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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Letter Article

Imidazole Hydrochloride Promoted Synthesis of Nitriles from Aldehydes

Author(s): Yin Wang, Xuetong Wang, Yanwu Li, Xiuyu Zhang, Lingli Li, Tingshu He, Jianyong Yuan* and Suqin Shang*

Volume 19, Issue 8, 2022

Published on: 22 July, 2022

Page: [923 - 929] Pages: 7

DOI: 10.2174/1570179419666220509143654

Price: $65

Abstract

Background and Objective: As a key pharmacophore, the cyano group widely exists in a variety of biologically active compounds. Besides, nitriles are also valuable intermediates for many common functional groups. In this current work, a new synthesis strategy was developed to obtain nitriles from aldehydes.

Methods: Using commercially available aldehydes as raw materials, and hydroxylamine and hydrochloride as nitrogen sources, the corresponding nitrile compounds were successfully synthesized by the one-pot method through the promotion of imidazole hydrochloride. And it was characterized by 1H NMR, 13C NMR, and mass spectrometry.

Results: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of nitriles. The highest yields (95%) were achieved using sulfolane as a solvent, and imidazole hydrochloride as a promoter.

Conclusion: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. Twenty seven examples of functionalized nitrile compounds have been synthesized in good to excellent yields. This methodology features that an environmentally benign imidazole hydrochloride replaces transition metal catalysts and oxidants required in conventional strategies to convert aldehydes into nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.

Keywords: Imidazole hydrochloride, aldehyde, aldoxime, nitrile, hydroxylamine hydrochloride, sufolane.

