Synthesis and evaluation antimicrobial activity of some new S-substituted Quinazolinone containing pentagonal, hexagonal heterocyclic ring


S. M. H. Al-Majidi & Redhab A.J Alfraij

College of Science, University  of Baghdad 


Abstract:
New 1,2,4-triazine, imidazole ,2-aminothiazole, phthalazine and  oxazoline derivatives of 2-mercapto-3-phenyl-4(3H)-quinazolinone were synthesized via an important intermediate compound(2) In which formed from reaction of compound(1) with chloroacetyl chloeide in dimethylformamide. The following different steps show the details of this work: The first step involves the conversion of compound (2) in to thiosemicarbazide and thiourea derivatives through its reaction with thiosemicarbazide,thiourea respectively to give compounds 3 and 4. Then cyclization of compounds 3 and 4 by using alkaline media 4N NaOH and concentrated H2SO4 to give compounds (5, 6 and 7) respectively. The second step involves treating compound (2) with hydrazine hydrate in dimethylformamide to give compound (8). Then reaction of prepared compound (8) with different aromatic anhydrides in acetic acid as a solvent to gives compounds (9-13). The third step involves preparation of compounds (14, 15 and 16) via reaction of compound (8) with (1-naphthyl isocyanate, phenylisocyanate and phenyl thioisocyanate) respectively in absolute ethanol. Then cyclization of compounds 14, 15 and 16 with alkaline media in the presence of 4N NaOH and p-bromophenacyl bromide to give compounds (17-22) respectively. The fourth step involves reaction of the prepared compound (8) with carbon disulfide in the presence of potassium hydroxide producing compound (23). The obtained salt (23) was treated with hydrazine hydrate to afford the desirable compound (24). The structure of newly synthesized compounds were identified by spectral methods such as FTIR, 1H-NMR, 13C-NMR, some other physical Properties and some specific reactions.

Keywords: quinazolinone  1,2,4-triazine imidazole 2-amino thiazole Phthalazine oxazoline    antimicrobial

References

[1] Ramesh, D., "Synthesis And Characterization of 3-((5-phenyl-1, 3, 4-oxadiazol-2-yl)methyl amino)-2methyl quinazolin-4(3H)-one" Intern. J. Anal. Pharma. And Biomed. Sci., vol.1, pp. 53-58,(2012).

[2] Phucho,T. Nongpiur,A. Tumtin,S. Nongrum,R. Myrboh,B. and Nongkhlaw R. L., "Novel one pot synthesis of substituted 1,2,4-triazines" ARKIVOC , vol.15, pp. 79-87,(2008).

[3] Sztanke, K. Fidecka, S. Kedzierska, E.  Karczmarzyk, Z. Pihlaja, K. and Matosiuk, D., "Antinociceptive activity of new imidazolidine carbonyl derivatives. Part 4. Synthesis and pharmacological activity of 8aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo[2,1-c] [1,2,4]triazines" Eur. J. Med. Chem., vol.40, pp. 127134,(2005).

[4] Saeed-ur-R., Muhammad K., Sadia R., Alia F. and Shahnawaz, "Synthesis, characterization and antimicrobial studies of transition metal complexes of imidazole derivatives" Bull. Chem. Soc. Ethiop., vol.24 (2), pp. 201-207,(2010).

[5] Priya V. F., Girish K. S. and Balakrishna K., "Solvent-free microwave-assisted synthesis of oxadiazoles containing imidazole moiety"  J. Chem. Sci., vol.119, ( 1) , pp. 41–46,(2007).

[6] Eduardo A. Ve´liz and Peter A. Beal,"6-Bromopurine Nucleosides as Reagents for Nucleoside Analogue"Synthesis J. Org. Chem.,vol. 66, pp. 8592-8598,(2001).

[7] Sahar A. Kadem,"Synthesis of New Imidazole Derivative" Mustansiriya J. Sci., vol. 3(17), pp. 50-58,( 2010).

[8] Chorghade, M. S.," In Drug Discovery and Development" John Wiley & Sons: Hoboken, New Jersey, Vol. 2,(2007). Al-Majidi & Alfraiji/ JZS (2015) 17-1 (Part-A)

[9] Lednicer, D. and Mitscher, L. A.,"In The Organic Chemistry of Drug Synthesis" John Wiley & Sons: New York,Chichester, Brisbane, Toronto, Vol. 1,(1977).

