Eco-friendly reactions in PEG-400: A highly efficient and green approach for stereoselective access to multisubstituted 3,4-dihydro-2(1: H)-quinazolines using 2-aminobenzylamines

Article abstract of DOI:10.1039/c7ra13487h

An efficient and stereoselective synthesis of novel 3,4-dihydro-2(1H)-quinazolines has been developed through cyclization reactions of 2-aminobenzylamines with α-oxoketene dithioacetals using PEG-400 as an inexpensive, easy to handle, non-toxic and recycl

Full text of DOI:10.1039/c7ra13487h

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Eco-friendly reactions in PEG-400: a highly
efficient and green approach for stereoselective
access to multisubstituted 3,4-dihydro-2(1H)-
quinazolines using 2-aminobenzylamines†
Cite this: RSC Adv., 2018, 8, 8721
*
Nutan Sharma, Pankaj Sharma and Sunita Bhagat
An efficient and stereoselective synthesis of novel 3,4-dihydro-2(1H)-quinazolines has been developed
through cyclization reactions of 2-aminobenzylamines with a-oxoketene dithioacetals using PEG-400 as
an inexpensive, easy to handle, non-toxic and recyclable reaction medium. The developed protocol is
operationally simple and tolerates various substrates having different functionalities. This protocol
features several attributes such as excellent yields, no work up, green reaction conditions, and being
environmentally benign. The attractive feature of this new strategy is that all the reported final
Received 20th December 2017
Accepted 20th February 2018
DOI: 10.1039/c7ra13487h
1
compounds have been isolated as single (E)-stereoisomeric forms, which was confirmed by HNMR and
rsc.li/rsc-advances
X-ray crystallographic studies.
nanoclusters of bi-metallic Pt/Ir alloy as a catalyst, 5,50,6,60-tet-
rahydroxy-3,3,30,30-tetramethyl-1,10-spiro-bisindane, (TTSBI) as
Introduction
a co-catalyst, K2CO3 as a base with CDCl3/H2O as solvent for
a longer reaction duration11b (Scheme 1, b); (iii) a CuCl/DABCO/
4-HO-TEMPO/O2 catalytic system in CH3CN at 80 C (ref. 12a)
Quinazolines are a class of fused heterocyclic ring systems
containing multiple pharmacophores which are undoubtedly
well established as biologically and pharmaceutically important
compounds.1 Quinazoline-based heterocycles and their
hydrated congeners have been reported to possess diverse bio-
logical and therapeutic properties such as inhibition of the
epidermal growth factor (EGF) receptors of tyrosine kinase,2a
and analgesic,2b–d anticancer,3 anti-inammatory,4 antidiuretic,5
anticonvulsant6 and anti-Alzheimer7 activities. Commercialized
drug compounds such as getinib (I), erlotinib (II), alfuzosin
(III), and aoqualone (IV) are some notable examples of drugs
containing quinazoline as a core nucleus (Fig. 1). Considering
these applications, development of novel synthetic routes
towards the formation of these pharmaceutically important
scaffolds attracts the interest of synthetic organic chemists.
Substituted quinazolines have been reported to be con-
structed by numerous methods involving several substrates.8–10
Among them, many of the synthetic methodologies have craily
employed 2-aminobenzylamines as substrates with aldehydes
for the synthesis of quinazolines (Scheme 1, i–iv). These reac-
tions have been carried out by using (i) [Cp*IrCl2]2 as a catalyst,
four equivalents of styrene in xylene solvent under inert atmo-
sphere of N2, 24 h, reux conditions11a (Scheme 1, a); (ii)
ꢀ
(Scheme 1, c) and (iv) four equivalents of NaOCl as oxidant in
MeOH solvent for longer reaction hours12b (Scheme 1, d).
However, despite the synthetic utility of these protocols, the
reported techniques suffer from drawbacks such as the use of
expensive metal catalyst along with a co catalyst and require-
ment of a stoichiometric amount of toxic oxidant NaOCl for the
transformation to take place. In such a scenario, development
of a catalyst free and eco friendly methodology to deliver func-
tionalized quinazolines will provide an intriguing and green
alternative to the conventional approach.
Over the years, there has been a growing public concern
towards the adverse effects of toxic and volatile organic solvents
Organic Synthesis Research Laboratory, Department of Chemistry, A. R. S. D. College,
University of Delhi, New Delhi-110021, India. E-mail: sunitabhagat28@gmail.com
† Electronic supplementary information (ESI) available: Datas and spectral copies
of 1H, 13C NMR for target compounds. X-ray crystallographic data of compound 4o
with CCDC No. 1055453. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c7ra13487h
Fig. 1 Some popular marketed drugs containing quinazoline as a core
nucleus.
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Scheme 1 Previous synthetic approaches and our designed approach.
and the search for alternate nonhazardous reaction media is
gaining progress. Meanwhile, using water as a green solvent has
been well documented13 but its practical use is limited due to
the hydrophobic nature of organic compounds.14 On the
contrary, PEGs have been explored as powerful, novel, eco-
friendly reaction media for innumerable organic trans-
formations15 owing to their non toxic, inexpensive, thermally
stable, readily recyclable, and biodegradable nature.16 In
continuation of our research studies aimed at developing
environmentally benign and improved synthetic methodologies
for organic reactions,17 we herein report for the rst time an
efficient and green approach for the stereoselective synthesis of
3,4-dihydro-2(1H)-quinazolines via substituted 2-amino ben-
zylamines and a-oxoketene dithioacetals as building blocks
using PEG-400 as an eco-friendly reaction medium (Scheme 1,
e). To the best of our knowledge, there have been no reports on
the synthesis of 3,4-dihydro-2(1H)-quinazolines using PEG-400
as a solvent under catalyst-free conditions.
