Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by succinimide-N-sulfonic acid as a mild and efficient catalyst

Article abstract of DOI:10.1007/s11164-013-1447-y

A simple, green and environmentally benign procedure was developed for the synthesis of 2,3-dihydro-2-phenylquinazolin-4(1H)-ones using catalytic amounts of succinimide-N-sulfonic acid via the cyclocondensation of 2-aminobenzamide with an aldehyde. The present methodology offers several advantages such as high yields, simple procedure, low cost, short reaction times, mild reaction conditions, and use of a reusable catalyst.

Full text of DOI:10.1007/s11164-013-1447-y

Res Chem Intermed
DOI 10.1007/s11164-013-1447-y
Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
catalyzed by succinimide-N-sulfonic acid as a mild
and efficient catalyst
•
Majid Ghashang Syed Sheik Mansoor
Krishnamoorthy Aswin
•
Received: 8 September 2013 / Accepted: 14 October 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A simple, green and environmentally benign procedure was developed
for the synthesis of 2,3-dihydro-2-phenylquinazolin-4(1H)-ones using catalytic
amounts of succinimide-N-sulfonic acid via the cyclocondensation of 2-amino-
benzamide with an aldehyde. The present methodology offers several advantages
such as high yields, simple procedure, low cost, short reaction times, mild reaction
conditions, and use of a reusable catalyst.
Keywords 2,3-Dihydroquinazolin-4(1H)-one Á Succinimide-N-sulfonic acid Á
2-Amino benzamide Á Catalyst recovery
Introduction
2,3-Dihydroquinazolin-4(1H)-ones are an important class of heterocyclic com-
pounds that have attracted considerable attention. The natural quinazolinones and
their synthetic analogous have been reported to possess a wide range of
pharmacological and biological activities including antitumor [1], sodium/calcium
exchanger inhibitors [2], tubulin polymerization inhibitors [3], a1-adrenoreceptor
antagonists [4], and antibacterial and antifungal activity [5]. Some novel 6,8-
diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide deriva-
tives were synthesized in good yields and evaluated for their possible antibacterial
M. Ghashang
Faculty of Sciences, Islamic Azad University, Najafabad Branch, P.O. Box 517, Najafabad, Esfahan,
Iran
S. S. Mansoor (&) Á K. Aswin
Bioactive Organic Molecule Synthetic Unit, Research Department of Chemistry, C. Abdul Hakeem
College, Melvisharam 632 509, Tamil Nadu, India
e-mail: smansoors2000@yahoo.co.in
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M. Ghashang et al.
and anti-inflammatory activities and acute toxicity [6]. Novel quinazolinone
library of 85 compounds were synthesized and the binding affinities of all the
synthesized compounds were obtained by radio-ligand binding assay for the
5-HT7 receptor. Among the 85 compounds, 24 compounds show very good
binding affinities with IC50 values below 100 nM [7]. Therefore, considerable
efforts have been made to explore new simple and direct approaches towards the
construction of 2,3-dihydroquinazolin-4(1H)-ones skeletons.
In the past few years, several methods for the synthesis of 2,3-dihydroqui-
nazolin-4(1H)-ones have been reported. The typical procedure for the synthesis
of this compound involves the condensation reaction of 2-aminobenzamide with
aldehydes or ketones using various promoting agents, such as trichloroacetic acid
[8], SiO2–FeCl3 [9], aerosil silica-supported acidic ionic liquid [10], sulfamic
acid [11], poly(4-vinylpyridine)-supported acidic ionic liquid [12], trifluoroeth-
anol [13], supported N-propylsulfamic acid on magnetic nanoparticles [14],
supramolecular synthesis [15], heteropoly acids [16], tetrabutyl ammonium
bromide [17], amberlyst-15 [18], ZrCl4 [19], and heteropolyacid–clay nano-
composite [20]. Three-component reaction of isatoic anhydride, aldehyde, and
amine are also reported for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones
[21–26]. Many of these methods, however, suffer from drawbacks, such as low
yields of products, the requirement of longer reaction time and high temperature,
along with the use of non-recyclable catalysts. Moreover, preparation of required
catalysts is cumbersome in some cases. Thus, development of a facile, atom-
efficient, and eco-friendly method is highly desirable. In recent years, hetero-
geneous catalysis has played the central role in various organic transformations.
