Expeditious synthesis and spectroscopic characterization of 2-methyl-3-substituted-quinazolin-4(3H)-one derivatives

Article abstract of DOI:10.13005/ojc/330203

Quinazoline and quinazolinone derivatives are well-known bioactive heterocycles owing to their therapeutic diversity and extensive medicinal application in drug design and pharmaceutics. A series of 2-methyl-3-substituted quinazolin-4(3H)-one derivatives 8a-q was herein synthesized from synthetic conversion of anthranilic acid to 2-methyl-4H-3,1-benzoxazi-4-one, 7 which was subsequently transformed to the targeted 2,3-disubstituted quinazolin-4(3H)-one derivatives 8a-q by reacting with some notable amino-containing moieties via an ameliorable pathway. The catalyst-free synthesis was successful achieved by careful reaction optimization study using solvent choice and reaction temperature variability as key parameters. The chemical structures of the synthesized compounds were confirmed by IR, UV, ¹H-NMR, ¹³C-NMR and DEPT-135 as well as analytical data.

Full text of DOI:10.13005/ojc/330203

ISSN: 0970-020 X
CODEN: OJCHEG
2017, Vol. 33, No. (2):
Pg. 562-574
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Expeditious Synthesis and Spectroscopic Characterization of
2-Methyl-3-substituted-quinazolin-4(3H)-one Derivatives
OLAYINKA O. AJANI1*, OLUWATOSINY. AUDU1,
MARKUS W. GERMANN2 and BABATUNDE L. BELLO2
1Department of Chemistry, Covenant University, CST, Canaanland,
Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria.
2Department of Chemistry, Georgia State University, Atlanta GA, 30302, USA.
*Corresponding author E-mail: ola.ajani@covenantuniversity.edu.ng
http://dx.doi.org/10.13005/ojc/330203
(Received: June 18, 2016; Accepted: March 29, 2017)
ABSTRACT
Quinazoline and quinazolinone derivatives are well-known bioactive heterocycles owing to
their therapeutic diversity and extensive medicinal application in drug design and pharmaceutics.
A series of 2-methyl-3-substituted quinazolin-4(3H)-one derivatives 8a-q was herein synthesized
from synthetic conversion of anthranilic acid to 2-methyl-4H-3,1-benzoxazi-4-one, 7 which was
subsequently transformed to the targeted 2,3-disubstituted quinazolin-4(3H)-one derivatives 8a-q
by reacting with some notable amino-containing moieties via an ameliorable pathway.The catalyst-
free synthesis was successful achieved by careful reaction optimization study using solvent choice
and reaction temperature variability as key parameters.The chemical structures of the synthesized
1
compounds were confirmed by IR, UV, H-NMR, 13C-NMR and DEPT-135 as well as analytical
data.
Keywords: Solvent-dependent synthesis, spectral study,
quinazolin-4(3H)-one, DEPT-135 analysis.
INTRODUCTION
hundred branded drugs, we have more than 75%
of them which have heterocyclic fragments in their
structures4. One of these organic compounds of
interest among the heterocycles is quinazoline
otherwise known as 1,3-diazanaphthalene, benzo-
1,3-diazine, benzopyrimidine which was first
synthesized by Gabriel in 19035. Quinazoline
can have different types of substituents attached
to it, forming different derivatives of the parent
Heterocyclic compounds form the basis for
pharmaceutical industry especially in the synthesis
of drugs1. Also, most marketed drugs constitute of
common structural units of heterocyclic compounds
which could also be useful in the synthesis of
biologically active agrochemicals2,3. For instance,
in the pharmaceutical industry, among the top two

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
quinazoline.Substituted quinazolines have properties
which largely depend on: the nature and position of
the substituent as well as type of conjugation in
EXPERIMENTAL
All chemical compounds and reagents
pyrimidine ring6. quinazolinones alkaloids form used were obtained from Sigma-Aldrich, USA except
small but important group of naturally occurring methanol and dichloromethane which were obtained
bases which have been isolated from a number from B.D.H.Chemicals, UK and were made available
of different families e.g. seeds of P. nigellastium by Department of Chemistry, Covenant University.
Bunge7. Quinazoline occurs mostly as alkaloid in Solvents used were of analytical grade and were
root and leaves of some medicinal plants such as used directly without further purification. Melting
Dichroa febrifuga (also called Chinese quinine) which points were determined in open capillary tubes using
belongs to the Saxifragaceae family8. Numerous Stuart melting point apparatus and were uncorrected.
quinazoline derivatives have also be synthesized in The IR spectra were run in solid state using the Bruker
order to achieve biologically active template which FT-IR; while UV Spectrophotometric analyses of all
are essential in drug development. For instance, the samples were run in ethanol, using UV-Genesys
quinazoline motifs have been reported to exhibit spectrophotometer in the Instrumentation Laboratory
diverse biological and pharmacological activities of Chemistry Department.The 1H-NMR and 13C-NMR
which include anticonvulsant9, anti-inflammatory10, of the compounds were run on Bruker NMR machine
antileishmanial11, antimalarial12, antioxidant13, at 500 MHz AND 125 MHz respectively.Distortionless
antitubercular14, antiviral15 among others.Vast amount Enhancement Proton Transfer (DEPT-135) analysis
of literature has been documented for the synthesis was also investigated for effective characterization.
of quinazoline and quinazolinone on the catalyst The chemical shifts were measured with reference
supported synthesis of this crucial heterocyclic core, to tetramethylsilane (TMS) and the solvent used
some of which are Ceryl ammonium nitrate (CAN) were CDCl3 and deuteriated DMSO depending on
for synthesis of 116, Ru3(CO2)12 for 217, CuCl for 318, the solubility properties of the required compound.
b-cyclodextrin/Montmorillonite for 419, iodine for 520 The elemental analysis (C, H, N) of the synthesized
and Fe/HCl for 621 (Fig. 1). Some of these catalysts compounds were performed using a Flash EA 1112
are costly to get. Hence, we have herein embarked CHN elemental analyzer. Results were found to be
on the synthesis of our targeted quinazolinone in good agreement with the calculated values (Table
derivatives in the catalyst-free medium by engaging 3). All compounds were routinely checked by TLC
reaction optimization study using variation of solvents on silica gel G plates and column chromatographic
and temperature parameters.
purifications were carried out on Merck silica gel F
(Mesh 200-300). The progress of the reaction and
N
C
O
N
S
N
N
Bn
N
N
N
N
2
3
1
O
N
N
O
O
N
NH NH2
N
CH3
N
N
H
H
O
6
5
4
Fig. 1: Some quinazoline and quinazolinone compounds synthesized by catalytic support

