Novel Synthesis of Dihydroisoxazoles by p-TsOH-Participated 1,3-Dipolar Cycloaddition of Dipolarophiles withα-Nitroketones
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of the Reaction Conditions
2.2. Substrate Scope Studies
2.3. Mechanistic Studies
3. Materials and Methods
3.1. General Experimental Methods
3.2. General Procedure for the Cycloaddition of Alkenes and α-Nitroketones
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
- Hemmerling, F.; Hahn, F. Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides. Beilstein J. Org. Chem. 2016, 12, 1512–1550. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sysak, A.; Obminska-Mrukowicz, B. Isoxazole ring as a useful scaffold in a search for new therapeutic agents. Eur. J. Med. Chem. 2017, 137, 292–309. [Google Scholar] [CrossRef] [PubMed]
- Gutierrez, M.; Matus, M.F.; Poblete, T.; Amigo, J.; Vallejos, G.; Astudillo, L. Isoxazoles: Synthesis, evaluation and bioinformatic design as acetylcholinesterase inhibitors. J. Pharm. Pharmacol. 2013, 65, 1796–1804. [Google Scholar] [CrossRef]
- Koufaki, M.; Fotopoulou, T.; Kapetanou, M.; Heropoulos, G.A.; Gonos, E.S.; Chondrogianni, N. Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity. Eur. J. Med. Chem. 2014, 83, 508–515. [Google Scholar] [CrossRef]
- Bano, S.; Alam, M.S.; Javed, K.; Dudeja, M.; Das, A.K.; Dhulap, A. Synthesis, biological evaluation and molecular docking of some substituted pyrazolines and isoxazolines as potential antimicrobial agents. Eur. J. Med. Chem. 2015, 95, 96–103. [Google Scholar] [CrossRef] [PubMed]
- Liao, J.; Ouyang, L.; Jin, Q.; Zhang, J.; Luo, R. Recent advances in the oxime-participating synthesis of isoxazolines. Org. Biomol. Chem. 2020, 18, 4709–4716. [Google Scholar] [CrossRef] [PubMed]
- Hyean Kim, B.; Jun Chung, Y.; Jung Ryu, E. Synthesis of α-hydroxy ketomethylene dipeptide isosteres. Tetrahedron Lett. 1993, 34, 8465–8468. [Google Scholar] [CrossRef]
- Goncalves, I.L.; Machado das Neves, G.; Porto Kagami, L.; Eifler-Lima, V.L.; Merlo, A.A. Discovery, development, chemical diversity and design of isoxazoline-based insecticides. Bioorg. Med. Chem. 2021, 30, 115934. [Google Scholar] [CrossRef]
- Pohjakallio, A.; Pihko, P.M.; Laitinen, U.M. Synthesis of 2-isoxazolines: Enantioselective and racemic methods based on conjugate additions of oximes. Chemistry 2010, 16, 11325–11339. [Google Scholar] [CrossRef]
- Liu, X.; Ma, X.; Feng, Y. Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction. Beilstein J. Org. Chem. 2019, 15, 1434–1440. [Google Scholar] [CrossRef]
- Akagawa, K.; Kudo, K. Iterative Polyketide Synthesis via a Consecutive Carbonyl-Protecting Strategy. J. Org. Chem. 2018, 83, 4279–4285. [Google Scholar] [CrossRef]
- Lopes, E.F.; Penteado, F.; Thurow, S.; Pinz, M.; Reis, A.S.; Wilhelm, E.A.; Luchese, C.; Barcellos, T.; Dalberto, B.; Alves, D.; et al. Synthesis of Isoxazolines by the Electrophilic Chalcogenation of beta, gamma-Unsaturated Oximes: Fishing Novel Anti-Inflammatory Agents. J. Org. Chem. 2019, 84, 12452–12462. [Google Scholar] [CrossRef]
- Kaur, K.; Kumar, V.; Sharma, A.K.; Gupta, G.K. Isoxazoline containing natural products as anticancer agents: A review. Eur. J. Med. Chem. 2014, 77, 121–133. [Google Scholar] [CrossRef]
- Goyard, D.; Konya, B.; Chajistamatiou, A.S.; Chrysina, E.D.; Leroy, J.; Balzarin, S.; Tournier, M.; Tousch, D.; Petit, P.; Duret, C.; et al. Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition. Eur. J. Med. Chem. 2016, 108, 444–454. [Google Scholar] [CrossRef] [Green Version]
