Novel synthesis of some new fluoerescent 2-amino-3-cyanopyridines

Article abstract of DOI:10.3987/COM-12-12566

Novel synthesis of some new fluorescent 2-amino-3-cyanopyridines 2a-m in the presence of N-hydroxybenzamide or p-toluenesulfonic acid is described. Photophysical data including λ_Abs. and λ_Flu. of 2a-m in CH₂Cl₂,

Full text of DOI:10.3987/COM-12-12566

HETEROCYCLES, Vol. 85, No. 11, 2012
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HETEROCYCLES, Vol. 85, No. 11, 2012, pp. 2713 - 2721. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 7th August, 2012, Accepted, 12th September, 2012, Published online, 20th September, 2012
DOI: 10.3987/COM-12-12566
NOVEL SYNTHESIS OF SOME NEW FLUOERESCENT 2-AMINO-3-
CYANOPYRIDINES
Afsaneh Zonouzi,*a Zakieh Izakian,a and Seik Weng Ngb
aSchool of Chemistry, University College of Science, University of Tehran,
Tehran, Iran, E-mail: zonouzi@khayam.ut.ac.ir
bDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
Abstract – Novel synthesis of some new fluorescent 2-amino-3-cyanopyridines
2a-m in the presence of N-hydroxybenzamide or p-toluenesulfonic acid is
described. Photophysical data including λAbs. and λFlu. of 2a-m in CH2Cl2, MeCN
and MeOH have been measured.
INTRODUCTION
Aminopyridine derivatives have attracted more attention due to their biological activities, such as
cardioprotective,1 antibacterial,2 antioxidant,3 anti-inflammatory4 and anti-HIV-1.5 For example
sulfapyridine which contains 2-aminopyridine moiety is an old marked antibacterial drug. Synthesis of
aminopyridine derivatives with cyano substitution is rather new. In 2005 Shi and coworkers have reported
the synthesis of 2-amino-3-cyanopyridine derivatives using one-pot reaction of aromatic aldehydes,
ketones and malononitrile in ammonium acetate under microwave irradiation.6 In 2009 Sarda and
coworkers have reported 2-amino-4,6-diphenylpyridine-3-carbonitrile through condensation of chalcones
with malononitrile and ammonium acetate by ionic liquid ethylammonium nitrate as a catalyst.7 In 2011,
Tang and coworkers have used ytterbium perfluoroacetate as catalyst for the synthesis of similar 2-amino-
4,6-diaryl-3-cyanopyridines in a similar manner.8 Synthesis of heteroaromatic rings contain amino
substitution is still desired9 and in continuation of our quest for developing one-pot synthetic procedure
for heterocyclic frameworks,10-13 herein we wish to report the one-pot condensation of 2,4-pentanedione
(acetylacetone), malononitrile and some different amines in acidic media at room temperature. In this
procedure non hydrated p-toluenesulfonic acid (P-TSA) and N-hydroxybenzamide (N-HB) applied as
catalysts and new compounds 2a-m produced in fairly high yields (Scheme 1).

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HETEROCYCLES, Vol. 85, No. 11, 2012
CN
O
O
acid
RR'NH
NC
CN
R
rt
N
N
CH2Cl2
1
2
R'
acid= N-HB or P-TSA
Scheme 1
RESULTS AND DISCUSSION
In this procedure primary and secondary amines, benzyl- and phenylethylamine, cyclic amines such as
pyrrolidine, piperidine and morpholine also ethanolamine can be used. These amines could reacted a little
different. In the similar condition, primary amines reacted faster (5-8 h), secondary amines reacted
relatively slower (8-9 h) and cyclic amines reacted even slower (9-12 h). Ethanolamine reacted more
slowly (15 h) probably as a result of hydroxyl group (Table 1). It has been already reported which P-TSA
and N-HB can work as Brønsted acid.14 Using N-hydroxybenzamide in CH2Cl2 catalyzed this reaction
more efficient (shorter times and more yields). P-TSA in CH2Cl2 on the other hand was not as well as the
other one. The results are compared in Table 1.