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[1]
Huber, U.; Moore, R.E.; Patterson, G.M.L. Isolation of a nitrile-containing indole alkaloid from the terrestrial blue-green alga hapalosiphon delicatulus. J. Nat. Prod., 1998, 61(10), 1304-1306.
[http://dx.doi.org/10.1021/np9801561] [PMID: 9784177]
[2]
Schulze, C.J.; Bray, W.M.; Loganzo, F.; Lam, M.H.; Szal, T.; Villalobos, A.; Koehn, F.E.; Linington, R.G.; Borrelidin, B. Isolation, biological activity, and implications for nitrile biosynthesis. J. Nat. Prod., 2014, 77(11), 2570-2574.
[http://dx.doi.org/10.1021/np500727g] [PMID: 25393949]
[3]
Fleming, F.F. Nitrile-containing natural products. Nat. Prod. Rep., 1999, 16(5), 597-606.
[http://dx.doi.org/10.1039/a804370a]
[4]
Fu, T.; Wang, X.L.; Wang, Y.Z. Flame-responsive aryl ether nitrile structure towards multiple fire hazards suppression of thermoplastic polyester. J. Hazard. Mater., 2021, 403, 123714.
[http://dx.doi.org/10.1016/j.jhazmat.2020.123714] [PMID: 33264893]
[5]
Miller, J.S.; Manson, J.L. Designer magnets containing cyanides and nitriles. Acc. Chem. Res., 2001, 34(7), 563-570.
[http://dx.doi.org/10.1021/ar0000354] [PMID: 11456474]
[6]
Wang, Y.; Du, Y.; Huang, N. A survey of the role of nitrile groups in protein-ligand interactions. Future Med. Chem., 2018, 10(23), 2713-2728.
[http://dx.doi.org/10.4155/fmc-2018-0252] [PMID: 30518255]
[7]
Zhang, Z.; Wallace, M.B.; Feng, J.; Stafford, J.A.; Skene, R.J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D.B.; Kaldor, S.W.; Navre, M.; Webb, D.R.; Gwaltney, S.L. Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J. Med. Chem., 2011, 54(2), 510-524.
[http://dx.doi.org/10.1021/jm101016w] [PMID: 21186796]
[8]
Horino, T.; Hatakeyama, Y.; Ichii, O.; Matsumoto, T.; Shimamura, Y.; Inoue, K.; Terada, Y.; Okuhara, Y. Effects of topiroxostat in hyperuricemic patients with chronic kidney disease. Clin. Exp. Nephrol., 2018, 22(2), 337-345.
[http://dx.doi.org/10.1007/s10157-017-1452-3] [PMID: 28752287]
[9]
Bassetto, M.; Ferla, S.; Pertusati, F.; Kandil, S.; Westwell, A.D.; Brancale, A.; McGuigan, C. Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer. Eur. J. Med. Chem., 2016, 118, 230-243.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.052] [PMID: 27131065]
[10]
Ferretti, F.; Boffito, M. Rilpivirine long-acting for the prevention and treatment of HIV infection. Curr. Opin. HIV AIDS, 2018, 13(4), 300-307.
[http://dx.doi.org/10.1097/COH.0000000000000474] [PMID: 29794818]
[11]
Hota, P.K.; Maji, S.; Ahmed, J.; Rajendran, N.M.; Mandal, S.K. NHC-catalyzed silylative dehydration of primary amides to nitriles at room temperature. Chem. Commun. (Camb.), 2020, 56(4), 575-578.
[http://dx.doi.org/10.1039/C9CC08413D] [PMID: 31830152]
[12]
Liu, R.Y.; Bae, M.; Buchwald, S.L. Mechanistic insight facilitates discovery of a mild and efficient copper-catalyzed dehydration of primary amides to nitriles using hydrosilanes. J. Am. Chem. Soc., 2018, 140(5), 1627-1631.
[http://dx.doi.org/10.1021/jacs.8b00643] [PMID: 29353477]
[13]
Okabe, H.; Naraoka, A.; Isogawa, T.; Oishi, S.; Naka, H. Acceptor-controlled transfer dehydration of amides to nitriles. Org. Lett., 2019, 21(12), 4767-4770.
[http://dx.doi.org/10.1021/acs.orglett.9b01657] [PMID: 31184196]
[14]
Achard, T.; Egly, J.; Sigrist, M.; Maisse-François, A.; Bellemin-Laponnaz, S. Easy ruthenium-catalysed oxidation of primary amines to nitriles under oxidant-free conditions. Chemistry, 2019, 25(58), 13271-13274.
[http://dx.doi.org/10.1002/chem.201902557] [PMID: 31287194]
[15]
Lu, G-P.; Li, X.; Zhong, L.; Li, S.; Chen, F. Ru@UiO-66(Ce) catalyzed acceptorless dehydrogenation of primary amines to nitriles: The roles of Lewis acid–base pairs in the reaction. Green Chem., 2019, 21(19), 5386-5393.
