An efficient, one-pot three components synthesis of [1,2,4] triazoloquinazolinone derivatives using anthranilic acid as green catalyst

Article abstract of DOI:10.1007/s11164-017-2896-5

A simple, efficient and convenient approach has been reported for the synthesis of quinazolines by the condensation of 3-amino, 1,2,4-triazole with dimedone and different aromatic aldehydes in the presence of anthranilic acid as a catalyst through a one-p

Full text of DOI:10.1007/s11164-017-2896-5

Res Chem Intermed
DOI 10.1007/s11164-017-2896-5
An efficient, one-pot three components synthesis
of [1,2,4] triazoloquinazolinone derivatives using
anthranilic acid as green catalyst
Sunil Vibhute1 Dattatraya Jamale1
•
•
Santosh Undare2 Navanath Valekar3
Govind Kolekar3 Prashant Anbhule3
•
•
•
Received: 26 November 2016 / Accepted: 2 February 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract A simple, efficient and convenient approach has been reported for the
synthesis of quinazolines by the condensation of 3-amino, 1,2,4-triazole with
dimedone and different aromatic aldehydes in the presence of anthranilic acid as a
catalyst through a one-pot reaction. The high yield, at low cost, with no need of
chromatographic separation, and the environmentally friendly catalyst are the
prominent features of this protocol. The zwitterion of anthranilic acid plays an
important role in this one-pot reaction.
Keywords Quinazolinones Á 3-Amino 1,2,4-triazole Á Dimedone Á Anthranilic acid Á
Zwitterions
Introduction
Amino acids, being building blocks of proteins, are found in every part of every cell.
Tryptophan is one of the most important essential amino acids and anthranilic acid
plays a vital role both in the anabolism and catabolism of tryptophan. In the
Electronic supplementary material The online version of this article (doi:10.1007/s11164-017-2896-5)
contains supplementary material, which is available to authorized users.
&
Prashant Anbhule
pvanbhule@gmail.com
1
2
3
Chemistry Research Laboratory, Department of Chemistry, Shri Shivaji Mahavidyalaya, Barshi,
Dist. Solapur, M.S, India
Department of Chemistry, Balbhim College of Arts, Science & Commerce, Beed, Dist. Beed,
M.S, India
Medicinal Chemistry Research Laboratory, Department of Chemistry, Shivaji University,
Kolhapur, M.S 416004, India
123

S. Vibhute et al.
catabolism of tryptophan, one of the intermediates is 3-hydroxy anthranilic acid,
which serves as a precursor in the biosynthesis of the vitamin-nicotinic acid.
Deficiency of nicotinic acid leads to the disease pellagra in man and black tongue in
dogs. Moreover, intermediates in tryptophan catabolism act as the precursors for the
biosynthesis of the important biomolecule serotonin, which is a neurotransmitter
substance and vasoconstrictor. Anthranilic acid and tryptophan are equally
important as biosynthesis of tryptophan occurs through a series of enzymatic
reactions from anthranilic acid. In continuation of this text, it is stated that
anthranilic acid flows in our veins as a byproduct of many biochemical reactions
occurring in cells [1–4].
Major biochemical pathways of bacteria, plants and animals exhibit the
importance of anthranilic acid as it acts as the starting material for several other
types of compounds in nature. Among these are alkaloids [5] like nicotine,
nicotinamide, plant signaling compounds like DIMBOA [6], plant growth hormone
indole–3 acetic acid [7, 8], and that the concentration of methyl anthranilate in
grapes generally increases on ripening [9], wine, such as Pinot Noir from Burgundy
contains ethyl and methyl anthranilate as odorants [10]. A beetle ‘black chafer’ use
anthranilic acid as a pheromone [11]. The presence of N-acetylated derivatives of
anthranilic acid in oats has been proved [12].
In addition, anthranilic acid and its derivatives are playing a significant role in
industry. In perfumes, methyl anthranilate is used as an important ingredient;
moreover, it is a flavor additive in soft drinks. The annual production of methyl
anthranilate is estimated to be over 1000 tons [13].
O
CONH2
NH2
COOMe
NH2
O
N
H
O
methyl anthranilate
anthranilamide
isatonic anhydride
Anthranilamide is also widely applied in numerous synthetic procedures for
pharmaceuticals and natural products [14].
Use of anthranilic acid in stoichiometric amounts in the synthesis of quinazo-
lines, substituted quinazolines, benzodiazepines and benzoxazine-4-ones is well
documented in the literature [14]. Rastogi et al. [15] have reported anthranilic acid
as a co-catalyst in the synthesis of conjugated nitroalkanes in THF along with the
catalyst imidazole via the Morita–Baylis–Hillman reaction. Kassehin et al. [16]
proved anthranilic acid as being an innovative green nucleophilic catalyst in the
synthesis of antitrypansomal thiosemicarbazones. These reported protocols signif-
icantly exhibit the capability of anthranilic acid to act as a catalyst. Moreover,
anthranilic acid is non-toxic, inexpensive, readily available, easy to handle and its
nucleophilic moiety (–NH2) and acidic moiety (–COOH) are in close vicinity, which
leads to the formation of a zwitterion that facilitates the desired transformations.
123