Results and discussion
To check feasibility of this route, a model reaction between 2b
and 3a was performed by varying different protic and aprotic
solvents and various bases (Table 1). When the reaction was
performed using EtOH as polar protic solvent and CH3CN as
low boiling aprotic solvent under reux conditions using K2CO3
as base, the desired product 4b was obtained in lower yields
(Table 1, entries 1 and 2). Whereas under similar conditions,
high boiling aprotic solvent such as toluene was not proven very
effective and gave the desired product 4b in 50% yield aer 12 h
(Table 1, entry 3). High boiling polar aprotic solvents like DMF
and DMSO afforded the desired product in higher yield taking
less time (Table 1, entries 4 and 5). It should be noted that use of
polar protic solvents like n-BuOH and t-BuOH increased the
yield to 65% and 70% in the presence of K2CO3 as base in 10 h
(Table 1, entries 6 and 7). Keeping in view the economical and
environmental concerns, H2O was screened as the reaction
8722 | RSC Adv., 2018, 8, 8721–8731
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Table 1 Optimization of reaction conditionsa
13C NMR & HRMS data. Compound 4b existed in one stereo-
isomeric form (E-form) as evident from its IR & 1HNMR data. IR
spectra strongly indicated
a hydrogen-bonded carbonyl
stretching vibration, which was merged with bands around and
below 1600 cmꢁ1 (1594 cmꢁ1 in this case). The signals for vinylic
proton appeared as sharp singlets, indicating the purity of the
geometrical isomers. 1HNMR spectrum showed a characteristic
chelated –NH proton far downeld at d 13.66, assigned to the
amino group which participated in a strong hydrogen bond
with oxygen of the carbonyl group in a six membered, planar
Entry Solvent
Base
Temp (ꢀC) Time (h) Yieldb (%)
1
EtOH
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
80
15
18
12
10
10
10
10
15
8
40
45
50
60
62
65
70
Trace
90
81
72
90
80
85
65
68
20
1
chelate19 (Fig. 2). Moreover, HNMR analysis of crude reaction
2
3
4
CH3CN
Toluene
DMF
90
mixture of 4g (see ESI,† page 31) also indicated the formation of
one stereoisomeric form of the product. Its spectral data anal-
ysis conrmed the structure.
110
120
120
120
85
5
DMSO
In the 1H NMR spectrum, presence of peaks as sharp singlets
at d 5.43 (s, 1H) and d 4.45 (s, 2H), werꢁe characterized for vinylic
proton and methylene group –NCH2 in 4b. In the 13C NMR
spectrum of 4b, characteristic peak at d 75.9 and d 50.7 was
observed for vinylic carbon and methylene carbon. HRMS data
of the compound showed M + 1 peak. Similarly all other
6
7
8
n-BuOH
t-BuOH
H2O
100
110
110
110
120
90
9
PEG 400
PEG 400 : H2O
PEG 400 : EtOH K2CO3
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
PEG 400
10
11
12
13
14
15
16
17
8
10
8
K2CO3
K2CO3
Na2CO3 110
TEA
DIPEA
—
8
1
compounds were also characterized by IR, H NMR, 13C NMR
8
and HRMS studies. The structure of the product 4o was deter-
mined by single crystal X-ray diffraction (Fig. 3). The structures
of the other products were concluded by analogy.
110
110
110
8
8
8
a
With these optimized conditions in hand, the scope and
robustness of the protocol was explored by employing diversely
substituted 2-amino benzylamines 2a–j with a-oxoketene
dithioacetals 3a–c (Table 2). We observed that amines 2a–g
having aliphatic substitution such as methyl, ethyl, n-propyl,
isopropyl, n-butyl and tert-butyl at R1 afforded the desired
stereoselective products 4a–g, 4l & 4n in good to excellent yields
of 80–92% with a-oxoketene dithioacetals 3a–c (Table 2, entries
1–7, 12, 14). However, the same a-oxoketene dithioacetals 3a–c
provided the products 4h–k, 4m & 4o–p in comparatively lower
yields of 65–71% when amines 2h–j bearing aromatic and cyclic
Reactions were performed using 1 equiv. of 3a, 1.2 equiv. of 2b, 3.0
equiv. of base. b Isolated yield.
medium but observations indicated trace amount of product
formation due to solubility problem (Table 1, entry 8). In order
to improve the efficiency of the reaction, we next performed our
ꢀ
model reaction in PEG-400 at 110 C using K2CO3 as base, and
to our delight corresponding product 4b was obtained in
a maximum yield of 90% within 8 h (Table 1, entry 9).
Encouraged by the above result, a mixture of PEG-400 and H2O
(1 : 1), was used as reaction medium which resulted in the
formation of product 4b in 81% yield (Table 1, entry 10).
Moreover, change of combination of solvents from PEG-400 and
H2O to PEG-400 and EtOH (1 : 1) also had a detrimental effect
on the yield of the product (Table 1, entry 11). Further increase
or decrease in the temperature of the reaction could not
increase the yield of the desired product 4b (Table 1, entries 12
and 13). From Table 1, it is clear that PEG-400 unanimously
dominates as effective solvent medium because it increases the
solubility of reactants, which leads to larger interfacial area and
lower mass transfer resistance.18 When base was changed from
K2CO3 to Na2CO3 at 110 ꢀC, 85% yield was observed in 8 h (Table
1, entry 14).
Fig. 2 Stereoselectivity via formation of six membered planar chelate.
Screening of other organic bases such as TEA and DIPEA in
same reaction conditions resulted in 65% and 68% yields
respectively (Table 1, entries 15 and 16). However the yield of
reaction was drastically reduced to 20% when the reaction was
performed in the absence of base (Table 1, entry 17). These
optimization studies led to the conclusion that PEG-400 with
K2CO3 is the reaction medium of choice for this transformation.
The reaction product was fully characterized by the IR, 1H NMR,
Fig. 3 Ortep diagram of compound 4o.
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Table 2 Substrate scope of substituted 3,4-dihydro-2(1H)-quinazolinesa
Entry
Substrate (2)
Amine (3)
Product (4)
Yieldb (%)
1
80
2
3
4
3a
3a
3a
90
88
85
5
6
7
3a
3a
3a
82
92
86
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Table 2 (Contd.)
Entry
Substrate (2)
Amine (3)
Product (4)
Yieldb (%)
8
3a
70
9
3a
71
68
10
3a
11
2i
65
12
2f
3b
82
13
2h
3b
70
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Table 2 (Contd.)