In recent years, succinimide-N-sulfonic acid (SuSA) has drawn much interest in
different organic reactions due to its experimental simplicity. SuSA has shown
considerable catalytic efficiency in different transformations, such as chemoselec-
tive trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS)
[27], chemoselective conversion of amines to their corresponding N-Boc protected
derivatives with (Boc)2O [28], and the synthesis of xanthene derivatives via three-
component condensation of aldehydes with 2-naphthol, 1,3-cyclohexanedione and/
or a mixture of 2-naphthol and 1,3-cyclohexanediones under solvent-free conditions
[29], and also for the acetylation reactions in the absence of a solvent [30].
The use of water as a solvent has many advantages in organic synthesis from both
economic and environmental points of view. Water has therefore become an
attractive medium for many organic reactions, not only because one can avoid using
drying reactants and expensive catalysts and solvents but also for rendering unique
reactivity and selectivity [25].
In continuation of our efforts in the development of green synthetic
methodologies [31–35], we report here a facile, efficient, and environmentally
friendly procedure for the synthesis of 2,3-dihydro-2-phenylquinazolin-4(1H)-ones
using catalytic amounts of SuSA via the cyclocondensation of 2-aminobenzamide
with an aldehyde in water at 70 °C (Scheme 1).
123

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
O
O
O
CHO
N
SO3H
NH
NH2
O
+
Water, 70 oC
N
H
NH2
R
R
1
2a-l
3a-l
Scheme 1 Preparation of various 2,3-dihydroquinazolin-4(1H)-ones
Experimental
Chemicals and apparatus
Chemicals were purchased from Merck, Fluka, and Aldrich. All yields refer to
isolated products unless otherwise stated. 1H-NMR (500 MHz) and 13C-NMR
(125 MHz) spectra were obtained using Bruker DRX-500 Avance at ambient
temperature, using TMS as internal standard. FT-IR spectra were obtained as KBr
discs on Shimadzu spectrometer. Mass spectra were determined on a Varion-Saturn
2000 GC/MS instrument. Elemental analysis were measured by means of Perkin
Elmer 2400 CHN elemental analyzer flowchart.
General procedure for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones
To a solution of 2-aminobenzamide (1 mmol) and aromatic aldehyde (1 mmol) in
water (3 mL), SuSA (5 mol%) was added. The mixture was stirred at 70 °C for an
appropriate time. After completion of the reaction, as indicated by TLC (ethyl
acetate: n-hexane 1:1), water was decanted, hot ethanol (5 mL) was added to the
residue which was then filtered. The resulting solution was condensed under
reduced pressure. Finally, the crude product was purified by recrystallization from
EtOH to afford the corresponding 2,3-dihydroquinazolin-4(1H)-ones in 86–95 %
yield.
Spectroscopic data for synthesized compounds (3a–l)
2,3-Dihydro-2-phenylquinazolin-4(1H)-one (3a) White solid; IR (KBr): 3,302,
1
3,166, 3,044, 1,662, 1,611, 1,501, 1,477 cm-1; H-NMR (500 MHz, DMSO-d6) d:
5.68 (s, 1H, CH), 6.72 (t, J = 7.2 Hz, 1H, Ar–H), 6.81 (d, J = 8.0 Hz, 1H, Ar–H),
7.13 (brs, 1H, NH), 7.29 (t, J = 7.2 Hz, 1H, Ar–H), 7.39–7.49 (m, 3H, Ar–H), 7.63
(d, J = 7.0 Hz, 2H, Ar–H), 7.72 (d, J = 7.7 Hz, 1H, Ar–H), 8.37 (brs, 1H, NH)
ppm; 13C-NMR (125 MHz, DMSO-d6) d: 68.3, 113.3, 116.7, 117.8, 127.5, 128.7,
129.2, 129.7, 133.3, 142.7, 148.6, 166.9 ppm; MS (ESI): m/z 225 (M ? H)?. Anal.
