Facile synthesis of 2,6-diaryl-4-secondary aminonicotinonitriles and highly substituted unsymmetrical 2,2′-bipyridines

Article abstract of DOI:10.1002/jhet.380

(Chemical Equation Presented) The ring transformation of 2H-pyran-2-one by N-aryl amidine in the presence of KOH in DMF at room temperature resulted in a facile synthesis of the 2,6-diaryl-4-secondary aminonicotinonitrile and highly substituted unsymmetrical 2,2′-bipyridines in moderate yield.

Full text of DOI:10.1002/jhet.380

May 2010
Facile Synthesis of 2,6-Diaryl-4-Secondary Aminonicotinonitriles
and Highly Substituted Unsymmetrical 2,20-Bipyridines
691
Sidhanath V. Bhosale,* Umesh D. Patil, Mohan B. Kalyankar,
Santosh V. Nalage, Vijay S. Patil, and Kamlesh R. Desale
Department of Organic Chemistry, North Maharashtra University, Jalgaon 425001, India
*E-mail: sidhanath2003@yahoo.co.in
Received November 7, 2009
DOI 10.1002/jhet.380
Published online 11 May 2010 in Wiley InterScience (www.interscience.wiley.com).
The ring transformation of 2H-pyran-2-one by N-aryl amidine in the presence of KOH in DMF at
room temperature resulted in a facile synthesis of the 2,6-diaryl-4-secondary aminonicotinonitrile and
highly substituted unsymmetrical 2,20-bipyridines in moderate yield.
J. Heterocyclic Chem., 47, 691 (2010).
INTRODUCTION
of 1,3-dicarbonyl compounds and 3-aminoenones or
nitriles [12]. Saikai et al. reported indium trichloride
catalyzed synthesis of tetrasubstituted pyridines [13].
Penieres et al. have synthesized pyridine by using
microwave irradiated Hantzsch reaction [14]. A transi-
tion metal mediated 6-endo-dig cyclization of N-propar-
gylamine derivative was carried out by Abbiati et al. to
generate a pyridine ring [15]. Combinatorial approach
also has been used for the synthesis of pyridine deriva-
tives [16]. 2,4,6-trisubstituted pyridine derivatives were
prepared from aroylketene dithioacetal by Potts et al.
[17]. Recently, Ram and coworkers [18] have described
the use of 2H-pyran-2-one for the synthesis of substi-
tuted pyridines, prompted us to carry out the synthesis
of novel pyridines.
2H-pyran-2-ones are extensively used for the synthe-
sis of a wide variety of heterocyclic compounds via ring
transformation [1]. Ram and coworkers applied this
strategy for the synthesis of various organic compounds
like pyrimidine, fused heterocycles, congested benzene
[1j], and pyridine [2]. The pyridine ring is one of the
fundamental heterocycle present in many biologically
active natural products. The compounds containing pyri-
dine ring possess a broad range of biological activities
[3]. Kawamura et al. have synthesized 4-substituted 2,6-
diphenyl pyridines and reported there bleaching herbici-
dal activity [3b]. It was also found that 2-(p-aminoben-
zamido) pyridines exhibit a powerful inhibiting effect
on gastric ulcers in rats [3g]. The pyridines 2,20-bi- and
2,20,200-ter-pyridine were used as metal chelating legends
with various substituents [4a]. Similarly, pyridine deriv-
atives are of growing relevance in material science and
supramolecular chemistry [4b]. Therefore, there is a
continuous interest to develop the new synthetic meth-
ods for pyridines and their derivatives. Classical routes
to pyridine preparation are Hantzsch [5], Chichibabin
[6], Petrenko-Kritschenko and Zoneff [7], Krohnke [8],
and Guareschi-Thorpe [9] condensation reactions. The
condensation of 1,5-diketone with ammonia followed by
nitric acid oxidation is a common approach for the syn-
thesis of pyridines [10]. The reaction of dienamine and
ketone in the presence of Vilsmeier type 1-substituted-
1,2,3-benzotriazole reagent results in the formation of
nicotinonitriles [11]. The construction of unsymmetri-
cally substituted pyridines was achieved by the reaction
RESULT AND DISCUSSION
We investigated that compound 3 in moderate yield
can be constructed from 2H-pyran-2-one 1 and the N-
aryl amidine 2 via a ring transformation reaction using
KOH in DMF at room temperature (Scheme 1).
