氰基官能团因广泛存在于药物、农用化学品、染料和精细化学品中,且可方便地转化为其他重要官能团如醛基、羧基、酰胺、伯胺、亚胺等或构建杂环体系而受到化学家的大量关注。传统的腈类制备方法如烷基、芳基(拟)卤代物与氰化物反应、酰胺或醛肟脱水等存在剧毒氰源的使用、剧烈反应条件和原子经济性差等问题。而温和条件下酰胺的催化脱水是制备腈类的理想途径。本文将重点讨论近年来酰胺催化脱水制备腈的研究进展。
The cyano functional group widely exists in pharmaceuticals, agrochemicals, dyes and fine chemicals. As it can be easily converted into other functional groups such as aldehyde, ester, amide, primary amine, and imine, its preparation has attracted numerous attention from organic chemists. Traditional methods for nitrile synthesis including reactions of alkyl- or aryl (pseudo)halides with cyanides and dehydration of amides or aldoximes often require highly toxic reagents, harsh conditions and suffer from poor atom economy. Catalytic amide dehydration under mild conditions is an ideal approach to nitriles. This article focuses on recent advances in catalytic dehydration of amides to nitriles.
The cyano functional group widely exists in pharmaceuticals, agrochemicals, dyes and fine chemicals. As it can be easily converted into other functional groups such as aldehyde, ester, amide, primary amine, and imine, its preparation has attracted numerous attention from organic chemists. Traditional methods for nitrile synthesis including reactions of alkyl- or aryl (pseudo)halides with cyanides and dehydration of amides or aldoximes often require highly toxic reagents, harsh conditions and suffer from poor atom economy. Catalytic amide dehydration under mild conditions is an ideal approach to nitriles. This article focuses on recent advances in catalytic dehydration of amides to nitriles.
王明慧. 酰胺催化脱水制备腈的研究进展Research Progress of Catalytic Dehydration of Amides to Nitriles[J]. 有机化学研究, 2021, 09(04): 59-67. https://doi.org/10.12677/JOCR.2021.94008
参考文献ReferencesPollak, P., Romeder, G., Hagedorn, F. and Gelbke, H.-P. (2000) Nitriles. In Bohnet, M., Brinker, C.G. and Cornils, B., Eds., Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 251-265.
<br>https://doi.org/10.1002/14356007.a17_363Wöuhrle, D. and Knothe, G. (1988) Polymers from Nitriles.VII. Polymerization of Fumaronitrile with Triethylamine Asinitiator. Journal of Polymer Science Part A: Polymer Chemistry, 26, 2435-2447.
<br>https://doi.org/10.1002/pola.1988.080260915Fleming, F.F., Yao, L, Ravikumar, P.C., Funk, L. and Shook, B.C. (2010) Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore. Journal of Medicinal Chemistry, 53, 7902-7917.
<br>https://doi.org/10.1021/jm100762rAhren, B., Landin-Olsson, M., Jansson, P.A., Svensson, M., Holmes, D. and Schweizer, A. (2004) Inhibition of Dipeptidyl Peptidase-4 Reduces Glycemia, Sustains Insulin Levels, and Reduces Glucagon Levels in Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 89, 2078-2084. <br>https://doi.org/10.1210/jc.2003-031907Bhatnagar, A.S. (2007) The Discovery and Mechanism of Action of Letrozole. Breast Cancer Research and Treatment, 105, 7-17. <br>https://doi.org/10.1007/s10549-007-9696-3Jakesz, R., Jonat, W., Gnant, M., Mittlboeck, M., Greil, R., Tausch, C., Hilfrich, J., Kwasny, W., Menzel, C., Samonigg, H., Seifert, M., Gademann, G., Kaufmann, M. and Wolfgang, J. (2005) Switching of Postmenopausal Women with Endocrine-Responsive Early Breast Cancer to Anastrozole after 2 Years’ Adjuvant Tamoxifen: Combined Results of ABCSG Trial 8 and ARNO 95 Trial. Lancet, 366, 455-462. <br>https://doi.org/10.1016/S0140-6736(05)67059-6Larock, R.C. (2018) Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 3rd Edition, John Wiley & Sons, Inc., Hoboken. <br>https://doi.org/10.1002/9781118662083Zhong, Y.-H., Lee, J., Reamer, R.A. and Askin, D. (2004) New Method for the Synthesis of Diversely Functionalized Imidazolesfrom N-Acylated α-Aminonitriles. Organic Letters, 6, 929-931. <br>https://doi.org/10.1021/ol036423yStorz, T., Heid, R., Zeldis, J., Hoagland, S.M., Rapisardi, V., Hollywood, S. and Morton, G. (2011) Convenient and Practical One-Pot Synthesis of 4-Chloropyrimidinesvia a Novel Chloroimidate Annulation. Organic Process Research & Development, 15, 918-924. <br>https://doi.org/10.1021/op1002352Yeung, K.S., Farkus, M.E., Kadow, J.F. and Meanwell, N.A. (2005) ABase-Catalyzed, Direct Synthesis of 3, 5-Disubstituted 1,2,4-Triazoles from Nitriles and Hydrazides. Tetrahedron Letters, 46, 3429-3432.
