Efficient synthesis of novel quinazoline-4(1H)-one derivatives by N-halosulfonamides

Article abstract of DOI:10.1007/s11164-016-2678-5

Abstract: In this research, a facile, effective and one-pot synthesis of new quinazoline-4(1H)-one derivatives is reported. Isatoic anhydride, acid hydrazides or ammonium acetate and aromatic aldehydes in the presence of N-halosulfonamides; N,N,N′,N′-tetr

Full text of DOI:10.1007/s11164-016-2678-5

Res Chem Intermed
DOI 10.1007/s11164-016-2678-5
Efficient synthesis of novel quinazoline-4(1H)-one
derivatives by N-halosulfonamides
Ramin Ghorbani-Vaghei1 Azadeh Shahriari1
•
•
Yaser Maghbooli1 Jafar Mahmoudi1
•
Received: 21 May 2016 / Accepted: 26 July 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract In this research, a facile, effective and one-pot synthesis of new quinazoline-
4(1H)-one derivatives is reported. Isatoic anhydride, acid hydrazides or ammonium
acetate and aromatic aldehydes in the presence of N-halosulfonamides; N,N,N0,N0-te-
trabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethylbenzene-1,3-disulfon-
amide) are used to produce the above-mentioned compounds. In addition, the reaction
medium is in agreement with green chemistry principles.
Graphical Abstract
O
O
R3
R2
O
H
TBBDA and PBBS
N
H2N
O
N
H
R1
R2
O
Reflux, EtOH/H2O
or
N
H
N
H
O
Solventless -100 oC
Or
NH4OAC
R1=aryl, alkyl R2 = aryl
R3= NHCOR1 or H
Keywords N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide
Á
Poly(N-bromo-N-
ethylbenzene-1,3,5-disulfonamide Á Quinazoline-4(1H)-one Á Isatoic anhydride Á
Acid hydrazide
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2678-5)
contains supplementary material, which is available to authorized users.
&
Ramin Ghorbani-Vaghei
rgvaghei@yahoo.com
1
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University,
PO Box 65174, Hamedan, Iran
123

R. Ghorbani-Vaghei et al.
Introduction
According to literature survey, quinazolin-4 (1H)-one derivatives are well known as
important and valuable physiological compounds containing various medical
properties. For example, they are active against bacteria, fungi, and tumors or they
have a mono amine oxidase inhibitor trait [1]. Also, quinazolin-4(1H)-ones can be
converted to quinazolin-4(3H)-one derivatives, which are biologically active
heterocyclic materials and can also be found in some natural products. Specifically,
the quinazolinone core scaffold has been extensively used as a drug-like template in
medicinal chemistry [2]. For example, some novel nonpeptide antagonists for
formyl peptide receptor-like1 with general structure 1 (Fig. 1) were synthesized
when substitution on the para position of the 2-phenyl group of the quinazolinone
backbone could alter the pharmacological properties of the compound [3].
Dihydroquinazolin-4-one with general structure 2 (Fig. 1) was identified as a
thyroid-stimulating hormone receptor agonist [4]. Also, general structure 3 (Fig. 1)
is well known as a TNKS inhibitor [5] and methaqualon structure 4 (Fig. 1) which
has the antimalarial effect currently being used for the assessment of the abuse
liability of sedative hypnotic drugs [6].
In recent years, this type of heterocyclic compound has attracted more attention
due to a wide range of interesting properties; therefore, several techniques have
been designed for their manufacture [7–11]. However, methods for the synthesis of
this heterocycle include multi-step and low-yield reaction sequences.
