138222-93-2Relevant academic research and scientific papers
β-AMINOMETHYLATION REACTIONS INVOLVING N-AZAHETEROARYL-SUBSTITUTED 2,5-DIMETHYLPYRROLES: UNUSUAL EFFECTS OF α-AZA GROUPS
Biava, Mariangela,Fioravanti, Rossella,Porretta, Giulio Cesare,Mencarelli, Paolo,Sleiter, Giancarlo
, p. 9 - 16 (2007/10/02)
The reactions of a number of N-aryl- and N-α-azaheteroaryl-substituted 2,5-dimethylpyrroles with Mannich reagents formed by formaldehyde and a secondary cyclic amine have been investigated in aqueous acetic acid at various temperatures and different Mannich reagent : pyrrole ratios.Using a 1:1 Mannich reagent : pyrrole molar ratio, all the pyrroles investigated cleanly afforded the corresponding single Mannich bases, with the exception of the N-(2-pyrimidinyl) derivative which, in its reaction with the morpholine Mannich reagent, always gave the double Mannich base, unless the reaction was stopped after a few minutes.On the other hand, even in the presence of a large excess of the Mannich reagents, it proved impossible to bisaminoalkylate the N-aryl-2,5-dimethylpyrrole derivatives, whatever the amine and the reaction conditions adopted, and the N-heteroaryl-2,5-dimethylpyrroles when the amine was the 4-methylpiperazine, double substitution being achieved only with performed Mannich salts.An explanation is offered for these unprecedented substituent and reagent effects in heteroaromatic aminoalkylation reactions.
Study of the Mannich reaction: β-amino-methylation of N-aryl and N-azaheteroaryl-substituted 2,5-dimethylpyrroles, compounds with potential biological activity
Biava,Fioravanti,Porretta,Frachey,Mencarelli,Sleiter,Perazzi,Simonetti,Villa
, p. 431 - 438 (2007/10/02)
Owing to the increasing need of drugs for the treatment of a variety of fungal and bacterial opportunistic infections, a study has been started with the aim of synthesizing structures amenable to a number of easy-to-perform structural modifications in order to meet the requirement of bypassing resistance phenomena. This paper reports on the synthesis of several N-(α-azaheteroaryl)-substituted 2,5-dimethyl-pyrroles bearing in one β-position (or in both β-positions) aminomethyl groups, introduced via a Mannich reaction. Electronic and steric effects by the N-(azaheteroaryl) substituents and the 2- and 5-methyl groups on the course of the Mannich reaction are discussed along with the results of in vitro tests against many Candida species, some bacteria, and several pathogenic plant fungi.