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
the level of purity of the compounds were routinely
checked by TLC on silica gel plates using different
solvent system based on the variation of polarity of
the product of interest and the developed plates were
visualized under UV light. All drying was conducted
at reduced pressure with DHG-9023A Vacuum
Oven.
TLC monitoring. The reaction mixture was allowed
to cool, filtered by suction and air-dried to afford
moderate to excellent yields of various 2-methyl-3-
substituted quinazolin-4(3H)-one derivatives, 8a-q.
Synthesis of 2,3-dimethylquinazolin-4(3H)-one,
8a.
Treatment of 2-methyl-4H-3,1-benzoxazin-
4-one, 7(3.00g, 18.60mmol)withmethylamine(0.62
ml, 18.60 mmol) afforded 2,3-dimethylquinazolin-
Synthesis of 2-methyl-4H-3,1-benzoxazin-
4-one, 7
1
Acetic anhydride (30 ml) was added to
4(3H)-one, 8a. H-NMR (500 MHz, CDCl3) dH:
anthranilic acid (30 g, 220 mmol), under continuous
stirring for 5 mins at room temperature.An exothermic
reaction was observed, then the reaction mixture
was cooled in a refrigerator for 5 mins, after which it
was heated under reflux and the progress of reaction
was monitored byTLC using dichloromethane (DCM)
as the eluting solvent. The reaction was completed
in 6 h. The reaction mixture was then cooled to
room temperature, filtered by suction and washed
with few portion of cold water. It was then air-dried
to afford 2-methyl-4H-3,1-benzoxazin-4-one, 7 as
7.96-7.94 (d, J = 9.65 Hz, 1H of Ar-H), 7.77-7.73 (t,
J = 9.00 Hz, 1H, Ar-H), 7.46-7.42 (t, J = 10.00 Hz,
1H, Ar-H), 7.42-7.40 (d, J = 9.30 Hz, 1H of Ar-H),
3.35 (s, 3H, CH3), 2.59 (s, 3H, CH3-C=N). 13C-NMR
(125 MHz, DMSO-d6) dC: 168.77, (C=O), 140.37,
134.91, 130.74, 129.04, 127.82, 117.24, 114.52,
25.26, 20.92 ppm. DEPT 135 (125 MHz, CDCl3)
dC: Positive signals are 129.11 (CH), 127.91 (CH),
117.14 (CH), 114.04 (CH), 25.24 (CH3), 20.92
(CH3) ppm. No Negative signals. UV-Vis.: lmax in nm
(log emax mol-1cm-1): 212 (4.192), 251 (4.897), 293
(4.401). IR (KBr, cm–1) nmax: 3020 (C-H aromatic),
2929 (C-H aliphatic), 2845 (C-H aliphatic), 1691
(C=O of amide), 1620 (C=C), 1576 (C=N), 1445m,
1388s (CH3 deformation), 975s (=C-H), 826 (C=C,
out-of-plane bending), 757 (Ar-H, bending and ring
puckering).
1
white crystalline solid in excellent yield. H-NMR
(500 MHz, CDCl3) dH: 7.96-7.94 (d, J = 9.68 Hz, 1H
of Ar-H), 7.77-7.73 (t, J = 9.68 Hz, 1H, Ar-H), 7.46-
7.42 (t, J = 10.00 Hz, 1H, Ar-H), 7.42-7.40 (d, J =
10.00 Hz, 1H of Ar-H), 2.59 (s, 3H, CH3). 13C-NMR
(125 MHz, DMSO-d6) dC: 168.77, (C=O), 140.37,
134.91, 130.74, 129.04, 127.82, 117.24, 114.52,
20.92 ppm.DEPT 135 (125 MHz, CDCl3) dC:Positive
signals are 129.11 (CH), 127.91 (CH), 117.14
(CH), 114.04 (CH), 20.92 (CH3) ppm. No Negative
signals. UV-Vis.: lmax in nm (log emax mol-1cm-1): 214
Synthesis of 2-methyl-3-pentylquinazolin-4(3H)-
one, 8b
Treatment of 2-methyl-4H-3,1-benzoxazin-
4-one, 7 (3.00 g, 18.60 mmol) with pentylamine
(1.74 ml, 18.60 mmol) afforded 2-methyl-3-
(4.108), 250 (4.936), 263 (4.423).IR (KBr, cm–1) nmax
:
1
3020 (C-H aromatic), 2929 (C-H aliphatic), 2846
(C-H aliphatic), 1743 (C=O of ester), 1620 (C=C),
1576 (C=N), 1388s (CH3 deformation), 1109 (C-O
of alkoxyl), 975s (=C-H), 826 (C=C, out-of-plane
bending), 757 (Ar-H, bending and ring puckering).
pentylquinazolin-4(3H)-one, 8b. H-NMR (500
MHz, CDCl3) dH: 7.71-7.63 (dd, J1 = 10.30 Hz, J2
= 12.30 Hz, 2H, Ar-H), 7.28-7.26 (d, J = 12.3 Hz,
2H, Ar-H), 4.74-4.73 (m, 1H, CH), 3.72-3.69 (d, J =
10.20 Hz, 1H), 3.23-3.17 (t, J = 12.65 Hz, 1H), 2.41
(s, 3H, CH3-C=N), 2.18-2.15 (d, J = 12.65 Hz, 1H),
1.67-1.59 (m, 4H, 2 × CH2), 1.38-1.31 (t, J = 13.16
Hz, 3H, CH3-CH2). 13C-NMR (125 MHz, DMSO-d6)
dC: 171.39 (C=O), 153.92, 145.83, 133.65, 127.42,
126.75, 126.25, 118.88, 40.98, 30.51, 27.38, 24.49
(CH3), 22.58, 14.51 (CH3) ppm.DEPT 135 (125 MHz,
CDCl3) dC: Positive signals are 133.65 (CH), 127.42
(CH), 126.75 (CH), 126.25 (CH), 24.49 (CH3), 14.51
(CH3). Negative signals are 40.98, 30.51, 27.38,
22.58 ppm. UV-Vis.: lmax in nm (log emax mol-1cm-1):
251 (4.915), 251 (4.979), 293 (4.440).IR (KBr, cm–1)
General procedure for synthesis of 2-methyl-3-
substituted quinazolin-4(3H)-ones, 8a-q.
2-Methyl-4H-3,1-benzoxazin-4-one, 7 (3.00
g, 18.60 mmol) was dissolved in 10 ml of ethanol in
a 250 ml round bottom flask and the reaction mixture
was allowed to stir for 5 mins.at room temperature for
complete dissolution, followed by the addition of the
corresponding amino containing compounds (18.60
mmol).The mixture was then heated under reflux for
the required number of periods as determined by the