Pyridine 3 isolated in this study could arise by nucle-
ophilic attack of amidine N-1 at C-6 position of 2H-py-
ran-2-one. The intermediate 4 formed is unstable and it
undergoes cyclization with a retro [2 þ 2] process to
yield 3a–i with the loss of carbon dioxide. In the event
of ring transformation of 2H-pyran-2-one 1 (Scheme 2)
with N-aryl amidine 2, the N-1 takes part in the reaction
as a nucleophile rather than N-3. It might be due to the
lone pair electrons on N-3 are delocalized over the
C
V
2010 HeteroCorporation

692
S. V. Bhosale, U. D. Patil, M. B. Kalyankar, S. V. Nalage, V. S. Patil, and K. R. Desale
Vol 47
Scheme 1. Preparation of 2,6-diaryl-4-secondary aminonicotinonitriles
3 from 2H-pyran-2-one 1 and N-aryl amidine 2.
Thus, in both cases (Schemes 1 and 3), the 2,6-diaryl
nicotonitriles were formed exclusively without any side
product.
Finally, we used our strategy to synthesize highly
substituted unsymmetrical 2,2-bipyridines (Scheme 5) in
presence of powdered KOH and DMF at room tempera-
ture. The results show that the yield of obtained bipyri-
dine was moderate (Table 2). We believe that the reac-
tion proceeds with the same mechanistic pathway as
depicted in Scheme 2.
benzene nucleus by orbital overlap with the p-orbital of
the aromatic ring; therefore, they are less available for
nucleophilic attack.
To generalize our strategy, we examined this method
for the reaction of 2H-pyran-2-one 1 with N-heteroaryl
amidine 6 in the presence of KOH/DMF catalytic sys-
tem (Scheme 3). The reaction of 2H-pyran-2-one with
N-heteroaryl amidine furnished the corresponding 2,6-
disubstituted nicotinonitrile 3 in the poor yields (Table
1). The structure of the newly synthesized compounds
was confirmed by spectroscopic data. It was observed
that there is no improvement of yield even after 48 h
also. The plausible mechanistic pathway is shown in
Scheme 4.
CONCLUSIONS
In summary, this study demonstrates that the ring sys-
tem proposed for nicotonitrile is correct with the substi-
tution pattern. An additional finding is that the ring
transformation of 2H-pyran-2-one by N-pyridyl amidine
provides useful information for construction of the nico-
tonitrile ring system with 2,6-diaryl substituent. Further-
more, we synthesized highly substituted unsymmetrical
bipyridine using this method. Further studies on the
applications of this method for the synthesis of nicotoni-
trile with the 2,6-heteryl substituent are underway.
In 2H-pyran-2-one 1, three electrophilic centers are
present C-3, C-4, and C-6, in which C-6 is more electro-
philic in nature due to presence of an electron withdraw-
ing group (ACN) at C-3 position of the ring system.
The synthesis of 2,6-diaryl nicotonitrile involves the
nucleophilic attack by more basic N-1 of amidine 6 at
C-6 of 2H-pyran-2-one. The attack of amidine N-1 leads
to form unstable intermediate 7 followed by ring closure
and a retro [2 þ 2] process with the elimination of car-
bon dioxide to form 2,6-diaryl nicotonitrile 3. It is note-
worthy that the pyridine ring nitrogen of amidine does
not involve in ring transformation reaction. The struc-
tures of compounds 3a–i (Table 2) were determined
based on the spectroscopic data and elemental analysis.
