Silica-bonded S-sulfonic acid as a recyclable catalyst for synthesis of 2,3-dihydroquinazolin-4(1H)-ones

Article abstract of DOI:10.1002/cjoc.201180261

2,3-Dihydroquinazolin-4(1H)-one derivatives were synthesized via a one-pot, three component reaction of isatoic anhydride and an aromatic aldehyde with ammonium acetate or primary amine catalyzed by silica-bonded S-sulfonic acid in ethanol at 80°C. The re

Full text of DOI:10.1002/cjoc.201180261

FULL PAPER
Silica-bonded S-sulfonic Acid as a Recyclable Catalyst for
Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
Niknam, Khodabakhsh*
Mohammadizadeh, Mohammad Reza
Mirzaee, Salimeh
Chemistry Department, Faculty of Sciences, Persian Gulf University, Bushehr, 75169, Iran
2,3-Dihydroquinazolin-4(1H)-one derivatives were synthesized via a one-pot, three component reaction of isa-
toic anhydride and an aromatic aldehyde with ammonium acetate or primary amine catalyzed by silica-bonded
S-sulfonic acid in ethanol at 80 ℃. The reaction work-up is simple and the catalyst is easily separated from the
products by filtration. The heterogeneous catalyst was recycled for ten runs upon the condensation reaction of isa-
toic anhydride and 4-chlorobenzaldehyde with ammonium acetate without losing its catalytic activity.
Keywords silica-bonded S-sulfonic acid, aldehydes, 2,3-dihydroquinazolin-4(1H)-one, isatoic anhydride, amines
Introduction
ous chemical transformations processes by catalysts
under heterogeneous conditions has occurred. Silica
bonded S-sulfonic acid (SBSSA) is a versatile catalyst
that makes reaction processes convenient, more eco-
nomic, and environmentally benign19 (Scheme 1). Ow-
ing to the numerous advantages associated with this
non-expensive and non-hazardous reagent, SBSSA has
been explored as a powerful catalyst for various organic
transformations under mild conditions.20-25
2,3-Dihydroquinazolinones are a class of heterocy-
cles that attracted much attention because they have
been reported to possess a wide range of pharmaceutical
activities including antifertility, antibacterial, antitumor,
antifungle, and mono amine oxidize inhibition.1-4 Sev-
eral synthetic methods for the preparation of
2,3-dihydroquinazolinones have been reported. Among
them, the most direct procedure includes condensation
of aryl, alkyl, and heteroaryl aldehydes with an-
thranilamide in the presence of p-toluenesulfonic acid as
a catalyst.5,6 The synthesis of 2,3-dihydroquinazolinones
was also achieved by reductive cyclisation of
o-nitrobenzaldehyde or o-azidobenzamide.7,8 Some of
the recently reported methods include isatoic anhydride,
and aldehydes with ammonium acetate or primary
amine in the presence of different reagents or catalysts,
namely p-toluenesulfonic acid,9 amberlyst-15 micro-
waved-assisted,10 montmorillonite K-10,11 ionic liq-
uid,12 silica sulfuric acid,13 Zn(PFO)2,14 ceric ammo-
nium nitrate,15 and MCM-41-SO3H.16
Experimental
General
Chemicals were purchased from Merck, Fluka and
Aldrich chemical companies. IR spectra were run on a
Perkin Elmer FT-IR Spectrum BX. The NMR spectra
were run on Bruker Ultrashield 400 (400 MHz). Melting
points were recorded on a Melting Point SMP1 appara-
tus in open capillary tubes and are uncorrected. With
TLC using silica gel SILG/UV 254 plates the progress
of reaction was followed. All of the products are char-
acterized by comparison of their spectral (IR, 1H NMR),
TLC and physical data with those reported in the litera-
ture.11-16 Silica bonded S-sulfonic acid (SBSSA) was
prepared according to our previously reported proce-
dure.19-25
In recent years, the use of solid acidic catalysts has
offered important advantages in organic synthesis, for
example, operational simplicity, environmental com-
patibility, non-toxicity, reusability, low cost, and ease of
isolation.17,18 A tremendous upsurge of interest in vari-
Scheme 1 Preparation of silica-bonded S-sulfonic acid (SBSSA)
*
E-mail: khniknam@gmail.com, niknam@pgu.ac.ir; Fax: (0098)-0771-4545188
Received August 10, 2010; revised December 1, 2010; accepted December 20, 2010.