Entry
14
Substrate (2)
Amine (3)
Product (4)
Yieldb (%)
2f
80
15
2h
3c
65
16
2i
3c
66
a
Unless otherwise specied, reactions were performed using 1 equiv. of 3a, 1.2 equiv. of 2b, 3.0 equiv. of base. b Isolated yield.
groups such as benzyl, cyclopropyl and cyclohexyl at R1 were approximately 5% of PEG was observed from cycle to cycle due
used (Table 2, entries 8–11, 13, 15–16). This can be attributed to to mechanical loss.
the lesser reactivity of aromatic and cyclic amines due to the
A plausible mechanism for the 3,4-dihydro-2(1H)-quinazo-
involvement of lone pair of –NH2 in conjugation in the former line ring formation is depicted in Scheme 2. The mechanism
and attachment of –NH2 group to a sp2 hybridized carbon atom rst involves the substitution of the thiomethyl group of a-
in the later as compared to aliphatic amines.
oxoketene dithioacetal 3 by that amino group of reactant 2
In order to justify sustainable chemistry issues, recovery and which is directly attached to aromatic ring, resulting in the
reusability of PEG-400 was studied using the reaction of 2g & 3a formation of intermediate 4A at rst.
in the presence of PEG-400 (10 ml) at 110 ꢀC for 6–10 h. Aer the
This can be assigned to the presence of characteristic
completion of reaction, reaction mass was then cooled and chelated proton of –NH at very high chemical shi values (d 14–
solvent was evaporated under vacuum. Since PEG is immiscible
with diethyl ether, it was washed (two times) with this solvent to
remove any unwanted organic impurities and was used
successfully in consecutive runs (the yield decreased from 86%
to 72% aer 5 runs, Table 3), although a weight loss of
Table 3 Recycling of PEG-400
Runs
1
2
3
4
5
Yield (%)
86
84
80
76
72
Scheme 2 Plausible Mechanism.
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15 ppm) in the HNMR data of compounds 4(a–p). Aer that,
second thiomethyl group is replaced by second amino group of
reactant 2 resulting in formation of cyclized product 4 with
subsequent elimination of –MeSH.
Analytical data of 2-amino benzylamines
2-(aminomethyl)aniline (2a). The compound was obtained
as a light brown solid, yield: 80%; 1H NMR (400 MHz, DMSO-d6)
d: 7.03 (dd, J ¼ 7.33, 1.37 Hz, 1H), 6.94 (td, J ¼ 7.79, 1.37 Hz, 1H),
6.60 (dd, J ¼ 7.79, 0.92 Hz, 1H), 6.50 (td, J ¼ 7.33, 0.92 Hz, 1H),
4.98 (t, J ¼ 5.50 Hz, 2H, –CH2NH2–), 4.88 (bs, 2H, –NH2), 4.36 (s,
2H, –CH2NH2–); 13C NMR (100 MHz, DMSO-d6) d: 146.3, 127.7,
127.6, 125.3, 115.8, 114.5, 61.2 (benzylic–CH2–); HRMS (ESI) (M
+ H)+ calcd for C7H10N2: 123.0922, found 123.0913.
Conclusions
In conclusion, we have succeeded in developing rst novel, inex-
pensine, cleaner and green methodology for the synthesis of 3,4-
dihydro-2(1H)-quinazolines. Moreover, avoid of work-up make this
new strategy attractive, easy to execute and facile for the assembly
of a wide variety of biologically relevant dihydroquinazolines. As
the methodology is completely devoid of anhydrous solvents or any
catalysts, this approach therefore exemplies the reconciliation of
operational simplicity and economic viability in an environmental
friendly time and cost effective manner. It is noteworthy that a-
oxoketene dithioacetals and substituted 2-amino benzylamines
selectively afforded a single isomer. Further applicability of PEG-
400 as solvent system to a wide range of substrates towards the
development of catalyst free pathways for synthesizing diverse
range of biologically important heterocycles is an ongoing goal of
research in our laboratory.
2-((methylamino)methyl)aniline (2b). The compound was
obtained as a dark green solid, yield: 85%; H NMR (400 MHz,
1
DMSO-d6) d: 7.20 (dd, J ¼ 7.33, 1.37 Hz, 1H), 7.05 (td, J ¼ 7.33,
1.37 Hz, 1H), 6.70 (dd, J ¼ 8.24, 1.37 Hz, 1H), 6.54 (td, J ¼ 7.33,
1.37 Hz, 1H), 3.96 (s, 2H, benzylic–CH2–), 2.49 (s, 3H, –NHCH3);
13C NMR (100 MHz, DMSO-d6) d: 147.7, 132.0, 129.8, 116.1,
115.8, 115.2, 47.5 (benzylic–CH2–), 32.0 (–NHCH3); HRMS (ESI)
(M + H)+ calcd for C8H12N2: 137.1078, found 137.1073.
2-((ethylamino)methyl)aniline (2c). The compound was ob-
tained as a dark green solid, yield: 83%; 1H NMR (400 MHz,
DMSO-d6) d: 7.16 (d, J ¼ 7.79 Hz, 1H), 7.02 (t, J ¼ 8.24 Hz, 1H),
6.68 (d, J ¼ 7.79 Hz, 1H), 6.55 (t, J ¼ 7.33 Hz, 1H), 5.69 (bs, 2H,
–NH2), 3.86 (s, 2H, benzylic–CH2–), 2.81 (q, J ¼ 7.33 Hz, 2H,
–CH2CH3), 1.16 (t, J ¼ 7.33 Hz, 3H, –CH3); 13C NMR (100 MHz,
DMSO-d6) d: 147.6, 131.0, 129.5, 128.8, 117.4, 115.4, 47.2
(benzylic–CH2–), 42.1 (–CH2CH3), 11.9 (–CH3); HRMS (ESI) (M +
H)+ calcd for C9H14N2: 151.1235, found 151.1228.
Experimental
General information and method
2-((propylamino)methyl)aniline (2d). The compound was
obtained as a dark green solid, yield: 80%; H NMR (400 MHz,
1
All the reactions were performed in an oven-dried Schlenk ask DMSO-d6) d: 7.21 (d, J ¼ 7.79 Hz, 1H), 7.01 (t, J ¼ 8.24 Hz, 1H),
under nitrogen atmosphere. Column chromatography was 6.68 (d, J ¼ 8.24 Hz, 1H), 6.53 (t, J ¼ 7.33 Hz, 1H), 3.94 (s, 2H,
performed using silica gel (mesh 100–200). TLC analysis was benzylic–CH2–), 2.79 (t, 2H, J ¼ 7.79 Hz, –CH2CH2CH3), 1.65
(sext, 2H, J ¼ 7.79 Hz, –CH2CH2CH3), 0.84 (t, 3H, J ¼ 7.33 Hz,
performed on commercially prepared 60 F254 silica gel plates.
Visualization of spots on TLC plate was accomplished with UV
–CH3); 13C NMR (100 MHz, DMSO-d6) d: 147.4, 132.7, 131.8,
119.5, 118.1, 116.9, 49.8 (–CH2CH2CH3), 47.8 (benzylic–CH2–),
20.1 (–CH2 CH2CH3), 11.9 (–CH3); HRMS (ESI) (M + H)+ calcd for
light (254 nm) and staining over I2 chamber. IR spectra was
recorded in CHCl3 on a Perkin Elmer Spectrum RX-1 FT-IR
spectrophotometer. CDCl3 was used as NMR solvent for char-
acterization of compounds. The 1H NMR spectra were recorded
C
10H16N2: 165.1391, found 165.1379.