- Picconi, P.; Prabaharan, P.; Auer, J.L.; Sandiford, S.; Cascio, F.; Chowdhury, M.; Hind, C.; Wand, M.E.; Sutton, J.M.; Rahman, K.M. Novel pyridyl nitrofuranyl isoxazolines show antibacterial activity against multiple drug resistant Staphylococcus species. Bioorg. Med. Chem. 2017, 25, 3971–3979. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dallanoce, C.; Meroni, G.; De Amici, M.; Hoffmann, C.; Klotz, K.N.; De Micheli, C. Synthesis of enantiopure Delta2-isoxazoline derivatives and evaluation of their affinity and efficacy profiles at human beta-adrenergic receptor subtypes. Bioorg. Med. Chem. 2006, 14, 4393–4401. [Google Scholar] [CrossRef]
- Filali, I.; Bouajila, J.; Znati, M.; Bousejra-El Garah, F.; Ben Jannet, H. Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities. J. Enzyme Inhib. Med. Chem. 2015, 30, 371–376. [Google Scholar] [CrossRef]
- Basappa; Sadashiva, M.P.; Mantelingu, K.; Swamy, S.N.; Rangappa, K.S. Solution-phase synthesis of novel delta2-isoxazoline libraries via 1,3-dipolar cycloaddition and their antifungal properties. Bioorg. Med. Chem. 2003, 11, 4539–4544. [Google Scholar] [CrossRef]
- Vinay Kumar, K.S.; Lingaraju, G.S.; Bommegowda, Y.K.; Vinayaka, A.C.; Bhat, P.; Pradeepa Kumara, C.S.; Rangappa, K.S.; Gowda, D.C.; Sadashiva, M.P. Synthesis, antimalarial activity, and target binding of dibenzazepine-tethered isoxazolines. RSC Adv. 2015, 5, 90408–90421. [Google Scholar] [CrossRef] [Green Version]
- Alshamari, A.; Al-Qudah, M.; Hamadeh, F.; Al-Momani, L.; Abu-Orabi, S. Synthesis, Antimicrobial and Antioxidant Activities of 2-Isoxazoline Derivatives. Molecules 2020, 25, 4271. [Google Scholar] [CrossRef] [PubMed]
- Tangallapally, R.P.; Sun, D.; Rakesh; Budha, N.; Lee, R.E.; Lenaerts, A.J.; Meibohm, B.; Lee, R.E. Discovery of novel isoxazolines as anti-tuberculosis agents. Bioorg. Med. Chem. Lett. 2007, 17, 6638–6642. [Google Scholar] [CrossRef] [Green Version]
- Karthikeyan, K.; Veenus Seelan, T.; Lalitha, K.G.; Perumal, P.T. Synthesis and antinociceptive activity of pyrazolyl isoxazolines and pyrazolyl isoxazoles. Bioorg. Med. Chem. Lett. 2009, 19, 3370–3373. [Google Scholar] [CrossRef]
- Yang, J.; Guan, A.; Wu, Q.; Cui, D.; Liu, C. Design, synthesis and herbicidal evaluation of novel uracil derivatives containing an isoxazoline moiety. Pest Manag. Sci. 2020, 76, 3395–3402. [Google Scholar] [CrossRef] [PubMed]
- Mita, T.; Kikuchi, T.; Mizukoshi, T.; Yaosaka, M.; Komoda, M. Preparation of Isoxazoline-Substituted Benzamide Derivatives as Insecticides, Acaricides, and Parasiticides. CN1930136; Nissan Chemical Industries Co., Ltd.: Tokyo, Japan, 2007; 2007-03-14. [Google Scholar]
- Slagbrand, T.; Kervefors, G.; Tinnis, F.; Adolfsson, H. An Efficient One-pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides. Adv. Synth. Catal. 2017, 359, 1990–1995. [Google Scholar] [CrossRef]
- Boruah, M.; Konwar, D. KF/Al2O3: Solid-Supported Reagent Used in 1,3-Dipolar Cycloaddition Reaction of Nitrile Oxide. Synth. Commun. 2012, 42, 3261–3268. [Google Scholar] [CrossRef]
- Kesornpun, C.; Aree, T.; Mahidol, C.; Ruchirawat, S.; Kittakoop, P. Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles. Angew. Chem. Int. Ed. Engl. 2016, 55, 3997–4001. [Google Scholar] [CrossRef]
