Progress in the Synthesis of Imidazole Compounds

doi:10.6023/cjoc202507027

Abstract

Imidazole compounds are a class of substances with important structural skeletons, which are not only the components of histidine, but also the components of ribonucleic acid and purine of DNA. Imidazole itself has a special “acid-base amphoteric” aromatic heterocycle structure and good electron transfer ability, so it is widely used in the fields of medicine and materials. Based on the research reports in the past five years, the common synthesis strategies are summarized according to the types of catalysts, and the future development trend of this field is prospected.

Key words: imidazole, synthesis, catalyst, mechanism

Cite this article

Mina Zhao, Jiayi Tang. Progress in the Synthesis of Imidazole Compounds[J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 455-474.

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Fig. & Tab. 38

Figure 1. Some important imidazole compounds

Scheme 1. Reaction of o-phenylenediamine with benzyl alcohol

Scheme 2. Three-component reactions of aldehyde, benzoin and ammonium acetate

Scheme 3. [3＋2] cycloaddition of 2H-azirine and oxime

Scheme 4. Reactions of thiopicolinamide and N-(phenoxyl) amine

Scheme 5. Cyclization rearrangement reaction of 2-(indol-3-yl)cyclohexanone and amidine

Scheme 6. Three-component reactions of o-iodoanilines, anilines and ethyl trifluoropyruvate

Scheme 7. Tandem cyclization of 2-propargylamino/oxy-arylaldehydes and o-phenylenediamines

Scheme 8. Three-component tandem reaction of α,β-unsaturated ketoximes, paraformaldehyde and amines

Scheme 9. [3＋2] cycloaddition of azomethine ylides and trifluoroacetimidoyl chlorides

Scheme 10. One-pot tandem reaction of 3-cyanochromone and methyl α-isocyanoacetate

Scheme 11. Three-component reactions of 1-naphthylamine, N-cyclohexylhydroxylamine and paraformaldehyde

Scheme 12. Synthesis of 1,4,5-trisubstituted imidazole from DMF and 2H-azirine

Scheme 13. Reaction of benzil and benzaldehyde dimethyl acetal with ammonium acetate/amine

Scheme 14. Oxidation [4＋1] cyclization of enamine and TMSN3

Scheme 15. Cyclization of 2-amino[1,3,5]triazines and ketones

Scheme 16. Tandem Strecker/C(sp3)—H amination of pyridin-2-formaldehyde, benzylamine and NH4SCN

Scheme 17. Reactions of phthalenediamine, TMTD and enamine

Scheme 18. [3＋2] cycloaddition of methyl-azaarenes with alkyl 2-isocyanoacetates or amino acid ester hydrochlorides

Scheme 19. Intramolecular C(sp3)—H amination of aniline derivatives

Scheme 20. Domino reaction between aurone derivatives and amidines

Scheme 21. Oxidative cyclization of enamine and tBuONO

Scheme 22. [3＋2] cycloaddition of β-perfluoroalkyl α,β-enone and amidine

Scheme 23. Reaction of CF3-hydrobenzimidazole

Scheme 24. Region-selective [3＋2]cyclization of TosMIC with ketoimines

Scheme 25. Multicomponent tandem reactions of anisylsulfanylmethylisocyanide, alkyl halide and cyanide

Scheme 26. Ring condensation of 2-(α-diazoacyl)-2H-azirine, amidine hydrochloride and 1,3,5-trimethylbenzene

Scheme 27. Azidative/cycloamination reaction of THIQ enamine

Scheme 28. Light-facilitated addition of N-nitrosopiperidines to terminal alkynes

Scheme 29. Domino cyclization of oxime esters, aldehydes and amines

Scheme 30. Three-component reactions of α-keto vinyl azides, anilines and aldehydes

Scheme 31. Three-component reaction of isothiocyanate, isocyanate, and thianthrenium salt-functionalized arene

Scheme 32. Electrochemical C(sp3)—H amination of enamines and amines

Scheme 33. Electrochemical oxidation intramolecular cyclization of amines, alkynes and TMSN3

Scheme 34. Multicomponent tandem reaction of isothiocyanate/isoselenocyanate, isocyanate and H-phosphonate