Project supported by the Research Council of Persian Gulf University and University of Manchester for running NMR.
Chin. J. Chem. 2011, 29, 1417— 1422
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1417

Niknam, Mohammadizadeh & Mirzaee
FULL PAPER
General procedure for synthesis of 2,3-dihydro-
quinazolinone derivatives
100 MHz) δ: 65.79, 114.44, 114.92, 117.28, 121.55,
127.35, 129.06, 131.22, 133.39, 141.08, 147.61, 163.46;
IR νmax: 3307.94, 3188.80, 3025.12, 1665.97, 1651.50,
1605.61, 1504.15, 1480.89, 1430.38, 1382.00,－1292.03,
To a mixture of isatoic anhydride (1 mmol), aro-
matic aldehyde (1 mmol), and ammonium acetate or
primary amine (1 mmol) in 5 mL ethanol was added
0.005 g silica-bonded S-sulfonic acid (SBSSA) and
heated at 80 ℃ in an oil bath. After completion of the
reaction, as indicated by TLC, the reaction mixture was
filtered and remaining washed with warm ethanol (5
mL×2). After cooling, the corresponding 2,3-dihydro-
quinazolinone products were obtained and they were
purified by recrystallization from hot ethanol. The re-
covered catalyst was dried and reused for subsequent
runs.
1
1132.94, 1072.04, 1012.00, 833.85, 750.48 cm .
2-(4-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-
one (3e) m.p. 194—197 ℃; 1H NMR (DMSO-d6, 400
MHz) δ: 5.78 (s, 1H), 6.69 (dt, J1＝7.4 Hz, J2＝1.0 Hz,
1H), 6.76 (dd, J1＝8.3 Hz, J2＝0.5 Hz, 1H), 7.11 (s, 1H),
7.20—7.28 (m, 3H), 7.52—7.57 (m, 2H), 7.62 (dd, J1＝
7.8 Hz, J2 ＝1.5 Hz, 1H), 8.30 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ: 65.92, 114.43, 114.93, 114.98,
115.19, 117.24, 127.35, 128.99, 129.07, 133.35, 137.78,
147.78, 163.30, 163.55; IR νmax: 3297.82, 3176.42,
3025.14, 1665.90, 1651.05, 1609.67, 1503.95, 1482.63,
1436.20, 1385.28, 1299.35, 1227.22, 1156.24, 1013.18,
2-(4-Methylphenyl)-2,3-dihydroquinazolin-4(1H)-
one (3a) m.p. 227—228 ℃ (Lit.11 233—234 ℃); 1H
NMR (DMSO-d6, 400 MHz) δ: 2.30 (s, 3H), 5.72 (s,
1H), 6.67 (dt, J1＝7.3 Hz, J2＝1.0 Hz, 1H), 6.75 (dd,
J1＝8.2 Hz, J2＝0.5 Hz, 1H), 7.06 (s, 1H), 7.19 (d, J＝
7.8 Hz, 2H), 7.24 (dt, J1＝7.3 Hz, J2＝1.5 Hz, 1H), 7.38
(d, J＝8.1 Hz, 2H), 7.62 (dd, J1＝7.7 Hz, J2＝1.5 Hz,
1H), 8.25 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ:
20.73, 66.36, 114.39, 114.98, 117.05, 126.79, 127.32,
128.79, 133.24, 137.24, 137.70, 138.64, 147.90, 163.63;
IR νmax: 3310.62, 3190.28, 3015.10, 1667.15, 1655.22,
1606.59, 1507.08, －1482.62, 1382.76, 1296.48, 1180.47,
－1
864.95, 839.49, 791.97, 744.04 cm .
2,3-Dihydro-2-(thiophen-2-yl)quinazolin-4(1H)-
1
one (3f) m.p. 216—219 ℃ (Lit.26 213—216 ℃); H
NMR (DMSO-d6, 400 MHz) δ: 5.87 (s, 1H), 6.55 (t, J＝
7.3 Hz, 1H), 6.60 (d, J＝8.1 Hz, 1H), 6.81—6.84 (m,
1H), 6.96—6.98 (m, 1H), 7.08—7.12 (m, 2H), 7.30 (d,
J＝4.5 Hz, 1H), 7.46 (d, J＝7.3 Hz, 1H), 8.30 (s, 1H);
13C NMR (DMSO-d6, 100 MHz) δ: 62.54, 114.68,
115.09, 117.50, 125.69, 125.88, 126.44, 127.29, 133.35,
146.39, 147.21, 163.09; IR νmax: 3287.72, 3168.38,
3035.76, 1650.43, 1606.77, 1513.82, 1487.23, 1437.91,
1371.93, 1295.86, 1171.5－4, 1133.18, 855.62, 804.71,
1
907.91, 749.54 cm .
