Cyanopyridines. Synthesis and recyclization of their quaternary salts

Article abstract of DOI:10.1007/s11178-005-0348-y

3-Cyanopyridines containing an acetyl, ester, nitro, or cyano group in the 5-position were synthesized via various versions of the Hantzsch reaction. Recyclization of quaternary pyridinium salts by the action of aqueous-alcoholic alkali afforded 2-methyla

Full text of DOI:10.1007/s11178-005-0348-y

Russian Journal of Organic Chemistry, Vol. 41, No. 9, 2005, pp. 1367–1373. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 9, 2005,
pp. 1395–1401.
Original Russian Text Copyright © 2005 by Sagitullina, Glizdinskaya, Oleinikova, Atavin, Sagitullin.
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on His 70th Anniversary
Cyanopyridines. Synthesis and Recyclization
of Their Quaternary Salts
G. P. Sagitullina, L. V. Glizdinskaya, S. I. Oleinikova, E. G. Atavin, and R. S. Sagitullin
Omsk State University, pr. Mira 55a, Omsk, 644077 Russia
fax: (3812)642410; e-mail: Sagitullina@orgchem.univer.omsk.su
Received February 14, 2005
Abstract—3-Cyanopyridines containing an acetyl, ester, nitro, or cyano group in the 5-position were
synthesized via various versions of the Hantzsch reaction. Recyclization of quaternary pyridinium salts by the
action of aqueous–alcoholic alkali afforded 2-methylaminopyridine derivatives and 6-methylamino-3-nitro-2,4-
diphenylbenzonitrile.
In continuation of our studies on recyclization of
pyridinium salts having a cyano group in position 3
[1–3] we synthesized previously unknown cyanopyri-
dines IIa–IIg with a view to examine the effect of
structural and electronic factors on the direction of
recyclization of quaternary salts derived therefrom.
Symmetrically substituted 3,5-dicyanopyridines IIa–
IIe were obtained by cyclocondensation of 3-amino-
2-butenenitrile with various aldehydes (Hantzsch–
Meyer–Mohr reaction), by analogy with the synthesis
of 3,5-dicyanopyridines reported previously [4–6].
1,4-Dihydropyridines Ia–Ie were oxidized with
sodium nitrite in acetic acid. Both stages in the syn-
thesis of pyridines IIa–IIe (Scheme 1) were charac-
terized by fairly high yields.
5-Acetyl-6-methyl-2-phenylpyridine-3-carbonitrile
(IIf) was prepared by three-component condensation
of benzoylacetonitrile, triethyl orthoformate, and
4-amino-3-penten-2-one at a ratio of 1:3:1 at 70°C.
Under these conditions, addition of the β-carbon atom
in the enamine fragment of 4-amino-3-penten-2-one
to ethoxymethylene derivative of benzoylacetonitrile
gave rise to a new carbon–carbon bond and closure of
pyridine ring [7, 8] (Scheme 2). The synthesis of ethyl
5-cyano-2-methyl-4-phenylpyridine-3-carboxylate
(IIg) included structural modification of previously
described ethyl 5-cyano-2-methyl-6-oxo-4-phenyl-1,6-
dihydropyridine-3-carboxylate [9] via nucleophilic re-
placement of the hydroxy group by chlorine and sub-
sequent reductive dechlorination (Scheme 3). Nitro-
Scheme 1.
R
R
NC
Me
CN
Me
NC
Me
CN
Me
Me
CN
NaNO2, AcOH
RCHO
+
2
H2N
N
H
N
Ia–Ie
IIa–IIe
R
NC
Me
CN
Me2SO4, NaClO4
ClO4
N
Me
Me
IIIa–IIIe
R = 4-ClC6H4 (a), 4-MeOC6H4 (b), 2,4-(MeO)2C6H3 (c), 2-furyl (d), Me (e).
1070-4280/05/4109-1367 © 2005 Pleiades Publishing, Inc.

SAGITULLINA et al.
1368
Scheme 2.
NC
COMe
Me
NC
Ph
COMe
ClO4
Me
COMe
Ph
O
CN
AcOH
Me2SO4, NaClO4
CH(OEt)3
+
+
H2N
Ph
N
N
Me
Me
IIf
IIIf
Scheme 3.
