Microwave assisted synthesis of five membered nitrogen heterocycles

Abstract

Our continuously changing environment demands sensible and sustainable chemistry. Consequently, organic synthesis started to follow green chemistry principles in recent years. It is observed that microwave (MW) radiation has been widely used as a source of energy in organic synthesis in the past decade. The MW heating approach has evolved into a new green method in organic synthesis since it provides short reaction time, high yields, and high product purities along with a decrease in the rate of by-product formation. Solvent-free reaction protocols worked well under MW irradiation. All these features make MW assisted organic synthesis an environment-friendly approach. In organic synthesis, heterocycles are vital targets especially nitrogen-containing ones because of their prominent presence in natural products and widespread applications in pharmaceutical industries. Five membered nitrogen heterocycles include pyrroles, oxazoles, pyrrolidones, etc. among which pyrroles are the most important ones due to their potent biological properties. Even though there are a variety of reaction protocols for the synthesis of pyrroles, a significant development materialized in MW assisted synthesis of pyrroles in the past few years. In this review, we focus on the developments in MW assisted synthesis of pyrroles and other five-membered nitrogen heterocycles.

Scheme 1. Microwave assisted ruthenium catalysed synthesis of pyrroles.

Scheme 2. Three-component reaction between sodium diethyl oxaloacetate, amines and aromatic aldehydes under MW irradiation for the synthesis of pyrrole.

Scheme 3. Microwave assisted protocol for the synthesis of 2-amino-4,5-diphenylpyrrole-3-carbonitriles.

Scheme 4. Microwave assisted synthesis of imidazole substituted pyrroles.

Scheme 5. Microwave assisted one-pot three component (amine, α-bromoacetophenone and ethyl acetoacetate) synthesis of N-substituted 2-methyl-1H-pyrrole-3-carboxylate derivatives.

Scheme 6. Microwave assisted synthesis of trisubstituted pyrroles from substituted β-amino unsaturated ketone and substituted phenacyl bromide.

Scheme 7. Microwave assisted protocol for the synthesis of 6-(pyrrolyl) coumarin/quinolone derivatives through an indium(iii) catalysed one pot three component reaction.

Scheme 8. Proposed mechanism for the formation of 6-(pyrrolyl) coumarin/quinolones. This figure has been adapted from ref. 18 with permission from John Wiley and Sons, copyright 2020.

Scheme 9. Microwave assisted synthesis of pyrroles from chalcones with different aldehydes and ammonium acetate in the presence of sodium cyanide.

Scheme 10. Microwave assisted one pot stereoselective synthesis of dihydro-2′H-spiro[indene-2,1′-pyrrolo[3,4-c]pyrrole]-tetraone derivatives.

Scheme 11. Proposed mechanism for the formation of dihydro-2′H-spiro[indene-2,1′-pyrrolo[3,4-c]pyrrole]-tetraone derivatives. This figure has been reproduced from ref. 20 with permission from Elsevier, copyright 2020

Scheme 12. Microwave assisted synthesis of benzothiophene-fused pyrrole derivatives.

Scheme 13. Microwave assisted regioselective synthesis of polyfunctionalized 3-ferrocenyl-1H pyrroles from pentane-2,4-dione or non-symmetrical 1,3-dicarbonyl compounds and ferrocenyl vinyl azide.

Scheme 14. Microwave assisted synthesis of derivatives of pyrrolo[1,2-c]quinazolines.

Scheme 15. Microwave mediated synthesis of regioselective diisospiropyrrolidine analogs.

Scheme 16. Microwave assisted reaction protocol for the synthesis of derivatives of spiroindenoquinoxaline pyrrolidine fused nitrochromenes.

Scheme 17. Microwave assisted synthesis of spiro indanone pyrrolidine/piperidine fused nitrochromene derivatives.

Scheme 18. Proposed plausible mechanism. This figure has been adapted/reproduced from ref. 26 with permission from John Wiley and Sons, copyright 2020.

Scheme 19. Microwave assisted solvent-free methodology for the synthesis of different antibacterial fluoroquinolone compounds from 7-halo-6-fluoroquinolone-3-carboxylic acids with a variety of amines.

Scheme 20. Four component reaction for the synthesis of spiroindeno[1,2-b]quinoxaline-11,3′-pyrrolizines.

Scheme 21. Microwave assisted synthesis of a number of malononitrile derivatives of substituted N-phenylpyrrolidine-2,5-diones.

Scheme 22. Microwave assisted protocol for the synthesis of a series of 2,5-disubstituted pyrrolidines.

Scheme 23. Microwave assisted three-component Heck isomerization–Fischer indolization (HIFI) and the four-component Heck isomerization–Fischer indolization–alkylation (HIFIA) for the synthesis of 3-arylmethylindoles and 1-alkyl-3-benzylindoles.

Scheme 24. Microwave assisted three component synthesis of functionalized spirooxindoles.

Scheme 25. Microwave assisted synthesis of azomethine and amidine derivatives of isoindole and pyrrolopyrazine from different dicarboxylic acids.

Scheme 26. Synthesis of hexahydro-2H-pyrrolo[2,3-c:5,4-c′]dipyrazoles from chalcone through a microwave mediated protocol.

Scheme 27. Microwave assisted synthesis of bis-isoxazoles by the reaction of N-5-methyl pyridine succinimide and substituted benzaldehyde.

Scheme 28. Microwave assisted synthesis of 7H-pyrrolo[2,3-c:5,4-c′] diisoxazole derivatives.

Gopinadh Meera

K. R. Rohit

Salim Saranya

Gopinathan Anilkumar