Methyl 7-aminocoumarin-4-carboxylate

Among polyheterocyclic systems, coumarins are synthesized by many routes, including the Pechmann reaction [51], which involves condensation of phenols with yS-ketoesters. This reaction, which has been the most widely applied method, has recently been studied under the action of MW irradiation by several authors [52], including the GS-MW process for 4-substituted 7-aminocoumarins [53]. Synthesis of methyl 7-aminocoumarin-4-carboxylates (51 and 52) by the Pechmann reaction involves heating a mixture of m-aminophenol and dimethyl oxalate at 130 °C (Scheme 9.17). Under such conditions, however, the yield of the reaction is variable, usually low (36%). Use of graphite as a support led to the expected lactone in slightly better yield (44%). 

The synthesis of methyl 7-aminocoumarin-4-carboxylate (93) was reported by heating m-aminophenol (84) (R = H, R = NH2) with dimethyloxalacetate (92) at 130 °C for 2h (84CPB3926). The yield of coumarin under such conditions was variable, sometimes low and accompanied by colored impurties that were very difficult to eliminate, even by column chromatography and recrystallization. This procedure in a focused MW reactor gave 93 in a similar yield (39%), but in less time (85min). Moreover, a better yield (44%) and a shorter time (50 min) were achieved by irradiation of a mixture of 84 and 92, adsorbed on graphite (Scheme 18) (01TL2791). 

Hoare DG, Koshland DE. A procedure for selective modification of carboxyl groups in proteins. J. Am. Chem. Soc. 1966 88 2057. DeMar JC, Disher RM, Wensel TG. HPLC analysis of protein-linked fatty acids using fluorescence detection of 4-(diazo-methyl)-7-diethyl aminocoumarin derivatives. FASEB J. 1992 61 A81. 

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