Solvent Effects on the [3+2] Cycloaddition of 2-Furfural Oxime and Ethyl Propiolate: Unexpected Change in Regioselectivity

Promi Rahman¹, Amy Glanzer¹, Jaffarguriqbal Singh¹, Nanette M. Wachter¹, Jonathan Rhoad² and Richard W. Denton^3,

¹Department of Chemistry, Hofstra University, Hempstead, United States of America

²Department of Chemistry, Missouri Western State University, St. Joseph, United States of America

³Department of Chemistry, Barnard College, New York, United States of America

Cite this paper:
Promi Rahman, Amy Glanzer, Jaffarguriqbal Singh, Nanette M. Wachter, Jonathan Rhoad and Richard W. Denton. Solvent Effects on the [3+2] Cycloaddition of 2-Furfural Oxime and Ethyl Propiolate: Unexpected Change in Regioselectivity. World Journal of Organic Chemistry. 2017; 5(1):6-10. doi: 10.12691/wjoc-5-1-2

Abstract

The effect of solvents on the 1,3-dipolar cyclization reaction between ethyl propiolate and 2-furfuryl nitrile oxide was studied in various organic solvents. As expected, the major product was ethyl-3-(2-furanyl)-5-carboxylate. The relative ratio of the 3,5- to 3,4- disubstituted isoxazoles in dichloromethane, toluene, ethanol and dimethyl sulfoxide were 3.4, 2.0, 1.9 and 1.5 respectively. Experimental regioselectivity was found to be dissimilar to density functional theory predictions.

Keywords:
13-Dipolar cyclization isoxazole solvent effect regioselectivity density functional theory calculations