Ph
Ph
Ph
N
EtOCO
Me
CN
Cl
EtOCO
Me
CN
EtOCO
CN
Zn (dust)
Me2SO4, NaClO4
ClO4
N
N
Me
Me
IV
IIg
IIIg
pyridine IIh was obtained by us previously [10]. The
alkylation of weakly basic pyridines IIa–IIh was
effected with the aid of dimethyl sulfate. Quaternary
pyridinium salts were isolated as the corresponding
perchlorates which were prepared by anion exchange
reaction.
methylaminopyridines Va–Ve. Likewise, recyclization
of unsymmetrically substituted salt IIIf via double
rearrangement yields 3-acetyl-5-benzoyl-2-methyl-6-
methylaminopyridine (Vf). The recyclization direction
is determined by the site of addition of hydroxide ion
which attacks the most electron-deficient C6 atom in
salt IIIf. The recyclization of pyridinium salt IIIg
having both cyano and ester groups may involve both
these (Scheme 5). The major product is methylamino-
pyridine Vg which is formed from open-chain pre-
cursor A. The regioselectivity of this reaction origi-
nates from predominant attack by hydroxide ion on the
least sterically shielded C6 atom in pyridinium salt
IIIg. Intramolecular acylation by the ester group of the
secondary amino group in open-chain structure B gives
pyridinone VI.
Recyclization of pyridinium salts IIIa–IIIg by the
action of aqueous–alcoholic alkali followed the double
rearrangement scheme described in [1] and afforded
6-methylaminopyridine derivatives Va–Vf as shown in
Scheme 4. Attack by hydroxide ion on symmetrically
substituted salts IIIa–IIIe is directed at the α-carbon
atom of the pyridine ring to give a pseudobase which
may be considered to be a neutral analog of anionic
σ-complex. Heterocyclization of open-chain tautomer
A involves attack by the secondary amino group on the
electron-deficient carbon atom of the cyano group,
leading to cyclic amidine B. Recyclization of the latter
follows a Dimroth-type reaction to produce 5-acetyl-6-
As shown in [3], recyclization of 3-cyano-5-ethoxy-
carbonyl-1,2,6-trimethyl-4-phenylpyridinium per-
chlorate under analogous conditions leads to formation
Scheme 4.
R'
R'
R'
X
CN
OH
X
CN
OH
X
COR
OH–
IIIa–IIIe
CN
Me
N
Me
N
Me
NH
R
R
Me
Me
Me
A
R'
R'
R'
COR
NH
X
X
COR
NH
X
COR
OH–
Me
Me
N
Me
N
NHMe
O
HN
Me
Me
B
Va–Vf
R = Me, X = CN, R' = 4-ClC6H4 (a), 4-MeOC6H4 (b), 2,4-(MeO)2C6H3 (c), 2-furyl (d), Me (e); R = Ph, R' = H, X = COMe (f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

CYANOPYRIDINES. SYNTHESIS AND RECYCLIZATION
1369
Scheme 5.
Ph
Ph
Ph
NC
COOEt
Me
NC
COOEt
OH
NC
COMe
COOEt
OH–
IIIg
+
N
NH
Me
O
Me
HN
Me
Me
A
B
Ph
N
Ph
N
OCH
COOEt
Me
NC
COMe
O
MeNH
Me
Vg
VI
of 5-acetyl-1,2-dimethyl-6-oxo-4-phenyl-1,6-dihydro-
pyridine-3-carbonitrile as the only product. From un-
symmetrically substituted 5-cyano-3-nitropyridinium
salt IIIh we obtained substituted terphenyl VII
(Scheme 6). Here, attack by hydroxide ion is directed
at the most π-deficient 2-position of the pyridine ring
(at the ortho position with respect to the nitro group) to
give pseudobase A. Closure of benzene ring involves
intramolecular aldol-type condensation of the emerg-
ing benzoyl group with the methyl group of open-chain
intermediate C. The recyclization yields difficultly
accessible terphenyl derivative VII with a high regio-
selectivity.
the α-carbon atom of the pyridine ring in the ortho
position with respect to the cyano group, the latter is
involved in the recyclization. When hydroxide ion
adds at the para position with respect to the cyano
group, the recyclization occurs without its participation
but involves ester moiety to afford the corresponding
pyridinone or gives carbocycle provided that a nitro
group is present in the pyridine ring.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
AC-200 spectrometer operating at 200 MHz; the
chemical shifts were measured relative to tetramethyl-
silane as internal reference. The IR spectra were
obtained from solutions in chloroform on a Specord
IR-75 instrument. The mass spectra (electron impact,
70 eV) were run on a Finnigan MAT-8200 mass spec-
Our results led us to draw the following conclu-
sions. Recyclization of 3-cyanopyridinium salts by the
action of alkali can occur with participation of the
cyano group in the formation of new pyridine ring or
without it. When hydroxide ion is covalently bound to
Scheme 5.