- Svejstrup, T.D.; Zawodny, W.; Douglas, J.J.; Bidgeli, D.; Sheikh, N.S.; Leonori, D. Visible-light-mediated generation of nitrile oxides for the photoredox synthesis of isoxazolines and isoxazoles. Chem. Commun. 2016, 52, 12302–12305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dai, P.; Tan, X.; Luo, Q.; Yu, X.; Zhang, S.-G.; Liu, F.; Zhang, H.-W. Synthesis of 3-Acyl-isoxazoles and Δ2-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and tert-Butyl Nitrite via a Csp3-H Radical Functionalization/Cycloaddition Cascade. Org lett. 2019, 21, 5096–5100. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.-W.; Xiao, Z.-F.; Zhuang, Y.-J.; Wang, M.-M.; Kang, Y.-B. Metal-Free Autoxidative Nitrooxylation of Alkenyl Oximes with Molecular Oxygen. Adv. Synth. Catal. 2016, 358, 1942–1945. [Google Scholar] [CrossRef]
- Liu, R.-H.; Wei, D.; Han, B.; Yu, W. Copper-Catalyzed Oxidative Oxyamination/Diamination of Internal Alkenes of Unsaturated Oximes with Simple Amines. ACS Catal. 2016, 6, 6525–6530. [Google Scholar] [CrossRef]
- Wang, L.-J.; Chen, M.; Qi, L.; Xu, Z.; Li, W. Copper-mediated oxysulfonylation of alkenyl oximes with sodium sulfinates: A facile synthesis of isoxazolines featuring a sulfone substituent. Chem. Commun. (Camb). 2017, 53, 2056–2059. [Google Scholar] [CrossRef]
- Triandafillidi, I.; Kokotos, C.G. Green Organocatalytic Synthesis of Isoxazolines via a One-Pot Oxidation of Allyloximes. Org. Lett. 2017, 19, 106–109. [Google Scholar] [CrossRef] [PubMed]
- Wei, W.; Tang, Y.; Zhou, Y.; Deng, G.; Liu, Z.; Wu, J.; Li, Y.; Zhang, J.; Xu, S. Recycling Catalyst as Reactant: A Sustainable Strategy To Improve Atom Efficiency of Organocatalytic Tandem Reactions. Org. Lett. 2018, 20, 6559–6563. [Google Scholar] [CrossRef] [PubMed]
- Tu, K.N.; Hirner, J.J.; Blum, S.A. Oxyboration with and without a Catalyst: Borylated Isoxazoles via B-O sigma-Bond Addition. Org. Lett. 2016, 18, 480–483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chary, R.G.; Reddy, G.R.; Ganesh, Y.S.S.; Prasad, K.V.; Raghunadh, A.; Krishna, T.; Mukherjee, S.; Pal, M. Effect of Aqueous Polyethylene Glycol on 1,3-Dipolar Cycloaddition of Benzoylnitromethane/Ethyl 2-Nitroacetate with Dipolarophiles: Green Synthesis of Isoxazoles and Isoxazolines. Adv. Synth. Catal. 2014, 356, 160–164. [Google Scholar] [CrossRef]
- Zhang, X.-W.; He, X.-L.; Yan, N.; Zheng, H.X.; Hu, X.-G. Oxidize Amines to Nitrile Oxides: One Type of Amine Oxidation and Its Application to Directly Construct Isoxazoles and Isoxazolines. J. Org. Chem. 2020, 85, 15726–15735. [Google Scholar] [CrossRef]
- Li, B.-B.; Jiang, Q. Preparation of a novel isoxazoline compound, fluorelamine. Guangzhou Chem. Ind. 2020, 47, 215–216. [Google Scholar]
- Gao, M.; Gan, Y.; Xu, B. From Alkenes to Isoxazolines via Copper-Mediated Alkene Cleavage and Dipolar Cycloaddition. Org. Lett. 2019, 21, 7435–7439. [Google Scholar] [CrossRef]
- Morita, T.; Fukuhara, S.; Fuse, S.; Nakamura, H. Gold(I)-Catalyzed Intramolecular S(E)Ar Reaction: Efficient Synthesis of Isoxazole-Containing Fused Heterocycles. Org. Lett. 2018, 20, 433–436. [Google Scholar] [CrossRef]
- Ueda, M.; Ikeda, Y.; Sato, A.; Ito, Y.; Kakiuchi, M.; Shono, H.; Miyoshi, T.; Naito, T.; Miyata, O. Silver-catalyzed synthesis of disubstituted isoxazoles by cyclization of alkynyl oxime ethers. Tetrahedron 2011, 67, 4612–4615. [Google Scholar] [CrossRef]
- Pan, X.-H.; Xin, X.-B.; Mao, Y.; Li, X.; Zhao, Y.-N.; Liu, Y.-D.; Zhang, K.; Yang, X.-D.; Wang, J.-H. 3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of alpha-Nitroketones with Dipolarophiles. Molecules 2021, 26, 3491. [Google Scholar] [CrossRef] [PubMed]
