROMON-2-KARBONSYROR

摘要

1374981 Chromone-2-carboxylic acids and intermediates FISONS Ltd 3 Jan 1972 [22 Jan 1971 31 March 1971] 2925/71 and 8767/71 Heading C2C Bis-chromone-2-carboxylic acids of Formula I in which R1 to R6 are the same or different and each is a hydrogen or halogen atom or an alkyl, hydroxy, alkoxy or substituted alkyl or alkoxy group, and X is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain which may be interrupted by a carbocyclic or heterocyclic ring, or by one or more oxygen atoms or carbonyl groups, and pharmaceutically acceptable derivatives thereof, are obtained by cyclising a compound of Formula II in which each pair of groups A1, A2 denotes a pair of groups -OH and -COCH 2 COCOOH, or the chain -O-C(COOH)=CH-CO- or a derivative (e.g. ester), thereof, provided that at least one of the pairs of groups A1, A2 represents the pair of groups -OH and and where necessary or desired converting the resulting compound of Formula I to a pharmaceutically acceptable derivative or vice versa. The cyclization may be effected by heating, preferably in the presence of an acid, e.g. HCl, and in an inert solvent, at temperatures from 20‹ to 150‹ C. Compounds (I) are useful in the treatment of allergic asthma. Novel compounds of Formula II may be obtained by reacting together the compounds (III), (IV) and compound (V), A-X1-B and reacting the product with diethyl oxalate in manner known per se to form the diethyl ester of (I), and carefully treating this compound, or its hydrolysis product of Formula (I), with dilute NaOH at approximately ambient temperature (A and B in (V) being groups capable of reacting with -OH to form an ether linkage, and X1 being such that with the residues of A and B it forms an X group). Compound (II) may also be obtained by treating a compound of formula (VIII) in which R is an alkyl group, with alkali under controlled conditions, e.g. by extracting a chloroform solution with aqueous alkali.