An experimental study of special leaving group behavior in the reaction of arylidenebarbituric acids with carbon nucleophiles

Article abstract of DOI:10.3987/COM-10-12073

The reaction of benzylidenebarbituric acid and 1,3- dimethylbenzylidenebarbituric acid with malononitrile as well as with dimedone in piperidine is investigated. In reaction with malononitrile, substituted pyridine-3,5-dicarbonitriles are obtained, while

Full text of DOI:10.3987/COM-10-12073

HETEROCYCLES, Vol. 83, No. 1, 2011
107
HETEROCYCLES, Vol. 83, No. 1, 2011, pp. 107 - 116. © The Japan Institute of Heterocyclic Chemistry
Received, 29th September, 2010, Accepted, 29th November, 2010, Published online, 6th December, 2010
DOI: 10.3987/COM-10-12073
AN EXPERIMENTAL STUDY OF SPECIAL LEAVING GROUP
BEHAVIOR IN THE REACTION OF ARYLIDENEBARBITURIC ACIDS
WITH CARBON NUCLEOPHILES
Mohammad A. Bigdeli,a Enayatollah Sheikhhosseini,a,* Azizollah Habibi,a
and Saeed Balalaieb
aFaculty of Chemistry, Tarbiat Moallem Uinversity, no. 49, Mofateh Ave. Tehran,
Iran, bFaculty of science, Department of Chemistry, K. N. Toosi University of
Technology, PO Box 15875-4416, Tehran, Iran. *Corresponding author. Fax: +98
21 88820993, E-mail address: sheikhhosseiny@gmail.com (E. Sheikhhosseini)
Abstract
–
The
reaction
of
benzylidenebarbituric
acid
and
1,3-dimethylbenzylidenebarbituric acid with malononitrile as well as with
dimedone in piperidine is investigated. In reaction with malononitrile, substituted
pyridine-3,5-dicarbonitriles are obtained, while with dimedone, xanthenes and/or
6-hydroxy-5-((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)(aryl)methyl)-1,3-
dimethyl pyrimidine-2,4(1H,3H)-dione derivatives are isolated.
Benzylidenebarbituric acids which are potential organic oxidizers1,2 are used in preparation of
oxadeazaflavines,3 unsymmetrical synthesis of disulphides,4 synthesis of Merocyanine dyes5 and as
antibacterial agents.6 Benzylidenebarbiturate derivatives such as benzylidene(thio)barbiturate-β-D-
glycosides act as mushroom tyrosinase inhibitors.7,8 Furthermore, benzylidenebarbituric acids are
important
building
blocks
in
the
synthesis
of
pyrazolo[3,4-d]pyrimidines
and
pyrido[2,3-d]pyrimidines,9-11 which show a broad spectrum of biological activities.12-14 Some of these
compounds have also been studied as nonlinear optical materials.15
The nucleophilic attack at the electron-deficient double bond of Michael acceptors has long been a field of
great interest in physical organic chemistry.16,17 Benzylidenebarbituric and thiobarbituric acids are
characterized by their strongly polarized exocyclic double bond with a positive partial charge on the

108
HETEROCYCLES, Vol. 83, No. 1, 2011
arylidene carbon.18,19
The reaction of enones 1a-e with two equivalents of dimedone (2) in the presence of an excess piperidine
in EtOH furnished xanthene derivatives 3a-e. Under the same conditions the N,N-dimethylderivatives
1f-j
gave 6-hydroxy-5-((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)(aryl)methyl)-1,3-dimethyl-
pyrimidine-2,4-(1H,3H)-dione derivatives 4f-j, while the compounds 1k and 1l did not react at all
(Scheme 1 and Table 1).
O
Ar
O
O
O
Ar
O
O
piperidine
RN
RN NR
or
EtOH, reflux
O
O
N
R
O
O
OH
OH
Ar
1a-l
3a-e
2
4f-j
Scheme 1
Table 1. Reaction of enones 1a-l with dimedone (2)
1
R
Ar
product Yield (%)
a
b
c
d
e
f
g
h
i
H
H
H
H
C6H5-
4-MeOC6H4-
4-ClC6H4-
2-ClC6H4-
4-MeC6H4-
C6H5-
3a
3b
3c
3d
3e
4f
4g
4h
4i
75
45
79
80
71
70
65
68
73
69
--
H
Me
Me
Me
Me
Me
Me
Me
4-MeC6H4-
4-ClC6H4-
3-O2NC6H4-
4-BrC6H4-
4-MeOC6H4-
2,4-MeOC6H4-
j
k
l
4j
--
--
--
Along with the formation of products 3a-e, barbiturate salts precipitate from the reaction mixture. No
such precipitations were observed in formation of 4f-j. To investigate further, the reaction of 1b,c,e with
1,3-indanedione was also carried out which lead to the corresponding 2-benzylidene-1,3-indanediones
5b,c,d containing no barbituric acid moiety.