An efficient, one-pot three components synthesis of…
Quinazolines and condensed quinazolines have been proved to be advantageous
to human beings due to their various therapeutic and pharmacological properties
like antihypertensives [17, 18], antihistamines, antibacterials [19], analgesics, anti-
inflammatories [20], anti-HIV, anti-fungals [21] and anticancer agents [22]. The
excellent biological activities and wide applications of quinazolines and condensed
quinazolines prompted us to investigate studies on [1,2,4] triazoloquinazolinone
derivatives. In recent years, multicomponent reactions are more efficient and are a
green alternative [23–25] to conventional bimolecular reactions due to their atom
economy, multiple bond forming efficiency, and high selectivity as well as enabling
straight forward access to a series of structurally related drug-like compounds.
These features made multicomponent reactions (MCR) a powerful tool [26–28] in
medicinal, combinatorial and organic chemistry.
It is evident from the literature that the most common methodology for the
synthesis of substituted triazolo/benzimidazolo quinazolinones is the one-pot
reaction of substituted aldehydes with 3-amino-1,2,4 triazole or 2-aminobenzim-
idazole with dimedone in the presence of an acid or a basic catalyst. Furthermore,
recent reported protocols of the synthesis of 6,6-dimethyl-9-phenyl-5,6,7,9-
tetrahydro-[1,2,4] triazolo [5,1-b] quinazolin-8(4H)-one included heating of starting
materials in DMF under reflux conditions [29, 30], in the presence of sulfamic acid
[31] using acetonitrile as solvents, utilising catalysts like ionic liquids [32],
heteropolyacids [33], molecular iodine [34], boric acid [35] and chitosan [36]
biopolymers. Despite the potential utility of these strategies, they exhibit various
drawbacks such as harsh reaction conditions, use of toxic organic solvents, use of
metal catalysts as well as expensive, moisture sensitive, hazardous catalysts,
unsatisfactory yields and cumbersome experimental procedures. All these literature
facts attracted us to use biodegradable anthranilic acid as a green catalyst in the
present protocol.
Results and discussion
As per our best knowledge, anthranilic acid was herein explored for the first time as
a catalyst in the synthesis of 1,2,4 triazoloquinazolines in a one-pot three
components coupling of substituted aromatic aldehydes, dimedone and 3-amino-
1,2,4-triazole as an amine source in alcohol (Scheme 1).
R
O
CHO
O
N
N
N
N
Anthranilic acid
Ethanol, Reflux
N
+
+
R
N
H
CH3
CH3
NH2
CH3
CH3
O
N
H
1
2
3
4a-4p
Scheme 1 Synthesis of [1,2,4] triazolo [5,1-b] quinazoline-8 (4H)—one derivatives
123

