Synthesis of 2-hydroxy-5,6-diarylnicotinonitriles and 2-chloro-5,6-diarylnicotinonitriles from β-chloroenones We dedicate this article to the memories of Dr. C. V. Asokan who was a great teacher and an eminent researcher

Article abstract of DOI:10.1016/j.tet.2014.07.031

Vilsmeier-Haack reaction of β-ketoaldehydes leads to the formation of β-chloroenones and these chloroenones on treatment with malononitrile afford 2-hydroxy-5,6-diarylnicotinonitriles. But a one-pot reaction of β-ketoaldehydes with Vilsmeier-Haack reagent

Full text of DOI:10.1016/j.tet.2014.07.031

Tetrahedron 70 (2014) 6450e6456
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 2-hydroxy-5,6-diarylnicotinonitriles and 2-chloro-
5,6-diarylnicotinonitriles from b-chloroenones
y
*
K.U. Krishnaraj , K.S. Devaky
School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala, India
a r t i c l e i n f o
a b s t r a c t
Article history:
VilsmeiereHaack reaction of
b-ketoaldehydes leads to the formation of b-chloroenones and these
Received 28 February 2014
Received in revised form 20 June 2014
Accepted 8 July 2014
chloroenones on treatment with malononitrile afford 2-hydroxy-5,6-diarylnicotinonitriles. But a one-pot
reaction of -ketoaldehydes with VilsmeiereHaack reagent and malononitrile or cyanoacetamide results
in the formation of 2-chloro-5,6-diarylnicotinonitriles in good yields.
Ó 2014 Elsevier Ltd. All rights reserved.
b
Available online 12 July 2014
We dedicate this article to the memories of
Dr. C. V. Asokan who was a great teacher
and an eminent researcher
Keywords:
VilsmeiereHaack reaction
2-Hydroxy-5,6-diarylnicotinonitriles
2-Chloro-5,6-diarylnicotinonitriles
b
b
-Ketoaldehydes
-Chloroenones
1. Introduction
b
-Ketoaldehydes, synthesized from chalcones, were treated
with VilsmeiereHaack reagent to form
b
-chloroenones.8 These
b-
Diarylnicotinonitriles form an important class of organic com-
pounds and these kinds of molecules possess important biological
properties.1 Anti-inflammatory, analgesic, antimicrobial, and anti-
pyretic properties of these compounds have already been reported.2
A variety of chalcones were reported as important starting materials
for the synthesis of 4,6-diarylnicotinonitriles.3 There are reports on
one-pot synthesis of diarylnicotinonitriles, but poor substrate se-
lection, lower yield, and lack of selectivity of the product were the
chloroenones on treatment with malononitrile in the presence of
ammonium acetate and acetic acid afforded 2-hydroxy-5,6-
diarylnicotinonitriles in good yields. Further
b-ketoaldehydes,
could be treated with malononitrile under VilsmeiereHaack con-
dition to synthesize 2-chloro-5,6-diarylnicotinonitriles. These se-
ries of reactions led to a novel facile method for the synthesis of b-
chloroenones, 2-hydroxy-5,6-diarylnicotinonitriles, and 2-chloro-
5,6-diarylnicotinonitriles in good yields. The results of the in-
vestigations are the topic of discussion of the paper.
problems
associated
with
the
method.4
Many
5,6-
diarylnicotinonitriles were synthesized using deoxybenzoins as the
staring materials, but the method required long hauling work and
the yields of diarylnicotinonitriles derived from deoxybenzoins were
very low.5 Our investigations on the VilsmeiereHaack reaction6,7 of
2. Results and discussion
Ducker et al. have reported the reaction of b-ketoaldehydes with
b-ketoaldehydes led to the development of an alternate facile
malononitrile/cyanoacetamide in the presence of sodium hydrox-
method for the synthesis of -chloroenones, which could be effec-
b
ide to afford 2-pyridone derivatives.9 However, the competing
tively transformed into 2-oxo/2-hydroxy-5,6-diarylnicotinonitriles
and 2-chloro-5,6-diarylnicotinonitriles in good yields.
deformylation reactions of b-ketoaldehydes under basic conditions
deteriorate the potential of the reaction as a valuable synthetic
method. As per earlier reports on the synthesis of chalcones and
chalcone aldehydes, a series of 1,3-diarylpropenones and 3-oxo-
2,3-diarylpropanals were synthesized.10 We tried an alternate
* Corresponding author. School of Chemical Sciences, Mahatma Gandhi Univer-
sity, Priyadarshini Hills P.O., Kottayam 686 560, Kerala, India. Tel.: þ91 481 2731036;
fax: þ91 481 2731002; e-mail address: ksdevakyscs@yahoo.com (K.S. Devaky).
method in which
b-ketoaldehydes could be easily transformed into
y
Fax: þ91 481 2731002.
b-chloroenones under VilsmeiereHaack condition and from these
http://dx.doi.org/10.1016/j.tet.2014.07.031
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
6451
chloroenones 2-oxo/2-hydroxypyridines were synthesized in ex-
cellent yields. In a pilot experiment 3-oxo-2,3-diphenylpropanal 1a
was treated with 1.5 equiv of VilsmeiereHaack reagent at room
temperature(30 ꢀC) forming 3-chloro-1,2-diphenyl-2-propen-1-
one 2a. The reaction was monitored by TLC and was found to be
completed within 20 h with a yield of 94%. The product 2a was then
treated with malononitrile in the presence of ammonium acetate
and acetic acid at 78 ꢀC for 8 h to form 2-oxo/2-hydroxy-5,6-
diphenylnicotinonitrile 3a(Scheme 1).
3463 cmꢁ1 and the aromatic CeH stretching at 3284 cmꢁ1. The C]
C stretching and C]N stretching were observed at 1627 and
1645 cmꢁ1, respectively. Elemental analysis results also support the
formation of 3a.
1H NMR and 13C NMR spectral analysis showed that in solution
5,6-diphenyl-2-hydroxynicotinonitrile 3a exists in
a
pyr-
idoneepyridol equilibrium, which is a general property of 2-
pyridones.11 In the 1H NMR (DMSO-d6) spectrum there was a broad
singlet of two protons at
d
6.87, which disappeared in D2O indicating
O
OH
O
O
O
CN
CN
HN
N
NC CN
H
Cl
POCl3
DMF
R1
R1
NH4OAc
R1
CH3COOH
R1
o
78 C
R2
R2
R2
R2
1a-i
2a-i
3a-i
Scheme 1. Synthesis of 2-hydroxy-5,6-diarylnicotinonitriles.
