СОВРЕМЕННЫЕ ТЕНДЕНЦИИ В ХИМИИ N-ФОРМАМИДОВ
Аннотация
Производные N-формамидов представляют собой уникальный и широко исследуемый класс соединений благодаря их широкому спектру биомедицинской значимости, включая противоопухолевую и антимикробную активность, ингибирование обратного захвата серотонина, а также применение в терапии астмы и хронической обструктивной болезни легких. Кроме того, данные структурные фрагменты часто встречаются в природных соединениях и были выделены из разнообразных биологических источников. В связи с их важными практическими применениями N-формилирование аминов остается активно развивающимся направлением в области органического синтеза. Современные методологии в основном основаны на использовании четырех источников углерода: диоксида углерода, метанола, муравьиной кислоты и N,N-диметилформамида (DMF). В подходах, основанных на CO2, необходимая стадия восстановления обычно осуществляется с использованием гидросиланов или молекулярного водорода. Методики, использующие метанол, как правило, включают неорганические полианионные комплексы хрома(III) с лигандной поддержкой, такие как (NH4)3[CrMo6O18(OH)6], либо соли меди(II), в частности Cu(NO3)2. Муравьиная кислота также зарекомендовала себя как эффективный формилирующий агент в сочетании с гетерогенными или наноструктурированными катализаторами, включая цеолит CuO/HZSM-5, сульфатированный полиборат, наноклиноптилолит (Nano-CP) и Pd@MCP. В качестве альтернативы DMF может выступать одновременно в роли растворителя и источника углерода при исключительно мягких условиях активации с использованием таких реагентов, как HOAc, POCl3 или Tf2O. В совокупности данные стратегии представляют значительный интерес благодаря простоте проведения реакций, относительно мягким условиям, короткому времени реакции и способности обеспечивать получение N-формамидов с высокими выходами.
Для цитирования:
Нго Лан Ань, Нгуен Ван Дат Современные тенденции в химии N-формамидов. Изв. вузов. Химия и хим. технология. 2026. Т. 69. Вып. 6. С. 6-19. DOI: 10.6060/ivkkt.20266906.6998.
Литература
Sheehan J.C., Yang D.-D.H. The Use of N-Formylamino Acids in Peptide Synthesis. Am. Chem. Soc. 1958. V. 80. N 5. P. 1154–1158. DOI: 10.1021/ja01538a036.
Greene T.W., Wuts P.G.M. Protective groups in organic synthesis. New York: Willey-Interscience. 1999. DOI: 10.1002/0471220574.
Kotha S., Behera M., Khedkar P. Environmentally benign process for the synthesis of N-formyl amino acid es-ters. Tetrahed. Lett. 2004. V. 45. N 41. P. 7589–7590. DOI: 10.1016/j.tetlet.2004.08.129.
Sonke T., Kaptein B., Wagner A.F.V., Quaedflieg P.J.L.M., Schultz S., Ernste S., Schepers A., Mommers J.H.M., Broxterman Q.B. Peptide deformylase as biocat-alyst for the synthesis of enantiomerically pure amino acid derivatives. J. Molec. Catal. B: Enzymatic. 2004. V. 29. N 1 – 6. P. 265–277. DOI: 10.1016/j.molcatb.2004.02.008.
Jackson A., Cohn O.M. A new short and efficient strategy for the synthesis of quinolone antibiotics. J. Chem. Soc. Chem. Commun. 1995. V. 13. P. 1319–1319. DOI: 10.1039/C39950001319.
Jahngen Jr E.G.E., Rossomando E.F. The Synthesis of Hadacidin: Sodium Cyanoborohydride Reduction of α-Oximinoic Acids, Synthetic Communications. Int. J. Rapid Commun. Synth. Org. Chem. 1982. V. 12. N 8. P. 601–606. DOI: 10.1080/00397918208061889.
Zecchini G. P., Nalli M., Mollica A., Lucente G., Paradisi M.P., Spisani S. Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine-containing fMLF analogs. J. Peptide Res. 2002. V. 59. P. 283–291. DOI: 10.1034/j.1399-3011.2002.02999.x.
