International Journal of Chemical Science and Technology (ISSN: 2248-9797)

Volume 1-Issue4, October 2011.pp.150-157

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Syntheses of Novel Schiff bases and N-Nucleosides Bearing

2-Ethoxy quinazolin-4(3H)-one-3-yl or 2-Ethoxy
quinazolin-4-yl Moieties
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: The present work describes convenient syntheses of the novel Schiff bases 2 and 4 by reaction of each of the
previously synthesized quinazolinones 1 and 3 with p-methoxybenzaldehyde.
Dapsone was reacted with pmethoxyacetophenone to afford
4-[(4-aminophenyl) sulfonyl]-N-[(1E)-1-(4-methoxyphenyl)ethylidene]aniline
5
which was, in turn, reacted with 4-chloro-2-ethoxyquinazoline 6 affording Schiff base 7. The latter was reacted with 2furoyl chloride affording Schiff base 8. Also, 1 and 2 reacted with -bromoglucose tetraacetate giving peracetylated Nglycosides of quinazolinones 9 and 11 which were then deacetylated to afford N-glycosylated quinazolinones 10 and 12,
respectively. On the other hand, 2-Ethoxy (4H)-3, 1-benzoxazin-4-one 13 was condensed with dapsone affording the new
N-(2-ethoxyquinazolin-3-yl) dapsone 14 which was then reacted with -bromoglucose tetraacetate and subsequently
deacetylated giving products 15 and 16 respectively. The structures of the novel Schiff bases and N-glycosides were
confirmed by the IR, 1H NMR, 13C-NMR, MS and elemental analysis.
Keywords: 2-Ethoxy(4H)-3, 1-benzoxazin-4-one, N-glycosylated quinazolinone , Dapsone , Schiff base, 2-furoyl chloride

1. Introduction:
Quinazolines are a big family of heterocyclic compounds, which have shown broad variety of
biological activity profiles. e.g. analgesic, antiinflammatory, antipyretic,1, 2 antimicrobial,
anticonvulsant, anticancer,3-5 antitumoral,6 antihypertensive,7 antimalarial,8 diuretic,9 antidiabetic,10
antihistamine / sedative,11 antibiotic 12 and many others. It is well known that the heterocyclebearing N-glycosides play a significant role as inhibitors. A representat ive example for that is the
tetrazole-bearing N-glycosides which are used as SGLT2 inhibitors,13 where their hypoglycemic
activity is tested in vivo by mice oral glucose tolerance test (OGTT).
2. Experimental
All melting points recorded are uncorrected. The IR spectra were recorded on a Pye Unicam SP 1200
spectrophotometer using the KBr wafer technique. The 1H NMR spectra were determined on a Varian
FT-200, Brucker AC-200 MHz spectrophotometry experiment using TMS as an internal standard.
Chemical shifts () are expressed in ppm. The mass spectra were determined by MP model NS-5988
and Shimadzu single focusing mass spectrometer (70 eV). All solvents used were of HPLC / AnalaR
grade. All reagents were used as received from Alfa Aesar.
Compounds 1, 3, and 13 were prepared according to methods available in the literature and to our
published work.14, 15 Compound 6 was prepared by fusing 2-ethoxy (4H)-3, 1-benzoxazin-4-one 13
with ammonium acetate (0.01 mol each) using an oil bath for 2 h. The mixture was then poured onto
ice/water with stirring, leaving a white solid to settle down. This was in turn filtered, washed thoroughly,
air-dried, and crystallized from ethanol affording white crystals of 2-ethoxy quinazolin-4(3H) - one
(m.p. 155-156 C, yield 85 %). The resulting quinazolinone (0.01 mol) was heated under reflux with
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phosphoryl