S. Vibhute et al.
For the selection of the most appropriate solvent, condensation of dimedone,
4-chlorobenzaldehyde and 3-amino-1,2,4 triazole, as a model reaction, was
examined in water, 50% ethanol, ethanol, DMF, and acetonitrile (Table 1). The
synthesis of a target product in the ethanol at 80 °C with anthranilic acid as the
catalyst was obtained in high yield (Table 1, entry-5). The yields are much lower
with other solvents.
Our next task was to optimize the appropriate concentration of the catalyst. We,
therefore, carried out a model reaction at various mole percentages, and the results
were compared (Table 2).
The highest yield was obtained with 30 mol% anthranilic acid in alcohol as the
solvent (Table 2, entry-6). Increase in the concentration of catalyst did not increase
the yield. It was noticed that at low concentration of the catalyst, lower yield of the
product is encountered, and, of course, without catalyst we did not get any product.
To optimize the reaction time on the yield of the desired product, the model
reaction was screened at different time intervals (Table 3).
To our delight, we obtained the maximum yield of the product within 6 h.
(Table 3, entry-6) Furthermore, increase in reaction time did not show any effect on
Table 1 Synthesis of 9-(4-chlorophenyl)-6-6 dimethyl-5,6,7,9-tetrahydro [1,2,4] triazolo [5,1-b]
quinazolin-8(4H) one
Entry
Solvent
Temperature (°C)
Time (h)
Yielda (%)
1
2
3
4
5
DMF
100
85
10
10
10
10
10
Trace
Trace
Trace
30
CH3CN
Water
100
90
50% EtOH
EtOH
80
80
Reagents and reaction conditions—reaction was carried out using dimedone (1 mmol), 4-chlorobenzal-
dahyde (1 mmol), 3-amino, 1,2,4 triazole and 20 mol% anthranilic acid as a catalyst
Bold values indicate optimized conditions
a
Isolated yields
Table 2 Optimization of
catalyst
Entry
Anthranilic acid mol%
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
5
10
15
20
25
30
35
40
–
10
10
10
10
10
10
10
10
10
Trace
Reagents and reaction
20
conditions—reaction was
carried out using dimedone
(1 mmol),
60
80
4-chlorobenzaldehyde
88
(1 mmol), 3-amino 1,2,4 triazole
(1 mmol) and various mol% of
anthranilic acid as a catalyst at
80 °C for 10 h under reflux
Bold values indicate optimized
conditions
95
95
95
No reaction
123

An efficient, one-pot three components synthesis of…
Table 3 Optimization of reaction time
Entry
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
Traceb
12b
45b
82b
92
95
95
95
Reagents and reaction conditions—reaction was carried out with dimedone (1 mmol), 4-chloroben-
zaldehyde (1 mmol), 3-amino 1,2,4 triazole in 5 ml EtOH using 30 mol % anthranilic acid at 80 °C
Bold values indicate optimized conditions
a
Isolated yields
b
Knoevenagel condensation product was obtained as byproduct
the yield of the product. In the present protocol, we initiated our studies by
employing a trial reaction in which a mixture of dimedone (1 mmol), 4-chloroben-
zaldehyde (1 mmol) and 3-amino-1,2,4 triazole (1 mmol) in the presence of
30 mol% anthranilic acid was refluxed in 5 mL of ethanol at 80 °C for the stipulated
period of time. The formation of title compound (4-a) was evident from the
appearance of[C=O stretching at 1647 cm-1, C–Cl stretching at 728 cm-1 and N–
H stretching at 3089 cm-1 in IR, with appearance of the characteristic methine
proton as a singlet at ë 6.43, and the appearance of [M ? H]? at m/z 329 in the
mass spectrum (ESI) was in agreement with the proposed structure.
To establish the scope and utility of our catalyst for the synthesis of [1,2,4]
triazolo-[5,1-b]-8(4H)-one derivatives, different substituted aromatic aldehydes
were reacted with dimedone and 3-amino-1,2,4-triazole in the presence of
anthranilic acid and ethanol as the reaction medium at 80 °C (Table 4).
From the analysis of reaction data (Table 4), we noticed that electron
withdrawing groups on aromatic aldehydes are favorable for this transformation
as they exhibit higher yields with low reaction time. However, electron donating
groups on aromatic aldehydes showed slightly lower yield with increased reaction
time. All the compounds reported in Table 4 have been characterized by IR, 1H, 13
NMR, MS and elemental analysis, and data is consistent with their structures.
C
The implementation of an efficient catalyst and an adequate solvent is thus
planned in the context of green chemistry [37, 38]. In chemical research and
engineering, the aim of green chemistry is to encourage the design of products and
processes that minimize the use and generation of hazardous substances.
To evaluate the present protocol according to green chemistry principles, green
metrics such as Mass Intensity (MI), Reaction Mass Efficiency (RME), Carbon
Efficiency (CE), and Atom Economy (AE) [39] are the terms which reveal the
greenness of the reaction. In an ideal situation, it is expected that MI & 1% [40],
123

