A two-step protocol for the synthesis of highly substituted pyrroles in aqueous media and without catalyst is described. The first step is the dimerization of a 1,3-dicarbonyl compound by ceric ammonium nitrate/ultrasound to produce a tetracarbonyl derivative. This derivative is then combined with an amine in the absence of any catalysts to obtain the pyrrole via a Paal–Knorr reaction. This route is an improvement when compared with classical methodologies toward Green Chemistry objectives.
Synthesis of highly substituted pyrroles using ultrasound in aqueous media
- DOI:
- 10.1080/17518253.2012.713999
- http://www.tandfonline.com/doi/full/10.1080/17518253.2012.713999 ———copy and paste link
Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos, 149 – 21941-909 Rio de Janeiro, Rio de Janeiro, Brazil
Green Chemistry Letters and Reviews, 2012, 1-5
Pyrroles are heterocycles, which are present in natural molecules such as porphyrins and bilirubins 1–4 and many other compounds that possess antioxidant 5, antitumor 6–8, and anticancer 9 10 properties. The classic methods for the synthesis of pyrroles described in the literature are Knorr 11–14, Hantzsch 15, Paal–Knorr 16–20, and Barton–Zard21 22 reactions. The Paal–Knorr reaction, in which 1,4-dicarbonyl compounds react with primary amines under slightly acidic conditions, is a very attractive approach. Ranu et al. reported a process in aqueous media catalyzed by a water-tolerant Lewis acid that can lead to penta-substituted pyrroles 23.
In the literature, there is an effort to optimize this methodology leading to environmentally friendly processes. Current publications describe the use of solvent-free conditions with Lewis acid catalysts 24, microwave heating 25 26, ionic liquids 27, and ultrasound 28. Most of these processes lead to tri- and tetra-substituted pyrroles.
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