chloride (20 mL) and phosphorus pentachloride (1 g) on a water bath at 70C for 2 h. The
mixture was cooled and poured onto ice/water with stirring and the resulting precipitate was collected
by filtration and then crystallized affording 4-chloro-2-ethoxyquinazoline 6 as brown crystals from
ethanol; m.p. 180-182 C; yield 82 %.
2.1.General Procedure for the Synthesis of the Schiff Bases 3 and 4:
A mixture of compounds 1 or 3 and p-methoxybenzaldehyde (0.01 mol each) was heated under
reflux in absolute ethanol (20 ml) for 6 h. The resulting mixture was cooled and then poured onto an
ice/water mixture. The separated solid was filtered, washed with water, air-dried and crystallized
from ethanol to give colorless crystals of products 2 or 4.
2.1.1.(E)-2-ethoxy -3-(4-((4-methoxybenzylidene) amino) phenyl) quinazolin-4(3H)-one (2):
m.p. 169-171 C; yield 76 %; Anal. for C24H21N3O3 (m.w. 399). Anal: Calcd: C, 72.16; H, 5.30; N,
10.52; Found: C, 72.23; H, 5.34; N, 10.55. IR (cm-1) 1666 (C=O), 1610 (C=N), 2993 (CH); MS: m/z
(int. %) [M+H]+ 399 (100), 400 (27.4), 401 (3.3); 1H-NMR (DMSO-d6) 1.22 (t, 3H, OCH2CH3), 3.82
(s, 3H, OCH3), 4.26 (q, 2 H, -OCH2CH3), 7.18-7.78 (m, 8 H, 2 Ph-H), 7.34-8.19 (m, 4 H,
quinazolinone), 8.68 (s, 1H, =CH-); 13C-NMR: 15.01, 55.79, 64.89, 114.41, 114.39, 120.81,
122.48, 122.51, 126.59, 126.68, 127.31, 128.72, 129.59, 129.62, 130.18, 131.18, 133.41, 146.92,
147.58, 154.01, 160.02, 160.60, 162.90.
2.1.2. (E)-2-Ethoxy -3-(4'-((4-methoxybenzylidene) amino) -3, 3-dimethyl -[1,1'-biphenyl]-4-yl) quinazolin4(3H)-one (4):
m.p. 182-184 C; yield 68 %; Anal. for C32H29N3O3 (m.w. 503), Calcd: C, 76.32; H, 5.80; N, 8.34;
Found: C, 76.37; H, 5.84; N, 8.39. IR (cm-1) 1668 (C=O), 1622 (C=N), 2992 (CH). MS: m/z (int. %)
[M+H]+ 503 (100), 504 (35.7 ), 505 (6.6); 1H-NMR (DMSO-d6) 1.22 (t, 3H, -OCH2CH3), 2.19,
2.41 (2s, 2H, 2CH3 of biphenyl), 3.84 (s, 3H, -OCH3), 4.52 (q, 2H, -OCH2CH3), 6.95-7.50 (m, 4H,
PhH), 7.33-8.10 (m, 6H, biphenyl), 7.48-8.19 (m, 4H, quinazoline), 8.72 (s, 1H, =CH-); 13CNMR: 15.01, 17.59, 18.61, 55.80, 64.91, 114.41, 114.41, 120.82, 122.01, 122.69, 125.11, 126.19,
126.61, 126.72, 127.32, 128.69, 130.21, 130.21, 131.01, 131.01, 132.12, 133.39, 134.42, 134.78,
137.21, 140.11, 146.89, 150.01, 154.00, 160.58, 160.00, 162.91.
2.1.3. Synthesis of (E)-4-((4-Aminophenyl) sulfonyl)-N-(1-(4-methoxyphenyl) ethylidene) aniline (5):
A mixture of p-methoxyacetophenone and dapsone (0.01 mol each) in 20 mL boiling absolute ethanol
was heated under reflux for 4h. The resulting mixture was cooled and poured onto ice/water. The solid
that separated out was filtered, washed, dried and crystallized from ethanol giving colorless crystals of
5; m.p. 177-178 C; yield 63 %; Anal. for C21H20N2O3S (m.w. 380): Calcd: C, 66.29; H, 5.30; N,
7.36; S, 8.43; Found: C, 66.37; H, 5.35; N, 7.41; S, 8.47. IR (cm-1) 1160 (S=O), 1610 (C=N),
2993 (CH) and 3430 (NH); MS: m/z (int. %) [M+H]+ 380 (100), 381 (24.4 ), 382 (5.5), 383
(1.1); 1H-NMR (DMSO-d6) 2.27 (s, 3H, CH3), 3.94 (s, 3H, OCH3), 6.27 (s, 2H, NH2), 6.99 - 7.88
(m, 12H, 3 ArH).