EXPERIMENTAL
General procedures. Melting points were determined in
open capillaries and are uncorrected. Progress of the reaction
was monitored by TLC (visualization was effected by exposure
to UV light). Commercial reagents were used without purifica-
tion. IR spectra were recorded on a Perkin-Elmer Spectrum
One spectrometer. Mass spectra were recorded under ESI
mode, on Thermo Finnigan (model-LCQ Advantage MAX)
mass spectrometer. 1H NMR and 13C NMR were recorded in
CDCl3 on a Bruker Spectrometers, operating at 300 MHz and
75 MHz for 1H NMR and 13C NMR, respectively, and shifts
are given in ppm downfield from TMS as an internal standard.
Scheme 2. The plausible mechanism [18] for the formation of substituted compounds 3.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
Facile Synthesis of 2,6-Diaryl-4-Secondary Aminonicotinonitriles and Highly Substituted
Unsymmetrical 2,20-Bipyridines
693
Scheme 3. Reaction between 2H-pyran-2-one 1 and N-heteroaryl ami-
dine 6 for synthesis of 2,6-disubstituted nicotinonitrile.
ice with vigorous stirring. The aqueous solution was neutral-
ized with 10% HCl, the precipitate obtained was filtered, and
the obtained residue was purified by column chromatography
on silica gel 60–120 by eluting 5% ethyl acetate:hexane.
2,6-Diphenyl-4-(piperidin-1-yl)pyridine-3-carbonitrile
(3a). White solid, IR (KBr): 2209 (CBN), 1568 (C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 1.73 (d, J ¼ 5.7 Hz,
2H, CH2), 1.83 (d, J ¼ 3.3 Hz, 4H, 2CH2), 3.54 (t, J ¼ 9.9
Hz, 4H, 2CH2N), 6.91 (s, 1H, CH), 7.5 (m, 5H, ArH), 7.84 (d,
J ¼ 4.7 Hz, 2H, ArH), 8.05 (t, J ¼ 9.5 Hz, 3H, ArH). 13C
NMR (75 MHz, CDCl3) d ¼ 24.2, 26.1, 52.1, 96.4, 106.7,
118.7, 124.4, 125.3, 127.6, 128.5, 128.9, 129.6, 130.1, 138.9,
159.8, 162.9, 164.2. MS (ESI, 70 eV) m/z (%) ¼ 340 (100)
[Mþ], 341(27) [(MþH)þ]. Anal. Calcd. for C23H21N3: C,
81.38; H, 6.24; N, 12.38. Found: C, 81.42; H, 6.20; N, 12.38.
6-(4-Bromophenyl)-2-phenyl-4-(piperidin-1-yl)pyridine-3-
carbonitrile (3b). White solid, IR (KBr): 2212 (CBN), 1568
Elemental analysis was carried out on Thermo Quest micro-
analysis instrument, Whitehouse, NJ.
General experimental procedure for the synthesis of 3a–
l. The mixture of 2H-pyran-2-one-3-carbonitrile (1.0 mmol),
N-phenyl/heteroaryl benzamidine (1.0 mmol) and powdered
KOH (2.0 mmol) in 5 mL DMF was stirred for 5–6 h at room
temperature. The reaction was monitored by TLC. After com-
pletion of the reaction, excess DMF was removed under
reduced pressure. Then the residue was poured into crushed
1
(C¼¼N) cmꢀ1. H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 1.72 (d,
2H, CH2), 1.8 (d, J ¼ 5 Hz, 4H, 2CH2), 3.54 (t, J ¼ 10.6 Hz,
4H, 2CH2N), 7.12 (s, 1H, CH), 7.51 (m, 3H, ArH), 7.59 (s,
Scheme 4. The plausible mechanism [18] for the formation of substituted 2,6-disubstituted nicotinonitrile.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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S. V. Bhosale, U. D. Patil, M. B. Kalyankar, S. V. Nalage, V. S. Patil, and K. R. Desale
Vol 47
Table 1
Preparation of 2,6-diaryl-4-secondary aminonicotinonitriles 3a from 2H-pyran-2-one 1 and N-aryl amidine 2b.