1H NMR spectroscopic analyses showed that the product 3a
formed in this reaction is an equilibrium mixture of 2-
hydroxypyridine/2-pyridone tautomers. The reaction is general
and other 3-oxo-2,3-diarylpropanals 1bei were converted to 3-
chloro-1,2-diaryl-2-propen-1-ones 2aei and 2-hydroxy/2-oxo-
5,6-diarylnicotinonitriles 3bei (Table 1).
the presence of NH and OH protons, which are D2O exchangeable.
The peaks at 7.82 and 7.92 correspond the CH of the heterocyclic
ring. Other aromatic protons resonated in the 6.98e7.32 ppm re-
gion as multiplets with an integration of 20 protons. In the 13C NMR
spectrum signals at 160.4 (C]O), and 157.7 ppm (CeOH),115.8 and
d
d
d
115.5 (CN) also indicate the existence of pyridoneepyridol equilib-
rium. However, the single crystal X-ray analysis of both compounds
3a and 3i showed that in solid state they exist as 2-hydroxy-5,6-
diarylnicotinonitrile and two neighboring molecules are bound to-
gether with intermolecular hydrogen bonding between adjacent
hydroxypyridine moieties (NeHeO) (Figs. 1 and 2). In 2-hydroxy-5-
(4-methoxyphenyl)-6-phenylnicotinonitrile 3i an interaction be-
tween nitrile nitrogen (N1) and pyridine ring hydrogen (H9) was also
observed, which may be due to weak polar interactions between
methoxy group and aromatic stacking interaction (Fig. 2b). The OeH
Table 1
Synthesis of 3-chloro-1,2-diaryl-2-propen-1-ones 2ai and 5,6-diaryl-2-hydroxyni
cotinonitriles 3aei
2, 3
R1
R2
Yield
2
3
a
b
c
d
e
f
g
h
i
H
Br
H
H
H
H
94
92
95
93
92
91
91
95
95
85
75
82
88
78
82
77
71
90
4-OCH3
4-Cl
4-CH3
4-Cl
H
ꢀ
ꢀ
bond lengths in 3a and 3i are 0.821 A and 0.820 A respectively.
The mechanism for the formation of 2-hydroxy-5,6-
diarylnicotinonitriles 3 from 3-oxo-2,3-diarylpropanal 1 via 3-
chloro-1,2-diphenyl-2-propen-1-one 2 can be explained as follows.
Addition of VilsmeiereHaack reagent to 3-oxo-2,3-
diarylpropanal 1 forms an iminoalkylated intermediate 4 fol-
lowed by elimination of one molecule of DMF resulting in the for-
H
2-Cl
2-Cl
4-OCH3
4-OCH3
4-CH3
H
IR spectrum of 2a exhibited absorption bands due to carbonyl
group at 1670 cmꢁ1 and CeCl stretching at 694 cmꢁ1. The (Mþ2)
peak at m/z 244 and molecular ion peak at m/z 242 in the GCeMS
spectrum indicate the formation of 2a. 1H NMR and 13C NMR
spectra of 2a revealed that a mixture of both E and Z isomers are
formed in certain cases in the reaction, but for the derivatives 2f, 2g,
and 2h only one isomer is formed. The reason for favoring only one
isomer in certain cases may be due to some stereoelectronic or
steric factors and it is beyond the scope of the investigations. In the
1H NMR spectrum of 2a the vinylic hydrogen appeared twice at
mation of
b-chloroenone 2. Michael reaction of 2 with
malononitrile gives the adduct 5 and which undergoes subsequent
cyclization and aromatization to afford nicotinonitrile
(Scheme 2).
3
b-Chloroenone 2 was treated with cyanoacetamide under sim-
ilar conditions, but no 2-hydroxypyiridine derivative could be
isolated.
In an earlier report we had shown that enones or enolizable
ketones undergo condensation with malononitrile under Vils-
meiereHaack reaction condition, followed by in situ cyclization and
aromatization to form 2-chloronicotinonitriles.6 In light of the above
reaction, 3-oxo-2,3-diphenylpropanal 1a was treated with Vils-
meiereHaack reagent at room temperature for 20 h followed by
addition of malononitrile/cyanoacetamide. The temperature was
elevated to 70 ꢀC and the reaction was continued for another 3 h to
get 2-chloro-5,6-diphenylnicotinonitrile 7a in 55% and 70% yield,
respectively (Scheme 3, Table 2). The formation of product 7a was
via chloroenone intermediate 2. The reaction was extended to other
3-oxo-2,3-diarylpropanals 1bee to get 2-chloro-5,6-diarylnicotin
onitrile 7aee in good yields.
d
6.76 and
a multiplet between
atoms were observed at
decoupled 13C NMR spectrum of 2a the peaks corresponding to the
vinylic carbon atoms were present at 137.1 and 143.0 and the
carbonyl carbon atoms at 193.9 and 194.8.
d
7.01 and 16 aromatic protons were appeared as
7.33 and 7.59. The remaining four hydrogen
7.79 and
8.01 as two doublets. In the 1H
d
d
d
d
d
1H NMR spectroscopic analyses showed that the product 3a
formed in this reaction is an equilibrium mixture of 2-
hydroxypyridine/2-pyridone tautomers. The reaction is general to
other 3-oxo-2,3-diarylpropanals 1bei to get 3-chloro-1,2-diaryl-2-
propen-1-ones 2aei and 2-hydroxy/2-oxo-5,6-diarylnicotin
onitriles 3bei (Table 1). In the FTIR spectrum of 2-hydroxy-5,6-
diphenylnicotinonitrile 3a showed the OeH stretching at
Apparently, underthe VilsmeiereHaack reaction condition, the3-
oxo-2,3-diphenylpropanal 1a reacted with malononitrile or

6452
K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
Fig. 1. . a. Ortep diagram of 2-hydroxy-5,6-diphenylnicotinonitrile 3a. b. Three-dimensional arrays of 2-hydroxy-5,6-diphenylnicotinonitrile 3i in its crystal lattice.
Fig. 2. . a. Ortep diagram of 2-hydroxy-5-(4-methoxyphenyl)-6-phenylnicotinonitrile 3i. b. Three-dimensional arrays of 2-hydroxy-5-(4-methoxyphenyl)-6-phenylnicotinonitrile 3i
in its crystal lattice.