The formation of xanthenes 3 could be rationalized by an initial Micheal addition of 2, followed by a
sequence involving concurrent retro-Micheal elimination of the barbiturate moiety, followed by the
second Micheal addition of 2 and cyclization (Scheme 2).

HETEROCYCLES, Vol. 83, No. 1, 2011
109
Scheme 2
The presence of hydrogens or nitrogen atoms is clearly a determining factor in the type of products
formed. The reaction of enones 1a-f with two equivalent of malononitrile (6) in presence of an excess
amount of piperidine in EtOH afforded pyridinedinitrile derivatives 7a-e in 45-65% yields, presumably
through a similar addition-elimination-addition sequence as dimedone 2 and final cyclization as shown
(Scheme 3 and Table 2).
Table 2. Reaction of enones 1a-f with malononitrile
1
R
Ar
product
Yield (%)
a
b
c
d
e
f
H
H
H
H
H
Me
C6H5-
7a
7b
7c
7d
7e
7a
60
45
63
65
53
58
4-MeOC6H5-
4- ClC6H5-
2-ClC6H5-
4-MeC6H5-
C6H5-
In products isolated from the reactions 1a-f with malononitrile, barbituric acid units are absent. A possible
mechanism20 is shown in Scheme 3.
Ar
Ar
N
Ar
N
Ar
NC
CN
NC
N
CN
CN
NC
N
CN
N
piperidine
6
6
1a-f
NC
piperidine
C
N
CN
C
NC
8
9
11
Ar
10
Ar
NC
N
CN
NH2
NC
CN
NH2
O
N
N
N
7a-e
12
Scheme 3

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HETEROCYCLES, Vol. 83, No. 1, 2011
The reaction of arylidenebarbituric acids with dimedone was found to give two types of products
depending upon the presence of N-H bonds or otherwise. Starting materials 1a-e gave xanthenes where as
1f-j gave substituted pyrimidinediones. Similar results were obtained from the reaction of malononitrile
with arylidenbarbituric acids except for compound 1f.
EXPERIMENTAL
1. Instruments and characterization
Melting points were measured on an Electrothermal 9200 apparatus and are uncorrected. 1H NMR and 13C
NMR spectra were recorded on a Bruker DRX-300 AVANCE spectrometer at 300.13 MHz. IR spectra
were recorded on a Bomem MB-Series FTIR. Electrospray ionization (ESI) mass spectrometry (MS)
experiments were performed on Finnigan-MAT-8430 mass spectrometer, at 70 eV, in m/z. Elemental
analyses were carried out on a Heraeus CHN-O-Rapid analyzer.
2. General procedure for the preparation of 5-((aryl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-6-
hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (4f-j).
Piperidine (8 mmol) was added dropwise to a solution of enone 1 (2 mmol) and dimedone (2, 4 mmol) in
absolute EtOH (15 mL) at room temperature. The reaction mixture was refluxed until the disappearance of
the starting material (4-6 h), (monitored by TLC), solution was evaporated and was diluted with H2SO4
(10%) (15 mL), precipitate solid product was recrystallized from water/acetone.
2.1.
6-Hydroxy-5-((2-hydroxy-6-oxocyclohex-1-enyl)(phenyl)methyl)-1,3-dimethylpyrimidine-2,4-
◦
1
(1H,3H)-dione (4f). Yield 70%. Mp 186-188 C. IR (KBr cm-1) 2200-3383, 1700, 1631, 1616. H NMR
(CDCl3) δ: 1.15 (s, 3H, Me), 1.28 (s, 3H, Me), 2.30-2.54 (m, 4H, 2CH2), 3.36 (s, 3H, N-Me), 3.45 (s, 3H,
N-Me), 5.58 (s, 1H, CH), 7.12-7.33 (m, 5H, aryl), 10.6 (br, 1H, OH), 12.85 (s, 1H, OH). 13C NMR
(CDCl3) δ: 27.1, 28.9, 29.2, 29.7, 31.12, 33.6, 45.7, 47.0, 92.4, 116.4, 126.2, 126.5, 128.3, 137.2, 150.7,
162.3, 164.2, 190.6, 191.5. MS: m/z (%) = 384 (M+, 68), 263 (8), 243 (26), 227 (100), 171 (14), 156 (22),
129 (12), 116 (19), 102 (27), 83 (13), 71 (9), 55 (14), 42 (33). Anal. Calcd for C21H24N2O5: C, 65.61; H,
6.29; N, 7.29. Found: C, 65.71; H, 6.32; N, 7.08.