2-((isopropylamino)methyl)aniline (2e). The compound was
1
on a Jeol JNM-ECX400P at 400 MHz. The 13C NMR spectra on obtained as dark green solid, yield: 81%; H NMR (400 MHz,
Jeol JNM-ECX400P at 100 MHz. Chemical shis for carbons are CDCl3) d: 7.16 (d, J ¼ 7.79 Hz, 1H), 7.02 (t, J ¼ 8.24 Hz, 1H), 6.68
(d, J ¼ 7.79 Hz, 1H), 6.55 (t, J ¼ 7.33 Hz, 1H), 3.92 (s, 2H,
reported in ppm from tetramethylsilane and are referenced to
the carbon resonance of the solvent. Data are reported as
benzylic–CH2–), 4.29–4.23 (m, 1H, –NHCH), 1.25 (s, 6H, 2 ꢂ
CH3); 13C NMR (100 MHz, DMSO-d6) d: 147.6, 131.0, 129.5,
follows: chemical shi, multiplicity (s ¼ singlet, d ¼ doublet, t
128.8, 117.4, 115.4, 50.9 (–NHCH), 46.5 (benzylic–CH2–), 23.6
¼ triplet, q ¼ quartet, m ¼ multiplet, dd ¼ doublet of doublet,
br s ¼ broad singlet), coupling constants in Hertz, and inte- (–CH3); HRMS (ESI) (M + H)+ calcd for C10H16N2: 165.1391,
gration. HRMS (ESI) were recorded with Q-TOF electrospray found 165.1358.
mass spectrometer. All purchased chemicals were used as
received. All melting points are uncorrected.
2-((butylamino)methyl)aniline (2f). The compound was ob-
tained as a green solid, yield: 86%; H NMR (400 MHz, DMSO-
1
d6) d: 7.21 (dd, J ¼ 7.32, 1.46 Hz, 1H), 7.07 (dt, J ¼ 8.05, 1.46 Hz,
1H), 6.70 (dd, J ¼ 8.05, 1.46 Hz, 1H), 6.57 (t, J ¼ 7.32, 1.46 Hz,
1H), 3.97 (s, 2H, benzylic–CH2–), 2.87 (t, 2H, J ¼ 8.05 Hz,
–CH2CH2CH2), 1.62 (q, 2H, J ¼ 8.05 Hz, –CH2CH2CH2), 1.30
(sext, 2H, J ¼ 7.32 Hz –CH2CH2CH2CH3), 0.87 (t, 3H, J ¼ 7.69 Hz,
–CH3); 13C NMR (100 MHz, DMSO-d6) d: 147.6, 132.1, 129.8,
116.2, 115.9, 115.2, 46.2 (benzylic–CH2–), 38.4 (–NCH2), 27.3
(–CH2CH2CH2), 19.4 (–CH2CH3), 13.5 (–CH3); HRMS (ESI) (M +
H)+ calcd for C11H18N2: 179.1548, found 179.1537.
General procedure for synthesis of 2-N-aryl/alkyl substituted
anilines (2a–j)
Compounds 2a–j were synthesized by reductive amination20 of
2-nitro benzaldehyde with various aliphatic, aromatic and cyclic
amines followed by reduction21 of nitro group using 10% Pd–C/
H2 in EtOH at 50 Psi for 2–3 h. Formation of compounds 2a–j
1
was conrmed by H NMR, 13C NMR and HRMS data.
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2358, 1589; H NMR (400 MHz, CDCl3) d: 13.23 (bs, 1H, NH),
7.90 (dd, J ¼ 9.0, 3.3 Hz, 2H), 7.34–7.27 (m, 1H), 7.14–7.06 (m,
4H), 7.00 (d, J ¼ 7.8 Hz, 1H), 5.68 (s, 1H, vinylic CH), 5.19 (s, 2H,
–NHCH2); 13C NMR (100 MHz, CDCl3) d: 187.2 (C]O), 165.8,
164.2, 135.7, 132.8, 129.5, 129.0, 124.5, 123.8, 119.3, 115.3,
115.1, 79.1 (vinylic CH), 45.7 (–NHCH2); HRMS (ESI) (M + H)+
calcd for C16H13FN2O: 269.1090, found 269.1085.
2-((tert-butylamino)methyl)aniline (2g). The compound was
obtained as a dark green solid, yield: 87%; H NMR (400 MHz,
1
DMSO-d6) d: 7.00 (d, J ¼ 7.33 Hz, 1H), 6.93 (t, J ¼ 7.79 Hz, 1H),
6.60 (d, J ¼ 7.79 Hz, 1H), 6.48 (t, J ¼ 7.33 Hz, 1H), 3.62 (s, 2H,
benzylic–CH2–), 1.14 (s, 9H, 3 ꢂ CH3); 13C NMR (100 MHz,
DMSO-d6) d: 147.5, 130.0, 127.5, 116.6, 115.3, 114.3, 51.5
(–NHC), 42.5 (benzylic–CH2–), 27.6 (–CH3); HRMS (ESI) (M + H)+
calcd for C11H18N2: 179.1548, found 179.1540.
(E)-1-(4-uorophenyl)-2-(3-methyl-3,4-dihydroquinazolin-2(1H)-
ylidene)ethanone (4b). The compound was obtained as a yellow
solid, yield: 90%; mp 138–140 ꢀC; IR (nmax cmꢁ1) (CHCl3): 2923,
2-((cyclopropylamino)methyl)aniline (2h). The compound
1
was obtained as a light green solid, yield: 87%; H NMR (400
1
1594; H NMR (400 MHz, DMSO-d6) d: 13.66 (s, 1H, NH), 7.92
MHz, DMSO-d6) d: 6.97 (d, J ¼ 7.32 Hz, 1H), 6.92 (t, J ¼ 7.93,
7.32 Hz, 1H), 6.58 (d, J ¼ 7.32 Hz, 1H), 6.47 (t, J ¼ 7.32 Hz, 1H),
3.63 (s, 2H, benzylic–CH2–), 2.06–2.03 (m, 1H,–NHCH), 0.36–
0.31 (m, 2H, cyclopropyl CH2), 0.25–0.22 (m, 2H, cyclopropyl
CH2); 13C NMR (100 MHz, DMSO-d6) d: 147.2, 129.1, 127.4,
123.6, 115.8, 114.6, 51.2 (benzylic–CH2–), 30.2 (–NHCH), 5.8
(cyclopropyl CH2).
