Microwave Radiation Applied in the N-Aryl-N′-Aminoеthylureas

Authors: Kalistratova A.V., Oshchepkov M.S., Ivanova M.S., Kovalenko L.V., Boldyrev V.S. Published: 04.11.2021
Published in issue: #5(98)/2021  
DOI: 10.18698/1812-3368-2021-5-125-141

Category: Chemistry | Chapter: Organic Chemistry  
Keywords: aryl substituted ureas, microwave radiation, aryl isocyanates, oxalates, oxamates, oxamides, carbamoyl imidazoles

The paper considers methods for the N-aryl-N'-aminoethylureas synthesis. The methods can be used as base products for the preparation of potential cytokinin active compounds with oxamate and oxamide functional groups. The previous studies showed that upon the interaction between aryl isocyanates and ethylenediamine, symmetric bisureas become the main reaction products, while the yield of the target 2-aminoethylureas is no more than 10 %. The high yield of N-aryl-N'-(oxamoylamino)ethylurea is also not provided by using one group aminoprotected ethylenediamine. Thus, when using Boc-protection, the yield of target products does not exceed 13 %. In this research, we used the methodology of microwave synthesis in acylation and aminolysis reactions. As a result, N-2-aminoethyl-N'-arylureas with various substituents in the aromatic ring were obtained in good yields. We compared the microwave radiation aminolysis of N,N'-bis(arylcarbamoyl)ethylenediamines, N-aryl-carbamoylimidazoles and diarylureas with ethylenediamine under microwave conditions. Findings of research show that reactions without microwaves proceed with the formation of only trace amounts of the target compounds, which are used for synthesis of structural analogs of phytoactive compounds, in the molecules of which carbamate and urea groups are replaced by oxamate ones

This work is supported by grants from the Russian Foundation for Basic Research (RFBR project no. 19-03-00492)


[1] Kochetkov K.A., Kovalenko L.V., Kalistratova A.V., et al. N-alkoksikarbonila-minoetil-N′-arilmocheviny, proyavlyayushchie rost-reguliruyushchuyu aktivnost’ [N-alcoxycarbonylaminoethyl-N′-aryl-urea showing growth-regulating activity]. Patent RU 2632466. Appl. 07.10.2016, publ. 05.10.2017 (in Russ.).

[2] Sheshenev A.E., Boltukhina E.V., Chernyshev V.P., et al. Sposob polucheniya regulyatora rosta rasteniy N-(izopropoksikarbonil)-O-(4-khlorfenilkarbamoil)etanolamina [Method of producing a plant growth regulator of N-(isopropoxycarbonyl)-O-(4-chlorophenylcarbamoyl)ethanolamine]. Patent RU 2711231. Appl. 20.08.2019, publ. 15.01.2020 (in Russ.).

[3] Oshchepkov M.S., Kalistratova A.V., Savelieva E.M., et al. Natural and synthetic cytokinins and their applications in biotechnology, agrochemistry and medicine. Russ. Chem. Rev., 2020, vol. 89, no. 8, pp. 787--810. DOI: https://doi.org/10.1070/RCR4921

[4] Kalistratova A.V., Kovalenko L.V., Oshchepkov M.S., et al. Biological activity of the novel plant growth regulators: N-alkoxycarbonylaminoethyl-N′-arylureas. Bulg. J. Agric. Sci., 2020, vol. 26, no. 4, pp. 772--776.

[5] Lomin S.N., Krivosheev D.M., Steklov M.Y., et al. Receptor properties and features of cytokinin signaling. Acta Naturae, 2012, vol. 4, no. 3, pp. 31--45.

[6] Davies P.J. The plant hormones: their nature, occurrence, and functions. In: Davies P.J. (eds). Plant Hormones. Dordrecht, Springer, 2010, pp. 1--15. DOI: https://doi.org/10.1007/978-1-4020-2686-7_1

[7] Khan N.A., Nazar R., Iqbal N., et al. (eds). Phytohormones and abiotic stress tolerance in plants. Berlin, Heidelberg, Springer, 2012. DOI: https://doi.org/10.1007/978-3-642-25829-9

[8] Kalistratova A.V., Kovalenko L.V., Oshchepkov M.S., et al. Synthesis of new compounds in the series of aryl-substituted ureas with cytotoxic and antioxidant activity. Mendeleev Commun., 2020, vol. 30, iss. 2, pp. 153--155. DOI: https://doi.org/10.1016/j.mencom.2020.03.007

[9] Lipinski C.A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol., 2004, vol. 1, iss. 4, pp. 337--341. DOI: https://doi.org/10.1016/j.ddtec.2004.11.007

[10] Petyunin P.A., Choudry A.M. Synthesis of benzimidazole-2-carboxylic acid amides from o-phenylenediamine and oxamic acid esters. Chem. Heterocycl. Compd., 1982, vol. 18, no. 5, pp. 519--521. DOI: https://doi.org/10.1007/BF00526091

[11] Gajeles G., Lee S.H. Imidazole derivatives as thermal latent catalyst for thiol-Michael reaction thermosetting resins. Eur. Polym. J., 2019, vol. 120, art. 109240. DOI: https://doi.org/10.1016/j.eurpolymj.2019.109240

[12] Perveen S., Fatima N., Khan M.A., et al. Antidepressant activity of carbamates and urea derivatives. Med. Chem. Res., 2012, vol. 21, no. 9, pp. 2709--2715. DOI: https://doi.org/10.1007/s00044-011-9797-8

[13] Padiya K.J., Gavade S., Kardile B., et al. Unprecedented "in water" imidazole carbonylation: paradigm shift for preparation of urea and carbamate. Org. Lett., 2012, vol. 14, iss. 11, pp. 2814--2817. DOI: https://doi.org/10.1021/ol301009d

[14] Wang T.C., Qiao J.X. Microwave-assisted transamidation of ureas. Tetrahedron Letters, 2016, vol. 57, iss. 18, pp. 1941--1943. DOI: https://doi.org/10.1016/j.tetlet.2016.02.103

[15] Kovalenko L.V., Kochetkov K.A., Oshchepkov M.S., et al. Oxalylamino substituted O-ethyl-N-aryl carbamates and Р-N-ethyl-N′-aryl ureas, encapsulated in micelles copolymer of vinylcaprolactam and vinylimidazole. Doklady Akademii nauk, 2017, vol. 473, no. 6, pp. 669--672 (in Russ.). DOI: https://doi.org/10.7868/S086956521712009X