Yang S., Shi W., Xing D., Zhao Z., Lv F., Yang L., Yang Y., Hu W. Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria. Eur. J. Med. Chem. 2014. V. 86. P. 133–152. DOI: 10.1016/j.ejmech.2014.07.106.
Steiropoulos P., Tzouvelekis A., Bouros D. Formoterol in the management of chronic obstructive pulmonary disease. Int. J. Chronic. Obstr. Pulmon. Dis. 2008. V. 3. N 2. P. 205–216. DOI: 10.2147/copd.s1059.
Torino D., Mollica A., Pinnen D., Feliciani F., Spisani S., Lucente G. Novel chemotactic For-Met-Leu-Phe-OMe (fMLF-OMe) analogues based on Met residue replacement by 4-amino-proline scaffold: Synthesis and bioactivity. Bioorg.Med. Chem. 2009. V. 17. N 1. P. 251–259. DOI: 10.1016/j.bmc.2008.11.010.
Yin X.-J., Huang X.-Y., Ma Y.-B., Geng C.-A., Li T.-Z., Chen X.-L., Yang T.-H., Zhou J., Zhang X.-M., Chen J.-J. Bioactivity-guided synthesis of gramine derivatives as new MT1 and 5-HT1A receptors agonists. J. Asian Nat. Prod. Res. 2017. V. 19. N 6. P. 610–622. DOI: 10.1080/10286020.2017.1323885.
Garson M.J., Simpson J.S., Flowers A.E., Dumdei E.J. Cyanide and thiocyanate-derived functionality in marine organisms - structures, biosynthesis and ecology. Stud. Nat. Prod. Chem. 2000. V. 21. Part B. P. 329–372. DOI: 10.1016/S1572-5995(00)80010-1.
Chang C.W.J. Naturally Occurring Isocyano/Isothiocyanato and Related Compounds, Fortschritte der Chemie organischer Naturstoffe. Progress in the Chemistry of Organic Natural Products. Springer. 2000. V. 80. P. 1–186. DOI: 10.1007/978-3-7091-6331-3_1.
Garson M.J., Simpson J.S. Marine isocyanides and related natural products – structure, biosynthesis and ecology. Nat. Prod. Rep. 2004. V. 21. P. 164–179. DOI: 10.1039/B302359C.
Chang C.W.J., Scheuer P.J. Marine isocyano com-pounds. Marine Natural Products - Diversity and Biosyn-thesis. Springer. 1993. V. 167. P. 33–75. DOI: 10.1007/BFb0034370.
Emsermann J., Kauhl U., Opatz T. Marine Isonitriles and Their Related Compounds. Marine Drugs. 2016. V. 14. N 1. DOI: 10.3390/md14010016.
Motokura K., Takahashi N., Kashiwame D., Yamaguchi S., Miyaji A., Baba T. Copper-diphosphine complex cata-lysts for N-formylation of amines under 1 atm of carbon dioxide with polymethylhydrosiloxane. Catal. Sci. Tech-nol. 2013. V. 9. P. 2392–2396. DOI: 10.1039/C3CY00375B.
Motokura K., Takahashi N., Miyaji A., Sakamoto Y., Yamaguchi S., Baba T. Mechanistic studies on the N-formylation of amines with CO2 and hydrosilane catalyzed by a Cu–diphosphine complex. Tetrahedron. 2014. V. 70. N 39. P. 6951–6956. DOI: 10.1016/j.tet.2014.07.089.
Li W., Wu X.-F. A Practical and General Base-Catalyzed Carbonylation of Amines for the Synthesis of N-Formamides. Chem. – A Eur. J. 2015. V. 21. N 42. P. 14943–14948. DOI: 10.1002/chem.201502107.
Jung, S.H., Ahn J.H., Park S.K., Choi J.K. A practical and convenient procedure for the N-formylation of amines using formic acid. Bull. Korean Chem. Soc. 2002. V. 23. N 1. P. 149–150. DOI: 10.5012/bkcs.2002.23.1.149.
Luca L.D., Giacomelli G., Porcheddu A., Salaris M. A New, Simple Procedure for the Synthesis of Formyl Am-ides. Synlett. 2004. V. 18. N 14. P. 2570–2572. DOI: 10.1055/s-2004-834788.