2-((cyclohexylamino)methyl)aniline (2i). The compound was
obtained as a dark green liquid, yield: 84%; 1H NMR (400 MHz,
DMSO-d6) d: 7.21 (dd, J ¼ 7.32, 1.46 Hz, 1H), 7.06 (t, J ¼ 8.05 Hz,
1H), 6.70 (d, J ¼ 8.05 Hz, 1H), 6.57 (t, J ¼ 7.32 Hz, 1H), 3.96 (s,
2H, benzylic–CH2–), 2.99–2.94 (m, 1H, –NCH), 2.13–2.10 (d, 2H),
1.77–1.74 (d, 2H), 1.60–1.57 (d, 1H), 1.42–1.33 (m, 2H), 1.25–
1.06 (m, 3H); 13C NMR (100 MHz, DMSO-d6) d: 147.4, 131.8,
130.6, 117.6, 116.8, 57.3 (–NHCH), 31.2, 25.2, 24.6.
2-((benzylamino)methyl)aniline (2j). The compound was
obtained as a light green solid, yield: 82%; 1H NMR (400 MHz,
DMSO-d6) d: 7.59 (d, J ¼ 7.32 Hz, 1H), 7.50 (d, J ¼ 7.32 Hz, 1H),
7.41–7.34 (m, 3H), 7.22 (d, J ¼ 7.32 Hz, 1H), 7.06 (t, J ¼ 7.32 Hz,
1H), 6.72 (d, J ¼ 7.32 Hz, 1H), 6.68 (d, J ¼ 7.32 Hz, 1H) 4.14 (s,
2H, benzylic–CH2a–), 4.00 (s, 2H, benzylic–CH2b–); 13C NMR
(100 MHz, CDCl3) d: 146.9, 140.2, 129.8, 128.5, 127.5, 127.3,
127.1, 124.2, 118.5, 116.3, 56.8 (benzylic–CH2a–), 48.9 (benzylic–
CH2b–); HRMS (ESI) (M + H)+ calcd for C14H16N2: 213.1391,
found 213.1387.
(dd, J ¼ 9.16, 3.05 Hz, 2H), 7.18 (t, J ¼ 9.16 Hz, 3H), 7.07 (d, J ¼
6.71 Hz, 1H), 6.96 (t, J ¼ 7.32 Hz, 1H), 6.91 (d, J ¼ 7.93 Hz, 1H),
5.43 (s, 1H, vinylic CH), 4.45 (s, 2H, –NCH2), 3.03 (s, 3H,–CH3);
13C NMR (100 MHz, CDCl3) d: 184.1 (C]O), 165.2, 162.7, 157.4,
137.5, 134.2, 128.6, 125.4, 122.8, 117.9, 115.3, 115.0, 114.8, 75.9
(vinylic CH), 50.7 (–NCH2), 37.5 (–CH3); HRMS (ESI) (M + H)+
calcd for C17H15FN2O: 283.1246, found 283.1245.
(E)-2-(3-ethyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-
uorophenyl)ethanone (4c). The compound was obtained as
yellow solid, yield: 88%; mp 84–86 C; IR (nmax cmꢁ1) (CHCl3):
ꢀ
2925, 1593; 1H NMR (400 MHz, DMSO-d6) d: 13.86 (s, 1H, NH),
7.93 (dd, J ¼ 9.16, 3.05 Hz, 2H), 7.21 (t, J ¼ 8.85 Hz, 3H), 7.11 (d, J
¼ 7.32 Hz, 1H), 6.99 (t, J ¼ 7.32 Hz, 1H), 6.93 (d, J ¼ 7.93 Hz, 1H),
5.50 (s, 1H, vinylic CH), 4.49 (s, 2H, –NCH2), 3.51 (q, 2H,
–CH2CH3), 1.21 (t, 3H, –CH3); 13C NMR (100 MHz, CDCl3) d:
183.9 (C]O), 165.1, 162.6, 156.7, 137.7, 134.3, 128.6, 128.5,
125.4, 122.8, 117.9, 115.2, 114.9, 114.7, 75.7 (vinylic CH), 48.1
(–NCH2), 45.0 (–CH2CH3), 11.2 (–CH3); HRMS (ESI) (M + H)+
calcd for C18H17FN2O: 297.1403, found 297.1396.
(E)-1-(4-uorophenyl)-2-(3-propyl-3,4-dihydroquinazolin-2(1H)-
ylidene)ethanone (4d). The compound was obtained as light
yellow solid, yield: 85%; mp 130–132 ꢀC; IR (nmax cmꢁ1) (CHCl3):
2924, 1590; 1H NMR (300 MHz, DMSO-d6) d: 13.91 (s, 1H, NH),
7.93 (dd, J ¼ 8.70, 3.6 Hz, 2H), 7.23 (t, J ¼ 8.70 Hz, 3H), 7.12 (d, J
¼ 7.2 Hz, 1H), 7.01 (d, J ¼ 7.2 Hz, 1H), 6.96 (t, J ¼ 8.1 Hz, 1H),
5.50 (s, 1H, vinylic CH), 4.51 (s, 2H, –NCH2), 3.44 (t, 2H,
–CH2CH2CH3), 1.75–1.62 (m, 2H, –CH2CH2CH3), 0.94 (t, 3H,
–CH3); 13C NMR (100 MHz, CDCl3) d: 183.8 (C]O), 165.1, 162.6,
157.1, 137.7, 134.4, 128.6, 125.3, 122.8, 117.9, 115.2, 115.0,
114.7, 75.9 (vinylic CH), 52.1 (–CH2CH2CH3), 49.0 (–NCH2), 19.8
(–CH2CH3), 11.3 (–CH3); HRMS (ESI) (M + H)+ calcd for
General procedure for the synthesis 3,4-dihydro-1H-
quinazolin-2-ylidenes (4a–p)
In an oven-dried two-neck RBF, a-oxoketene dithioacetal 3a–c (1
equiv.), 1.2 equiv. of 2-substituted aniline 2a–j, 3.0 equiv. of
K2CO3 was added in 10 mL of PEG-400. Reaction mass was
heated at 110 ꢀC for 6–10 h. Progress of reaction was monitored
by TLC. The reaction mixture was then cooled and solvent was
evaporated under vacuum. Crude was directly puried by
column chromatography using silica gel (100 : 200 mesh) in 5–
10% ethyl acetate/hexane as eluent to afford the corresponding
product. Since PEG is immiscible with diethyl ether, it was
washed (two times) with this solvent to remove any unwanted
organic impurities and was used successfully in consecutive
runs. Although a weight loss of approximately 5% of PEG was
observed from cycle to cycle due to mechanical loss.