2.2.
6-Hydroxy-5-((2-hydroxy-6-oxocyclohex-1-enyl)(p-tolyl)methyl)-1,3-dimethylpyrimidine-2,4-
◦
1
(1H,3H)-dione (4g). Yield 68%. Mp 176-179 C. IR (KBr cm-1) 2200-3200, 1703, 1604. H NMR
(CDCl3) δ: 1.10 (s, 3H, Me), 1.27 (s, 3H, Me), 2.32 (s, 3H, Me-aryl), 2.34-2.53 (m, 4H, 2CH2), 3.35 (s,
3H, N-Me), 3.44 (s, 3H, N-Me), 5.53 (s, 1H, CH), 7.01 (d, J = 7.7 Hz, 2H, aryl) 7.10 (d, J = 8.1 Hz, 2H,
13
aryl), 11.0 (br, 1H, OH), 12.8 (s, 1H, OH). C NMR (CDCl3) δ: 20.9, 27.1, 28.8, 29.2, 29.9, 31.2, 33.2,

HETEROCYCLES, Vol. 83, No. 1, 2011
111
46.9, 50.7, 92.5, 116.5, 126.4, 129.0, 133.9, 135.6, 150.7, 162.3, 164.1, 190.7, 191.4. MS: m/z (%) = 398
(M+, 6), 364 (17), 349 (12), 273 (21), 257 (18), 241 (25), 227 (100), 171 (21), 156 (30), 129 (14), 115 (49),
97 (17), 83 (29), 69 (46), 57 (30), 43 (39). Anal. Calcd for C22H26N2O5: C, 66.32; H, 6.58; N, 7.03. Found:
C, 65.99; H, 6.58; N, 7.03.
2.3.
5-((4-Chlorophenyl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-6-hydroxy-1,3-dimethyl-
◦
1
pyrimidine-2,4(1H,3H)-dione (4h). Yield 62%. Mp 176 C. IR (KBr cm-1) 2200-3385, 1703, 1604. H
NMR (CDCl3) δ: 1.13 (s, 3H, Me), 1.26 (s, 3H, Me), 2.29-2.53 (m, 4H, 2CH2), 3.35 (s, 3H, N-Me), 3.44
(s, 3H, N-Me), 5.50 (s, 1H, CH), 7.05 (d, J = 11.4 Hz, 2H, aryl) 7.25 (d, J = 11.4 Hz, 2H, aryl), 9.50 (br,
1H, OH), 12.79 (s, 1H, OH). 13C NMR (CDCl3) δ: 27.1, 28.9, 29.1, 29.9, 31.2, 33.3, 46.0, 46.5, 47.0, 92.2,
116.1, 128.0, 128.4, 131.9, 135.8, 150.6, 162.3, 146.1, 191.1, 191.2. MS: m/z (%) = 418 (M+, 7), 400 (11),
289 (30), 207 (15), 186 (13), 167 (43), 149 (100), 80 (48), 64 (59), 41 (43). Anal. Calcd for
C21H23N2O5Cl: C, 60.22; H, 5.53; N, 6.69. Found: C, 60.83; H, 5.43; N, 6.75.
2.4.
6-Hydroxy-5-((2-hydroxy-6-oxocyclohex-1-enyl)(3-nitrophenyl)methyl)-1,3-dimethyl-
◦
pyrimidine-2,4(1H,3H)-dione (4i). Yield 59%. Mp 180-182 C. IR (KBr cm-1) 2200-3392, 1703, 1609.