Table 2
Synthesis of 2-chloro-5,6-diarylnicotinonitrile 7 from 3-oxo-2,3-diphenylpropanal 1
and malononitrile/cyanoacetamide
7
R1
R2
Yields (%)
Malononitrile
Cyanoacetamide
a
b
c
d
e
H
4-Cl
4-OMe
4-Br
4-CH3
H
H
H
H
55
35
45
36
12
70
77
80
90
67
Ο
4-OMe
Scheme 2. Plausible mechanism for the formation of 2-hydroxy-5,6-
diarylnicotinonitriles 3.
cyanoacetamide to get 5, which was in situ cyclized and aromatized
in the presence of chloromethyleneiminium salt (VilsmeiereHaack
reagent) present in the medium to afford 2-chloro-5,6-
diarylnicotinonitriles 7aee (Scheme 4). The yields of 7 obtained
from malononitrile were low when compared to cyanoacetamide.
Malononitrile may react with excess Vilsmeier reagent (VR) present
in the medium thereby lowering the yield. Reactivity of cyanoace-
tamide toward VR is less.
Scheme
4. Plausible
mechanism
for
the
formation
of
2-chloro-5,6-
diarylnicotinonitriles 7aee.
In conclusion the VilsmeiereHaack reaction of
resulted in the formation of -chloroenones, which could be easily
transformed into 2-hydroxy-5,6-diarylnicotinonitriles, while re-
action of -ketoaldehydes with malononitrile or cyanoacetamide
b-ketoaldehydes
b
b
Scheme 3. Synthesis of 2-chloro-5,6-diarylnicotinonitrile 7aee.

K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
6453
under VilsmeiereHaack reaction condition resulted in the forma-
tion of 2-chloro-5,6-diarylnicotinonitriles.
ArH), 7.37e7.58 (8H, m, ArH), 7.79 (2H, d, J¼8.4 Hz, ArH), 7.99 (2H,
d, J¼7.2 Hz, ArH); 13C NMR (400 MHz, CDCl3)
¼55.2 (OMe), 55.3
d
(OMe), 113.9, 114.5, 115.3 (vinylic), 125.7, 126.9, 127.3, 128.5, 128.9,
129.7, 129.8, 130.6, 132.9, 134.0, 135.4, 137.2, 142.5 (vinylic), 142.7
(vinylic), 159.6 (aromatic), 160.1 (aromatic), 194.3 (CO), 195.1
(CO) ppm; GCeMS m/z (%) 274 ((Mþ2), 3), 272 (Mþ, 10), 237 (17),
209 (23), 132 (100). Anal. Calcd for C16H13ClO2: C, 70.46; H, 4.80.
Found: C, 70.50; H, 4.90.
3. Experimental
Melting points were determined on a Buchi 530 melting point
apparatus and were uncorrected. The IR spectra were recorded as
KBr pellets on a Shimadzu IR-470 spectrometer and the frequencies
are reported in cmꢁ1. The 1H NMR spectra were recorded on
a Brucker WM 400 (400 MHz) spectrometer using TMS as internal
standard and CDCl3 and DMSO-d6 as solvents. The 13C NMR spectra
were recorded on a Brucker WM 400 (400 MHz) spectrometer
using CDCl3 or DMSO-d6 as solvent. The Electron Impact Mass
spectra were obtained on a GCeMS-Shimadzu 5050 model in-
strument. The CHN analyses were done on an ElementarVario EL III
Carlo Erba 1108 instrument. The X-ray single crystal analysis was
done on Bruker AXS SMART APEX single crystal X-ray diffractom-
eter. All reagents were commercially available and were purified
before use. Anhydrous sodium sulfate was used as drying agent. All
purified compounds gave a single spot upon TLC analyses on silica
gel 7GF using ethyl acetateehexane mixture as eluent. Iodine vapor
or KMnO4 solution in water was used as developing agent for TLC.
3.1.4. 3-Chloro-1-(4-chlorophenyl)-2-phenyl-2-propen-1-one
2d. Yellow viscous liquid, yield¼93% (2.58 g); (KBr, ymax)¼3066,
3031,1662,1581, 705 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d¼6.56 (1H, s,
vinylic), 7.04 (1H, s, vinylic), 7.16e7.58 (14H, m, ArH), 7.79 (4H, d,
J¼7.2 Hz, ArH); 13C NMR (400 MHz, CDCl3)
¼117.1 (vinylic), 128.6,
d
128.7, 129.3, 129.8, 130.7, 131.0, 131.8, 133.1, 134.6, 137.0, 142.0 (vi-
nylic), 193.6 (CO) ppm; GCeMS m/z (%) 280 ((Mþ4), 2), 278 ((Mþ2),
20), 276 (Mþ, 32), 241 (56), 212 (5), 139 (100), 141 (29), 139 (100).
Anal. Calcd for C15H10Cl2O: C, 65.01; H, 3.64. Found: C, 65.02; H, 3.70.
3.1.5. 3-Chloro-1-(4-methylphenyl)-2-phenyl-2-propen-1-one
2e. Yellow viscous liquid, yield¼92% (2.36 g); (KBr, ymax)¼3058,
3028,1674,1604, 698 cmꢁ1; 1H NMR (400 MHz, CDCl3)
CH3), 2.41 (3H, s, CH3), 6.75 (1H, s, vinylic), 6.96 (1H, s, vinylic),
d
¼2.38 (3H, s,
3.1. General procedure for the synthesis of 3-chloro-1,2-
diaryl-2-propen-1-ones 2aei
7.18e7.47 (14H, m, ArH), 7.72 (2H, d, J¼8 Hz, ArH), 7.91 (2H, d, J¼8 Hz,
ArH); 13C NMR (400 MHz, CDCl3)
d¼21.2 (CH3), 115.3 (vinylic), 116.7
(vinylic), 126.0, 128.1, 128.2, 128.9, 129.8, 133.4, 134.1, 143.7 (vinylic),
142.8 (vinylic), 193.0 (CO) 193.9 (CO) ppm; GCeMS m/z (%) 258
(Mþ2, 3), 256 (Mþ, 7), 221 (58),193 (7),119 (100), 91 (65). Anal. Calcd
for C16H13ClO: C, 74.85; H, 5.10. Found: C, 74.90; H, 5.17.
The VilsmeiereHaack reagent was prepared by mixing DMF
(8 mL, 100 mmol) and POCl3 (1.4 mL, 15 mmol) at 0 ꢀC followed by
stirring at room temperature for 15 min. To the VilsmeiereHaack
reagent, appropriate 2-oxo-1,2-diarylpropanal 1 (10 mmol) was
added and the solution was stirred at room temperature for 20 h.