Scheme 35. [3＋2] cycloaddition of α-amino carbonyls and tosylmethyl isocyanide

Scheme 36. Rapid one-pot reaction of glyoxal, aniline and amidine

Scheme 37. Oxidative C—N coupling reaction of benzil, benzylamine and aniline

References 62

[1]	Vyas V. K.; Ghate M. Mini-Rev. Med. Chem. 2010, 10, 1366.
[2]	Bansal Y.; Silakari O. Bioorg. Med. Chem. 2012, 20, 6208.
[3]	Narasimhan B.; Sharma D.; Kumar P. Med. Chem. Res. 2011, 20, 1119.
[4]	Shah K.; Chhabra S.; Shrivastava S. K.; Mishra P. Med. Chem. Res. 2013, 22, 5077.
[5]	Rajamouli B.; Devi R.; Mohanty A.; Krishnan V.; Vaidyanathan S. New J. Chem. 2017, 41, 9826.
[6]	He Y. X.; Huang Y. Y.; Li J. Y.; Pang X.; Yang G. C. Org. Electron. 2017, 50, 220.
[7]	He L.; Wang Z.; Yang C.; Duan L.; Tang R.; Song X. Z.; Pan C. Y. Dyes Pigm. 2016, 131, 76.
[8]	Cao Y. J.; Zhang R. B.; Cheng T.; Guo J.; Xian M.; Liu H. Z. Appl. Microbiol. Biotechnol. 2017, 101, 521.
[9]	Meng X.; Wang H. N.; Song S. Y.; Zhang H. J. Chem. Soc. Rev. 2017, 46, 464.
[10]	Qu Z.; Zhang F.; Deng G. J.; Huang H. W. Org. Lett. 2019, 21, 8239.
[11]	Shi S. J.; Xu K.; Jiang C.; Ding Z. H. J. Org. Chem. 2018, 83, 14791.
[12]	Zhao M.-N.; Yang Z.-M.; Yang D.-S. Chin. J. Org. Chem. 2022, 42, 111 (in Chinese).
	( 赵咪娜, 杨梓墨, 杨得锁, 有机化学, 2022, 42, 111.)
[13]	Xi J. M.; Wei Z. L.; Liao W. W. Org. Lett. 2025, 27, 734.
[14]	Xu C. Z.; Xu Z. Y.; Chen Y. F.; Chen M.; Liu Y. H. Chem.-Eur. J. 2025, 31, e202404368.
[15]	Panneerselvam S.; Selvaraj E.; Mannathan S.; Saravanan T.; Baskar B. J. Org. Chem. 2025, 90, 3359.
[16]	Gribanov P. S.; Philippova A. N.; Smol'yakov A. F.; Tukhvatullina D. N.; Vlasova V. A.; Topchiy M. A.; Asachenko A. F.; Osipov S. N. Molecules 2025, 30, 1401.
[17]	Naresh P.; Hemasri Y.; Limbadri P.; Jayaprakash Rao Y. Russ. J. Gen. Chem. 2025, 95, 538.
[18]	Zhou K.; Sheng X.; Liu H. B.; Ye Z.; Gao J. W.; Xie F. J. Mol. Struct. 2025, 1333, 141747.
[19]	Mahajan S.; Bag D.; Kour H.; Sawant S. D.; Xie F. Chem. Commun. 2025, 61, 3021.
[20]	Enjilzadeh M.; Keivanloo A.; Bakherad M. Tetrahedron 2025, 175, 134521.
[21]	Gao Q.; Dong X. R.; Lin Z.; Xu L. J. Mol. Struct. 2025, 1340, 142503.
[22]	Tian A. Q.; Luo X. H.; Ren Z. L.; Zhao J.; Wang L. New J. Chem. 2021, 45, 9614.
[23]	Kadu V. D.; Mali G. A.; Khadul S. P.; Kothe G. J. RSC Adv. 2021, 11, 21955.
[24]	Sun S. F.; Huang J.; Yuan C.; Wang G. Q.; Guo D. H.; Wang J. Org. Chem. Front. 2022, 9, 3006.
[25]	Begam H. M.; Nandi S.; Jana R. Chem. Sci. 2022, 13, 5726.
[26]	Chen S. P.; Xia Y.; Feng W.; You K. Y.; Mao G. J.; Deng G. J. Org. Chem. Front. 2022, 9, 5885.
[27]	You C. H.; Huang Y. J.; You Y.; Weng Z. Q. Org. Chem. Front. 2022, 9, 3247.
[28]	Rajput D.; Kumar A.; Jandial T.; Karuppasamy M.; Bhuvanesh N.; Kumar R. S.; Almansour I. A.; Sridharan V. J. Org. Chem. 2022, 87, 8956.
[29]	Xu G. C.; Jia C. L.; Wang X. M.; Yan H.; Zhang S.; Wu Q. H.; Zhu N.; Duan J. D.; Guo K. Org. Lett. 2022, 24, 1060.
[30]	Yang H. F.; Lu S. N.; Chen Z. K.; Wu X. F. J. Org. Chem. 2021, 86, 4361.
[31]	Lv Y.; Chen L.; Li K.; Yun X. H.; Yan S. J. J. Org. Chem. 2022, 87, 15187.