Ph
Ph
Ph
NC
Me
NO2
Ph
NC
Me
NO2
OH
NC
Me
NO2
OH
OH–
MeSO4
N
N
N
Ph
Ph
Me
IIIh
Me
A
Me
B
Ph
Ph
NC
MeNH
NO2
Ph
NC
NO2
Ph
MeNH
Me
O
C
VII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

SAGITULLINA et al.
1370
trometer with direct sample admission into the ion
source. The progress of reactions and the purity of
products were monitored by TLC on Silufol UV-254
plates using chloroform or chloroform–ethyl acetate
(9:1 or 1:1) as eluent. The melting points were deter-
mined on a Boetius apparatus.
volume of an ice–water mixture, and neutralized with
ammonia. The precipitate was filtered off and washed
with water. Yield 2.43 g (90%), mp 232–234°C (from
1
ethanol). IR spectrum: ν(CN) 2230 cm–1. H NMR
spectrum (CDCl3), δ, ppm: 2.87 s (6H, CH3), 7.47 d
(2H, 3'-H, 5'-H, J = 8.8 Hz), 7.57 d (2H, 2'-H, 6'-H, J =
8.8 Hz). Found, %: C 67.39; H 3.74. C15H10ClN3. Cal-
culated, %: C 67.30; H 3.77.
Commercial 3-amino-2-butenenitrile (from Fluka)
was used. Compounds Ib–IIIb were synthesized as
described in [4], 1,4-dihydropyridine Ie was prepared
by the procedure reported in [6], and benzoylaceto-
nitrile was obtained according to [11]. The synthesis of
cyanopyridine IIe was described in [12], and of pyri-
dinium methyl sulfate IIIh, in [10].
4-(2,4-Dimethoxyphenyl)-2,6-dimethylpyridine-
3,5-dicarbonitrile (IIc) was synthesized in a similar
way. Yield 87%, mp 134–135°C (from ethanol). IR
1
spectrum: ν(CN) 2230 cm–1. H NMR spectrum
(CDCl3), δ, ppm: 2.84 s (6H, CH3), 3.85 s (3H, CH3O),
3.88 s (3H, CH3O); ABX: 6.61 (1H, 5'-H), 6.65 (1H,
4-(4-Chlorophenyl)-2,6-dimethyl-1,4-dihydro-
pyridine-3,5-dicarbonitrile (Ia). A solution of 0.82 g
(10 mmol) of 3-amino-2-butenenitrile and 0.70 g
(5 mmol) of p-chlorobenzaldehyde (the aldehyde was
added in 3 portions) in 10 ml of glacial acetic acid was
heated for 2 h at 100°C. After 12 h, the precipitate was
filtered off and washed with cold ethanol. Yield 0.99 g
(74%), mp 237–238°C (from ethanol). IR spectrum,
3'-H), 7.23 (1H, 6'-H), J5',3' = 2.3, J6',3' = 0, J5',6'
=
8.8 Hz). Found, %: C 69.40; H 5.31. C17H15N3O2. Cal-
culated, %: C 69.61; H 5.15.
4-(2-Furyl)-2,6-dimethylpyridine-3,5-dicarbo-
nitrile (IId) was synthesized in a similar way. Yield
85%, mp 143–145°C (from ethanol). IR spectrum:
ν(CN) 2235 cm–1. 1H NMR spectrum (CDCl3), δ, ppm:
1
ν, cm–1: 2210 (CN), 3450 (NH). H NMR spectrum
2.85 s (6H, CH3), 6.70 d.d (1H, 4'-H, J4',3' = 3.8, J4',5'
=
(DMSO-d6), δ, ppm: 2.04 s (6H, CH3), 4.47 s (1H,
4-H), 7.32 d (2H, 3'-H, 5'-H, J = 8.5 Hz), 7.52 d (2H,
2'-H, 6'-H, J = 8.5 Hz), 9.57 s (1H, NH). Found, %:
C 66.73; H 4.50. C15H12ClN3. Calculated, %: C 66.79;
H 4.48.
1.8 Hz), 7.67 d.d (1H, 3'-H, J3',4' = 3.8, J3',5' = 0.6 Hz),
7.80 d.d (1H, 5'-H, J5',4' = 1.8, J5',3' = 0.6 Hz). Found,
%: C 69.99; H 3.94. C13H9N3O. Calculated, %:
C 69.95; H 4.06.