Entry
Ar
Ar0
Ar00
Yieldsc (%)
m.p.
3a
3a
3b
3b
3c
3c
3d
C6H5
C6H5
Piperidine
Piperidine
Piperidine
Piperidine
Morpholine
Morpholine
Morpholine
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-F-C6H4
C6H5
C6H5
4-F-C6H4
4-F-C6H4
C6H5
48%
48%
48%
42%
46%
44%
39%
160ꢁC
161ꢁC
173ꢁC
173ꢁC
172ꢁC
172ꢁC
198ꢁC
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Cl-C6H4
4-F-C6H4
a All products were characterized by using I.R., 1H, 13C NMR, mass spectroscopy, and elemental analysis.
b 2H-pyran-2-one 1 (1.0 mmol), N-aryl amidine 2 (1.0 mmol), KOH (2.0 mmol), and DMF (5 mL), room temperature.
c Isolated yield.
1H, ArH), 7.62 (s, 1H, ArH), 7.93 (m, 4H, ArH). 13C NMR
(75 MHz, CDCl3) d ¼ 24.2, 26.1, 52.0, 96.8, 106.4, 118.6,
124.7, 128.6, 129.2, 129.6, 130.1, 132.1, 137.7, 138.7, 158.5,
162.9, 163.9. MS (ESI, 70 eV) m/z (%) ¼ 418 (100) [Mþ],
420 (92) [(Mþ2H)þ]. Anal. Calcd. for C23H20BrN3: C, 66.04;
H, 4.82; N, 10.04. Found: C, 66.01; H, 4.77; N, 10.08.
J ¼ 14.1 Hz, 4H, 2CH2N), 3.94 (q, J ¼ 13.9 Hz, 4H, 2CH2O),
7.14 (s, 1H, CH), 7.51 (m, 5H, ArH), 7.89 (m, 2H, ArH), 8.00
(s, 1H, ArH), 8.04 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3)
d ¼ 50.9, 66.8, 97.2, 106.3, 118.2, 128.6, 128.9, 129.3, 129.5,
130.3, 136.7, 136.9, 138.3, 159.0, 162.7, 164.2. MS (ESI, 70
eV) m/z (%): 376 (100) [Mþ], 378 (33) [(Mþ2H)þ]. Anal.
Calcd. for C22H18ClN3O: C, 70.30; H, 4.83; N, 11.18. Found:
C, 70.34; H, 4.94; N, 11.23.
6-(4-Bromophenyl)-4-(morpholin-4-yl)-2-phenylpyridine-3-
carbonitrile (3c). White solid, IR (KBr): 2210 (CBN), 1582
1
(C¼¼N) cmꢀ1. H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 3.55 (q,
2,6-Bis(4-bromophenyl)-4-(piperidin-1-yl)pyridine-3-car-
bonitrile (3e). White solid, IR (KBr): 2214 (CBN), 1580
J ¼ 13.5 Hz, 4H, 2CH2N), 3.94 (q, J ¼ 14 Hz, 4H, 2CH2O),
6.73 (s, 1H, CH), 7.51 (q, J ¼ 9.9 Hz, 3H, ArH), 7.59 (s, 1H,
ArH), 7.63 (s, 1H, ArH), 7.92 (m, 3H, ArH), 7.97 (s, 1H,
ArH). 13C NMR (75 MHz, CDCl3) d ¼ 50.9, 66.8, 97.3,
106.3, 118.2, 125.1, 128.6, 129.2, 129.5, 130.3, 132.2, 137.3,
138.3, 159.1, 162.6, 164.2. MS (ESI, 70 eV) m/z (%) ¼ 420
(28%) [Mþ], 422 (12%) [(Mþ2H)þ], 393 (8). Anal. Calcd. for
C22H18BrN3O: C, 62.87; H, 4.32; N, 10.00. Found: C, 62.82;
H, 4.37; N, 10.11.
