Anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds in the synthesis of new sulfur-containing pyridines and quinolines

Article abstract of DOI:10.1023/A:1020939712830

Simple methods for the synthesis of previously unknown sulfur-containing pyridin-2-ones and 5,6,7,8-tetrahydroquinolines from cyanothioacetamide and anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds were developed. Structures and chemical transformations of compounds obtained were studied.

Full text of DOI:10.1023/A:1020939712830

1556
Russian Chemical Bulletin, International Edition, Vol. 51, No. 8, pp. 1556—1561, August, 2002
Anilinomethylidene derivatives of cyclic 1,3ꢀdicarbonyl compounds
in the synthesis of new sulfurꢀcontaining pyridines and quinolines
V. V. Dotsenko,a S. G. Krivokolysko,a A. N. Chernega,b and V. P. Litvinovc
ꢀ
aEastꢀUkrainian National University,
20a kv. Molodyojny, 91034 Lugansk, Ukraine.
Fax: +7 (064 2) 46 3061. Eꢀmail: ksg@lep.lg.ua
bInstitute of Organic Chemistry, National Academy of Sciences of the Ukraine,
5 ul. Murmanskaya, 02094 Kiev, Ukraine.
Fax: +7 (044) 573 2643. Eꢀmail: iochkiev@ukrpack.net
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: vpl@cacr.ioc.ac.ru
Simple methods for the synthesis of previously unknown sulfurꢀcontaining pyridinꢀ2ꢀones
and 5,6,7,8ꢀtetrahydroquinolines from cyanothioacetamide and anilinomethylidene derivaꢀ
tives of cyclic 1,3ꢀdicarbonyl compounds were developed. Structures and chemical transforꢀ
mations of compounds obtained were studied.
Key words: pyridinones, tetrahydroquinolines, alkylation, bromination, Xꢀray diffraction
analysis.
Scheme 1
Derivatives of sulfurꢀcontaining pyridines and quinoꢀ
lines possess a rather broad spectrum of useful biological
activity.1,2 At the same time, the progress in this area of
heterocyclic chemistry is impeded by a limited number
of methods for their synthesis, which in turn is due to
the fact that the starting substrates and reagents are diffiꢀ
cultly accessible. Aiming at the development of conveꢀ
nient methods for the synthesis of functionalized azines
based on cascade heterocyclization and multiꢀcompoꢀ
nent condensation of simple and accessible reagents,3
we studied the reactions of cyanothioacetamide with
anilinomethylidene derivatives of cyclic 1,3ꢀdicarbonyl
compounds 1a—c.
Results and Discussion
Reactions of diketones 1a,b with thioamide 2 in EtOH
in the presence of KOH at 20 °C afford the correspondꢀ
ing thiones 3 in 80—82% yield, while Meldrum´s acid
derivative 1c reacts with compound 2 to give acid 4 in
64% yield (Scheme 1).
R = H, X = CH2 (a); R = Me, X = CH2 (b); R = Me, X = O (c)
Reactions of compounds 3 with alkyl halides 5a—c
yielded sulfides 6. In the case of compounds 5d—f havꢀ
ing an active methylene group, the corresponding sulꢀ
fides 6 undergo the in situ Thorpe—Ziegler cyclization
into thieno[2,3ꢀb]quinolines 7 (Scheme 2).
tion 6 of the tetrahydroquinoline ring to give bromide 8
(see Scheme 2).
Alkylation of thiol 4 with halides 5 in aqueous ethaꢀ
nol in the presence of KOH is also highly Sꢀregioselective
to give substituted pyridinones 9 and 10 as the reaction
products (Scheme 3). Heating of the pyridine derivaꢀ
tive 9d with I2 in EtOH yields 90% of dihydrothiazoꢀ
Like 3ꢀcyanoꢀ1,2,5,6,7,8ꢀhexahydroquinolineꢀ2,5ꢀ
dione,4 compound 6b is brominated in MeOH at posiꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1432—1436, August, 2002.
1066ꢀ5285/02/5108ꢀ1556 $27.00 © 2002 Plenum Publishing Corporation

