Patent GB-994572-A (GB)
Title: Lyxopyranoyloxy-coumarins
IPC: C07H17/07
Filed: 1961-11-07
Abstract: The invention comprises compounds of the formulae <FORM:0994572/C2/1> and <FORM:0994572/C2/2> wherein R1 represents a chlorine, bromine or iodine atom or an alkyl group, R2 represents a nitro or acylamino group, the bonds shown as broken lines denote that the R substituents attached thereto are optional and wherein the asterisks indicate that the bonds so marked are appropriate to a -glycosides and the alkyl groups contain up to 7 carbon atoms.  Compounds of the Formula II are prepared by condensing a b  - [5,5 - dialkyl - 4 - (O - alkyl) - 2,3-cyclocarbonato] - L - lyxopyrenose halide with a coumarin derivative of the formula <FORM:0994572/C2/3> preferably in an anhydrous medium conveniently in the presence of a silver salt or silver oxide.  When the process is carried out with a compound of the Formula I where R2 represents an acylamino group, the product can be debenzylated be catalytic hydrogenolysis.  When R2 represents a nitro group, the product may be catalytically hydrogenated to convert the nitro to an amino group and hydrogenolyse the benzyloxy group and then if desired, acylated. When R2 represents a hydrogen atom, the product is debenzylated and the resulting 3-hydroxy compound coupled with a diazotized arylamine to give the 3-hydroxy-4-azo-derivative which if desired may be catalytically reduced to the 3-hydroxy-4-amino compound which may be acylated.  4 - Benzyloxy - 7 - hydroxy - coumarins of the Formula I can be obtained from the corresponding 4-hydroxy compound by an acid catlysed etherifications with benzyl alcohol.  3 - Acyl - 4,7 - dihydroxy - coumarin can be obtained by coupling the corresponding 3-unsubstituted coumarin with a diazotized arylamine; reductively splitting the resulting azo compound to give the 3-amino-4, 7-dihydroxy-coumarin which can be acylated.  3 - Nitro - 4 - benzyloxy - coumarin derivatives may be obtained by nitrating and benzylating 4,7-dihydroxy coumarins, the 7-position being protected prior to nitration.  3 - [4 - Methoxy - 3 - (3 - methyl - butyl)-benzoylamino] - 4 - benzyloxy - 7 - hydroxy - 8-methyl-coumarin is prepared by etherifying 4-hydroxy - 3 - [3 - methyl - butene - (2) - yl]-benzoic acid ethyl ester to give 4-methoxy-3-[3-methyl - buten - (2) - yl] - benzoic acid ethyl ester which is hydrolysed to the free benzoic acid, hydrogenated to the saturated acid and converted to the acid chloride which is reacted with 3 - amino - 4,7 - dihydroxy - 8 - methyl - coumarin to give 3 - [4 - methoxy - 3 - (3 - methylbutyl) - benzoylamino] - 4,7 - dihydroxy - 8-methyl-coumarin which is converted to the 4-benzyloxy derivative by reaction with phenyldiazomethane.  3 - [4 - Acetoxy - 3 - [3 - methyl - buten - (2)-yl] - benzoylamino] - 4 - benzyloxy - 7 - hydroxy-coumarin may be prepared by reacting 4-acetoxy - 3 - [3 - methyl - buten - (2) - yl], benzoyl chloride with 3-amino-4,7-dihydroxy-coumarin and treating the resulting 4,7-hydroxy-coumarin with phenyldiazomethane.  3 - (4 - Acetoxy - benzoylamino) - 4 - benzyloxy-7 - hydroxy - 8 - methyl - coumarin, 3 - (4 - acetoxy - 3 - propyl - benzoylamino) - 4 - benzyloxy-7 - hydroxy - 8 - methyl - coumarin, 3 - (3,4,5-trimethoxy - benzoylamino) - 4 - benzyloxy - 7-hydroxy - 8 - methyl - coumarin, 3 - benzylcar, bonylamino - 4 - benzyloxy - 7 - hydroxy - coumarin, 3 - [2,4 - diacetoxy - 5 - (3 - methylbutyl) - benzoylamino] - 4 - benzyloxy - 7 - hydroxy - 8 - methyl - coumarin and 3 - phenoxymethyl carbonylamino - 4 - benzyloxy - 7 - hydroxy - 8 - methyl - coumarin are prepared in a similar manner from 3-amino-4,7-dihydroxy-8-methyl-coumarin and p-acetoxy-benzoyl chloride, 3 - propyl - 4 - acetoxy - benzoyl chloride, 3,4,5 - trimethoxy - benzoyl chloride, phenylacetic acid anhydride, 2,4-diacetoxy-5-(3-methyl-butyl)-benzoic acid with dicyclohexyl-carbodiimide and phenoxyacetic acid with tributylamine and ethyl chloroformate respectively.  3 - [2,2 - Dimethyl - chromen - (6) - carbonylamino] - 4 - benzyloxy - 7 - hydroxy - 8 - methyl-coumarin may be prepared by 3-amino-4,7-dihydroxy - 8 - methyl - coumarin with 2,2 - dimethyl - chroman - (6) - carbonyl chloride to give 3 - [2,2 - dimethyl - chroman - (6) - carbonyl-amino] - 4 - hydroxy - 7 - [2,2 - dimethyl - chromanoyloxy - (6) - ] - 8 - methyl - coumarin which is etherified to give the 4-benzyloxy derivative which is hydrolysed to remove the 2,2-dimethylchromonyloxy group. Specification 994,573 is referred to.