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2.1.4. Synthesis of (E)-Ethoxy-N-(4-((4-((1-(4-methoxy phenyl)ethylidene)amino)phenyl)sulfonyl)phenyl)quinazolin -4amine (7)

4-Chloro-2-ethoxyquinazoline 6 and product 5 (0.01 mol each) in 20 mL absolute ethanol was heated
under reflux for 6 h. The resulting mixture was cooled and poured onto ice / water. The solid that
separated out was filtered, washed with water, air-dried and crystallized from ethanol to afford white
crystals of 7; m.p. 226-228 C; yield 58 %; Anal. for C31H28N4O4S (m.w. 552): Calcd: C, 67.37;
H, 5.11; N, 10.14; S, 5.80; Found: C, 67.41; H, 5.14; N, 10.18; S, 5.83. IR (cm-1) 1158 (S=O),
1619 (C=N), 2992 (CH) and 3330 (NH); MS: m/z (int. %) [M+H]+ 552 (100), 553 (34.0), 554 (6.7),
553 (2.3), 555 (1.6); 1H-NMR (DMSO-d6) 1.20 (t, 3H, -OCH2CH3), 2.27 (s, 3H, CH3), 3.94 (s, 3H,
-OCH3), 4.00 (s, 1H, sec NH), 4.26 (q, 2H, -OCH2CH3), 7.25-8.08 (m, 12H, 3Ph-H), 7.46-8.81 (m,
4H, quinazoline); 13C-NMR: 14.79, 18.41, 55.80, 60.52, 111.89, 114.42, 114.38, 114.52, 114.52,
123.31, 123.31, 124.19, 127.49, 127.60, 128.69, 128.69, 129.11, 129.11, 129.62, 129.62, 131.41,
132.02, 132.49, 139.90, 145.91, 150.91, 156.29, 162.88, 165.31, 171.42, 192.80.
2.1.5. (E)-N-(2-ethoxyquinazolin-4-yl)-N-(4-((4-((1-(4-methoxyphenyl) ethylidene) amino) phenyl) sulfonyl )
phenyl)furan-2-carboxamide (8):
A mixture of Schiff base 7 (0.01 mol) and the 2-furoyl chloride (0.01 mol) was refluxed in 50 mL
of dry pyridine for 4 h. 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 water, dried and crystallized from ethanol to give 8; m.p. 264-265 C; yield
78%. Anal. for C36H30N4O6S (m.w. 646): Calcd: C, 66.87; H, 4.64; N, 8.69; S, 4.95; Found: C, 66.93;
H, 4.69; N, 8.74; S, 4.99. IR (cm-1) 1157 (S=O), 1588 (C=N), 1734 (C=O), and 2988 (CH); MS: m/z
(int.%) [M+H]+ 646 (18.2), 119 (100); 1H-NMR(DMSO-d6) 1.22 (t, 3H, OCH2CH3), 2.21 (s, 3H,
CH3), 3.95 (s, 3H, OCH3), 4.00 (s, 1H, NH), 4.52 (q, 2H, OCH2CH3), 7.28-8.33 (m, 12H, 3PhH),
7.24, 7.67, 8.41 (3q, 3H, 3CH of furan), 7.55-8.83 (m, 4 H, quinazoline); 13H-NMR: 14.80, 18.39,
55.82, 60.49, 111.68, 111.92, 114.40, 114.4, 115.3, 122.60, 122.60, 123.29, 123.29, 124.21, 127.48,
127.6, 128.52, 128.52, 128.68, 129.61, 129.61, 132.0, 132.49, 137.0, 139.92, 143.78, 147.01,
147.71, 150.89, 156.32, 157.68, 162.9, 165.31, 171.39, 192.78.
2.1.6. Synthesis of Acetylated Derivatives 9 and 11 and Deacetylated Derivatives 10 and 12:
A crude mixture of quinazolinones 1 or 3 (0.05 mol) and -bromoglucose tetraacetate (0.01 mol) in 100
mL 1, 4-dioxane was heated with frequent stirring under reflux for 4h. The mixture was cooled to room
temperature and the solvent was removed under reduced pressure. The residue was dissolved in ethyl
acetate, washed sequentially with saturated NaHCO3 and dried over MgSO4. The purification and
separation was achieved by column chromatography (3:1 EtOAc: Hexane) giving the acetylated
products 9 and 11 as a white solid which was later on recrystallized using dichloromethane - diethyl
ether hexane solvents. A solution of 9 or 11 in MeOH (0.02 mol / 65 mL) was treated with sodium
carbonate solution (0.01mol). A white solid syrupy began to settle. The residue was then purified by
column chromatography (3:1, EtOAc:Hexane) giving the deacetylated derivatives each as a white solid,
which was crystallized by dichloromethane-diethyl ether-hexane solvents affording 10 or 12.