Table 1. Reaction times and yields of 2a-m using P-TSA or N-HB as catalyst in CH2Cl2
Comp.2
R
R΄
Time (h)
Yield *(%)
MP
(˚C)
(P-TSA)
(N-HB)
(P-TSA)
(N-HB)
A
B
C
D
E
F
G
H
i
j
k
l
Me
Et
n-Pr
i-Pr
n-Bu
i-Bu
(CH2)2OH
PhCH2
Ph(CH2)2
Me
H
H
H
H
H
H
H
H
H
12
14
12
15
14
14
28
12
15
24
24
28
26
7
7
6
7
6
8
15
5
5
9
55
50
60
55
45
60
40
65
56
47
50
42
60
90
85
80
80
76
70
54
87
85
75
70
60
65
126
99
69
68
65
74
75
138
106
48
Me
piperidino
pyrrolidino
morpholino
8
12
9
46
-
100
m
* The isolated yields
1
13
Structures 2a-m were assigned on the basis of their elemental analysis, IR, H, C NMR, and mass
spectral data. The mass spectra of these compounds displayed molecular ion peaks at the appropriate m/z
values. IR spectra of compounds 2a-m have shown a single sharp band at 2198-2215 cm-1 for C≡N group.
The 1H, 13C NMR spectra of 2a-m displayed resonances in agreement with their structure. In the1H NMR
of compounds 2a-i there are single N-H absorption at δ 5.03-5.58 ppm and for all of compounds there is a

HETEROCYCLES, Vol. 85, No. 11, 2012
2715
distinguished single peak at δ 6.34-6.60 ppm for aromatic C-H protons (Experimental Section). Single
crystals of 2h were obtained from a mixture of EtOAc and n-hexane and its X-ray crystal structure was
performed to confirm unambiguously the proposed structure.15 X-Ray crystal analysis have shown a
monoclinic crystal structure with space group= p 21/c, R=0.635, wR2=0.1760 and Z=4 for compound 2h.
Other crystallographic data can be obtained as supplementary publication No. CCDC 891215 (Figure 1).
Figure 1. X-Ray crystal structure of 2h
A possible mechanism for the formation of products 2 is shown in Scheme 2. Acetylacetone and
malononitrile were initially condensed to produce adduct 3. Nucleophilic addition of amine to one of the
CN groups of 3, cyclization followed by elimination of H2O in acidic media converted intermediate 3 to
the final product 2 through the cyclic structure 4. Adduct 3 could be recognized as an intermediate in IR
spectra of reaction mixture. Two sharp absorptions for CN groups (2054-2209 cm-1) and a sharp
absorption for carbonyl group (1738-1740 cm-1) in the IR spectra of reaction mixture were evidences for
3 which were good for monitoring the progress of reactions. So, in the last stage of reactions the CO and
one of the CN absorptions were highly decreased and in the IR spectra of final products only one of the
CN absorptions (2198-2209 cm-1) remained. Our attempt to isolate 3 was not successful. It seems that
stability gained from aromatization led to rapid transformation of intermediate 3 to final product.
CN
O
O
rt
NC
CN
RR' NH
C
N
O
3
CN
CN
CN
H+
NRR'
NRR'
C
NRR'
NH
- H2O
N
O
NH
HO
2
4
Scheme 2

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HETEROCYCLES, Vol. 85, No. 11, 2012
Optoelectronic devices such as optical fiber switchers, tunable lasers and amplifiers, modulators with
various applications need compounds emitting in blue spectral region,16-18 there are some reports on using
the fluorescent compounds in biochemical and medical research.19 On the other hand 2-aminopyridine has
already being used as one of the fluorescence quantum yield standards,20 so developing a procedure for
the synthesis of thermally stable, highly fluorescent materials emitting in blue spectral region can be
urgently interesting for technology upgrading and biochemical researches. Figure 2 shows photograph of
compound 2e solutions to represent the fluorescence features of the synthesized compounds.
