Synthesis, Characterization and Antibacterial Screening of 3-Hydroxy-2-[3-(2/3/4-Methoxybenzoyl)Thioureido]Butyric Acid

Authors: M. S. M. Yusof, R. Ramli, S. K. C. Soh, N. Ismail, N. Ngah

Abstract:

This study presents the synthesis of a series of methoxybenzoylthiourea amino acid derivatives. The compounds were obtained from the reactions between 2/3/4-methoxybenzoyl isothiocyanate with threonine. All of the compounds were characterized via mass spectrometry, ¹H and ¹³C NMR spectrometry, UV-Vis spectrophotometer and FT-IR spectroscopy. Mass spectra for all of the compounds showed the presence of molecular ion [M]⁺ peaks at m/z 312, which are in agreement to the calculated molecular weight. For ¹H NMR spectra, the presence of OCH₃, C=S-NH and C=O-NH protons were observed within range of δ_H 3.8-4.0 ppm, 11.1-11.5 ppm and 10.0-11.5 ppm, respectively. ¹³C NMR spectra in all compounds displayed the presence of OCH₃, C=O-NH, C=O-OH and C=S carbon resonances within range of δ_C 55.0-57.0 ppm, 165.0-168.0 ppm, 170.0-171.0 ppm and 180.0-182.0 ppm, respectively. In UV spectra, two absorption bands have been observed and both were assigned to the n-π* and π-π* transitions. Six vibrational modes of v(N-H), v(O-H), v(C=O-OH), v(C=O-NH), v(C=C) aromatic and v(C=S) appeared in the FT-IR spectra within the range of 3241-3467 cm^-1, 2976-3302 cm^-1, 1720-1768 cm^-1, 1655-1672 cm^-1, 1519-1525 cm^-1 and 754-763 cm^-1, respectively. The antibacterial activity for all of the compounds was screened against Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium and Escherichia coli. However, no activity was observed.

Keywords: Methoxybenzoyl isothiocyanate, amino acid, threonine, antibacterial.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.3607735

References:

