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International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.

net

Reactivity of 3-Amino-2-Ethoxyquinazolin-4(3H)-one in the Synthesis of NovelQuinazolinone Derivatives


Maher A. El-Hashash, Sameh A. Rizk, Fakhry A. El-Bassiouny
Chemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo, Egypt.

Khalid M. Darwish*
Chemistry Department, Science Faculty, University of Garyounis, Benghazi, Libya * Corresponding Author: khaliddarwish1962@yahoo.com, Abstract: 3-Amino-2-ethoxyquinazolin-4(3H)-one 1 was synthesized and allowed to react with p-methoxybenzaldehyde, p-methoxyacetophenone and chloroacetyl chloride to give the Schiff bases 2 and 3 and 3-chloroacetylamino-2ethoxyquinazolin-4(3H)-one 6, respectively. Products 2 and 3 were reacted with phenyl isothiocyanate to give 4 and 5. Derivative 6 were reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol affording 7-9 respectively. In turn, product 8 was reacted with -bromoglucose tetraacetate giving product 8a, whereas product 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording product 9a. Moreover, the reactions of product 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate affording derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1H-NMR and elemental analysis. Products 8a, 9a and 15 were also confirmed by 13C-NMR spectra. Keywords: Quinazolinyl thiazolidine , Thioxodiazetidinyl quinazoline, Piperazinyl thiomorpholine, Triazinoquinazoline quinazolinone, Quinazolinyl

1. Introduction: Quinazolines constitute a big family of heterocyclic compounds which have shown broad variety of biological activity profiles, e.g. analgesic, anti-inflammatory, anti-pyretic,1, 2 anti-microbial,3 anticonvulsant,4 anti-cancer, anti-tumoral, anti-hypertensive, anti-malarial, diuretic, anti-diabetic, antihistamine /sedative, anti-biotic5-12 and many others. Heterocycle-bearing N-glycosides are well known to play significant role as inhibitors. An example for that is the tetrazole-bearing N-glycosides used as SGLT2 inhibitors,13 where the hypoglycemic activity is tested in vivo by mice oral glucose tolerance test (OGTT). On the other hand, sugar hydrazones have the ability for exhibiting biological activity.14 2. Experimental 2.1. General All melting points recorded are uncorrected. The IR spectra were recorded on a Pye Unicam SP1200 spectrophotometer using the KBr wafer technique. The 1H-NMR spectra were determined on a Varian FT-200, or Bruker AC-200 MHz instrument using TMS as an internal standard. Chemical shifts () are expressed in ppm. The mass spectra were determined using MP model NS-5988 and Shimadzu single focusing mass spectrometer (70 eV). All solvents used were of HPLC/Anala R grade. All reagents were used as received from Alfa Aesar. 2.2. Preparation of the starting material 3-amino-2-ethoxyquinazolin-4(3H)-one (1): 2-Ethoxy-4H-3, 1-benzoxazin-4-one (0.01 mol) was heated under reflux with hydrazine hydrate (0.02 mol) in 20 mL ethanol for 3h. The mixture was cooled, filtered off and recrystallized from ethanol as off-white needles; yield 68 %; m.p. 172-173 C. Anal. for C10H11N3O2 (m.w. 205); Found: C, 58.59; 141