S. Vibhute et al.
Table 4 Synthesis of (1,2,4) triazoloquinazolone derivatives by using anthranilic acid catalyst
Entry Aldehyde [1–3]
Product [6]
Time Yielda M.P. (°C)
(h)
(%)
Found
Literature
Cl
Cl
4a
6
95
302–304 304–306 [34]
O
N
N
CHO
Br
CH3
CH3
N
N
H
Br
4b
6
95
285–287 286–288 [34]
O
CHO
OH
N
N
CH3
CH3
N
N
H
OH
4c
6
90
302–304 [300 [34]
O
N
N
CHO
NO2
CH3
CH3
N
N
H
NO2
4d
6
95
305–307 [300 [34]
O
CHO
N
N
CH3
CH3
N
N
H
N(CH3
)
N(CH3
)
2
4e
7
87
288–300 285–287 [35]
2
O
CHO
N
N
N
CH3
CH3
N
H
123

An efficient, one-pot three components synthesis of…
Table 4 continued
Entry Aldehyde [1–3]
Product [6]
Time Yielda M.P. (°C)
(h)
(%)
Found
Literature
4f
6
91
286–288 287–290 [31]
CHO
O
N
N
CH3
CH3
N
N
H
OCH3
OCH3
CHO
4g
7
94
224–226 228–230 [35]
O
N
N
N
CH3
CH3
N
H
NO2
NO2
O
4h
7
90
268–270 266–269 [31]
CHO
N
N
N
CH3
CH3
N
H
Br
Br
O
4i
7
92
278–280 280–282 [32]
CHO
N
N
N
CH3
CH3
N
H
4j
6
95
252–254 250–252 [34]
O
CHO
CH3
N
N
N
CH3
CH3
N
H
CH3
4k
7
90
265–269 266–268 [34]
O
N
N
CHO
N
CH3
CH3
N
H
123

S. Vibhute et al.
Table 4 continued
Entry Aldehyde [1–3]
Product [6]
Time Yielda M.P. (°C)
(h)
(%)
Found
Literature
OH
OH
O
4l
7
92
288–290 289–290 [34]
CHO
N
N
CH3
CH3
N
N
H
4m
8
92
241–243 240–243 [34]
H3CO
O
OCH3
CHO
N
N
CH3
CH3
N
N
H
OCH3
OCH3
CHO
4n
8
86
278–280
–
OCH3
O
OCH3
N
N
N
CH3
CH3
N
H
4o
6
91
288–290 290–292 [34]
NO2
O2N
N
O
CHO
F
N
CH3
CH3
N
N
H
F
4p
7
94
306–308 301–303 [34]
O
CHO
N
N
N
CH3
CH3
N
H
a
Isolated yield
RME & 100%, %CE & 100 and %AE & 100. We have represented the green
metrics calculations for all the reactions in Table 5.
The results demonstrate that MI values for all compounds are quite excellent as
well as excellent yields produced good values of RME while moderate yield
123

An efficient, one-pot three components synthesis of…
Table 5 Green metrics calculations
Entry Compound code %Yield FW (product) Yield (g) MI
%RME %CE
%AE
1
4a
4b
4c
4d
4e
4f
95
95
90
95
87
91
94
90
92
95
90
92
92
85
91
94
328.796
373.247
310.350
339.348
337.418
344.409
324.377
339.348
373.247
294.351
308.301
310.350
324.377
354.402
339.348
312.341
0.311
0.354
0.279
0.322
0.293
0.313
0.304
0.305
0.348
0.279
0.277
0.285
0.298
0.309
0.308
0.293
1.17 85.43
1.15 86.55
1.24 80.36
1.16 89.06
1.27 73.10
1.21 82.36
1.18 84.44
1.22 81.33
1.17 84.87
1.19 83.53
1.24 80.06
1.21 82.36
1.20 82.77
1.26 79.23
1.21 82.13
1.11 89.66
94.80 90.44
94.90 91.21
90.00 89.91
94.90 90.43
86.90 90.37
90.90 90.55
93.80 90.22
89.90 90.42
91.95 91.21
94.89 89.96
90.00 89.53
91.95 89.59
91.96 90.00
85.02 90.80
90.90 90.40
93.90 89.75
2
3
4
5
6
7
4g
4h
4i
8
9
10
11
12
13
14
15
16
4j
4k
4l
4m
4n
4o
4p
produced moderate RME values. Moreover, our reactions show excellent CE
because all the carbon atoms of the reactants are present in the product. Atom
economy values &90% reveals that the present protocol is of high atom economy.
Table 5 clearly exhibited that anthranilic acid is an excellent catalyst for this one pot
three components reaction since it gives desired product in good to excellent yields
and leads to excellent green metrics.
A plausible reaction mechanism for a three components reaction of dimedone,
aromatic aldehydes and 3-amino 1,2,4 trizole catalysed by anthranilic acid is shown
in Scheme 2. We believe that the zwitter ionic property of anthranilic acid
accelerates the reaction. The free amino group of anthranilic acid attacks the
carbonyl group of aldehyde (1) through nucleophilic attack to produce the
intermediate-A. Further dimedone (2) reacts with intermediate-A through the
Knoevenagel type condensation and produces Knoevenagel condensate via
formation of intermediate-B and elimination of catalyst, which again participates
in the mechanism. The Knoevenagel condensate undergoes nucleophilic attack of
the amine moiety of triazole, which is followed by cyclization to afford the target
product (4a–4p).
Experimental section
Melting points were measured by an open capillary tube method and are
uncorrected. IR spectra were recorded on a FTIR Nicolet, iS 10, Thermoscientific,
USA, 1H and 13C NMR spectra were recorded using a 400 MHz Bruker
123