An atom-efficient and more attractive procedure for the production of
quinazolinones is through a three-component and one-pot reaction of isatoic
anhydride, hydrazides and aldehydes. Until now, only a few strong acid catalysts
such as montmorillonite K-10 [12], silica sulfuric acid [13, 14], zinc(II)
perfluorooctanoate [15], [Zn(PFO)2] [15], KAl(SO4)2Á12H2O [9], Al(H2PO4)3 [9],
gallium(III) triflate [16], molecular iodine [17], MCM-41-SO3H [18], 1-butyl-3-
methylimidazolium tetrafluoroborate ([bmim]BF4) [19, 20], and Amberlyst-15 [21]
have been applied to this reaction. Although most of those methods are
accompanied by different limitations such as use of expensive reagents, strongly
acidic conditions, longer reaction time, low yields and need of an additional
microwave oven, still it is a requirement that we develop new procedures for the
synthesis of quinazolinone derivatives [12].
N-halo sulfonamides have been widely used in organic synthesis; for example,
N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide [TBBDA] and poly(N-bromo-N-
O
O
N
O
O
O
N
N
H
N
O
NH
N
N
N
H
CH3
CH3
N
H
R
O
Me
Me
O
Me
OMe
NHAc
Me
1
2
3
4
Fig. 1 Some examples of quinazolin-4-one derivatives with different properties
123

Efficient synthesis of novel quinazoline-4(1H)-one…
Br
N
Br
N
Br
N
Br
N
CH2
CH2
Br
Br
S
S
S
S
n
O
O
O
O
O
O
O
O
TBBDA
PBBS
Fig. 2 The structure of TBBDA and PBBS
O
O
R3
O
H
TBBDA and PBBS
N
H2N
O
N
H
R1
R2
O
Reflux, EtOH/H2O
or
N
H
R2
N
H
O
Solventless -100 oC
Or
NH4OAC
R1=aryl, alkyl R2 = aryl
R3= NHCOR1 or H
Scheme 1 Synthesis of quinazolin-4(1H)-one derivatives
ethylbenzene-1,3-disulfonamide) [PBBS] (Fig. 2)] as catalyst or reagent utilized in
the synthesis of various compounds in our older research [22–27]. Some unique
advantages of their applications include high stability, availability of the catalyst, a
metal-free nature, low toxicity, neutral media and simple reaction conditions; thus,
they are utilized in synthesis of diverse and new quinazoline-4(1H)-one derivatives,
from the reaction of isatoic anhydride, aldehydes, N-halo sulfonamides (TBBDA
and PBBS as reagent or catalyst) with acid hydrazides or ammonium acetate under
reflux in ethanol/water or solvent-free conditions (Scheme 1).
Results and discussion
Preparation of TBBDA and PBBS is not difficult and they are unchanged even up to
2 months. TBBDA and PBBS are non-volatile, harmless, and low-cost reagents and
they have not been used for quinazolin-4(1H)-one derivative synthesis before. In
addition, products in this study have not been reported in previous literature except
for a case rendered in Table 3, entry 10. However, the improvement in reaction time
and yield from 3–6 h/64 % [32] to 2 h/95 % have been found in current research.
Furthermore, the advancement of the reaction condition from a step-by-step
synthesis to a one-pot reaction has occurred and the method of purification has been
modified from column chromatography to purification with solvent (our research).
Considering the benefits such as time and resources preservation, avoiding a long
separation process, purification of intermediates and increasing the efficiency of a
chemical reaction, this reaction was carried out in one-pot condition with various
amounts of reagents, while optimizing the conditions for the formation of N-(2-(4-
123

R. Ghorbani-Vaghei et al.
chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl)-3-methoxybenzamide using
3-methoxybenzhydrazide, isatoic anhydride, and 4-chlorobenzaldehyde (Table 1).
With attention paid to Table 1, due to the lack of proper results about using only
water or ethanol and solvent-free conditions, a mixture of ethanol and water was
chosen as the best solvent for these reactions (entry 4). This selection provides an
environmentally safe method without any carcinogenic effect of common organic
solvents.
Also, we test this one-pot reaction with ammonium acetate instead of acid
hydrazide to study the effects of solvent, temperature and amount of catalysts in
increments of yield of 2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one using
ammonium acetate, isatoic anhydride, and 4-chlorobenzaldehyde (Table 2).
