We herein report our studies into the effects of microwave irradiation on the solvent-free esterification of L-leucine with alcohols. In the absence of solvent, microwave irradiation accelerated the reaction compared to conventional oil bath heating. Measurement of the dielectric properties under the reaction conditions revealed that the high dielectric loss factor of the reaction mixture containing L-leucine, n-butanol, and a p-toluene sulfonic acid catalyst could be attributed to the acceleration of the reaction. The depth of microwave penetration into the reaction mixture as derived from the in-situ measurement of the dielectric properties was ~13 mm, which suggested that a thinner reaction vessel was favorable for the esterification of L-leucine. In addition to the batch reaction using a desktop microwave reactor, two types of flow reaction were also performed using a desktop tubular reactor and a semi-bench-scale tubular reactor. These flow reactions also exhibited high performances, thus allowing the scale-up of this reaction system for industrial use.
References
[1]
Metaxas, A.C. and Meredith, R.J., Eds. (1983) Industrial Microwave Heating. Peter Peregrinus Ltd., London.
[2]
Kappe, C.O., Stadler, A. and Dallinger, D., Eds. (1982) Microwaves in Organic and Medicinal Chemistry. Wiley-VCH, Weinheim.
[3]
de la Hoz, A. and Loupy, A., Eds. (2013) Microwaves in Organic Synthesis, Vols. 1 & 2. Wiley-VCH, Weinheim.
[4]
Bogdal, D. (2009) Microwave-Assisted Organic Synthesis. Elsevier Ltd., Oxford.
[5]
Takeuchi, K. and Wada, Y., Eds. (2013) Microwave-Assisted Chemical Process Technology II. CMC, Tokyo.
[6]
Leadbeater, N.E., Ed. (2010) Microwave Heating as a Tool for Sustainable Chemistry. CRC Press, Boca Raton.
[7]
Polshettiwar, V. and Varma, R., Eds. (2010) Aqueous Microwave Assisted Chemistry. RSC Publishing, Cambridge.
[8]
Nakamura, T., Nagahata, R., Kunii, K., Soga, H., Sugimoto, S. and Takeuchi, K. (2010) Large-Scale Polycondensation of Lactic Acid Using Microwave Batch Reactors. Organic Process Research & Development, 14, 781-786. https://doi.org/10.1021/op900325e
[9]
Schmink, J.R., Kormos, C.M., Devine, W.G. and Leadbeater, N.E. (2010) Exploring the Scope for Scale-Up of Organic Chemistry Using a Large Batch Microwave Reactor. Organic Process Research & Development, 14, 205-214. https://doi.org/10.1021/op900287j
[10]
Morschhäuser, R., Krull, M., Kayser, C., Boberski, C., Bierbaum, R., Pushner, P.A., Glasnov, T.N. and Kappe, C.O. (2012) Microwave-Assisted Continuous Flow Synthesis on Industrial Scale. Green Processing and Synthesis, 1, 281-290. https://doi.org/10.1515/gps-2012-0032
[11]
Patil, N.G., Benaskar, F., Rebrov, E.V., Meuldijk, J., Hulshof, L.A., Hessel, V. and Shouten, J.C. (2014) Scale-Up of Microwave Assisted Flow Synthesis by Transient Processing through Monomode Cavities in Series. Organic Process Research & Development, 18, 1400-1407. https://doi.org/10.1021/op500064k
[12]
Lall, M.S., Ramtohul, Y.K., James, M.N.G. and Vederas, J.C. (2002) Serine and Threonine β-Lactones: A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors. Journal of Organic Chemistry, 67, 1536-1547. https://doi.org/10.1021/jo0109016
[13]
Greenstein, J.P. and Winitz, M. (1961) Chemistry of the Amino Acids. John Wiley & Sons, New York, 763.
[14]
Pollini, G.P., Baricordi, N., Benetti, S., De Risi, C. and Zanirato, V. (2005) A Simple Entry to Chiral Non-Racemic 2-Piperizinone Derivatives. Tetrahedron Letters, 46, 3699-3701. https://doi.org/10.1016/j.tetlet.2005.03.163
[15]
Horiuchi, T., Miura, H., Sumioka, K. and Uchida, S. (2004) High Efficiency of Dye-Sensitized Solar Cells Based on Metal-Free Iodine Dyes. Journal of the American Chemical Society, 126, 12218-12219. https://doi.org/10.1021/ja0488277
[16]
Sanda, F. and Endo, T. (1999) Synthesis and Functions of Polymers based on Amino Acids. Macromolecular Chemistry and Physics, 200, 2651-2661. https://doi.org/10.1002/(SICI)1521-3935(19991201)200:12<2651::AID-MACP2651>3.0.CO;2-P
[17]
Fischer, E. and Speier, A. (1895) Darstellung der Ester. Chemische Berichte, 28, 3252-3258. https://doi.org/10.1002/cber.189502803176
[18]
Curtius, T. and Goebel, F. (1888) Ueber Glycocolläther. Journal für Praktische Chemie, 37, 150-181. https://doi.org/10.1002/prac.18880370113
[19]
Penny, C.L., Shah, P. and Landi, S.A. (1985) A Simple Method for the Synthesis of Long-Chain Alkyl Esters of Amino Acids. Journal of Organic Chemistry, 50, 1457. https://doi.org/10.1021/jo00209a018
[20]
Eelanger, B.F. and Hall, R.M. (1954) Improved Synthesis of Amino Acid Benzyl Esters. Journal of the American Chemical Society, 76, 5781-5782. https://doi.org/10.1021/ja01651a049
[21]
Cipera, J.D. and Nicholls, R.V.V. (1955) Preparation of Benzyl Esters of Amino-Acids. Chemistry & Industry, 1, 16-17.
