Login Register Cart 0
Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Efficient Monoalkylation of Anilines with Chalcones using Microwave-Assisted aza-Michael Addition

Author(s): Hirokazu Iida*, Mitsuki Okawa, Siriwat Leeanansaksiri and Kie Takahashi

Volume 19, Issue 8, 2022

Published on: 24 March, 2022

Page: [608 - 615] Pages: 8

DOI: 10.2174/1570178619666220128142833

Price: $65

Abstract

The aza-Michael addition is an attractive methodology for synthetic organic chemistry because the resulting β-aminocarbonyl compounds are valuable building blocks for the synthesis of pharmaceutically useful compounds. However, monoalkylation of aniline and its derivatives is quite difficult because anilines are poor nucleophiles compared to monoalkylated ones. Since the publication of pioneering articles in 1986, the development of microwave-assisted organic synthesis has been remarkable. Therefore, we began by investigating the monoalkylation of aniline and its derivatives under microwave irradiation. Because of the ready formation of bisalkylated products, the monoalkylation reaction between anilines and Michael acceptors is quite difficult. To overcome the difficulty, we investigated the effect of microwave irradiation for the alkylation of anilines with chalcones as Michael acceptors. Microwave-assisted aza-Michael addition proceeded smoothly to obtain mainly the monoalkylated Michael adduct. The substitution effects of both chalcone and aniline concerning the yield were also studied. We supposed that dimer formation by two monoalkylated compounds produces a bulky environment around the amino group, which prevents monoalkylated compounds from undergoing a second alkylation. We confirmed a highly efficient and rapid method for preparing monoalkylated anilines using microwave-assisted aza-Michael addition between anilines and chalcones.

Keywords: aza-Michael addition, microwave irradiation, monoalkylation, β-aminocarbonyl compounds, aniline, chalcone.