<br>https://doi.org/10.1016/j.tetlet.2005.02.167Horneff, T., Chuprakov, S., Chernyak, N., Gevorgyan, V. and Fokin, V.V. (2008) Rhodium-Catalyzed Transannulation of 1,2,3-Triazoles with Nitriles. Journal of the American Chemical Society, 130, 14972-14974.
<br>https://doi.org/10.1021/ja805079vGanesan, M. and Nagaraaj, P. (2020) Recent Developments in Dehydration of Primary Amides to Nitriles. Organic Chemistry Frontiers, 7, 3792-3814. <br>https://doi.org/10.1039/D0QO00843EBlum, J. and Fisher, A. (1970) A Novel Synthesis of Nitriles from Secondary Amides. Tetrahedron Letters, 11, 1963-1966. <br>https://doi.org/10.1016/S0040-4039(01)98128-6Blum, J., Fisher, A. and Greener, E. (1973) The Catalytic Decomposition of Secondary Carboxamides by Transition-Metal Complexes. Tetrahedron, 29, 1073-1081. <br>https://doi.org/10.1016/0040-4020(73)80064-XCampbell, J.A., McDouglad, G., McNab, H., Rees, L.V.C. and Tyas, R.G. (2007) Laboratory Scale Synthesis of Nitriles by Catalysed Dehydration of Amides and Oximes under Flash Vacuum Pyrolysis (FVP) Conditions. Synthesis, 20, 3179-3184. <br>https://doi.org/10.1055/s-2007-990782Itagaki, S., Kamata, K., Yamaguchi, K. and Mizuno, N. (2013) Amonovacant Lacunary Silicotungstate as an Efficient Heterogeneous Catalyst for Dehydration of Primary Amides Tonitriles. ChemCatChem, 5, 1725-1728.
<br>https://doi.org/10.1002/cctc.201300063Watanabe, Y., Okuda, F. and Tsuji, Y.J. (1990) Ruthenium Complex Catalyzed Dehydration of Carboxamides to Nitriles in the Presence of Urea Derivatives. Journal of Molecular Catalysis, 58, 87-94.
<br>https://doi.org/10.1016/0304-5102(90)85181-GFuruya, Y., Ishihara, K. and Yamamoto, H. (2007) Perrhenic Acid-Catalyzed Dehydration from Primary Amides, Aldoximes, N-Monoacylureas, and α-Substituted Ketoximes to Nitrile Compounds. Bulletin of the Chemical Society of Japan, 80, 400-406. <br>https://doi.org/10.1246/bcsj.80.400Sueoka, S., Mitsudome, T., Mizugaki, T., Jitsukawa, K. and Kaneda, K. (2010) Supported Monomeric Vanadium Catalyst for Dehydration of Amides to Form Nitriles, Chemical Communications, 46, 8243-8245.
<br>https://doi.org/10.1039/c0cc02412kRuck, R.T. and Bergman, R.G. (2004) Zirconium-Mediated Conversion of Amides to Nitriles: A Surprising Additive Effect. Angewandte Chemie International Edition, 43, 5375-5377. <br>https://doi.org/10.1002/anie.200461064Maffioli, S.I., Marzorati, E. and Marazzi, A. (2005) Mild and Reversible Dehydration of Primary Amides with PdCl2 in Aqueous Acetonitrile. Organic Letters, 7, 5237-5239. <br>https://doi.org/10.1021/ol052100lManjula, K. and Pasha, M.A. (2007) Rapid Method of Converting Primary Amides to Nitriles and Nitriles to Primary Amides by ZnCl2 Using Microwaves under Different Reaction Conditions. Synthetic Communications, 37, 1545-1550.
<br>https://doi.org/10.1080/00397910701230147Zhang, W.D., Haskins, C.W., Yang, Y. and Dai, M.J. (2014) Synthesis of Nitriles via Palladium-Catalyzed Water Shuffling from Amides to Acetonitriles. Organic & Biomolecular Chemistry, 12, 9109-9112.