Sarvari M.H., Sharghi H. ZnO as a New Catalyst for N-Formylation of Amines under Solvent-Free Conditions. J. Org. Chem. 2006. V. 71. N 17. P. 6652–6654. DOI: 10.1021/jo060847z.
Reddy M.B.M., Ashoka S., Chandrappa G.T., Pasha M.A. Nano-MgO: An Efficient Catalyst for the Synthesis of Formamides from Amines and Formic Acid Under MWI. Catal. Lett. 2010. V. 138. P. 82–87. DOI: 10.1007/s10562-010-0372-6.
Brahmachari G., Laskar S. A very simple and highly efficient procedure for N-formylation of primary and sec-ondary amines at room temperature under solventfree conditions. Tetrahed. Lett. 2010. V. 51. N 17. P. 2319–2322. DOI: 10.1016/j.tetlet.2010.02.119.
Krishnakumar B., Swaminathan M. A convenient meth-od for the N-formylation of amines at room temperature using TiO2-P25 or sulfated titania. J. Molec. Catal. A: Chem. 2011. V. 334. N 1–2. P. 98–102. DOI: 10.1016/j.molcata.2010.11.002.
Reddy G.G., Kumar G.D.K., Baskaran S. A convenient method for the N-formylation of secondary amines and anilines using ammonium formate. Tetrahed. Lett. 2000. V. 41. N 47. P. 9149–9151. DOI: 10.1016/S0040-4039(00)01636-1.
Dhake K.P., Tambade P.J., Singhal R.S., Bhanage B.M. An efficient, catalyst- and solvent-free N-formylation of aromatic and aliphatic amines. Green Chem. Lett. Rev. 2011. V. 4. N 2. P. 151–157. DOI: 10.1080/17518253.2010.524168.
Yang D., Yeon H.B. Convenient N-formylation of amines in dimethylformamide with methyl benzoate under micro-wave irradiation. Bull. Korean Chem. Soc. 2010. V. 31. N 5. P. 1424 – 1426. DOI: 10.5012/bkcs.2010.31.5.1424.
Ishida T., Haruta M. N-formylation of amines via the aerobic oxidation of methanol over supported gold nano-particles. ChemSusChem. 2009. V. 2. N 6. P. 538–541. DOI: 10.1002/cssc.200800260.
Preedasuriyachai P., Kitahara H., Chavasiri W., Sa-kurai H. N-formylation of amines catalyzed by nanogold under aerobic oxidation conditions with MeOH or formalin. Chem. Lett. 2010. V. 39. N 11. P. 1174–1176. DOI: 10.1246/cl.2010.1174.
Ortega N., Richter C., Glorius F. N-formylation of amines by methanol activation. Org. Lett. 2013. V. 15. N 7. P. 1776–1779. DOI: 10.1021/ol400639m.
Bobbink F.D., Das S., Dyson P.J. N-formylation and N-methylation of amines using metal-free N-heterocyclic carbene catalysts and CO2 as carbon source. Nat. Proto-cols. 2017. V. 12. P. 417 – 428. DOI: 10.1038/nprot.2016.175.
Li X.-D., Xia S.-M., Chen K.-H., Liu X.-F., Li H.-R., He L.-N. Copper catalysis: ligand-controlled selective N-methylation or N-formylation of amines with CO2 and phenylsilane. Green Chem. 2018. V. 20. P. 4853–4858. DOI: 10.1039/C8GC02280A.
Li W.-D., Zhu D.-Y., Li G., Chen J., Xia J.-B. Iron-catalyzed selective N-methylation and N-formylation of amines with CO2. Adv. Synth. Catal. 2019. V. 361. N 22. P. 5098–5104. DOI: 10.1002/adsc.201900906.
Zhang Q., Lin X.-T., Fukaya N., Fujitani T., Sato K., Choi J.-C. Selective N-formylation/N-methylation of amines and N-formylation of amides and carbamates with carbon dioxide and hydrosilanes: promotion of the basic counter anions of the zinc catalyst. Green Chem. 2020. V. 22. P. 8414–8422. DOI: 10.1039/D0GC02890H.