« Previous Next »
Graphical Abstract

[1]
de Boer, T. Multicomponent reactions under microwave irradiation conditions; Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim: Germany, 2006, pp. 788-819.
[2]
Yang, H-M.; Li, L.; Li, F.; Jiang, K-Z.; Shang, J-Y.; Lai, G-Q.; Xu, L-W. Org. Lett., 2011, 13(24), 6508-6511.
[http://dx.doi.org/10.1021/ol202803b] [PMID: 22087568]
[3]
Bosica, G.; Spiteri, J.; Borg, C. Tetrahedron, 2014, 70(14), 2449-2454.
[http://dx.doi.org/10.1016/j.tet.2014.02.021]
[4]
Polshettiwar, V.; Varma, R.S. Acc. Chem. Res., 2008, 41(5), 629-639.
[http://dx.doi.org/10.1021/ar700238s] [PMID: 18419142]
[5]
Nikoorazm, M.; Khanmoradi, M.; Mohammadi, M. Appl. Organomet. Chem., 2020, 34(4), e5504.
[http://dx.doi.org/10.1002/aoc.5504]
[6]
Hussain-Khil, N.; Ghorbani-Choghamarani, A.; Mohammadi, M. Sci. Rep., 2021, 11(1), 15657.
[http://dx.doi.org/10.1038/s41598-021-94846-6] [PMID: 34341402]
[7]
Nikoorazm, M.; Mohammadi, M.; Khanmoradi, M. Appl. Organomet. Chem., 2020, 34(8), e5704.
[http://dx.doi.org/10.1002/aoc.5704]
[8]
Mohammadi, M.; Khodamorady, M.; Tahmasbi, B.; Bahrami, K.; Ghorbani-Choghamarani, A. J. Ind. Eng. Chem. (Amsterdam, Neth.), 2021, 97, 1-78.
[9]
Ghorbani-Choghamarani, A.; Mohammadi, M.; Tamoradi, T.; Ghadermazi, M. Polyhedron, 2019, 158, 25-35.
[http://dx.doi.org/10.1016/j.poly.2018.10.054]
[10]
Paira, M.; Mandal, S.K.; Roy, S.C. Tetrahedron Lett., 2008, 49(15), 2432-2434.
[http://dx.doi.org/10.1016/j.tetlet.2008.02.054]
[11]
Scettri, A.; Massa, A.; Palombi, L.; Villano, R.; Acocella, M.R. Tetrahedron Asymmetry, 2008, 19(18), 2149-2152.
[http://dx.doi.org/10.1016/j.tetasy.2008.09.006]
[12]
Mansour, E.S.M.E.; El-Sadany, S.K.; Kassem, A.A.; Maksoud, H.A. J. Chem. Eng. Data, 1989, 34(3), 368-370.
[http://dx.doi.org/10.1021/je00057a030]
[13]
Jenner, G. Tetrahedron Lett., 1995, 36(2), 233-236.
[http://dx.doi.org/10.1016/0040-4039(94)02215-W]
[14]
Kobayashi, S.; Kakumoto, K.; Sugiura, M. Org. Lett., 2002, 4(8), 1319-1322.
[http://dx.doi.org/10.1021/ol0256163] [PMID: 11950352]
[15]
Reboule, I.; Gil, R.; Collin, J. Tetrahedron Lett., 2005, 46(45), 7761-7764.
[http://dx.doi.org/10.1016/j.tetlet.2005.09.039]
[16]
Shaikh, N.S.; Deshpande, V.H.; Bedekar, A.V. Tetrahedron, 2001, 57(43), 9045-9048.
[http://dx.doi.org/10.1016/S0040-4020(01)00911-5]
[17]
Yuvaraj, P.; Kathirvelan, D.; Reddy, B.S.R. Sect. B: Org. Chem. Incl. Med. Chem., 2015, 54B(6), 825-828.
[18]
Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, J. Tetrahedron Lett., 1986, 27(3), 279.
[http://dx.doi.org/10.1016/S0040-4039(00)83996-9]
[19]
Giguere, R.J.; Bray, T.L.; Duncan, S.M.; Majetich, G. Tetrahedron Lett., 1986, 27(41), 4945.
[http://dx.doi.org/10.1016/S0040-4039(00)85103-5]
[20]
de la Hoz, A.; Loupy, A., Eds.; Microwaves in Organic Synthesis, Third Edition; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany. 2012, 1.
[21]
de la Hoz, A.; Loupy, A., Eds.; Microwaves in Organic Synthesis, Third Edition; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany. 2012, 2.
[22]
Leadbeater, N.E. Adv. Polym. Sci., 2016, 274, 1-44.
[23]
Verma, P.; Samanta, S.K. Environ. Chem. Lett., 2018, 16(3), 969-1007.
[http://dx.doi.org/10.1007/s10311-018-0739-2]
[24]
Elgemeie, G.H.; Mohamed, R.A. J. Carbohydr. Chem., 2019, 38(1), 20-66.
[http://dx.doi.org/10.1080/07328303.2018.1543430]
[25]
Stefane, B. Microwave-Assisted Cu-Catalyzed Organic Reactions, Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany. 2020, p. 119.
[26]