565
max:3038 (C-H aromatic), 2935 (C-H aliphatic), 2851 1.67 (m, 2H, CH2), 1.31-1.29 (2H, CH2-CH2-CH3),
AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
n
(C-H aliphatic), 1688 (C=O of amide), 1615 (C=C), 1.29-1.25 (m, 20H, 10 × CH2), 0.95 (t, J = 8.54 Hz,
1576 (C=N), 1436m (CH2 deformation), 1388s (CH3 3H, CH3-CH2). 13C-NMR (125 MHz, DMSO-d6) dC:
deformation), 977s (=C-H), 821(C=C, out-of-plane 171.21 (C=O), 154.61, 146.92, 133.54, 130.73 (2 ×
bending), 754 (Ar-H, bending and ring puckering), CH olefin), 127.42, 126.84, 126.62, 120.92, 40.53
658.
(CH2), 31.80 (CH2), 30.91 (CH2), 29.90 (2 × CH2),
29.71 (4 × CH2), 29.33 (2 × CH2), 27.84 (2 × CH2),
Synthesis of 3-hexadecyl-2-methylquinazolin- 26.70 (CH2), 22.90 (CH3), 22.61 (CH2), 14.33 (CH3)
4(3H)-one, 8c ppm.DEPT 135 (125 MHz, CDCl3) dC:Positive signals
Treatment of 2-methyl-4H-3,1-benzoxazin- are 133.54 (CH), 130.73 (2 × CHolefin), 127.42 (CH),
4-one, 7 (3.00 g, 18.60 mmol) with hexadecylamine 126.84 (CH), 126.62 (CH), 22.90 (CH3), 14.33 (CH3)
(4.98 g, 18.60 mmol) afforded 3-hexadecyl-2- ppm.Negative signals are 40.53 (CH2), 31.80 (CH2),
methylquinazolin-4(3H)-one, 8c.1H-NMR (500 MHz, 30.91 (CH2), 29.90 (2 × CH2), 29.71 (4 × CH2), 29.33
CDCl3) dH: 8.64-8.62 (d, J = 7.10 Hz, 1H of Ar-H), (2 × CH2), 27.84 (2 × CH2), 26.70 (CH2), 22.61 (CH2)
7.95-7.94 (d, J = 7.60 Hz, 1H of Ar-H), 7.39-7.38 (t, ppm. UV-Vis.: lmax in nm (log emax mol-1cm-1): 215
J = 6.65 Hz, 1H of Ar-H), 6.99-6.96 (t, J = 6.95 Hz, (5.434), 251(5.321), 293(4.762). IR (KBr, cm–1) nmax
:
1H of Ar-H), 2.11 (s, 3H, CH3-C=N), 1.56-1.54 (t, J 3038 (C-H aromatic), 3010 (C-H alkene), 2935 (C-H
= 6.80 Hz, 2H, N-CH2-CH2), 1.22-1.11 (m, 28H, 2 × aliphatic), 2851 (C-H aliphatic), 1688 (C=O of amide),
CH2), 0.86-0.83 (t, J = 6.80 Hz, 3H, CH3-CH2). 13C- 1615 (C=C), 1576 (C=N), 1436m (CH2 deformation),
NMR (125 MHz, DMSO-d6) dC:174.38 (C=O), 168.33, 1388s (CH3 deformation), 977s (=C-H), 821 (C=C,
141.04, 132.45, 130.78, 121.80, 119.90, 39.69 (CH2), out-of-plane bending), 754 (Ar-H, bending and ring
31.65 (CH2), 29.52 (7 × CH2), 29.28 (CH2), 28.84 puckering), 658.
(CH2), 28.25 (CH2), 27.93 (CH2), 26.47 (CH2), 25.33
(CH3), 24.98 (CH2), 22.60 (CH2), 14.02 (CH3). DEPT Synthesis of 3-cyclohexyl-2-methylquinazolin-
135 (125 MHz, CDCl3) dC:Positive signals are 132.65 4(3H)-one, 8e
(CH), 130.98 (CH), 121.95 (CH), 119.96 (CH), 25.39
Treatment of 2-methyl-4H-3,1-benzoxazin-
(CH3), 14.09 (CH3). Negative signals are 39.74 4-one, 7 (3.00 g, 18.60 mmol) with cyclohexylamine
(CH2), 31.65 (CH2), 29.52 (7 × CH2), 29.28 (CH2), (2.13 ml, 18.60 mmol) afforded 3-cyclohexyl-2-
28.84 (CH2), 28.25 (CH2), 27.93 (CH2), 26.47 (CH2), methylquinazolin-4(3H)-one, 8e.1H-NMR (500 MHz,
24.98 (CH2), 22.60 (CH2).UV-Vis.:lmax in nm (log emax CDCl3) dH: 8.03-8.01 (d, J = 5.09 Hz, 1H of Ar-H),
mol-1cm-1): 209 (4.915), 248 (4.629), 299(3.833). IR 7.86-7.82 (t, J = 9.45 Hz, 1H, Ar-H), 7.45-7.42 (t, J
(KBr, cm–1) nmax: 3433 (O-H), 3142 (C-H aromatic), = 10.00 Hz, 1H, Ar-H), 7.38-7.41 (d, J = 5.12 Hz,
2918 (CH aliphatic), 2851 (CH aliphatic), 1690 (C=O 1H of Ar-H), 3.54-3.51 (quintet, J = 4.50 Hz, 1H,
of amide), 1660 (C=C), 1588 (C=N), 1437m (CH2 CH2-CH-CH2), 2.59 (s, 3H, CH3-C=N), 1.77-1.63 (m,
deformation), 1375s (CH3 deformation), 970s (=C-H), 4H, 2 × CH2), 1.50-1.47 (quintet, J = 7.54 Hz, 2H,
825 (C=C, out-of-plane bending), 753 (Ar-H, bending CH2-CH2-CH2), 1.21-1.13 (m, 4H, 2 × CH2). 13C-NMR
and ring puckering).
(125 MHz, CDCl3) dC:170.21 (C=O), 154.11, 146.12,
133.25, 127.80, 126.91, 126.36, 120.54, 63.12, 31.42
Synthesis of (Z)-2-methyl-3-(octadec-9-en-1-yl) (2 × CH2), 25.80, 24.63 (2 × CH2), 22.98 (CH3) ppm.
quinazolin-4(3H)-one, 8d DEPT 135 (125 MHz, CDCl3) dC:Positive signals are
Treatment of 2-methyl-4H-3,1-benzoxazin- 133.25, 127.80, 126.91, 126.36 (CHs), 22.98 (CH3)
4-one, 7 (3.00 g, 18.60 mmol) with oleylamine (4.48 ppm. Negative signals are 31.42 (2 × CH2), 25.80,
g, 18.60 mmol) afforded (Z)-2-methyl-3-(octadec-9- 24.63 (2 × CH2) ppm. UV-Vis.: lmax in nm (log emax
en-1-yl)quinazolin-4(3H)-one, 8d.1H-NMR (500 MHz, mol-1cm-1): 215 (5.273), 251 (5.059), 296 (4.545).
CDCl3) dH: 8.13-8.12 (d, J = 5.05 Hz, 1H of Ar-H), IR (KBr, cm–1) nmax: 3040 (C-H aromatic), 2919 (CH
7.87-7.85 (t, J = 9.42 Hz, 1H, Ar-H), 7.46-7.42 (t, J aliphatic), 2845 (CH aliphatic), 1690 (C=O of amide),
= 10.00 Hz, 1H, Ar-H), 7.42-7.41 (d, J = 5.12 Hz, 1620 (C=C), 1585 (C=N), 1435m (CH2 deformation),
1H of Ar-H), 5.42-5.40 (t, J = 12.80 Hz, 2H, CH2- 1370s (CH3 deformation), 970s (=C-H), 830 (C=C,
CH=CH-CH2), 4.12 (t, J = 8.20 Hz, 2H, CH2-CH2), out-of-plane bending), 755 (Ar-H, bending and ring
2.58 (s, 3H, CH3-C=N), 2.18-2.15 (m, 4H, 2 × CH2), puckering), 658.