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2.1.7. (2R, 3R, 4S, 5R, 6S)-2-(acetoxymethyl)-6-((4-(2-ethoxy-4-oxoquinazolin-3(4H)-yl) phenyl) amino) tetrahydro2H-pyran-3, 4, 5-triyl triacetate (9):
M.p. 123 - 125 C; yield 58 %. Anal. for C30H33N3O11 (m.w. 611): Calcd: C, 58.91; H, 5.44; N,
6.87; Found: C, 58.94; H, 5.48; N, 6.91. IR (cm-1) 1662, 1738 (C=O), 2988 (CH), 3334 (NH); MS:
m/z (int. %) [M+H]+ 611 (100), 612 (33.6), 613 (7.6), 614 (1.4); 1H-NMR (DMSO-d6) 1.22 (t,
3H, OCH2CH3), 2.05-2.06 (s, 12H, 4Ac-H), 4.00 (s, 1H, sec NH), 4.52 (q, 2H, OCH2CH3), 3.75-5.11
(m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b), 5.22 (d, 1H, Hanom), 7.37-7.54 (m, 4H, PhH), 7.47-8.19
(m, 4H, quinazolinone); 13H-NMR: 15.01, 20.70, 21.02, 21.02, 21.02, 62.39, 64.89, 69.01, 69.38,
73.0, 77.18, 87.89, 117.89, 117.89, 120.8, 121.11, 122.42, 122.42, 126.59, 126.71, 127.32, 133.38,
143.19, 146.90, 154.01, 160.58, 170.20, 170.20, 170.21, 170.21.
2.1.8.
2-Ethoxy-3-(4-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6
phenyl) quinazolin-4(3H)-one (10):

-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)

