• Svetlana A. Konovalova Донбаська державна машинобудівна академія
  • Anatoly P. Avdeenko Донбаська державна машинобудівна академія
  • Igor Yu. Yakimenko ДВНЗ «Український державний хіміко-технологічний університет»



benzamide, quinone imine, hydrochlorination, hydrobromination, thiocyanate addition, bioactivity, thiocyanate, addition of hydrogen halides.


N-{3-[(Aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamides have been synthesized by the reaction of the corresponding N-(4-oxocyclohexa-2,5-diene-1-ylidene)arylsulfonamides with N-chloramides with a ratio of reagents 1:2 in a solution of propan-2-one in the presence of triethylamine. The products of addition of hydrogen halides with the entry of halogen atoms in position 4 or 5 of the quinoid ring have been obtained as a result of hydrochlorination and hydrobromination of N-{3-[(aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-diene-1-yl}benzamides. The possibility of hydrohalogenation and thiocyanation of these benzamides is determined by a steric factor. The presence of bulk substituents in the quinoid ring does not allow the introduction of a halogen atom in the 2 position of the quinoid ring. The product of aromatization of the quinoid cycle, N-{2-hydroxy-3,4-dimethyl-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}-4-methylbenzamide, was only obtained as a result of the action of hydrogen halides on 4-methyl-N-{4,5-dimethyl-3-[(4-methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamide. The thiocyanate ion addition product was obtained only for 4-chloro-N-{4-methyl-3-[(4-methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamide, which has a free ortho-position relative to the carbonyl carbon of the quinoid ring. The activities Insulysin inhibitor, CTGF expression inhibitor, Glutamyl endopeptidase II inhibitor, Transcription factor STAT3 inhibitor are possible for the products of hydrohalogenation and thiocyanation of N-{3-[(aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamides.

Author Biographies

Svetlana A. Konovalova, Донбаська державна машинобудівна академія

Доцент кафедри хімії і охорони праці

Anatoly P. Avdeenko, Донбаська державна машинобудівна академія

Завідуючий кафедрою хімії і охорони праці

Igor Yu. Yakimenko, ДВНЗ «Український державний хіміко-технологічний університет»

Викладач кафедри фармації та технології органічних речовин


Hernandes, M.Z., Cavalcanti, S.M.T., Moreira, D.R.M., de Azevedo, W.F., Junior, Leite, A.C.L. (2010). Halogen atoms in the modern medicinal chemistry: hints for the drug design Curr. Drug Targets., 11(3), 303–314.

Gribble G.W. (2004). Natural Organohalogens: A New Frontier for Medicinal Agents? J. Chem. Educ., 81(10), 1441–1449.

Huang, C.-H., Ren, F.-R., Shan, G.-Q., Qin, H., Mao, L., Zhu, B.-Z. (2015). Molecular Mechanism of Metal-Independent Decomposition of Organic Hydroperoxides by Halogenated Quinoid Carcinogens and the Potential Biological Implications. Chem. Res. Toxicol., 28(5), 831–837.

Avdeenko, A. P., Konovalova, S. A. (2018). [Quinone imines: from anti-cancer drugs to molecular computers: monograph]. Kramatorsk, Ukraine: DSEA. ISBN 978-617-7415-40-3; 978-966-379-835-6. (In Russian)

Konovalova, S., Avdeenko, A. (2020) Biological Activity of Halogen-Containing Derivatives of N-Substituted Quinone Imines. Biointerface Res. Appl. Chem., 10(6), 7070–7076.

Dmitrikova, L. V., Kopteva, S. D., Markov, V. I. (2016). N-Alkylation of sulfonamides by alkyl halides in the presence of electrophilic catalysts and transformations of alkylated compounds. Bulletin of Dnipropetrovsk University. Series Chemistry., 24(2), 73–80.

Avdeenko, A. P., Konovalova, S. A. (2006). Halogenation of N-substituted para-quinone monoimine and para-quinone monooxime esters: V. Chlorination and bromination of N-arylsulfonyl-1,4-benzoquinone monoimines dialkyl-substituted in the quinoid ring. Russ. J. Org. Chem., 42(5), 669–682.

Wang, Y. Zhu, S. Zou, L.‐H. (2019). Recent Advances in Direct Functionalization of Quinones. Eur. J. Org. Chem., 2019(12), 2179–2201.

Konovalova, S.A., Avdeenko, A.P., Lysenko, E.N. (2017). Synthesis of halogen derivatives of N-carbamoyl-1,4-benzoquinone monoimines. Voprosy Khimii i Khimicheskoi Tekhnologii, (4), 21–27.

Konovalova, S.A., Avdeenko, A.P., Dʼyakonenko, V.V., Shishkina, S.V. (2020). Synthesis of 1,3-Benzoxathiol-2-one Derivatives from N-(4-Oxocyclohexa-2,5-dien-1-ylidene)ureas. Russ. J. Org. Chem., 56(4), 613–619.