5-Acetyl-6-methyl-2-phenylpyridine-3-carbo-
nitrile (IIf). Triethyl orthoformate, 5 ml (30 mmol),
and 4-amino-3-penten-2-one, 0.99 g (10 mmol), were
added to a solution of 1.45 g (10 mmol) of benzoyl-
acetonitrile in 5 ml of glacial acetic acid. The mixture
was stirred for 4 h at 70°C, cooled, diluted with water,
and left overnight. The precipitate was filtered off and
washed with water. The product was purified by
column chromatography on Silicagel L (100/160 μm)
using benzene–ethyl acetate (9:1) as eluent. Yield
1.42 g (60%), mp 132–133°C (from 2-propanol). IR
4-(2,4-Dimethoxyphenyl)-2,6-dimethyl-1,4-dihy-
dropyridine-3,5-dicarbonitrile (Ic) was synthesized
in a similar way. The product was purified by flash
chromatography on a dry column charged with
Silicagel L (5/40 μm); gradient elution with hexane,
chloroform, and chloroform–ethyl acetate (1:1). Yield
85%, mp 225–227°C (from ethanol). IR spectrum, ν,
1
cm–1: 2205 (CN), 3450 (NH). H NMR spectrum
(DMSO-d6), δ, ppm: 2.01 s (6H, CH3), 3.77 s (6H,
CH3O), 4.65 s (1H, 4-H); ABX: 6.57 (1H, 5'-H), 6.59
1
spectrum, ν, cm–1: 2230 (CH), 1690 (C=O). H NMR
(1H, 3'-H), 7.08 (1H, 6'-H), J5',3' = 2.4, J6',3' = 0, J5',6'
=
8.0 Hz; 9.41 s (1H, NH). Found, %: C 69.15; H 5.67.
C17H17N3O2. Calculated, %: C 69.14; H 5.80.
spectrum (CDCl3), δ, ppm: 2.66 s (3H, CH3), 2.89 s
(3H, COCH3), 7.53–7.56 (3H, Ph), 7.95–8.02 m (2H,
Ph), 8.35 s (1H, 4-H). Found, %: C 76.39; H 5.12.
C15H12N2O. Calculated, %: C 76.25; H 5.12.
4-(2-Furyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarbonitrile (Id) was synthesized in a similar
way. Yield 62%, mp 174–175°C (from ethanol) [5].
Ethyl 6-chloro-5-cyano-2-methyl-4-phenylpyri-
dine-3-carboxylate (IV). Anhydrous dimethylform-
amide, 0.1 ml, was added to a suspension of 2.70 g
(10 mmol) of ethyl 5-cyano-2-methyl-6-oxo-4-phenyl-
1,6-dihydropyridine-3-carboxylate [9] in 8 ml of
POCl3. The mixture was heated for 2.5 h under reflux,
cooled, and poured onto ~30 g of ice under vigorous
4-(4-Chlorophenyl)-2,6-dimethylpyridine-3,5-
dicarbonitrile (IIa). Sodium nitrite, 1.04 g (15 mmol),
was added in portions to a suspension of 2.70 g
(10 mmol) of dihydropyridine Ia in 30 ml of glacial
acetic acid under stirring at 60–70°C. The mixture was
stirred for 1 h at that temperature, diluted with a 4-fold
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CYANOPYRIDINES. SYNTHESIS AND RECYCLIZATION
1371
stirring. The precipitate was filtered off and washed
with water. Yield 2.44 g (84%), mp 107–108°C (from
ethanol). IR spectrum, ν, cm–1: 1720 (C=O), 2230
(CN). 1H NMR spectrum (CDCl3), δ, ppm: 0.92 t (3H,
CH2CH3, J = 7.2 Hz), 2.67 s (3H, CH3), 4.05 q (2H,
CH2CH3, J = 7.2 Hz), 7.34–7.39 m (5H, Ph). Found,
%: C 63.54; H 4.25. C16H13ClN2O2. Calculated, %:
C 63.90; H 4.36.
J5',6' = 8.0, J3',6' = 0, J5',3' = 2.1 Hz). Found, %: C 52.71;
H 4.44. C18H18ClN3O6. Calculated, %: C 53.01; H 4.45.
3,5-Dicyano-4-(2-furyl)-1,2,6-trimethylpyridi-
nium perchlorate (IIId). The reaction mixture was
heated for 30 h at 65–70°C. Yield 96%, mp 189–191°C
(decomp., from EtOH). 1H NMR spectrum (DMSO-d6),
δ, ppm: 3.13 s (6H, CH3), 4.19 s (3H, CH3), 7.14 d.d
(1H, 4'-H, J4',3' = 3.9, J4',5' = 1.7 Hz), 8.11 d (1H, 3'-H,
J3',4' = 3.9 Hz), 8.53 d (1H, 5'-H, J5',3' = 1.4 Hz). Found,
%: C 49.76; H 3.38. C14H12ClN3O5. Calculated, %:
C 49.79; H 3.58.