1H NMR (CDCl3) δ: 1.16 (s, 3H, Me), 1.33 (s, 3H, Me), 2.32-2.58 (m, 4H, 2CH2), 3.36 (s, 3H, N-Me),
3.47 (s, 3H, N-Me), 5.58 (s, 1H, CH), 7.47 (d, J = 4.5 Hz, 2H, aryl), 8.02 (d, J = 1.1 Hz, H, aryl), 8.09
13
(m, 1H, aryl), 9.80 (br, 1H, OH), 12.79 (s, 1H, OH). C NMR (CDCl3) δ: 27.0, 28.9, 29.3, 29.9, 31.2,
33.72, 46.1, 46.9, 91.5, 115.7, 121.4, 122.4, 129.2, 132.7, 139.9, 148.5, 150.5, 162.4, 164.2, 191.4, 191.6.
MS: m/z (%) = 429 (M+, 11), 378 (11), 289 (27), 273 (60), 256 (100), 242 (15), 226 (44), 189 (19), 156
(61), 129 (29), 115 (28), 101 (37), 69 (21), 55 (43), 42 (89). Anal. Calcd for C21H23N3O7: C, 58.71; H,
5.40; N, 9.79. Found: C, 58.94; H, 5.41; N, 9.56.
2.5.
5-((4-Bromophenyl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-6-hydroxy-1,3-dimethyl-
◦
pyrimidine-2,4(1H,3H)-dione (4j). Yield 70%. Mp 193-195 C. IR (KBr cm-1) 2200-3391, 1705, 1607.
1H NMR (CDCl3) δ: 1.14 (s, 3H, Me), 1.26 (s, 3H, Me), 2.29-2.53 (m, 4H, 2CH2), 3.35 (s, 3H, N-Me),
3.44 (s, 3H, N-Me), 5.48 (s, 1H, CH), 7.00 (d, J = 8.5 Hz, 2H, aryl) 7.41 (d, J = 8.5 Hz, 2H, aryl), 9.65 (br,
13
1H, OH), 12.70 (s, 1H, OH). C NMR (CDCl3) δ: 27.1, 29.2, 29.5, 29.9, 31.2, 33.3, 46.0, 46.9, 92.1,
116.1, 120.0, 128.5, 131.2, 136.4, 150.6, 162.3, 164.1, 191.1, 191.2. MS: m/z (%) = 464 (M+, 33), 462
(33), 323 (20), 307 (53), 227 (100), 209 (7), 196 (10), 171 (26), 141 (11), 115 (23), 101 (16), 83 (16), 69
(10), 55 (20), 42 (40). Anal. Calcd for C21H23N2O5Br: C, 54.44; H, 5.40; N, 6.05. Found: C, 54.86; H,
5.44; N, 6.04.

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HETEROCYCLES, Vol. 83, No. 1, 2011
3. General procedure for the preparation of 9-(aryl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-
anthracene-1,8(2H,5H,9H,10H)-dione (3a-e).
Piperidine (8 mmol) was added dropwise to a solution of enone 1 (2 mmol) and dimedone (2, 4 mmol) in
absolute EtOH (15 mL) at room temperature. The reaction mixture was refluxed until the disappearance of
the starting material (3.5-5 h), (monitored by TLC) and barbituric acid salt was filtered off. The filtrate
was evaporated and was diluted with H2SO4 (10%) (15 mL), precipitate solid product was recrystallized
from water/acetone.
3.1. 3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-phenyl-2H-xanthene-1,8(5H,9H)-dione (3a). Yield 75%.
Mp 199-203 ◦C. IR (KBr cm-1) 2958, 1677, 1662, 1623. 1H NMR (acetone) δ: 0.96 (s, 6H, CH(Me)2), 1.08
(s, 6H, CH(Me)2), 2.02-2.55 (m, 8H, 4CH2), 4.64 (s, 1H, CH), 7.04-7.26 (m, 5H, aryl). 13C NMR
(acetone) δ: 27.1, 32.5, 32.6, 41.0, 51.1, 115.9, 126.9, 128.5, 129.3, 145.6, 163.4, 196.2. Anal. Calcd for
C23H26O3: C, 78.85; H, 7.42; N, 0.00. Found: C, 78.30; H, 7.60; N, 0.21.
3.2.