S. Vibhute et al.
COO-
O
O
O
NH+2
COO-
- H2O
COO-
+
Ph
H
H
O
Ph
NH+3
NH+
H
1
O
2
zwitter ion of anthranilic acid
Ph
intermidiate-A
intermidiate-B
Ph
Ph
H
N
H
Ph
O
O
H
COO-
O
O
NH2
..
N
N
N
N
NH
3
- H2O
+
N
NH+3
N
N
H
4a-4p
N
N
zwitter ion
Knoevenagel condensate
intermidiate-C
Scheme 2 Plausible mechanism for the synthesis of [1,2,4] triazoloquinazolone derivatives using
anthranilic acid
spectrometer in CDCl3/DMSO solvents. Mass spectra were recorded on a Shimadzu
Toshvin. All chemicals and reagents were purchased from Aldrich, Alfa Asar and
Spetrochem and used without any purification. The progress of the reaction was
monitored on readymade silica gel plates (Merck) using the ethyl acetate-pet ether
solvent system.
General procedure for the synthesis of [1,2,4] triazolo [5,1-b] quinazolin–
8(4H)-ones
A mixture of aromatic aldehyde (1 mmol), dimedone (1 mmo1), 3-amino 1,2,4
triazole (1 mmol) in the presence of 30 mol % anthranilic acid was refluxed in
5 mL of ethanol at 80 °C for the stipulated period of time. The reaction was
monitored by TLC. After completion of the reaction, yellowish white product
appeared in the flask. Then the reaction mixture was allowed to cool at room
temperature. The solid obtained was filtered and washed with alcohol to afford the
title compounds (4a–4p) in excellent yield with good purity. All the compounds
were characterized by using their data in the literature.
Conclusion
In conclusion, we have developed an environmentally benign protocol for the
synthesis of 1,2,4 triazolo-[5,1-b]-quinazolin-8(4H)-one derivatives by using
aromatic aldehydes, dimedone and 3-amino-1,2,4 triazole by employing anthranilic
acid as a biodegradable green catalyst. This protocol offers several advantages such
as mild reaction conditions, low cost, easy operation, high reaction yields, and no
need of column chromatography for separation, and it has a simple purification.
Moreover, the use of anthranilic acid as a new catalyst proved to be superior on the
basis of green metrics.
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An efficient, one-pot three components synthesis of…
Spectral data of synthesized compounds
9-(4-Chlorophenyl) 6,6-dimethyl-5,6,7,9 tetrahydro-[1,2,4]–triazolo [5,1-b] quina-
zolin-8(4H)-one (4a) Pale yellow solid, yield—95%, mp-302–304 °C; IR: 3089,
2963, 1647, 1575, 1364, 1253, 759 cm-1; 1H NMR (400 MHz, CDCl3)—d = 1.11
(s, 3H, CH3), 1.18 (s, 3H, CH3), 2.25–2.35 (q, J = 16.8 Hz, J = 16.8 Hz, 2H, H-5),
2.58 (s, 2H, H-7), 6.43 (s, 1H, H-9), 7.25–7.31 (m, 4H, Ar–H) 7.69 (s, 1H, H-2)
11.20 (s, 1H, NH); 13C NMR (100 MHz, CDCl3) 193.47, 148.90, 148.72, 147.30,