M.p. 159-161 C; yield 48 %. Anal. for C22H25N3O7 (m.w. 443): Calcd: C, 59.59; H, 5.68; N, 9.48;
Found: C, 59.63; H, 5.70; N, 9.53. IR (cm-1) 1662 (C=O), 3268, 3384 (OH bonded and nonbonded); MS: m/z (int. %) [M+H]+ 443 (100), 444 (25.2), 445 (2.8); 1H-NMR (DMSO-d6) 1.22 (t,
3H, OCH2CH3), 4.00 (s, 1H, sec NH), 4.37 (q, 2H, OCH2CH3), 3.29-3.87 (m, 6H, H-2, H-3, H-4, H-5,
H-6a, H-6b), 3.58 (m, 2'-OH, 3'-OH, 4'-OH), 3.65 (s, 6'-OH), 5.01 (d, 1H, Hanom) 7.30-7.44 (m, 4H,
Ph-H), 7.32- 8.19 (m, 4H, quinazolinone); 13H-NMR: 15.01, 61.89, 64.89, 71.21, 77.38, 74.11, 82.59,
91.62, 117.9, 117.9, 120.78, 121.11, 122.4, 122.4, 126.6, 126.70, 127.29, 133.39, 143.18, 146.90,
154.0, 160.59.
2.1.9. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((4'-(2-ethoxy -4-oxoquinazolin-3(4H)-yl)-3, 3'-dimethyl-[1, 1'biphenyl]-4-yl)amino)tetrahydro-2H-pyran-3,4,5-triyl triacetate (11):
M.p. 163-165 C; yield 56%. Anal. for C38H41N3O11 (m.w. 715): Calcd: C, 63.77; H, 5.77; N, 5.87;
Found: C, 63.83; H, 5.80; N, 5.90. IR (cm-1) 1666, 1736 (C=O), 2992 (CH), 3334 (NH); MS: m/z
(int. %) [M+H]+ 715 (100), 716 (42), 717 (10.9), 718 (2.1), 716 (1.1); 1H-NMR (DMSO-d6) 1.22 (t,
3 H, -OCH2CH3), 2.05-2.06 (s, 12 H, 4 Ac-H), 2.29, 2.22 (2 s, 6 H, 2 CH3), 4.0 (s, 1H, sec-NH), 4.52
(q, 2H, -OCH2CH3), 3.74-5.14 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b), 5.47 (d, 1H, anom-H), 6.667.72 (m, 6 H, PhH), 7.50-8.19 (m, 4H, quinazolinone); 13H-NMR: 15.01, 17.61, 17.89, 20.72, 21.01,
21.01, 21.01, 62.39, 64.90, 69.01, 69.39, 73.01, 77.18, 88.21, 113.89, 120.78, 122.01, 125.11,
125.68, 126.59, 126.72, 126.72, 127.29, 130.00, 131.00, 131.62, 133.41, 134.38, 134.78, 137.20,
145.41, 146.89, 154.00, 160.59, 170.20, 170.20, 170.20, 170.20.
2.1.10. 3-(3,3'-dimethyl-4'-(((1S,2S,3S,4R,5R)-2,3,4-tri hydroxy-5-( methyl)cyclohexyl)amino-[1, 1'-biphenyl]4-yl)-2-ethoxyquinazolin-4(3H)-one (12):
M.p. 188-189 C; yield 48 %. Anal. for C31H35N3O6 (m.w. 545): Calcd: C, 68.24; H, 6.47; N, 7.70;
Found: C, 68.29; H, 6.49; N, 7.73. IR (cm-1) 1669 (C=O), 3266, 3382 (OH bonded and nonbonded); MS: m/z (int. %) [M+H]+ 545 (100), 546 (34.2), 547 (66.9), 546 (1.1), 548 (1.1); 1H-NMR
(DMSO-d6) 1.22 (t, 3H, OCH2CH3), 4.0 (s, 1H, sec NH), 4.47 (q, 2H, OCH2CH3), 3.33-3.67 (m, 6H,
H-2, H-3, H-4, H-5, H-6a, H-6b), 3.58 (m, 2'-OH, 3'-OH, 4'-OH), 3.65 (s, 6'-OH), 5.38 (d, 1H,
Hanom), 6.90 - 7.99 (m, 4 H, Ph-H), 7.29 - 8.19 (m, 4 H, quinazolinone); 13H-NMR: 15.01, 17.61,
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17.89, 61.92, 64.90, 71.18, 74.11, 77.38, 82.60, 91.90, 113.89, 120.78, 122.01, 125.11, 125.68,
126.59, 126.72, 126.72, 127.29, 130.00, 131.00, 131.62, 133.41, 134.39, 134.78, 137.20, 145.41,
146.89, 154.00, 160.59.
2.1.11. Synthesis of 3-(4-((4-Aminophenyl)sulfonyl) phenyl)-2-ethoxyquinazolin-4(3H)-one (14):