Leong B.-X., Teo Y.-C., Condamines C., Yang M.-C., Su M.-D., So C.-W. A NHC-silyliumylidene cation for cata-lytic N-formylation of amines using carbon dioxide. ACS Catal. 2020. V. 10. N 24. P. 14824–14833. DOI: 10.1021/acscatal.0c03795.
Newar R., Kalita R., Akhtar N., Antil N., Chauhan M., Manna K. N-formylation of amines utilizing CO2 by a heterogeneous metal–organic framework supported single-site cobalt catalyst. Catal. Sci.Technol. 2022. V. 12. P. 6795–6804. DOI: 10.1039/D2CY01231F.
Zhang L., Han Z., Zhao Z., Wang Z., Ding K. Highly efficient ruthenium-catalyzed N-formylation of amines with H2 and CO2. Angew. Chem. Int. Ed. 2015. V. 54. N 21. P. 6186–6189. DOI: 10.1002/anie.201500939.
Liu H., Mei Q., Xu Q., Song J., Liu H., Han B. Synthesis of formamides containing unsaturated groups by N-formylation of amines using CO2 with H2. Green Chem. 2017. V. 19. P. 196–201. DOI: 10.1039/C6GC02243J.
Jayarathne U., Hazari N., Bernskoetter W.H. Selective iron-catalyzed N-formylation of amines using dihydrogen and carbon dioxide. ACS Catal. 2018. V. 8. N 2. P. 1338–1345. DOI: 10.1021/acscatal.7b03834.
Morozov L.N., Vorobyov A.S., Kunin A.V., Egorov N.A., Timoshin E.S. Effect of the feed gas mixture composition at methanol dehydrogenation to formaldehyde on supported oxide catalysts. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 7. P. 88–95. DOI: 10.6060/ivkkt.20246707.7003.
Kang B., Hong S.H. Hydrogen acceptor- and base-free N-formylation of nitriles and amines using methanol as C1 source. Adv. Synth. Catal. 2015. V. 357. N 4. P. 834–840. DOI: 10.1002/adsc.201400982.
Choi G., Hong S.H. Selective N-formylation and N-methylation of amines using methanol as a sustainable C1 source. ACS Sustain. Chem. Eng. 2018. V. 7. N 1. P. 716–723. DOI: 10.1021/acssuschemeng.8b04286.
Han Y., Wu Z., Wei Z., Zhai Y., Ru S., Zhao Q., Wang J., Han S., Wei Y. N-formylation of amines using methanol as a potential formyl carrier by a reusable chromium catalyst. Commun. Chem. 2019. V. 2. Art. 15. DOI: 10.1038/s42004-019-0109-4.
Zhang Y., Dai X., Wang J., Liang J., Rabeah J., Tian X., Yao X., Wang Y., Pang S. In situ-generated CuI catalytic system for oxidative N-formylation of N-heterocycles and acyclic amines with methanol. ChemSusChem. 2022. V. 16. N 3. Art. e202202104. DOI: 10.1002/cssc.202202104.
Tajbakhsh M., Alinezhad H., Nasrollahzadeh M., Kamali T.A. Preparation, characterization and application of nanosized CuO/HZSM-5 as an efficient and heterogeneous catalyst for the N-formylation of amines at room temperature. J. Colloid Interface Sci. 2016. V. 471. P. 37–47. DOI: 10.1016/j.jcis.2016.02.062.
Khatri C.K., Chaturbbhuj G.U. Sulfated polyborate-catalyzed N-formylation of amines: a rapid, green and ef-ficient protocol. J. Iran. Chem. Soc. 2017. V. 14. P. 2513–2519. DOI: 10.1007/s13738-017-1186-x.
Wu Z., Zhai Y., Zhao W., Wei Z., Yu H., Han S., Wei Y. An efficient way for the N-formylation of amines by inor-ganic-ligand supported iron catalysis. Green Chem. 2020. V. 22. N 3. P. 737–741. DOI: 10.1039/C9GC03564H.
Amirsoleimani M., Khalilzadeh M.A., Zareyee D. Nano-sized clinoptilolite as a green catalyst for the rapid and chemoselective N-formylation of amines. Reac. Kinet. Mech. Cat. 2020. V. 131. P. 859–873. DOI: 10.1007/s11144-020-01886-6.