According to Table 2, solvent-free conditions in entry 7 were selected as the best
choice for these reactions, which are in agreement with green chemistry principles
as well.
After optimization of the reaction conditions, in order to study the generality of
the procedure, isatoic anhydride was mixed with various aromatic aldehydes or
salicylaldehyde derivatives and different acid hydrazides or ammonium acetate as a
nucleophile. These reactants were subjected to the reaction conditions and provided
correspondingly good to high yields (Table 3) and only in one case oxidation was
occurred (Table 3, entry 14).
The possible mechanism shown in Scheme 2 may be suggested for the
conversion of various aldehydes and acid hydrazides or ammonium acetate with
isatoic anhydride into quinazolin-4(1H)-ones [28–30]. In the beginning, due to these
N-sulfonamides focusing on liberating Br? as an electrophile and their capability of
producing active carbonyl compounds [17–23], the reaction requires a Br? transfer
from the reagents to isatoic anhydride to form (A). Afterward, nucleophilic attack of
Table 1 Optimization of reaction conditions for the synthesis of N-(2-(4-chlorophenyl)-1,2-dihydro-4-
oxoquinazolin-3(4H)-yl)-3-methoxybenzamide using 3-methoxybenzhydrazide, isatoic anhydride, and
4-chlorobenzaldehyde
Entry
Solvent
[TBBDA (1–7)/PBBS
(8–10) (g)]
Temperature (°C)
Time (h)
Yieda (%)
1
2
3
4
5
6
7
8
9
10
a
EtOH
0
25
3.5
3.5
2
–
EtOH–H2O (4:1)
EtOH–H2O (4:1)
EtOH–H2O (4:1)
Solvent-free
0
Reflux
Reflux
Reflux
100
Trace
80
95
–
0.03
0.05
0.05
0.05
0.05
0.05
0.08
0.10
1
4
H2O
100
4
–
Acetonitrile
Reflux
Reflux
Reflux
Reflux
2.5
2.2
2.2
2.2
70
5
EtOH–H2O (4:1)
EtOH–H2O (4:1)
EtOH–H2O (4:1)
60
88
Experimental conditions: Isatoic anhydride (1 mmol), 4-cholorobenzaldehyde (1 mmol) and
3-methoxybenzhydrazide (1 mmol)
123

Efficient synthesis of novel quinazoline-4(1H)-one…
Table 2 Optimization of reaction conditions for the synthesis of 2-(4-chlorophenyl)-2,3-dihydroquina-
zolin-4(1H)-one using ammonium acetate, isatoic anhydride, and 3,5-dichlorosalsiylaldehyde
Enty
Solvent
TBBDA
Temperature (°C)
Time (h)
Yieda (%)
1
2
3
4
5
6
7
8
a
EtOH
0
25
4
Trace
50
EtOH
0.05
0.1
0.1
0.1
0.05
0.1
0.1
Reflux
Reflux
Reflux
Reflux
100
4
EtOH
3
50
H2O
3
35
EtOH–H2O (4:1)
Solvent free
Solvent free
Acetonitrile
4
60
2
63
100
0.5
3
98
Reflux
55
Experimental conditions: Isatoic anhydride (1 mmol), 4-cholorobenzaldehyde (1 mmol) and ammo-
nium acetate (2 mmol)
acid hydrazide or ammonium acetate to (A) produced (B). After the reaction of
(B) with activated aldehyde via TBBDA followed by intramolecular cyclization and
elimination of H2O, quinazolin-4(1H)-one derivatives (D) were obtained. In order to
find out the role of catalysts when we mixed isatoic anhydride with nucleophile
species (hydrazide or ammonium acetate) without catalysts, not in this step for
yielding (B) nor with addition of aldehyde, no product was observed. In a
multicomponent reaction with free catalyst conditions, no product was obtained, as
well (Tables 1, 2, entries 1). Furthermore, benzene-1,3-disulfonamide was recov-
ered and then reused for preparation of TBBDA or, in another case (with
ammonium acetate), catalyst was recovered as TBBDA.