139.01, 134.22, 128.88, 128.55, 107.23, 58.26, 50.35, 40.77, 32.81, 28.98, 27.62;
Anal. Calcd (%) C: 62.10, H: 5.17, N: 17.05; C17H17N4OCl; found: (%) C: 62.12, H:
5.14, N: 16.98 MS m/z (ESI): 329 [M ? H]?.
9-(4-Bromophenyl)-6,6-dimethyl 5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-b] quina-
zolin-8 (4H)-one (4b) Pale yellow solid, yield-95%, mp 285–287 °C, IR: 3066,
2956, 2919, 1636, 1568, 1363, 1255, 841 cm-1 1H NMR (400 MHz, DMSO)
d = 0.96 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.05–2.19 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.48–2.50 (m, 2H, H-7), 6.19 (s, 1H, H-9), 7.08–7.35 (m, 4H, Ar–H), 7.49
(s, 1H, H-2), 11.03 (s, 1H, NH); Anal calcd (%): C:54.71, H:4.56, N:15.02,
C17H17N4OBr, found (%): C:54.46, H:4.28, N:15.34; MS m/z (ESI): 373 [M]?.
9-(4–Hydroxyphenyl)-6,6-dimethyl-5,6,7,9–tetrahydro-[1,2,4]-triazolo-[5,1-b] quina-
zolin-8 (4H)-one (4c) Pale yellow solid, yield—90%, mp 302–304 °C; IR: 3088,
2964, 1630, 1580, 1363, 1267, 730 cm-1
;
1H NMR (400 MHz, DMSO)
d = 0.95–0.96 (d, 3H, CH3), 1.01–1.03 (d, 3H, CH3), 2.02–2.08 (q, J = 7.2 Hz,
J = 7.2 Hz, 2H, H-5), 2.11–2.17 (m, 2H, H-7), 6.08–6.10 (d, 1H, H-9), 6.58–7.47
(m, 5H, Ar–H, H-2), 9.31 (s, 1H, OH), 10.87 (s, 1H, NH); Anal, Calcd (%) C: 65.81,
H: 5.81, N: 18.06; C17H18N4O2, found (%): C: 65.34, H: 5.71, N: 17.90; MS m/z
(ESI): 311 [M ? H]?.
9-(4-Nitrophenyl)-6,6
dimethyl-5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-b]-quina-
zolin-8 (4H)-one (4d) Pale yellow solid, yield—95%, mp—305-307 °C; IR—
1
2964, 1644, 1577, 1351, 1252, 729 cm-1; H NMR (400 MHz, DMSO) d = 0.95
(s, 3H, CH3), 1.05 (s, 3H, CH3), 2.05–2.20 (q, J = 16.4 Hz, J = 16.4 Hz, 2H, H-5),
2.50 (s, 2H, H-7), 6.34 (s, 1H, H-9), 7.40–7.42 (d, J = 8.4 Hz, 2H, Ar–H),
8.06–8.09 (d, J = 8.8 Hz, 2H, Ar–H), 7.54 (s, 1H, H-2), 11.19 (s, 1H, NH); 13C
NMR (100 MHz, DMSO) d = 193.84, 151.27, 150.44, 148.15, 147.29, 128.35,
123.65, 105.49, 58.00, 50.26, 32.57, 28.84, 27.41; Anal calcd (%) C: 60.18, H:
5.015, N: 20.6, C17H17N5O3; found (%): C: 60.17, H: 5.44, N: 20.61; MS m/z (ESI):
353.12.
9-(4-Dimethylaminophenyl)-6,6-dimethyl-5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-
b]quinazolin-8 (4H)-one (4e) Pale yellow solid, yield—87%, mp—288–300 °C;
IR—3085, 2961, 1646, 1579, 1366, 1253, 735 cm-1; 1H NMR (400 MHz, DMSO)
d = 0.99 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.04-2.18 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.46 (s, 2H, H-7), 2.82 (s, 6H, 2NCH3 group), 6.11 (s,1H, H-9), 6.50–6.52
(d, J = 8.4 Hz, 2H, Ar–H), 7.00-7.02 (d, J = 8.4 Hz, 2H, Ar–H), 7.44 (s, 1H, H-2)
10.75 (s, 1H, NH); 13C NMR (100 MHz, DMSO) d = 193.81, 150.16, 149.74,
123