2-(4-Methoxyphenyl)-2,3-dihydroquinazolin-
1
4(1H)-one (3b) m.p. 179—180 ℃ (Lit.9 178—180
762.48, 709.83, 682.78 cm .
1
2,3-Dihydro-3-phenyl-2-(4-methylphenyl)quinazo-
lin-4(1H)-one (3g) m.p. 223—226 ℃;27 1H NMR
(DMSO-d6, 400 MHz) δ: 2.22 (s, 3H), 6.24 (d, J＝2.5
Hz, 1H), 6.71 (dt, J1＝7.6 Hz, J2＝1.0 Hz, 1H), 6.76 (dd,
J1＝8.1 Hz, J2＝0.5 Hz, 1H), 7.10 (d, J＝7.8 Hz, 2H),
7.16—7.21 (m, 1H), 7.25—7.35 (m, 7H), 7.61 (d, J＝
℃); H NMR (DMSO-d6, 400 MHz) δ: 3.83 (s, 3H),
5.79 (s, 1H), 6.76 (dt, J1＝7.4 Hz, J2＝1.0 Hz, 1H), 6.83
(d, J＝7.6 Hz, 1H), 7.04 (dt, J1＝8.6 Hz, J2＝2.0 Hz,
2H), 7.10 (s, 1H), 7.30—7.35 (m, 1H), 7.51 (dt, J1＝8.6
Hz, J2＝2.0 Hz, 2H), 7.70 (dd, J1＝7.8 Hz, J2＝1.8 Hz,
1H), 8.28 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ:
55.16, 66.29, 113.61, 114.39, 114.98, 117.07, 127.33,
2.7 Hz, 1H), 7.74 (dd, J1＝7.8 Hz, J2＝1.5 Hz, 1H); 13
C
NMR (DMSO-d6, 100 MHz) δ: 20.62, 72.44, 114.80,
115.40, 117.44, 125.92, 126.09, 126.48, 127.94, 128.58,
128.91, 133.70, 137.56, 137.80, 140.88, 146.56, 162.28;
IR νmax: 3296.14, 3015.10, 1633.11, 1611.42, 1586.33,
1505.80, 1486.97, 1392.11, 1312.22, 1262.68, 1161.73,
128.20, 133.22, 133.43, 148.00, 159.40, 163.69; IR νmax
:
3296.30, 3174.22, 2832.14, 1650.64, 1608.28, 1503.15,
1482.92, 1386.55, 1301.71, 1240.53, 1173.37, 1030.28,
－1
834.03, 791.93, 754.81 cm .
2-(4-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-
－1
1
one (3c) m.p. 203—205 ℃ (Lit.11 198—200 ℃); H
1112.32, 1022.90, 872.50, 821.29, 787.82, 749.83 cm .
2,3-Dihydro-3-phenyl-2-(4-methoxyphenyl)quina-
NMR (DMSO-d6, 400 MHz) δ: 5.77 (s, 1H), 6.68 (dt,
J1＝7.4 Hz, J2＝0.5 Hz, 1H), 6.75 (d, J＝8.1 Hz, 1H),
7.15 (s, 1H), 7.25 (dt, J1＝7.8 Hz, J2＝1.5 Hz, 1H), 7.46
(d, J＝8.6 Hz, 2H), 7.51 (d, J＝8.8 Hz, 2H), 7.61 (dd,
J1＝7.8 Hz, J2＝1.3 Hz, 1H), 8.34 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ: 65.73, 114.43, 114.92, 117.27,
127.34, 128.29, 128.74, 132.94, 133.38, 140.65, 147.63,
163.46; IR νmax: 3307.85, 3186.90, 3025.09, 1667.20,
1651.54, 1607.30, 1504.47, 1483.08, 1383.22,－1292.59,
zolin-4(1H)-one (3h)
m.p. 205—207 ℃ (Lit.14
1
204—205 ℃); H NMR (DMSO-d6, 400 MHz) δ: 3.68
(s, 3H), 6.24 (d, J＝2.5 Hz, 1H), 6.72 (dt, J1＝7.4 Hz,
J2＝1.0 Hz, 1H), 6.77 (d, J＝8.8 Hz, 1H), 6.85 (dt, J1＝
8.8 Hz, J2 ＝2.0 Hz, 2H), 7.16—7.20 (m, 1H),
7.24—7.35 (m, 7H), 7.57 (d, J＝2.5 Hz, 1H), 7.74 (dd,
J1＝7.8 Hz, J2＝1.5 Hz, 1H); 13C NMR (DMSO-d6, 100
MHz) δ: 55.02, 72.32, 113.65, 114.78, 115.33, 117.42,
125.95, 126.29, 127.91, 128.56, 132.60, 133.69, 140.83,
146.66, 159.10, 162.32; IR νmax: 3292.89, 3017.10,
2842.14, 1631.59, 1609.33, 1586.96, 1504.46, 1485.67,
1385.99, 1297.78, 1248.75, 1180.83, 1170.43, 1027.73,
1
1133.67, 1091.92, 1015.63, 835.74, 751.04 cm .
