A density functional theory study of the mechanism of the Paal–Knorr pyrrole synthesis

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…Mechanistic aspects of the Paal-Knorr synthesis have been addressed in a density functional theory study [704], supporting the previously suggested pathway [71] that involves a cyclization of a hemiaminal intermediate in the rate-limiting step (Section 4.4.1). Although the extensive arsenal of well-established routes for pyrrole ring synthesis gives access to a wide variety of products, there is a continuous stream of new approaches that attempt to target pyrroles with rare substitution patterns, or serve as complementary methods for construction of known groups of useful derivatives.…”

Theoretical study of the scavenging mechanism to 1,4-dicarbonyls by pyridoxamine: The water-assisted reaction

“…If not specially pointed out, the following analyses were referring to the energies obtained with MP2/6-31+G(d,p) method. To estimate the solvent effect of water, the single-point energies were calculated at the MP2/6-31+G(d,p) level with the Onsager self-consistent reaction field (SCRF) model [27] on the basis of the optimized geometries in the gas phase, and such treatment has been applied in many reaction systems [14,28,29]. What's more, the natural bond orbital (NBO) analysis was also performed to obtain reliable atomic charges [30].…”

“…The water molecular acts as both a proton donor and a proton acceptor and serves as a bridge for proton relay, participating in the reaction processes. The results in references [10,12,13] showed that the water-assisted mechanism was different from solvent effect, and it is essential to include a water molecule in the reaction because the nucleophilic attack at the carbonyl carbons could lead to barrierless reactions, along a pathway that was not available in the presence of a solvent [14][15][16].…”

Mechanism of the Paal–Knorr reaction: the importance of water mediated hemialcohol pathway

“…53,54 Quantum chemical studies on this reaction supported the hemiaminal path on a relative scale. 55 On the thiophene generation path, no studies on the mechanism have been reported, but the generally suggested path (Scheme 3) is quite similar to that of furan synthesis. Clearly, no common theme is being considered for the three reactions.…”