Pyridinecarboxylic acids and tetrahydroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1557
Scheme 2
Scheme 3
5
Hal
R´
a
I
H
b
Cl
Ph
c
Br
Me
d
Cl
e
Cl
f
Br
Bz
CONH2 CONHPh
6
R
R´
a
H
H
b
Me
H
c
Me
Ph
d
Me
Me
7
R
a
H
b
H
c
H
Bz
d
Me
e
Me
f
Me
Bz
5g: R´ = CH=CH2, Hal = Br (R´ and Hal for 5a—f see Scheme 2)
R´ CONH2 CONHPh
CONH2 CONHPh
9
a
b
c
d
10
a
b
c
R´
H
Ph
Me CH=CH2
R´
CONH2 CONHPh Bz
lo[3,2ꢀa]pyridine 11. Oxidation of compound 4 with H2O2
under mild conditions gives disulfide 12.
Reagents and conditions: i. KOH/EtOH. ii. I2/EtOH, ∆.
iii. H2O2, KOH, 50% EtOH, 20 °C.
The structure of product 11 was proved unambiguꢀ
ously by Xꢀray diffraction analysis (Fig. 1). Selected bond
lengths and angles are given in Table 1. The bicyclic
S(1)N(1)C(1)—C(7) system can be regarded as approxiꢀ
mately planar since the deviations of the atoms from the
meanꢀsquare plane reach 0.14 Å. The fiveꢀmembered
Table 1. Selected bond lengths (d) and angles (ω) in comꢀ
pound 11
O(3)
C(5)
C(10)
O(2)
Bond
d/Å
Angle
ω/deg
C(4)
N(2)
C(6)
C(7)
C(9)
I(1)—C(8)
S(1)—C(1)
S(1)—C(3)
2.136(5)
1.822(5)
1.712(5)
C(1)—S(1)—C(3)
C(2)—N(1)—C(3)
C(2)—N(1)—C(7)
C(3)—N(1)—C(7)
S(1)—C(1)—C(2)
N(1)—C(2)—C(1)
S(1)—C(3)—N(1)
N(1)—C(3)—C(4)
C(3)—C(4)—C(5)
C(4)—C(5)—C(6)
C(5)—C(6)—C(7)
N(1)—C(7)—C(6)
N(2)—C(9)—C(4)
92.5(3)
115.6(4)
121.0(4)
123.4(4)
108.1(4)
107.4(4)
114.4(3)
120.0(4)
119.0(4)
121.7(4)
119.9(4)
116.0(4)
177.4(5)
C(3)
H(2)
O(1)—C(7) 1.241(6)
O(2)—C(10) 1.341(6)
O(3)—C(10) 1.197(6)
N(1)—C(2) 1.489(6)
N(1)—C(3) 1.356(6)
N(1)—C(7) 1.396(6)
C(1)—C(2) 1.525(8)
C(3)—C(4) 1.389(7)
C(4)—C(5) 1.382(7)
C(5)—C(6) 1.373(7)
C(6)—C(7) 1.442(7)
C(6)—C(10) 1.491(7)
S(1)
N(1)
O(1)
C(1)
C(2)
C(8)
I(1)
Fig. 1. General view of structure 11 with the numbering of
nonhydrogen atoms.