International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.net

H, 5.42; N, 20.56; Calcd: C, 58.53; H, 5.37; N, 20.49; IR (cm-1) 1671 (C=O), 1528 (C=N); 3389 (NH); 3443 (CH); MS: m/z (int. %) [M+H]+ 205 (78.3); 1H-NMR (DMSO-d6) 1.14 (t, 3H; OCH2CH3), 4.33 (q, 2H; OCH2CH3), 7.29-8.19 (m, 4H; ArH), 2.0 (s, NH, amine). 2.3. Synthesis of Schiff bases (2, 3): Heating a mixture of compound 1 (0.01 mol) and p-methoxybenzaldehyde or p-methoxyacetophenone (0.01 mol) in absolute ethanol (10 mL) in a water bath for 30 min then leaving it to cool in ice-water afforded a solid material which was filtered, washed with 2 % HCl then water and crystallized from ethanol affording derivatives 2 and 3 respectively. 2.3.1. 3-{[(E)-(4-methoxyphenyl) methylidene] amino}-2-ethoxyquinazolin-4(3H)-one (2): White crystals from ethanol; m.p. 221-222 C, yield 48 %. Anal. for C18H17N3O3 (m.w. 323); Found: C, 66.99; H, 5.32; N, 13.08; Calcd: C, 66.87; H, 5.26; N, 13.00; IR (cm-1) 1514 (N=H), 1671, 1710 (C=O), 2720, 2820 (CH); MS: m/z (int. %) [M+H]+ 323 (55.7); 1H-NMR (DMSO-d6) 1.15 (t, 3H; -OCH2CH3), 4.36 (q, 2H; -OCH2CH3), 7.30 - 7.55 (m, 4H, PhH), 7.48 - 8.21 (m, 4H, quinazolinone), 8.58 (s, 1H, N=CH). 2.3.2. 3-{[(1E)-1-(4-methoxyphenyl) ethylidene] amino}-2-ethoxy quinazolin-4(3H)-one (3): White crystals from ethanol, m.p. 231-233 C, yield 68 %. Anal. for C19H19N3O3 (m.w. 337); Found: C, 67.76; H, 5.71; N, 12.66; Calcd: C, 67.66; H, 5.64; N, 12.46; IR (cm-1) 1519 (N=H), 1668, 1730 (C=O), 3447 (CH); MS: m/z (int. %) [M+H]+ 337 (61.3); 1H-NMR (DMSO-d6) 1.15 (t, 3H; -OCH2CH3), 3.80 (s, 3H, -OCH3), 4.47 (q, 2H; -OCH2CH3), 6.94-7.56 (m, 4H, PhH), 7.328.21 (m, 4H, quinazolinone), 8.58 (s, 1H, CCH3). 2.4. Synthesis of Compounds 4 and 5: Equimolar amounts of 3 or 4 (0.01 mol) and phenyl isothiocyanat in 25 mL toluene was refluxed for 6 h. The solvent was distilled off and the residue was washed with ethanol followed by water, and the product was crystallized from ethanol as yellow crystals. 2.4.1. 3-[2-(4-methoxyphenyl)-3-phenyl-4-thioxo-1,3-diazetidin-1-yl]-2-ethoxyquinazolin-4(3H)-one (4): M.p. 278-280 C, yield 68 %. Anal. for C25H22N4O3S (m.w. 458); Found: C, 65.58; H, 4.87; N, 12.45; S, 7.03; Calcd: C, 65.50 ; H, 4.80; N, 12.23; S, 6.99; IR (cm-1) 1519 (N=H), 1669 (C=O), 3318, 3443 (CH); 1319 (C=S); MS: m/z (int. %) [M+H]+ 458 (59.1); 1H-NMR (DMSOd6) 1.22 (t, 3H; -OCH2CH3), 3.76 (s, 3H, -OCH3), 4.37 (q, 2H; -OCH2CH3), 6.70-6.95 (m, 4H, C6H4OCH3), 7.18-7.30 (m, 5H, -C6H5), 7.44-8.20 (m, 4H, quinazolinone). 2.4.2. 3-[2-methyl-2-(4-methoxyphenyl)-3-phenyl-4-thioxo-1,3-diazetidin-1-yl]-2-ethoxyquinazolin 4(3H)-one (5): -

M.p. 284-286 C, yield 72 %. Anal. for C26H24N4O3S (m.w. 472); Found: C, 66.18; H, 5.13; N, 11.98; S, 6.89; Calcd: C, 66.10; H, 5.08; N, 11.86; S, 6.78; IR (cm-1) 1522 (N=H), 1671 (C=O), 3327, 3433 (CH); 1322 (C=S); MS: m/z (int. %) [M+H]+ 472 (66.3); 1H-NMR