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Synthesis of 2-methyl-3-phenylquinazolin-4(3H)-
one, 8f
S y n t h e s i s o f 3 - ( 4 - b ro m o p h e ny l ) - 2 -
methylquinazolin-4(3H)-one, 8h
Treatment of 2-methyl-4H-3,1-benzoxazin-
Treatment of 2-methyl-4H-3,1-benzoxazin-
4-one, 7 (3.00 g, 18.60 mmol) with 4-bromoaniline
(3.20 g, 18.60 mmol) afforded 3-(4-bromophenyl)-
4-one, 7 (3.00 g, 18.60 mmol) with aniline (1.70 ml,
18.60 mmol) afforded 2-methyl-3-phenylquinazolin-
4(3H)-one, 8f. 1H-NMR (500 MHz, CDCl3) dH: 7.61-
7.59 (d, J = 10.00 Hz, 2H of Ar-H), 7.24-7.21 (m,
5H, Ar-H), 7.10-7.08 (m, 2H, Ar-H), 2.40 (s, 3H,
CH3-C=N).13C-NMR (125 MHz, DMSO-d6) dC:168.77
(C=O), 139.75, 137.18, 132.91, 132.07, 129.33,
129.15, 127.94, 125.64, 125.00, 123.40, 122.17,
121.18, 118.64, 22.39 (CH3) ppm. DEPT 135 (125
MHz, CDCl3) dC: Positive signals are 129.33 (CH),
129.11 (CH), 125.50 (CH), 125.00 (CH), 123.40
(CH), 122.17 (CH), 121.18 (CH), 118.64 (CH),
22.35 (CH3) ppm. No negative signals. UV-Vis.: lmax
in nm (log emax mol-1cm-1): 218 (5.188), 302(4.403).
IR (KBr, cm–1) nmax: 3108 (C-H aromatic), 3041 (C-H
aromatic), 2929 (CH aliphatic from CH3), 1690 (C=O
of amide), 1610 (C=C), 1575 (C=N), 1450, 1375 (CH3
deformation), 970s (=C-H), 831 (C=C, out-of-plane
bending), 755 (Ar-H, bending and ring puckering),
651.
1
2-methylquinazolin-4(3H)-one, 8h. H-NMR (500
MHz, DMSO-d6) dH: 1H-NMR (500 MHz, CDCl3) dH:
8.18-8.14 (d, J = 5.80 Hz, 1H of Ar-H), 8.02-7.98
(d, J = 7.86 Hz, 1H, Ar-H), 7.74-7.58 (m, 2H, ArH),
7.53-7.51 (d, J = 10.00 Hz, 2H, Ar-H), 7.28-7.25 (d,
J = 10.54 Hz, 1H, Ar-H), 7.03-7.01 (d, J = 5.00 Hz,
1H, Ar-H), 2.25 (s, 3H, CH3-C=N). 13C-NMR (125
MHz, DMSO-d6) dC: 168.75 (C=O), 140.22, 137.40,
134.82, 131.15, 131.01, 130.32, 129.00, 128.13,
127.71, 125.31, 122.14, 117.04, 114.11, 25.12 ppm.
DEPT 135 (125 MHz, CDCl3) dC:Positive signals are
131.15, 131.01, 130.32, 129.00, 128.13, 127.71,
117.04, 114.11 (CHs), 25.12 (CH3) ppm.No negative
signals. UV-Vis.: lmax in nm (log emax mol-1cm-1): 245
(5.405), 206 (5.392), 296 (4.719).IR (KBr, cm–1) nmax
:
3188 (C-H aromatic), 3110 (C-H aromatic), 2925
(CH aliphatic from CH3), 1688 (C=O of amide), 1600
(C=C), 1582 (C=N), 1449, 1373 (CH3 deformation),
968s (=C-H), 835 (C=C, out-of-plane bending), 755
(Ar-H, bending and ring puckering), 650, 505 (C-Br
stretching).
S y n t h e s i s o f 3 - ( 4 - ch l o ro p h e ny l ) - 2 -
methylquinazolin-4(3H)-one, 8g
Treatment of 2-methyl-4H-3,1-benzoxazin-4-one,
7 (3.00 g, 18.60 mmol) with 4-chloroaniline (2.38
g, 18.60 mmol) afforded 3-(4-chlorophenyl)-2-
methylquinazolin-4(3H)-one, 8g.1H-NMR (500 MHz,
CDCl3) dH: 8.68-8.67 (d, J = 5.40 Hz, 1H of Ar-H),
8.09-8.08 (d, J = 10.09. Hz, 1H, Ar-H), 7.77-7.60
(m, 2H, ArH), 7.54-7.52 (d, J = 10.00 Hz, 2H, Ar-H),
7.32-7.29 (d, J = 10.50 Hz, 1H, Ar-H), 7.09-7.08
(d, J = 5.00 Hz, 1H, Ar-H), 2.23 (s, 3H, CH3-C=N).
13C-NMR (125 MHz, DMSO-d6) dC: 168.77, (C=O),
140.37, 134.91, 130.74, 129.04, 127.82, 117.24,
114.52, 25.26, 20.92 ppm. DEPT 135 (125 MHz,
CDCl3) dC: Positive signals are 129.11 (CH), 127.91
(CH), 117.14 (CH), 114.04 (CH), 25.24 (CH3), 20.92
(CH3) ppm. No negative signals. UV-Vis.: lmax in nm
(log emax mol-1cm-1): 218 (5.369), 245 (5.287), 299
(4.690). IR (KBr, cm–1) nmax: 3477, 3378 (N-H, two
bands), 3191 (C-H aromatic), 3113 (C-H aromatic),
2925 (CH aliphatic from CH3), 1693 (C=O of amide),
1650, 1606 (C=C), 1582 (C=N), 1452, 1377 (CH3
deformation), 968s (=C-H), 833 (C=C, out-of-plane
bending), 805 (C-Cl stretching), 756 (Ar-H, bending
and ring puckering), 655.
S y n t h e s i s o f 3 - ( 2 - a m i n o p h e ny l ) - 2 -
methylquinazolin-4(3H)-one, 8i
Treatmentof2-methyl-4H-3,1-benzoxazin-4-
one, 7 (3.00 g, 18.60 mmol) with o-phenylenediamine
(2.02 g, 18.60 mmol) afforded 3-(2-aminophenyl)-2-
methylquinazolin-4(3H)-one, 8i. 1H-NMR (500 MHz,
DMSO-d6) dH: 1H-NMR (500 MHz, CDCl3) dH: 8.10-
8.07 (d, J = 5.70 Hz, 1H of Ar-H), 7.88-7.85 (d, J =
7.80 Hz, 1H, Ar-H), 7.72-7.66 (m, 2H, ArH), 7.44-
7.40 (d, J = 10.05 Hz, 1H, Ar-H), 7.28-7.25 (d, J =
10.54 Hz, 1H, Ar-H), 7.11-7.07 (m, 1H, Ar-H), 6.42
(s, 2H, NH2), 2.35 (s, 3H, CH3-C=N). 13C-NMR (125
MHz, DMSO-d6) dC: 171.05 (C=O), 154.60, 140.22,
137.33, 134.81, 131.00, 130.32, 129.00, 128.13,
127.71, 125.31, 122.14, 117.04, 114.11, 25.20 ppm.
DEPT 135 (125 MHz, CDCl3) dC:Positive signals are
131.00, 130.32, 129.00, 128.13, 127.71, 125.31,
117,04, 114.11 (CHs), 25.20 (CH3) ppm.No negative
signals. UV-Vis.: lmax in nm (log emax mol-1cm-1): 206
(4.997), 248 (4.598), 290 (4.223). IR (KBr, cm–1)
n
max: 3411 (N-H), 3255 (N-H), 3015 (C-H aromatic),
2929 (C-H aliphatic), 2854 (C-H aliphatic), 1949,
1685 (C=O of amide), 1615 (C=C aromatic), 1575

