Mechanism of acid catalysis in the cyclisation of 5-aminolevulinic acid and acetylacetone to 3-acetyl-4-(2-carboxyethyl)-2-methylpyrrole

Abstract

Under acid conditions 5-aminolevulinic acid reacts with acetylacetone to give 3-acetyl-4-(2-carboxyethyl)-2-methylpyrrole (1). There is also formation of a small amount of the Fischer–Fink product (2). Use of ¹³C and ¹⁵N NMR spectroscopy showed that the first condensation product to accumulate is the enaminoketone (5). The trifluoro analogue of 5 can be isolated and its cyclisation to 8 was monitored. There is a substantial spontaneous reaction and the acid-catalysed process occurs by specific acid catalysis.