A mixture of 2-ethoxy (4H)-3,1-benzoxazin -4-one 13 and dapsone (0.01 mol each) in 20 mL of
absolute ethanol was heated under reflux for 3 h. The mixture was then cooled and poured onto
ice/water. The solid which separated out was filtered, washed thoroughly with water, dried and
recrystallized from ethanol to give colorless crystals of 14; m.p. 183-185 C; yield 73 %; Anal.
for C22H19N3O4S (m.w. 421): Calcd: C, 62.71; H, 4.51; N, 9.98; S, 7.60; Found: C, 62.74; H, 4.54; N,
9.99; S, 7.63. IR (cm-1) 1158 (S=O), 1666 (C=O), 3440 (NH); MS: m/z (int. %) [M+H]+ 421 (100),
422 (25.9), 423 (5.8), 424 (1.1). 1H-NMR (DMSO-d6) 6.27 (s, 2H, NH2), 7.22-8.35 (m, 8H, 2ArH),
7.3 - 8.2 (m, 4 H, quinazolinone); 13H-NMR: 15.01, 64.9, 113.02, 113.02, 122.59, 122.59, 126.60,
126.71, 127.28, 128.50, 128.50, 129.11, 129.11, 131.39, 133.38, 137.01, 137.69, 146.89,
153.41, 154.00, 160.60.
2.1.12. Synthesis of Compounds 15 and 16:
A crude mixture of compound 14 (0.05 mol) and -bromoglucose tetraacetate (0.01 mol) in 100 mL
1,4-dioxane was heated with frequent stirring under reflux for 6 h. The mixture was then cooled to
room temperature and the solvent was removed under reduced pressure. The residue was dissolved in
ethyl acetate, washed sequentially with saturated NaHCO3, dried over MgSO4. The Purification and
separation was achieved using column chromatography (3:1, EtOAc : Hexane) affording the per-Oacetylated derivative 15 as a white solid which was then crystallized using dichloromethane-diethyl
ether-hexane solvents. A solution of 15 in MeOH (0.004 mol / 65mL) was treated with sodium
carbonate solution (0.002 mol). A white solid syrupy began to precipitate. The residue was purified
by the column chromatography (3:1, EtOAc:Hexane) giving deacetylated derivative 16 as a white
solid, which was crystallized by dichloromethane-diethyl ether-hexane solvents affording 16.
2.1.13. (2R,3R,4S,5R,6S)-2-(Acetoxymethyl)-6-((4-(2- ethoxy-4-oxoquinazolin-3(4H)-sulfonyl)phenyl) amino)tetra
hydro-2H-pyran-3,4,5-triyl triacetate (15):
M.p. 166 - 168 C; yield 51 %. Anal. for C36H37N3O13S (m.w. 751): Calcd: C, 57.52; H, 4.96;
N, 5.59; S, 4.27; Found: C, 57.56; H, 4.98; N, 5.61; S, 4.29. IR (cm-1) 1160 (S=O), 1669, 1736
(C=O), 2992 (CH), 3334 (NH); MS: m/z (int. %) [M+H]+ 751 (100),752 (39.9), 753 (11.2), 754 (2.2);
1
H-NMR (DMSO-d6) 1.22 (t, 3H, OCH2CH3), 2.05-2.06 (s, 12 H, 4 Ac-H), 2.29, 2.22 (2s, 6H, 2
CH3), 4.00 (s, 1H, sec-NH), 4.52 (q, 2H, OCH2CH3), 3.74-5.14 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H6b), 5.47 (d, 1 H, anom-H), 6.66-7.72 (m, 6 H, Ph-H), 7.50-8.19 (m, 4H, quinazolinone); 13H-NMR:
15.01, 20.71, 21.01, 21.01, 21.01, 62.39, 64.89, 69.00, 69.38, 73.01, 77.18, 87.91, 111.8, 111.8,
120.78, 122.59, 122.59, 126.61, 126.72, 127.29, 128.51, 128.51, 129.11, 129.11, 129.78, 133.39,
137.00, 137.69, 146.89, 152.61, 154.00, 160.58, 170.20, 170.20, 170.20, 170.20.