C
19H19FN2O: 311.1559, found 311.1553.
(E)-1-(4-uorophenyl)-2-(3-isopropyl-3,4-dihydroquinazolin-
2(1H)-ylidene)ethanone (4e). The compound was obtained as
a light yellow viscous material; yield: 82%; IR (nmax cmꢁ1
)
1
(CHCl3): 2925, 1584; H NMR (400 MHz, DMSO-d6) d: 13.75 (s,
1H, –NH), 8.12 (dd, J ¼ 8.54, 3.0 Hz, 2H), 7.44 (t, J ¼ 8.54 Hz,
2H), 7.34–7.23 (m, 3H), 7.18 (d, J ¼ 7.32 Hz, 1H), 5.10 (s, 1H,
vinylic CH), 4.84 (s, 2H, –NCH2), 4.24 (q, J ¼ 6.41 Hz, 1H, –NCH),
1.25 (d, J ¼ 6.41 Hz, 6H, 2 ꢂ CH3); 13C NMR (100 MHz, DMSO-
d6) d: 191.1 (C]O), 166.9, 164.4, 156.5, 135.3, 133.1, 131.7,
131.4, 128.9, 126.8, 126.5, 117.6, 116.1, 115.9, 115.7, 79.0 (vinylic
CH), 52.3 (–NCH), 41.5 (–NCH2), 18.6 –CH3); HRMS (ESI) (M +
Analytical data of 3,4-dihydro-1H-quinazolin-2-ylidenes
(E)-2-(3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-uorophenyl) H)+ calcd for C19H19F2O: 311.1559, found 311.1553; ESI-MS
ethanone (4a). The compound was obtained as light yellow (m/z).
solid, yield: 80%; mp 104–106 ꢀC; IR (nmax cmꢁ1) (CHCl3): 2923,
8728 | RSC Adv., 2018, 8, 8721–8731
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(E)-2-(3-butyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-
RSC Advances
¼ 7.32 Hz, 1H), 7.03–6.96 (m, 3H), 6.92 (t, J ¼ 7.32 Hz, 1H), 5.46
(s, 1H, vinylic CH), 4.61 (s, 2H, –NCH2,ring), 4.41 (s, 2H,
–NHCH2); 13C NMR (100 MHz, CDCl3) d: 184.3 (C]O), 165.2,
162.7, 157.5, 137.4, 134.9, 134.2, 130.3, 129.0, 128.6, 127.9,
126.8, 125.4, 123.0, 117.9, 115.4, 115.0, 114.7, 76.3 (vinylic CH),
48.7 (–NCH2), 44.5 (–NCH2,ring); HRMS (ESI) (M + H)+ calcd for
uorophenyl)ethanone (4f). The compound was obtained as
a light yellow solid, yield: 92%; mp 108–110 C; IR (nmax cmꢁ1
)
ꢀ
1
(CHCl3): 2924, 1590; H NMR (400 MHz, DMSO-d6) d: 13.89 (s,
1H, NH), 7.93 (dd, J ¼ 9.0, 3.3 Hz, 2H), 7.23 (t, J ¼ 9.0 Hz, 3H),
7.13 (t, J ¼ 7.5 Hz, 1H), 7.01 (d, J ¼ 7.5 Hz, 1H), 6.96 (t, J ¼ 7.8 Hz,
1H), 5.49 (s, 1H, vinylic CH), 4.51 (s, 2H, –NCH2), 3.47 (t, 2H,
CH2CH2CH2CH3), 1.65 (q, 2H, CH2CH3), 1.44–1.32 (m, 2H,
–CH2CH2CH3), 0.94 (t, 3H, –CH3); 13C NMR (100 MHz, CDCl3) d:
183.7 (C]O), 165.1, 162.6, 157.0, 137.7, 134.5, 128.6, 125.3,
122.8, 117.9, 115.2, 115.0, 114.7, 75.8 (vinylic CH), 50.3 (–CH2-
CH2CH2CH3), 48.9 (–NCH2), 28.4 (–CH2CH2CH3), 20.1
(–CH2CH3), 13.8 (–CH3); HRMS (ESI) (M + H)+ calcd for
C
23H19FN2O: 359.1559, found 359.1583.
(E)-2-(3-cyclohexyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-
(4-uoro-2-methoxy phenyl)ethanone (4k). The compound was
ꢀ
obtained as a light yellow solid, yield: 65%; mp 148–150 C; IR
(nmax cmꢁ1) (CHCl3): 2937, 1580; H NMR (400 MHz, CDCl3) d:
1
13.86 (s, 1H, NH), 7.68 (t, J ¼ 8.54 Hz, 1H), 7.18 (t, J ¼ 6.71 Hz,
1H), 6.98–6.90 (m, 3H), 6.73–6.61 (m, 2H), 5.47 (s, 1H, vinylic
CH), 4.28 (s, 2H, –NCH2), 3.85 (s, 3H, Ar–OCH3), 3.73–3.68 (m,
1H, –NCH), 1.72–1.54 (m, 6H), 1.40–1.30 (m, 2H), 1.26–1.13 (m,
2H); 13C NMR (100 MHz, CDCl3) d: 183.7 (C]O), 165.1, 162.7,
158.2, 157.5, 134.9, 131.8, 128.5, 128.1, 125.2, 122.6, 118.6,
115.1, 107.0, 106.7, 99.4, 99.1, 81.0 (vinylic CH), 56.4 (–NCH),
55.8 (Ar–OCH3), 41.6 (–NCH2), 29.5 (–NCHCH2), 25.7
(–NCHCH2CH2CH2), 25.4 (–NCHCH2CH2CH2); HRMS (ESI) (M +
H)+ calcd for C21H23FN2O2: 381.1978, found 381.1975.
C
20H21FN2O: 325.1716, found 325.1724.