Figure 2. Photograph of 2e solutions in dichloromethane, acetonitrile and methanol under lamp λ=366 nm
The photophysical data of compounds 2a-m including λAbs. (nm) and λFlu. (nm) have been measured for
2×10-5 M solution in CH2Cl2, MeCN and MeOH. The maximum absorption and emission wavelengths of
2a-m in different solvents have been in the range of 285-300 nm and 366-413 nm respectively. The
results are shown in Table 2.
Table 2. The photophysical data: electronic absorption (Abs.) and fluorescence (Flu.) of 2a-m
Comp.
λAbs.(nm)
(CH2Cl2)
292
λFlu.(nm)
. (CH2Cl2)
371
λAbs.(nm)
(CH3CN)
291
λFlu.(nm)
(CH3CN)
377
λAbs.(nm)
(CH3OH)
295
λFlu.(nm)
(CH3OH)
381
2a
2b
2c
2d
2e
2f
295
290
295
290
393
373
373
371
295
295
290
300
400
380
373
376
292
295
295
295
380
382
378
384
285
370
295
375
295
380
2g
2h
2i
285
290
293
371
366
368
287
290
295
375
374
376
285
293
293
385
380
383
2j
294
389
295
396
294
402
2k
2l
293
285
390
413
295
285
393
402
289
285
398
398
2m
293
388
290
405
293
403

HETEROCYCLES, Vol. 85, No. 11, 2012
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CONCLUSION
In summary, we have reported the novel acid catalyzed condensation of acetylacetone, malononitrile and
different amines by a one-pot multi component reaction. Fluorescent 2-amino-3-cyanopyridine
derivatives 2a-m are synthesized in fairly high yields. High atom economy, easy procedure and high
yields are the other advantages of this method. Photophysical data of compounds 2a-m including λAbs. and
λFlu. in CH2Cl2, MeCN and MeOH are measured. Further investigation of this method is currently in
progress to establish its scope and utility.
EXPERIMENTAL
Chemicals and solvents were obtained from Merck (Germany) and Fluka (Switzerland). Melting points
were measured on Barnstead Electrothermal melting point apparatus and are not corrected. Elemental
analyses for C, H and N were performed using a Thermo Finnigan Flash EA1112 instrument. IR spectra
1
13
were measured on a Bruker EQUINOX 55 spectrophotometer as ATR method. H NMR and C NMR
spectra were determined on a Bruker at 500 MHz and 128 MHz. Mass spectra were recorded on a
Finnigan-MAT 8430 spectrometer at an ionization potential of 70 ev. All fluorescence intensity
measurements were made with a Carry Eclipse Fluorescence spectrophotometer. The photo is taken under
lamp λ=366 nm TL8W/08F8T5/BLC Philips made in Holland.
General procedure for the synthesis of compounds 2
To a stirred mixture of acetylacetone (2 mmol, 0.2 mL), malononitrile (2 mmol, 0.132 g), amine 1 (2
mmol) in CH2Cl2 (5 mL) was added N-hydroxybenzamide (50 mol %, 0.137 g) or p-toluenesulfonic acid
(50 mol%, 0.172 g). The solution was stirred at room temperature for 5-15 h for N-hydroxybenzamide or
12-28 h for p-toluenesulfonic acid. The reaction was monitored by IR. When one of the CN and the CO
absorptions were disappeared the solvent was removed under reduced pressure and the product was
purified using column chromatography (silica gel, EtOAc/n-hexane: 1/4). The colorless crystals of
product (except 2i) were obtained by recrystalization from EtOAc.