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Mao, J: Yuan H., Wang, Y, Wan, B., Pieroni, M, Huang, Q, van Breemen, R. B., Kozikowski, A. P. and Franzblau, S.G., From serendipity to rational antituberculosis drug discovery of mefloquine-isoxazole carboxylic acid esters, J. Med. Chem., 52 (22), 6966-7978, 2009.
[2]	Kohl, M., Thunus, L. and Lejeune, R., Synthesis of 17β-Hydroxy Esters of 4-Estren-17β-ol-3-one and Carbenicillin, Ticarcillin, or Functionalized Oxacillin: Potentially Useful Conjugates for β-Lactamase-Based Homogeneous Immunoassays, Bioconjugate Chem., 8 (5), 772-779, 1997.
[3]	Neelarapu, R., Holzle, D. L., Velaparthi, S., Bai, H., Brunsteiner, M., Blond, S. Y. and Petukhov, P. A., Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole-and pyrazole-based histone deacetylase probes. J. Med. Chem., 54 (13), 4350-4364, 2011.
[4]	Dong, K., Qin, H., Bao, X., Liu, F. and Zhu, C., Oxime-Mediated Facile Access to 5-Methylisoxazoles and Applications in the Synthesis of Valdecoxib and Oxacillin. Organic Lett., 16 (20), 5266-5268, 2014.
[5]	Harris, P. A., King, B. W., Bandyopadhyay, D., Berger, S. B., Campobasso, N., Capriotti, C. A. and Grady, L. C., DNA-encoded library screening identifies benzo [b][1, 4] oxazepin-4-ones as highly potent and monoselective receptor interacting protein 1 kinase inhibitors J. Med. Chem., 59 (5), 2163-2178, 2016.
[6]	Kalwat, M. A., Huang, Z., Wichaidit, C., McGlynn, K., Earnest, V., Savoia, C., Dioum, E. M., Schneider, J. W., Michele R. and Cobb, M. H. Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells, ACS Chem. Bio., 11 (4), 1128-1136, 2016.
[7]	Manning, J. R. and Davies, H. M. One-pot synthesis of highly functionalized pyridines via a rhodium carbenoid induced ring expansion of isoxazoles. J. Am. Chem., 130 (27), 8602-8603, 2008.
[8]	Caplan, J. F., Zheng, R., Blanchard, J. S. and Vederas, J C., Vinylogous amide analogues of diaminopimelic acid (DAP) as inhibitors of enzymes involved in bacterial lysine biosynthesis Organic lett., 2 (24), 3857-3860, 2000.
[9]	Guo, S., Song, Y., Huang, Q., Yuan, H., Wan, B., Wang,Y., He, R., Beconi, M. G., Franzblau, S. G. and Kozikowski, A. P., Identification, synthesis, and pharmacological evaluation of tetrahydroindazole based ligands as novel antituberculosis agents J. Med. Chem., 53(2), 649-659, 2010.
[10]	Vicentini C. B., Romagnoli, C., Andreotti, E. and Mares, D., Synthetic pyrazole derivatives as growth inhibitors of some phytopathogenic fungi. Journal of agricultural and food chemistry, J. Agric. Food Chem., 55(25), 10331-10338, 2007.
[11]	Schmitt, D. C., Lam, L. and Johnson, J. S. Three-component coupling approach to trachyspic acid. Organic Lett., 13 (19), 5136-5139, 2011.
[12]	Kaiser, T. M., Huang, J. and Yang, J., Regiochemistry discoveries in the use of isoxazole as a handle for the rapid construction of an all-carbon macrocyclic precursor in the synthetic studies of celastrol J. Org. Chem., 78 (12), 6297-6302, 2103.
[13]	Pei, Y. and Wickham, B. O. Regioselective syntheses of 3-aminomethyl-5-substituted isoxazoles: A facile and chemoselective reduction of azide to amine by sodium borohydride using 1, 3-propanedithiol as a catalyst. Tetrahedron Lett., 34 (47), 7509-7512, 1993.
[14]	Csimbók, E., Takács, D., Balog, J. A., Egyed, O., May-Nagy, N. V. and Keserű, G. M. The first synthesis of isoxazolo [3, 4-c] pyridine-7-ones. Tetrahedron Lett., 57 (39), 4401-4404, 2016.
[15]	Rao, S. P., Kurumurthy, C., Veeraswamy, B., Poornachandra, Y., Ganesh K. C. and Narsaiah, B. Synthesis of novel 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives and their cytotoxic activity Bioorg. Med. Chem, Lett., 24 (5), 1349-1351. 2014.
[16]	Chalyk, B. A., Kandaurova, I. Y., Hrebeniuk, K. V. , Manoilenko, O. V. , Kulik, I. B., Iminov, R. T., Kubyshkin, V., Tverdokhlebov, A. V., Ablialimov, O. K. and Mykhailiuk, P. K., A base promoted multigram synthesis of aminoisoxazoles: valuable building blocks for drug discovery and peptidomimetics, RSC Adv., 6 (31), 25713-25723, 2016.
[17]	Kankala, S., Kankala, R. K., Gundepaka, P., Thota, N., Nerella, S., Gangula, M. R., Guguloth, H.,Kagga, M., Vadde, R. and Vasam, C. S., Regioselective synthesis of isoxazole–mercaptobenzimidazole hybrids and their in vivo analgesic and anti-inflammatory activity studies, Bioorg. Med. Chem. Lett., 23 (5), 1306-1309, 2013.
[18]	Dorostkar-Ahmadi, N., Bakavoli, M., Moeinpour, F. and Davoodnia, A. Investigation into the regiochemistry of some isoxazoles derived from 1,3-dipolar cycloaddition of 4-nitrobenzonitrile oxide with some dipolarophiles: A combined theoretical and experimental studies, Spectrochim Act A Mol. Biomol. Spectrosc., 79 (5), 1375-1380, 2011.
[19]	Hu, Y. and Houk, K.N. Quantitative predictions of substituent and solvent effects on the regioselectivities of nitrile oxide cycloadditions to electron-deficient alkynes. Tetrahedron, 56 (42), 8239-8243, 2000.
[20]	Himo, F., Lovell, T., Hilgraf, R., Rostovtsev, V. V., Noodleman, L., Sharpless, K. B. and Fokin, V. V., Copper (I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates, J. Am. Chem. Soc., 127 (1), 210-216, 2005.
[21]	Vieira, A. A., Bryk, F. R., Conte, G., Bortoluzzi, A. J. and Gallardo, H. 1, 3-Dipolar cycloaddition reaction applied to synthesis of new unsymmetric liquid crystal compounds-based isoxazole Tetrahedron Lett., 50 (8), 905-908, 2009.
[22]	Paudyal, M. P., Wu, L., Zhang, Z., Spilling, C.D. and Wong, C. F. A new class of salicylic acid derivatives for inhibiting YopH of Yersinia pestis, Bioorg. Med. Chem, 22 (24), 6781-6788, 2014.
[23]	Datta, A., Walia, S. and Parmar, B. S., Some furfural derivatives as nitrification inhibitors, Journal of Agricultural and Food Chemistry, 49 (10), 4726-473, 2001.
[24]	W. M. Haynes ed., "Physical Constants of Organic Compounds," in CRC Handbook of Chemistry and Physics, 97th Edition (Internet Version 2017), CRC Press/Taylor & Francis, Boca Raton, FL.
[25]	Gaussian 09, Revision E.01, Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J. A., Jr., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, J. M., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Orti
[26]	Becke, A.D., Density-functional thermochemistry. The role of exact exchange, J. Chem. Phys., 98 (7) 5648-5652, 1993.
[27]	Lee, C., Yang, W. and Parr, R.G, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B, 37(2) 785-789, 1988.
[28]	Vosko, S.H., Wilk, L. and Nusair, M. Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis, Can. J. Phys., 58 (8), 1200-1211, 1980.
[29]	Stephens, P.J., Devlin, F.J., Chabalowski, C.F. and Frisch, M. J. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields., J. Phys. Chem., 98 (45), 11623-11627, 1994.
[30]	Krishnan, R., Binkley, J. S., Seeger, R. and Pople, J. A. Self-consistent molecular orbital methods. XX. A basis set for correlated wave functions, J. Chem. Phys., 72 (1), 650-654, 1980.
[31]	Benchouk, W., Mekelleche, S. M., Silvi, B., Aurell, M.J. and Domingo, L.R., Understanding the kinetics solvent effects on the 1,3-dipolar cycloaddition of benzonitrile N-oxide: a DFT study, J. Phys. Org. Chem. 24(7), 611-618, 2011.