Recent developments using malononitrile in ultrasound-assisted multicomponent synthesis of heterocycles

Abstract

Ultrasonic irradiation serves as a vigorous and environmentally sustainable approach for augmenting multicomponent reactions (MCRs), offering benefits such as thermal enhancement, agitation, and activation, among others. Malononitrile emerges as a versatile reagent in this context, participating in a myriad of MCRs to produce structurally diverse heterocyclic frameworks. This review encapsulates the critical role of malononitrile in the sonochemical multicomponent synthesis of these heterocyclic structures. The paper further delves into the biochemical and pharmacological implications of these heterocycles, elucidating their reaction mechanisms as well as delineating the method's scope and limitations. We furnish an overview of the merits and challenges inherent to this synthetic approach and offer insights for potential avenues in future research.

Keywords: Heterocycles; Malononitrile; Multicomponent reactions; Sonochemistry; Synthesis; Ultrasound.

Graphical abstract

Fig. 1

Sonic frequencies.

Fig. 2

General application of ultrasound.

Fig. 3

Historical background of ultrasound.

Fig. 4

Classification of sonosynthesis.

Fig. 5

Some applications of sonosynthesis.

Fig. 6

Schematic of acoustic cavitation.

Scheme 1

Synthesis of highly functionalized seleno-1,4-dihydropyridines.

Scheme 2

Synthesis of polyfunctionalized hexahydroquinolines.

Scheme 3

Synthesis of polysubstituted 1,4-dihydropyridines.

Scheme 4

Synthesis of 2-amino-5-oxo-4-aryl-5H-chromeno[4,3-b]pyridin-3-yl cyanides.

Scheme 5

The proposed mechanism for the formation of 2-amino-5-oxo-4-aryl-5H-chromeno[4,3-b]pyridin-3-yl cyanides.

Scheme 6

Synthesis of polyfunctionalized pyridine-annulated heterocyclic compounds.

Scheme 7

Synthesis of 2-amino-3-cyanopyridine derivatives.

Scheme 8

Synthesis of 2-amino-4-(hetero)aryl-3,5-dicarbonitrile-6-sulfanylpyridines.

Scheme 9

Synthesis of thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives.

Scheme 10

Synthesis of benzopyranopyrimidines.

Scheme 11

Synthesis of 5-pyrimidinecarbonitriles.

Scheme 12

Synthesis of imidazopyrimidines.

Scheme 13

Plausible mechanism for s-Fe₃O₄ catalyzed synthesis of imidazopyrimidine.

Scheme 14

Synthesis of imidazo[1,2-a]pyridine-6-carbonitrile derivatives.

Scheme 15

Synthesis of benzo, thiazolo[3,2-a]pyrimidine derivatives.

Scheme 16

Synthesis of 5-thioxopyridopyrimidine derivatives.

Scheme 17

Synthesis of pyrano-chromene and benzopyrano-chromene derivatives.

Scheme 18

Synthesis of a series of dihydropyrano[3,2-d], dioxin heterocycles.

Scheme 19

Synthesis of pyrano[3,2-b]pyrans.

Scheme 20

Synthesis of tetrahydrobenzo[b]pyran derivatives.

Scheme 21

Synthesis of pyrano[2,3‐d]pyrimidine derivatives.

Scheme 22

Synthesis of benzo[a]pyrano-[2,3-c]phenazine compounds.

Scheme 23

Ultrasound-assisted synthesis of diverse 2-amino-4H-chromenes.

Scheme 24

Synthesis of a wide variety of pyran derivatives.

Scheme 25

Synthesis of tetrahydrobenzo[b]pyrans and 2-amino-7-hydroxy-4H-chromenes.

Scheme 26

Synthesis of pyrano[2,3-d] pyrimidine diones derivatives.

Scheme 27

Synthesis of 5-amino-8-oxo-7-phenyl-5,6,7,8 dihydropyrano[2′,3′,4,5]pyrido[3,2,1-jk]carbazol-6-carbonitriles.