(C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 1.79
(m, 6H, 3CH2), 3.53 (t, J ¼ 15 Hz, 4H, 2CH2N), 7.12 (s, 1H,
CH), 7.62 (m, 4H, ArH), 7.77 (d, J ¼ 4.7 Hz, 1H, ArH), 7.81
(d, J ¼ 3 Hz, 1H, ArH), 7.89 (d, J ¼ 3 Hz, 1H, ArH), 7.93 (s,
1H, ArH). MS (ESI, 70 eV) m/z (%) ¼ 497.8 (25) [Mþ], 499
(12) [(Mþ2H)þ]. Anal. Calcd. for C23H19Br2N3: C, 55.56; H,
3.85; N, 8.45. Found: C, 55.59; H, 3.81; N, 8.48.
6-(4-Chlorophenyl)-2-phenyl-4-(piperidin-1-yl)pyridine-3-
carbonitrile (3f). White solid, IR (KBr): 2214 (CBN), 1568
6-(4-Chlorophenyl)-4-(morpholin-4-yl)-2-phenylpyridine-3-
carbonitrile (3d). White solid, IR (KBr): 2216 (CBN), 1583
1
(C¼¼N) cmꢀ1. H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 1.73 (d,
1
(C¼¼N) cmꢀ1. H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 3.54 (q,
J ¼ 532 Hz, 2H, CH2), 1.82 (d, J ¼ 5.0 Hz, 4H, 2CH2), 3.55
Table 2
Reaction conditions with yields and m.p. for productsa 3.
Entry
Ar
Ar0
R
Yieldsb (%)
m.p.
3a
3b
3c
3d
3e
3f
3g
3g
3h
3i
C6H5
Piperidine
Piperidine
Morpholine
Morpholine
Piperidine
Piperidine
Pyrolidine
Pyrolidine
Piperidine
Pyrolidine
C6H5
C6H5
C6H5
H
H
13%
26%
24%
24%
22%
16%
19%
22%
38%
44%
160ꢁC
173ꢁC
172ꢁC
198ꢁC
168ꢁC
172ꢁC
156ꢁC
156ꢁC
166ꢁC
122ꢁC
4-Br-C6H4
4-Br-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-CH3O-C6H4
4-Cl-C6H4
H
C6H5
H
H
4-Br-C6H4
C6H5
C6H5
H
H
C6H5
C6H5
4-Br-C6H4
4-Br
H
H
a All products were characterized by using I.R., 1H, 13C NMR, mass spectroscopy, and elemental analysis.
b Isolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
Facile Synthesis of 2,6-Diaryl-4-Secondary Aminonicotinonitriles and Highly Substituted
Unsymmetrical 2,20-Bipyridines
695
Table 3
Reaction conditions with yields and m.p. for productsa 3.
Entry
Ar
Ar00
Yieldsb (%)
m.p.
3j
3k
3l
4-Br-C6H4
4-Cl-C6H4
C6H5
Pyrolidine
Morpholine
Morpholine
4-Br-C6H4
4-Br-C6H4
3,4-Cl-C6H3
43%
48%
52%
206–208ꢁC
164–166ꢁC
152–154ꢁC
a All products were characterized by using I.R., 1H, 13C NMR, mass spectroscopy, and elemental analysis.
b Isolated yield.
(t, J ¼ 10.6 Hz, 4H, 2CH2N), 7.13 (s, 1H, CH), 7.44 (m, 5H,
ArH), 7.93 (q, J ¼ 9.68 Hz, 2H, ArH), 8.00 (s, 1H, ArH), 8.03
(s, 1H, ArH). MS (ESI, 70 eV) m/z (%) ¼ 374 (100) [Mþ],
376 (35) [(MþH)þ]. Anal. Calcd. for C23H20ClN3: C, 73.89;
H, 5.39; N, 11.24. Found: C, 73.97; H, 5.35; N, 11.36.