The reaction mixture was poured into ice-cold K2CO3 solution and
extracted with ethyl acetate (3ꢂ20 mL). The organic layer was
washed with water, dried on anhydrous sodium sulfate, and the
solvent was removed by distillation. The crude reaction mixture
was purified by column chromatography (60e120 mesh) using
hexane/ethyl acetate (97:3) as the eluent.
3.1.6. 3-Chloro-2-(2-chlorophenyl)-1-(4-chlorophenyl)-2-propen-1-
one 2f. Yellow viscous liquid, yield¼91% (2.84 g); IR (KBr, ymax)¼
3085, 3060; 1660, 1587, 765 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
¼7.19 (1H, s, vinylic), 7.30e7.43 (6H, m, ArH), 7.78 (1H, d, J¼6, ArH),
7.80 (1H, d, J¼5, ArH); 13C NMR (400 MHz, CDCl3)
¼96.2, 126.8,
d
128.82, 129.7, 130.2, 131.1, 131.9, 132.9, 133.1, 135.1, 135.6, 139.3
(vinylic), 141.8 (vinylic), 191 (CO) ppm; GCeMS m/z (%) 312 ((Mþ2),
1), 310 (Mþ,1), 275 (65), 277 (43), 246 (6), 212 (8),176 (4),139 (100),
141 (30), 115 (15), 111 (50). Anal. Calcd for C15H9Cl3O: C, 57.82; H,
2.91. Found: C, 57.91; H, 3.01.
3.1.1. 3-Chloro-1,2-diphenyl-2-propen-1-one 2a. Yellow viscous
liquid, yield¼94% (2.28 g); IR (KBr, ymax)¼3062, 3031, 1670, 1581,
694 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
¼6.76 (1H, s, vinylic), 7.01
(1H, s, vinylic), 7.33e7.58 (16H, m, ArH), 7.81 (2H, d, J¼7.2 Hz, ArH),
3.1.7. 3-Chloro-2-(2-chlorophenyl)-1-phenyl-2-propen-1-one
8.01 (2H, d, J¼6.8 Hz, ArH); 13C NMR (400 MHz, CDCl3)
d
¼117.3
2g. Yellow viscous liquid, yield¼91% (2.52 g); IR (KBr, ymax)¼3066,
(vinylic), 126.0, 128.4, 128.5, 128.6, 128.7, 128.8, 128.9, 129.0, 129.2,
129.7, 129.8, 129.98, 131.2, 132.9, 133.5, 134.0, 137.1 (vinylic), 143.0
(vinylic),193.9 (CO),194.8 (CO) ppm; GCeMS m/z (%) 244 (Mþ2,19),
242 (Mþ,56), 207 (56), 209 (10), 178 (100). Anal. Calcd for
3037, 1658, 1596, 694 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
¼6.82 (1H,
s, vinylic), 7.26 (1H, br, ArH), 7.21 (2H, m, ArH), 7.35e7.49 (5H, m,
ArH), 7.86 (1H, d, J¼6.8, ArH); 13C NMR (400 MHz, CDCl3)
¼126.8,
d
128.5, 128.7, 129.6, 129.7, 130.1, 130.2, 131.2, 131.8, 132.7, 133.1, 135.5,
137.4 (vinylic), 188.5 (CO) ppm; GCeMS m/z (%) 278 ((Mþ2), 1), 276
(Mþ, 2), 243 (35), 207 (7), 241 (100), 105 (77), 77 (79). Anal. Calcd
for C15H10Cl2O: C, 65.01; H, 3.64. Found: C, 65.2; H, 3.65.
C
15H11ClO: C, 74.23; H, 4.57. Found: C, 74.31; H, 4.59.
3.1.2. 1-(4-Bromophenyl)-3-chloro-2-phenyl-2-propen-1-one
2b. Yellow viscous liquid, yield¼92% (2.96 g); (KBr, ymax)¼3062,
3028, 1662, 1585, 698 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d¼6.75 (1H,
3.1.8. 3-Chloro-2-(4-methoxyphenyl)-1-(4-methylphenyl)-2-propen-
s, vinylic), 7.03 (1H, s, vinylic), 7.31e7.39 (5H, m, ArH), 7.51e7.65
1-one 2h. Yellow viscous liquid, yield¼95% (2.72 g); IR (KBr, ymax)¼
(9H, m, ArH), 7.83 (4H, d, J¼10 Hz, ArH); 13C NMR (400 MHz, CDCl3)
3008, 3035, 1666, 1606, 771 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
¼96.0, 117.5 (vinylic), 125.9, 128.01, 128.4, 128.6, 128.9, 129.0, 129.1,
d
¼2.45 (3H, s, CH3), 3.85 (3H, s, OMe), 6.97 (2H, d, J¼8.7 Hz, ArH),
7.22e7.30 (4H, m, ArH), 7.46 (2H, d, J¼8.1 Hz, ArH), 6.74 (1H, s, vi-
nylic); 13C NMR (400 MHz, CDCl3)
129.4, 129.8, 130.9, 131.2, 131.7, 132.2, 133.1, 134.1, 134.1, 135.7 (vi-
nylic), 142.7 (vinylic), 192.3 (CO), 193.2 (CO) ppm; GCeMS m/z (%)
324 ((Mþ4), 2), 322 (Mþ2, 10), 320 (Mþ, 8), 287 (15), 289 (10), 183
(98), 185 (97), 155 (40), 157 (35), 241 (10), 243 (8), 102 (100). Anal.
Calcd for C15H10BrClO: C, 56.02; H, 3.13. Found: C, 55.9; H, 3.20.
d¼21.4 (methyl), 55.0 (OMe), 96.1,
113.6 (vinylic), 126.0, 129.2, 130.2, 131.2, 133.1, 139.9, 141.2 (vinylic),
154.7, 159.4, 189.9 (carbonyl) ppm; GCeMS m/z (%) 288 ((Mþ2), 11),
286 (Mþ, 31), 271 (17), 251 (13), 222 (17), 178 (16), 179 (12),119 (37),
135 (100). Anal. Calcd for C17H15ClO2: C, 71.20; H, 5.27. Found: C,
71.28; H, 5.31.