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M. Ghashang et al.
Calcd. for C14H12N2O (%): C, 75.00; H, 5.36; N, 12.50. Found: C, 74.91; H, 5.31;
N, 12.44.
2-(4-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3b) White solid; IR
(KBr): 3,296, 3,170, 3,052, 1,661, 1,611, 1,511, 1,473 cm-1
;
1H-NMR
(500 MHz, DMSO-d6) d: 5.79 (s, 1H, CH), 6.77 (t, J = 8.1 Hz, 1H, Ar–H), 6.92
(d, J = 6.6 Hz, 1H, Ar–H), 7.19 (brs, 1H, NH), 7.33–7.47 (m, 3H, Ar–H), 7.55 (d,
J = 8.8 Hz, 2H, Ar–H), 7.77 (d, J = 7.8 Hz, 1H, Ar–H), 8.44 (brs, 1H, NH) ppm;
13C-NMR (125 MHz, DMSO-d6) d: 67.7, 112.6, 116.6, 117.4, 127.0, 128.5, 129.4,
129.6, 133.3, 142.6, 148.6, 167.2 ppm; MS (ESI): m/z 243 (M ? H)?. Anal. Calcd.
for C14H11FN2O (%): C, 69.42; H, 4.55; N, 11.57. Found: C, 69.33; H, 4.46; N,
11.50.
2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (3c) White solid; IR
(KBr): 3,295, 3,172, 3,060, 1,659, 1,615, 1,513, 1,472 cm-1
;
1H-NMR
(500 MHz, DMSO-d6) d: 5.69 (s, 1H, CH), 6.73–6.81 (m, 2H, Ar–H), 7.17 (s,
1H, NH), 7.35 (d, J = 7.8 Hz, 1H, Ar–H), 7.47 (d, J = 8.4 Hz, 2H, Ar–H),
7.61–7.69 (m, 3H, Ar–H), 8.42 (s, 1 H, NH) ppm; 13C-NMR (125 MHz, DMSO-d6)
d: 68.0, 113.1, 116.6, 117.2, 127.2, 128.5, 129.0, 129.4, 133.5, 143.0, 148.3,
167.7 ppm; MS (ESI): m/z 303.5 (M ? H)?. Anal. Calcd. for C14H11BrN2O (%): C,
55.46; H, 3.63; N, 9.24. Found: C, 55.35; H, 3.57; N, 9.19.
2-(3-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (3d) White solid; IR
;
1H-NMR
(KBr): 3,305, 3,174, 3,061, 1,658, 1,615, 1,505, 1,480 cm-1
(500 MHz, DMSO-d6) d: 5.72 (s, 1H, CH), 6.79 (t, J = 8.2 Hz, 1H, Ar–H), 6.90
(d, J = 6.4 Hz, 1H, Ar–H), 7.16 (brs, 1H, NH), 7.29–7.42 (m, 3H, Ar–H), 7.58 (d,
J = 8.4 Hz, 2H, Ar–H), 7.63–7.67 (m, 1H, Ar–H), 8.44 (brs, 1H, NH) ppm; 13C-
NMR (125 MHz, DMSO-d6) d: 67.6, 112.7, 116.7, 117.0, 127.0, 128.3, 129.3,
129.7, 133.6, 143.2, 148.8, 166.8 ppm; MS (ESI): m/z 270 (M ? H)?. Anal. Calcd.
for C14H11N3O3 (%): C, 62.45; H, 4.09; N, 15.61. Found: C, 62.40; H, 4.03; N,
15.63.