4,6-Dimethyl-2-(methylamino)pyridine-3-carbonitrile (2a):
1
Colorless crystals; mp 126 °C; νmax (KBr) 3384 (N-H), 2204 (C≡N), 1570, 1517, 1467 (C-N) cm-1; H
NMR (CDCl3, 500 MHz): δH 2.36, 2.40 (6H, 2s, 2CH3), 3.06 (3H, d, J=4.86 Hz, CH3), 5.15 (1H, br s,
13
NH), 6.35 (1H, s, C-H of pyridine) ppm. C NMR (CDCl3, 125 MHz): δH 20.57, 25.36 (2CH3), 28.71
(CH3-N), 89.38 (C≡N), 113.51 (C-H of pyridine), 117.37, 152.62, 159.73, 162.15 (pyridine carbons)
ppm; MS: m/z: 161 (M+), 131 (M+- CH3NH), 104 (C7H7N+), 90 (C6H4N+); Anal. Calcd for C9H11N3: C,
67.06; H, 6.88; N, 26.07. Found: C, 67.12; H, 6.84; N, 26.12.
2-(Ethylamino)-4,6-dimethylpyridine-3-carbonitrile (2b):
1
Colorless crystals; mp 99 °C; νmax (KBr) 3360 (N-H), 2207 (C≡N), 1571, 1528 (C-N) cm-1; H NMR

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HETEROCYCLES, Vol. 85, No. 11, 2012
(CDCl3, 500 MHz): δH 1.26 (3H, t, J=7.2 Hz, CH3), 2.35, 2.38 (6H, 2s, 2CH3), 3.51 (2H, q of d, J=14.18
Hz, 5.62 Hz, CH2), 5.03 (1H, br s, NH), 6.34 (1H, s, C-H of pyridine) ppm. 13C NMR (CDCl3, 125 MHz):
δC 15.34 (CH3 of Et), 20.58, 25.37 (2CH3), 36.64 (CH2), 89.17 (C≡N), 113.46 (C-H of pyridine), 117.39,
152.60, 159.13, 162.15 (pyridine carbons) ppm; MS: m/z: 175 (M+), 160 (M+-CH3), 146 (M+-C2H5), 131
(M+-C2H5N), 57 (C3H7N+); Anal. Calcd for C10H13N3: C, 68.54; H, 7.48; N, 23.98. Found: C, 68.50; H,
7.51; N, 23.99.
4,6-Dimethyl-2-(propylamino)pyridine-3-carbonitrile (2c):
1
Colorless crystals; mp 69 °C; νmax (KBr) 3375 (N-H), 2209 (C≡N), 1568, 1524 (C-N), cm-1; H NMR
(CDCl3, 500 MHz): δH 1.00 (3H, t, J=7.45 Hz, CH3), 1.63-1.71 (2H, m, CH2), 2.37, 2.40 (6H, 2s, 2CH3),
3.47-3.51 (2H, d of t, J=14.17 Hz, J=5.57 Hz, CH2-N), 5.07 (1H, br s, NH), 6.35 (1H, s, C-H of pyridine)
13
ppm. C NMR (CDCl3, 125 MHz): δC 11.84 (CH3 of propyl.), 20.61, 25.40 (2CH3 of pyridine), 23.27
(CH2), 43.55 (CH2-N), 89.15 (C≡N), 113.46 (C-H of pyridine), 117.44, 152.63, 159.28, 162.18 (pyridine
carbons) ppm; MS: m/z: 189 (M+), 174 (M+-CH3), 160 (M+-C2H5), 132 (M+-C3H7N), 106 (M+-C4H7N2),
91 (C6H5N+), 57; Anal. Calcd for C11H15N3: C, 69.81; H, 7.99; N, 22.20. Found: C, 69.78; H, 7.94; N,
22.25.
2-(Isopropylamino)-4,6-dimethylpyridine-3-carbonitrile (2d):
1
Colorless crystals; mp 68 °C, νmax (KBr) 3356 (N-H), 2207 (C≡N), 1585, 1525 (C-N) cm-1; H NMR
(CDCl3, 500 MHz): δH 1.23-1.32 (6H, q of d, J=22.42 Hz, J=5.57 Hz, 2CH3 of i-propyl), 2.36, 2.40 (6H,
13
2s, 2CH3), 4.35-4.42 (1H, m, CH), 4.85 (1H, br s, NH), 6.34 (1H, s, C-H of pyridine) ppm. C NMR
(CDCl3, 125 MHz): δC 20.63, 25.43 (2CH3 of pyridine), 23.32 (2CH3 of i-propyl), 43.14 (CH), 89.11
(C≡N), 113.30 (C-H of pyridine), 117.48, 152.63, 158.59, 162.20 (pyridine carbons) ppm; MS: m/z: 189
(M+), 174 (M+-CH3), 132 (M+-C3H7N), 91 (C6H5N+), 57, 43; Anal. Calcd for C11H15N3: C, 69.81; H,
7.99; N, 22.20. Found: C, 69.77; H, 7.97; N, 22.26.