3.1.3. 3-Chloro-1-(4-methoxyphenyl)-2-phenyl-2-propen-1-one
2c. Yellow viscous liquid, yield¼95% (2.59 g); (KBr, ymax)¼3066,
1670, 1604, 713 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
¼3.78 (3H, s,
3.1.9. 3-Chloro-2-(4-methoxyphenyl)-1-phenyl-2-propen-1-one
OMe), 3.81 (3H, s, OMe), 6.66 (1H, s, vinylic), 6.91e6.93 (3H, m,
vinylic and ArH), 6.85 (2H, d, J¼8.8 Hz, ArH), 7.27 (2H, d, J¼10.4 Hz,
2i. Yellow viscous liquid, yield¼95% (2.59 g); IR (KBr, ymax)¼3055,
1666, 1555, 702 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d¼3.76 (3H, s,

6454
K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
OMe), 3.79 (3H, s, OMe), 6.76 (1H, s, vinylic), 6.85e6.99 (5H, m,
vinylic and aromatic), 7.24e7.58 (8H, m, ArH), 7.82 (4H, d, J¼8.4 Hz,
NMR (400 MHz, CDCl3)
d
¼171.5, 164.0, 132.4, 131.1, 129.5, 128.2,
121.6, 113.8 (CN), 113.7 (CN), 55.5 ppm; GCeMS m/z (%) 325
((MþNa)þ, 100), 309 (13), 294 (18), 281 (14), 265 (9), 227 (7), 155
(11), 141 (16), 127 (14), 114 (21), 100 (15). Anal. Calcd for
ArH), 7.99 (2H, d, J¼8 Hz, ArH); 13C NMR (400 MHz, CDCl3)
¼54.4
d
(OMe), 55.3 (OMe), 110.7, 114.4 (vinylic), 114.8 (vinylic), 115.1, 117.6,
118.6, 121.6, 128.5, 128.6, 128.9, 129.4, 129.7, 129.8, 130.2, 133.0,
134.1, 134.8, 137.1, 143.0 (vinylic), 143.2 (vinylic), 159.5, 160.0, 193.8
(CO), 194.7 (CO) ppm; GCeMS m/z (%) 274 ((Mþ2), 1), 272 (Mþ, 4),
237 (18), 209 (23), 105 (100), 77 (56). Anal. Calcd for C16H13ClO2: C,
70.46; H, 4.80. Found: C, 70.52; H, 4.91.
C19H14N2O2: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.41; H, 4.77; N,
9.50.
3.2.4. 6-(4-Chlorophenyl)-2-hydroxy-5-phenylnicotinonitrile 3d. Pale
yellow crystals; mp, 200e202 ꢀC; yield¼88% (1.35 g); IR (KBr, ymax)¼
3407, 3342, 3232, 2219, 1649, 1591 cmꢁ1; 1H NMR (400 MHz, CDCl3)
3.2. General procedure for the synthesis of 5,6-diaryl-2-
hydroxynicotinonitriles3aei
d
¼7.71 (1H, s, pyridine C(4)eH), 7.65 (1H, s, pyridine C(4)eH),
7.25e7.29 (5H, m, ArH), 7.17e7.22 (6H, m, ArH), 7.05e7.11 (4H, m,
ArH), 6.91e6.96 (3H, m, ArH), 5.3 (2H, br, OH and NH); 13C NMR
Appropriate 3-chloro-1,2-diaryl-2-propen-1-one 2aei (5 mmol)
was treated with malononitrile (660 mg, 10 mmol) in the presence
of ammonium acetate (5 mmol) and acetic acid (2 mL) at 78 ꢀC. The
reaction was monitored by TLC. After 8 h the reaction was com-
pleted and the reaction mixture was cooled and poured into ice-
cold water. The product was extracted with chloroform (25ꢂ3),
dried over anhydrous sodium sulfate, and the chloroform layer was
distilled off to get the crude product, which was purified by column
chromatography over 60e120 mesh silica gel using ethyl acetate/
hexane (1:9) as eluent.
(400 MHz, CDCl3)
d
¼158.9, 157.7, 150.8, 147.9, 143.7, 138.2, 138.0,
137.6, 137.2, 135.1, 135.0, 134.8, 131.8, 131.1, 131.0, 129.4, 129.3, 128.9,
128.7, 128.6, 128.4, 128.2, 127.4, 126.8, 116.5, 115.6 (CN), 115.4 (CN),
98.8, 96.7, 90.1 ppm GCeMS m/z (%) 308 ((Mþ2)þ, 5), 307 (32), 306
(Mþ, 47), 305 (100), 304 (98), 269 (53), 253 (8), 252 (16), 226 (7), 214
(7),134 (47), 121 (17), 107 (29). Anal. Calcd for C18H11ClN2O: C, 70.48.
H, 3.61; N, 9.13. Found: C, 70.61; H, 3.71; N, 9.20.
3.2.5. 2-Hydroxy-6-(4-methylphenyl)-5-phenylnicotinonitrile
3e. Pale yellow crystals; mp, 178e180 ꢀC; yield¼78% (1.12 g); IR
(KBr, ymax)¼3456, 3402, 3350, 3340, 3249, 3056, 3029, 2223, 1656,
3.2.1. 2-Hydroxy-5,6-diphenylnicotinonitrile 3a. Pale yellow crys-
tals; mp, 182e184 ꢀC; yield, 85% (1.16 g); IR (KBr, ymax)¼3463, 3452,
1649, 1589, 1546 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d¼7.09 (4H, d,
J¼10 Hz, ArH), 7.72 (1H, s, pyridine C(4)eH), 7.63 (1H, s, pyridine
C(4)eH), 7.22e7.15 (6H, m, ArH), 7.02 (4H, d, J¼10 Hz, ArH),
6.97e6.93 (4H, m, ArH), 5.24 (2H, br, OH and NH), 2.32 (6H, s, CH3);
3155, 2216, 1645, 1627 cmꢁ1
;
1H NMR (400 MHz, DMSO)
d¼6.87
(2H, br, NH and OH), 6.97e7.00 (4H, m, ArH), 7.07e7.11 (4H, m,
ArH), 7.14e7.17 (6H, m, ArH), 7.21e7.32 (6H, m, ArH), 7.82 (1H, s,
pyridine C(4)eH), 7.93 (1H, s, pyridine C(4)eH); 1H NMR (400 MHz,
DMSO-d6, D2O exchange) 6.98e7.01 (3H, m, ArH), 7.09e7.11 (2H, M,
ArH), 7.16e7.17 (5H, m, ArH), 7.24e7.34 (9H, m, ArH), 7.81 (1H, s,
pyridine C(4)eH), 7.92 (1H, s, pyridine C(4)eH); 13C NMR
13C NMR (400 MHz, CDCl3)
d
¼160.0, 157.0, 150.8, 149.6, 143.5, 138.8,
138.1, 138.0, 133.4, 131.9, 129.6, 129.4, 129.0, 128.7, 128.4, 128.2,
127.1, 115.9 (CN), 115.7 (CN), 99.1, 96.1, 89.1, 21.3 ppm; GCeMS m/z
(%) 286 (Mþ,14), 285 (80), 284 (100), 269 (13), 252 (12), 240 (6), 227
(4), 207 (46), 141 (15), 128 (8), 101 (3). Anal. Calcd for C19H14N2O: C,
79.70; H, 4.93; N, 9.78. Found: C, 79.87; H, 4.97; N, 9.83.