[http://dx.doi.org/10.1039/C9GC02181G]
[16]
Dutta, I.; Yadav, S.; Sarbajna, A.; De, S.; Hölscher, M.; Leitner, W.; Bera, J.K. Double dehydrogenation of primary amines to nitriles by a ruthenium complex featuring pyrazole functionality. J. Am. Chem. Soc., 2018, 140(28), 8662-8666.
[http://dx.doi.org/10.1021/jacs.8b05009] [PMID: 29956921]
[17]
Wang, Y.; Furukawa, S.; Zhang, Z.; Torrente-Murciano, L.; Khan, S.A.; Yan, N. Oxidant free conversion of alcohols to nitriles over Ni-based catalysts. Catal. Sci. Technol., 2019, 9(1), 86-96.
[http://dx.doi.org/10.1039/C8CY01799A]
[18]
Yuan, L.; Yin, G.; Zhang, H-y.; Zhang, Y.; Zhao, J. Aerobic oxidative conversion of benzylic alcohols with ammonia to nitriles catalyzed by CuCl/TEMPO/PIC. Chem. Pap., 2018, 72(10), 2679-2685.
[http://dx.doi.org/10.1007/s11696-018-0468-9]
[19]
Ding, R.; Liu, Y.; Han, M.; Jiao, W.; Li, J.; Tian, H.; Sun, B. Synthesis of nitriles from primary amides or aldoximes under conditions of a catalytic swern oxidation. J. Org. Chem., 2018, 83(20), 12939-12944.
[http://dx.doi.org/10.1021/acs.joc.8b02190] [PMID: 30240220]
[20]
Zhang, X.; Sun, J.; Ding, Y.; Yu, L. Dehydration of aldoximes using PhSe(O)OH as the pre-catalyst in air. Org. Lett., 2015, 17(23), 5840-5842.
[http://dx.doi.org/10.1021/acs.orglett.5b03011] [PMID: 26574922]
[21]
Liu, Q.; Sun, B.; Liu, Z.; Kao, Y.; Dong, B-W.; Jiang, S-D.; Li, F.; Liu, G.; Yang, Y.; Mo, F. A general electrochemical strategy for the Sandmeyer reaction. Chem. Sci. (Camb.), 2018, 9(46), 8731-8737.
[http://dx.doi.org/10.1039/C8SC03346C] [PMID: 30627393]
[22]
Wang, S.; Qiu, D.; Mo, F.; Zhang, Y.; Wang, J. Metal-free aromatic carbon-phosphorus bond formation via a sandmeyer-type reaction. J. Org. Chem., 2016, 81(23), 11603-11611.
[http://dx.doi.org/10.1021/acs.joc.6b01820] [PMID: 27792351]
[23]
Leas, D.A.; Dong, Y.; Vennerstrom, J.L.; Stack, D.E. One-pot, metal-free conversion of anilines to aryl bromides and iodides. Org. Lett., 2017, 19(10), 2518-2521.
[http://dx.doi.org/10.1021/acs.orglett.7b00771] [PMID: 28481557]
[24]
Pradal, A.; Evano, G. A vinylic Rosenmund-von Braun reaction: Practical synthesis of acrylonitriles. Chem. Commun. (Camb.), 2014, 50(80), 11907-11910.
[http://dx.doi.org/10.1039/C4CC05557H] [PMID: 25154349]
[25]
Zanon, J.; Klapars, A.; Buchwald, S.L. Copper-catalyzed domino halide exchange-cyanation of aryl bromides. J. Am. Chem. Soc., 2003, 125(10), 2890-2891.
[http://dx.doi.org/10.1021/ja0299708] [PMID: 12617652]
[26]
Rokade, B.V.; Prabhu, K.R. Chemoselective schmidt reaction mediated by triflic acid: Selective synthesis of nitriles from aldehydes. J. Org. Chem., 2012, 77(12), 5364-5370.
[http://dx.doi.org/10.1021/jo3008258] [PMID: 22616901]
[27]
Al-Huniti, M.H.; Rivera-Chávez, J.; Colón, K.L.; Stanley, J.L.; Burdette, J.E.; Pearce, C.J.; Oberlies, N.H.; Croatt, M.P. Development and utilization of a palladium-catalyzed dehydration of primary amides to form nitriles. Org. Lett., 2018, 20(19), 6046-6050.
[http://dx.doi.org/10.1021/acs.orglett.8b02422] [PMID: 30221526]
[28]
Noh, J-H.; Kim, J. Aerobic oxidative conversion of aromatic aldehydes to nitriles using a Nitroxyl/NOx catalyst system. J. Org. Chem., 2015, 80(22), 11624-11628.
[http://dx.doi.org/10.1021/acs.joc.5b02333] [PMID: 26505657]
[29]
Wu, Q.; Luo, Y.; Lei, A.; You, J. Aerobic copper-promoted radical-type cleavage of coordinated cyanide anion: Nitrogen transfer to aldehydes to form nitriles. J. Am. Chem. Soc., 2016, 138(9), 2885-2888.
[http://dx.doi.org/10.1021/jacs.5b10945] [PMID: 26907853]
[30]
Reddy, M.B.M.; Pasha, M.A. Efficient and high-yielding protocol for the synthesis of nitriles from aldehydes. Synth. Commun., 2010, 40(22), 3384-3389.
[http://dx.doi.org/10.1080/00397910903419894]
[31]
