GB682457A - Synthesis of 4-methylcoumarins - Google Patents

Abstract

4-Methylcoumarins of the general formula <FORM:0682457/IV (b)/1> (wherein R1 represents hydrogen or an alkyl group and R2, R3, R4 and R5 represent hydrogen or substituents which are substantially o-p-directing, and especially wherein R1 represents hydrogen and not more than two of R2, R3, R4 and R5 represent alkyl or hydroxy groups, one of them preferably in the 5- or 7-position, the remaining positions being unsubstituted) are manufactured by treating phenyl acetoacetates of the general formula <FORM:0682457/IV (b)/2> with a dehydrating agent at temperatures of about 10-100 DEG C. (preferably about 40-60 DEG C.). The reaction is advantageously effected in the presence of an inert diluent (e.g. nitrobenzene), and using a small amount only of the dehydrating catalyst together with an inert entraining agent to remove the liberated water by azeotropic distillation. The entraining agent (which may also be the diluent) is preferably a liquid hydrocarbon (e.g. benzene or toluene), a chlorinated hydrocarbon (e.g. ethylene dichloride) or an alcohol (e.g. n-butanol), or especially a liquid hydrocarbon containing a small amount of a high-boiling alcohol. In examples: (1) and (2) phenyl acetoacetate is heated with 75 per cent sulphuric acid, or with aluminium chloride in nitrobenzene, to produce 4-methylcoumarin; (3) and (4) resorcinol monoacetoacetate is heated with 98 per cent sulphuric acid, or with 93 per cent sulphuric acid in n-butanol to give b -methylumbelliferone; (5) pyrogallol monoacetoacetate is treated as in (3), producing b - methyldaphnetin; (6) hydroquinone monoacetoacetate is heated with various concentrations of sulphuric acid to form 4 - methyl - 6 - hydroxycoumarin; (7)-(9) m-, o- and p-cresol similarly yield respectively 4 : 7-, 4 : 8- and 4 : 6-dimethylcoumarin. Additional dehydrating catalysts specified are benzenesulphonic acid, zinc chloride and phosphorus oxychloride. Other substituents which may be represented by R2, R3, R4 and R5 ar halogens and alkoxy, dialkylamino, aryl and chloromethyl groups. Phenyl acetoacetates of the second general formula above are obtainable by reacting the appropriate phenols with diketene in the presence of a basic catalyst, and, if desired, introducing an alkyl group at R1 by the action of an alkyl halide or sulphate in the presence of sodium. The preparation of the starting materials of the examples above is described in detail.