2-(4-Methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (3e) White solid; IR
1
(KBr): 3,299, 3,174, 3,055, 1,666, 1,612, 1,507, 1,481 cm-1; H-NMR (500 MHz,
DMSO-d6) d: 2.17 (s, 3H, CH3), 5.74 (s, 1H, CH), 6.81 (t, J = 8.1 Hz, 1H, Ar–H),
6.98 (d, J = 6.4 Hz, 1H, Ar–H), 7.12 (brs, 1H, NH), 7.31–7.44 (m, 3H, Ar–H), 7.54
(d, J = 8.8 Hz, 2H, Ar–H), 7.69 (d, J = 7.8 Hz, 1H, Ar–H), 8.39 (brs, 1H, NH)
ppm; 13C-NMR (125 MHz, DMSO-d6) d: 20.9, 68.2, 113.0, 116.5, 117.8, 127.6,
128.4, 129.5, 129.9, 133.7, 142.9, 148.3, 167.5 ppm; MS (ESI): m/z 239 (M ? H)?.
Anal. Calcd. for C15H14N2O (%): C, 75.63; H, 5.88; N, 11.76. Found: C, 75.60; H,
5.86; N, 11.77.
2-(4-Methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3f) White solid; IR
1
(KBr): 3,304, 3,172, 3,056, 1,664, 1,616, 1,509, 1,475 cm-1; H-NMR (500 MHz,
DMSO-d6) d: 3.57 (s, 3H, OCH3), 5.75 (s, 1H, CH), 6.74–6.83 (m, 2H, Ar–H), 7.19
(s, 1H, NH), 7.32 (d, J = 7.9 Hz, 1H, Ar–H), 7.50 (d, J = 8.5 Hz, 2H, Ar–H),
7.66–7.72 (m, 3H, Ar–H), 8.46 (s, 1 H, NH) ppm; 13C-NMR (125 MHz, DMSO-d6)
d 54.4, 67.5, 112.5, 116.5, 117.7, 127.6, 128.4, 129.3, 129.8, 133.4, 143.3, 148.6,
166.9 ppm; MS (ESI): m/z 255 (M ? H)?. Anal. Calcd. for C15H14N2O2 (%): C,
70.87; H, 5.51; N, 11.02. Found: C, 70.79; H, 5.47; N, 11.01.
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Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
2-(3-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (3g) White solid; IR
(KBr): 3,301, 3,168, 3,060, 1,655, 1,614, 1,511, 1,475 cm-1
;
1H-NMR
(500 MHz, DMSO-d6) d 5.68 (s, 1H, CH), 6.75 (t, J = 8.2 Hz, 1H, Ar–H), 6.88
(d, J = 6.8 Hz, 1H, Ar–H), 7.09 (brs, 1H, NH), 7.19–7.36 (m, 3H, Ar–H), 7.46 (d,
J = 8.4 Hz, 2H, Ar–H), 7.63–7.71 (m, 1H, Ar–H), 8.48 (brs, 1H, NH) ppm; 13C-
NMR (125 MHz, DMSO-d6) d: 68.1, 113.3, 116.7, 117.7, 127.4, 128.8, 129.3,
129.7, 133.5, 142.8, 148.9, 167.3 ppm; MS (ESI): m/z 303.5 (M ? H)?. Anal.
Calcd. for C14H11BrN2O (%): C, 55.46; H, 3.63; N, 9.24. Found: C, 55.43; H, 3.60;
N, 9.25.