Experimental
All commercially available chemicals were obtained from Merck Fluka and Aldrich
companies, and used without further purification unless otherwise stated. Proton
nuclear magnetic resonance (1H NMR) and carbon-13 (13C NMR) spectra were
recorded on Bruker Evans 400 MHz FT NMR spectrometers (undertaken at the
University of Isfahan and University of Urmia). Infrared (IR) spectroscopy was
conducted on a Perkin Elmer GX Fourier transform (FT)-IR spectrometer followed
by mass spectra recordation on a Shimadzu QP 1100 BX mass spectrometer
(University of Tehran, Iran).
Typical procedure for the preparation of N-(2-(4-chlorophenyl)-1,2-dihydro-4-
oxoquinazolin-3(4H)-yl)-3-methoxybenzamide (Table 2, entry 7): In a round flask,
a mixture of isatoic anhydride (0.163 g, 1 mmol) and 3-methoxy benzhydrazide
(0.16 g, 1 mmol) in 5 mL EtOH/H2O (4:1) were heated and refluxed. Then,
TBBDA (0.05 g, 0.10 mmol) or PBBS (0.1 g) and 4-chlorobenzaldehyde (0.14 g,
1 mmol) was added to the mixture and stirred for an appropriate time (Table 2,
entry 7). After completion of the reaction, when bright blue spot appeared on thin
123

R. Ghorbani-Vaghei et al.
Table 3 Synthesis of quinazolin-4(1H)-one derivatives with aldehydes, hydrazides or ammonium
acetate, isatoic anhydride using TBBDA and PBBS as reagents
Time(h)/Yield (%)b
Entry
Aldehyde
Nucleophile
Producta
PBBS
TBBDA
O
O
N
H2N
MeO
O
N
H
NH
1
1.5/80
3.2/78
CHO
N
H
OMe
O
F
O
N
O
H2N
N
H
NH
CHO
2
3
2.5/68
3.6/60
N
H
F
Cl
O
O
N
O
H2N
N
H
NH
CHO
2/85
1/90
2.8/75
1.9/85
N
H
Cl
Cl
O
O
N
O
H2
N
N
H
NH
4
5
CHO
N
H
Cl
O
N
Me
O
Br
O
NH
H2
N
N
Me
Me
CHO
1.5/95
2.1/75
2.6/83
3.5/60
H
N
H
Br
O
Me
O
Cl
O
NH
N
H2
N
N
H
N
6
7
H
CHO
Cl
OMe
Cl
O
H2N
OMe
O
N
H
O
CHO
1/95
2.2/88
NH
N
N
H
Cl
layer chromatography (TLC) [solvent ratio: acetone/n-hexane (8:20)], the solid was
filtered and washed with ethanol (2 9 3 mL) and ether. The crude product was
recrystallized in hot ethanol (to obtain sulfonamide, the solid was filtered; then,
solvent was evaporated and CH2Cl2 (5 mL) was added, the precipitated sulfonamide
was recovered by filtration. Furthermore, sulfonamide can be reused for preparation
of TBBDA), the pure product (0.38 g, 95 %) was obtained as a cream powder. Mp:
199–200 °C; IR (KBr): t (cm-1) 3417, 3199, 1660, 1651, 1580, 1284, 804;1H NMR
(400 MHz, DMSO-d6): dH (ppm) 3.75 (s, OCH3, 3H), 4.65 (s, CH, 1H), 6.38 (s, NH,
1H), 6.69–7.95 (m, CH aromatic, 12H), 8.9 (s, NH, 1H).13C NMR (100 MHz,
DMSO-d6): dc (ppm) 55.29, 74.35, 111.78, 114.66, 114.74, 118.96, 119.29, 119.84,
129.05, 129.14, 129.20, 129.34, 129.48, 131.49, 132.55, 134.63, 135.74, 135.85,
146.43, 159.46, 164.52, 166.35. MS: m/z 408 (M?, 4 %), 257 (98), 242 (72), 214
(13), 180 (84), 151 (18).