(400 MHz, CDCl3)
d¼160.3 (CO), 157.7, 150.8, 149.4, 143.5, 138.9,
138.0, 136.4, 131.9, 129.6, 129.6, 129.4, 128.8, 128.8, 128.4, 128.3,
128.2, 128.0, 127.2, 126.8, 116.6, 115.8 (CN), 115.5 (CN), 99.1, 96.4,
89.9 ppm; GCeMS m/z (%) 272 (Mþ,12), 271 (74), 270 (100), 253
(14), 226 (21), 135 (25), 140 (9), 121 (14), 94 (11), 77 (13). Anal. Calcd
for C18H12N2O: C, 79.39; H, 4.44; N, 10.29. Found: C, 79.45; H, 4.51;
N, 10.36. Single crystal data: molecular formula¼C18H12N2O, space
group¼P21/c, cell lengths¼a, 8.2637(4); b, 21.1060(10); c, 9.1661(6),
3 . 2 . 6 . 5 - ( 2 - C h l o r o p h e n y l ) - 6 - ( 4 - c h l o r o p h e n y l ) - 2 -
hydroxynicotinonitrile 3f. Pale yellow crystals; mp, 178e180 ꢀC;
yield¼82% (1.40 g); IR (KBr, ymax)¼3417, 3342, 3245, 3184, 2221,
1649 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
¼7.57 (1H, s, pyridine ring
hydrogen), 7.34e7.28 (3H, m, pyridine ring hydrogen, ArH),
7.25e7.21 (4H, m, ArH), 7.21e7.16 (2H, m, ArH), 7.14e7.07 (6H, m,
ArH), 6.95e6.91 (2H, m, ArH), 5.35 (2H, br, OH and NH); 13C NMR
cell angles¼a, 90.00;
b, 113.039(7);
g
, 90.00; cell volume¼1471.18,
Z, Z0¼Z: four Z0: 0, R-factor [%]¼6.82 and CCDC 996731.
(400 MHz, CDCl3)
d
¼162.1, 161.8, 152.1, 145.7, 140.7, 140.1, 139.5,
135.9, 134.8, 133.2, 132.6, 132.5, 132.0, 130.4, 130.0, 129.7, 129.0,
128.8, 128.5, 128.2, 125.4, 119.1, 116.1, 114.3 (CN), 114.8 (CN), 102.9,
96.8 ppm; GCeMS m/z (%) 344 ((Mþ4)þ, 14), 342 ((Mþ2)þ, 7), 340
(Mþ, 45), 339 (100), 316 (20), 325 (21), 324 (5), 306 (18), 249 (41),
230 (6), 168 (7), 112 (21), 76 (24). Anal. Calcd for C18H12Cl2N2O: C,
63.36; H, 2.95; N, 8.21. Found: C, 63.39; H, 3.03; N, 8.23.
3.2.2. 6-(4-Bromophenyl)-2-hydroxy-5-phenylnicotinonitrile
3b. Pale yellow crystals; mp, 204e206 ꢀC; yield¼75% (1.32 g); IR
(KBr, ymax)¼3402, 3150, 3050, 2221, 1656 cmꢁ1; 1H NMR (400 MHz,
CDCl3)
d
¼7.74 (1H, s, pyridine C(4)eH), 7.64 (1H, s, pyridine C(4)e
H), 7.43 (4H, d, J¼10 Hz, ArH), 7.16e7.23 (5H, m, ArH), 7.03 (4H, d,
J¼10 Hz, ArH), 6.91e6.97 (5H, m, ArH), 5.83 (2H, br, NH and OH);
13C NMR (400 MHz, CDCl3)
d¼207.0, 157.7, 150.9, 147.9, 143.7, 138.2,
3.2.7. 5-(2-Chlorophenyl)-2-hydroxy-6-phenylnicotinonitrile
137.9, 137.6, 135.3, 131.7, 131.6, 131.3, 131.2, 129.4, 129.3, 128.6, 128.3,
127.4, 126.7, 123.4, 116.4, 115.6 (CN), 115.4 (CN), 98.7, 96.7, 90.1 ppm;
GCeMS m/z (%) 352 ((Mþ2), 10), 350 (Mþ, 10), 288 (21), 286 (40),
270 (100), 255 (12), 242 (34), 227 (14), 214 (65), 184 (40), 156 (13),
140 (12), 75 (56). Anal. Calcd for C18H11BrN2O: C, 61.56; H, 3.16; N,
7.98. Found: C, 61.63; H, 3.21; N, 8.21.
3g. Pale yellow crystals; mp, 132e134 ꢀC; yield¼77% (1.18 g); IR
(KBr, ymax)¼3417, 3340, 3244, 3056, 2219, 1650 cmꢁ1
;
1H NMR
(400 MHz, CDCl3)
d
¼7.55 (2H, br s, pyridine C4eH), 7.31e7.27 (2H,
m, ArH), 7.18e7.13 (2H, m, ArH), 7.09e7.02 (12H, m, ArH), 6.94e6.90
(2H, m, ArH), 5.35 (2H, br, OH and NH); 13C NMR (400 MHz, CDCl3)
d
¼151.3, 150.4, 138.8, 138.5, 136.8, 133.5, 133.0, 132.0, 129.4, 129.1,
129.0, 128.8, 126.4, 115.7 (CN), 115.6 (CN), 98.7, 95.7 ppm; GCeMS
m/z (%) 308 ((Mþ2)þ, 3), 306 (Mþ, 37), 305 (68), 304 (53), 281 (22),
270 (34), 253 (12), 242 (19), 226 (4), 207 (48), 191 (14), 174 (6), 147
(6), 134 (13), 121 (15), 107 (14), 94 (6), 83 (100). Anal. Calcd for
3.2.3. 2-Hydroxy-6-(4-methoxyphenyl)-5-phenylnicotinonitrile
3c. Pale yellow crystals; mp, 178e180 ꢀC; yield¼1.24 g (82%); IR
(KBr, ymax)¼3413, 3348, 3249, 3060, 3028, 3002, 2217, 1660, 1602,
1512, 1492, 1452, 1425 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
¼7.85 (1H,
C18H12N2O: C, 70.48; H, 3.61; N, 9.13. Found: C, 70.56; H, 3.73; N,
9.22.
