Synthesis, Characterization and Antibacterial Screening of 3-Hydroxy-2-[3-(2/3/4-Methoxybenzoyl)Thioureido]Butyric Acid
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 δH 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 δC 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.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.3607735Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 750
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 A. Yahyazadeh, Z. Ghasemi, “Synthesis of unsymmetrical thiourea derivatives,” European Chemical Bulletin, vol. 2, no. 8, pp. 573-575, Apr. 2013.
 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.
 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.
 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.
 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.
 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.
 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.
 G. Wu. “Amino acids, biochemistry and nutrition,” CRC Press, 2010.
 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.
 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.
 R. M. Silverstein, F. X. Webster, D. J. Kiemle, “Spectrometric Identification of Organic Compounds,” 7th Edition. New York: John Wiley & Sons, Inc. 2005.
 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.
 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.
 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.
 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.
 S. Kumar, “Spectroscopy of organic compounds,” 2006.
 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.
 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.