<br>https://doi.org/10.1039/C4OB01825GDubey, P., Gupta, S. and Singh, A.K. (2017) Trinuclear Complexes of Palladium(II) with Chalcogenated N-Hetero- cyclic Carbenes: Catalysis of Selective Nitrile-Primary Amide Interconversion and Sonogashira Coupling. Dalton Transactions, 46, 13065-13076. <br>https://doi.org/10.1039/C7DT02592KAl-Huniti, M.H., Rivera-Chávez, J., Colón, K.L., Stanley, J.L., Burdette, J.E., Pearce, C.J., Oberlies, N.H. and Croatt, M.P. (2018) Development and Utilization of a Palladium-Catalyzed Dehydration of Primary Amides to Form Nitriles. Organic Letters, 20, 6046-6050. <br>https://doi.org/10.1021/acs.orglett.8b02422Okabe, H., Naraoka, A., Isogawa, T., Oishi, S. and Naka, H. (2019) Acceptor-Controlled Transfer Dehydration of Amides to Nitriles. Organic Letters, 21, 4767-4770. <br>https://doi.org/10.1021/acs.orglett.9b01657Hanada, S., Motoyama, Y. and Nagashima, H. (2008) Hydrosilanes Are Not Always Reducing Agents for Carbonyl Compounds but Can Also Induce Dehydration: A Ruthenium-Catalyzed Conversion of Primary Amides to Nitriles. European Journal of Organic Chemistry, 2008, 4097-4100. <br>https://doi.org/10.1002/ejoc.200800523Zhou, S.L., Addis, D., Das, S., Junge, K. and Beller, M. (2009) New Catalytic Properties of Iron Complexes: Dehydration of Amides to Nitriles. Chemical Communications, 45, 4883-4885. <br>https://doi.org/10.1039/b910145dBezier, D., Venkanna, G.T., Sortais, J.B. and Darcel, C. (2011) Well-Defined Cyclopentadienyl NHC Iron Complex as the Catalyst for Efficient Hydrosilylation of Amides to Amines and Nitriles. ChemCatChem, 3, 1747-1750.
<br>https://doi.org/10.1002/cctc.201100202Enthaler, S. and Weidauer, M. (2011) Copper-Catalyzed Dehydration of Primary Amides to Nitriles. Catalysis Letters, 141, Article No. 1079. <br>https://doi.org/10.1007/s10562-011-0660-9Enthaler, S. (2011) Straightforward Uranium-Catalyzed Dehydration of Primary Amides to Nitriles. Chemistry—A European Journal, 17, 9316-9319. <br>https://doi.org/10.1002/chem.201101478Enthaler, S. (2011) Straightforward Iron-Catalyzed Synthesis of Nitrilesby Dehydration of Primary Amides. European Journal of Organic Chemistry, 2011, 4760-4763. <br>https://doi.org/10.1002/ejoc.201100754Enthaler, S. and Inoue, S. (2012) An Efficient Zinc-Catalyzed Dehydration of Primary Amides to Nitriles. Chemistry—An Asian Journal, 7, 169-175. <br>https://doi.org/10.1002/asia.201100493Mineno, T., Shinada, M., Watanabe, K., Yoshimitsu, H., Miyashita, H. and Kansui, H. (2014) Highly-Efficient Conversion of Primary Amides to Nitriles Using Indium(III) Triflate as the Catalyst. International Journal of Organic Chemistry, 4, 1-6. <br>https://doi.org/10.4236/ijoc.2014.41001Elangovan, S., Quintero-Duque, S., Dorcet, V., Roisnel, T., Norel, L., Darcel, C. and Sortais, J.B. (2015) Knölker-Type Iron Complexes Bearing an N-Heterocyclic Carbene Ligand: Synthesis, Characterization, and Catalytic Dehydration of Primary Amides. Organometallics, 34, 4521-4528. <br>https://doi.org/10.1021/acs.organomet.5b00553Xue, B.J., Sun, H.J., Wang, Y., Zheng, Y.Y., Li, X.Y., Fuhr, O. and Fenske, D. (2016) Efficient Reductive Dehydration of Primary Amides to Nitriles Catalyzed by Hydrido Thiophenolato Iron (II) Complexes under Hydrosilation Conditions. Catalysis Communications, 86, 148-150. <br>https://doi.org/10.1016/j.catcom.2016.08.024Ren, S., Xie, S., Zheng, T., Wang, Y., Xu, S., Xue, B., Li, X., Sun, H., Fuhr, O. and Fenske, D. (2018) Synthesis of Silyl Iron Hydride via Si–H Activation and Its Dual Catalytic Application in the Hydrosilylation of Carbonyl Compounds and Dehydration of Benzamides. Dalton Transactions, 47, 4352-4359. <br>https://doi.org/10.1039/C8DT00289DLiu, R.Y., Bae, M. and Buchwald, S.L. (2018) Mechanistic Insight Facilitates Discovery of a Mild and Efficient Copper-Catalyzed Dehydration of Primary Amides to Nitriles Using Hydrosilanes. Journal of the American Chemical Society, 140, 1627-1631. <br>https://doi.org/10.1021/jacs.8b00643Wang, Y.Y., Fu, L.Y., Qi, H.M., Chen, S.W. and Li, Y.H. (2018) Bioinspired Synthesis of Nitriles from Primary Amides via Zinc/Anhydride Catalysis. Asian Journal of Organic Chemistry, 7, 367-370.