6-(4-Chlorophenyl)-2-phenyl-4-(pyrrolidin-1-yl)pyridine-3-
carbonitrile (3g). White solid, IR (KBr): 2199 (CBN), 1590
[(Mþ2H)þ, 55%]. Anal. Calcd. for C22H17BrClN3: C 60.22; H
3.91; N 9.58. Found: C, 60.42; H, 3.83; N, 9.42.
6-(4-Bromophenyl)-2-(pyridine-2-yl)-4-(pyrrolidin-1-yl)pyri-
dine-3-carbonitrile (3j). Yellowish red solid, IR (KBr): 2190
(CBN), 1566 (C¼¼N) cmꢀ1. 1H NMR (300 MHz, CDCl3, 25ꢁC)
d ¼ 2.07 (bs, 4H, CH2), 3.82 (bs, 4H, 2NCH2), 6.91 (s, 1H,
CH), 7.39 (s, 1H, ArH), 7.59 (s, 2H, ArH), 7.91 (bs, 3H, ArH),
8.02 (bs, 1H, ArH), 8.77 (bs, 1H, ArH). 13C NMR (125 MHz,
CDCl3) d ¼ 25.7, 50.4, 94.4, 103.9, 116.4, 123.9, 124.3, 128.8,
131.8, 136.7, 137.6, 146.7, 148.7, 158.3. MS (ESI, 70 eV) m/z
(%) ¼ 405 (100) [Mþ]. Anal. Calcd. for C21H17BrN4: C, 62.23;
H, 4.23; N, 13.82. Found: C, 62.43; H, 4.364; N, 13.87.
(C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25ꢁC) d 2.09 (m,
4H, 2CH2), 3.81 (t, J ¼ 13.2 Hz, 4H, 2CH2N), 6.85 (s, 1H,
CH), 7.48 (m, 5H, ArH), 7.86 (q, J ¼ 9.6 Hz, 2H, ArH), 7.98
(d, J ¼ 8.66 Hz, 2H, ArH). 13C NMR (75 MHz, CDCl3) d ¼
25.9, 50.5, 96.1, 106.5, 118.6, 128.4, 128.6, 129.0, 129.6,
129.8, 135.9, 137.5, 139.3, 158.6, 162.8, 163.1. MS (ESI, 70
eV) m/z (%) ¼ 360 (100) [Mþ], 362 (32) [(Mþ2H)þ]. Anal.
Calcd. for C22H18ClN3: C, 73.43; H, 5.04; N, 11.68. Found: C,
73.42; H, 5.04; N, 11.03.
6-(4-Chlorophenyl)-4-morpholino-2-(pyridine-2-yl)pyridine-
3-carbonitrile (3k). Yellowish red solid, IR (KBr): 2225 (CBN),
1566 (C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25ꢁC) d ¼
3.55–3.58 (t, 4H, 2NCH2), 3.94–3.97 (t, 4H, 2OCH2), 7.21 (s, 1H,
CH), 7.41–7.49 (m, 3H, ArH), 7.85–7.91 (m, 1H, ArH), 8.02–8.05
(q, 2H, ArH), 8.17–8.19 (d, J ¼ 7.8 Hz, 1H, ArH), 8.78–8.79 (dd,
1H, ArH). 13C NMR (125 MHz, CDCl3) d ¼ 50.8, 66.6, 97.4,
107.3, 117.5, 123.7, 124.8, 128.8, 129.2, 136.7, 148.8, 155.4,
158.3, 162.8. MS (ESI, 70 eV) m/z (%) ¼ 377 [Mþ, 100%], 379
[(Mþ2H)þ, 35%]. Anal. Calcd. for C21H17ClN4O: C, 66.93; H,
4.55; N, 14.87. Found: C, 66.83; H, 4.64; N, 14.94.