Lee, H. G., Cho, N., Jeong, A. J., Li, Y.-C., Rhie, S.-J., Choi, J. S., Lee, K.-H., Kim, Y., Kim, Y.-N., Kim, M.-H., Pae, A. N., Ye, S.-K., Kim B.-H. (2016). Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice. J. Invest. Dermatol., 136(1), 107–116.

Vellasco, W. T., Gomes, C. R. B., Vasconcelos, T. R. A. (2011). Chemistry and Biological Activities of 1,3-Benzoxathiol-2-ones. Mini-Rev. Org. Chem., 8(1), 103–109.

Mostert S., Petzer A., Petzer J. P. (2016). Mostert S. Inhibition of monoamine oxidase by benzoxathiolone analogues. Bioorg. Med. Chem. Lett., 26(4), 1200–1204.

Chandler, J. D., Day, B. J. (2012). Thiocyanate: a potentially useful therapeutic agent with host defense and antioxidant properties. Biochem. Pharmacol., 84(11), 1381–1387.

Castanheiro, T., Suffert, J., Donnard, M., Gulea, M. (2016). Recent advances in the chemistry of organic thiocyanates. Chem. Soc. Rev., 45(3), 494–505.

Tabong, C. D., Yufanyi, D. M., Paboudam, A. G., Nono, K. N., Eni, D. B., Agwara, M. O. (2016). Synthesis, Crystal Structure, and Antimicrobial Properties of [Diaquabis(hexamethylenetetramine)diisothiocyanato-κN]nickel(II) Complex. Adv. Chem., 2016, Article ID 5049718.

Ito, Y., Touyama, A., Uku, M., Egami, H., Hamashima, Y. (2019). Thiocyanation of Aromatic and Heteroaromatic Compounds with 1-Chloro-1,2-benziodoxol-3-(1H)-one and (Trimethylsilyl)isothiocyanate. Chem. Pharm. Bull., 67(9), 1015-1018.

Bezverhij, N. P., Jakimenko, I. Ju., Harchenko, A. V. (2010). Interaction of N-arylsulfonylquinone imines with O-acylbenzhydroxamic acids. Voprosy Khimii i Khimicheskoi Tekhnologii, (3), 9–12. (in Russian)

Asif, M. (2016). Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry. Mod. Chem. Appl., 4(4), ID article 1000194.

Gao, X.-h., Liu, L.-b., Liu, H.-r., Tang, J.-j., Kang, L., Wu, H., Cui, P., Yan, J. (2018). Structure–activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors. J. Enzyme Inhib. Med. Chem., 33(1), 110–114.

Avdeenko, A. P., Konovalova, S. A., Ludchenko, O. N., Ledeneva, O. P., Vakulenko, A. V. (2011). Hydrohalogenation of N-Acetyl(aroyl)-1,4-benzoquinone Monoimines. Rus. J. Org. Chem., 47(2), 214–229.

Burmistrov, K. S., Toropin, N. V., Burmistrov, S. I. (1993). Reaction of hydrogen bromide with N-aryl-1,4-benzoquinonemonoimines. Rus. J. Org. Chem., 29(6), 1170–1174. (in Russian)

Burmistrov, K. S., Murashevich, B. V., Toropin, N. V. (2011). Unusual addition of hydrogen chloride to N-substituted quinone imines. Russ. J. Org. Chem., 47(1), 140.

Avdeenko, A. P., Konovalova, C. O., Bezverkhyi, M. P. (2013). Ukraine Patent No. 84243. Kyiv, Ukraine. Ukrainian Institute of Industrial Property.

Bron, M., Holze, R. (1995). Cyanate and thiocyanate adsorption at copper and gold electrodes as probed by in situ infrared and surface-enhanced Raman spectroscopy. J. Electroanal. Chem., 385(1), 105-113.

Blankenburg, L., Schroeder, L., Habenstein, F., Błasiak, B., Kottke, T., Bredenbeck, J. (2019). Following local light-induced structure changes and dynamics of the photoreceptor PYP with the thiocyanate IR label. Phys. Chem. Chem. Phys., 21(12), 6622-6634.

Burmistrov, K. S., Toropin, N. V., Burmistrov, S. I., Nichvoloda, V. M. (1992). Interaction of N-(p-tolyl)-1,4-benzoquinone monoimine with thiocyanate acid. Russ. J. Org. Chem., 28(9), 1900–1904. (In Russian)

Huynh, M. T., Anson, C. W., Cavell, A. C., Stahl, S. S., Hammes-Schiffer, S. (2016). Quinone 1 e– and 2 e–/2 H+ Reduction Potentials: Identification and Analysis of Deviations from Systematic Scaling Relationships. J. Am. Chem. Soc., 138(49), 15903–15910.

Filimonov, D. A., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Druzhilovskii, D. S., Pogodin, P. V., Poroikov, V. V. (2014). Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chem. Heterocycl. Compd., 50(3), 444–457.

Bezverhij, N. P., Zinuhov, V. D., Kremlev, M. M., Kachanov, A. V., Litvinova, T. N. (1984). Amidation of N,N'-bis[aryl(alkyl)sulfonyl]benzoquinone diimines. Russ. J. Org. Chem., 20(5), 1040–1045. (in Russian)