(E)-2-(3-(tert-butyl)-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-
uorophenyl)ethanone (4g). The compound was obtained as
a light yellow solid, yield: 86%; mp 106–108 C; IR (nmax cmꢁ1
)
ꢀ
1
(CHCl3): 2925, 1581; H NMR (400 MHz, DMSO-d6) d: 14.3 (s,
1H, NH), 7.83 (dd, J ¼ 9.16, 3.66 Hz, 2H), 7.23–7.17 (m, 4H), 6.97
(t, J ¼ 7.32 Hz, 1H), 6.93 (d, J ¼ 7.93 Hz, 1H), 5.60 (s, 1H, vinylic
CH), 4.34 (s, 2H, –NCH2), 1.51 (s, 9H, 3 ꢂ CH3); 13C NMR (100
MHz, DMSO-d6) d: 182.9 (C]O), 159.0, 137.8, 135.4, 128.6,
124.6, 122.9, 121.6, 115.1, 114.8, 82.4 (vinylic CH), 57.1 (–NCH2),
43.9 (–C(CH3)3), 29.7 (–CH3); HRMS (ESI) (M + H)+ calcd for
(E)-2-(3-butyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-uoro-2-
methoxyphenyl) ethanone (4l). The compound was obtained as
a light brown solid, yield: 82%; mp 102–104 C; IR (nmax cmꢁ1
)
ꢀ
(CHCl3): 2924, 1584; 1H NMR (400 MHz, CDCl3) d: 13.66 (s, 1H,
NH), 7.65 (t, J ¼ 7.34 Hz, 1H), 7.22–7.14 (m, 1H), 6.94–6.88 (m,
3H), 6.65–6.60 (m, 2H), 5.36 (s, 1H, vinylic CH), 4.40 (s, 2H,
–NCH2), 3.83 (s, 3H, Ar–OCH3), 3.28 (t, J ¼ 7.34 Hz, 2H, –CH2-
CH2CH2CH3), 1.75–1.67 (m, 2H, CH2CH2CH2CH3), 1.40–1.34
(m, 2H, CH2CH3), 0.98–0.91 (m, 3H, –CH3); 13C NMR (100 MHz,
CDCl3) d: 183.7 (C]O), 158.1, 156.6, 153.6, 134.5, 131.0, 128.6,
125.2, 122.6, 115.3, 107.0, 106.7, 99.4, 99.1, 80.9 (vinylic CH),
55.8 (Ar–OCH3), 50.4 (–NCH2,ring), 29.6 (–CH2CH2CH2CH3), 20.1
(–CH2CH3), 13.8 (–CH3); HRMS (ESI) (M + H)+ calcd for
C
20H21FN2O: 325.1716, found 325.1716.
(E)-2-(3-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-
(4-uorophenyl) ethanone (4h). The compound was obtained as
a yellow viscous material; yield: 70%; IR (nmax cmꢁ1) (CHCl3):
2924, 1595; H NMR (400 MHz, DMSO-d6) d: 13.5 (s, 1H, NH),
7.87 (dd, J ¼ 8.79, 2.93 Hz, 2H), 7.18 (t, J ¼ 7.32 Hz, 1H), 7.06 (t, J
¼ 8.79 Hz, 2H), 7.00–6.95 (m, 2H), 6.91 (d, J ¼ 8.05 Hz, 1H), 5.82
(s, 1H, vinylic CH), 4.37 (s, 2H, –NCH2), 2.60–2.55 (m, 1H,
–NCH), 1.00–0.96 (q, 2H, cyclopropyl CH2), 0.81–0.79 (m, 2H,
cyclopropyl CH2); 13C NMR (100 MHz, CDCl3) d: 184.2 (C]O),
165.2, 162.7, 159.2, 137.4, 134.1, 128.7, 125.3, 122.8, 119.2,
115.1, 115.0, 114.8, 77.9 (vinylic CH), 48.7 (–NCH2), 30.5 (–NCH),
1
C
21H23FN2O2: 355.1822, found 355.1820.
(E)-2-(3-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-
9.0 (cyclopropyl CH2); HRMS (ESI) (M
19H17FN2O: 309.1403, found 309.1405.
(E)-2-(3-cyclohexyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-
+
H)+ calcd for
(4-uoro-2-methoxy phenyl)ethanone (4m). The compound was
obtained as a light brown solid, mp 108–110 ꢀC; IR (nmax cmꢁ1
)
C
1
(CHCl3): 2928, 1588; H NMR (400 MHz, yield: 82%; CDCl3) d:
13.53 (s, 1H, NH), 7.67 (t, J ¼ 8.70 Hz, 1H), 7.61 (t, J ¼ 7.79 Hz,
1H), 6.96 (t, J ¼ 7.33 Hz, 1H) 6.91 (d, J ¼ 7.79 Hz, 1H), 6.88 (d, J ¼
7.79 Hz, 1H), 6.67 (dd, J ¼ 8.70, 2.29 Hz, 1H), 6.65–6.61 (m, 1H),
5.84 (s, 1H, vinylic CH), 4.34 (s, 2H, –NCH2), 3.84 (s, 3H, Ar–
OCH3), 2.52–2.45 (m, 1H, –NCH), 0.92–0.87 (q, 2H, cyclopropyl
CH2), 0.79–0.75 (m, 2H, cyclopropyl CH2); 13C NMR (100 MHz,
CDCl3) d: 184.4 (C]O), 165.2, 162.8, 158.8, 158.3, 134.3, 131.1,
128.5, 127.8, 125.3, 122.6, 119.2, 115.1, 106.9, 99.4, 83.0 (vinylic
CH), 55.7 (Ar–OCH3), 48.7 (–NHCH2), 30.5 (–NCH), 8.8 (cyclo-
propyl CH2); HRMS (ESI) (M + H)+ calcd for C20H19FN2O2:
339.1509, found 339.1498.
(4-uorophenyl)ethanone (4i). The compound was obtained as
a light yellow solid, yield: 71%; mp 116–118 C; IR (nmax cmꢁ1
)
ꢀ
(CHCl3): 2927, 2360, 1584; 1H NMR (400 MHz, CDCl3) d: 13.97 (s,
1H, NH), 7.82 (dd, J ¼ 8.79, 2.93 Hz, 2H), 7.24–7.17 (m, 3H), 7.06
(t, J ¼ 8.79 Hz, 1H), 7.00–6.93 (m, 2H), 5.38 (s, 1H, vinylic CH),
4.30 (s, 2H, –NCH2), 3.80–3.74 (m, 1H, –NCH), 1.76–1.60 (m,
6H), 1.47–1.38 (m, 2H), 1.26–1.15 (m, 2H); 13C NMR (100 MHz,
CDCl3) d: 183.9 (C]O), 165.1, 162.6, 157.8, 137.9, 134.9, 128.6,
125.2, 122.8, 118.7, 115.0, 114.8, 75.9 (vinylic CH), 56.5 (–NCH),
41.7 (–NCH2), 29.5 (–NCHCH2), 25.7 (–NCHCH2CH2CH2), 25.4
(–NCHCH2CH2CH2); HRMS (ESI) (M
22H23FN2O: 351.1872, found 351.1892.
