• Home
  • Search Results
  • Development of four-component synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles: free permutation and combination of aromatic and aliphatic amines.

Development of four-component synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles: free permutation and combination of aromatic and aliphatic amines.

ACS combinatorial science (2013-02-22)
Longyun Lv, Sichao Zheng, Xiaotie Cai, Zhipeng Chen, Qiuhua Zhu, Shuwen Liu
ABSTRACT

We previously reported the novel efficient proton/heat-promoted four-component reactions (4CRs) of but-2-ynedioates, two same/different primary amines, and aldehydes for the synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles. If aromatic and aliphatic amines were used as reagents, four different series of products should be obtained via the permutation and combination of aromatic and aliphatic primary amines. However, only three/two rather four different series of tetra-/pentasubstisuted dihydropyrroles could be prepared via the proton/heat-promoted 4CRs. Herein, Cu(OAc)2·H2O, a Lewis acid being stable in air and water, was found to be an efficient catalyst for the 4CR synthesis of all the four different series of tetra-/pentasubstisuted dihydropyrroles. The copper-catalyzed 4CR could produce target products at room temperature in good to excellent yields. Interestingly, benzaldehyde, in addition to being used as a useful reactant for the synthesis of pentasubstituted dihydropyrroles, was found to be an excellent additive for preventing the oxidation of aromatic amines with copper(II) and ensuring the sooth conduct of the 4CRs for the synthesis of tetrasubstituted dihydropyrroles with aryl R(3). In addition, salicylic acid was found to be needed to increase the activities and yields of the copper-catalyzed 4CRs for the synthesis of petasubstituted diyhydropyrroles. On the basis of experimental results, the enamination/amidation/intramolecular cyclization mechanism was proposed and amidation is expected to be the rate-limited step in the copper-catalyzed 4CRs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzaldehyde, ReagentPlus®, ≥99%
Sigma-Aldrich
Benzaldehyde, purified by redistillation, ≥99.5%
Supelco
Benzaldehyde, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Benzaldehyde, analytical standard
Sigma-Aldrich
Benzaldehyde, puriss. p.a., ≥99.0% (GC)
Sigma-Aldrich
Benzaldehyde, natural, FCC, FG
Sigma-Aldrich
Benzaldehyde, ≥98%, FG, FCC
Benzaldehyde, European Pharmacopoeia (EP) Reference Standard

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.