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
(C=N), 1450, 1385 (CH3 deformation), 1245 (C-N), 970s (=C-H), 833 (C=C, out-of-plane bending), 756
968s (=C-H), 869 (C=C, out-of-plane bending), 760 (Ar-H, bending and ring puckering), 651.
(Ar-H, bending and ring puckering), 650.
Synthesis of 3,3'-(1,4-phenylene)bis(2-
Synthesis of 3,3-(1,2-phenylene)bis(2- methylquinazolin-4(3H)-one), 8l
methylquinazolin-4(3H)-one, 8j
Treatmentof2-methyl-4H-3,1-benzoxazin-4-
Treatment of 2-methyl-4H-3,1-benzoxazin- one, 7 (3.00 g, 18.60 mmol) with o-phenylenediamine
4-one, 7 (3.00 g, 18.60 mmol) with o-phenylene (1.01 g, 9.30 mmol, 0.5 equiv.) afforded 3,3'-(1,4-
diamine (1.01 g, 9.30 mmol, 0.5 equiv.) afforded phenylene)bis(2-methyl quinazolin-4(3H)-one), 8l.
3,3-(1,2-phenylene)bis(2-methyl quinazolin-4(3H)- 1H-NMR (500 MHz, CDCl3) dH:8.10-8.07 (d, J = 5.60
one, 8j. 13C-NMR (125 MHz, CDCl3) dC: 171.05 (2 Hz, 2H of 2 × Ar-H), 7.89-7.87 (d, J = 7.82 Hz, 2H, 2
× C=O), 144.12 (2 × C), 140.91 (2 × C), 134.21 (2 × Ar-H), 7.70-7.65 (m, 4H, 2 × Ar-H), 7.36-7.34 (d, J
× C), 133.88 (2 × C), 127.31 (2 × C), 126.71 (2 × = 10.00 Hz, 4H, 2 × Ar-H), 2.26 (s, 6H, 2 × CH3). 13C-
C), 126.60 (2 × C), 123.18 (2 × C), 120.77 (2 × C), NMR (125 MHz, CDCl3) dC:170.23 (2 × C=O), 145.21
114.33 (2 × C), 25.12 (2 × CH3). DEPT 135 (125 (2 × C), 137.19 (2 × C), 134.02 (2 × C), 130.16 (2 ×
MHz, CDCl3) dC:Positive signals are 127.31 (2 × CH), C), 129.38 (2 × C), 122.77 (2 × C), 117.09 (2 × C),
126.71 (2 × CH), 126.60 (2 × CH), 123.18 (2 × CH), 25.22 (2 × CH3) ppm. DEPT 135 (125 MHz, CDCl3)
120.77 (2 × CH), 114.33 (2 × CH), 25.12 (2 × CH3) dC: Positive signals are 137.19 (2 × CH), 134.02 (2
ppm. No negative signals. UV-Vis.: lmax in nm (log × CH), 129.38 (2 × CH), 122.77 (2 × CH), 25.22
e
max mol-1cm-1): 206 (4.909), 251(4.568), 296(4.130). (2 × CH3) ppm. No negative signals. UV-Vis.: lmax
IR (KBr, cm–1) nmax: 3050 (C-H aromatic), 3011 (C-H in nm (log emax mol-1cm-1): 218(4.793), 251(4.545),
aromatic), 2925 (C-H aliphatic), 2857 (C-H aliphatic), 305(3.851).IR (KBr, cm–1) nmax:3056 (C-H aromatic),
1688 (C=O of amide), 1620 (C=C aromatic), 1576 3022 (C-H aromatic), 2925 (CH aliphatic from CH3),
(C=N), 1451, 1386 (CH3 deformation), 1247 (C-N), 1688 (C=O of amide), 1600 (C=C), 1575 (C=N),
969s (=C-H), 879 (C=C, out-of-plane bending), 760 1450, 1370 (CH3 deformation), 969s (=C-H), 831
(Ar-H, bending and ring puckering), 655.
(C=C, out-of-plane bending), 755 (Ar-H, bending
and ring puckering), 650.
Synthesis of 3-(2-mercaptophenyl)-2-
methylquinazolin-4(3H)-one, 8k
Synthesis of 1-(2-methyl-4-oxoquinazolin-3(4H)-
Treatment of 2-methyl-4H-3,1-benzoxazin- yl)urea, 8m
4-one, 7 (3.00 g, 18.60 mmol) with 2-aminothiophenol
Treatment of 2-methyl-4H-3,1-benzoxazin-
(2.00 ml, 18.60 mmol) afforded 3-(2-mercaptophenyl)- 4-one, 7 (3.00 g, 18.60 mmol) with semicarbazone
1
2-methylquinazolin-4(3H)-one, 8k. H-NMR (500 (1.39 g, 18.60 mmol) afforded 1-(2-methyl-4-
MHz, CDCl3) dH: 8.11-8.07 (d, J = 5.68 Hz, 1H of oxoquinazolin-3(4H)-yl)urea, 8m.
Ar-H), 7.89-7.87 (d, J = 7.80 Hz, 1H, Ar-H), 7.70- 1H-NMR (500 MHz, CDCl3) dH: 10.96 (s, 1H, NH),
7.65 (m, 2H, ArH), 7.46-7.43 (d, J = 10.00 Hz, 1H, 8.08-8.06 (d, J = 9.56 Hz, 2H, Ar-H), 7.81-7.68 (m,
Ar-H), 7.7-7.22 (d, J = 10.50 Hz, 1H, Ar-H), 7.10-7.05 2H, Ar-H), 7.08 (s, 2H, NH2), 2.22 (s, 3H, CH3-C=N).
(m, 1H, Ar-H), 3.42 (s, 1H, SH), 2.33 (s, 3H, CH3- 13C-NMR (125 MHz, CDCl3) dC:173.21 (C=O), 171.81
C=N).13C-NMR (125 MHz, CDCl3) dC:171.11 (C=O), (C=O), 151.18, 135.00, 132.27, 127.43, 117.04,
144.38, 141.09, 137.13, 134.27, 131.09, 130.88, 116.82, 109.99, 25.23 (CH3) ppm. DEPT 135 (125
129.20, 128.11, 127.23, 125.73, 122.10, 117.04, MHz, CDCl3) dC: Positive signals are 135.00 (CH),
114.11, 25.23 ppm.DEPT 135 (125 MHz, CDCl3) dC: 132.27 (CH), 117.04 (CH), 116.82 (CH), 25.23 (CH3)
Positive signals are 131.09, 130.88, 129.20, 128.11, ppm.No Negative signals.UV-Vis.:lmax in nm (log emax
127.23, 125.73, 118.23, 114.11 (CHs), 25.23 (CH3) mol-1cm-1): 221 (5.349), 302 (4.464), 545 (3.079). IR
ppm. No negative signals. UV-Vis.: lmax in nm (log (KBr, cm–1) nmax: 3415 (N-H), 3260 (N-H), 3176 (C-H
e
max mol-1cm-1):218 (5.310), 248 (4.969), 296 (4.497). aromatic), 2921 (C-H aliphatic), 2850 (C-H aliphatic),
IR (KBr, cm–1) nmax: 3112 (C-H aromatic), 3029 (C-H 1949, 1688 (C=O of amide), 1606 (C=C aromatic),
aromatic), 2925 (CH aliphatic from CH3), 2556w (S-H 1584 (C=N), 1453, 1383 (CH3 deformation), 1248
of thiol, sharp & weak), 1690 (C=O of amide), 1610 (C-N), 967s (=C-H), 879 (C=C, out-of-plane bending),
(C=C), 1585 (C=N), 1452, 1375 (CH3 deformation), 766 (Ar-H, bending and ring puckering).