Telvekar, V.N.; Rane, R.A.; Namjoshi, T.V. Novel system for the synthesis of nitriles from aldehydes using aqueous ammonia and bis(trifluoroacetoxy) iodo benzene. Synth. Commun., 2010, 40(4), 494-497.
[http://dx.doi.org/10.1080/00397910902985549]
[32]
Chill, S.T.; Mebane, R.C. A facile one-pot conversion of aldehydes into nitriles. Synth. Commun., 2009, 39(20), 3601-3606.
[http://dx.doi.org/10.1080/00397910902788174]
[33]
Quinn, D.J.; Haun, G.J.; Moura-Letts, G. Direct synthesis of nitriles from aldehydes with hydroxylamine-O-sulfonic acid in acidic water. Tetrahedron Lett., 2016, 57(34), 3844-3847.
[http://dx.doi.org/10.1016/j.tetlet.2016.07.047]
[34]
Gurjar, J.; Bater, J.; Fokin, V.V. Sulfuryl fluoride mediated conversion of aldehydes to nitriles. Chemistry, 2019, 25(8), 1906-1909.
[http://dx.doi.org/10.1002/chem.201805175] [PMID: 30346050]
[35]
Fang, W.Y.; Qin, H.L. Cascade process for direct transformation of Aldehydes (RCHO) to Nitriles (RCN) using inorganic reagents NH2OH/Na2CO3/SO2F2 in DMSO. J. Org. Chem., 2019, 84(9), 5803-5812.
[http://dx.doi.org/10.1021/acs.joc.8b03164] [PMID: 30868885]
[36]
Laulhé, S.; Gori, S.S.; Nantz, M.H.; Chemoselective, A. A chemoselective, one-pot transformation of aldehydes to nitriles. J. Org. Chem., 2012, 77(20), 9334-9337.
[http://dx.doi.org/10.1021/jo301133y] [PMID: 22928794]
[37]
An, X.D.; Yu, S. Direct synthesis of nitriles from aldehydes using an O-Benzoyl Hydroxylamine (BHA) as the nitrogen source. Org. Lett., 2015, 17(20), 5064-5067.
[http://dx.doi.org/10.1021/acs.orglett.5b02547] [PMID: 26418564]
[38]
Ali, S.I.; Nikalje, M.D.; Dewkar, G.K.; Paraskar, A.S.; Jagtap, H.S.; Sudalai, A. Formamide assisted one-pot conversion of aromatic aldehydes into the corresponding nitriles. J. Chem. Res., 2000, (1), 30-31.
[http://dx.doi.org/10.3184/030823400103165572]
[39]
Supsana, P.; Liaskopoulosa, T.; Tsoungas, P.G.; Varvounis, G. DMF-Catalysed thermal dehydration of aldoximes: A convenient access to functionalized aliphatic and aromatic Nitriles. Synlett, 2007, (17), 2671-2674.
[40]
Dewan, S.K.; Singh, R.; Kumar, A. One pot synthesis of nitriles from aldehydes and hydroxylamine hydrochloride using sodium sulphate (anhyd) and sodium bicarbonate in dry media under microwave irradiation. ARKIVOC, 2006, 41-44.
[41]
Wang, X.; Wang, Y.; Liu, X.; He, T.; Li, L.; Wu, H.; Zhou, S.; Li, D.; Liao, S.; Xu, P.; Huang, X.; Yuan, J. Imidazole hydrochloride promoted synthesis of 3,5-disubstituted-1,2,4-oxadiazoles. Tetrahedron, 2021, 100, 132496.
[http://dx.doi.org/10.1016/j.tet.2021.132496]
[42]
Gan, Z.J.; Tian, Q.Q.; Shang, S.Q.; Luo, W.; Dai, Z.S.; Wang, H.J.; Li, D.; Wang, X.T.; Yuan, J.Y. Imidazolium chloride-catalyzed synthesis of benzimidazoles and 2-substituted benzimidazoles from o-phenylenediamines and DMF derivatives. Tetrahedron, 2018, 74(52), 7450-7456.
[http://dx.doi.org/10.1016/j.tet.2018.11.014]
[43]
Tian, Q.; Luo, W.; Gan, Z.; Li, D.; Dai, Z.; Wang, H.; Wang, X.; Yuan, J. Eco-Friendly syntheses of 2-substituted benzoxazoles and 2-substituted benzothiazoles from 2-aminophenols, 2-aminothiophenols and DMF derivatives in the presence of imidazolium chloride. Molecules, 2019, 24(1), 12.
[http://dx.doi.org/10.3390/molecules24010174] [PMID: 30621218]
[44]
Mudshinge, S.R.; Potnis, C.S.; Xu, B.; Hammond, G.B. HCl center dot DMPU-assisted one-pot and metal-free conversion of aldehydes to nitriles. Green Chem., 2020, 22(13), 4161-4164.
[http://dx.doi.org/10.1039/D0GC00757A] [PMID: 33795972]
[45]
Liang, S.; Ebule, R.; Hammond, G.B.; Xu, B. A chlorinating reagent yields vinyl chlorides with high regioselectivity under heterogeneous gold catalysis. Org. Lett., 2017, 19(17), 4524-4527.
[http://dx.doi.org/10.1021/acs.orglett.7b02101] [PMID: 28809497]

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