S. Vibhute et al.
147.04, 129.42, 127.94, 112.11, 106.82, 57.98, 50.47, 32.51, 29.10, 27.38; MS m/z
(ESI): 337.183 [M]?.
9-(2-Naphthyl)-6,6 dimethyl-5,6,7,9-tetrahydro-[1,2,4] triazolo-[5,1-b]-quinazolin-8
(4H)-one (4f) Pale yellow solid, yield—91%, mp—286–288 °C; IR—3081, 2962,
1
1651,1573, 1362, 1250, 729 cm-1; H NMR (400 MHz, CDCl3) d = 1.11 (s, 3H,
CH3), 1.17 (s, 3H, CH3), 2.24–2.35 (q, J = 16.4 Hz, J = 16.8 Hz, 2H, H-5), 2.61
(s, 2H, H-7), 6.64 (s, 1H, H-9), 7.37–7.88 (m, 7H, Ar–H), 7.70 (s, 1H, H-2), 11.22
(s, 1H, NH); 13C NMR (100 MHz, CDCl3), d = 193.55, 150.80, 150.19, 147.29,
138.99, 132.92, 132.89, 128.19, 127.67, 126.49, 126.46, 124.94, 106.12, 58.73,
50.42, 32.58, 29.05, 27.35; Anal calcd (%) C: 73.25, H: 5.81, N: 16.28,C21H20N4O
found (%): C: 71.72, H: 5.92, N: 15.90; MS m/z (ESI): 356.102 [M]?.
9-(4-Methoxyphenyl)-6,6 dimethyl-5,6,7,9 tetrahydro-[1,2,4]-triazolo-[5,1-b]-quina-
zolin-8 (4H)-one (4g) Pale yellow solid, yield—94%, mp—224–226 °C; IR—
1
3093, 2964, 1649, 1576, 1363, 1245, 1174 cm-1; H NMR (400 MHz, DMSO)
d = 0.98 (s, 3H, CH3), 1.05 (s, 3H, CH3), 2.04–2.18 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.48–2.51 (d, 2H, H-7), 3.67 (s, 3H, OCH3), 6.15–6.16 (d, 1H, H-9),
6.71–7.47 (m, 5H, Ar–H, H-2), 10.90 (s, 1H, NH); 13C NMR (100 MHz, DMSO)
d = 193.89, 159.10, 150.16, 149.92, 147.10, 133.69, 128.27, 113.75, 106.73, 57.97,
55.17, 50.43, 32.52, 28.98, 27.38; MS m/z (ESI): 324.175 [M]?.
9-(3-Nitrophenyl)-6,6 dimethyl-5,6,7,9 tetrahydro-[1,2,4]–triazolo-[5,1-b]-quina-
zolin-8 (4H)-one (4h) Pale yellow solid, yield—90%, mp—268–270 °C; IR—
1
2965, 1646, 1578, 1352, 1254, 731 cm-1; H NMR (400 MHz, DMSO) d = 0.98
(s, 3H, CH3), 1.06 (s, 3H, CH3), 2.07–2.21(q, J = 16.0 Hz, J = 16.4 Hz, 2H, H-5),
2.52 (s, 2H, H-7), 6.36 (s, 1H, H-9), 7.45–8.03 (m, 5H, Ar–H, H-2), 11.17(s, 1H,
NH); 13C NMR (100 MHz, DMSO) d = 193.60, 151.32, 150.50, 148.09, 147.26,
143.48, 133.68, 129.81, 122.93, 122.11, 105.30, 57.99, 50.29, 32.61, 28.92, 27.44;
Anal calcd (%) C: 60.18, H: 5.015, N: 20.65, C17H17N5O3; found (%): C: 59.94, H:
4.76, N: 20.58; MS m/z (ESI): 340 [M ? H]?.
9-(3-Bromophenyl)-6,6 dimethyl-5,6,7,9-tetrahydro-[1,2,4]–triazolo-[5,1-b]-quina-
zolin-8 (4H)-one (4i) Pale yellow solid, yield-92%, mp—278–280 °C; IR—
1
3065, 2964, 1640, 1570, 1364, 1253, 840 cm-1; H NMR (400 MHz, DMSO)
d = 0.98 (s, 3H, CH3), 1.05 (s, 3H, CH3), 2.07–2.19 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.49 (s, 2H, H-7), 6.19 (s, 1H, H-9), 7.11–7.48 (m, 4H, Ar–H), 7.51 (s,
1H, H-2), 11.03 (s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO) d = 193.60,
150.92, 150.27, 147.20, 143.83, 130.93, 130.32, 130.28, 126.02, 122.14, 105.75,
58.00, 50.36, 32.59, 28.93, 27.42; Anal calcd (%) C: 54.71, H: 4.56, N: 15.02,
C17H17N4OBr, found (%): C: 54.44, H: 4.30, N: 15.22; MS m/z (ESI): 373 [M]?.
9-Phenyl-6,6
dimethyl-5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-b]-quinazolin-8
(4H)-one (4j) Pale yellow solid, yield—95%, mp—252–254 °C; IR—3032,
1
2961, 1647, 1576, 1365, 1253, 727 cm-1; H NMR (400 MHz, DMSO) d = 0.97
(s, 3H, CH3), 1.05 (s, 3H, CH3), 2.04–2.19 (q, J = 16.4 Hz, J = 16.0 Hz, 2H, H-5),
2.49 (s, 2H, H-7), 6.19 (s, 1H, H-9), 7.14–7.23 (m, 5H, Ar–H), 7.50-7.51 (d, 1H,
123