<br>https://doi.org/10.1002/ajoc.201700664Zheng, T., Wang, Y., Yang, Z., Sun, H. and Li, X. (2019) Catalytic Effect of Iron Hydrides on Dehydration of Primary Amides to Nitriles. Chinese Journal of Organic Chemistry, 39, 2941-2945. <br>https://doi.org/10.6023/cjoc201903075Ren, S., Wang, Y., Yang, D., Sun, H. and Li, X. (2019) Dehydration of Primary Amides to Nitriles Catalyzed by [CNC]-Pincer Hydrido Cobalt(III) Complexes. Catalysis Communications, 120, 72-75.
<br>https://doi.org/10.1016/j.catcom.2018.12.002Li, Y., Zhao, Y., Wang, S. and Ma, X. (2019) Silica Supported Potassium Oxide Catalyst for Dehydration of 2-Picolinamide to form 2-Cyanopyridine. Chinese Chemical Letters, 30, 494-498.
<br>https://doi.org/10.1016/j.cclet.2018.04.012Yao, W., Fang, H., He, Q., Peng, D., Liu, G. and Huang, Z. (2019) A BEt3-Base Catalyst for Amide Reduction with Silane. The Journal of Organic Chemistry, 84, 6084-6093. <br>https://doi.org/10.1021/acs.joc.9b00277Das, H.S., Das, S., Dey, K., Singh, B., Haridasan, R.K., Das, A., Ahmed, J. and Mandal, S.K. (2019) Primary Amides to Amines or Nitriles: A Dual Role by a Single Catalyst. Chemical Communications, 55, 11868-11871.
<br>https://doi.org/10.1039/C9CC05856GLi, K., Sun, H., Yang, W., Wang, Y., Xie, S., Li, X., Fuhr, O. and Fenske, D. (2020) Efficient Dehydration of Primary Amides to NitrilesCatalyzed by Phosphorus-Chalcogen Chelated Iron Hydrides. Applied Organometallic Chemistry, 34, Article No. e5337. <br>https://doi.org/10.1002/aoc.5337Chang, G., Li, X., Zhang, P., Yang, W., Li, K., Wang, Y., Sun, H., Fuhr, O. and Fenske, D. (2020) Lewis Acid Promoted Dehydration of Amides to Nitriles Catalyzed by [PSiP]-Pincer Iron Hydrides. Applied Organometallic Chemistry, 34, Article No. e5466. <br>https://doi.org/10.1002/aoc.5466Wang, Y., Zhang, H., Xie, S., Sun, H., Li, X., Fuhr, O. and Fenske, D. (2020) An Air-Stable N-Heterocyclic [PSiP] Pincer Iron Hydride and an Analogous Nitrogen Iron Hydride: Synthesis and Catalytic Dehydration of Primary Amides to Nitriles. Organometallics, 39, 824-833. <br>https://doi.org/10.1021/acs.organomet.9b00880Zhou, S.L., Junge, K., and Addis, D., Das, S. and Beller, M. (2009) A General and Convenient Catalytic Synthesis of Nitriles from Amides and Silanes. Organic Letters, 11, 2461-2464. <br>https://doi.org/10.1021/ol900716qHota, P.K., Maji, S., Ahmed, J., Rajendran, N.M. and Mandal, S.K. (2020) NHC-Catalyzed Silylative Dehydration of Primary Amides to Nitriles at Room Temperature. Chemical Communications, 56, 575-578.
<br>https://doi.org/10.1039/C9CC08413DShipilovskikh, S.A., Vaganov, V.Y., Denisova, E.I., Rubtsov, A.E. and Malkov, A.V. (2018) Dehydration ofAmides to Nitriles under Conditions of a Catalytic Appel Reaction. Organic Letters, 20, 728-731.
<br>https://doi.org/10.1021/acs.orglett.7b03862Ding, R., Liu, Y.G., Han, M.R., Jiao, W.Y., Li, J.Q., Tian, H.Y. and Sun, B.G. (2018) Synthesis of Nitriles from Primary Amides or Aldoximes under Conditions of a Catalytic Swern Oxidation. The Journal of Organic Chemistry, 83, 12939-12944. <br>https://doi.org/10.1021/acs.joc.8b02190Rai, A. and Yadav, L.D.S. (2013) Cyclopropenone-Catalyzed Direct Conversion of Aldoximes and Primary Amides into Nitriles. European Journal of Organic Chemistry, 2013, 1889-1893. <br>https://doi.org/10.1002/ejoc.201300059