Ethyl 5-cyano-2-methyl-4-phenylpyridine-3-car-
boxylate (IIg). A solution of 1.98 g (6.6 mmol) of
chloropyridine IV in a mixture of 14 ml of acetic acid,
14 ml of ethanol, and 4 ml of water was heated on a
water bath to the boiling point, and 2.10 g (26.4 mmol)
of zinc dust was added in portions over a period of 1 h.
The mixture was cooled and filtered, the filtrate was
diluted with water, and the precipitate was filtered off.
Yield 1.33 g (76%), mp 113–114°C (from ethanol). IR
3,5-Dicyano-1,2,4,6-tetramethylpyridinium per-
chlorate (IIIe). The reaction mixture was heated for
50 h at 80–85°C. Yield 64%, mp 151–152°C (from
1
ethanol). H NMR spectrum (DMSO-d6), δ, ppm:
2.93 s (3H, CH3), 3.10 s (6H, CH3), 4.19 s (3H, CH3).
Found, %: C 46.41; H 4.25. C11H12ClN3O4. Calculated,
%: C 46.25; H 4.23.
1
spectrum, ν, cm–1: 1720 (C=O), 2230 (CN). H NMR
spectrum (CDCl3), δ, ppm: 0.94 t (3H, CH2CH3, J =
7.2 Hz), 2.70 s (3H, CH3), 4.08 q (2H, CH2CH3, J =
7.2 Hz), 7.38–7.51 m (5H, Ph), 8.87 s (1H, 6-H).
Found, %: C 72.24; H 5.25. C16H14N2O2. Calculated,
%: C 72.16; H 5.30.
3-Acetyl-5-cyano-1,2-dimethyl-6-phenylpyridi-
nium perchlorate (IIIf). The reaction mixture was
heated for 48 h at 80–85°C. Yield 66%, mp 222–224°C
1
(from water). H NMR spectrum (DMSO-d6), δ, ppm:
2.77 s (3H, CH3), 2.92 s (3H, COCH3), 3.95 s (3H,
CH3), 7.65–7.86 m (5H, Ph), 9.46 s (1H, 4-H). Found,
%: C 54.98; H 4.21; N 7.77. C16H15ClN2O5. Calculat-
ed, %: C 54.79; H 4.31; N 7.99.
General procedure for the synthesis of quater-
nary cyanopyridinum salts IIIa–IIIg. A mixture of
5 mmol of pyridine IIa–IIg and 1.4 ml (15 mmol) of
freshly distilled dimethyl sulfate was heated under the
conditions given below. The mixture was washed with
diethyl ether (3×10 ml), and the ether extracts were
separated by decanting. The residue was dissolved in
a minimal amount of water, and a saturated aqueous
solution of 0.64 g (5.3 mmol) of NaClO4 was added.
The precipitate was filtered off, dried, and purified by
recrystallization.
5-Cyano-3-ethoxycarbonyl-1,2-dimethyl-4-
phenylpyridinium perchlorate (IIIg). The reaction
mixture was heated for 4 h at 75–80°C. Yield 76%,
1
mp 169–171°C (from 50% ethanol). H NMR spec-
trum (DMSO-d6), δ, ppm: 0.91 t (3H, CH2CH3, J =
7.1 Hz), 2.87 s (3H, CH3), 4.15 q (2H, CH2CH3, J =
7.1 Hz), 4.35 s (3H, CH3), 7.49–7.71 m (5H, Ph),
9.96 s (1H, 6-H). Found, %: C 53.65; H 4.62.
C17H17ClN2O6. Calculated, %: C 53.62; H 4.50.
4-(4-Chlorophenyl)-3,5-dicyano-1,2,6-trimethyl-
pyridinium perchlorate (IIIa). The reaction mixture
was heated for 55 h at 90–95°C. Yield 92%, mp 232–
General procedure for the synthesis of α-meth-
ylaminopyridines Va–Vf. Pyridinium perchlorate
IIIa–IIIg, 1 mmol, was dispersed in 4 ml of ethanol,
and 1.8 ml (5 mmol) of 10% aqueous sodium hy-
droxide was added. The mixture immediately turned
brightly colored, and the color disappeared after
heating for a short time (10–20 min) on a water bath.
The mixture was cooled, and the precipitate was
filtered off. The product was purified from tarry
impurities by filtering through a thin layer of silica gel
using chloroform as eluent.
