International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.168-170 www.ijcst.

net

A Facile Synthesis of 4-[(4-{[(1E)-1-(4-methoxyphenyl) ethylidene] amino} phenyl)sulfonyl]-N-(2-ethoxyquinazolin-4-yl) -N-(2-furoyl)aniline

Khalid M Darwish
Science Faculty, Chemistry Department, Garyounis University, Benghazi-Libya E-mail: khaliddarwish1962@yahoo.com ABSTRACT: The present work describes a convenient synthesis of the novel Schiff base, 4 - [(4 - {[(1E)-1-(4methoxyphenyl) ethylidene] amino} phenyl) sulfonyl]-N-(2-ethoxy- quinazolin-4-yl) aniline 6 by reacting the novel 4chloro-2-ethoxyquinazoline 3 with 4, 4'-sulfonyldianiline 4. 3 was prepared by phosphorylation of 2-ethoxyquinazolin-4one 2. The structures of the newly synthesized Schiff bases 6 and 7 were confirmed by the IR, 1H NMR, MS and elemental analysis. KEYWORDS: 4-Choro-2-ethoxyquinazoline, Dapsone, D-glucose , Schiff base

1. Introduction: Quinazolines are a big family of heterocyclic compounds, which have shown broad variety of biological activity profiles, e. g. analgesic, anti-inflammatory, antipyretic [1, 2], anti-microbial [3], anti-convulsant [4], anti-cancer [5], anti-tumoral [6], anti-hypertensive [7], anti-malarial [8], diuretic [9], anti-diabetic [10], anti-histamine / sedative [11], antibiotic [12] and many others. Heterocycle bearing N - glycosides are well known to play a significant role as inhibitors. An example is the tetrazole-bearing N-glycosides used as SGLT2 inhibitors [13] where their hypoglycemic activity is tested in vivo by mice oral glucose tolerance test (OGTT). In this paper we report the overall synthesis of a new quinazoline-containing Schiff base with the aim of obtaining more precise information about the course of reaction. (Fig: 1) 2. Syntheses: 2-Ethoxy (4H)-3, 1-benzoxazin-4-one 1 was prepared according to methods in the literature [14]. Compounds 1 (1.91g, 0.01 mol) and ammonium acetate (0.8 g, 0.01 mol) were fused using an oil bath for 2h. The mixture was poured onto an ice / water mixture and stirred. The white precipitate that separated out was filtered, washed, dried, and then crystallized from ethanol affording white crystals of 2-ethoxyquinazolinone 2 (m.p. 155-156 C, yield 85%). Compound 2 (1.9 g, 0.01 mol) was heated with phosphorus oxychloride (20 mL) over a water bath at 70 C for 2 h. The mixture was cooled and diluted with ice/water and the resulting precipitate was collected by filtration and then recrystallized from ethanol affording 4-chloro-2-ethoxyquinazoline 3 as brown crystals from ethanol; m.p. 180-182 C; yield 82 %. 2.1. Preparation of N-{4-[(4-aminophenyl) sulfonyl] phenyl}-2-ethoxyquinazolin-4-amine 5 Compound 3 (2.09 g, 0.01 mol) was dissolved in 20 ml of ethanol and then 4, 4'-sulfonyldianiline 4 (7.44 g, 0.03 mol) was added to it. The mixture was refluxed for 4 h and cooled. The separated solid was recrystallized from ethanol affording derivative 5 (m.p. 188 C, yield 72%). 2.2. Preparation of Schiff Base 6 A mixture of compound 5 (4.2 g, 0.01 mol), p-methoxyacetophenone (1.5 g, 0.01 mol) in ethanol (20 ml) was refluxed for 6 h. The resulting mixture was cooled and then poured onto an ice/water mixture. The separated solid was filtered, washed with water, dried and crystallized from ethanol affording colorless crystals of 6 (m.p. 222-224 C; yield 78%). 168

International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.168-170 www.ijcst.net

Fig: 1

IR (KBr) / cm-1 1160 (S=O), 1610 (C=N), 2993 (CH) and 3200 (NH); MS: m/z 552 (M+, 12 %), 119 (100 %); 1H - NMR (DMSO - d6) 1.22 (t, 3H, CH3 of ethoxy), 2.27 (s, 3H, CH3), 3.94 (s, 3H, CH3 of methoxy), 4.26 (q, 2H, CH2 of ethoxy), 7.25 8.08 (m, 12H, 3Ph-H), 7.46 8.81 (m, 4H, quinazoline), 10.86 (s, 1H, sec NH); Anal. for C31H28N4O4S (M.wt 552): Calcd: C, 67.39; H,5.07; N, 10.14; S, 5.80; Found: C, 67.42; H, 5.09; N, 10.18; S, 5.88. 2.3. Preparation of Schiff Base 7 A mixture of Schiff base 6 (0.01 mol) and the 2-furoyl chloride (0.01 mol) was refluxed in 50 mL of dry pyridine for 4h. The excess solvent was distilled off and the reaction solution was cooled, then poured into crushed ice with frequent stirring leaving a crude product which was filtered off, washed with cold water, dried and crystallized from ethanol to afford 7. IR (KBr) / cm-11157 (S=O), 1588 (C=N), 1734 (C=O), 2988 (CH) and 3200 (NH); MS: m/z 552 (M+, 18 %), 119 (100 %); 1H NMR (DMSO - d6) 1.26 (t, 3H, CH3 of ethoxy), 2.21 (s, 3H, CH3), 3.95 (s, 3H, CH3 of methoxy), 4.34 (q, 2H, CH2 of ethoxy), 7.28-8.33(m, 12H, 3Ph-H), 7.24, 7.67, 8.41 (3q, 3H, 3 CH of furan), 7.55-8.83 (m, 4H, quinazoline); Anal. for C36H30N4O6S (M. wt 646): Calcd: C, 67.39; H,5.07; N, 10.14; S, 5.80; Found: C, 67.42; H, 5.09; N, 10.18; S, 5.88. 169