2-(Butylamino)-4,6-dimethylpyridine-3-carbonitrile (2e):
1
Colorless crystals; mp 65 °C; νmax (KBr) 3362 (N-H), 2208 (C≡N), 1570, 1525 (C-N), cm-1; H NMR
(CDCl3, 500 MHz): δH 0.98 (3H, t, J=7.36 Hz, CH3 of butyl), 1.40-1.48 (2H, m, CH2 of butyl), 1.60-1.65
(2H, m, CH2 of butyl), 2.36, 2.43 (6H, 2s, 2CH3), 3.50-3.54 (2H, d of t, J=14.10 Hz, J=5.59 Hz, CH2-N),
13
5.04 (1H, br s, NH), 6.34 (1H, s, C-H of pyridine) ppm. C NMR (CDCl3, 125 MHz): δC 14.25 (CH3),
20.49 (CH2), 20.59, 25.39 (2CH3 of pyridine), 32.17 (CH2), 41.48 (CH2-N), 89.12 (C≡N), 113.41 (C-H of
pyridine), 117.42, 152.60, 159.27, 162.16 (pyridine carbons) ppm; MS: m/z: 203 (M+), 188 (M+-CH3),
174 (M+-C2H5), 131 (M+-C4H10N), 91 (C6H5N+), 57, 43; Anal. Calcd for C12H17N3: C, 70.90; H, 8.43; N,
20.67. Found: C, 70.86; H, 8.42; N, 20.70.
2-(Isobutylamino)-4,6-dimethylpyridine-3-carbonitrile (2f):
1
Colorless crystals; mp 74 °C; νmax (KBr) 3369 (N-H), 2208 (C≡N), 1574, 1535 (C-N), cm-1; H NMR

HETEROCYCLES, Vol. 85, No. 11, 2012
2719
(CDCl3, 500 MHz): δH 1.00, 1.02 (6H, 2d, J=1.64 Hz, 2CH3), 1.90-1.95 (1H, m, CH), 2.36, 2.39 (6H, 2s,
2CH3), 3.34-3.37 (2H, m, CH2), 5.12 (1H, br s, NH), 6.34 (1H, s, C-H of pyridine) ppm. 13C NMR
(CDCl3, 125 MHz): δC 20.59, 25.39 (2CH3 of pyridine), 20.62 (2CH3 of i-butyl), 28.84 (CH2), 49.15 (CH-
N), 89.10 (C≡N), 113.43 (C-H of pyridine), 117.42, 152.60, 159.40, 162.13 (pyridine carbons) ppm; MS:
m/z: 203 (M+), 188 (M+-CH3), 160 (M+-C3H7), 131 (M+-C4H10N), 105 (M+-C5H10N2), 57, 43; Anal. Calcd
for C12H17N3: C, 70.90; H, 8.43; N, 20.67. Found: C, 70.93; H, 8.47; N, 20.71.
