The synthesis of N-[4-methyl(41-chlorophenyl)-2-R-phenylіmіnothіazol-3-yl]-morpholine derivatives by Hantzsch reaction

L. O. Perekhoda, H. O. Yeromina, I. V. Drapak, I. A. Sych, A. M. Demchenko, S. O. Komykhov

Abstract


Continuing the search for biologically active substances among 2-R-phenylіmіnothіazole derivatives a new series of N-[4-methyl(41-chlorophenyl)-2-R-phenylіmіnothіazol-3-yl]-morpholine derivatives has been synthesized by Hantzsch reaction. Hydrochlorides of N-[4-methyl-2-R-phenylіmіnothіazol-3-yl]-morpholine 3 and hydrobromides of N-[4-(41-chlorophenyl)-2-R-phenylіmіnothіazol-3-yl]-morpholine 5 were obtained by boiling the equimolar amounts of asymmetric thioureas 1 with α-chloroacetone 2 and α-bromo-4-chloroacetophenone 4, respectively, in the ethanol medium. N-[4-(41-Chlorophenyl)-2-R-phenylіmіnothіazol-3-yl]-morpholine 6 were obtained by neutralizing compounds 5 using 10% NH4OH solution. Satisfactory yields of compounds 3, 5, 6 were obtained within 1-3 hours. N-[4-methyl(41-chlorophenyl)-2-R-phenylіmіnothіazol-3-yl]-morpholine derivatives 3, 5, 6 were crystallized from organic solvents and obtained with the yields of 74-87%. The structures and purity of 3, 5, 6 have been confirmed by elemental analysis, 1H NMR-spectra and chromato-mass spectroscopy. As a result of Hantzsch reaction formation of two isomeric structures is possible. Therefore, to determine a true structure of the compounds obtained NMR spectroscopy with its special techniques was used. The studies have been conducted on the example of the reaction product 6i, and it has been proven that this structure is exactly N-[4-(41chlorophenyl)-2-(4’-chlorophenylimino)thiazol-3-yl]-morpholine 6i. Based on the research results of the structure of the compounds synthesized a possible mechanism of the reaction studied has been proposed.

Keywords


2-R-phenyliminothiazole derivatives; synthesis; Hantzsch reaction; physical and chemical properties

References


Vovk M. V. Vіsn. NAN Ukraini, 2015, No.3, рр.38-43.

Demchenko S. A., Jadlovs’kij O. Ye., Bobkova L. S., Buhtіarova T. A. Farm. zhurn. – Pharm. journal, 2012, No.3, pp.49-54.

Chupahin O. N., Sidorova L. P., Perova N. M., Rusinov V. L., Makarov V. A., Logvinova Ju. S., Vasil’eva T. M. Patent 2456284 Rossijskaja Federacija, MPK C 07 D 417/12 A 61 K 31/549 A 61 K 31/5377 A 61 K 31/427 A 61 P 7/02, 2012, Bjul. No.20.

El-Wahaba H. A., El-Fattahb M. A., El-Khalikc N. A., Nassara H.S., Abdelall M. M. Progress in Organic Coatings, 2014, Vol. 77, Is. 9, pp.1506-1511.

Mohort M. A., Pupisheva O. V. Dosiagnennja bіologіi ta medicini — The achievements of biology and medicine, 2011, No.2(18), pp.7-10.

Yeromina H. O., Drapak I. V., Perekhoda L. O., Yaremenko V. D., Demchenko A. M. Der Pharma Chemica, 2016, Vol. 8, Is. 3, pp.64-70.

Demchenko A. M., Yanchenko V. A., Kisly V. V., Lozinskii M. S. Chemistry of Heterocyclic Compounds, 2005, Vol. 41, No.5, pp.668-672.

Chidan K., Chong K., SiauHui M., TzeShyang C., Wan-Sin L., ChingKheng Q. Molecules, 2015, Vol. 20, Is. 10, pp.18827-18846.


GOST Style Citations






DOI: https://doi.org/10.24959/ophcj.16.890

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)