International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.168-170 www.ijcst.net

3. Acknowledgement The author wishes to express his gratitude to the chemistry department of Ain-Shams University for providing the research assistance for carrying out the pilot project. 4. References and Footnotes

[1] [2] [3] [4]

[5] [6] [7] [8] [9] [10] [11] [12]

[13] [14]

Alagarsamy, V; Shankar, D and Solomon, V R; Synthesis of some novel 2-mercapto-3- (substituted amino)5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin- 4 -ones as analgesic and anti-inflammatory agents, Arkivoc, 2006, 16, 149-159. Ghorab, MM; Ismail, ZH and Abdalla, M; Synthesis and biological activities of some novel triazoloquinazolines and triazinoquinazolines containing benzenesulfonamide moieties, Arzneimittelforschung, 2010, 60(2), 87-95. Mehta, S; Swarnkar, N; Vyas, M; Vardia, J; Punjabi, PB and Ameta, S C; Synthesis and Characterization of Some Quinazoline Derivatives as Potential Antimicrobial Agents under Microwave Irradiation, Bull. Korean Chem. Soc., 2007, 28(12), 2338-2342. Laddha, S S and Bhatnagar, S P; Novel Fused quinazolinones: Further studies on the anti-convulsant activity of 1,2,9,11-tetrasubstituted-7H-thieno[2,3:4,5]pyrimido[6,1-b]-quinaz-olin-7-one and 1,3,10,12-tetrasubstituted-8Hpyrido[2,3:4,5]pyrimido[6,1-b]quinazolin-8-one. In proceedings of the 13th International Electronic Conference on Synthetic Organic Chemistry, http://www.usc.es/congresos/ecsoc/, 1-30 November 2009, pp. 1-19. Khalil, A A; AbdelHamide, S G; Al-Obaid, A M and El-Subbagh, H I; Substituted Quinazolines, Part 2. Synthesis and In-Vitro Anticancer Evaluation of New 2-Substituted Mercapto-3H-quinazoline Analogs, Arch. Pharm. Pharm. Med. Chem., 2003, 2, 95-103. Kundu, S K; Mahindaratne, M P D; Quinrero, M V; Bao, A and Negrete, G R; One-pot reductive cyclization to antitumor quinazoline precursors, Arkivoc, 2008, 2, 33-42. Alagar, V and Pathak, U S; Synthesis and antihypertensive activity of novel 3-benzyl -2-substituted-3H[1,2,4]triazolo[5,1-b]quinazolin-9-ones, Bioorg. and Med. Chem., 2007, 15, 34573462. Guan J; Zhang Q; O'Neil M; Obaldia N 3rd; Ager A; Gerena L and Lin AJ; Antimalarial activities of new pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives, Antimicrob Agents Chemother., 2005, 49(12), 4928-4933. Maarouf, A R; El-Bendary, E R and Goda, F E , Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents, Arch Pharm (Weinheim)., 2004, 337(10), 527-532. Deacon, C F and Holst J J; Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes, Expert Opin Investig Drugs, 2010 ,19(1),133-140. Alagarsamy, V; Giridhar, R and Yadav, M R; Synthesis and H1-antihistaminic activity of some novel 1substituted-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones, Biol Pharm Bull., 2005, 28(8), 15311534. Chevalier, J; Mahamoud, A; Baitiche, M; Adam, E; Viveiros, M; Smarandache, A; Militaru, A; Pascu M L; Amaral, L and Pags, J-M; Quinazoline derivatives are efficient chemosensi-tizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudo-monas aeruginosa resistant strains, J. Antimicrob. Agents, 2010, 36(2), 64-168. Gao, Y L; Zhao, G L; Liu, W; Shao, H; Wang, Y L; Xu, W R; Tang, L D and Wang, J W; Design, synthesis and in vivo hypoglycemic activity of tetrazole-bearing N-glycosides as SGLT2 inhibitors, Ind. J. of Chem., 2010, 49B, 1499-1508. Krantz, A; Spencer, R W; Tam,T F; Liak,T J; Copp, L J; Thomas, E M and Rafferty, S P; Design and synthesis of 4H-3,1-benzoxazin-4-ones as potent alternate substrate inhibitors of human leukocyte elastase, J. Med. Chem., 1990, 33, 464-479.

170