2-(3-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3h) White solid; IR
(KBr): 3,294, 3,162, 3,061, 1,658, 1,609, 1,514, 1,478 cm-1
;
1H-NMR
(500 MHz, DMSO-d6) d: 5.83 (s, 1H, CH), 6.73 (t, J = 8.4 Hz, 1H, Ar–H), 6.91
(d, J = 6.6 Hz, 1H, Ar–H), 7.11 (brs, 1H, NH), 7.25–7.40 (m, 3H, Ar–H), 7.50 (d,
J = 8.6 Hz, 2H, Ar–H), 7.60–7.72 (m, 1H, Ar–H), 8.42 (brs, 1H, NH) ppm; 13C-
NMR (125 MHz, DMSO-d6) d: 67.5, 112.9, 116.4, 117.8, 127.2, 128.6, 129.0,
129.6, 133.4, 143.1, 148.9, 167.0 ppm; MS (ESI): m/z 243 (M ? H)?. Anal. Calcd.
for C14H11FN2O (%): C, 69.42; H, 4.55; N, 11.57. Found: C, 69.39; H, 4.53; N,
11.55.
2-(4-N,N-Dimethylaminophenyl)-2,3-dihydroquinazolin-4(1H)-one (3i) White
1
solid; IR (KBr): 3,308, 3,160, 3,057, 1,659, 1,606, 1,513, 1,480 cm-1; H-NMR
(500 MHz, DMSO-d6) d: 2.87 (s, 6H, N(CH3)2), 5.65 (s, 1H, CH), 6.76 (t,
J = 8.2 Hz, 1H, Ar–H), 6.91 (d, J = 6.8 Hz, 1H, Ar–H), 7.12 (brs, 1H, NH),
7.31–7.45 (m, 3H, Ar–H), 7.56 (d, J = 8.8 Hz, 2H, Ar–H), 7.67 (d, J = 7.8 Hz, 1H,
Ar–H), 8.47 (brs, 1H, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 40.4, 68.3,
113.1, 116.9, 117.9, 127.2, 128.0, 129.2, 129.6, 133.3, 142.6, 148.4, 166.8 ppm; MS
(ESI): m/z 268 (M ? H)?. Anal. Calcd. for C16H17N3O (%): C, 71.91; H, 6.37; N,
15.73. Found: C, 71.84; H, 6.30; N, 15.69.
2-(4-Hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3j) White solid; IR
1
(KBr): 3,304, 3,172, 3,059, 1,663, 1,612, 1,507, 1,481 cm-1; H-NMR (500 MHz,
DMSO-d6) d: 5.70 (s, 1H, CH), 6.77–6.84 (m, 2H, Ar–H), 7.19 (s, 1H, NH), 7.33 (d,
J = 7.9 Hz, 1H, Ar–H), 7.49 (d, J = 8.6 Hz, 2H, Ar–H), 7.62–7.75 (m, 3H, Ar–H),
8.45 (s, 1H, NH), 9.97 (s, 1H, OH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 67.9,
11292, 116.4, 117.2, 127.1, 128.1, 129.4, 129.7, 133.2, 143.0, 148.5, 166.9 ppm;
MS (ESI): m/z 241 (M ? H)?. Anal. Calcd. for C14H12N2O2 (%): C, 70.00; H, 5.00;
N, 11.67. Found: C, 69.88; H, 4.94; N, 11.64.
2-(4-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3k) White solid; IR
1
(KBr): 3,292, 3,175, 3,060, 1,662, 1,611, 1,506, 1,477 cm-1; H-NMR (500 MHz,
DMSO-d6) d: 5.71 (s, 1H, CH), 6.79 (t, J = 8.3 Hz, 1H, Ar–H), 6.86 (d,
J = 6.5 Hz, 1H, Ar–H), 7.07 (brs, 1H, NH), 7.27–7.39 (m, 3H, Ar–H), 7.48 (d,
J = 8.8 Hz, 2H, Ar–H), 7.72 (d, J = 7.8 Hz, 1H, Ar–H), 8.49 (brs, 1H, NH) ppm;
13C-NMR (125 MHz, DMSO-d6) d: 67.8, 113.0, 116.6, 117.3, 127.8, 128.6, 129.5,
129.9, 133.4, 142.8, 148.5, 166.6 ppm; MS (ESI): m/z 259 (M ? H)?. Anal. Calcd.
for C14H11ClN2O (%): C, 65.00; H, 4.26; N, 10.83. Found: C, 64.96; H, 4.23; N,
10.79.