s, pyridine C(4)eH), 7.87 (1H, s, pyridine C(4)eH), 7.20e7.11 (4H, m,
ArH), 7.39 (2H, d, J¼8.8 Hz, ArH), 7.46 (2H, d, J¼8.8 Hz, ArH), 6.95
(6H, m, ArH), 6.81 (2H, d, J¼8.0 Hz, ArH), 6.74 (2H, d, J¼8.0 Hz, ArH),
3.2.8. 2-Hydroxy-5-(4-methoxyphenyl)-6-(4-methylphenyl)nic-
otinonitrile 3h. Pale yellow crystals; mp, 188e190 ꢀC; yield¼71%
5.08, 5.10 (2H, NH and OH), 3.89 (3H, 3, OMe), 3.79 (3H, s, OMe); 13
C

K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
6455
(1.12 g); IR (KBr, ymax)¼3481, 3363, 3234, 3014, 2217, 1631 cmꢁ1
;
(3H, m, ArH), 7.44e7.2 (7H, m, ArH) ppm; 13C NMR (400 MHz,
1H NMR (400 MHz, CDCl3)
d
¼7.60 (2H, br s, pyridine ring hydro-
CDCl3)
d
¼143.4, 139.5, 135.0, 129.5, 129.5, 128.9, 128.9, 128.7, 128.7,
gen), 7.11 (4H, m, ArH), 7.03 (4H, d, J¼10 Hz, ArH), 6.89e6.83 (4H,
m, ArH), 6.70 (4H, d, J¼10 Hz, ArH), 5.22 (2H, br, OH and NH), 3.75
(6H, s, OMe), 2.33 (6H, s, CH3); 13C NMR (400 MHz, CDCl3)
128.1, 127.3, 126.8 ppm; GCeMS m/z (%) 326 ((Mþ2), 16), 324 (Mþ,
39), 323 (25), 299 (13), 297 (13), 281 (13), 278 (7), 253 (6), 245 (37),
218 (11), 207 (45), 190 (15), 178 (7), 164 (3), 139 (15), 113 (13), 103
(17), 77 (100). Anal. Calcd for C18H10Cl2N2: C, 66.48; H, 3.10; N, 8.61.
Found: C, 66.53; H, 3.2; N, 8.68.
d
¼170.5, 164, 155.7, 150.6, 149.4, 138.7, 137.9, 133.6, 132.3, 131.6,
130.5, 130.4, 130.2, 129.4, 129.2, 129.1, 127.9, 126.5, 122.8, 121.6,
117.5, 116.0, 115.8, 114.8 (CN), 113.7 (CN), 113.6, 99.1, 96.1, 30.9, 21.5,
21.3 ppm; GCeMS m/z (%) 316 (Mþ, 20), 315 (100), 314 (63), 300
(17), 285 (4), 271 (12), 257 (9), 256 (12), 239 (3), 227 (3), 207 (3),
170 (4), 150 (16), 135 (16), 128 (13), 101 (6), 88 (5). Anal. Calcd for
3.3.3. 2-Chloro-6-(4-methoxyphenyl)-5-phenylnicotinonitrile
7c. Pale yellow crystals; yield, 45% (1.44 g, Method A) and 80%
(2.56 g, Method B); mp, 200e202 ꢀC; IR (KBr, ymax)¼2991, 2836,
C
20H16N2O2: C, 75.93; H, 5.10; N, 8.86. Found: C, 75.99; H, 5.13; N,
2215,1599,1553, 709 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
¼7.67e7.50
8.93.
(4H, m, ArH), 7.46 (2H, d, J¼8.4 Hz, ArH), 7.4e7.2 (m, 2H, ArH), 7.01
(2H, d, J¼8.4 Hz, ArH), 3.92 (3H, s, OMe); 13C NMR (400 MHz, CDCl3)
3.2.9. 2-Hydroxy-5-(4-methoxyphenyl)-6-phenylnicotinonitrile
d
¼162.6, 157.1, 152.3, 135.1, 134.8, 132.2, 130.0, 129.7, 129.2, 128.5,
3i. Pale yellow crystals; mp, 204e206 ꢀC; yield¼90% (1.36 g); IR
114.7, 114.4 (CN), 110.1, 83.8, 55.7 ppm; GCeMS m/z (%) 322 ((Mþ2),
15), 320 (Mþ, 45), 305 (2), 294 (11), 285 (100), 270 (20), 253 (5), 242
(48), 227 (7), 214 (26), 189 (7), 165 (12), 158 (9), 139 (7), 121 (6), 113
(5), 93 (6), 88 (6), 77 (15). Anal. Calcd data for C19H13ClN2O: C, 71.14;
H, 4.08; N, 8.73. Found: C, 71.19; H, 4.10; N, 8.78.