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
Synthesis of 3-Amino-2-methylquinazolin-4(3H)-
one, 8n
970s (=C-H), 881 (C=C, out-of-plane bending), 755
(Ar-H, bending and ring puckering), 665.
Treatment of 2-methyl-4H-3,1-benzoxazin-
4-one, 7 (3.00 g, 18.60 mmol) with hydrazine
hydrate (0.91 ml, 18.60 mmol) afforded 3-amino-
Synthesis of 2-Methyl-3-(naphthalen-2-yl)
quinazolin-4(3H)-one, 8p
1
2-methylquinazolin-4(3H)-one, 8n. H-NMR (500
Treatment of 2-methyl-4H-3,1-benzoxazin-
MHz, CDCl3) dH: 7.92-7.90 (d, J = 9.56 Hz, 2H,
Ar-H), 7.30-7.27 (m, 2H, Ar-H), 6.50 (s, 2H, NH2),
2.07 (s, 3H, CH3-C=N). 13C-NMR (125 MHz, CDCl3)
dC: 173.21 (C=O), 151.18, 135.00, 132.27, 122.89,
117.04, 116.82, 109.99, 20.78 (CH3) ppm. DEPT
135 (125 MHz, CDCl3) dC: +ve signals are 135.00
(CH), 132.27 (CH), 117.04 (CH), 116.82 (CH), 20.78
(CH3) ppm. No –ve signals. UV-Vis.: lmax in nm (log
4-one, 7 (3.00 g, 18.60 mmol) with á-naphthylamine
(2.67 g, 18.60 mmol) afforded 2-methyl-3-
(naphthalen-2-yl)quinazolin-4(3H)-one, 8p.1H-NMR
(500 MHz, CDCl3) dH: 8.07-8.05 (d, J = 5.88 Hz, 1H,
Ar-H), 8.03-8.01 (d, J = 5.68 Hz, 1H, Ar-H), 7.69-7.67
(d, J = 8.00 Hz, 1H, Ar-H), 7.55-7.52 (m, 3H, Ar-H),
7.47-7.43 (m, 2H, Ar-H), 7.28-7.26 (d, J = 10.29 Hz,
1H, Ar-H), 2.41 (s, 3H, CH3-C=N). 13C-NMR (125
MHz, DMSO-d6) dC: 168.74 (C=O), 144.21, 139.70,
137.43, 132.61, 132.01, 129.36, 129.14, 127.89,
126.82, 126.12, 125.57, 125.02, 124.71, 123.40,
122.17, 121.18, 118.64, 22.40 (CH3) ppm.DEPT 135
(125 MHz, CDCl3) dC: Positive signals are 139.70,
132.61, 129.36 (CH), 129.14 (CH), 126.81, 126.12,
125.57 (CH), 125.02 (CH), 123.40 (CH), 121.18
(CH), 118.64 (CH), 22.40 (CH3) ppm. No negative
signals. UV-Vis.: lmax in nm (log emax mol-1cm-1): 224
(5.349), 242 (5.444), 305 (4.971).IR (KBr, cm–1)
e
max mol-1cm-1): 230 (5.443), 245(5.439), 320(5.089).
IR (KBr, cm–1) nmax: 3479 (N-H of NH2), 3394 (N-H),
3185 (C-H aromatic), 3049 (C-H aromatic), 2921
(C-H aliphatic), 1948 (C=C asym. stretching), 1689
(C=O), 1652 (C=C), 1581 (C=N), 1453, 1376 (CH3
deformation), 1245 (C-N), 968s (=C-H), 880 (C=C,
out-of-plane bending), 756 (Ar-H, bending and ring
puckering), 660.
Synthesis of 3-(2,4-dinitrophenylamino)-2-
methylquinazolin-4(3H)-one, 8o
n
max: 2919 (C-H aliphatic), 2084, 1690 (C=O), 1610
Treatment of 2-methyl-4 H-3, 1-
(C=C aromatic), 1485, 1369 (CH3 deformation),
1246 (C-N), 960s (=C-H), 829 (C=C, out-of-plane
bending), 758 (Ar-H, bending and ring puckering),
654.
benzoxazin-4-one, 7 (3.00 g, 18.60 mmol) with
2,4-dinitrophenylhydrazine (2,4-DNP) (3.59 g,
18.30 mmol) afforded 3-(2,4-dinitrophenylamino)-2-
methylquinazolin-4(3H)-one, 8o.1H-NMR (500 MHz,
CDCl3) dH: 9.01 (s, 1H, Ar-H), 8.52-8.50 (d, J = 8.00
Hz, 2H, Ar-H), 8.04-8.01 (d, J = 9.22 Hz, 1H, Ar-H),
7.45-7.40 (d, J = 9.22 Hz, 1H, Ar-H), 7.38-7.36 (d, J
= 8.00 Hz, 2H, Ar-H), 7.11.7.15 (m, 2H, Ar-H), 5.60
(s, 1H, NH), 2.55 (s, 3H, CH3). 13C-NMR (125 MHz,
CDCl3) dC: 171.21 (C=O), 151.18, 146.33, 140.12,
135.15, 138.19, 132.03, 129.70, 126.73, 122.89,
120.13, 117.84, 116.29, 109.99, 24.78 (CH3) ppm.
DEPT 135 (125 MHz, CDCl3) dC:Positive signals are
146.33, 140.12, 138.19, 135.15, 132.03, 117.84,
116.29 (CHs), 24.78 (CH3) ppm.No negative signals.
UV-Vis.: lmax in nm (log emax mol-1cm-1): 218 (4.650),
248(4.354), 347(4.130). IR (KBr, cm–1) nmax: 3420
(N-H), 3365 (N-H), 3100 (C-H aromatic), 3045
(C-H aromatic), 2925 (C-H aliphatic), 2850 (C-H
aliphatic), 1945 (C=C asym.stretching), 1690 (C=O),
1622 (C=C), 1585 (C=N), 1535 (N-O Asymmetric
stretching of NO2), 1455, 1376 (CH3 deformation),
1315 (N-O symmetric stretching of NO2),1245 (C-N),
Synthesis of 2-Methyl-3-(3-(trimethoxysilyl)
propyl)quinazolin-4(3H)-one, 8q
Treatment of 2-methyl-4H-3,1-benzoxazin-
4-one, 7 (3.00 g, 18.60 mmol) with 3-amino
propyltrimethoxysilane (3.25 ml, 18.60 mmol)
afforded 2-methyl-3-(3-(trimethoxysilyl) propyl)
quinazolin-4(3H)-one, 8q.1H-NMR (500 MHz, CDCl3)
dH: 7.94-7.92 (d, J = 9.56 Hz, 1H, Ar-H), 7.37-7.35
(d, J = 8.00 Hz, 1H, Ar-H), 7.15-7.09 (m, 2H, Ar-H),
4.14-4.11 (t, J = 5.44 Hz, 2H, N-CH2-CH2), 3.52 (s,
9H, 3 × CH3, Si-O-CH3), 2.52 (s, 3H, CH3-C=N),
1.68-1.65 (m, 2H, CH2), 1.22-1.25 (t, J = 7.56 Hz, 2H,
Si-CH2-CH2). 13C-NMR (125 MHz, CDCl3) dC:171.31
(C=O), 135.20, 132.27, 127.45, 126.25, 122.89,
117.04, 51.32 (3 × O-CH3), 46.27 (CH2), 23.48
(CH2), 16.61 (S-CH2), 22.49 (CH3) ppm. DEPT 135
(125 MHz, CDCl3) dC: Positive signals are 132.27,
127.45, 126.25, 117.04 (CHs), 116.82 (CH), 51.32 (3
× CH3), 22.49 (CH3) ppm.Negative signals are 46.27

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
(CH2), 23.48 (CH2), 16.61 (CH2) ppm. UV-Vis.: lmax temperature for the effective synthesis of 8a being the
in nm (log emax mol-1cm-1): 215 (4.924), 248 (4.691), first and simplest 2-methyl-3-substitutedquinazolin-
299(4.196).IR (KBr, cm–1) nmax:3101 (C-H aromatic), 4(3H)-one since the substituent at position-3 of its
3022 (C-H aromatic), 2929 (C-H aliphatic), 2855 template was a methyl group. The synthesis of 8a
(C-H aliphatic), 1945 (C=C asym. stretching), 1690 was attempted in four different entries via thermal
(C=O), 1620 (C=C), 1575 (C=N), 1450, 1377 (CH3 reaction of 2-methyl-4H-3,1-benzoxazine-4-one
deformation), 1245 (C-N), 1050 (Si-OCH3, str.& brd.), with methyl amine at reflux condition for 6 h using
973s (=C-H), 885 (C=C, out-of-plane bending), 755 three solvents which were butanol, ethanol and
(Ar-H, bending and ring puckering), 668.
RESULT AND DISCUSSIONS
Chemistry
dichloromethane as well as under solvent-free media
(Table 1).This was done for comparative study of the
efficiency of each solvent system for obtaining 8a. It
was observed that the reaction in ethanol gave the
most suitable condition for the synthesis of 8a, since
Quinazolinone derivatives are important it resulted in the highest yield (79.78%), followed by
structural scaffolds found in various library of butanol (55.83%) and then dichloromethane which
biologically active compounds which are medicinally gave the lowest yield (45.35%). However, it was
useful agents in formulation, discovery of drugs interesting to note that solvent-less medium resulted
and medicinal chemistry research. Hence, in in no isolable product but reverted back to the staring
the continuation of our effort on the synthesis of material as indicated by the observation found in
N-heterocyclic motifs1,2,4, we have herein achieved the TLC spotting which showed the presence of the
expeditious synthesis of 2-methyl-3-substituted starting material without any new spot for the product,
quinazoline-4(3H)-one derivatives 8a-q, in a two while the solvent free medium gave the least yield
steps technique. The first step of the synthesis in (18.21%) as most of the starting material was not
this present research work, involved the reaction effectively converted to product as noticed in theTLC
of anthranilic acid with acetic anhydride according spotting monitoring. and therefore it was used in all
to a known procedure reported by Hassan et al22. subsequent experiments. The effect of temperature
in modified version to afford reactive intermediate was studied by carrying out the synthesis of 8a
o
2-methyl-4H-3,1-benzoxazin-4-one, 7 which was at different temperatures; 40, 70, 100 and 130 C
used as the reactive intermediate for the second step. (Table 2) using ethanol solvent which was unveiled
Thecompletionofthereactionwasmonitoredwiththin as the best solvent during the solvent-dependent
layer chromatography (TLC) using dichloromethane: optimization study and the result was as shown in
methanol (9.5:0.5) as the eluting solvent system.The Table 2. At refluxing reaction temperature of 40 oC,
solid formed was filtered via suction and air-dried the yield of 8a was 18.53% obtained; and as the
o
in order to afford 2-methyl-4H-3,1-benzoxazin-4- temperature increased to 70 C, the percentage
one 7 in good yield (Scheme 1). However, before yield of 8a also increased to 55.82%, while the
this intermediate was taking further to achieve all highest yield of 8a was observed to be 79.78%
o
targeted compounds 8a-q, the reaction optimization at a reacting temperature of 100 C. However, the
study was carried out via the synthesis of 8a which percentage yield decreased sharply to 35.48% when
was the first member of this series. Preliminary the reaction was experimented at temperature of
optimization of reaction conditions was done by 130 oC (Table 2). Hence, it was concluded that the
considering the effect of solvent type and reaction optimum temperature for the expeditious synthesis
Table 1: Investigation of solvent-dependent
synthesis of (8a) under reflux condition
Table 2: Investigation of temperature-
dependent synthesis of (8a) in ethanol
Entry Solvent Temperature / oC Yield / %
Entry
Solvent
Time / h
Yield / %
1
2
3
4
Ethanol
Butanol
Dichloromethane
Solvent free
6
6
6
6
79.78
55.83
45.35
NIPO
1
2
3
4
Ethanol
Ethanol
Ethanol
Ethanol
130
100
70
35.48
79.78
55.62
18.53
40