2-(3-Hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3l) White solid; IR
1
(KBr): 3,298, 3,173, 3,063, 1,659, 1,614, 1,512, 1,472 cm-1; H-NMR (500 MHz,
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M. Ghashang et al.
DMSO-d6) d: 5.73 (s, 1H, CH), 6.81 (t, J = 8.2 Hz, 1H, Ar–H), 6.97 (d,
J = 6.6 Hz, 1H, Ar–H), 7.09 (brs, 1H, NH), 7.20–7.38 (m, 3H, Ar–H), 7.55 (d,
J = 8.4 Hz, 2H, Ar–H), 7.66–7.70 (m, 1H, Ar–H), 8.44 (brs, 1H, NH), 9.88 (s, 1H,
OH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 68.1, 112.7, 116.7, 117.4, 127.9,
128.7, 129.4, 129.9, 133.7, 143.2, 148.3, 166.3 ppm; MS (ESI): m/z 241 (M ? H)?.
Anal. Calcd. for C14H12N2O2 (%): C, 70.00; H, 5.00; N, 11.67. Found: C, 69.95; H,
5.01; N, 11.68.
Results and discussion
SuSA as a stable reagent was easily prepared by the reaction of succinimide with
neat chlorosulfonic acid (Scheme 2) [27]. The prepared SuSA was assessed for its
O
N
O
CH Cl , ClSO H
2
2
3
+ HCl
SO H
NH
3
Solvent-free,
Ice bath, r.t
O
O
Succinimide
SuSA
Scheme 2 Preparation of succinimide-N-sulfonic acid
Table 1 Synthesis of 2,3-dihydro-2-phenylquinazolin-4(1H)-ones in the presence of SuSA as catalyst in
different reaction conditions
Entry
Solvent
Catalyst (mol%)
Temperature (°C)
Time (h)
Yield (%)a
1
1,4-Dioxane
CHCl3
DMF
5
5
5
5
5
5
5
2
3
4
7
8
5
5
5
Reflux
Reflux
Reflux
Reflux
Reflux
70
4.0
5.0
5.0
5.0
5.0
1.0
3.0
1.0
1.0
1.0
1.0
1.0
2.0
1.5
1.0
44
42
43
82
68
94
63
53
69
83
94
93
57
76
94
2
3
4
EtOH
5
CH3CN
Water
6
7
Solvent-free
Water
70
8
70
9
Water
70
10
11
12
13
14
15
Water
70
Water
70
Water
70
Water
50
Water
60
Water
80
Reaction conditions: 2-aminobenzamide (1 mmol) and benzaldehyde (1 mmol)
a
Isolated yield
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Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
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M. Ghashang et al.
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Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
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M. Ghashang et al.
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Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
catalytic activity in the synthesis of 2,3-dihydro-2-arylquinazolin-4(1H)-ones by
studying the condensation reaction between 2-aminobenzamide and aromatic
aldehydes. For the selection of the optimized condition, the cyclo-condensation
reaction of 2-aminobenzamide (1 mmol) and benzaldehyde (1 mmol) to form 2,3-
dihydro-2-phenylquinazolin-4(1H)-one was chosen as model of the reaction.
Initial studies addressed the effect of solvent and solvent-free condition on the
reaction conversion using 5 mol% of SuSA as catalyst. Various solvents like 1,4-
dioxane, CHCl3, DMF, EtOH, CH3CN, and water was examined. Among the
various solvents (Table 1, entries 1–6) and solvent-free conditions (Table 1, entry
7), water was selected to be the best reaction media for its higher yielding and
shorter reaction time (Table 1, entry 6). The results of the optimization experiments
are summarized in Table 1.