2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-
one (3d) m.p. 201—203 ℃;10 1H NMR (DMSO-d6,
400 MHz) δ: 5.76 (s, 1H), 6.69 (dt, J1＝7.2 Hz, J2＝1.0
Hz, 1H), 6.75 (d, J＝8.07 Hz, 1H), 7.15 (s, 1H), 7.25 (dt,
J1＝7.7 Hz, J2＝1.5 Hz, 1H), 7.45 (d, J＝8.6 Hz, 2H),
7.58—7.62 (m, 3H), 8.35 (s, 1H); 13C NMR (DMSO-d6,
－1
834.06, 792.24, 748.50, 693.68 cm .
2,3-Dihydro-3-phenyl-2-(4-chlorophenyl)quinazo-
lin-4(1H)-one (3i) m.p. 216—218 ℃ (Lit.9 216
1418
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1417— 1422

Silica-bonded S-sulfonic Acid as a Recyclable Catalyst
1
—217 ℃); H NMR (DMSO-d6, 400 MHz) δ: 6.33 (d,
(DMSO-d6, 400 MHz) δ: 2.26 (s, 3H), 2.70—2.77 (m,
1H), 2.85—2.98 (m, 2H), 3.98—4.04 (m, 1H), 5.80 (d,
J＝1.8 Hz, 1H), 6.61—6.77 (m, 2H), 7.15—7.29 (m,
11H), 7.65 (d, J＝7.6 Hz, 1H); 13C NMR (DMSO-d6,
100 MHz) δ: 20.66, 33.60, 46.12, 70.28, 114.17, 114.76,
117.00, 126.17, 126.23, 127.36, 128.35, 128.58, 129.05,
J＝2.7 Hz, 1H), 6.74 (dt, J1＝7.4 Hz, J2＝1.0 Hz, 1H),
6.77 (d, J ＝ 7.8 Hz, 1H), 7.18—7.22 (m, 1H),
7.25—7.29 (m, 3H), 7.31—7.42 (m, 6H), 7.67 (d, J＝
2.5 Hz, 1H), 7.73 (dd, J1＝7.8 Hz, J2＝1.3 Hz, 1H); 13
C
NMR (DMSO-d6, 100 MHz) δ: 71.93, 114.85, 115.28,
117.71, 126.12, 126.25, 128.00, 128.38, 128.52, 128.67,
133.15, 137.80, 138.05, 139.03, 146.46, 162.24; IR νmax:
132.90, 133.85, 139.67, 140.59, 146.41, 162.15; IR νmax
:
3282.06, 3027.47, 1628.10, 1609.15, 1583.56, 1506.09,
1485.13, 1408.10, 1311.22, 1173.2＋1, 822.25, 750.40,
3294.11, 3025.11, 1631.02, 1613.60, 1506.60, 1486.18,
1414.12, 1385.87, 1312.74, 1160.81, 1088.42, 1014.52,
＋
－1
693.83 cm ; Mass m/z (%): 343 (M ＋1, 18), 342 (M ,
61), 341 (29), 320 (37), 291 (15), 264 (25), 237 (29),
217 (31), 155 (68), 118 (68), 82 (base peak), 57 (77).
Anal. calcd for C23H22N2O: C 80.67, H 6.48, N 8.18;
found C 80.49, H 6.38, N 8.01.
－1
833.14, 787.94, 754.04, 693.82 cm .