3,4,6,7-Tetrahydro-9-(4-methoxyphenyl)-3,3,6,6-tetramethyl-2H-xanthene-1,8(5H,9H)-dione
◦
1
(3b). Yield 45%. Mp 245-247 C. IR (KBr cm-1) 2953, 1679, 1678, 1659, 1619. H NMR (DMSO-d6) δ:
0.88 (s, 6H, CH(Me)2), 1.02 (s, 6H, CH(Me)2), 2.02-2.52 (m, 8H, 4CH2), 3.66 (s, 3H, OMe), 4.44 (s, 1H,
13
CH), 6.75 (d, J = 8.6 Hz, 2H, aryl), 7.05 (d, J = 8.6 Hz, 2H, aryl). C NMR (DMSO-d6) δ: 26.4, 28.6,
30.2, 31.8, 48.3, 50.0, 113.2, 114.6, 128.9, 136.4, 162.6, 196.0. Anal. Calcd for C24H28O4: C, 75.79; H,
7.37; N, 0.00. Found: C, 75.60; H, 7.30; N, 0.15.
3.3. 9-(4-Chlorophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8(5H,9H)-dione (3c).
Yield 79%. Mp 214-217 ◦C. IR (KBr cm-1) 2951, 1679, 1662, 1624. 1H NMR (DMSO-d6) δ: 0.88 (s, 6H,
CH(Me)2), 0.97 (s, 6H, CH(Me)2), 2.09-2.59 (m, 8H, 4CH2), 4.48 (s, 1H, CH), 7.16 (d, J = 8.5 Hz, 2H,
13
aryl), 7.26 (d, J = 8.5 Hz, 2H, aryl). C NMR (DMSO-d6) δ: 26.5, 28.6, 30.9, 31.8, 49.9, 113.9, 127.8,
129.9, 130.7, 143.2, 163.0, 196.0. Anal. Calcd for C23H25O3Cl: C, 71.78; H, 6.50; N, 0.00. Found: C, 72.2;
H, 6.47; N, 0.09.
3.4. 9-(2-Chlorophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8(5H,9H)-dione (3d).
◦
1
Yield 80%. Mp 217-218 C. IR (KBr cm-1) 2959, 1680, 1655, 1625. H NMR (DMSO-d6) δ: 0.9 (s, 6H,
CH(Me)2 ), 1.03 (s, 6H, CH(Me)2), 2.06-2.6 (m, 8H, 4CH2), 4.82 (s, 1H, CH), 7.08-7.26 (m, 4H, aryl). 13C
NMR (DMSO-d6) δ: 26.3, 28.6, 30.5, 31.6, 50.0, 113.1, 126.4, 127.7, 129.4, 131.9, 132.8, 140.7, 168.2,
195.8. Anal. Calcd for C23H25O3Cl: C, 71.78; H, 6.50; N, 0.00. Found: C, 71.30; H, 6.61; N, 0.07.

HETEROCYCLES, Vol. 83, No. 1, 2011
113
3.5. 3,4,6,7-Tetrahydro-9-(4-methylphenyl)-3,3,6,6-tetramethyl-2H-xanthene-1,8(5H,9H)-dione (3e).
Yield 45%. Mp 222-225◦C. IR (KBr cm-1) 2950, 1677, 1676, 1660, 1617. 1H NMR (DMSO-d6) δ: 1.00 (s,
6H, C(Me)2), 1.11 (s, 6H, C(Me)2), 1.99-2.22 (m, 8H, 4CH2), 2.44 (s, 3H, Me), 4.6 (s, 1H, CH), 6.69 (d, J
13
= 8.6 Hz, 2H, aryl), 7.13 (d, J = 8.6 Hz, 2H, aryl). C NMR (DMSO-d6) δ: 22.5, 26.4, 28.5, 30.2, 31.8,
50.1, 113.0, 114.6, 128.7, 136.2, 163.6, 197.0. Anal. Calcd for C24H28O3: C, 79.09; H, 7.74; N, 0.00.
Found: C, 78.73; H, 7.65; N, 0.09.
4. General procedure for the preparation 2-(benzyliden)-2H-indene-1,3-dione (5b,c,e)
Piperidine (8 mmol) was added dropwise to a solution of enone 1 (2 mmol) and 2H-indene-1,3-dione (2
mmol) in absolute EtOH (15 mL) at room temperature. The reaction mixture was refluxed until the
disappearance of the starting material (5-7 h), (monitored by TLC) and barbituric acid salt was filtered off.
The filtrate was evaporated and was diluted with H2SO4 (10%) (15 mL), precipitate solid product was
recrystallized from hot EtOH.