[10]         Al’-Assar, F. Zelenin, K. N. Lesiovskaya, E. E. Bezant, I. P. and Chakchir, B. A., "Synthesis and Pharmacological Activity of 1-Hydroxy-, 1-Amino-,and 1-Hydrazino-Substituted 2,3-Dihydro-1Hpyrazolo[1,2-a] pyridazine -5,8-diones and 2,3-Dihydro-1H-pyrazolo[1,2-b]phthalazine-5,10diones" Pharm. Chem. J.,vol. 36, pp. 598-603,(2002).

[11]         Carling, R. W. Moore, K. W. Street, L. J. Wild, D. Isted, C. Leeson, P. D. Thomas, S. O’Connor, D. McKernan, R. M. Quirk, K. Cook, S. M. Atack, J. R. Wafford, K. A. Thompson, S. A. Dawson, G. R. Ferris,P. and Castro, J. L., 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1, . J. Med. Chem.,vol. 47, pp. 1807-1822,(2004)

[12]         Maher, A. EL-HASHASH1, Ahmed, Y. SOLIMAN, Ibrahim, E. EL-SHAMY,"Synthesis and antimicrobial evaluation of some annelated phthalazine derivatives and acyclo C-nucleosides from 1chloro-4-(2,4,6-trimethylphenyl) phthalazine precursor" Turk. J. Chem., vol.36, pp. 347-366,( 2012)

[13]         Wiley,R. and  Bennett,L. ,The chemistry of the oxazolines, Chem. Rev., vol.44(3) pp. 447-476,( 1959).

[14]         Ayad, K. Khan,"Synthesis and Characterization of New Heterocyclic Derivatives from 1,8Naphthalic Anhydride and Studying Their Applications as Antimicrobial Agents" Ph.D. thesis.Department of Chemistry,College of Science,University of Baghdad(2013).

[15]         Alafeefy, A."Some new quinazolin-4(3H)-one derivative, synthesis and antitumor activity", J. Saudi Chem. Soc., vol. 18, 337-343,(2011).

[16]         Suaad, M. Al-Majidi, "Synthesis, Characterization and Evaluation of Antimicrobial Activity of Several New N-Substituted Carbazole" J.Al-Nahrain Un.,vol. 16(4),pp.67-79,( 2013).

[17]         Wafaa,W., "Synthesis of some new derivatives of 1,2,4-triazole and thiazole from 1,2,3,4tetrahydrocarbazole and study their biological activity"  J.Al-Nahrain Univ.Sci.,vol.13(2),pp.54-62,( 2010).

[18]         Mohammed, G. Abass, "Synthesis and characterization of some new substituted-2-mercapto-3phenyl-4(3H)quinazolinone and evaluation of their biological activity" M.Sc. thesis, Chem. Dept. College of Sci., Baghdad University(2014).

[19]         Alaa,S., "Synthesis and some biological studies of new triazine, diazine, oxazoline, thiazole, and oxazepine derivatives" M.Sc. Thesis, Chem.Dept. College of Sci., Al-Nahrain University (2006).

[20]         Suaad, M. Al-Majidi, Mohammed,R. and Ayad, K., "Synthesis and characterization of novel 1,8Naphthalimide derivatives containing 1,3-oxazoles, 1,3-thiazoles, 1,2,4-triazoles as antimicrobial agents" J.Al-Nahrain University,vol. 16(4),pp.55-66,(2013).

[21]         Suaad, M.H. Al-Majidi and Wafa,a,W.N.Al-Kaisy,"Synthesis and Some Biological studies of new diazine, triazine, diazole, thiazole and 4-Oxazoline derivatives" Proceeding of 3rd scientific conference,pp.1413-1423,( 2009).

[22]         Anesini,C. and Perez,C."Screening of plants used in argentic folk medicine for antibacterial activity" J. Ethnrophrmacol, vol. 39(2),pp.35-47,(1993).

[23]         Ralph, L. Shriner, Later Reynold, C., and David, Y., ,In the systematic identification of organic compounds, 6th Ed., John Wiley & Sons, New York(1980).