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(DMSO-d6) 1.22 (t, 3H; -OCH2CH3), 1.72 (s, 3H, -CH3), 3.76 (s, 3H, -OCH3), 4.45 (q, 2H; -OCH2CH3), 7.17-7.33 (m, 5H, -C6H5), 6.70-6.95 (m, 4H, -C6H4OCH3), 7.30-8.20 (m, 4H, quinazolinone). 2.5. Synthesis of compound (6): Compound 1 (0.01 mol) was dissolved in 50 mL of dry toluene and cooled to 15 C. To this solution was added drop wise an equimolar amount of chloroacetyl chloride with frequent stirring. The temperature of the reaction was brought slowly to room temperature and then the solution was heated under reflux for 4 h. The excess toluene was distilled off and the resultant precipitate was filtered, washed repeatedly with dry toluene, dried and recrystallized from aqueous dioxane. 2.5.1. 2-chloro-N-(2-ethoxy-4-oxoquinazolin-3(4H)-yl)acetamide (6): White crystals from dioxane; m.p. 149 - 151 C, yield 73 %. Anal. for C12H12Cl N3O3 (m.w. 281.5); Found: C, 51.15; H, 4.26; N, 14.92; Cl, 12.61; Calcd: C, 51.22 ; H, 4.29; N, 14.99; Cl, 12.66; IR (cm-1) 3205 (N-H), 3010 (Ar-H), 2935 (CH2), 1666, 1694 (CO), 1568, 1328 (CN), 775 (CCl); MS: m/z (int. %) [M+H]+ 281 (73.4); 1H-NMR (DMSO-d6) 1.15 (t, 3H; OCH2CH3), 4.31 (s, 2H, CH2Cl), 4.43 (q, 2H; -OCH2CH3), 8.0 (s, 1H, NH), 7.28-8.20 (m, 4H, ArH). 2.6. Synthesis of compounds 7 and 8 Compound 1 (0.01 mol) was heated under reflux with thioglycolic acid or ethyl glycinate (0.01 mol) in 20 mL pyridine for 8 h. The mixture was cooled down then poured onto icewater mixture and stirred allowing the white precipitate to settle down. The precipitate was filtered, washed thoroughly, dried and recrystallized from ethanol affording white needles of compounds 7 or 8. 2.6.1. 4-(2-Ethoxy-4-oxoquinazolin-3(4H)-yl) thiomorpholine-3, 5-dione (7): Yield 54 %; m.p. 279 281 C. Anal. for C14H13N3O4S (m.w. 319); Found: C, 52.69; H, 4.12; N, 13.23; S, 10.10; Calcd: C, 52.66 ; H, 4.08; N, 13.17; S, 10.03; IR (cm-1) 1671, 1698, 1736 (C=O), 2829, 2930 (C-H); MS: m/z (int. %) [M+H]+ 319 (62.7); 1H-NMR (DMSO-d6) 1.19 (t, 3H; -OCH2CH3), 3.76, 4.12 (4 d, 4H, 2 -CH2), 4.36 (q, 2H; -OCH2CH3), 7.44 - 8.20 (m, 4H, quinazolinone). 2.6.2. 1-(2-ethoxy-4-oxoquinazolin-3(4H)-yl) piperazine-2,6-dione (8): Yield 58 %; m.p. 211-213 C. Anal. for C14H14N4O4 (m.w. 302); Found: C, 55.68; H, 4.67; N, 18.61; Calcd: C, 55.63; H, 4.64; N, 18.54; IR (cm-1) 1668, 1735 (C=O), 2808, 2937 (C-H), 3180 (NH); MS: m/z (int. %) [M+H]+ 302 (57.3); 1H-NMR (DMSO-d6) 1.19 (t, 3H; OCH2CH3), 1.91 (s, 1H, NH), 3.34, 3.72 (4 d, 4H, 2 -CH2), 4.36 (q, 2H; -OCH2CH3), 7.44 - 8.20 (m, 4H, quinazolinone).

