Patent GB-728767-A (GB)
Title: 2-substituted chromone compounds, and a method of making same
IPC: C07D311/22
Filed: 1952-10-07
Abstract: The invention comprises chromones of the general formula <FORM:0728767/IV (b)/1> wherein R1-R4 all represent H or one or more represent alkyl or alkoxy radicals containing up to 4 carbon atoms; R5 is H or an alkyl radical containing up to 3 carbon atoms; and X represents CnH2n.N.R6R7, R6 being H or an alkyl or acyl radical containing up to 4 carbon atoms, R7 being an alkyl or acyl radical containing up to 4 carbon atoms and n being an integer, or CnH2n.Y, Y being a single ring N-heterocyclic radical, with or without nuclear alkyl substituents, and n being an integer, or X is a single ring N-heterocyclic radical with or without nuclear alkyl substituents and attached to the chromone 2-carbon atom by a carbon-carbon linkage. These compounds are prepared by condensing a compound of the formula <FORM:0728767/IV (b)/2> wherein R1-R5 are as above defined, with an ester of an acid X.COOH (X is as defined above), in the presence of a condensing agent, e.g. alkali metals, their hydrides, amides or alcoholates, and treating the resulting diketone with a concentrated acid, e.g. hydrochloric, sulphuric or phosphoric acid, to effect ring-closure to the 2-substituted chromone.  The condensation is preferably effected in a solvent, e.g. pyridine, a -picoline or dioxane, and the ring-closure carried out at room temperature.  In an example, o-hydroxy acetophenone and dimethylaminoacetic acid ethyl ester are condensed in pyridine in the presence of sodium hydride, the sodium salt of the diketone isolated and cyclised in cold concentrated hydrochloric acid to yield 2-(dimethylaminomethyl)-chromone as its hydrochloride. Numerous other detailed examples are given in which the 2-substituent is b -dimethylaminoethyl-, b -diethylaminoethyl-, b -dimethylaminopropyl-, n-dibutylaminomethyl-, piperidinomethyl-, b -piperidinoethyl-, morpholinomethyl-, b -morpholinoethyl-, 21,, 31- and 41-pyridyl-, acetylaminomethyl-, b -acetaminoethyl-, 21-, 31- and 41-piperidyl-, 21-, 31- and 41-N-methylpiperidyl-, 41 - N - ethylpiperidyl-, or 51 - thiazolyl - 21 - methyl-.  Substituents in the aromatic ring include 6-, 7- and 8-methyl-, 5-, 6-, 7- and 8-methoxy, 6-iso-propoxy-, 5-n-butoxy-, 5-ethoxy-, and 5-n-propoxy-, while in the 3-position there may be a methyl group. A further list of possible 2-substituents mentions 21-pyrrolyl-, 31-pyrazolyl-, 21- and 41-thiazolyl-, and 21-imidazolyl-.ALSO:Pharmaceutical and veterinary compositions comprise novel chromones of the general formula <FORM:0728767/VI/1> (wherein R1-R4 all represent H or one or more represent alkyl or alkoxy radicals containing up to 4 carbon atoms, R5 is H or an alkyl radical containing up to 3 carbon atoms; and X represents CnH2nN.R6R7, R6 being H or an alkyl or acyl radical containing up to 4 carbon atoms, R7 being an alkyl or acyl radical containing up to 4 carbon atoms and n being an integer, or CnH2nY, Y being a single ring N-heterocyclic radical, with or without nuclear alkyl substituents and n being an integer, or X is a single ring N-heterocyclic radical with or without nuclear alkyl substituents and attached to the chromone 2-carbon atom by a carbon-carbon linkage) together with an inert carrier.  Specified compositions are (a) injections, comprising the chromone derivatives in water or isotonic salt solution; (b) dispersions of chromones in vegetable oils, e.g. sesame or olive oil, preferably incorporating an emulsifier, and (c) tablets, pills and powders, comprising the chromones and a binder, e.g. lactose, sugar, bolus alba, talcum, starch, gelatine, gum arabic, tragacanth, methyl cellulose and yeast extract.