2-(2-Hydroxyethylamino)-4,6-dimethylpyridine-3-carbonitrile (2g):
Colorless crystals; mp 75 °C; νmax (KBr) 3356 (N-H), 3465-3265 (O-H), 2209 (C≡N), 1568, 1536 (C-N),
1
1243 (C-O) cm-1; H NMR (CDCl3, 500 MHz): δH 2.41-2.45 (6H, 2s, 2CH3), 3.68-3.71 (2H, d of t,
J=9.38 Hz, J=5.42 Hz, CH2-NH), 3.84-3.86 (2H, t, J=4.69 Hz, CH2-OH), 4.75 (1H, br s, OH), 5.58 (1H,
br s, NH), 6.44 (1H, s, C-H of pyridine) ppm. 13C NMR (CDCl3, 125 MHz): δC 20.74, 24.92 (2CH3),
45.84 (CH2-NH), 64.62 (CH2-OH), 90.18 (C≡N), 114.40 (C-H of pyridine), 116.82, 153.70, 159.58,
161.49 (pyridine carbons) ppm; MS: m/z: 190 (M+-1), 173 (M+-H2O), 141 (M+-H2O, C2H4N+), 131 (M+-
C2H6NO), 103 (M+-C3H6N2O), 91 (C6H5N+); Anal. Calcd for C10H13N3O: C, 62.81; H, 6.85; N, 21.97.
Found: C, 62.84; H, 6.89; N, 22.04.
2-(Benzylamino)-4,6-dimethylpyridine-3-carbonitrile (2h):
1
Colorless crystals; mp 138 °C; νmax (KBr) 3392 (N-H), 2198 (C≡N), 1574, 1522 (C-N) cm-1; H NMR
(CDCl3, 500 MHz): δH 2.40, 2.43 (6H, 2s, 2CH3), 4.75 (2H, d, J=5.56 Hz, CH2), 5.42 (1H, br s, NH), 6.42
(1H, s, C-H of pyridine), 7.29-7.33, 7.37-7.41 (5H, 2m, phenyl protons) ppm. 13C NMR (CDCl3, 125
MHz): δC 20.65, 25.39 (2CH3), 45.71(CH2), 89.48 (C≡N), 114.08 (C-H of pyridine), 127.82, 128.30,
129.05, 139.42 (phenyl carbons), 117.23, 152.84, 158.90, 162.22 (pyridine carbons) ppm; MS: m/z: 237
(M+), 222 (M+-CH3), 146 (M+-C7H7), 131 (M+-PhCH2N), 107 (PhCH2N+), 91, 77; Anal. Calcd for
C15H15N3: C, 75.92; H, 6.37; N, 17.71. Found: C, 75.90; H, 6.40; N, 17.74.
4,6-Dimethyl-2-(phenethylamino)pyridine-3-carbonitrile (2i):
1
Colorless crystals; mp 106 °C; νmax (KBr) 3368 (N-H), 2208 (C≡N), 1566, 1518 (C-N) cm-1; H NMR
(CDCl3, 500 MHz): δH 2.38, 2.42 (6H, 2s, 2CH3), 2.94-2.97 (2H, t, J=7.13 Hz, CH2), 3.77-3.81 (2H, d of
t, J=13.59 Hz, J=5.97 Hz, CH2-N), 5.15 (1H, br s, NH), 6.38 (1H, s, C-H of pyridine), 7.26-7.30, 7.35-
13
7.38 (5H, 2m, phenyl protons) ppm. C NMR (CDCl3, 125 MHz): δC 20.63, 25.42 (2CH3 of pyridine),
36.28 (Ph-CH2), 43.18 (CH2-NH), 89.48 (C≡N), 113.74 (C-H of pyridine), 126.90, 129.05, 129.24,
139.58 (phenyl carbons), 117.18, 152.70, 159.02, 162.17 (pyridine carbons) ppm; MS: m/z: 251 (M+), 160
(M+-PhCH2), 131 (M+-C8H10N), 120 (C8H10N+), 91 (C6H5N+), 57, 43; Anal. Calcd for C16H17N3: C,
76.46; H, 6.82; N, 16.72. Found: C, 76.49; H, 6.84; N, 16.77.