1
234°C (decomp., from ethanol). H NMR spectrum
(DMSO-d6), δ, ppm: 3.18 s (6H, CH3), 4.30 s (3H,
CH3), 7.75 d (2H, 3'-H, 5'-H, J = 8.8 Hz), 7.86 d (2H,
2'-H, 6'-H, J = 8.8 Hz). Found, %: C 50.35; H 3.58.
C16H13Cl2N3O4. Calculated, %: C 50.28; H 3.43.
3,5-Dicyano-4-(2,4-dimethoxyphenyl)-1,2,6-tri-
methylpyridinium perchlorate (IIIc). The reaction
mixture was heated for 48 h at 80–85°C. Yield 65%,
1
mp 115–116°C (from ethanol). H NMR spectrum
(DMSO-d6), δ, ppm: 3.13 s (6H, CH3), 3.89 s (3H,
CH3O), 3.92 s (3H, CH3O), 4.22 s (3H, CH3); ABX:
6.68 (1H, 5'-H), 6.70 (1H, 3'-H), 7.50 (1H, 6'-H),
5-Acetyl-4-(4-chlorophenyl)-2-methyl-6-methyl-
aminopyridine-3-carbonitrile (Va). Yield 77%,
mp 173–174°C (from ethanol). IR spectrum, ν, cm–1:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

SAGITULLINA et al.
1372
1
1650 (C=O), 2220 (CN), 3370 (NH). H NMR spec-
trum (CDCl3), δ, ppm: 1.70 s (3H, CH3), 2.67 s (3H,
COCH3), 3.09 d (3H, NCH3, J = 4.9 Hz), 7.33 d (2H,
3'-H, 5'-H, J = 8.6 Hz), 7.50 d (2H, 2'-H, 6'-H, J =
8.6 Hz), 8.23 br.s (1H, NHCH3). Mass spectrum, m/z
(Irel, %): 301 (25.4), 300 (23.5), 299 (74.2) [M]+, 298
(36.1), 286 (32.9), 285 (17.8), 284 (100), 282 (21.9),
249 (14.7), 43 (20.0), 30 (12.4). Found, %: C 64.47;
H 4.78. C16H14ClN3O. Calculated, %: C 64.11; H 4.71.
3-Acetyl-2,4-dimethyl-6-methylaminopyridine-3-
carbonitrile (Ve). Yield 66%, mp 137–138°C (from
ethanol). IR spectrum, ν, cm–1: 1650 (C=O), 2220
(CN), 3370 (NH). 1H NMR spectrum (CDCl3), δ, ppm:
2.53 s (3H, CH3), 2.59 s (6H, CH3), 3.02 d (3H, NCH3,
J = 4.9 Hz), 7.84 br.s (1H, NHCH3). Mass spectrum,
m/z (Irel, %): 203 (51.2) [M]+, 202 (14.8), 189 (12.0),
188 (100), 186 (20.1), 161 (12.4), 160 (13.8), 132
(13.8), 131 (9.3), 43 (14.7). Found, %: C 65.32;
H 6.42. C11H13N3O. Calculated, %: C 65.01; H 6.45.
3-Acetyl-4-(4-methoxyphenyl)-2-methyl-6-
methylaminopyridine-3-carbonitrile (Vb). Yield
92%, mp 176–177°C (from ethanol). IR spectrum, ν,
3-Acetyl-5-benzoyl-2-methyl-6-methylamino-
pyridine (Vf). Yield 70%, mp 144–145°C (from
ethanol). IR spectrum, ν, cm–1: 1660 (C=O), 3330
cm–1: 1650 (C=O), 2220 (CN), 3360 (NH). H NMR
1
1
spectrum (CDCl3), δ, ppm: 1.68 s (3H, CH3), 2.66 s
(3H, COCH3), 3.08 d (3H, NCH3, J = 4.9 Hz), 3.87 s
(3H, CH3O), 7.01 d (2H, 3'-H, 5'-H, J = 8.8 Hz), 7.31 d
(2H, 2'-H, 6'-H, J = 8.8 Hz), 8.11 br.s (1H, NHCH3).
Mass spectrum, m/z (Irel, %): 296 (14.3), 295 (74.4)
[M]+, 294 (35.0), 281 (18.8), 280 (100), 278 (19.3),
265 (12.4), 252 (11.4), 237 (11.8), 43 (17.8). Found,
%: C 69.01; H 5.68. C17H17N3O2. Calculated, %:
C 69.14; H 5.80.