- Nazarenko, K.G.; Shvidenko, K.V.; Pinchuk, A.M.; Tolmachev, A.A. Synthesis of 7-Amino-1-nitro-2-heptanone Derivatives. Synth. Commun. 2003, 33, 4241–4252. [Google Scholar] [CrossRef]
- Arumugam, N.; Raghunathan, R.; Almansour, A.I.; Karama, U. An efficient synthesis of highly functionalized novel chromeno [4,3-b] pyrroles and indolizino [6,7-b] indoles as potent antimicrobial and antioxidant agents. Bioorg. Med. Chem. Lett. 2012, 22, 1375–1379. [Google Scholar] [CrossRef]
- Quan, X.-J.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H. p-Toluenesulfonic acid mediated 1,3-dipolar cycloaddition of nitroolefins with NaN3 for synthesis of 4-aryl-NH-1,2,3-triazoles. Org. Lett. 2014, 16, 5728–5731. [Google Scholar] [CrossRef]
- Itoh, K.-i.; Aoyama, T.; Satoh, H.; Fujii, Y.; Sakamaki, H.; Takido, T.; Kodomari, M. Application of silica gel-supported polyphosphoric acid (PPA/SiO2) as a reusable solid acid catalyst to the synthesis of 3-benzoylisoxazoles and isoxazolines. Tetrahedron Lett. 2011, 52, 6892–6895. [Google Scholar] [CrossRef]
- Itoh, K.; Horiuchi, C.A. Formation of isoxazole derivatives via nitrile oxide using ammonium cerium nitrate (CAN): A novel one-pot synthesis of 3-acetyl- and 3-benzoylisoxazole derivatives. Tetrahedron 2004, 60, 1671–1681. [Google Scholar] [CrossRef]
- June, L.J.; Jihye, K.; Moo, J.Y.; Min, L.B.; Hyo, K.B. Indium-mediated one-pot synthesis of benzoxazoles or oxazoles from 2-nitrophenols or 1-aryl-2-nitroethanones. Tetrahedron 2009, 65, 8821–8831. [Google Scholar]
- Zhang, H.Q.; Pan, X.H.; Zhang, K.; Wang, H.Y.; Wang, J.H. Synthesis of α-nitroketones. J. Shihezi Univ. (Nat. Sci. Ed.) 2017, 35, 602–605. [Google Scholar]
- Lindsay, A.C.; Kilmartin, P.A.; Organic, J.S.J.; Sperry, J. Synthesis of 3-nitroindoles by sequential paired electrolysis. Org. Biomol. Chem. 2021, 19, 7903–7913. [Google Scholar] [CrossRef]
Entry | Acid | Amount (eq.) of Acid | Solvent (μ/10−30C·m) b | Yield c (%) of 3a |
1 | -- | -- | i-PrOH (5.63) | <5 |
2 | Concd. HCl (37%) | 5 | -//- | 31 |
3 | Concd. HNO3 (70%) | 5 | -//- | 83 |
4 | Concd. H2SO4 (98%) | 5 | -//- | 87 |
5 | TFA | 5 | -//- | <5 |
6 | H3PO4 (85%) | 5 | -//- | <5 |
7 | Fluoroboric acid | 5 | -//- | 33 |
8 | MsOH | 5 | -//- | 60 |
9 | p-TsOH | 5 | -//- | 67 |
10 | -//- | 5 | ACN (10.68) | 90 |
11 | -//- | 5 | DMF (7.10) | <5 |
12 | -//- | 5 | DMSO (14.00) | <5 |
13 | -//- | 5 | H2O (6.24) | <5 |
Entry a | Series | Products | Yields b |
1 | 5a | 86% | |
2 | 5b | 87% | |
3 | 5c | 85% | |
4 | 5d | 85% | |
5 | 5e | 89% | |
6 | 5f | 69% |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yang, C.; Hu, S.; Pan, X.; Yang, K.; Zhang, K.; Liu, Q.; Xin, X.; Li, J.; Wang, J.; Yang, X. Novel Synthesis of Dihydroisoxazoles by p-TsOH-Participated 1,3-Dipolar Cycloaddition of Dipolarophiles withα-Nitroketones. Molecules 2023, 28, 2565. https://doi.org/10.3390/molecules28062565
Yang C, Hu S, Pan X, Yang K, Zhang K, Liu Q, Xin X, Li J, Wang J, Yang X. Novel Synthesis of Dihydroisoxazoles by p-TsOH-Participated 1,3-Dipolar Cycloaddition of Dipolarophiles withα-Nitroketones. Molecules. 2023; 28(6):2565. https://doi.org/10.3390/molecules28062565
Chicago/Turabian StyleYang, Caiyun, Sirou Hu, Xinhui Pan, Ke Yang, Ke Zhang, Qingguang Liu, Xiaobing Xin, Jie Li, Jinhui Wang, and Xiaoda Yang. 2023. "Novel Synthesis of Dihydroisoxazoles by p-TsOH-Participated 1,3-Dipolar Cycloaddition of Dipolarophiles withα-Nitroketones" Molecules 28, no. 6: 2565. https://doi.org/10.3390/molecules28062565