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International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.net

2.6.3. 1-(2-ethoxy-4-oxoquinazolin-3(4H)-yl)-4-(-glucopyranosyl-1-yl) piperazine-2, 6-dione (8a): Yield 42 %; m.p. 288 - 291C. Anal. for C20H24N4O9 (m.w. 464); Found: C, 51.22; H, 5.22; N, 12.22; Calcd: C, 51.17; H, 5.17; N, 12.07; IR (cm-1) 1675, 1737 (C=O), 3236 (OH bonded), 3400 (OH non - bonded). MS: m/z (int. %) [M+H]+ 464 (47.8); 1H-NMR (DMSOd6) 1.19 (t, 3H; -OCH2CH3), 3.25 (4 d, 4H, 2 -CH2), 3.40-3.79 (m, 6H, H-2', H-3', H-4', H-5', H-6a' and H-6b'), 3.58 (q, 2H; -OCH2CH3), 3.58 (m, 2'-OH, 3'-OH, 4'-OH), 3.65 (s, 6'-OH), 4.81 (dd, 1H, H-1'), 7.63-8.03 (m, 4H, quinazolinone). 13C-NMR: 15.01, 44.61, 44.59, 61.91, 64.60, 71.18, 71.69, 77.72, 82.90, 110.39, 120.78, 126.59, 126.72, 127.29, 133.39, 146.90, 154.00, 160.62, 168.28, 168.28. 2.6.4. 2-Ethoxy-3-(2-oxopiperazin-1-yl) quinazolin-4(3H)-one (9): Yield 53 %; m.p. 201-203 C. Anal. for C14H16N4O3 (m.w. 288); Found: C, 55.68; H, 4.67; N, 18.61; Calcd: C, 55.63 ; H, 4.64; N, 18.54; IR (cm-1) 1668, 1735 (C=O), 2808, 2937 (C-H), 3180 (N-H); MS: m/z (int. %) [M+H]+ 288 (78.9); 1H-NMR (DMSO-d6) 1.19 (t, 3H; -OCH2CH3), 2.96 - 3.76 (4 m, 4H, CH2CH2), 3.43, 3.51 (2 d, 2H, -COCH2), 4.35 (q, 2H; -OCH2CH3), 7.43 - 8.20 (m, 4H, quinazolinone). 2.6.5. 1-(2-ethoxy-4-oxoquinazolin-3(4H)-yl)-4-(p-acetylaminobenzensulfonyl) piperazine-2-one (9a): Yield 43 %; m.p. 282 - 284C. Anal. for C22H21N5O7S (m.w. 499); Found: C, 52.98; H, 4.26; N, 14.12; Calcd: C, 52.90 ; H, 4.21; N, 14.03; IR (cm-1) 1160 (S=O), 1668, 1712, 1735 (C=O), 2808, 2992 (C-H), 3371 (N-H); MS: m/z (int. %) [M+H]+ 499 (56.3); 1H-NMR (DMSOd6) 1.10 (t, 3H; -OCH2CH3), 3.38-3.65 (4 m, 4H, -CH2CH2), 4.04, 4.29 (2 d, 2H, -COCH2), 3.58 (q, 2H; -OCH2CH3), 7.23 (s, 1H, NH), 7.64-7.84 (m, 4H, Ph-H), 7.63-8.20 (m, 4H, quinazolinone). 13C-NMR: 15.0, 24.0, 45.7, 49.8, 53.3, 64.6, 118.0, 118.0, 120.8, 126.6, 126.7, 127.3, 129.4, 133.4, 135.3, 144.8, 146.9, 154.0, 160.6, 168.5, 168.9, 2.6.6. Synthesis of 3-(2-Ethoxy-4-oxoquinazolin-3(4H)-yl)-1, 3-thiazolidine-2,4-dione (10):