N-(1,2-dihydro-2-(4-methoxyphenyl)-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 1) Cream powder. Mp: 224–226 °C; IR (KBr): t (cm-1) 3390, 3312,
123

Efficient synthesis of novel quinazoline-4(1H)-one…
Table 3 continued
Time(h)/Yield (%)b
PBBS
Entry
Aldehyde
Nucleophile
Producta
TBBDA
O
N
Me
O
Cl
O
NH
H2N
8
2/85
3.5/70
N
H
Me
CHO
N
H
Cl
O2N
O
O
O
H2N
N
H
CHO
NH
9
N
1.5/94
2.5/80
N
H
NO2
O
N
Me
O
O
10
Cl
Cl
NH
H2N
2/95
3.5/82
2.4/88
N
Me
H
CHO
N
H
Cl
Cl
OHC
O
O
N
O
H2N
N
H
NH
Br
1.5/96
11
12
N
H
Br
OH
O
OHC
NH4OAC
OH
NH
1/95
1/93
1/98
1.5/83
1.5/88
1/ 95
N
H
Cl
Cl
OH
O
OHC
OH
NH
NH4OAC
NH4OAC
13
14
N
H
Br
Br
O
OH
OHC
OH
NH
N
OMe
OMe
OH
O
OHC
Cl
Cl
NH4OAC
NH
OH
15
Cl
1.5/93
2/90
N
H
Cl
a
The known compounds were characterized from their physical properties, in comparison with authentic
samples, and by spectroscopic methods
b
Isolated yield
1685, 1653, 1610, 1252; 1H NMR (400 MHz, DMSO-d6): dH (ppm) 3.74 (s, OCH3,
3H), 6.14 (s, CH, 1H), 6.80–7.62 (m, CH aromatic, 13H), 7.29 (s, NH, 1H), 10.39 (s,
NH, 1H). 13C NMR (100 MHz, DMSO-d6): dc (ppm) 55.15, 74.02, 113.49, 113.73,
114.60, 117.74, 127.37, 127.66, 128.01, 128.30, 129.45, 129.80, 129.85, 131.77,
132.23, 132.28, 133.88, 148.03, 148.08, 159.87, 163.30, 165.47.MS: m/z 373 (M?,
1.7 %), 371 (1.8), 321 (4), 295 (3.8), 280 (25), 253 (98), 238 (7), 210 (21).
N-(2-(4-fluorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 2) Cream powder. Mp: 243 °C; IR (KBr): t (cm-1) 3303, 3241, 1687, 1650,
1
1615, 1225; H NMR (400 MHz, DMSO-d6): dH (ppm) 6.2 (s, CH, H), 6.80–7.61
(m, CH aromatic, 13H, 6.80 (s, NH, 1H), 10.44 (s, NH, 1H), 13C NMR (100 MHz,
DMSO-d6): dc (ppm) 73.77, 113.68, 114.63, 114.92, 115.13, 117.06, 117.93,
127.32, 128.02, 128.34, 130.27, 130.35, 131.85, 132.15, 134.01, 147.84, 147.89,
123

R. Ghorbani-Vaghei et al.
Br
O
[TBBDA]
H2N
O
O
O
R1
R1
N
H
[TBBDA]
O
O
NH2
N
H
O
N
H
O
CO2
(B)
(A)
H
O
Br
[TBBDA]
R3
O
R1
N
R1
R3
H
N
Br
N
N
[TBBDA]
H
H2O
R3
H2N
NH2
(D)
(C)
S
S
R1: NHCOR2 or HOAC
R2 : aryl or alkyl
R3 : aryl
O
O
O
O
HOBr
Or
[TBBDA]
Scheme 2 Suggested mechanism for the synthesis of substituted quinazolin-4(1H)-ones
161.27, 163.11, 163.70, 165.50. MS: m/z 361 (M?, 3 %), 360 (3), 319 (5), 295 (8),
280 (35), 241 (98), 226 (80), 210 (10), 198 (33).
N-(2-(2-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 3) White powder. Mp: 223–224 °C; IR (KBr): t (cm-1) 3295, 3199, 1682,
1
1665, 1615, 1289; H NMR (400 MHz, DMSO-d6): dH (ppm) 6.66 (s, CH, H),
6.79–7.90 (m, CH aromatic, 13H), 6.82 (s, NH, 1H), 10.51 (s, NH, 1H) 13C NMR
(100 MHz, DMSO-d6): dc(ppm) 70.56, 113.17, 114.44, 117.78, 127.43, 127.97,
128.34, 129.27, 129.95, 130.64, 131.87, 132.16, 132.21, 132.97, 134.15,
135.74,135.78, 147.38, 147.43, 162.81, 165.55.MS: m/z 378 (M?, 8 %), 360 (4),
257 (98), 242.(67), 214 (12).
N-(2-(4-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 4) Cream powder. Mp: 267 °C; IR (KBr): t (cm-1) 3327, 3253, 1686, 1683,
1
1653, 1675, 1614; H NMR (400 MHz, DMSO-d6): dH (ppm) 6.18(s, CH, H),
6.79–7.73 (m, CH aromatic, 13H), 7.34 (s, NH, 1H), 10.47 (s, NH, 1H).13C NMR
(100 MHz, DMSO-d6): dc (ppm), 73.76, 113.60, 114.61, 117.94, 127.35, 128.00,
128.23, 128.37, 129.94, 131.91, 132.03, 132.08, 133.67, 134.06, 137.05, 137.09,
147.70, 147.75, 162.95, 165.51. MS: m/z 378 (M?, 1.6 %), 375 (4), 257 (88), 242
(41), 214 (10).
N-(2-(2-bromophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) acetamide (Table 2,
entry 5) Cream powder. Mp: 271–273 °C; IR (KBr): t (cm-1) 3338, 3233, 3206,
1
1698, 1637, 1612, 1508; H NMR (400 MHz, DMSO-d6): dH (ppm) 1.77 (s, CH3,
3H), 6.42 (s, CH, H), 6.73–7.70 (m, CH aromatic, 8H), 6.77 (s, NH, 1H), 9.91 (s,
NH, 1H). 13C NMR (100 MHz, DMSO-d6): dc (ppm) 20.31, 73.05, 112.85, 114.32,
117.56, 122.85, 127.86, 128.16, 129.36, 130.88, 132.78, 134.10, 137.88, 146.86,
162.22, 168.30. MS: m/z 360 (M?, 6 %), 301 (98), 286 (39), 218 (9), 180 (17).
123

Efficient synthesis of novel quinazoline-4(1H)-one…
N-(2-(3-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) acetamide (Table 2,
entry 6) Cream powder. Mp: 200–203 °C; IR(KBr): t (cm-1) 3308, 3242.1, 1704,
1
1637, 1615, 1513; H NMR (400 MHz, DMSO-d6): dH (ppm) 1.76 (s, CH3, 3H),
6.02 (s, CH, 1H), 6.76–7.70 (m, CH aromatic, 8H), 7.32 (s, NH, 1H), 9.98 (s, NH,
1H). 13C NMR (100 MHz, DMSO-d6): dc (ppm) 20.23, 73.32, 113.43, 114.51,
117.78, 126.22, 127.22, 127.90, 128.97, 130.27, 133.00, 134.04, 141.31, 147.13,
162.29, 168.36.MS: m/z 316 (M?, 4 %), 303 (5), 291 (9), 257 (98), 242 (82), 214
(7), 180 (17).
N-(2-(2-chlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) acetamide (Table 2,
entry 8) Cream powder. Mp: 269 °C; IR (KBr): t (cm-1) 3215, 3180, 1650, 1607,
1581, 1562;1H NMR (400 MHz, DMSO-d6): dH (ppm) 1.76 (s, CH3, 3H), 6.45 (s,
CH, 1H), 6.73–7.70 (m, CH aromatic, 8H), 7.31 (s, NH, 1H), 9.93 (s, NH, 1H) 13C
NMR (100 MHz, DMSO-d6): dc (ppm) 20.28, 70.45, 112.92, 114.30, 114.34,
117.61, 127.56, 127.86, 129.17, 129.55, 130.57, 134.09, 136.25, 146.92, 162.26,
168.30.MS: m/z 316 (M?, 8 %), 298 (2), 257 (98), 242 (46), 214 (5), 180 (6).
N-(1,2-dihydro-2-(4-nitrophenyl)-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 9) Cream powder. Mp: 260–261 °C; IR (KBr): t (cm-1) 3325, 3273,
1
1683, 1651, 1614; H NMR (400 MHz, DMSO-d6): dH (ppm) 6.32(s, CH, H),
6.81–8.28 (m, CH aromatic, 13H), 6.84 (s, NH, 1H), 10.58 (s, NH, 1H). 13C NMR
(100 MHz, DMSO-d6): dc (ppm) 73.41, 86.47, 87.22, 102.59, 103.51, 104.55,
114.63, 114.66, 118.09, 123.34, 127.42, 127.95, 128.40, 129.43, 132.04, 134.20,
134.26, 135.32, 145.46, 147.32, 154.63. MS: m/z 388 (M?, 5 %), 386 (10), 368 (11),
268 (98), 253 (51), 207 (23), 119 (17), 105 (88), 77 (65).
N-(2-(2,4-dichlorophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl)
acetamide
(Table 2, entry 10) Cream powder. Mp: 238 °C (235 °C) [31]; IR (KBr): t
1
(cm-1) 3260, 3243,1702, 1672, 1611, 1018; H NMR (400 MHz, DMSO-d6): dH
(ppm) 1.77 (s, CH3, 3H), 6.42 (s, CH, H), 6.72–7.69 (m, CH aromatic, 7H), 7.31 (s,
NH, 1H), 9.92 (s, NH). 13C NMR (100 MHz, DMSO-d6): dc (ppm) 20.79, 70.92,
113.36, 115.54, 117.55, 118.94, 129.14, 130.17, 131.97, 134.23, 134.72, 135.89,
135.95, 147.32, 162.64, 168.83. MS: m/z 350 (M?, 16 %), 332 (4), 291 (98), 276
(78), 248 (8), 214 (16).
N-(2-(4-bromophenyl)-1,2-dihydro-4-oxoquinazolin-3(4H)-yl) benzamide (Table 2,
entry 11) Cream powder. Mp: 300 °C; IR (KBr): t (cm-1) 3313, 3244, 1686,
1649, 1614; 1H NMR (400 MHz, DMSO-d6): dH (ppm) 6.15 (s, CH, 1H), 6.77–7.72
(m, CH aromatic, 13H), 6.77(s, NH, 1H), 10.45 (s, NH) .13C NMR (100 MHz,
DMSO-d6): dc (ppm) 74.31, 114.10, 115.80, 117.71, 119.13, 122.81, 127.10,
127.75, 127.81, 128.61, 129.61, 131.29, 132.40, 132.58, 133.61, 138.04, 148.18,
148.24,158.81, 163.39, 166.01.MS: m/z 422 (M?, 2 %), 368 (5), 339 (8), 313 (12),
264 (14), 239 (14), 138 (25).