Amirsoleimani M., Khalilzadeh M.A., Zareyee D. Prepa-ration and catalytic evaluation of a palladium catalyst deposited over modified clinoptilolite (Pd@MCP) for chemoselective N-formylation and N-acylation of amines. J. Molec. Struct. 2021. V. 1225. Art. 129076. DOI: 10.1016/j.molstruc.2020.129076.
Artemkina Yu.M., Odinaev U.N., Dzyuba V.Yu., Shcherbakov V.V. Effect of temperature on the electrical conductivity of concentrated solutions of 1-butyl-4-methylpyridinium tetrafluoroborate in acetonitrile, dime-thylformamide, and dimethyl sulfoxide. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2025. V. 68. N 6. P. 29–40. DOI: 10.6060/ivkkt.20256806.7196.
Sonawane R.B., Rasal N.K., Jagtap S.V. Nickel(II)-catalyzed N-formylation and N-acylation of amines. Org. Lett. 2017. V. 19. N 8. P. 2078–2081. DOI: 10.1021/acs.orglett.7b00660.
Sonawane R.B., Rasal N.K., Bhange D.S., Jagtap S.V. Copper(II)-catalyzed N-formylation and N-acylation of aromatic, aliphatic, and heterocyclic amines and a preventive study in the C–N cross coupling of amines with aryl halides. ChemCatChem. 2018. V. 10. N 17. P. 3907–3913. DOI: 10.1002/cctc.201800609.
Hien N., Dat V.N., Du D.N., Mai N.T.N., Hien T.T.N., Hoan Q.D. Synthesis and Fluorescent Properties of Some Benzothiazole Derivatives Synthesized via Suzuki Cross Coupling Reaction. Indian J. Chem. 2023. V. 62. N 12. P. 1276–1281. DOI: 10.56042/ijc.v62i12.5794.
Du N.D., Dat N.V., Mai N.T.N., Anh N.L., Anh D.Q., Phuong N.T., Lan B.N., Dien P.H., Hoan D.Q. Design and synthesis of some novel amino acid derivatives con-taining benzo[d]thiazole. J. Chem. Appl. 2024. V. 71. N 3B. P. 3–11.
Du D.N., Dat V.N., Hue V.N., Giang H.T.V., Ha X.N., Hai H.T.L., Dien H.P., Trang H.T.N., Tai M.T., Nga T.N., Hue M.T.N., Hoan Q.D. Synthesis, Formation Mechanisms, and Molecular Dynamics Simulation of Novel Benzothiazole and Benzo[1,4]oxazin-3(4H)-one as Potential Acetylcholinesterase Inhibitors. ACS Omega. 2025. V. 10. N 11. P. 10835–10851. DOI: 10.1021/acsomega.4c06760.
Du N.D., Dien P.H., Thao N.T.T., Mai N.T.N., Dat N.V., Hoan D.Q. Synthesis and biological activities of some benzo[d]thiazole derivatives containing an amide bond. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2025. V. 68. N 10. P. 19–25. DOI: 10.6060/ivkkt.20256810.7227.
Mai N.T.N., Dat N.V., Huan T.T., Hoan D.Q. N-Formylation of amines using a domestic microwave oven and bioactivities of some N-formamides. Vietnam J. Chem. 2021. V. 59. N 3. P. 389–394. DOI: 10.1002/vjch.202100006.
Kaboudin B., Esfandiari H., Kakavand M., Sohrabi M., Amirkhiz E.Y., Neshat A., Kawazoe T., Fukaya H., Yanai H. Phosphite–imidazole catalyzed N-formylation and N-acylation of amines. Org. Biomolec. Chem. 2023. V. 21. N 40. P. 8182–8189. DOI: 10.1039/D3OB01306E.
Sakaguchi T., Nishio R., Awata H., Tan J., Nakata R., Sato H., Matsumura Y., Shimomura O., Ohtaka A. N-formylation of secondary amines and their application in the synthesis of benzimidazole derivatives using DMF as a C1 source. J. Org. Chem. 2025. V. 90. N 31. P. 11372–11377. DOI: 10.1021/acs.joc.5c00363.