A mixture of product 6 (0.01 mol) and potassium thiocyanate (0.01 mol) in 25 mL of DMF was stirred at room temperature for 8 h. The mixture was then heated under reflux in 20 mL of ethanol with few drops of pyridine for 15 h. The mixture was poured onto dilute ice-water / HCl mixture with continuous stirring where a solid material began to precipitate. The mixture was filtered, washed thoroughly with water, dried and crystallized from ethanol affording yellowish white needles of product 10; yield 37 %; m.p. 144 - 146 C. Anal. for C13H11N3O4S (m.w. 305); Found: C, 51.26; H, 3.66; N, 13.81; S, 10.56; Calcd: C, 51.15; H, 3.61; N, 13.77; S, 10.49; IR (cm-1) 1669, 1696, 1734 (C=O), 2833, 2954 (C-H); MS: m/z (int. %) [M+H]+ 305 (77.2); 1H-NMR (DMSO-d6) 1.19 (t, 3H; -OCH2CH3), 3.94 (2 d, 2H, -CH2), 4.36 (q, 2H; -OCH2CH3), 7.44-8.20 (m, 4H, quinazolinone). 2.7. Synthesis of compounds 11 and 12: A mixture of compound 6 (0.01 mol) and potassium cyanate (0.01 mol) in 25 mL of ethanol was stirred at room temperature for 4 h. The mixture was heated under reflux in 20 mL of ethanol for 8 h. The mixture was poured onto ice-water mixture with continuous stirring where a solid material began to precipitate. The mixture was filtered, washed thoroughly with

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water, dried and crystallized from ethanol to give brownish white needles of derivative 11. Further heating of product 11 led to its oxidation affording product 12 as light brown crystals. 2.7.1. 2-Ethoxy-3-(2-imino-4-oxo-1,3-oxazolidin-3-yl)quinazolin-4(3H)-one (11): Yield 42 %; m.p. 138-140C; Anal. for C13H12N4O4 (m.w. 288); Found: C, 54.21; H, 4.21; N, 19.53; Calcd: C, 54.17 ; H, 4.17; N, 19.44; IR (cm-1) 1671, 1731 (C=O), 2954 (CH), 3105 (NH); MS: m/z (int. %) [M+H]+ 288 (88.2); 1H-NMR (DMSO-d6) 1.19 (t, 3H; -OCH2CH3), 5.31 (2d, 2H, CH2), 4.35 (q, 2H; -OCH2CH3), 7.44-8.20 (m, 4H, quinazolinone). 2.7.2. 3-(2-Ethoxy-4-oxoquinazolin-3(4H)-yl)-1,3-oxazolidine-2,4-dione (12): Yield 42 %; m.p. 147-149 C; Anal. for C13H11N3O5 (m.w. 289); Found: C, 54.00; H, 3.84; N, 14.57; Calcd: C, 53.98 ; H, 3.81; N, 14.53; IR (cm-1) 1671, 1731 (C=O), 2833, 2954 (C-H), 3330 (NH); MS: m/z (int. %) [M+H]+ 289 (76.3); 1H-NMR (DMSO-d6) 1.19 (t, 3H; OCH2CH3), 5.31 (2d, 2H, -CH2), 4.35 (q, 2H; -OCH2CH3), 7.44-8.20 (m, 4H, quinazolinone). 2.8. Synthesis of compounds 13 and 14: A mixture of compound 1 (0.01 mol) and malonitrile or ethyl cyanoacetate (0.01 mol) in 25 mL of dry pyridine was heated under reflux for 3 h. The mixture was cooled then poured onto ice-water with stirring where a solid began to precipitate. The mixture was filtered, washed with water, air-dried and crystallized from ethanol affording derivatives 13 and 14. 2.8.1. 1-(2-Ethoxy-4-oxoquinazolin-3(4H)-yl)-2-imino-5-oxopyrrolidine-3-carbonitrile (13): yield 65 %; m.p. 167 169 C; Anal. for C15H13N5O3 (m.w. 311); Found: C, 57.94; H, 4.21; N, 22.61; Calcd: C, 57.88; H, 4.18; N, 22.51; IR (cm-1) 1670, 1734 (C=O), 2246 (CN), 2951 (CH), 3330 (NH); MS: m/z (int. %) [M+H]+ 311 (44.4); 1H-NMR (DMSO-d6) 1.19 (t, 3H; - OCH2CH3), 2.99, 3.07 (2dd, 2H, CH2), 4.36 (q, 2H; -OCH2CH3), 7.44-8.20 (m, 4H, quinazolinone). 2.8.2. Ethyl 1-(2-ethoxy-4-oxoquinazolin-3(4H)-yl)-2-imino-5-oxopyrrolidine-3-carboxylate (14): Yield 65 %; m.p. 119 121 C; Anal. for C17H18N4O5 (m.w. 358); Found: C, 57.94; H, 4.21; N, 22.61; Calcd: C, 56.98; H, 5.03; N, 15.64; IR (cm-1) 1117 (C-O), 1668, 1726 (C=O), 2951 (C-H), 3330 (NH); MS: m/z (int. %) [M+H]+ 358 (57.3); 1H-NMR (DMSO-d6) 1.17 (t, 3H; -OCH2CH3 of pyrolid.), 1.19 (t, 3H; -OCH2CH3 of quinazolinone), 2.94, 3.00 (2 dd, 2H, CH2), 4.20 (q, 2H; -OCH2CH3 of pyrolidine), 4.36 (q, 2H; -OCH2CH3 of quinazolone), 7.44-8.20 (m, 4H, quinazolone). 2.9. Synthesis of compound 15: A mixture of compound 1 and ammonium acetate (0.01 mol each) was fused together on an oil bath at 110 C for 2 h. The fused solution was poured onto ice-water with stirring until a white solid was precipitated. The mixture was filtered, washed repeatedly with water, dried and recrystallized from ethanol affording off-white needles of product 15.

