Patent GB-803372-A (GB)
Title: Hydroxychromone derivatives and methods of preparing the same
Filed: 1956-11-01
Abstract: The invention comprises compounds having a coronaro-dilating action of the general formula <FORM:0803372/IV (b)/1> wherein (a) R and R1 are both methyl groups, the chain R2OOC.CH2O- is indifferently in position 6 or 7, and R2 is H, Na, K, C2H5, (C2H5)2N(HCl).CH2.CH2- or the hydrochloride of the b -piperidino-ethyl radical; (b) R is methyl, R1 is ethyl, the chain R2OOC.CH2O- is in the 7-position and R2 is as in (a) or (CH3)2N(HCl).CH2.CH2-; or (c) R is H and R1 is phenyl, the chain R2OOC.CH2O- is in the 7-position and R2 is as in (b), or another alkyl group of from one to six carbon atoms; and a process for their preparation by boiling in solution or suspension a substituted 6- or 7-hydroxychromone with an alkyl halogen acetate, in which the alkyl group has from one to six carbon atoms, in the presence of an alkali metal carbonate for between seven and twelve hours.  The oxyacetic ester is then recovered from the mixture and, if required, subjected to alkaline alcoholic hydrolysis at 40 DEG  C. to yield the corresponding alkali metal salt, which may then be acidified to give the free acid, or boiled with the hydrochlorides of b -dimethylaminoethyl chloride, b -diethylaminoethyl chloride or b -piperidinoethyl chloride in isopropanol for from four to five hours to yield the corresponding amino-esters.  The free acids may also be obtained direct by acid hydrolysis of the original oxyacetic esters. In examples: (1) 6-hydroxy-2,3 - dimethylchromone, ethyl bromoacetate, and potassium carbonate are refluxed in acetone, yielding 2,3 - dimethyl - chromone 6 - ethyl oxyacetate; similarly (2) to (15) are prepared following: 2,3 - dimethylchromone - 7 - ethyl oxyacetate, 2 - ethyl - 3 - methylchromone - 7 - ethyl oxyacetate and the methyl, ethyl, n-propyl, isopropyl, allyl, secbutyl, isobutyl, butyl, amyl, isoamyl, inactive amyl, and hexyl esters of flavone-7-oxyacetic acid; (16) 2,3-dimethylchromone-6-ethyl oxyacetate in ethanol is treated with ethanolic KOH when the potassium salt of 2,3-dimethylchromone-6-oxyacetic acid separates; likewise (17) to (19), are prepared 2,3-dimethylchromone-7-potassium oxyacetate, 2 - ethyl - 3 - methylchromone - 7 - potassium oxyacetate and flavone - 7 - sodium oxyacetate; (20) 2,3-dimethylchromone-6-ethyl oxyacetate is refluxed with 70 per cent H2SO4, giving 2,3-dimethylchromone-6-oxyacetic acid; (21) to (23), as in (20) are prepared 2,3-dimethylchromone - 7 - oxyacetic acid, 2 - ethyl - 3 - methylchromone-7-oxyacetic acid and flavone-7-oxyacetic acid; (24) the potassium salt of 2,3-dimethylchromone-6-oxyacetic acid is reacted with b  - diethylaminoethyl chloride hydrochloride in isopropanol giving 2,3-dimethylchromone - 6 - b  - diethylaminoethyl oxyacetate hydrochloride; likewise (25) to (33) are prepared the b -piperidinoethyl and b -diethylaminoethyl esters of 2,3-dimethylchromone-6- and 7-oxyacetic acids, of 2-ethyl-3-methylchromone-7-oxyacetic acid and of flavone 7-oxyacetic acid in the form of their hydrochlorides, and also the b -diethylaminoethyl esters of the two last-mentioned acids, again as their hydrochloride salts.