570
AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
o
of 8a was 100 C and in the presence of ethanol
melting point, percentage yield, sample colour and
elemental analytical result for carbon, hydrogen
and nitrogen.The molecular weights of the targeted
compounds ranged 174.08 for compound 8a to
410.64 for compound 8d. The Rf value for the
targeted compounds varied from 0.36 for compound
8l to 0.91 for compound 8n. The Rf values did not
only showed the level of purity for each compound
but also established the polarity of these targeted
compounds. The melting point of the targeted
compounds 8a-q was also presented in Table 3. It
showed that compound 8b and 8m had the highest
solvent.Therefore, the same reaction condition was
subsequently use for the synthesis of the remaining
sixteen 2-methyl-3-substituted quinazolin-4(3H)-one
motifs, 8b-q through synthetic modification of the
-COOC end by condensing it with various cheap
and readily available amino containing compounds
o
in the presence of ethanol at 100 C (Scheme 2).
The completion of the reaction was confirmed after
6 h of refluxing usingTLC spotting, then the solution
was left to stand overnight in freezer chest for proper
crystallization to afford the targeted 2-methyl-3-
substituted quinazolin-4(3H)-one derivative (8a-q)
in appreciable yields.
o
melting point value of > 300 C while compound
8f has the lowest melting point value of 117-121
oC. The melting points of other compounds, which
include 8i, 8j, 8k and 8l, were not determined due
to the fact that they were oily and liquid at room
temperature.The inability of compound 8m to melt at
the highest permissible limit (300 oC) of the melting
point apparatus might be due to the presence of the
Physico-chemical Analysis
The result of the physico-chemical
parameters of the synthesized compounds 8a-q
was as shown in Table 3. These parameters
investigated include molecular weight, Rf value,
O
O
O
O
O
OH
NH2
+
Reflux, 6 h
N
H3C
O
CH3
7
2-methyl-4H-3,1-benzoxazin-4-one
Scheme 1: Synthesis of 2-methyl-4H-3,1-benzoxazin-4-one, 7.
8a: R = CH3
8b:
O
R = n-C5H11
8c: R = n-C16H33
8d:
R
N
R = (CH2)8-CH=CH-(CH2)7CH3
8e: R = cyclohexyl
N
O
N
8a-e
R
O
N
R
N
N
k
,
i
-
f
a-e
p
-
q
8p-q
8p: R = 2-Naphthyl
8q: R = -(CH2)3-Si-(OCH3)3
O
8f: R = H
8g:
R = 4-Cl
8h: R = 4-Br
8i :
O
R = 2-NH2
8k : R = 2-SH
N
7
o
-
O
N
m
j
H
N
N
R
l
N
N
N
O
N
O
8m-o
8m: R = CONH2
8n:
O
O
N
8j
N
R = H
8o: R = 2,4-dinitrophenyl
N
N
8l
Reaction Condition: Reflux in ethanol at 100 oC for 6 h. Reagent: (a) methylamine (b) pentylamine
(c)
(d)
(e)
(f)
(g)
(h)
4-bromo
(n)
semicarbazide hyd
hexadecylamine
oleyl amine
(k)
aniline ( & ) o-phenylenediamine
cyclohexylamine
(l)
aniline
p-phenylenediamine
4-chloroaniline
(m)
i
j
2-thioaniline
(p)
(o)
(q)
1-nathylamine 3-aminopropyltrimethoxylsilane
razine hydrate
2,4-dinitrophenylhydrazine
Scheme 2: Synthesis of the 2-methyl-3-substitutedquinazolin-4(3H)-one, 8a-q.

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
additional side chain amide which had tendency to followed by compound 8c with cream colour while
exhibit hydrogen bong formation.The next parameter compounds 8f was black in colour. Compounds
is the percentage yield which varied from 49.90% for 8i, 8j and 8k were observed to be yellow in colour
compound 8i to 99.54% for compound 8n.The colour followed by compounds 8l, 8q and 8q which were
of the synthesized compounds was determined via purple whereas, compound 8m was noticed to be
virtual observation to be seven different colours white in colour.The result of the elemental analytical
which are brown, cream, black, yellow, purple, data for the carbon, hydrogen and nitrogen of the
red and white. Compounds 8a, 8b, 8d, 8e, 8g, 8h, intermediate 7 and the targeted compounds 8a-q was
8n and 8q were observed to be brown in colour, the last parameter presented in Table 3. The result
Table 3: Result of the physico-chemical parameters of synthesized compounds, 8a-q
Comp.
No.
Mol.
Formula
(Mol. Wt.)
Rf
Value
Melting
Pt. (oC)
Yield
(%)
Sample
Colour
Elemental Analysis %
Calcd. (% Found)
C
H
N
8a
8b
8c
8d
8e
8f
C10H10N2O
(174.08)
C14H18N2O
(230.31)
C25H40N2O
(384.60)
C27H42N2O
(410.64)
C15H18N2O
(242.32)
C15H12N2O
(236.27)
C15H11N2OCl 0.72b
(270.71)
C15H11N2OBr 0.82b
(315.16)
C15H13N3O
(251.28)
C24H18N4O2
(394.43)
C15H12N2OS 0.60a
(268.33)
C24H18N4O2
(268.33)
C10H10N4O2
(218.21)
C9H9N3O
(175.19)
C15H11N5O5
(341.28)
C19H14N2O
(286.33)
0.62a
0.83a
0.62a
0.58a
0.89a
0.71a
285
79.78
83.75
98.10
85.65
57.43
61.57
94.78
95.13
49.90
51.37
78.56
60.47
71.97
99.54
74.84
96.44
81.52
Brown
Brown
Cream
Brown
Brown
Black
68.95
5.79
9.18
(69.01) (5.73) (9.22)
73.01 7.88 12.16
(72.97) (8.06) (12.11)
78.07 10.48 7.28
(77.97) (10.31) (7.14)
78.97 10.31 6.82
(79.04) (10.28) (7.00)
74.35 7.49 11.56
(74. 28) (7.54) (11.61)
76.25 5.12 11.86
(76.33) (4.97) (12.01)
66.55 4.10 10.35
(66.41) (3.97) (10.42)
> 300
278-281
267-272
178-181
117-121
292-296
285-287
ND
8g
8h
8i
Brown
Brown
Yellow
Yellow
Yellow
Purple
White
Brown
Red
57.16
(57.22) (3.66)
71.70 5.21
3.52
8.89
(9.02)
16.72
0.68a
(71.55) (5.08) (16.61)
73.08 4.60 14.20
(72.97) (4.47) (14.32)
67.14 4.51 10.44
(66.98) (4.39) (10.54)
73.08 4.60 14.20
(72.94) (4.51) (14.37)
55.04 4.62 25.68
(54.97) (4.55) (25.75)
61.70
(61.88) (4.99)
52.79 3.25
(52.61) (3.31) (20.67)
79.70 4.93 9.78
(79.62) (5.02) (9.87)
55.88 6.88 8.69
(56.02) (7.04) (8.75)
8j
0.66a
ND
8k
8l
ND
0.36a
0.55a
0.91a
0.56b
0.72a
0.58a
ND
8m
8n
8o
8p
8q
> 300
138-140
153-155
213-215
258-261
5.18
23.99
(24.08)
20.52
Purple
Brown
C19H14N2O
(322.43)