(NH). H NMR spectrum (CDCl3), δ, ppm: 2.33 s
(3H, CH3), 2.77 s (3H, COCH3), 3.20 d (3H, NCH3,
J = 4.8 Hz), 7.46–7.62 m (5H, Ph), 8.20 s (1H, 4-H),
9.16 br.s (1H, NHCH3). Found, %: C 76.56; H 6.33;
N 5.10. C17H17NO2. Calculated, %: C 76.38; H 6.41;
N 5.24.
Recyclization of 5-cyano-3-ethoxycarbonyl-1,2-
dimethyl-4-phenylpyridinium perchlorate (IIIg).
The reactant ratio was the same as in the general
procedure for the synthesis of α-methylaminopyri-
dines. The reaction mixture was stirred for 1 h at room
temperature, diluted with an equal volume of water,
acidified with 50% acetic acid on cooling, and treated
with chloroform. The extract was dried over magne-
sium sulfate and evaporated, and the products,
α-methylaminopyridine Vg and pyridinone VI, were
separated by column chromatography on Silicagel L
(100/160 μm) using chloroform as eluent.
3-Acetyl-4-(2,4-dimethoxyphenyl)-2-methyl-6-
methylaminopyridine-3-carbonitrile (Vc). Yield
79%, mp 155–156°C (from ethanol). IR spectrum, ν,
cm–1: 1650 (C=O), 2220 (CN), 3360 (NH). H NMR
1
spectrum (CDCl3), δ, ppm: 1.77 s (3H, CH3), 2.64 s
(3H, COCH3), 3.07 d (3H, NCH3, J = 4.9 Hz), 3.83 s
(3H, CH3O), 3.86 s (3H, CH3O); ABX: 6.57 (1H, 5'-H),
6.58 (1H, 3'-H), 7.00 (1H, 6'-H), J5',3' = 2.3, J6',3' = 0,
J5',6' = 8.3 Hz; 8.35 br.s (1H, NHCH3). Mass spectrum,
m/z (Irel, %): 325 (78.5) [M]+, 311 (13.3), 310 (68.7),
308 (13.2), 295 (27.9), 294 (100), 282 (22.6), 266
(8.7), 43 (14.3), 28 (13.6). Found, %: C 66.82; H 5.78.
C18H19N3O3. Calculated, %: C 66.45; H 5.89.
Ethyl 5-formyl-6-methyl-2-methylamino-4-phen-
ylpyridine-3-carboxylate (Vg). Yield 43%, mp 81–
82°C (from ethanol). IR spectrum, ν, cm–1: 1715, 1645
1
(C=O); 3330 (NH). H NMR spectrum (CDCl3), δ,
3-Acetyl-4-(2-furyl)-2-methyl-6-methylamino-
pyridine-3-carbonitrile (Vd). Yield 73%, mp 140–
141°C (from ethanol). IR spectrum, ν, cm–1: 1650
ppm: 0.84 t (3H, CH2CH3, J = 7.1 Hz), 2.54 s (3H,
CH3), 3.15 d (3H, NCH3, J = 5.0 Hz), 3.89 q (2H,
CH2CH3, J = 7.2 Hz), 7.23–7.42 m (5H, C6H5),
9.06 br.s (1H, NHCH3), 9.53 s (1H, CHO). Mass spec-
trum, m/z (Irel, %): 299 (19.7), 298 (100) [M]+, 297
(12.9), 270 (19.9), 269 (41.7), 253 (24.2), 242 (25.5),
241 (56.2), 225 (40.3). Found, %: C 68.08; H 6.14.
C17H18N2O3. Calculated, %: C 68.44; H 6.08.
1
(C=O), 2210 (CN), 3370 (NH). H NMR spectrum
(CDCl3), δ, ppm: 1.78 s (3H, CH3), 2.67 s (3H,
COCH3), 3.06 d (3H, NCH3, J = 4.9 Hz), 6.67 d.d (1H,
4'-H, J4',3' = 3.5, J4',5' = 1.8 Hz), 7.17 d.d (1H, 3'-H,
J3',4' = 3.5, J3',5' = 0.7 Hz), 7.64 d.d (1H, 5'-H, J5',4'
=
1.8, J5',3' = 0.7 Hz), 7.83 br.s (1H, NHCH3). Mass
spectrum, m/z (Irel, %): 256 (15.8), 255 (100) [M]+, 240
(54.4), 226 (11.8), 213 (46.0), 212 (22.7), 201 (10.1),
198 (10.1), 197 (10.0), 196 (25.1), 185 (21.0), 184
(26.3), 169 (8.0), 156 (8.6), 43 (41.1). Found, %:
C 66.10; H 5.23. C14H13N3O2. Calculated, %: C 65.87;
H 5.13.