[22]
Zervas, L., Winitz, M. and Greenstein, J.P. (1957) Studies on Arginine Peptides. I. Intermediates in the Synthesis of N-Terminal and C-Terminal Arginine Peptides. Journal of Organic Chemistry, 22, 1515-1521. https://doi.org/10.1021/jo01362a052
[23]
Ramesh, C.A. and Vimal, A. (1998) A Mild and Convenient Procedure for the Esterification of Amino Acids. Synthetic Communications, 28, 1963-1965. https://doi.org/10.1080/00397919808007170
[24]
Li, J. and Sha, Y. (2008) A Convenient Synthesis of Amino Acid Methyl Esters. Molecules, 13, 1111-1119. https://doi.org/10.3390/molecules13051111
[25]
Yamashiro, D. and Li, C.H. (1973) Adrenocorticotropins. 44. Total Synthesis of the Human Hormone by the Solis-Phase Method. Journal of the American Chemical Society, 95, 1310-1315. https://doi.org/10.1021/ja00785a049
[26]
Patel, R.P. and Price, S. (1965) Synthesis of Benzyl Esters of α-Amino Acids. Journal of Organic Chemistry, 30, 3575-3576. https://doi.org/10.1021/jo01021a513
[27]
Zao, H., Song, Z., Cowins, J.V. and Olubajo, O. (2008) Microwave-Assisted Esterification of Involving Ionic Liquids. International Journal of Molecular Sciences, 9, 33-44. https://doi.org/10.3390/ijms9010033
[28]
Sureshbabu, V.V., Kantharaju and Krishna, G.C. (2007) Microwave Irradiation Accelerated Rapid, Efficient and High Yield Esterification of Boc-Amino Acid to Merrifield Resin Mediated by KF. Indian Journal of Chemistry—Section B, 46, 1466-1469.
[29]
Zhang, S. and Arvidsson, P.I. (2008) Facile Synthesis of N-Protected Amino Acid Esters Assisted by Microwave Irradiation. International Journal of Peptide Research and Therapeutics, 14, 219-222. https://doi.org/10.1007/s10989-008-9134-3
[30]
Cerón-Camacho, R., Burto, J.A., Montiel, L.E., Flores, E.A., Cuellar, F. and Martínez-Palou, R. (2011) Efficient Microwave-Assisted Synthesis of Ionic Esterified Amino Acids. Molecules, 16, 8733-8744. https://doi.org/10.3390/molecules16108733
[31]
Vangala, V.B., Hindupur, R.M. and Pati, H.N. (2014) A Review on Synthesis of Antihypertensive Sartan Drugs. International Journal of Pharmaceutical Sciences Review and Research, 3, 46-56.
[32]
Nakamura, T., Nagahata, R., Suemitsu, S. and Takeuchi, K. (2010) In-Situ Measurement of Microwave Absorption Properties at 2.45 GHz for the Polycondensation of Lactic Acid. Polymer, 51, 329-333. https://doi.org/10.1016/j.polymer.2009.11.036
[33]
Baghurst, D.R. and Mingos, D.M.P. (1992) Superheating Effects Associated with Microwave Dielectric Heating. Journal of the Chemical Society, Chemical Communications, 674-677. https://doi.org/10.1039/c39920000674
[34]
Saillard, R., Poux, M., Berlan, J. and Peaudecerf, M.A. (1995) Microwave Heating of Organic Solvents: Thermal Effects and Field Modelling. Tetrahedron, 51, 4033-4042. https://doi.org/10.1016/0040-4020(95)00144-W
[35]
Schanche, J.-S. (2003) Microwave Synthesis Solution from Personal Chemistry. Molecular Diversity, 7, 293-300. https://doi.org/10.1023/B:MODI.0000006866.38392.f7
[36]
Kappe, C.O. (2004) Controlled Microwave Heating in Modern Organic Synthesis. Angewandte Chemie International Edition, 43, 6250-6284. https://doi.org/10.1002/anie.200400655