2-(Dimethylamino)-4,6-dimethylpyridine-3-carbonitrile (2j):
1
Colorless crystals; mp 48 °C; νmax (KBr) 2198 (C≡N), 1581, 1557, 1513 (C-N) cm-1; H NMR (CDCl3,

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HETEROCYCLES, Vol. 85, No. 11, 2012
13
500 MHz): δH 2.40, 2.42 (6H, 2s, 2CH3), 3.27 (6H, s, 2CH3-N), 6.44 (1H, s, C-H of pyridine) ppm. C
NMR (CDCl3, 125 MHz): δC 21.13, 25.20 (2CH3 of pyridine), 40.97 (2CH3-N), 89.75 (C≡N), 114.33 (C-
H of pyridine), 118.82, 154.85, 160.92, 161.10 (pyridine carbons) ppm; MS: m/z: 175 (M+), 160 (M+-
CH3), 131 (M+-C2H6N), 105 (C7H7N+), 91 (C6H5N+); Anal. Calcd for C10H13N3: C, 68.54; H, 7.48; N,
23.98. Found: C, 68.56; H, 7.44; N, 24.03.
4,6-Dimethyl-2-(pyrrolidin-1-yl)pyridine-3-carbonitrile (2k):
1
Colorless crystals; mp 46 °C; νmax (KBr) 2201 (C≡N), 1555, 1554 (C-N) cm-1; H NMR (CDCl3, 500
MHz): δH 1.96-1.99 (4H, m, 2CH2 of pyrrolidine), 2.36, 2.39 (6H, 2s, 2CH3), 3.77-3.80 (4H, t, J=4.44 Hz,
2CH2-N of pyrrolidine), 6.35 (1H, s, C-H of pyridine) ppm. 13C NMR (CDCl3, 125 MHz): δC 21.15, 25.25
(2CH3 of pyridine), 25.99 (2CH3), 49.39 (CH2 of pyrrolidine), 88.10 (C≡N), 113.29 (C-H of pyridine),
119.34, 154.40, 157.95, 161.46 (pyridine carbons) ppm; MS: m/z: 203 (M+), 188 (M+-CH3), 131 (M+-
C4H10N), 116 (M+-C4H10N, CH3), 105 (C7H7N+), 43; Anal. Calcd for C12H17N3: C, 70.90; H, 8.43; N,
20.67. Found: C, 70.94; H, 8.46; N, 20.71.
4,6-Dimethyl-2-(piperidin-1-yl)pyridine-3-carbonitrile (2l):
Yellow liquid; IR (KBr) 2209 (C≡N), 1579, 1556 (C-N) cm-1; 1H NMR (CDCl3, 500 MHz): δH 1.65-1.74
(6H, m, 3CH2), 2.39, 2.41 (6H, 2s, 2CH3), 3.61-3.63 (4H, t, J=5.59 Hz, 2CH2-N), 6.49 (1H, s, C-H of
13
pyridine) ppm. C NMR (CDCl3, 125 MHz): δC 20.97, 25.05, 25.20, 26.38 (2CH3, 2CH2 of piperidine,
2CH2-N of piperidine) 50.24 (2CH2-N), 93.20 (C≡N), 115.49 (C-H of pyridine), 118.11, 152.30, 160.97,
162.54 (pyridine carbons) ppm; MS: m/z: 215 (M+), 200 (M+-CH3), 131 (M+-C5H10N), 105 (C7H7N+), 84
(C5H10N+), 91 (C6H5N+); Anal. Calcd for C13H17N3: C, 72.52; H, 7.96; N, 19.52. Found: C, 72.48; H,
7.91; N, 19.56.
4,6-Dimethyl-2-morpholinopyridine-3-carbonitrile (2m):
1
Colorless crystals; mp 100 °C; νmax (KBr) 2209 (C≡N), 1557, 1580 (C-N), 1148, 1066 (C-O) cm-1; H
NMR (CDCl3, 500 MHz): δH 2.44, 2.46 (6H, 2s, 2CH3), 3.67-3.69, (4H, 2t, J=4.59 Hz, CH2 of
13
morpholine), 3.86-3.88 (4H, 2t, J=4.89 Hz, CH2 of morpholine), 6.60 (1H, s, C-H of pyridine) ppm. C
NMR (CDCl3, 125 MHz): δC 20.94, 25.15 (2CH3 of pyridine), 49.36, 67.26 (CH2 of morpholine), 93.94
(C≡N), 116.62 (C-H of pyridine), 117.76, 154.52, 161.21, 162.10 (pyridine carbons) ppm; MS: m/z: 217
(M+), 202 (M+-CH3), 131 (M+-C4H8NO), 105 (C7H7N+), 91 (C6H5N+), 30; Anal. Calcd for C12H15N3O: C,
66.34; H, 6.98; N, 19.34. Found: C, 66.39; H, 7.01; N, 19.39.