◦
4.1. 2-(4-Methoxybenzylidene)-2H-indene-1,3-dione (5b). Yield 68%. Mp 156-157 C. IR (KBr cm-1)
1725, 1680. 1H NMR (CDCl3) δ: 3.9 (s, 3H, OMe), 7.02 (d, J = 8.9 Hz, 2H, aryl), 7.58 (s, 1H, =CH), 7.79
(m, 2H, aryl), 7.98 (m, 2H, aryl), 8.55 (d, J = 8.9 Hz, 2H, aryl), 13C NMR (CDCl3) δ: 55.6, 123.1, 123.5,
126.4, 126.5, 134.8, 135.1, 137.2, 139.9, 142.3, 146.8, 188.3, 190.8. Anal. Calcd for C17H12O3: C, 77.26;
H, 4.58; N, 0.00. Found: C, 77.73; H, 4.65; N, 0.06.
◦
4.2. 2-(4-Chlorobenzylidene)-2H-indene-1,3-dione (5c). Yield 72%. Mp 172-174 C. IR (KBr cm-1)
1
1727, 1690. H NMR (CDCl3) δ: 7.47 (d, j = 8.5 Hz, 2H, aryl), 7.81 (s, 1H, =CH), 7.83 (m, 2H, aryl),
8.01 (m, 2H, aryl), 8.41 (d, J = 8.5 Hz, 2H, aryl), 13C NMR (CDCl3) δ: 123.3, 123.4, 129.1, 129.4, 135.3,
135.5, 139.5, 140.1, 142.5, 145.1,188.9, 189.9. Anal. Calcd for C16H9ClO2: C, 71.52; H, 3.38; N, 0.00.
Found: C, 71.67; H, 3.15; N, 0.08.
◦
4.3. 2-(4-Methylbenzylidene)-2H-indene-1,3-dione (5e). Yield 80%. Mp 146-147 C. IR (KBr cm-1)
1726, 1683. 1H NMR (CDCl3) δ: 2.46 (s, 3H, Me), 7.32 (d, J = 8.1 Hz, 2H, aryl), 7.81(m, 2H, aryl), 7.88
(s, 1H, =CH), 8.01 (m, 2H, aryl), 8.40 (d, J = 8.2 Hz, 2H, aryl). 13C NMR (CDCl3) δ: 22.09, 123.2, 128.2,
129.6, 130.6, 134.5, 135.0, 135.2, 140.0, 142.5, 144.6, 147.1, 189.2, 190.5. Anal. Calcd for C17H12O2: C,
82.24; H, 4.87; N, 0.00. Found: C, 81.89; H, 4.70; N, 0.04.
5.
General
procedure
for
the
preparation
of
2-amino-4-(2-aryl)-6-(piperidinyl)-
pyridine-3,5-dicarbonitriles (7a-e).

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HETEROCYCLES, Vol. 83, No. 1, 2011
Piperidine (8 mmol) was added dropwise to a solution of enone 1 (2 mmol) and malononitrile (6, 4 mmol)
in absolute EtOH (15 mL) at room temperature. The reaction mixture was refluxed until the disappearance
of the starting material (8-10 h), (monitored by TLC) and barbituric acid salt was filtered off. The filtrate
was evaporated and was diluted with water (15 mL), precipitate solid product was recrystallized from
water/acetone. In some cases column chromatography was used using ethylacetate/chloroform mixture as
eluent.
◦
5.1. 2-Amino-4-phenyl-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile (7a). Yield 60%. Mp 203-205 C.
1
IR (KBr cm-1) 3474, 3325, 3222, 2202, 1624, 1583, 1567. H NMR (DMSO-d6) δ: 1.61 (m, 6H,
13
piperidine), 3.71 (m, 4H, piperidine), 7.44-7.53 (m, 7H, aryl and NH2). C NMR (DMSO-d6) δ: 24.9,
26.6, 49.4, 81.8, 82.5, 117.2, 118.8, 129.5, 129.7, 130.9, 136.3, 160.8, 161.7, 162.8. MS: m/z (%) = 303
(M+, 1), 302 (3), 277 (4), 238 (100), 213 (3), 183 (3), 162 (24), 145 (3), 127 (19), 103 (15), 84 (17), 56 (8),
41 (9). Anal. Calcd for C18H17N5: C, 71.28; H, 5.65; N, 23.09. Found: C, 71.78; H, 6.01; N, 22.76.
