Convenient One-Pot Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles

Abstract

A new one-pot strategy for the synthesis of a series of new N-substituted 3-trifluoroacetyl pyrroles is presented. These compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with primary amines, which generated 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In most cases these intermediates were not stable enough to be isolated. Thus, in the same reaction vessel they were directly submitted to oxidation with PCC (Corey's reagent) to furnish 1,1,1-trifluoro-3-(2-ethanal)-4-alkylaminobut-3-en-2-ones, which under reflux underwent intramolecular cyclization to give the desired N-substituted 3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles were tested against pan-susceptible Mycobacterium tuberculosis H37Rv and clinical isolates INH-and RMP-resistant strain and some of these compounds showed significant in vitro antimicrobial activity.

Preparation of α,β-unsaturated trifluoromethylketones and their application in the synthesis of heterocycles

“…87 The reaction of 215 with primary amines followed by oxidation with PCC leads to 1,1,1-trifluoro-3-(2-ethanal)-4-alkylaminobut-3-en-2-ones cyclizing to pyrroles 214. …”

The Wonderful World of β‐Enamino Diketones Chemistry

“…Compound 71 was treated with drops of trifluoroacetic acid (TFA) and water (at r. t. for 4 h) to furnish the intermediate 72 , which, upon losing a trifluoroacetyl group, furnished 73 at 83 % yield, in a one‐pot procedure. Pyrrole 73 was also synthesized by using aliphatic [ 81 ] or cyclic [ 82 ] trifluoroacetylated enol ethers. Compound 74 , on the other hand, experienced spontaneous cyclization, furnishing the poly‐substituted pyrrole 75 at 96 % yield.…”

Streamlined Synthesis of 6-((1H-1,2,3-Triazol-4-yl)methyl)-1H-pyrrolo [3,4-d]pyridazin-1-one System via Sequential N-Alkylation, CuAAC, and [4 + 2] Cyclization Reactions

“…Despite all the studies, documents and patents mentioning the numerous biological properties of pyrrolo [3,4-d]pyridazinone derivatives and 1,2,3-triazoles, no methodology has been developed in recent decades for the combination of these heterocycles as diheteroaryl methylene-spacer systems. Thus, due to our background in the synthesis of pyrroles [28][29][30][31][32] and 33 we envisioned the possibility of using an efficient methodology for the synthesis of a new series of a more complex heterocyclic system, which could have a wide range of biological activities for further applications.…”