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AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
of elemental analysis did not only correlate well with
the molecular masses of all synthesized compounds
but also showed a consistent minimum difference of
not more than 0.39 between % calculated and %
found for the carbon, hydrogen and nitrogen of the
targeted products 8a-q.
The 13C-NMR spectrum of reactive
intermediate 7 revealed the presence of nine carbon
atoms which include a carbonyl at d168.77 ppm, one
C=N carbon of imino at d 140.37 ppm six aromatic
carbon at d134.91 ppm to 114.52 ppm, and the
last carbon close to TMS was CH3 type at d 20.92
ppm. Careful observation of the signals of 8a in
comparison with that of compound 7 showed effective
transformation of 2-methyl-4H-3,1-benzoxazin-4-
one, 7 to 2,3-dimethyl quinazolin-4(3H)-one, 8a by
the virtue of one additional signal at d 20.92 ppm
which was that of second methyl group found in
8a but absent in 7. The most de-shielded signals
in the 13C-NMR spectra in all of the compounds
varied between d 173.3 and 172.8 ppm which were
attributed to the presence of carbonyl of ester in 7
and carbonyl of amide in 8a-q. It was in agreement
with the earlier reported value by Al-Kawkabani et
al. who investigated the synthesis of novel 2H,8H-
pyrano[2,3-f]chromene-2,8-dione based scaffolds
under tandem knoevenagel condition24.
Spectroscopic Characterization
The results of the electronic transition using
uv spectroscopy was investigated in ethanol solution
and the results is a presented in the experimental
section showing the wavelength (lmax) and the log of
molar absorptivity (Log emax). The infrared analysis
was carried out using Bruker Fourier-Transform
Infrared (FT-IR) and the various absorption bands
from stretching and bending vibrational frequencies
were duly reported. The results of the infrared
spectral data of all the synthesized compounds
were as presented in the experimental section.
1
The H-NMR and 13C-NMR as well as DEPT-135
(Distortionless Enhancement by Polarization
Transfer) of the reactive intermediate and targeted
quinazolin-4-one motifs 8a-q were run in either
DMSO-d6 or CDCl3 depending on the solubility
behaviour of each of the compound to be analyzed
Furthermore, the infrared spectrum of the
precursor 7 was run in KBr pellet and it showed
the presence of C-H aromatic stretching vibrational
frequency at 3020 cm-1 while that of C-H aliphatic
was noticed as two bands at stretching vibrational
frequencies of 2929 cm-1 and 2846 cm-1. The C=O
of ester was responsible for the band at 1743 cm-1
which was further confirmed by the presence of C-O
of alkoxy group at 1109 cm-1.The absorption bands
at n 1620 cm-1 and 1576 cm-1 depicted the presence
of C=C aromatic and C=N imino functionalities
respectively. The infrared spectroscopy spectrums
of the synthesized compounds were run in KBr
pellet using Bruker FT-IR machine. According to
the result of the 2-methylsubstituted quinazolinone
(8a-q), the C-H band of the aromatic were found
in the range 3188 cm-1 (8h) to 3011 cm-1 (8j); while
the highest band for C-H of aliphatic was observed
in 8b and 8d as 2935 cm-1 and the lowest was at
2845 as seen in compounds 8a and 8e. The bands
in the range of 1693 (8g) to 1685 (8i) depicted the
presence of C=O of amide in compounds 8a to 8q.
The C=C of compounds 8a-q absorbed at stretching
vibrational frequency of 1660 cm-1 (8c) to 1600 cm-1
(8l and 8h).The C=N imino functionality was present
in all compound 8a-q at the stretching vibrational
frequencies at region 1588 cm-1 (as found in 8c) to
1575 cm-1 (which was common to compound 8f, 8l,
1
per time. The H-NMR spectrum of precursor 7
was run in CDCl3. It showed the presence of four
aromatic protons between d 7.96 and 7.40 ppm.
They are 1H doublet at d 7.77-7.73 ppm which was
in the neighborhood of 1H triplet since they both
possessed the same coupling constant of 9.68 Hz.
Similarly, the remaining two aromatic protons were
observed as 1H doublet at d 7.46-7.42 ppm and 1H
triplet at d 7.42-7.40 ppm with coupling constant of
10.00 Hz.The 3H of methyl group was observed up-
field ofTMS as a singlet at d 2.59 ppm.Apart from all
other signals in 1H NMR of compound 7 which were
replicated in representative targeted product 8a, it is
crucial to note that the 1H NMR spectrum of 8a also
showed one addition signal at chemical shift value of
d 3.35 ppm.This authenticated the insertion of methyl
group at the position 3 of compound 7 to afford 8a.
It was worthy to note that these values fall within the
range for aromatic protons (8.28-7.09 ppm) earlier
reported by Ajani et al., (2010) who investigated the
microwave assisted synthesis of a series of novel
2-quinoxalinone-3-hydrazone23 which also belong to
benzodiazine family like quinazolinone but with its
own nitrogen heteroatom situated at position 1 and
4 of the hetero ring system.

573
AJANI et al., Orient. J. Chem., Vol. 33(2), 562-574 (2017)
8g). It was worthy to note that deformed alkyl group was due to the presence of an auxochrome imine
was presence in compound 8a-q, by the virtue of (N=C). This was as a result o p→n transition which
CH3 group in position 2 of the quinazolinone ring may be ascribed to the auxochromic C=N group.The
and as a result of availability of CH2, CH, in some noticeable peaks seen at lmax = 545 nm (Log emax
=
peculiar compounds. The vibrational frequencies 3.08) might be due to the p→n transition peculiar to
for the CH3, CH2, CH, (deformation) was noticed at the NH herein present in compound 2m, although,
1485 cm-1 highest value of 1485 cm-1 for 8p while the with low log of molar absorptivity. It is interesting
lowest value for this was found at 1370 cm-1 for 8e. to note that all the compounds have electronic
The absorption bands at 1248 cm-1 (8m) to 1245 cm-1 transition which culminated into specific peaks in
(8o and 8n), depicted the presence of C-N functional their uv spectra, including even the whitish coloured
moieties. Specifically speaking compound 8o alone compounds. In addition, the uv-visible spectra of the
showed an asymmetry stretching. The frequency quinazoline-4-one, 8a-8q experienced bathochromic
herein reported for carbonyl of ester at 1743 cm-1 was shifts of about 15 - 30 nm to give higher max values
further confirmed by comparing it with the findings at above 351 nm, which may be ascribed to the
of Lewis et al. who documented the various C=O chromophoric C=N group; characteristic of K bands
stretching absorption vibration frequencies in infrared of C=N functional group26.
spectra25 ranged between 1685 cm-1 to 1758 cm-1.
The C=N reported herein was within the ranged of
the C=N of benzimidazole earlier reported in our
previous study2.
CONCLUSION
As envisaged from reviewed literature and
chemical behavioural pattern of 2-methyl-4H-3,1-
The electronic absorption spectra featuring bnezoxazin-4-one, 7, the thermal annelation of this
lmax (Log emax) of the synthesized compounds was run reactive intermediate with various amino-based
in ethanol because they were all soluble in ethanol compounds to afford the corresponding 2-methyl-
and the result is as shown in the experimental section. 3-substitutedquinazolin-4(3H)-one derivatives, 8a-q
The lowest wavelength in the electronic transition of was successful. The reaction optimization study
the synthesized compounds in 8a-q was found at revealed the crucial role of the careful choice of
206 nm as seen in compounds 8i and 8j respectively. solvent and thermodynamic parameter in order
The lowest wavelength for the compounds were as to achieve the targeted compounds in good to
a result of the p→p* transition of C=C which showed excellent yields even in the absence of catalyst.The
the presence of benzene ring in all the compounds. spectroscopic assignments for structural elucidation
Other transitions found at longer wavelengths were was in concordance with the proposed structures for
bathochromic in nature and are due to presence of the synthesized compounds. The titled compounds
auxochromic group nitrogen atom which is able to are good candidate for further study in term of the
delocalize its lone pair into the chromophoric group investigation of their antimicrobial and antimalarial
thereby extending the wavelength and affecting potential for further drug development.
the intensity of the absorbance. The highest
wavelength 545 nm (Log emax = 3.08) was found in
the uv electronic transition of the compound 8m.
Specifically, the visible absorption spectrum of 8m,
ACKNOWLEDGMENT
O.O.Ajani gratefully acknowledges The
for instance, showed a low band at lmax = 221 nm (Log World Academy of Sciences for the sponsorship
max = 5.35) which was the value for the confirmation of this project under the TWAS Research Grants
e
of presence of phenyl ring while the bathochromic Programme in Basic Sciences for Individual
shift observed at lmax = 302 nm (Log emax = 4.46) Scientists (Grant No. 14-069 RG/CHE/AF/AC_1).
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