5.2. 2-Amino-4-(4-methoxyphenyl)-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile (7b). Yield 45%. Mp
◦
1
198-200 C. IR (KBr cm-1) 3512, 3401, 2196, 1602, 1580, 1554. H NMR (acetone) δ: 1.65 (m, 6H,
piperidine), 3.76 (m, 4H, piperidine), 3.87 (s, 3H, OMe), 6.71 (s, 2H, NH2), 7.06 (d, J = 6.8 Hz, 2H, aryl),
7.49 (d, J = 6.8 Hz, 2H, aryl). 13C NMR (acetone) δ: 25.1, 26.7, 49.7, 55.7, 81.7, 83.8, 114.7, 116.9, 118.4,
128.5, 131.4, 161.1, 162.1, 162.4, 162.5. MS: m/z (%) = 333 (M+, 68), 332 (100), 318 (23), 304 (9), 182
(14), 125 (23), 84 (8), 55 (7), 41 (5). Anal. Calcd for C19H19N5O: C, 68.45; H, 5.74; N, 21.01. Found: C,
67.92; H, 5.69; N, 21.50.
5.3. 2-Amino-4-(4-chlorophenyl)-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile (7c). Yield 63%. Mp
218-220 ◦C. IR (KBr cm-1) 3470, 3331, 3326, 2209, 1628, 1576, 1530. 1H NMR (acetone) δ: 1.65 (m, 6H,
13
piperidine), 3.79 (m, 4H, piperidine), 6.82 (s, 2H, NH2), 7.54-7.61 (m, 4H, aryl). C NMR (acetone) δ:
25.0, 26.6, 49.6, 81.3, 83.3, 116.4, 118.0, 129.6, 131.5, 132.1, 135.4, 136.4, 160.9, 161.5, 161.9. MS: m/z
(%) = 337 (M+, 46), 336 (100), 308 (10), 294 (41), 281 (5), 219 (5), 84 (7), 69 (8), 55 (7), 41 (8). Anal.
Calcd for C18H16N5Cl: C, 64.00; H, 4.77; N, 20.73. Found: C, 63.90; H, 4.71; N, 20.47.
5.4. 2-Amino-4-(2-chlorophenyl)-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile (7d). Yield 65%. Mp
188-189 ◦C. IR (KBr cm-1) 3467, 3327, 3321, 2207, 1622, 1572, 1531. 1H NMR (acetone) δ: 1.65 (m, 6H,
13
piperidine), 3.80 (m, 4H, piperidine), 6.85 (s, 2H, NH2), 7.47-7.61 (m, 4H, aryl). C NMR (acetone) δ:
25.0, 26.6, 49.4, 83.0, 84.1, 115.8, 117.4, 128.3, 130.6, 131.1, 132.0, 132.6, 135.8, 160.3, 160.6, 161.2.
MS: m/z (%) = 337 (M+, 75), 308 (33), 302 (100), 294 (9), 281 (9), 260 (15), 247 (19), 219 (20), 165 (13),

HETEROCYCLES, Vol. 83, No. 1, 2011
115
84 (21), 55 (12), 41 (15). Anal. Calcd for C18H16N5Cl: C, 64.00; H, 4.77; N, 20.73. Found: C, 64.06; H,
4.71; N, 20.77.
◦
5.5. 2-Amino-6-(piperidin-1-yl)-4-p-tolylpyridine-3,5-dicarbonitrile (7e). Yield 53%. Mp 198 C. IR
1
(KBr cm-1) 3479, 3327, 3221, 2201, 1623, 1579, 1556, 1535. H NMR (CDCl3) δ: 1.69 (m, 6H,
piperidine), 2.41 (s, 3H, Me) 3.79 (m, 4H, piperidine), 5.35 (s, 2H, NH2), 7.30 (d, J = 8.1 Hz, 2H, aryl),
7.39 (d, J = 8.1 Hz, 2H, aryl). 13C NMR (CDCl3) δ: 21.5, 24.4, 25.9, 49.2, 81.5, 83.5, 116.7, 117.8, 128.6,
129.5, 131.8, 140.7, 159.4, 161.2, 162.4. MS: m/z (%) = 317 (M+, 56), 316 (100), 302 (17), 288 (9), 219
(4), 179 (4), 84 (8), 69 (8), 55 (5), 41 (7). Anal. Calcd for C19H19N5: C, 71.90; H, 6.03; N, 22.07. Found: C,
72.09; H, 6.20; N, 21.69.
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