6-(4-Methoxyphenyl)-2-phenyl-4-(piperidin-1-yl)pyridine-3-
carbonitrile (3h). White solid, IR (KBr): 2209 (CBN), 1607
1
(C¼¼N) cmꢀ1. H NMR (300 MHz, CDCl3, 25ꢁC) d ¼ 1.72 (d,
J ¼ 5.1 Hz, 2H, CH2), 1.83 (d, J ¼ 4.6 Hz, 4H, 2CH2), 3.52
(t, J ¼ 10.5 Hz, 4H, 2CH2N), 3.88 (s, 3H, CH3O), 6.98 (s, 1H,
CH), 7.01 (s, 1H, ArH), 7.12 (s, 1H, ArH), 7.50 (m, 3H, ArH),
7.94 (q, J ¼ 9.6 Hz, 2H, ArH), 8.04 (s, 1H, ArH), 8.06 (s, 1H,
ArH). 13C NMR (75 MHz, CDCl3) d ¼ 24.3, 25.1, 52.1, 55.6,
95.9, 105.7, 114.3, 124.7, 124.9, 129.1, 131.2, 131.8, 131.8,
132.2, 137.5, 159.4, 161.5, 163.0. MS (ESI, 70 eV) m/z (%) ¼
370 (100) [Mþ], 371 (32) [(Mþ2H)þ]. Anal. Calcd. for
C24H23N3O: C, 78.02; H, 6.27; N, 11.37. Found: C, 78.06; H,
6.29; N, 11.34.
4-Morpholino-6-phenyl-2-(pyridin-2-yl)pyridine-3-carboni-
trile (3l). Yellowish red solid, IR (KBr): 2215 (CBN), 1574,
1538 (C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25ꢁC) d ¼
3.55–3.58 (t, 4H, 2NCH2), 3.94–3.97 (t, 4H, 2OCH2), 7.25 (s,
1H, CH), 7.40–7.51 (m, 4H, ArH), 7.85–7.91 (m, 1H, ArH),
8.07–8.09 (t, 2H, ArH), 8.20–8.23 (d, J ¼ 7.8 Hz, 1H, ArH),
8.77–8.79 (d, J ¼ 4.2 Hz, 1H, ArH). 13C NMR (125 MHz,
CDCl3) d ¼ 50.7, 66.6, 97.3, 107.5, 117.6, 123.7, 124.7,
127.4, 128.8, 130.2, 136.8, 138.1, 148.6, 155.5, 159.5, 161.3,
162.7, 165.3. MS (ESI, 70 eV) m/z (%) ¼ 343 [(MþH)þ,
78%]. Anal. Calcd. for C21H18N4O: C, 73.67; H, 5.30; N,
16.36. Found: C, 73.88; H, 5.42; N, 16.44.
2-(4-Bromophenyl)-6-(4-chlorophenyl)-4-(pyrrolidin-1-yl)
pyridine-3-carbonitrile (3i). White solid, IR (KBr): 2115
(CBN), 1590 (C¼¼N) cmꢀ1
.
1H NMR (300 MHz, CDCl3,
25ꢁC) d ¼ 2.08 (brs, 4H), 3.79 (brs, 4H), 6.84 (s, 1H), 7.43 (s,
2H), 7.63 (s, 2H), 7.73 (s, 2H), 7.96 (s, 2H). 13C NMR (75
MHz, CDCl3) d ¼ 25.2, 50.1, 88.5, 103.6, 119.5, 123.2, 128.6,
128.9, 131.1, 131.3, 134.3, 134.6, 136.7, 138.1, 155.1, 155.4,
162.7. MS (ESI, 70 eV) m/z (%) ¼ 438 [Mþ, 43%], 440
Acknowledgments. The authors thank Dr. K. B. Patil, Vice-
chancellor, North Maharashtra University, Jalgaon (India) for
providing necessary facilities. S. V. B. thank DST, New Delhi
(India) for financial assistance under Fast Track Young Scientist
Program (SR/FTP/CS-82/2007).
Scheme 5. Synthesis of highly substituted unsymmetrical bipyridine.
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