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2.9.1. 6-ethoxy-2H-[1,2,4]triazino[2,3-c]quinazolin-3(4H)-one (15): Yield 78 %; m.p. 102-104 C; Anal. for C12H12N4O2 (m.w. 244); Found: C, 57.94; H, 4.21; N, 22.61; Calcd: C, 59.02; H, 4.92; N, 22.95; IR (cm-1) 1660 (C=O), 2870, 2980 (C-H), 3230 (NH), 1605 (C=N); MS: m/z (int. %) [M+H]+ 244 (81.7); 1H-NMR (DMSO-d6) 1.19 (t, 3H; OCH2CH3), 4.04, 4.18 (2d, 2H, CH2), 4.33 (q, 2H; -OCH2CH3), 7.30-7.72 (m, 4H, quinazolinone), 8.00 (br s, 1H, NH). 13C-NMR: 15.0, 42.1, 64.6, 123.2, 126.7, 127.3, 132.3, 135.4, 148.6, 154.0, 156.2, 165.6. 3. Results and Discussion Herein we discuss and report the behavior of 3-amino-2-ethoxyquinazolin-4(3H)-one 1 towards two selected aldehyde and ketone and chloroacetyl chloride, to give Schiff bases and 3 chloroacetylamino -2- ethoxyquinazolin - 4 (3H)-one 6, respectively. Similarly, we report and interpret the behavior of product 6 towards various N-, O- or S-nucleophiles in synthesis of new cyclic and acyclic derivatives with the aim of obtaining more precise information about the course of the reaction. All the pathways assigned for the synthesis of these products are always terminated by a cyclization step, caused by elevation in the reaction temperature giving larger stable derivatives. In all the derivatives synthesized by this way, it was always noticed that the exocyclic amino nitrogen atom, at the 3-position of quinazolinone, became a member of the newly attached five-membered or six-membered heterocyclic ring (e.g. thiazolidine, diazetidine, piperazine, oxazolidine, pyrrolidine, triazine, thiomorpholine and many others). The large number of products explored in this way enhances the structure-to-property relationship. In synthesis of the Schiff bases, the reaction of compound 1 with p-methoxyacetophenone or pmethoxybenzaldehyde in absolute ethanol afforded the Schiff bases 2 and 3, respectively (Scheme 1). Thereafter, 2 and 3 were reacted with phenylisothiocyanate in refluxing toluene affording the 3-(4thioxo1, 3-diazetidin-1-yl)-2-ethoxyquinazolin-4(3H)-one products 4 and 5, respectively. The IR spectra of 2 and 3 showed absorption bands in the range 1710-1730 which are attributable for max of C=O of aldehyde and ketone respectively. Also, the IR spectra of 4 and 5 showed absorption bands in the range 1319-1322 attributable for max of C=S. Compound 1, on the other hand, was reacted with chloroacetyl chloride, in DMF and at room temperature, affording 3-chloroacetylamino-2-ethoxyquinazolinone 6 (Scheme 2). The 1HNMR showed singlets at 4.31 attributable to CH2Cl and at 8.0 attributable to sec-NH group. The mass spectrum showed a molecular ion peak for the parent product at m/z 281.5, 283.5. Compound 1 reacted with thioglycolic acid, ethyl glycinate in boiling pyridine, and with 2aminoethanol in boiling ethanol, affording the products 7-9 with thiomorpholine or piperazine ring at 3-position respectively (Scheme 3). The 7-9 were produced via ring closure. Their IR spectra showed absorption bands at 1735-1737 attributable for max of C=O groups in each of the thiomorpholino or piperazino moieties. In addition, the IR spectrum of 7 devoid any band for sec-NH group. Treatment of product 8 with -bromoglucose tetraacetate in 1, 4-dioxane, followed by a deacetylation step of the product by methanolic sodium carbonate, gave product 8a. Similarly, treatment of derivative 9 with p-acetylaminobenzenesulfonyl chloride in dry pyridine afforded product 9a. The IR spectrum of 8a