2,3-Dihydro-3-phenyl-2-(4-bromophenyl)quinazo-
lin-4(1H)-one (3j) m.p. 219—223 ℃ (Lit.14 222—
1
225 ℃); H NMR (DMSO-d6, 400 MHz) δ: 6.31 (d,
J＝2.5 Hz, 1H), 6.71—6.78 (m, 2H), 7.18—7.22 (m,
1H), 7.25—7.29 (m, 3H), 7.31—7.36 (m, 4H), 7.52 (dt,
J1＝8.6 Hz, J2＝2.0 Hz, 2H), 7.67 (d, J＝2.8 Hz, 1H),
7.73 (dd, J1＝7.8 Hz, J2＝1.5 Hz, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ: 71.96, 114.85, 115.29, 117.71,
121.52, 126.11, 126.19, 128.00, 128.68, 128.83, 131.31,
2-(4-Chlorophenyl)-2,3-dihydro-3-phenethylqui-
1
nazolin-4(1H)-one (3n) m.p. 156—158 ℃; H NMR
(DMSO-d6, 400 MHz) δ: 2.69—2.78 (m, 1H), 2.87—
3.01 (m, 2H), 4.01—4.08 (m, 1H), 5.89 (d, J＝2.5 Hz,
1H), 6.62 (d, J＝8.1 Hz, 1H), 6.67 (dt, J1＝7.6 Hz, J2＝
1.0 Hz, 1H), 7.17—7.23 (m, 4H), 7.26—7.30 (m, 2H),
7.34—7.38 (m, 3H), 7.41—7.45 (m, 2H), 7.65 (d, J＝
7.8 Hz, 1H); 13C NMR (DMSO-d6, 100 MHz) δ: 33.57,
46.10, 69.57, 114.26, 114.75, 117.26, 126.21, 127.41,
128.08, 128.36, 128.61, 132.98, 133.31, 134.84, 140.10,
162.09; IR νmax: 3282.50, 3015.10, 2983.12, 2881.16,
1627.48, 1606.11, 1582.06, 1507.09, 1484.60, 1433.27,
1402.09, 1358.90, 1310.08, 1228.17, 1174.75, 1089.19,
133.86, 140.10, 140.60, 146.37, 162.13; IR νmax
:
3292.59, 3059.72, 1631.15, 1612.28, 1505.74, 1484.31,
1412.02, 1385.56, 1312.64, 1160.08, 1114.22, 1070.57,
－1
1011.20, 827.21, 751.95, 694.06 cm .
2,3-Dihydro-3-phenyl-2-(4-fluorophenyl)quinazo-
lin-4(1H)-one (3k) m.p. 235—238 ℃;10 1H NMR
(DMSO-d6, 400 MHz) δ: 6.33 (d, J＝2.5 Hz, 1H), 6.74
(dt, J1＝7.6 Hz, J2＝1.0 Hz, 1H), 6.78 (d, J＝7.8 Hz,
1H), 7.10—7.21 (m, 3H), 7.24—7.30 (m, 3H),
7.31—7.35 (m, 2H), 7.40—7.45 (m, 2H), 7.63 (d, J＝
2.5 Hz, 1H), 7.74 (dd, J1＝7.8 Hz, J2＝1.5 Hz, 1H);
13C NMR (DMSO-d6, 100 MHz) δ: 72.03, 114.81,
115.07, 115.24, 115.29, 117.64, 126.12, 126.42, 127.98,
128.63, 128.78, 128.86, 133.82, 136.86, 140.60, 146.55,
160.64, 162.24, 163.07; IR νmax: 3291.98, 3020.12,
－1
1002.14, 849.17, 829.33, 788.50, 755.55, 693.59 cm ;
Ma＋ss m/z (%): 364 (M＋＋2, 18), 363 (M＋＋1, 28), 362
(M , 84), 361 (80), 360 (17), 321 (25), 291 (23), 264
(47), 244 (70), 237 (58), 155 (55), 118 (38), 98 (35), 82
(81), 57 (base peak). Anal. calcd for C22H19ClN2O: C
72.82, H 5.28, Cl 9.77, N 7.72; found C 72.63, H 5.19,
N 7.54.