ACKNOWLEDGEMENTS
The support of this study by the Research Council at the University of Tehran is gratefully acknowledged.

HETEROCYCLES, Vol. 85, No. 11, 2012
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REFERENCES
1. J. Stoltefuss, S. Goldmann, A. Straub, H. Boshagen, M. Bechem, R. Gross, S. Hebisch, J. Hutter, and
H. P. Rounding, 1995, US Patent 5432282 (Chem. Abstr., 1975, 122, p31344g).
2. G. D. Henry, Tetrahedron, 2004, 60, 6043.
3. M. R. P. Queiroz, I. C. F. R. Ferreira, R. C. Calhelha, and L. M. Estevinho, Bioorg. Med. Chem.,
2007, 15, 1788.
4. F. Manna, F. Chimenti, A. Bolasco, B. Bizzarri, W. Filippelli, A. Filippelli, and L. Gagliardi, Eur. J.
Med. Chem., 1999, 34, 245.
5. J. Deng, T. Sanchez, L. Q. Al-Mawsawi, R. Dayam, R. A. Yunes, A. Garofalo, M. B. Bolger, and N.
Neamati, Bioorg. Med. Chem., 2007, 15, 4985.
6. F. Shi, S. Tu, F. Fang, and T. Li, ARKIVOC, 2005, i, 137.
7. S. R. Sarda, J. D. Kale, S. K. Wasmatkar, V. S. Kadam, P. G. Ingole, W. N. Jadhav, and R. P. Pawar,
Mol. Divers., 2009, 13, 545.
8. J. Tang, L. Wang, Y. Yao, L. Zhang, and W. Wang, Tetrahedron Lett., 2011, 52, 509.
9. Q.-Z. Chen, Z.-C. Ding, Y.-L. Ma, Z.-D. Wang, and Z.-P. Zhan, Heterocycles, 2012, 85, 1891.
10. A. Zonouzi, R. Mirzazadeh, A. Peivandi, and S. Dehdari, Heterocycles, 2012, 85, 1447.
11. A. Zonouzi, H. Rahmani, A. Kamali, and M. Biniaz, Org. Prep. Proced. Int., 2011, 43, 276.
12. A. Zonouzi, R. Mirzazadeh, M. Talebi, R. Jafarypoor, A. Peivandi, and S. W. Ng, Heterocycles, 2010,
81, 2131.
13. A. Zonouzi, M. Biniaz, R. Mirzazadeh, M. Talebi, and S. W. Ng, Heterocycles, 2010, 81, 1271.
14. E. Bartmess, Patai's Chemistry of Functional Groups, The Brønsted Acid/Base Character of
Hydroxylamines, Oximes and Hydroxamic Acids, John Wiley & Sons. Inc., 2010, pp. 20-22.
15. Crystallographic data for the structure of compound 2h reported in this paper have been deposited
with the Cambridge Crystallographie Data Center as supplementary publication No. CCDC 891215.
These data can be obtained free of charge via www.ccdc.com.ac.uk/ data_request/cif
16. H. Kanbara, M. Asobe, K. Kubodera, T. Kaino, and T. Kurihara, Appl. Phys. Lett., 1992, 61, 2290.
17. F. J. Duarte, Appl. Opt., 1994, 33, 3857.
18. C. W. Tang and S. A. VanSlyke, Appl .Phys. Lett., 1987, 51, 913.
19. J. R. Lakowicz, Principles of Fluorescence Spectroscopy. Springer, New York, 2006, p. 63.
20. D. F. Eaton, Pure Appl. Chem., 1988, 60, 1107.