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International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.net Scheme-1 Synthetic pathway for compounds 2-5

Scheme-2 Synthetic pathway for compounds 6

Scheme-3 Synthetic pathway for compounds 7-9

Scheme-4 Synthetic pathway for compounds 10-12

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International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.net Scheme-5 Synthetic pathway for compounds 13-14

Scheme-6 Synthetic pathway for compounds 15

showed absorption bands at 3236, 3400 attributable for max of OH groups of the sugar moiety, and the 1 H-NMR spectrum devoid any band of NH group. The IR spectrum of product 9a showed absorptions at 1160 and 3371 which are attributable for max of S=O and NH groups of the pacetylaminobenzenesulfonyl moiety. Also, the 1H-NMR showed a singlet at 7.23 for the referred NH. The structures of 8a and 9a were also confirmed by 13C-NMR spectra. Product 6 and potassium thiocyanate were stirred in DMF at room temperature to give the open chain structure, which on reflux with few drops of pyridine and ethanol afforded product 10 (Scheme 4). Repeating this procedure with potassium cyanate in ethanol afforded the open structure which on reflux gave the 3-(2-imino-1,3-oxazolidinyl) quinazolinone 11, which on further heating oxidized to afford the more stable 1,3-oxazolidine-2,4-dione derivative 12. On the other hand, derivative 6 was heated under reflux with malonitrile and ethyl cyano- acetate, in dry pyridine, affording products 13 and 14 respectively (Scheme 5). The IR spectra of products 10-14 showed appearance of the absorption bands in the ranges 1668-1670 and 1696-1734 which are attributable for max of C=O of quinazolinone and the five-membered ring at 3-position and disappearance of band of C-Cl bond. Also, the IR spectra of 13 and 14 showed absorptions in the range 3105-3330 attributable for max for the =NH groups. Product 6 was also fused with ammonium acetate affording the annelated quinazoline 15 (Scheme 6). The IR spectrum for 15 showed the appearance of only one CO band at 1660 attributable for max of the triazine ring. The structure of product 15 was also confirmed by the 13C-NMR spectrum.

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International Journal of Chemical Science and Technology (ISSN: 2248-9797) Volume 1-Issue4, October 2011.pp.141-149 www.ijcst.net

4. 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. Competing Interests The authors declare no conflict of interest. 5. References and Footnotes
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