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2.1.14. 2-Ethoxy-3-(4-((4-(((2S,3R,4S,5S,6R)-3,4,5-tri hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)

phenyl) sulfonyl)phenyl)quinazolin-4(3H)-one (16):
M.p. 202-204 C; yield 52 %. Anal. for C28H29N3O9S (m.w. 583): Calcd: C, 57.62; H, 5.01; N, 7.20; S,
5.49; Found: C, 57.65; H, 5.04; N, 7.23; S, 5.53. IR (cm-1) 1670 (C=O), 3266, 3382 (OH); MS:
m/z (int. %) [M+H]+ 583 (100), 584 (31.0), 585 (6.7), 586 (1.1); 1H-NMR (DMSO-d6) 1.22 (t, 3H,
OCH2CH3), 4.00 (s, 1H, sec NH), 4.47 (q, 2H, OCH2CH3), 3.33-3.67 (m, 6H, H-2, H-3, H-4, H-5, H6a, H-6b), 3.58 (m, 2'-OH, 3'-OH, 4'-OH) 3.65 (s, 6'-OH), 5.38 (d, 1H, Hanom), 6.90-7.99 (m, 4H, PhH),
7.29-8.19(m, 4H,quinazolinone). 13C-NMR: 15.01, 61.89, 64.89, 71.18, 74.11, 77.39, 82.58, 91.60,
111.80, 111.80, 120.78, 122.59, 122.59, 126.61, 126.72, 127.29, 128.51, 128.51, 129.11, 129.11,
129.78, 133.39, 137.00, 137.69, 146.89, 152.61, 154.00, 160.58.
3. Results and Discussion:
In this paper we report the overall syntheses of some novel quinazolinone- or quinazolinecontaining Schiff bases, with the aim of obtaining more precise information about the course of
reaction. Thus, 3-(4-aminophenyl)-2-ethoxyquinazolin-4(3H)-one 1 and 3-(4'-amino- 3,3'dimethyl [1,1'-biphenyl] 4-yl)-2-ethoxy quinazolin-4(3H)-one 3, synthesized according to our previously
published work,14 each was reacted with p-methoxybenzaldehyde in boiling absolute ethanol
giving products 2 and 4 respectively (Scheme 1). The IR spectra of 2 and 4 devoid any bands
for the NH2 group and the mass spectra showed molecular ion peaks at m/z 399, 401 for derivative 2
and 503, 505 for derivative 4 respectively.
Dapsone was refluxed with an equimolar amount of p-methoxyacetophenone in boiling ethanol giving
the Schiff base 5 in good yield. The latter was reacted with 4-chloro-2-ethoxy quinazoline 6 in boiling
ethanol gave product 7 (Scheme 2). This product could be isolated by washing the crude reaction
mixture with water, to remove any ammonium salts formed, then crystallized from ethanol.
Purification of product 7 was rechecked by TLC. Formation of product 7 was confirmed by mass
spectrum that showed a molecular ion peak at m/z 552, 554 (M+). In its pure state, product 7 was
reacted with an equimolar amount of 2-furoyl chloride in dry pyridine affording derivative 8, whose
structure was inferred by the IR spectrum that showed a strong peak at 1734 attributable for max of
the C=O attached to the furoyl moiety. Also, the IR devoid any band for sec-NH. The chlorine test for
8 showed no indication for the presence of chlorine.
Compounds 1 and 3 were reacted with -bromoglucose tetraacetate in 1,4-dioxane giving 9 and 11
respectively (Scheme 3). The IR spectra of compounds 9 and 11 showed two peaks at 1666 and 1738
attributable for max of two C=O groups of quinazolinone and peracetyl moieties respectively, and
their 1H-NMR spectra each showed a singlet at 2.05-2.06, which is attributable for the CH3 of
acetyl groups. The deacetylation of 9 and 11 by sodium carbonate and methanol afforded 10 and 12
respectively. Formation of 10 and 12 was assigned by mass spectra that showed molecular ion peaks at
m/z 443, 445 and 547, 549 (M+), respectively.
2-Ethoxy (4H)-3,1-benzoxazin-4-one 13 was reacted with dapsone in boiling ethanol giving the
dapsone derivative 14 (Scheme 4). The formation of product 14 was confirmed by its mass spectrum

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International Journal of Chemical Science and Technology (ISSN: 2248-9797)

Volume 1-Issue4, October 2011.pp.150-157
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Scheme1
Synthetic pathway for compounds 2 and 4

Scheme 2
Synthetic pathway for compounds 5-8

Scheme 3
Synthetic pathway for compounds 9-12

Scheme 4
Synthetic pathway for compounds 14-16

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Volume 1-Issue4, October 2011.pp.150-157
www.ijcst.net

showing a molecular ion peak at m/z 421, 423 (M+) and its IR spectrum showing an absorption band
at 1160 attributable for max of S=O in dapsone. The reaction of derivative 14 with -bromoglucose
tetraacetate in 1,4-dioxane gave the per-O- acetylated quinazolinone 15, whose IR spectrum showed
two strong peaks at 1668 and 1736 attributable for max of the two C=O groups of quinazolinone and
peracetyl moieties, respectively, and the 1H-NMR spectrum showed a singlet at 2.05-2.06 which is
attributable for CH3 of acetyl groups. The deacetylation of 15 by sodium carbonate and ethanol gave
the deacetylated derivative 16. The structure of 16 was assigned by its mass spectrum that showed a
molecular ion peak at m/z 583, 585 (M+).
Competing Interests
The authors declare no conflict of interest.
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.
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