(E)-2-(1-benzyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-
+
H)+ calcd for
(E)-2-(3-butyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-(4-
(triuoromethyl)phenyl) ethanone (4n). The compound was
C
ꢀ
obtained as a light yellow solid, yield: 80%; mp 114–116 C; IR
uorophenyl)ethanone (4j). The compound was obtained as
1
(nmax cmꢁ1) (CHCl3): 2925, 1586; H NMR (400 MHz, CDCl3) d:
a light yellow viscous material; yield: 68%; IR (nmax cmꢁ1
)
1
13.76 (s, 1H, NH), 7.90 (d, J ¼ 7.79 Hz, 2H), 7.63 (d, J ¼ 7.79 Hz,
(CHCl3): 2937, 1592; H NMR (400 MHz, CDCl3) d: 13.8 (s, 1H,
NH), 7.76 (dd, J ¼ 8.79, 2.93 Hz, 2H), 7.39–7.31 (m, 6H), 7.21 (t, J
2H), 7.24–7.18 (m, 1H), 6.98–6.92 (m, 3H), 5.34 (s, 1H, vinylic
CH), 4.45 (s, 2H, –NCH2), 3.37 (t,
J
¼
7.33 Hz, 3H,
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–CH2CH2CH2CH3), 1.72 (q, J ¼ 7.33 Hz, 2H, CH2CH2CH3), 1.44–
1.39 (q, 2H, –CH2CH3), 0.98 (t, J ¼ 7.33 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3) d: 183.3 (C]O), 157.2, 145.1, 134.2, 128.8,
126.8, 125.4, 125.1, 123.1, 117.8, 115.4 (vinylic CH), 50.4
(–NCH2), 49.0 (–CH2CH2CH2CH3), 28.5 (CH2CH2CH3), 20.1
(–CH2CH3), 13.8 (CH3); HRMS (ESI) (M + H)+ calcd for
V. Muthukumar, N. Pavalarani, P. Vasanthanathan and
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N. C. Reddy, V. Sridhar and J. V. Rao, Eur. J. Med. Chem.,
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6 V. G. Ugale and S. B. Bari, Eur. J. Med. Chem., 2014, 80, 447.
7 (a) T. Mohamed, M. K. Mann and P. P. N. Rao, RSC Adv.,
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S. P. P. Nagesh, Pharm. Sin., 2011, 2, 146.
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Commun., 2008, 2935; (b) F. Portela-Cubillo, J. S. Scott and
J. C. Walton, J. Org. Chem., 2009, 74, 4934; (c) Y. P. Patil,
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B. M. Bhanage, Catal. Lett., 2009, 133, 201; (d) T. Mizuno,
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A. K. Verma, Org. Biomol. Chem., 2015, 13, 1521.
9 (a) Y. Lv, Y. Li, T. Xiong, W. Pu, H. Zhang, K. Sun, Q. Liu and
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6333; (c) R. Rohlmann, T. Stopka, H. Richter and
C
21H21F3N2O: 375.1684, found 375.1680.
(E)-2-(3-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ylidene)-
1-(4-(triuoromethyl) phenyl)ethanone (4o). The compound
was obtained as a uorescent yellow solid; yield: 65%; mp 123–
125 ꢀC; IR (nmax cmꢁ1) (CHCl3): 2923, 1590; 1H NMR (400 MHz,
CDCl3) d: 13.6 (bs, 1H, NH), 7.95 (d, J ¼ 8.24 Hz, 2H), 7.64 (d, J ¼
8.24 Hz, 2H), 7.20 (t, J ¼ 7.79 Hz, 1H), 7.01–6.92 (m, 3H), 5.86 (s,
1H, vinylic CH), 4.41 (s, 2H, –NCH2), 2.60 (m, 1H, –NCH), 1.02–
0.97 (q, J ¼ 5.50 Hz, 2H, cyclopropyl CH2), 0.83–0.79 (m, 2H,
cyclopropyl CH2); 13C NMR (100 MHz, CDCl3) d: 183.7 (C]O),
159.4, 144.6, 133.9, 128.7, 126.9, 125.4, 125.1, 123.1, 119.1,
115.3, 78.7 (vinylic CH), 48.7 (–NCH2), 30.6 (–NCH), 9.0 (cyclo-
propyl CH2); HRMS (ESI) (M + H)+ calcd for C20H17F3N2O:
359.1371, found 359.1394.
(E)-2-(3-cyclohexyl-3,4-dihydroquinazolin-2(1H)-ylidene)-1-
(4-(triuoromethyl) phenyl)ethanone (4p). The compound was
obtained as a light yellow viscous material; yield: 66%; IR
1
(nmax cmꢁ1) (CHCl3): 2928, 1584; H NMR (400 MHz, CDCl3) d:
13.96 (s, 1H, NH), 7.91 (d, J ¼ 8.39 Hz, 2H), 7.64 (d, J ¼ 8.39 Hz,
2H), 7.26–7.18 (m, 1H), 7.00–6.94 (m, 3H), 5.41 (s, 1H, vinylic
CH), 4.32 (s, 2H, –NCH2), 3.81–3.74 (m, 1H, –NCH), 1.92–1.84
(m, 3H), 1.64–1.60 (m, 1H), 1.43–1.39 (m, 2H), 1.26–1.21 (m,
4H); 13C NMR (100 MHz, CDCl3) d: 183.4 (C]O), 157.9, 145.1,
134.6, 131.5, 131.1, 128.7, 126.8, 125.3, 125.1, 123.1, 118.5,
115.1, 76.9 (vinylic CH), 56.6 (–NCH), 41.8 (–NCH2), 29.5
(–NCHCH2), 25.7 (–NCHCH2CH2CH2), 25.3 (–NCHCH2CH2-
CH2); HRMS (ESI) (M + H)+ calcd for C23H23F3N2O: 401.1840,
found 401.1832.
˜
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Conflicts of interest
There are no conicts to declare.
Acknowledgements
The authors are thankful to SERB, Department of Science &
Technology, INDIA for providing nancial support and USIC,
University of Delhi for providing instrumentation facilities.
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