[32]	Begam H. M.; Pradhan K. K.; Varalaxmiac K.; Varalaxmiac K.; Jana R. Chem. Commun. 2023, 59, 5595.
[33]	Zhao M. N.; Yang Z. M.; Li L. Q. Chem. Commun. 2024, 60, 1904.
[34]	Das B.; Bhattacharyya A.; Paul B.; Natarajan R.; Majumdar S. RSC Adv. 2024, 14, 33512.
[35]	Wang Z. Y.; Gan L.; Song Z. B.; Liu Y. Y.; Wang J.-P. Chin. J. Chem. 2024, 42, 3041.
[36]	Guo H. J.; Liu Y. Y.; Wang J.-P. Green Synth. Catal. 2025, 6, 206.
[37]	Wang C. X.; Liu Y. Y.; Wang J.-P. Org. Lett. 2025, 27, 3983.
[38]	Liu M. Q.; Chen Y. T.; Zhang J. Y.; Zhou H. Y.; Qin T.; Liu B. Chin. J. Org. Chem. 2025, 45, 1283 (in Chinese).
	( 刘梦琴, 陈贻庭, 张榉元, 周和烨, 秦涛, 刘彬, 有机化学, 2025, 45, 1283.)
[39]	Gao P.; Chen H.; Bai Z. J.; Zhang S.; Zhao M. N.; Yang D. S.; Li Y. C.; Zhang J. W.; Wang X. M. J. Org. Chem. 2021, 86, 10492.
[40]	Zhao W. Q.; Zhang C.; Zhong P. Z.; Zhou W.; Zhang C.; Cui D. M. Chem. Commun. 2021, 57, 10715.
[41]	Yang Q.; Yan X. T.; Feng C. T.; Chen D. X.; Yan Z. Z.; Xu K. Org. Chem. Front. 2021, 8, 6384.
[42]	Wu Y. X.; Huang M. H.; Peng K.; Shi Z.; Hao E. J.; Dong Z. B. J. Org. Chem. 2022, 87, 2446.
[43]	Hu Y. J.; Zhou Y.; Gao J. J.; Zhang H.; Yang K. R.; Li J. J.; Yan X. X.; Lia Y. L.; Zhu Y. P. Org. Chem. Front. 2022, 9, 1403.
[44]	Yi X.; Zhao Z.; Wang M.; Yu W. Q.; Chang J. B. Org. Lett. 2022, 24, 8703.
[45]	Xu H.; Chen H.; Hu X.; Xuan G.; Li P. H.; Zhang Z. J. Org. Chem. 2022, 87, 16204.
[46]	Li Y.; Qiu J.; Gao P.; Zhai L.; Bai Z. J.; Chen H. J. J. Org. Chem. 2022, 87, 15380.
[47]	Wang H. M.; Niu W. J.; He Y. J.; Wei Y. B.; Li X. X.; Lin Y. W. J. Org. Chem. 2023, 88, 15282.
[48]	Qiao X.; Zhao Y. D.; Rao M.; Bu Z. W.; Zhang G. W.; Xiong H. Y. J. Org. Chem. 2021, 86, 13548.
[49]	Zhao C.; Gu M. Z.; Chen Y. Y.; Hu X. W.; Xu Y. B.; Lin X. M.; Liu X. N.; Chen L.; Chen G. S.; Liu Y. L. Org. Biomol. Chem. 2022, 20, 8623.
[50]	Mueller L. G.; Keller T. M.; Fleming F. F. J. Org. Chem. 2023, 88, 909.
[51]	Zanakhov T. O.; Galenko E. E.; Novikov M. S.; Khlebnikov A. F. J. Org. Chem. 2024, 89, 8641.
[52]	Patel S. M.; Prasad P. E.; Bakthadoss M.; Sharada D. S. Org. Lett. 2021, 23, 257.
[53]	Patil D. V.; Lee Y.; Kim H. Y.; Oh K. Org. Lett. 2022, 24, 5840.
[54]	Cao S.; Ma C.; Teng X.; Chen R. S.; Li Y.; Yuan W. D.; Zhu Y. G. Org. Chem. Front. 2022, 9, 6817.
[55]	Borkotoky L.; Bora K.; Maurya R. A. Asian J. Org. Chem. 2023, 12, e202300146.
[56]	Zuo J. Z.; Li X. F.; Shi Y. J.; Lv J.; Yang D. S. Org. Lett. 2024, 26, 3541.
[57]	Wang W.; Zhang S.; Shi G.; Chen Z. W. Org. Biomol. Chem. 2021, 19, 6682.
[58]	Zhou K.; Xia S. D.; Liu Y. M.; Chen Z. W. Org. Biomol. Chem. 2022, 20, 7840.
[59]	Yin Y. H.; Yang J. J.; Yan K. L.; Zeng T.; Lin H. Y.; Ling J.; Wang S. B.; Wen J. W. Green Chem. 2024, 26, 832.
[60]	Mallick S.; Baidya M.; Sarkar S. D. Adv. Synth. Catal. 2024, 366, 241.
[61]	Jalani H. B.; Sivaraman A.; Min K.; Lee H. Y.; Oh N. K.; Kang H.; Keum G.; Choi Y.; Lee K. Green Chem. 2022, 24, 6501.
[62]	Bera D.; Sarkar R.; Dhar T.; Saha P.; Ghosh P.; Mukhopadhyay C. Org. Biomol. Chem. 2024, 22, 3684.

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