5-Acetyl-1-methyl-6-oxo-4-phenyl-1,6-dihydro-
pyridine-3-carbonitrile (VI). Yield 7%, mp 173–
173.5°C (from ethanol). IR spectrum, ν, cm–1: 2220
1
(CN); 1710, 1660 (C=O). H NMR spectrum (CDCl3),
δ, ppm: 2.19 s (3H, COCH3), 3.65 s (3H, NCH3), 7.30–
7.49 m (5H, Ph), 7.95 s (1H, 6-H). Mass spectrum, m/z
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

CYANOPYRIDINES. SYNTHESIS AND RECYCLIZATION
1373
(Irel, %): 253 (12.3), 252 (67.7) [M]+, 251 (100), 238
REFERENCES
(17.8), 237 (95.9), 210 (9.2), 196 (42.4), 140 (18.8),
127 (10.1), 43 (21.9), 42 (44.6), 31 (11.7). Found, %:
C 71.30; H 4.68. C15H12N2O2. Calculated, %: C 71.42;
H 4.79.
1. Gromov, S.P., Kost, A.N., and Sagitullin, R.V., Zh. Org.
Khim., 1978, vol. 14, p. 1316.
2. Shkil, G.P., Lusis, V., Muceniece, D., and Sagitul-
lin, R.S., Tetrahedron, 1995, vol. 51, p. 8599.
6-Methylamino-3-nitro-2,4-diphenylbenzonitrile
(VII). Pyridinium perchlorate IIIh, 0.44 g (1 mmol),
was dispersed in 4 ml of ethanol, and 1.8 ml (5 mmol)
of 10% aqueous sodium hydroxide was added. The
mixture was stirred for 6 h at room temperature and
diluted with water, and the precipitate was filtered off
and recrystallized from ethanol. Yield 0.21 g (62%),
yellow crystals, mp 194–195°C. IR spectrum, ν, cm–1:
3. Shkil’, G.P., Berdovich, L.V., Lusis, V., Mutsenietse, D.,
and Sagitullin, R.S., Khim. Geterotsikl. Soedin., 1995,
p. 86.
4. Zandersons, A.Z., Lusis, V.K., Mutsenietse, D.Kh., and
Dubur, G.Ya., Khim. Geterotsikl. Soedin., 1987, p. 81.
5. Balicki, R. and Mordarski, M., Polish Patent no. 86477,
1976; Ref. Zh., Khim., 1978, no. 13O120P.
6. Lukes, R. and Kuthan, J., Collect. Czech. Chem.
Commun., 1961, vol. 26, p. 1845.
1
3430 (NH); 2215 (CN); 1530, 1360 (NO2). H NMR
7. Bottorff, E.M., Jones, R.G., Kornfeld, E.C., and
Mann, M.J., J. Am. Chem. Soc., 1951, vol. 73, p. 4380.
8. Pyrko, A.N., Khim. Geterotsikl. Soedin., 1999, p. 774.
9. Krauze, A.A., Liepin’sh, E.E., Kalme, Z.A., Pel-
cher, Yu.E., and Dubur, G.Ya., Khim. Geterotsikl.
Soedin., 1984, p. 1504.
10. Sagitullina, G.P., Glizdinskaya, L.V., Sitnikov, G.V., and
Sagitullin, R.S., Khim. Geterotsikl. Soedin., 2002,
p. 1518.
11. Nesmeyanov, A.N. and Rybinskaya, M.I., Izv. Akad.
Nauk SSSR, Ser. Khim., 1961, p. 816.
12. Lukes, R. and Kuthan, J., Collect. Czech. Chem.
Commun., 1961, vol. 26, p. 1422.
spectrum (CDCl3), δ, ppm: 2.99 d (3H, NCH3, J =
4.8 Hz), 5.20 br.s (1H, NHCH3), 6.58 s (1H, 6-H),
7.30–7.54 m (10H, Harom). Mass spectrum, m/z
(Irel, %): 330 (23.8), 329 [M]+ (100), 312 (8.2), 300
(18.8), 299 (14.5), 297 (12.1), 284 (24.3), 283 (10.8),
282 (12.1), 281 (14.8), 272 (20.6), 255 (11.8), 254
(13.2), 253 (11.0), 240 (14.2), 220 (11.2), 28 (10.7).
Found, %: C 72.86; H 4.59. C20H15N3O2. Calculated,
%: C 72.94; H 4.59.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-32652).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005