A convenient and efficient methodology for the synthesis of densely substituted pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA) as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused isocoumarins were formed in good yields. This synthetic method has several advantages such as the employment of solvent-free reaction conditions without the use of any toxic reagents and metal catalysts, the ease of product isolation, the use of a recyclable catalyst, the low cost, the easy availability of the starting materials, and the excellent yields of products.
On the example of synthesis of 4-acetylamino-3-fluoroalkyl(aryl)-4,5,6,7-tetrahydro-1,2-benzisoxazoles, the effective approach to a synthesis of novel 4-acylamino-4,5,6,7-tetrahydro-1,2-benzisoxazoles is proposed. 3-Fluoroalkyl(aryl)- 6,7-dihydro-1,2-benzisoxazol-4-ones were reduced by a sodium borohydride in isopropanol to obtain 3-fluoroalkyl(aryl)- 4,5,6,7-tetrahydro-1,2-benzisoxazol-4-ols that in the conditions of the Ritter reaction (acetonitrile, acetic acid, sulfuric acid) gave target 4-acylamino derivatives with 80–94 % yields.
Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions