Design, synthesis and antibacterial evaluation of 2-alkyl- and 2-aryl-3-(phenylamino)quinazolin-4(3H)-one derivatives

Article abstract of DOI:10.1515/hc-2016-0201

2-Alkyl and 2-aryl-3-(phenylamino)quinazolin-4(3H)-ones 4a-h were synthesized in a one-pot three-component condensation of an isatoic anhydride 1a-h, ethyl or methyl ortho ester and phenylhydrazine in the presence of KAl(SO₄)₂·12H₂O (alum) as a nontoxic, reusable, inexpensive and easily available catalyst. The synthesis was conducted under microwave irradiation or classical heating. Products 4a and 4b show good antimicrobial activities.

Full text of DOI:10.1515/hc-2016-0201

Heterocycl. Commun. 2017; 23(2): 105–108
ADlieAssghigar nMo,hsamymnadtih*, ReeszaiAshdaennovdanadnAlitAibbolahacsatnei Sroioakli evaluation
of 2-alkyl- and 2-aryl-3-(phenylamino)quinazolin-
4(3H)-one derivatives
Received November 6, 2016; accepted January 13, 2017; previously
published online March 29, 2017
DOI 10.1515/hc-2016-0201
2-iodoanilines with trimethyl orthoformate and amines
in the presence of palladium on activated charcoal (Pd/C)
[25] and condensation of anthranilic acid with acyl chlo-
rides and aromatic/aliphatic amines in acidic ionic liquids
under microwave irradiation [26].
Abstract: 2-Alkyl and 2-aryl-3-(phenylamino)quinazolin-
4(3H)-ones 4a–h were synthesized in a one-pot three-
component condensation of an isatoic anhydride 1a–h,
ethyl or methyl ortho ester and phenylhydrazine in the
presence of KAl(SO4)2ꢀ·ꢀ12H2O (alum) as a nontoxic, reus-
able, inexpensive and easily available catalyst. The syn-
thesis was conducted under microwave irradiation or
classical heating. Products 4a and 4b show good antimi-
crobial activities.
Results and discussion
Multicomponent reactions (MCRs) are powerful tools in
the modern drug discovery process in terms of lead finding
and lead optimization. Recently, we have reported the
Keywords: alum; antimicrobial activity; isatoic anhydride; preparation of indenopyridine [27], bis[spiro(quinazoline-
ortho esters; quinazolin-4(3H)-one.
oxindole)]
[28],
bis-dihydroquinazolinone
[29],
1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione[30]
and 2-aryl-3-(phenylamino)-2,3-dihydroquinazolin-4(1H)-
one [31] via multicomponent reactions. Along this line,
we have designed a three-component one-step synthesis
of quinazolin-4(3H)-ones. The use of KAl(SO4)2ꢀ·ꢀ12H2O
(alum), which is relatively nontoxic and inexpensive, is
the center of our study [32, 33].
Introduction
Quinazolin-4(3H)-one and its derivatives possess a wide
spectrum of biological properties [1, 2], such as anti-
inflammatory [3], antihypertensive [4], anti-HIV [5], anti-
cancer [6], antiviral [7] and antibacterial activity [8]. In
addition, these structural fragments are present in several
bioactive natural products [9–11], such as l-vasicinone [12],
chrysogine [13] and drugs [14] such as methaqualone [15],
febrifugine and isofebrifugine [16, 17]. There are several
methods in the literature for the preparation of quinazo-
lin-4(3H)-ones [18–21]. These are cyclocondensation of
2-aminobenzamides with acyclic or cyclic 1,3-diketones
catalyzed by FeCl3 [22], condensation of 2-halobenzamides
(or 2-halonicotinamides), aldehydes and sodium azide
catalyzed by copper [23], reaction of benzoxazinones with
primary aliphatic and aromatic amines [24], reaction of
The reaction of isatoic anhydride 1a, phenylhydrazine
2 and triethyl orthoformate 3a in ethanol in the presence
of a catalytic amount of alum under reflux conditions was
completed in 130 min. Workup of the mixture furnished
3-(phenylamino)quinazolin-4(3H)-one (4a) in an 89%
yield (Scheme 1). Encouraged by this success, we extended
this reaction of phenylhydrazine 2 with a range of isatoic
anhydrides 1b–h and orthoesters 3b–h under similar con-
ditions, furnishing the respective 3-(phenylamino)quina-
zolin-4(3H)-one 4b–h in good yields (Scheme 1). We then
examined this reaction under microwave irradiation and
found that it furnishes 3-(phenylamino)quinazolin-4(3H)-
ones 4a–h in a much shorter time of 5 min. In order to
increase the energy input and provide a uniform heating,
a small amount of N,N-dimethylacetamide (DMAC), an
excellent energy-transfer solvent with a high dielectric
constant, was added to the reaction mixture. The struc-
tures of all products were fully consistent with IR, 1H NMR,
13C NMR, MS and elemental analysis data.
*Corresponding author: Ali Asghar Mohammadi, Department of
Chemistry, Sabzevar Branch, Islamic Azad University, Sabzevar,
Iran, e-mail: Aliamohammadi@iaus.ac.ir
Reza Ahdenov: Department of Chemistry, Sabzevar Branch, Islamic
Azad University, Sabzevar, Iran
Ali Abolhasani Sooki: Shaheed Beheshti University, Academic
Center for Education, Culture, and Research, Research Institute of
Applied Sciences, Tehran, Iran
The synthesized compounds were screened in vitro
for their antibacterial activities against Gram-negative
Brought to you by | University of Michigan
Authenticated
Download Date | 4/3/17 6:14 PM

ꢁꢁꢁꢂ
ꢀA.A. Mohammadi et al.: 2-Alkyl and 2-aryl-3-(phenylamino)quinazolin-4(3H)-ones
106ꢀ
O
O
H
N
R1
R1
KAl(SO4)2 12H2O
O
N
R2C(OR3)3
PhNHNH2
MW or ∆
N
R2
N
O
2
3a–h
H
1a–h
4a–h
a: R1 = H; R2 = H; R3 = Et; heating time: 130 min
b: R1 = H; R2 = Me; R3 = Et; heating time: 140 min
c: R1 = H; R2 = Et; R3 = Et; heating time: 150 min
d: R1 = H; R2
e: R1 = H; R2
=
=
nPr; R3 = Me; heating time: 160 min
nBu; R3 = Me; heating time: 180 min
f: R1 = H; R2 = Ph; R3 = Me; heating time: 160 min
g: R1 = Cl; R2 = Me; R3 = Et; heating time: 160 min
h: R1 = Cl; R2 = Et; R3 = Me; heating time: 170 min
Scheme 1ꢁSynthesis of 3-(phenylamino)quinazolin-4(3H)-ones 4a–h.
at 70 eV on a Shimadzu QP 1100BX mass spectrometer. IR spectra
were recorded in KBr pellets on a Shimadzu IR-470 spectrophotome-
ter. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were determined
on a Bruker 300 DRX Avance instrument. Elemental analyses for C, H
and N were performed using a Heraus CHN rapid analyzer.
bacteria Escherichia coli, ATCC 25922, Pseudomonas aer-
uginosa, ATCC 85327, Klebsiella pneumonia, ATCC 29655
and Gram-positive bacteria Enterococcus faecalis, ATCC
29737, Bacillus subtilis ATCC 465, Bacillus pumilus PTCC
1114, Micrococcus luteus PTCC 1110, Staphylococcus aureus
ATCC 25923, Staphylococcus epidermidis ATCC 12228 and
Streptococcus mutans, PTCC 1601. Inhibition zones (IZ)
were measured by the disk diffusion method [34] and,
subsequently, the minimum inhibitory concentrations
(MIC) were also obtained [35].
Activities of the compounds were compared with
those of tetracycline and gentamicin used as standards.
The screening results indicate that some of the tested
compounds exhibit significant antibacterial activities.
Compound 4a, unsubstituted at position 2 of the quinazo-
line moiety shows much better activity than the reference
drugs. 2-Alkylquinazolines 4b–d exhibit good activity,
while the remaining compounds generally show inferior
activities against the tested bacterial strains.
General procedures for the synthesis of 2-alkyl- and
2-aryl-3-(phenylamino)quinazolin-4(3H)ones 4a–h
Classical heatingꢁA mixture of an isatoic anhydride (1, 1 mmol),
phenylhydrazine (2, 2 mmol), an ortho ester (3, 2 mmol), alum (0.15 g)
and EtOH (10 mL) was stirred and heated under reflux for a period of
time indicated in Scheme 1. After completion of the reaction (moni-
tored by TLC, ethyl acetate/n-hexane, 1/1), the mixture was concen-
trated under reduced pressure and the residue was treated with water
(20 mL). The resultant solid was separated by filtration and crystal-
lized from ethanol.
Microwave irradiationꢁA mixture of an isatoic anhydride (1,
1 mmol), phenylhydrazine (2, 1 mmol), an ortho ester 3 (2 mmol),
alum (0.15 g) and five drops of N,N-dimethylacetamide (DMAC) was
mixed thoroughly in a Pyrex test tube. The homogenized mixture was
irradiated in a microwave oven in two stages, with a cooling period
between the irradiations: 210 W for 3 min, cooling, then 360 W for
5 min. After cooling to room temperature, the mixture was treated
with water (10 mL) and the resultant precipitate was filtered and crys-
tallized from ethanol.
Conclusions
This paper describes a convenient and efficient method
for the synthesis of 2-alkyl and 2-aryl-3-(phenylamino)
quinazolin-4(3H)-one derivatives through the three-com- 3-(Phenylamino)quinazolin-4(3H)-one(4a)ꢁThis compound was
obtained in yields of 89% (heat) and 93% (MW) as a white powder;
ponent reaction of an isatoic anhydride, an ortho ester
mp 164–166°C; (lit. [36]: mp 166–167°C, yield 59%).
and phenylhydrazine using KAl(SO4)2ꢀ·ꢀ12H2O (alum) as a
heterogeneous catalyst. The method offers a high yield of
2-Methyl-3-(phenylamino)quinazolin-4(3H)-one (4b)ꢁThis com-
products and an easy work-up and uses an inexpensive,
non-toxic and easily available catalyst.
pound was obtained in yields of 90% (heat) and 95% (MW) as a
white powder; mp 209–211°C; IR (ν/cm−1): 3296, 1634, 1602(Cꢀ=ꢀO); 1H
NMR (DMSO-d6) δ 3.39 (s, 3H, CH3), 6.65 (d, Jꢀ=ꢀ7.7 Hz, 2H, Ar), 6.83 (t,
Jꢀ=ꢀ7.3 Hz, 1H, Ar), 7.19 (t, Jꢀ=ꢀ7.9 Hz, 2H, Ar), 7.50 (t, J =7.1 Hz, 1H, Ar),
7.67 (d, Jꢀ=ꢀ8.0 Hz, 1H, Ar), 7.84 (t, Jꢀ=ꢀ8.0 Hz, 1H, Ar), 8.09 (d, J =7.2 Hz,
1H, Ar), 9.13 (s, 1H, NH); 13C NMR (DMSO-d6): δ 21.8, 112.8, 120.7, 121.5,
126.6, 126.9, 127.3, 129.6, 135.1, 147.22, 147.29, 158.1, 160.6; MS: m/z 251
Experimental
Melting points were obtained in open capillary tubes on an Electro-
thermal 9200 apparatus. Electron-impact mass spectra were recorded
+
(M ). Anal. Calcd for C15H13N3O: C, 71.70; H, 5.21; N, 16.72. Found: C,
71.59; H, 5.11; N, 16.61.
Brought to you by | University of Michigan
Authenticated
Download Date | 4/3/17 6:14 PM

ꢂꢁꢁꢁ
A.A. Mohammadi et al.: 2-Alkyl and 2-aryl-3-(phenylamino)quinazolin-4(3H)-onesꢀ
ꢀ107
2-Ethyl-3-(phenylamino)quinazolin-4(3H)-one (4c)ꢁThis com-
Council Organization of the Islamic Republic of Iran for
support.
pound was obtained in 85% (heat) and 91% (MW) yields as a white
1
powder; mp 163–165°C; IR (ν/cm−1): 3264, 1640, 1608(Cꢀ=ꢀO); H NMR
(DMSO-d6): δ 1.24 (t, Jꢀ=ꢀ7.5 Hz, 3H, CH3), 2.63–2.76 (m, 1H, CH), 2.89–
2.99 (m, 1H, CH), 6.61(d, Jꢀ=ꢀ7.9 Hz, 2H, Ar), 6.82 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar),
7.18 (t, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 7.50 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar), 7.69 (d, Jꢀ=ꢀ7.9 Hz,
1H, Ar), 7.83 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar), 8.06 (d, J =7.9 Hz, 1H, Ar), 9.12 (s, 1H,
NH); 13C NMR (DMSO-d6): δ 11.4, 27.1, 39.0, 112.8, 120.6, 121.4, 126.6,
References
[1] Baek, D. J.; Park, Y. K.; Il Heo, H.; Lee, M.; Yang, Z.; Choi, M.
Synthesis of 5-substituted quinazolinone derivatives and their
inhibitory activity in vitro. Bioorg. Med. Chem. Lett. 1998, 8,
3287–3290.
+
126.9, 127.6, 129.6, 135.1, 147.1, 147.4, 160.6, 161.3; MS: m/z 265 (M ).
Anal. Calcd for C16H15N3O: C, 72.43; H, 5.70; N, 15.84. Found: C, 72.33;
H, 5.58; N, 15.73.
[2] Hosseinzadeh, L.; Aliabadi, A.; Kalantari, M.; Mostafavi, A.;
Khajouei, M. R. Synthesis and cytotoxicity evaluation of some
new 6-nitro derivatives of thiazole-containing 4-(3H)-quina-
zolinone. Res. Pharm. Sci. 2016, 11, 210–218.
[3] Alagarsamy, V.; Murugesan, S. Synthesis and pharmacologi-
cal evaluation of some 3-(4-methoxyphenyl)-2-substituted
aminoquinazolin-4(3H)-ones as analgesic and anti-inflamma-
tory agents. Chem. Pharm. Bull. 2007, 55, 76–80.
[4] Hussain, M. A.; Chiu, A. T.; Price, W. A.; Timmermans, P. B.;
Shefter, E. Antihypertensive activity of 2[(2-hydroxyphenyl)
amino]-4(3H)-quinazolinone. Pharm. Res. 1988, 5, 242–244.
[5] Alagarsamy, V.; Murugesan, S.; Dhanabal, K.; Murugan, M.;
De Clercq, E. Anti-HIV, antibacterial and antifungal activities of
some novel 2-methyl-3-(substituted methylamino)-(3H)-quina-
zolin-4-ones. Ind. J. Pharm. Sci. 2007, 69, 304–307.
[6] Alafeefy, A. M.; Ashour, A. E.; Prasad, O.; Sinha, L.; Pathak,
S.; Alasmari, F. A.; Rishi, A. K.; Abdel-Aziz, H. A. Develop-
ment of certain novel N-(2-(2-(2-oxoindolin-3-ylidene)
hydrazinecarbonyl)phenyl)-benzamides and 3-(2-oxoindolin-
3-ylideneamino)-2-substituted quinazolin-4(3H)-ones as CFM-1
analogs: Design, synthesis, QSAR analysis and anticancer
activity. Eur. J. Med. Chem. 2015, 92, 191–201.
[7] Wang, Z.; Wang, M.; Yao, X.; Li, Y.; Tan, J.; Wang, L.; Qiao,
W.; Geng, Y.; Liu, Y.; Wang, Q. Design, synthesis and antiviral
activity of novel quinazolinones. Eur. J. Med. Chem. 2012, 53,
275–282.
[8] Tiwari, S.; Mujalda, V.; Sharma, V.; Saxena, P.; Shrivastava, M.
Synthesis and evaluation of schiff’s base of 4-quinazolinone
analogues as antimicrobial agents. Asian J. Pharmaceut. Clin.
Res. 2012, 5, 98–100.
[9] Ramamohan, M.; Raghavendrarao, K.; Sridhar, R.; Nagaraju,
G.; Chandrasekhar, K. B.; Jayapraksh, S. A concise approach to
substituted quinazolin-4(3H)-one natural products catalyzed by
iron(III) chloride. Tetrahedron Lett. 2016, 57, 1418–1420.
[10] Ma, C.; Li, Y.; Niu, S.; Zhang, H.; Liu, X.; Che, Y. N-Hydroxypyri-
dones, phenylhydrazones, and a quinazolinone from isaria
farinosa. J. Nat. Prod. 2011, 74, 32–37.
[11] Zhuang, Y.; Teng, X.; Wang, Y.; Liu, P.; Li, G.; Zhu, W. New
quinazolinone alkaloids within rare amino acid residue from
coral-associated fungus, aspergillus versicolor LCJ-5-4. Org.
Lett. 2011, 13, 1130–1133.
3-(Phenylamino)-2-propylquinazolin-4(3H)-one (4d)ꢁThis com-
pound was obtained in yields of 86% (heat) and 90% (MW) as a white
1
powder; mp 160–162°C; IR (ν/cm−1): 3311, 1648, 1607(Cꢀ=ꢀO); H NMR
(DMSO-d6): δ 0.93 (t, Jꢀ=ꢀ7.3 Hz, 3H, CH3), 1.72–1.82 (m, 2H, CH2), 2.61–
2.71 (m, 1H, CH), 2.86–2.95 (m, 1H, CH), 6.61 (d, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 6.82
(t, Jꢀ=ꢀ75 Hz, 1H, Ar), 7.18 (t, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 7.50 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar),
7.69 (d, Jꢀ=ꢀ7.9 Hz, 1H, Ar), 7.84 (t, Jꢀ=ꢀ7.9 Hz, 1H, Ar), 8.06 (d, Jꢀ=ꢀ7.9 Hz,
1H, Ar), 9.11 (s, 1H, NH); 13C NMR (DMSO-d6): δ 14.1, 20.1, 35.63, 112.8,
120.6, 121.5, 126.6, 126.9, 127.6, 129.6, 135.1, 147.1, 147.5, 160.3, 160.7;
+
MS: m/z 279 (M ). Anal. Calcd for C17H17N3O: C, 73.10; H, 6.13; N, 15.04.
Found: C, 73.01; H, 6.01; N, 14.93.
2-Butyl-3-(phenylamino)quinazolin-4(3H)-one (4e)ꢁThis com-
pound was obtained in yields of 82% (heat) and 88% (MW) as a white
1
powder; mp 172–174°C; IR (ν/cm−1): 3296, 1626, 1604(Cꢀ=ꢀO); H NMR
(DMSO-d6): δ 0.91(t, Jꢀ=ꢀ7.5 Hz, 3H, CH3), 1.28–1.40 (m, 2H, CH2), 1.69–
1.77 (m, 2H, CH2), 2.49 (m, 1H, CH), 2.71(m, 1H, CH), 6.61 (d, Jꢀ=ꢀ8.4 Hz,
2H, Ar), 6.82 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar), 7.20 (t, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 7.49 (t,
Jꢀ=ꢀ7.5 Hz, 1H, Ar), 7.68(d, Jꢀ=ꢀ8.0 Hz, 1H, Ar), 7.83 (t, Jꢀ=ꢀ8.0 Hz, 1H, Ar),
8.06 (d, Jꢀ=ꢀ7.9 Hz, 1H, Ar), 9.11 (s, 1H, NH); 13C NMR (DMSO-d6): δ 14.1,
22.2, 28.8, 33.4, 112.8, 120.6, 121.5, 126.6, 126.9, 127.6, 129.6, 135.1, 147.1,
+
147.5, 160.6, 160.7; MS: m/z 293 (M ). Anal. Calcd for C18H19N3O: C,
73.69; H, 6.53; N, 14.32. Found: C, 73.58; H, 6.40; N, 14.20.
2-Phenyl-3-(phenylamino)quinazolin-4(3H)-one (4f)ꢁThis com-
pound was obtained in yields of 87% (heat) and 93% (MW) as a white
1
powder; mp 185–187°C; IR (ν/cm−1): 3253, 3028, 1675(Cꢀ=ꢀO); H NMR
(DMSO-d6): δ 6.57 (d, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 6.75 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar), 7.11
(t, Jꢀ=ꢀ7.5 Hz, 2H, Ar), 7.38–7.44 (m, 3H, Ar), 7.58 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar),
7.73–7.81 (m, 3H, Ar), 7.91 (t, Jꢀ=ꢀ7.5 Hz, 1H, Ar), 8.13 (d, Jꢀ=ꢀ7.5 Hz, 1H,
Ar), 9.10 (s, 1H, NH); 13C NMR (DMSO-d6): δ 112.8, 114.7, 115.07, 117.8,
119.7, 126.8, 128.0, 128.7, 129.3, 134.2, 141.2, 147.3, 148.3, 163.0, 164.7;
+
MS: m/z 313 (M ). Anal. Calcd for C20H15N3O: C, 76.66; H, 4.82; N, 13.41.
Found: C, 76.56; H, 4.70; N, 13.32.
6-Chloro-2-methyl-3-(phenylamino)quinazolin-4(3H)-one
(4g)ꢁThis compound was obtained in yields of 81% (heat) and 88%
(MW) as a white powder; mp 197–198°C; (lit. [37]: mp 195–196°C, yield
64%).
6-Chloro-2-ethyl-3-(phenylamino)quinazolin-4(3H)-one
(4h)ꢁThis compound was obtained in yields of 80% (heat) and
90% (MW) yield as a white powder; mp 130–132°C; (lit. [37]: mp 131–
131.5°C, yield 63%).
[12] Eguchi, S.; Suzuki, T.; Okawa, T.; Matsushita, Y.; Yashima, E.;
Okamoto, Y. Synthesis of optically active vasicinone based on
intramolecular Aza-Wittig reaction and asymmetric oxidation1.
J. Org. Chem. 1996, 61, 7316–7319.
[13] Bergman, J.; Brynolf, A. Synthesis of Chrysogine, a metabolite
of Penicillium chrysogenum and some related 2-substituted
4-(3H)-quinazolin. Tetrahedron 1990, 46, 1295–1310.
Acknowledgments: We are grateful to the Islamic Azad
University, Sabzevar Branch, and the National Foundation
Brought to you by | University of Michigan
Authenticated
Download Date | 4/3/17 6:14 PM

ꢁꢁꢁꢂ
ꢀA.A. Mohammadi et al.: 2-Alkyl and 2-aryl-3-(phenylamino)quinazolin-4(3H)-ones
108ꢀ
[14] Johne, S.; Quinazoline Alkaloids. In Supplements to the 2nd
Edition of Rodd’s Chemistry of Carbon Compounds. Elsevier
Inc.: St. Louis, MO, USA, 2009; Vol. 4, pp 223–240.
[15] Kacker, I. K.; Zaheer, S. H. Potential analgesics. Part I. Synthe-
sis of substituted 4-quinazolones. J. Indian Chem. Soc. 1951,
28, 253–260.
[16] Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H.; Kim, H. S.;
Wataya, Y. Catalytic asymmetric synthesis of antimalarial
alkaloids febrifugine and isofebrifugine and their biological
activity. J. Org. Chem. 1999, 64, 6833–6841.
[17] Takaya, Y.; Tasaka, H.; Chiba, T.; Uwai, K.; Tanitsu, M. A.; Kim,
H. S.; Wataya, Y.; Miura, M.; Takeshita, M.; Oshima, Y. New
type of febrifugine analogues, bearing a quinolizidine moiety,
show potent antimalarial activity against Plasmodium malaria
parasite. J. Med. Chem. 1999, 42, 3163–3166.
[18] Mirza, B. An efficient metal-free synthesis of 2-amino-substi-
tuted-4(3H)-quinazolinones. Tetrahedron Lett. 2016, 57, 146–147.
[19] Yan, B. R.; Lv, X. Y.; Du, H.; Gao, M. N.; Huang, J.; Bao, X. P.
Synthesis and biological activities of novel quinazolinone
derivatives containing a 1,2,4-triazolylthioether moiety. Chem.
Pap. 2016, 70, 983–993.
[20] Zhu, X.; Kang, S. R.; Xia, L.; Lee, J.; Basavegowda, N.; Lee, Y.
R. Efficient Cu(OTf)2-catalyzed synthesis of novel and diverse
2,3-dihydroquinazolin-4(1H)-ones. Mol. Divers. 2015, 19, 67–75.
[21] Saad, S. M.; Saleem, M.; Perveen, S.; Alam, M. T.; Khan, K. M.;
Choudhary, M. I. Synthesis and biological potential assess-
ment of 2-substituted quinazolin-4(3H)-ones as inhibitors of
phosphodiesterase-I and carbonic anhydrase-II. Med. Chem.
(Shāriqah (United Arab Emirates)) 2015, 11, 336–341.
[22] Shen, G.; Zhou, H.; Sui, Y.; Liu, Q.; Zou, K. FeCl3-catalyzed
tandem condensation/intramolecular nucleophilic addition/
C–C bond cleavage: a concise synthesis of 2-substitued
quinazolinones from 2-aminobenzamides and 1,3-diketones in
aqueous media. Tetrahedron Lett. 2016, 57, 587–590.
[23] Li, T.; Chen, M.; Yang, L.; Xiong, Z.; Wang, Y.; Li, F.; Chen, D.
Copper-catalyzed consecutive reaction to construct quinazolin-
4(3H)-ones and pyrido[2,3-d]pyrimidin-4(3H)-ones. Tetrahe-
dron 2016, 72, 868–874.
[24] El-Hashash, M. A.; Azab, M. E.; Morsy, J. M. One-pot synthesis
of some dynamic 2-substituted benzoxazinones and their
corresponding qinazolinones of anticipated biological activity.
J. Heterocycl. Chem. 2016, 53, 95–101.
[25] Natte, K.; Neumann, H.; Wu, X. F. Pd/C as an efficient heteroge-
neous catalyst for carbonylative four-component synthesis of
4(3H)-quinazolinones. Catal. Sci. Technol. 2015, 5, 4474–4480.
[26] Li, X.; Lin, Q.; Wang, L. One-pot solvent-free synthesis of
2,3-disubstituted 4(3H)- quinazolinones catalyzed by long-
chain double SO3H-functionalized Brønsted acidic ionic liquids
under microwave irradiation. J. Iran. Chem. Soc. 2015, 12,
897–901.
[27] Mohammadi, A. A.; Taheri, S.; Amouzegar, A. Synthesis of
novel 1H-Imidazol[1,2-a]Indeno[2,1-e]pyridine-6(5H)-ones
derivatives via a one-pot four-component condensation reac-
tion. J. Heterocycl. Chem. 2015, 52, 1876–1879.
[28] Mohammadi, A. A.; Taheri, S.; Askari, S.; Ahdenov, R.
KAl(SO4)2.12H2O (Alum): an efficient catalyst for the synthesis
of novel bis[spiro(quinazoline-oxindole)] derivatives via one-
pot pseudo five-component reactions. J. Heterocycl. Chem.
2015, 52, 1871–1875.
[29] Mohammadi, A. A.; Tahery, S.; Askari, S. One-pot five-compo-
nent reaction for synthesis of some novel bis-dihydroquina-
zolinone derivatives. Arkivoc 2014, (v), 310–318.
[30] Mohammadi, A. A.; Dabiri, M.; Qaraat, H. A regioselec-
tive three-component reaction for synthesis of novel
1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione deriva-
tives. Tetrahedron 2009, 65, 3804–3808.
[31] Mohammadi, A. A.; Rohi, H.; Soorki, A. A. Synthesis and in vitro
antibacterial activities of novel 2-aryl-3-(phenylamino)-2,3-di-
hydroquinazolin-4(1H)-one derivatives. J. Heterocycl. Chem.
2013, 50, 1129–1133.
[32] Dabiri, M.; Salehi, P.; Otokesh, S.; Baghbanzadeh, M.;
Kozehgary, G.; Mohammadi, A. A. Efficient synthesis of mono-
and disubstituted 2,3-dihydroquinazolin-4(1H)-ones using
KAl(SO4)2ꢂ·ꢂ12H2O as a reusable catalyst in water and ethanol.
Tetrahedron Lett. 2005, 46, 6123–6126.
[33] Azizian, J.; Mohammadi, A. A.; Karimi, A. R.; Mohammadiza-
deh, M. R. KAl(SO4)2ꢂ·ꢂ12H2O supported on silica gel as a novel
heterogeneous system catalyzed biginelli reaction: one-pot
synthesis of dihydropyrimidinones under solvent-free condi-
tions. Appl. Catal., A-Gen 2006, 300, 85–88.
[34] Clinical and Laboratory Standards Institute. Performance
Standards for Antimicrobial Disk Susceptibility Tests.
Fourth Edition: Approved Standard M2-A4. Wayne, PA, USA,
1990.
[35] Clinical and Laboratory Standards Institute. Methods for Dilu-
tion Antimicrobial Susceptibility Tests for Bacteria that Grow
Aerobically. Fifth Edition: Approved Standard M7-A5. Wayne,
PA, USA, 2000.
[36] Kornet, M. J.; Varia, T.; Beaven, W. Synthesis and anticonvul-
sant activity of 3-amino-4(3H)-quinazolinones. J. Heterocycl.
Chem. 1983, 20, 1553–1555.
[37] Leiby, R. W. Synthesis of 3-amino-4(3H)-quinazolinones from
N-(2-carbomethoxyphenyl)imidate esters. J. Org. Chem. 1985,
50, 2926–2929.
Brought to you by | University of Michigan
Authenticated
Download Date | 4/3/17 6:14 PM