(KBr, ymax)¼3479, 3296, 3186, 2212, 1620 cmꢁ1
;
1H NMR
¼3.74 (3H, s, OMe), 3.79 (3H, s, OMe), 5.2 (2H,
(400 MHz, CDCl3)
d
br, NH and OH), 6.72e6.68 (2H, m, ArH), 6.80e6.75 (2H, m, ArH),
6.86e6.83 (2H, m, ArH), 7.01e6.97 (2H, m, ArH), 7.16e7.12 (2H, m,
ArH), 7.34e7.21 (8H, m, ArH), 7.63 (1H, s, pyridine ring hydrogen),
7.72 (1H, s, pyridine hydrogen); 13C NMR (400 MHz, CDCl3)
3.3.4. 2-Chloro-6-(4-bromophenyl)-5-phenylnicotinonitrile 7d. Pale
yellow crystals; yield, 36% (1.33 g, Method A) and 90% (3.33 g,
Method B); mp, 178e180 ꢀC; IR (KBr, ymax)¼3085, 3064, 3028, 2221,
d¼160.2 (CO), 158.8, 157.5, 150.5, 149.2, 144.3, 143.4, 142.0, 139.0,
138.0, 136.6, 131.6, 130.5, 130.5, 130.2, 129.6, 129.5, 128.7, 128.7,
128.3, 128.0, 126.5, 116.7, 115.9, 115.5, 113.9 (CN), 113.6 (CN), 104.2,
99.1, 96.4, 89.8, 77.3, 77.0, 76.7, 67.6, 61.2, 55.2, 30.9 ppm; GCeMS
m/z (%) 302 (Mþ, 20), 301 (100), 300 (60), 287 (3), 286 (13), 285
(5), 270 (8), 214 (8), 143 (14), 128 (23), 89 (4), 76 (4). Anal. Calcd
for C19H14N2O2: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.53; H, 4.73;
N, 9.33; Single crystal data: molecular formula¼C19H14N2O2, space
group¼P21/c, cell lengths¼a, 12.0731(14); b, 14.1000(17); c,
1677, 1583, 703 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
¼7.68 (2H, d,
J¼8.4 Hz, ArH), 7.54e7.52 (3H, m, ArH), 7.49 (1H, s, pyridine ring
hydrogen), 7.37 (2H, d, J¼8.4 Hz, ArH), 7.31e7.28 (2H, m, ArH); 13
C
NMR (400 MHz, CDCl3)
d¼155.8, 150.2, 136.3, 135.0, 134.3, 132.4,
131.4, 130.1, 129.8, 129.3, 126.5, 114.2 (CN), 109.6, 85.6 ppm; GCeMS
m/z (%) 372 ((Mþ4), 15), 370 ((Mþ2), 46), 368 (Mþ, 38), 368 (12),
336 (16), 335 (30), 333 (17), 332 (21), 291 (13), 289 (39), 255 (27),
254 (100), 253 (54), 227 (57), 201 (11),176 (14),175 (7), 151 (13),127
(77), 113 (77), 100 (89), 88 (20), 77 (35). Anal. Calcd data for
9.8157(12), cell angles¼
a, 90.00; b, 108.797(7); g, 90.00; cell vol-
ume¼1581.82, Z, Z0¼Z: 4, Z0: 0, R-factor [%]¼5.91 and CCDC 791271.
C18H10BrClN2: C, 58.49; H, 2.73; N, 7.58. Found: C, 58.50; H, 2.80; N,
3.3. General procedure for the synthesis of 2-chloro-5,6-
7.60.
diarylnicotinonitriles 7aee
3.3.5. 2-Chloro-5-(4-methoxyphenyl)-6-(4-methylphenyl)nicotinoni-
trile7e. Pale yellow crystals; yield, 12% (0.40 g, Method A) and 67%
(2.24 g, Method B); mp, 172e174 ꢀC; IR (KBr, ymax)¼3033, 3003,
The VilsmeiereHaack reagent was prepared by mixing DMF
(12 ml, 150 mmol) and POCl3 (1.4 ml, 15 mmol) at 0 ꢀC, followed by
stirring at room temperature for 15 min. 3-Oxo-2,3-diarylpropanal
(10 mmol) was added and the reaction mixture was stirred at
room temperature for 20 h. Malononitrile (2 g, 30 mmol) or cya-
noacetamide (2.5 g, 30 mmol) was added to this mixture, the
temperature was raised to 70 ꢀC, stirred for another 3 h, and
poured into ice-cold saturated potassium carbonate solution
(120 ml). The crude product was extracted with ethyl acetate
(3ꢂ50 ml). The combined organic layer was distilled off to get the
crude product, which was purified by column chromatography
over silica gel (60e120 mesh) using ethyl acetate/hexane (2:98) as
eluent.
2218, 1608, 1546, 738, 665 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d¼7.56
(1H, s, pyridine ring hydrogen), 7.37 (2H, d, J¼8.4 Hz, ArH), 7.31 (2H,
d, J¼8.4 Hz, ArH), 7.21 (2H, d, J¼8 Hz, ArH), 7.02 (2H, d, J¼8 Hz, ArH),
3.87 (3H, s, OMe), 2.46 (3H, s, eCH3); 13C NMR (400 MHz, CDCl3)
d
¼160.7, 157.6, 152.0, 142.6, 135.2, 133.6, 131.3, 130.1, 129.7, 127.1,
114.6 (CN), 110.2, 84.4, 55.3, 21.6 ppm; GCeMS m/z (%) 336 ((Mþ2),
19), 334 (Mþ,100), 319 (21), 299 (92), 284 (29), 278 (70), 269 (37),
256 (65), 241 (10), 226 (61), 207 (68), 191 (13), 189 (11), 163 (42),
152 (30), 128 (26), 119 (34), 99 (22), 91 (31). Anal. Calcd for
C20H15ClN2O: C, 71.75; H, 4.52; N, 8.37. Found: C, 71.78; H, 4.58; N,
8.41.
3.3.1. 2-Chloro-5,6-diphenylnicotinonitrile 7a. Pale yellow crystals;
yield, 55% (1.60 g, Method A) and 70% (2.04 g, Method B); mp,
168e170 ꢀC; IR (KBr, ymax)¼3045, 3031, 2221, 1566, 1548, 765,
Acknowledgements
K.K.U. is thankful to UGC for providing Junior and Senior re-
search Fellowships (Lett. No. F.17-107/98 (SA-1)) funding for his
research works. We are thankful to SAIF-IIT-Chennai; SAIF-CDRI,
Lucknow; NMR Research Center, IISc, Bangalore, Inter University
Instrumentation Centre (IUIC), Mahatma Gandhi University, and
IIRBS-Mahatma Gandhi University for providing spectral analytical
facilities.
700 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
¼7.60e7.45 (9H, m, ArH),
¼156.4, 152,
7.35e7.28 (2H, m, ArH); 13C NMR (400 MHz, CDCl3)
d
136.2, 136.0, 134.6, 131.7, 130.0, 129.9, 129.9, 129.3, 129.0, 114.4 (CN),
109.8, 84.9 ppm; GCeMS m/z (%) 292 ((Mþ2)þ, 7), 290 (Mþ, 22), 255
(100), 227 (35), 212 (12), 201 (10), 189 (8), 149 (15), 127 (7), 113 (28),
99 (32), 77 (18). Anal. Calcd for C18H11ClN2: C,74.38; H, 3.84; N, 9.68.
Found: C, 74.5; H, 4.1; N, 9.80.
3.3.2. 2-Chloro-6-(4-chlorophenyl)-5-phenylnicotinonitrile 7b. Pale
yellow crystals; yield, 35% (1.14 g, Method A) and 77% (2.50 g,
Method B); mp, 120e122 ꢀC; IR (KBr, ymax)¼3168, 3080, 2219, 1641,
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.07.031.
1554, 1535, 700, 639 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d¼7.95e7.85

6456
K.U. Krishnaraj, K.S. Devaky / Tetrahedron 70 (2014) 6450e6456
Anabha, E. R.; Sasikala, K. A.; Lethesh, K. C.; Krishnaraj, K. U.; Sreedevi, K. N.;
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