Ultrasound-assisted transition-metal-free catalysis: a sustainable route towards the synthesis of bioactive heterocycles

Abstract

Heterocycles of synthetic and natural origin are a well-established class of compounds representing a broad range of organic molecules that constitute over 60% of drugs and agrochemicals in the market or research pipeline. Considering the vast abundance of these structural motifs, the development of chemical processes providing easy access to novel complex target molecules by introducing environmentally benign conditions with the main focus on improving the cost-effectiveness of the chemical transformation is highly demanding and challenging. Accordingly, sonochemistry appears to be an excellent alternative and a highly feasible environmentally benign energy input that has recently received considerable and steadily increasing interest in organic synthesis. However, the involvement of transition-metal-catalyst(s) in a chemical process often triggers an unintended impact on the greenness or sustainability of the transformation. Consequently, enormous efforts have been devoted to developing metal-free routes for assembling various heterocycles of medicinal interest, particularly under ultrasound irradiation. The present review article aims to demonstrate a brief overview of the current progress accomplished in the ultrasound-assisted synthesis of pharmaceutically relevant diverse heterocycles using transition-metal-free catalysis.

Fig. 1. Some examples of bioactive natural and synthetic heterocyclic compounds.

Scheme 1. Ultrasound-assisted iodine-catalyzed one-pot three-component routes to access pyrroles 4.

Scheme 2. Acid-catalyzed chemoselective synthesis of pyrroles 9 under ultrasound irradiation.

Scheme 3. Ultrasound-assisted in situ generated hypervalent iodine-catalyzed synthesis of benzofurans.

Scheme 4. Ultrasound-assisted three-component synthesis of thiophenes 15.

Scheme 5. Ultrasound-assisted one-step synthesis of tetrasubstituted thiophenes 18.

Scheme 6. Ultrasound-assisted organocatalytic syntheses of tri-substituted imidazoles as reported by Piltan et al.

Scheme 7. 3-N-Morpholinopropanesulfonic acid (C-1)-catalyzed ultrasound-assisted synthesis of imidazoles.

Scheme 8. Secondary amine-catalyzed synthesis of substituted isoxazole under ultrasound irradiation.

Scheme 9. Itaconic acid-catalyzed three-component synthesis of isoxazoles under ultrasound irradiation.

Scheme 10. Ultrasound-assisted azo-linked benzoxazoles as reported by Nikpassand et al.

Scheme 11. IBX-mediated synthesis of 2-aryl substituted oxazoles under ultrasound irradiation.

Scheme 12. Ultrasound-assisted step-wise synthesis of thiourea-linked pyrazole derivatives.

Scheme 13. One-pot synthesis of tetrazole-linked pyrazole derivatives under ultrasound irradiation.

Scheme 14. Ultrasound-assisted triethylamine-catalyzed assembly of functionalized thiazoles as reported by Farghaly et al.

Scheme 15. SiW·SiO₂-catalyzed ultrasound-irradiated assembly of thiazole derivatives.

Scheme 16. Step-wise synthesis of diverse 1,3,4-oxadiazoles under ultrasound irradiation.

Scheme 17. Ultrasound-assisted oxidative cyclization approach to access amino-substituted oxadiazoles.

Scheme 18. Potassium bicarbonate-catalyzed ultrasound-assisted synthesis of 1,3,4-oxadiazole derivatives.

Scheme 19. Ultrasound-assisted synthesis of amino-substituted thiadiazole scaffolds.

Scheme 20. Ultrasound-assisted conversion of thioamides to thiadiazoles in an aqueous medium.

Scheme 21. Organocatalytic ultrasound-assisted synthesis of substituted 1,2,3-triazole derivatives.

Scheme 22. Water-mediated sonochemical-assisted synthesis of 1,5- and 1,4-substituted 1,2,3-triazoles.

Scheme 23. Ultrasound-irradiated one-pot synthesis of bis-tetrazole derivatives.

Scheme 24. Tetrazoles obtained by the ultrasound-assisted isocyanide-based multicomponent click reaction.

Scheme 25. Iodine-catalyzed ultrasound-assisted multicomponent synthesis of substituted pyridines.

Scheme 26. Sonochemical-assisted assembly of diverse pyridine derivatives.

Scheme 27. Expedient sonochemical synthesis of substituted quinolines.

Scheme 28. Ultrasound-assisted rapid access to quinolines bearing α-aminophosphonate.

Scheme 29. Iodine-catalyzed three-component sonochemical-assisted synthesis of 4H-pyrans.

Scheme 30. One-pot ultrasound-assisted construction of 4H-pyrans using Et₃N as a catalyst.

Scheme 31. Ultrasound-assisted multistep synthesis of diversely substituted pyrimidines 114.

Scheme 32. Base-catalyzed sonochemical synthesis of 2-aminopyrimidine in an aqueous medium.

Scheme 33. One-pot three-component sonochemical synthesis of quinoxalines.

Scheme 34. Organocatalytic ultrasound-assisted two-component synthesis of quinoxalines.

Scheme 35. Acid-catalyzed multicomponent synthesis of quinazolinones under sonication.

Scheme 36. Ultrasound-assisted multicomponent reaction mediated two-step synthesis of quinazolinones.

Scheme 37. Organocatalytic sonochemical synthesis of pyrano[2,3-c]pyrazoles linked with coumarin.

Scheme 38. Three-component organocatalyzed synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones under sonication.

Scheme 39. DMAP-catalyzed ultrasound-assisted synthesis of pyrido[2,3-d]pyrimidines 140.

Scheme 40. NaF-catalyzed MCRs to access pyrano[2,3-c]pyrazoles under sonication.

Scheme 41. NaHCO₃-catalyzed sonochemical synthesis of triazole-based pyrano[2,3-c]pyrazoles.

Scheme 42. Sulfamic acid-catalyzed multicomponent synthesis of chromeno[4,3-d]pyrido[1,2-a]pyrimidin-6(7H)-ones under sonication.

Scheme 43. Ultrasound-assisted synthesis of diverse fused quinoxalines.

Scheme 44. MgO-catalyzed ultrasound-assisted synthesis of furo[3,2-c]coumarin.

Scheme 45. Sonochemical access to chromeno[3,4-e]isoxazolo[5,4-b]pyridin-6-one using ionic liquid catalysis.

Scheme 46. Piperidine-catalyzed ultrasound-assisted multicomponent assembly of pyrano[3,2-c]coumarin.

Scheme 47. Supramolecular catalysis in the sonochemical synthesis of pyrazolo-pyrano[2,3-d]pyrimidine.

Scheme 48. l-Proline-NO₃-catalyzed three-component synthesis of pyrano[2,3-d]pyrimidine under sonication.

Scheme 49. Construction of a library of spiro-heterocycles under ultrasound irradiation.

Scheme 50. Secondary amine-catalyzed one-pot sonochemical synthesis of amino-substituted spiro-pyrano[2,3-c]pyrazoles.

Scheme 51. Ultrasound-assisted acid-catalyzed construction of spiro-oxindole-based quinazolines.

Scheme 52. Reverse 1,3-dipole-mediated [3 + 2]cycloaddition for the synthesis of spiropyrazolines under sonication.

Biplob Borah

L. Raju Chowhan