咪唑类化合物的合成研究进展

doi:10.6023/cjoc202507027

摘要/Abstract

咪唑类化合物是一类具有重要结构骨架的物质, 不仅是生物体内组氨酸的组分, 也是核糖核酸和脱氧核糖核酸嘌呤的组分. 同时, 咪唑本身具有特殊的“酸碱两性”芳杂环结构和良好的电子转移性, 因此被广泛应用在医药领域以及材料领域. 结合近五年来国内外的研究报道, 按照催化剂的类型对常见的合成策略进行了归纳总结, 并对该领域未来发展趋势进行了展望.

关键词: 咪唑, 合成, 催化剂, 机理

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

引用此文

赵咪娜, 唐嘉一. 咪唑类化合物的合成研究进展[J]. 有机化学, 2026, 46(2): 455-474.

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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图/表 38

图1. 一些重要的咪唑类化合物

Figure 1. Some important imidazole compounds

图式1. 邻苯二胺与苄醇的反应

Scheme 1. Reaction of o-phenylenediamine with benzyl alcohol

图式2. 醛、安息香和乙酸铵的三组分反应

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

图式3. 2H-氮杂环丙烯和肟酯的[3＋2]环加成反应

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

图式4. 硫代吡啶甲酰胺和N-(苯酰氧基)胺反应

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

图式5. 2-(吲哚-3-基)环己酮和脒的环化重排反应

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

图式6. 邻碘苯胺、苯胺和三氟丙酮酸乙酯的三组分反应

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

图式7. 2-丙炔氨基/氧基芳基醛和邻苯二胺的串联环化反应

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

图式8. α,β-不饱和酮肟、多聚甲醛和胺的三组分串联反应

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

图式9. 亚甲胺叶立德和三氟乙酰胺酰氯的[3＋2]环加成反应

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

图式10. 3-氰基色酮和α-异氰酸酯的一锅串联反应

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

图式11. 1-萘胺、N-环己基羟胺和多聚甲醛的三组分反应

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

图式12. DMF和2H-氮杂环丙烯合成1,4,5-三取代咪唑

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

图式13. 苯偶酰和苯甲醛二甲缩醛与乙酸铵/胺的反应

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

图式14. 烯胺与TMSN3的氧化[4＋1]环化反应

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

图式15. 2-氨基[1,3,5]三嗪和酮类化合物的环化反应

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

图式16. 吡啶-2-甲醛、苄胺和NH4SCN的串联Strecker/C(sp3)—H胺化反应

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

图式17. 邻苯二胺、TMTD和烯胺的反应

Scheme 17. Reactions of phthalenediamine, TMTD and enamine

图式18. 甲基-氮杂芳烃与2-异氰酸酯或氨基酸酯盐酸盐的[3＋2]环加成反应

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

图式19. 苯胺衍生物的分子内C(sp3)—H胺化反应

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

图式20. 苯并呋喃酮类化合物与脒类化合物的多米诺反应

Scheme 20. Domino reaction between aurone derivatives and amidines

图式21. 烯胺和tBuONO的氧化环化反应

Scheme 21. Oxidative cyclization of enamine and tBuONO

图式22. β-全氟烃基α,β-烯酮与脒的[3＋2]环加成反应

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

图式23. CF3-氢苯并咪唑的反应

Scheme 23. Reaction of CF3-hydrobenzimidazole

图式24. TosMIC与酮亚胺的区域选择性[3＋2]环化反应

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

图式25. 茴香基甲基硫烷基异氰化物、烷基卤化物和氰化物的多组分串联反应

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

图式26. 2-(α-二氮酰基)-2H-氮丙啶、盐酸脒和1,3,5-三甲苯的环缩合反应

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

图式27. THIQ烯胺的叠氮化/环胺化反应

Scheme 27. Azidative/cycloamination reaction of THIQ enamine

图式28. 光促进的N-亚硝基吡啶与末端炔烃的加成反应

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

图式29. 肟酯、醛和胺的多米诺环化反应

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

图式30. α-酮基叠氮化物、苯胺和醛的三组分反应

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

图式31. 异硫氰酸酯、异氰化物和芳基噻蒽盐的三组分反应

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

图式32. 烯胺和胺的电化学C(sp3)—H胺化反应

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

图式33. 胺、炔和TMSN3的电化学氧化分子内环化反应

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

图式34. 异硫氰酸酯/异硒氰酸酯, 异氰酸酯和H-膦酸酯的多组分串联反应

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

图式35. α-氨基羰基化合物和对甲苯磺酰甲基异氰的[3＋2]环加成反应

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

图式36. 乙二醛、苯胺和脒的快速一锅反应

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

图式37. 苯偶酰、苄胺和苯胺的氧化C—N偶联反应

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

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