With this result in hand, the effect of catalyst concentration on reaction
conversion was investigated. The optimized amount of the catalyst was determined
using 5, 2, 3, 4, 7, and 8 mol% of SuSA at 70 °C (Table 1, entries 6, 8–12). It was
observed that 5 mol% of SuSA was the best of amount of the catalyst at 70 °C
(Table 1, entry 6). Using lower amounts of catalyst resulted in lower yields, while
higher amounts of catalyst did not affect the reaction times and yields (Table 1,
entries 6, 8–12). Also, this reaction was checked under different temperatures
including 70, and 50, 60, and 80 °C (Table 1, entry 6, 13–15). The greatest yield in
the shortest reaction time was obtained in water at 70 °C in the presence of 5 mol%
of SuSA.
Encouraged by this result, in order to build the generality of the reaction, our
attention moved to the reactions of other aldehydes, and the results are summarized
in Table 2. As expected, this reaction proceeded smoothly and the desired products
were obtained in good to excellent yields. A series of aldehydes with either electron-
98
96
Recyclability of the catalyst SuSA
94%
94
92%
92
91%
90
89%
88
86
1
2
3
4
Number of Runs
Fig. 1 Recycling of catalyst SuSA for the synthesis of 2,3-dihydroquinazolin-4(1H)-one
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M. Ghashang et al.
donating or electron-withdrawing groups attaching to aromatic ring were investi-
gated. The substitution groups on the aromatic ring had no obvious effect on the
yield. From these experiments, it is clearly demonstrated that the synthesis of 2,3-
dihydroquinazolin-4(1H)-ones using SuSA as catalyst under thermal condition is
indeed an effective method and is undoubtedly superior to other procedures with
respect to reaction time, availability of catalyst, work-up procedure, and yields.
In the interests of green chemistry and developing an environmentally benign
process, the recyclability of the catalyst was investigated using a model reaction
between 2-aminobenzamide and benzaldehyde in the presence of 5 mol% of the
catalyst in the presence of water. After the separation of product, the catalyst was
washed with diethyl ether and vacuumed to remove diethyl ether, and the resulting
catalyst was reused directly for the next run. As shown in Fig. 1, the recycled
catalyst was used for further runs, and its activity did not show any significant
decrease even after four runs, the yields ranging from 94 to 89 %.
A plausible mechanism for the formation of products 3 is shown in Scheme 3.
The addition of nucleophiles to the aldehydes is promoted by protonation of the
carbonyl group with the aid of SuSA and enhancing the electrophilicity of this
O
O
O
O
N
N
SO3
H
SO3H
OH
O
O
Ar
H
Ar
H
Ar
H
O
2
N SO3
O
NH2
NH2
O
1
O
N SO3H
O
O
O
O
NH2
NH2
NH2
H
OH
OH2
N
H
-H2O
N
H
N
Ar
Ar
Ar
5
4
H
O
O
NH2
NH
Ar
N
H
Ar
N
H
3
Scheme 3 Proposed mechanism for the formation of 2,3-dihydroquinazolin-4(1H)-ones
123

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones
moiety. The proton from SuSA is donated to the oxygen atom of the aldehyde [29].
Therefore, it is proposed that, at first, the reaction starts through nucleophilic attack
of the amino group in 2-aminobenzamide at the activated carbonyl group in
arylaldehyde by SuSA. It seems that the reaction proceeds through intermediate 4,
such that, after dehydration, the imine intermediate 5 is produced. Then, the
intermediate 5 undergoes protonation and heterocyclization to furnish the
corresponding 2,3-dihydroquinazolin-4(1H)-ones (Scheme 3).
Conclusions
In summary, we have developed a direct and efficient method for the preparation of
2,3-dihydroquinazolin-4(1H)-ones using catalytic amount of SuSA via the cyclo-
condensation of 2-aminobenzamide with an aldehyde. The simplicity of the
procedure, eco-friendly, non-volatile, and easy handling are the advantages of these
methods.
Acknowledgment S.S. Mansoor expresses his gratitude to the management of C. Abdul Hakeem
College, Melvisharam, India, for the facilities and support.
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