An efficient, one-pot three components synthesis of…
H-2), 11.00 (s, 1H, NH); 13C NMR—(100 MHz, DMSO) d = 193.74, 150.57,
150.00, 147.22, 141.48, 128.42, 127.96, 127.17, 106.45, 58.48, 50.40, 32.54, 29.00,
27.36; MS m/z (ESI): 295.150 [M ? H]?.
9-(3, 4-Dimethoxylphenyl)-6, 6 dimethyl–5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-
b]-quinazolin-8 (4H)-one (4n) Pale yellow solid, yield—86%, mp—278–280 °C;
IR—3158, 2952, 1620, 1562, 1360, 1251, 833 cm-1; 1H-NMR (400 MHz, DMSO)
d = 1.00 (s, 3H, CH3), 1.05 (s, 3H, CH3), 2.06–2.20 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.48 (s, 2H, H-7), 3.32 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 6.11 (s, 1H,
H-9), 6.52–6.54 (d, J = 8.0 Hz 1H, Ar–H), 6.62–6.64 (d, J = 8.0 Hz, 1H Ar–H),
6.74 (s, 1H, Ar–H), 7.49 (s, 1H, H-2), 10.90 (s, 1H, NH); 13C NMR—(100 MHz,
DMSO) d = 193.52, 150.36, 147.47, 146.47, 132.98, 119.67, 115.44, 111.44,
106.53, 58.14, 55.88, 50.46, 32.51, 29.20, 27.23.
9-(4-Fluorophenyl)-6,6-dimethyl-5,6,7,9-tetrahydro-[1,2,4]-triazolo-[5,1-b]-quina-
zolin-8 (4H)-one (4p) Pale yellow solid, yield—93%, mp—279–280 °C; IR—
3137, 2962, 2888, 1646, 1577, 1363, 1254, 761 cm-1; 1H NMR (400 Hz, DMSO),
d = 0.97 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.05–2.19 (q, J = 16.4 Hz, J = 16.4 Hz,
2H, H-5), 2.49 (s, 2H, H-7), 6.21 (s, 1H, H-9), 6.90–7.50 (m, 5H, Ar–H, H-2), 10.99
(s, 1H, NH); Anal calcd (%) C: 54.70, H: 4.59, N: 15.01, C17H17N4OF, found (%):
C: 54.55, H: 4.60, N: 14.96.
Acknowledgements The author Sunil Vibhute is thankful to UGC, WRO, Pune for financial assistance.
Authors are also grateful to Principal, Shri Shivaji Mahavidyalaya, Barshi and Instrumentation Section,
Solapur University, Solapur for providing research facilities. The author PVA is thankful to RGSTC,
Mumbai and Shivaji University, Kolhapur for financial assistance.
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