2,3-Dihydro-3-(4-hydroxyphenyl)-2-(4-methylphe-
1628.56, 1611.78, 1504.33, 1485.78, 1384.85, 1311.20,
1223.52, 1－151.94, 1023.93, 840.10, 791.82, 752.57,
nyl)quinazolin-4(1H)-one (3o) m.p. 249—252 ℃;
1H NMR (DMSO-d6, 400 MHz) δ: 2.11 (s, 3H), 5.98 (d,
J＝2.5 Hz, 1H), 6.55—6.61 (m, 4H), 6.90 (dt, J1＝8.8
Hz, J2 ＝2.0 Hz, 2H), 6.98 (d, J ＝8.1 Hz, 2H),
7.11—7.15 (m, 3H), 7.35 (d, J＝2.3 Hz, 1H), 7.59 (dd,
J1＝7.6 Hz, J2＝1.5 Hz, 1H), 9.33 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ: 20.63, 73.05, 114.56, 115.09,
115.37, 117.30, 126.52, 127.82, 127.87, 128.84, 132.15,
＋
1
693.83 cm ; Mass ＋m/z (%): 320 (M ＋2, 27), 319
(M＋＋1, 79), 318 (M , 74), 316 (25), 264 (30), 243 (85),
155 (52), 118 (41), 98 (39), 82 (80), 57 (base peak).
2,3-Dihydro-3-phenyl-2-(thiophen-2-yl)quinazo-
lin-4(1H)-one (3l) m.p. 197—200 ℃; 1H NMR
(DMSO-d6, 400 MHz) δ: 6.54 (d, J＝2.5 Hz, 1H), 6.79
(dt, J1＝7.6 Hz, J2＝1.0 Hz, 1H), 6.84 (d, J＝7.8 Hz,
1H), 6.88 (dd, J1＝5.0 Hz, J2＝3.5 Hz, 1H), 6.97 (d, J＝
3.5 Hz, 1H), 7.22—7.27 (m, 1H), 7.31—7.40 (m, 6H),
7.70 (d, J＝2.8 Hz, 1H), 7.75 (dd, J1＝7.8 Hz, J2＝1.5
Hz, 1H); 13C NMR (DMSO-d6, 100 MHz) δ: 69.46,
115.24, 115.56, 118.05, 125.91, 126.33, 126.35, 126.39,
126.50, 127.94, 128.69, 133.81, 140.44, 144.58, 146.33,
161.54; IR νmax: 3285.57, 3024.17, 1631.48, 1608.48,
1503.89, 1483.82, 1387.92, 1366.69, 1318.02, 1257.82,
1190.50, 1157.93, －1070.09, 837.02, 793.49, 754.12,
133.45, 137.49, 137.95, 146.58, 155.45, 162.24; IR νmax
:
3310.99, 3119.71, 3015.12, 2891.15, 2359.28, 1633.60,
1612.53, 1596.03, 1580.32, 1514.24, 1444.59, 1421.41,
1266.33, 1225.42, 1150.33, 1117.79, 1018.36, 869.90,
－1
839.50, 806.42, 770.55, 752.3＋0, 695.18 cm ; Mass m/z
(%): 331 (M＋＋1, 9), 330 (M , 51), 329 (26), 328 (10),
254 (30), 217 (28), 155 (60), 118 (61), 82 (base peak),
57 (77). Anal. calcd for C21H18N2O2: C 76.34, H 5.49, N
8.48; found C 76.18, H 5.34, N 8.31.
2,3-Dihydro-2,3-di(4-methylphenyl)quinazolin-
1
714.14, 694.28 cm . Anal. calcd for C18H14N2OS: C
4(1H)-one (3p)
m.p. 243—247 ℃;27 1H NMR
70.56, H 4.61, N 9.14, S 10.47; found C 70.39, H 4.48,
N 9.02.
(DMSO-d6, 400 MHz) δ: 2.22 (s, 3H), 2.26 (s, 3H), 6.18
(d, J＝2.8 Hz, 1H), 6.68—6.75 (m, 2H), 7.09—7.15 (m,
6H), 7.23—7.28 (m, 3H), 7.55 (d, J＝2.5 Hz, 1H), 7.72
(dd, J1＝7.8 Hz, J2＝1.5 Hz, 1H); 13C NMR (DMSO-d6,
2,3-Dihydro-3-phenethyl-2-(4-methylphenyl)qui-
nazolin-4(1H)-one (3m) m.p. 151—154 ℃; 1H NMR
Chin. J. Chem. 2011, 29, 1417— 1422
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Niknam, Mohammadizadeh & Mirzaee
FULL PAPER
100 MHz) δ: 20.62, 72.56, 114.70, 115.38, 117.38,
126.05, 126.45, 127.88, 128.89, 129.05, 133.60, 135.18,
ble 1). To illustrate the need of SBSSA for this conden-
sation we examined the model reaction in the absence of
SBBSA under heating at 80 ℃ (Table 1, Entriy 1). The
results show clearly that SBSSA is an effective catalyst
for this transformation and without SBSSA the reaction
did not take place, even after 300 min. As indicated in
Table 1, the best results have been obtained at 80 ℃
with 0.005 g (0.016 mol%) SBSSA and the yield of re-
action with increasing the amount of SBSSA decreased.