[1] W. S. H. W. Zulkiplee, A. N. A. Halim, Z. Ngaini, M. A. M. Ariff, H. Hussain, “Bis-thiourea bearing aryl and amino acids side chains and their antibacterial activities,” Phosphorus Sulfur Silicon Relat. Elem., vol. 189, no. 6, pp. 832-838, Jun. 2014.
[2] G. Binzet, F. M. Emen, U. Flörke, T. Yesilkaynak, N. Külcü, H. Arslan, “4-Chloro-N-(N-(6-methyl-2-pyridyl)-carbamothioyl)benzamide,” Acta Crystallogr. Sect. E. Struct Rep. Online, vol. 65, no. 1, pp. 81-82, Jan. 2009.
[3] S. Jadhav, L. Khillare, M. Rai, A. Durrani, “Synthesis, characterization and antimicrobial activity of substituted arylthiourea,” Rasayan J. Chem., vol. 3, no. 1, pp. 27-31, Jan. 2010.
[4] T. Kimura, T. Eto, D. Takahashi, K. Toshima, “Stereocontrolled photoinduced glycosylation using an aryl thiourea as an organo photoacid,” Org. Lett., vol. 18, no. 13, pp. 3190-3193, Jun. 2016.
[5] H. Marquez, E. R. Perez, A. M. Plutin, M. Morales, A. Loupy, “Synthesis of 1-benzoyl-3-alkylthioureas by transamidation under microwave in dry media,” Tetrahedron Lett., vol. 41, pp. 1753-1756, Mar. 2000.
[6] N. Gunasekaran, S. W. Ng, E. R. T. Tiekink, R. Karvembu, “Hypodentate coordination of N,N-di(alkyl/aryl)-N’-acylthiourea derivatives in Cu(I) complexes,” Polyhedron, vol. 34, pp. 41-45, Feb. 2012.
[7] S. S. Elkholy, H. A. Salem, M. Eweis, M. Z. Elsabee, “Synthesis and characterization of some acyl thiourea derivatives of chitosan and their biocidal activities. Int. J. Bio. Macromol., vol. 70, pp. 199-207, Sep. 2014.
[8] Y. Zhao, C. W. Ge, Z. H. Wu, C. N. Wang, J. H. Fang, L. Zhu, “Synthesis and evaluation of aroylthiourea derivatives of 4-ß-amino-4’-O-demethyl-4-desoxypodophyllotoxin as novel topoisomerase II inhibitors,” Eur. J. Med. Chem., vol. 46, pp. 901-906, Mar. 2011.
[9] H. Y. Yuen, W. Henderson, A. G. Oliver, “Nickel(II) complexes of di- and tri-substituted thiourea mono- and di-anions. Inorg. Chim. Acta, vol. 368, pp. 1-5, Mar. 2011.
[10] P. P. Kumavat, A. D. Jangale, D. R. Patil, K. S. Dalal, J. S. Meshram, D. S. Dalal, “Green synthesis of symmetrical N,N’-disubstituted thiourea derivatives in water using solar energy,” Environ. Chem. Lett., vol. 11, pp. 177-182, Jun. 2013.
[11] P. K. Mohanta, S. Dhar, S. K. Samal, H. Ila, H. Junjappa, “1-(methyldithiocarbonyl)imidazole a useful thiocarbonyl transfer reagent for synthesis of substituted thioureas,” Tetrahedron, vol. 56, pp. 629-639, Jan. 2000.
[12] A. Yahyazadeh, Z. Ghasemi, “Synthesis of unsymmetrical thiourea derivatives,” European Chemical Bulletin, vol. 2, no. 8, pp. 573-575, Apr. 2013.
[13] M. Atis, F. Karipcin, B. Sariboga, M. Tas, H. Celik, “Structural, antimicrobial and computational characterization of 1-benzoyl-3-(5-chloro-2-hydroxyphenyl)thiourea,” Spectrochim. Acta Mol. Biomol. Spectrosc., vol. 98, pp. 290-301, Dec. 2012.
[14] M. M. Zhao, X. Y. Dong, G. Li, Y. H. Yang, Y. J. Zhang, X. Q. Yang, Antituberculosis and antifungal activities of synthesized benzoylthiourea derivatives. Asian J. Chem., vol. 25, no. 13, pp. 7548-7550, Sep. 2013.
[15] A. Saeed, M. S. Khan, H. Rafique, M. Shahid, J. Iqbal, “Design, synthesis, molecular docking studies and in vivo screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors,” Bioorg. Chem., vol. 52, pp. 1-7, Feb. 2014.
[16] D. M. H. Al-Mudhaffar, D. S. Al-Edani, S. M. Dawood, “Synthesis, characterization and biological activity of some complexes of some new amino acid derivatives N-((benzoylamino)-thioxomethyl)-amino acid (HL),” J. Korean Chem. Soc., vol. 54, no. 5, pp. 506-514, Jun. 2010.
[17] M. S. Rathod, S. Z. Jadhao, “Synthesis and structural investigation of nickel metal-ligand (thiourea derivative) complexes,” J. Chem. Pharm. Res., vol. 4, no. 3, pp. 1629-1631, 2012.
[18] C. Li, W. Yang, H. Liu, M. Li, W. Zhou, J. Xie, “Crystal structures and antifungal activities of fluorine-containing thioureido complexes with nickel(II),” Molecules, vol. 18, pp. 15737-15749, Dec. 2013.
[19] G. Wu. “Amino acids, biochemistry and nutrition,” CRC Press, 2010.
[20] N. Ngah, Darman, B. M. Yamin, S. W. Ng, “2-(3-(4-Methoxybenzoyl) thioureido)-3-methylbutyric acid,” Acta Crystallogr. Sect. E. Struct Rep. Online, 62(5):o1903-o1904, May. 2006.
[21] N. I. M. Halim, K. Kassim, A. H. Fadzil, B. M. Yamin, “Synthesis, characterisation and antibacterial studies of 1,2-bis(N’-2,3 and 4-methoxybenzoylthioureido)-4-nitrobenzene,” APCBEE Procedia, vol. 3, pp. 129-133, Dec. 2012.
[22] R. M. Silverstein, F. X. Webster, D. J. Kiemle, “Spectrometric Identification of Organic Compounds,” 7th Edition. New York: John Wiley & Sons, Inc. 2005.
[23] N. Ameram, B. M. Yamin, “Synthesis and characterization o-, m- and para- toluyl thiourea substituted para-pyridine and ethyl pyridine as a chromoionophore,” IOSR Journal of Applied Chemistry, vol. 4, no. 6, pp. 59-67, Jun. 2013.
[24] J. Han, H. Dong, Z. Xu, J. Wang, M. Wang, M. “Synthesis and activity of novel acylthiourea with hydantoin,” Int. J. Mol. Sci., vol. 14, pp. 19526-19539, Sep. 2013.
[25] M. S. M. Yusof, R. H. Jusoh, W. M. Khairul, B. M. Yamin, “Synthesis and characterisation a series of N-(3,4-dichlorophenyl)-N’-(2,3 and 4-methylbenzoyl)thiourea derivatives,” J. Mol. Struct., vol. 975, pp. 280-284, Jun. 2010.
[26] S. A. Zakaria, S. A. Muharam, M. S. M. Yusof, W. M. Khairul, M. A. Kadir, B. M. Yamin, “Spectroscopic and structural study of a series of pivaloylthiourea derivatives,” The Malaysian J. Analytical Sciences, vol. 15, no. 1, pp. 37-45, 2011.
[27] S. Kumar, “Spectroscopy of organic compounds,” 2006.
[28] H. M. Abosadiya, S. E. Ashoor, B. M. Yamin, “Synthesis and x-ray structure study of cis-trans 3-(3-biphenyl carbonylthioureido)propanoic acid(I) and N-(4-biphenyl carbonyl)-N’-(3-hydroxyphenyl)thiourea(II),” Rasayan J. Chem., vol. 2, no. 3, pp. 572-576, Jul. 2009.
[29] F. Odame, E. C. Hosten, R. Betz, K. Lobb, Z. R. Tshentu, “Characterization of some amino acid derivatives of benzoyl isothiocyanate: Crystal structures and theoretical prediction of their reactivity,” J. Mol. Struct., vol. 1099, pp. 38-48, Nov. 2015.