Soni, J.P.; Chemitikanti, K.S.; Joshi, S.V.; Shankaraiah, N. Org. Biomol. Chem., 2020, 18(48), 9737-9761.
[http://dx.doi.org/10.1039/D0OB01779E] [PMID: 33211792]
[27]
Salih, K.S.M.; Baqi, Y. Catalysts, 2020, 10(1), 4.
[http://dx.doi.org/10.3390/catal10010004]
[28]
Meera, G.; Rohit, K.R.; Saranya, S.; Anilkumar, G. RSC Advances, 2020, 10(59), 36031-36041.
[http://dx.doi.org/10.1039/D0RA05150K]
[29]
Díaz de Greñu, B.; Torres, J.; García-González, J.; Muñoz-Pina, S.; de Los Reyes, R.; Costero, A.M.; Amorós, P.; Ros-Lis, J.V. ChemSusChem, 2021, 14(1), 208-233.
[http://dx.doi.org/10.1002/cssc.202001865] [PMID: 32871058]
[30]
Matsumoto, K.; Hashimoto, S.; Uchida, T.; Iida, H.; Otani, S. Chem. Express, 1993, 8(7), 475-478.
[31]
Matsumoto, K.; Uchida, T.; Hashimoto, S.; Yonezawa, Y.; Iida, H.; Kakehi, A.; Otani, S. Heterocycles, 1993, 36(10), 2215-2219.
[http://dx.doi.org/10.3987/COM-93-6451]
[32]
Matsumoto, K.; Fukuyama, K.; Iida, H.; Toda, M.; Lown, J.W. Heterocycles, 1995, 41(2), 237-244.
[http://dx.doi.org/10.3987/COM-94-6952]
[33]
Matsumoto, K.; Okuno, S.; Iida, H.; Lown, J.W. Heterocycles, 1995, 40(2), 521-524.
[http://dx.doi.org/10.3987/COM-94-S74]
[34]
Choi, M.C.K.; Chan, S-s.; Chan, M-k.; Kim, J.C.; Iida, H.; Matsumoto, K. Heterocycles, 2004, 62, 643-653.
[http://dx.doi.org/10.3987/COM-03-S(P)58]
[35]
Kumamoto, K.; Iida, H.; Hamana, H.; Kotsuki, H.; Matsumoto, K. Heterocycles, 2005, 66, 675-681.
[http://dx.doi.org/10.3987/COM-05-S(K)69]
[36]
Matsumoto, K.; Hamana, H.; Iida, H. Helv. Chim. Acta, 2005, 88(8), 2033-2234.
[http://dx.doi.org/10.1002/hlca.200590156]
[37]
Matsumoto, K.; Kim, J.C.; Iida, H.; Hamana, H.; Kumamoto, K.; Kotsuki, H.; Jenner, G. Helv. Chim. Acta, 2005, 88(7), 1734-1753.
[http://dx.doi.org/10.1002/hlca.200590136]
[38]
Matsumoto, K.; Ikemi, Y.; Suda, M.; Iida, H.; Hamana, H. Heterocycles, 2007, 72, 187-190.
[http://dx.doi.org/10.3987/COM-06-S(K)51]
[39]
Matsumoto, K.; Joho, K.; Mimori, S.; Iida, H.; Hamana, H.; Kakehi, A. Heterocycles, 2008, 76(2), 1061-1067.
[http://dx.doi.org/10.3987/COM-08-S(N)111]
[40]
Iida, H.; Hamana, H.; Matsumoto, K. Synth. Commun., 2007, 37(11), 1801-1805.
[http://dx.doi.org/10.1080/00397910701316185]
[41]
Iida, H.; Moromizato, T.; Hamana, H.; Matsumoto, K. Tetrahedron Lett., 2007, 48(11), 2037-2039.
[http://dx.doi.org/10.1016/j.tetlet.2006.12.145]
[42]
Iida, H.; Suda, M.; Nakajima, E.; Hakamatsuka, H.; Nagashima, Y.; Joho, K.; Amemiya, K.; Moromizato, T.; Matsumoto, K.; Murakami, Y.; Hamana, H. Heterocycles, 2010, 81(9), 2057-2062.
[http://dx.doi.org/10.3987/COM-10-12006]
[43]
Iida, H.; Akatsu, Y.; Mizukami, K.; Natori, S.; Matsukawa, M.; Takahashi, K. Synth. Commun., 2016, 46(7), 581-585.
[http://dx.doi.org/10.1080/00397911.2016.1155714]
[44]
Jafari, A.A.; Moradgholi, F.; Tamaddon, F. Eur. J. Org. Chem., 2009, (8), 1249-1255.
[http://dx.doi.org/10.1002/ejoc.200801037]
[45]
Zeng, H.; Li, H.; Shao, H. Ultrason. Sonochem., 2009, 16(6), 758-762.
[http://dx.doi.org/10.1016/j.ultsonch.2009.03.008] [PMID: 19394889]
[46]
Li, H.; Zeng, H-y.; Shao, H-w. Tetrahedron Lett., 2009, 50(49), 6858-6860.
[http://dx.doi.org/10.1016/j.tetlet.2009.09.131]
[47]
Kozlov, N.G.; Basalaeva, L.I. Russ. J. Gen. Chem., 2004, 74(6), 926-932.
[http://dx.doi.org/10.1023/B:RUGC.0000042429.06729.93]
[48]
Ollevier, T.; Nadeau, E. J. Org. Chem., 2004, 69(26), 9292-9295.
[http://dx.doi.org/10.1021/jo048617c] [PMID: 15609969]

Rights & Permissions Print Cite
Article Metrics
23
1
© 2025 Bentham Science Publishers | Privacy Policy