137.52, 137.90, 138.31, 146.53, 162.20; IR νmax
:
3299.19, 3015.11, 2892.16, 1634.01, 1607.98, 1583.17,
1505.12, 1485.01, 1387.10, 1313.90, 1262.37, 1159.48,
1107.52, 1024.63,－ 877.72, 816.18, 780.88, 764.52,
＋
1
733.16,＋694.37 cm ; Mass m/z (%): 329 (M ＋1, 10),
328 (M , 51), 327 (19), 217 (27), 155 (60), 118 (58), 82
(base peak), 57 (80).
3-(5-Chloro-2-hydroxy-phenyl)-2-(4-chlorophen-
yl)-2,3-dihydro-1H-quinazolin-4-one (3q)
m.p.
Table 1 The reaction of isatoic anhydride and 4-chloro-ben-
1
235—237 ℃; H NMR (DMSO-d6, 400 MHz) δ: 6.21
(d, J＝1.3 Hz, 1H), 6.73—6.77 (m, 2H), 6.82 (d, J＝8.6
Hz, 1H), 7.00 (d, J＝2.5 Hz, 1H), 7.07 (dd, J1＝8.6 Hz,
J2＝2.5 Hz, 1H), 7.29—7.37 (m, 4H), 7.42—7.54 (m,
2H), 7.70 (dd, J1＝7.8 Hz, J2＝1.3 Hz, 1H), 10.05 (s,
1H); 13C NMR (DMSO-d6, 100 MHz) δ: 71.92, 114.46,
114.56, 118.75, 127.94, 128.17, 128.30, 129.24, 132.63,
141.30, 143.65, 152.37, 161.69; IR νmax: 3333.85,
1608.07, 1577.56, 1501.08, 1482.80, 1417.00, 1353.45,
1257.61, 1190.15, 1159.49, 1117.21,－1087.49, 1014.02,
zaldehyde with ammonium acetate in the presence of different
a
amounts of SBSSA at 80 ℃
Entry
The amounts of catalyst/g Time/min
Yieldb/%
1
2
3
4
5
6
7
—
0.2
300
130
130
130
130
130
130
—
50
65
75
80
90
90
0.15
0.1
0.03
0.01
0.005
1
822.17,＋756.46, 738.36, 709.90 cm ; Mass m/z (%):
384 (M , 40), 383 (27), 382 (15), 355 (11), 328 (28),
310 (28), 243 (35), 217 (67), 155 (76), 118 (34), 98 (30),
82 (83), 57 (base peak). Anal. calcd for C20H14Cl2N2O2:
C 62.35, H 3.66, Cl 18.41, N 7.27; found C 62.18, H
3.51, N 7.10.
a The molar ratio of isatoic anhydride∶4-chlorobenzaldehyde∶
NH4OAc was used as followed 1∶1∶1 mmol respectively, in
ethanol (5 mL) at 80 ℃. b Isolated yield.
The model reaction was also examined in various
solvents in the presence of 0.005 g of SBSSA (Table 2).
As shown in Table 2, condensation reaction in ethanol
and methanol gave the best results in the case of yield,
and we chose ethanol for environmental acceptance.
Results and discussion
During our studies towards the development of new
routes to the synthesis of highly substituted heterocycles
and the usage of solid acid catalysts,28-32 we wish to re-
port a valid and an efficient procedure for synthesis of
2,3-dihydroquinazolinones via one-pot condensation of
isatoic anhydride and aldehydes with NH4OAc or pri-
mary amine in the presence of silica-bonded S-sulfonic
acid (SBSSA) as an inexpensive solid acid catalyst
(Scheme 2).