Scheme 28

Synthesis of tetrahydro-4H-benzo[b]pyrans and dihydropyrano[3,2-c]chromenes.

Scheme 29

Synthesis of pyrano[3,2-b]pyran derivatives.

Scheme 30

Synthesis of pyrano[2,3-d]pyrimidine derivatives, pyrano[3,2-b]pyran derivatives, and chromeno[2,3-d]pyrimidine derivatives.

Scheme 31

Synthesis of pyrano[3,2-c]chromenes and tetrahydropyrano[3,2-b]pyrans.

Scheme 32

Synthesis of polyfunctionalized pyran derivatives.

Scheme 33

Synthesize 4H-pyrans.

Scheme 34

Synthesis of pyrano[3,2-b]pyran and 7-tosyl-4,7-dihydropyrano[2,3-e]indole derivatives.

Scheme 35

Synthesis of 4H-chromene-3-carbonitrile derivatives.

Scheme 36

Synthesis of dihydropyrano[3,2-b]pyrans.

Scheme 37

Synthesis of 2-amino-4H-pyranoquinoline frameworks.

Scheme 38

Synthesis of 2-Amino-3-cyano-4H-chromene frameworks.

Scheme 39

Synthesis of amino substituted-2,4-dihydro-pyrano[3,2-b]pyran-3-carbonitrile derivatives.

Scheme 40

Synthesis of 1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile derivatives, 5-thioxo-pyranopyrimidine, and 5-thioxopyridopyrimidine systems.

Scheme 41

Synthesis of tetrahydrobenzo[b]pyran derivatives.

Scheme 42

Synthesis of pyrano[2,3-d]pyrimidine-2,4(3H)-dione derivatives.

Scheme 43

Synthesis of pyrano-pyrazolone derivatives.

Scheme 44

Plausible strategy for synthesizing pyranopyrazolones.

Scheme 45

Synthesis of pyranopyrazoles.

Scheme 46

Synthesis of pyrano[2,3-c]pyrazoles-3-carboxylate derivatives.

Scheme 47

Synthesis of dihydropyrano[2,3-c]pyrazole derivatives.

Scheme 48

Synthesis of substituted pyrano[2,3-c]pyrazole-5-carbonitrile scaffolds.

Scheme 49

Synthesis of series of dihydropyrano [2,3-c]pyrazoles.

Scheme 50

Synthesized pyranopyrazole derivatives.

Scheme 51

Synthesized tetrahydro-6H-isothiochromene-6,6,8-tricarbonitrile derivatives.

Scheme 52

Synthesis of derivatives of thiopyrano[4,3-b]pyran structures.

Scheme 53

Plausible mechanism for synthesis of thiopyrano[4,3-b]pyran structures.

Scheme 54

Synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives.

Scheme 55

Synthesis of Spiro[2-amino-4H-pyran-oxindole]s.

Scheme 56

Synthesis of spirooxindole derivatives.

Scheme 57

Synthesis of spiro[substituted-1,4′-pyrano[2,3-c]pyrazoles.

Scheme 58

Synthesis of spirooxindole derivatives.

Scheme 59

The plausible mechanism of synthesis of Spiro oxindole.

Scheme 60

Synthesis of Spiro oxindoles.

Scheme 61

Synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole derivatives.

Scheme 62

Synthesis of spiropyrano[2,3-c]pyrazole carboxylate derivatives and Spiro[indoline-3,4′-pyridine] derivatives.

Scheme 63

Synthesis of spiro-[indeno[1,2-b]quinoxaline-11,4′-pyrano[3,2-b]pyran].

Scheme 64

Synthesis of spirooxindole derivatives.

Scheme 65

Synthesis of highly substituted pyrazole derivatives.

Scheme 66

Plausible mechanism for synthesizing pyrazole derivatives.

Scheme 67

Synthesis of bis(indole) derivatives.

Scheme 68

Synthesis of 3-substituted indole derivatives.