General procedure for preparation of 2-(3,5-dichloro-2-hydroxyphenyl)-2,3-dihy-
droquinazolin-4(1H)-one A mixture of isatoic anhydride (0.163 g, 1 mmol) and
ammonium acetate (0.15 g, 2 mmol), TBBDA (0.1 g, 0.2 mmol) or PBBS (0.12 g)
123

R. Ghorbani-Vaghei et al.
and 3,5-dichlorosalsiylaldehyde (0.19 g, 1 mmol) was added to the mixture and
stirred for an appropriate time (Table 3, entry 15). After completion of the reaction,
when bright blue spot appeared on TLC [solvent ratio: acetone/n-hexane (8:20)], the
solid was filtered and then washed with ethanol (2 9 3 mL) and water. The crude
product was recrystallized in hot ethanol. The pure product (0.29 g, 93 %) was
obtained as a white powder. Mp [ 310 °C; IR (KBr): t (cm-1) 3395, 3295, 3197,
1
1655; H NMR (400 MHz, DMSO-d6): dH (ppm) 6.12 (s, CH, 1H), 6.98 (s, NH,
1H), 6.77–7.59 (m, CH aromatic, 6H), 8.18 (s, OH, 1H). 10.12 (s, NH, 1H). 13C
NMR (100 MHz, DMSO-d6): dc (ppm) 61.43, 114.64, 114.68, 117.56, 122.10,
123.13, 126.09, 127.34, 128.78, 131.55, 133.43, 147.61, 149.45, 163.64. MS: m/z
309.
2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (Table 3, entry
12) Cream powder. Mp [ 300 °C; IR (KBr): t (cm-1) 3385, 3200, 3195, 1650;
1H NMR (400 MHz, DMSO-d6): dH (ppm) 6.15 (s, CH, 1H), 6.81–7.72 (m, CH
aromatic, 7H), 7.01 (s, NH, 1H), 8.21 (s, OH, 1H), 10.16 (s, NH, 1H) .13C NMR
(100 MHz, DMSO-d6): dc (ppm) 61.4, 114.64, 114.69, 117.56, 122.08, 123.12,
126.09, 127.34, 128.78, 131.53, 133.43, 147.62, 149.46, 163.64. MS: m/z 274.
2-(5-boromo-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (Table 3, entry
13) Cream powder. Mp [ 300 °C; IR (KBr): t (cm-1) 3390, 3285, 1667,1644;
1H NMR (400 MHz, DMSO-d6): dH (ppm) 6.01 (s, CH, 1H), 6.54–8.52 (m, CH
aromatic, 7H), 6.82 (s, NH, 1H), 8.10 (s, OH, 1H), 10.32 (s, NH, 1H) .13C NMR
(100 MHz, DMSO-d6): dc (ppm) 60.83, 109.80, 114.45, 117.22, 117.61, 120.07,
127.30, 129.66, 129.99, 131.83, 133.32, 147.77, 154.03, 163.74.
2-(2-hydroxy-5-methoxyphenyl) quinazolin-4(3H)-one : (Table 3, entry 14) Yel-
1
low powder. Mp [ 300 °C; IR (KBr): t (cm-1) 3204, 3150, 1672, 1612; H NMR
(400 MHz, DMSO-d6): dH (ppm) 3.86 (s, CH3, 3H), 6.99–8.21 (m, CH aromatic,
7H), 7.81 (s, OH, 1H), 13.53 (s, NH, 1H) .13C NMR (100 MHz, DMSO-d6): dc
(ppm) 55.81, 110.12, 112.98, 118.93, 120.627, 121.78, 126.01, 126.95, 128.08,
135.03, 146.08, 151.68, 153.65, 154.38, 161.51. MS: m/z 268.
Conclusions
We proposed a simple method and efficient procedure for the synthesis of
quinazolin-4(1H)-one derivatives using TBBDA and PBBS as novel reagents
utilizing an easy synthetic technique, low-cost reagents, a one-pot procedure, good
to high yields, environmental friendliness (non-corrosive reagent and green solvent)
and a facial isolation for synthesis of new quinazoline-4(1H)-one derivatives with
probable pharmacological properties like similar compounds [32].
Acknowledgments We would like to thank Bu-Ali Sina University, Center of Excellence in
Developmental of Environmentally Friendly Methods for Chemical Synthesis (CEDEFMCS) for
financial support of this study.
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