Table 2 The reaction of isatoic anhydride and 4-chlorobenza-
ldehyde with ammonium acetate catalyzed by SBSSA in different
solvents at reflux conditionsa
Entry
Solvent
Water
Time/min
130c
Yieldb/%
1
2
3
4
5
6
65
25
15
90
90
—
Dichloromethane
Acetonitrile
Ethanol
130
Scheme 2 SBSSA catalyzed synthesis of 2,3-dihydroquinazo-
linones
130
130c
Methanol
130
130c
Toluene
a The molar ratio of isatoic anhydride∶4-chlorobenzaldehyde∶
NH4OAc was used as followed 1∶1∶1 mmol with SBSSA
(0.016 mol%), respectively, in solvent (5 mL) at reflux conditions.
b Isolated yield. c Reaction was performed at 80 ℃.
The generality of this process was demonstrated by
the wide range of substituted and structurally divers
aldehydes to synthesize the corresponding products in
high to excellent yields (Table 3). Also, a series of ani-
line derivatives and 2-phenylethyl amine were em-
ployed and all 2,3-dihydroquinazolinones were obtained
in high to excellent yields.
To study the effect of catalyst loading on the con-
densation of isatoic anhydride, aldehydes, and ammo-
nium acetate as the corresponding 2,3-dihydroquina-
zolinones, the reaction of isatoic anhydride and
4-chlorobenzaldehyde with NH4OAc was chosen as a
model reaction in ethanol under heating conditions (Ta-
1420
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Chin. J. Chem. 2011, 29, 1417— 1422

Silica-bonded S-sulfonic Acid as a Recyclable Catalyst
Table 3 Preparation of 2,3-dihydroquinazolinones catalyzed by
model compound was made which revealed that SBSSA
is equally efficient, but much cheaper and reusable (Ta-
ble 4).
a
SBSSA in ethanol at 80 ℃
Entry
R1
R2
Product Time/min Yieldb/%
1
2
3
4
5
6
7
8
9
4-CH3C6H4
H
3a
3b
3c
3d
3e
3f
90
120
130
120
120
150
150
180
150
210
135
210
35
87
84
90
86
84
78
80
78
80
80
82
75
87
88
75
80
75
Table 4 Comparison of the efficiency of SBSSA with some of
the reported catalyst on the reaction of 4-methylbenzaldelyde
with isatoic anhydride and ammonium acetate
4-CH3OC6H4 H
4-ClC6H4
4-BrC6H4
4-FC6H4
2-thionyl
H
H
H
H
Catalyst
loading/g
0.5 mol
Catalyst
p-Ts-OH
Time/minYielda/% Ref.
120
300
120
240
210
15
80
73
92
79
90
90
9
Montmorillonite K-10 0.3
11
4-CH3C6H4 C6H5
4-CH3OC6H4 C6H5
3g
3h
3i
[bmim]BF4
0.2
12
Silica sulfuric acid
Silica sulfuric acid
MCM-41-SO3H
0.08
0.11
0.005
13a
13c
4-ClC6H4
C6H5
C6H5
C6H5
C6H5
10 4-BrC6H4
11 4-FC6H4
12 2-thionyl
3j
16
3k
3l
Present
Work
SBSSA
0.005
90
87
13 4-CH3C6H4 PhCH2CH2
14 4-ClC6H4 PhCH2CH2
3m
3n
3o
3p
a Isolated yield.
40
15 4-CH3C6H4 4-HO-C6H4
16 4-CH3C6H4 4-CH3C6H4
240
90
Conclusion
In conclusion, heterogeneous conditions, easy and
clean work-up, high yields and recovery of the catalyst
make this method practical for multi-component reac-
tions. We believe that the present methodology could
become an important addition to the existing method-
ologies.
17 4-ClC6H4
2-HO-5-ClC6H4 3q
120
a
The molar ratio of isatoic anhydride∶aldehyde∶amine was
used as followed 1∶1∶1 mmol with SBSSA (0.016 mol%),
respectively in ethanol (5 mL) at 80 ℃. b Isolated yield.
The possibility of recycling the catalyst was exam-
ined. For this reason, the reaction of isatoic anhydride
and 4-chlorobenzaldehyde with NH4OAc in the pres-
ence of SBSSA was studied at 80 ℃ and under sol-
vent-free conditions. Upon completion, the reaction
mixture was filtered and washed with warm ethanol.
The product was recrystallized from hot ethanol. The
recycled catalyst could be reused ten times without any
treatment. No observation of appreciable loss in its
catalytic activities was shown (Figure 1).
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www.cjc.wiley-vch.de
1421

Niknam, Mohammadizadeh & Mirzaee
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Chin. J. Chem. 2011, 29, 1417— 1422