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Dotsenko et al.
heterocycle has a substantially flattened envelope conꢀ
formation with a dihedral angle of 14.1° between the
S(1)C(1)C(2) fragment and the S(1)C(3)N(1)C(2) plane.
The interatomic S(1)—C(1) (1.822(5) Å) and S(1)—C(3)
bond angles is 360.0(1.2)°. The geometrical parameters
of the sixꢀmembered N(1)C(3)—C(7) ring indicate a
significant electron density delocalization.5,7 Strucꢀ
ture 11 contains a rather strong8 intramolecular hydroꢀ
gen O(2)—H(2)...O(1) bond (O(1)...O(2) 2.565(6) Å,
O(1)...H(2) 1.64(7) Å, O(2)—H(2) 0.97(7) Å, the
O(1)—H(2)—O(2) angle 158(3)°).
(1.712(5) Å) distances are typical of the S—Csp and
3
S—Csp bonds, respectively.5,6 The bond configuration
2
at the N(1) atom is planar trigonal; the sum of the N(1)
Table 2. Spectral characteristics of compounds 3, 4, and 6—12
Comꢀ
pound
IR, ν/cm–1
1H NMR, δ (J/Hz)
3a
3b
4
3170, 3090, 3070 (NH);
2224 (CN); 1660 (C=O)
3185, 3128, 3060 (NH);
2228 (CN); 1660 (C=O)
3230—3030 (NH, OH);
2227 sh, 2216 (CN);
2.07, 2.56, 3.05 (all m, 6 H, (СH2)3); 8.14 (s, 1 H, H(4));
14.15 (br.s, 1 H, NH)
1.05 (s, 6 H, 2 Me); 2.44, 2.93 (both br.s, 2 H each, (СH2)2);
8.28 (s, 1 H, H(4)); 14.31 (br.s, 1 H, NH)
7.89 (s, 1 H, H(4)); 11.95 (br.s, 1 H, NH);
13.93 (br.s, 1 H, СООH)a
1675, 1680 (2 C=O)
6a
6b
6c
2228 (CN); 1690 (C=O)
2.16, 2.63, 3.13 (all m, 6 H, (СH2)3); 2.67 (s, 3 H, SMe);
8.30 (s, 1 H, H(4))
1.07 (s, 6 H, 2 Me); 2.53, 3.11 (both br.s, 2 H each, (СH2)2);
2.66 (s, 3 H, SMe); 8.32 (s, 1 H, H(4))
1.11 (s, 6 H, 2 Me); 2.55, 3.12 (both br.s, 2 H each, (СH2)2);
4.56 (br.s, 2 H, SCH2); 7.28 (m, 3 H, Аr); 7.35 (m, 2 H, Аr);
8.34 (s, 1 H, H(4))
2227 (CN); 1686 (C=O)
2224 (CN); 1687 (C=O)
6d
2218 (CN); 1687 (C=O)
1.10 (s, 6 H, 2 Me); 1.42 (t, 3 H, SСH2СH3, 3J = 7.4);
2.53, 3.03 (both br.s, 2 H each, (СH2)2); 3.31 (q, 2 H, SCH2,
3J = 7.4); 8.30 (s, 1 H, H(4))
7a
7b
3415, 3375, 3245 (2 NH2);
1690, 1650 (2 C=O)
3420, 3357, 3295 (NH2, NH);
1675, 1624 (2 C=O)
2.20, 2.68, 3.18 (all m, 6 H, (СH2)3); 6.95, 7.30 (both br.s,
2 H each, NH2, CONH2); 8.94 (s, 1 H, H(4))
2.23, 2.72, 3.17 (all m, 6 H, (СH2)3); 7.07, 7.30 (both m, 3 H, Аr);
7.54 (br.s, 2 H, NH2); 7.72 (d, 2 H, Аr, 3J = 7.7); 9.05 (s, 1 H,
H(4)); 9.35 (s, 1 H, NHCO)
7c
7d
7e
3355, 3235, 3170 (NH2);
1675 (2 C=O)
3440, 3265, 3150 (2 NH2);
1676, 1641 (2 C=O)
3410—3280 (NH2, NH);
1670, 1632 (2 C=O)
2.20, 2.70, 3.15 (all m, 6 H, (СH2)3); 7.51, 7.75 (both m, 5 H, Ar);
8.54 (br.s, 2 H, NH2); 9.17 (s, 1 H, H(4))
1.11 (s, 6 H, 2 Me); 2.57, 3.12 (both br.s, 2 H each, (СH2)2);
6.97, 7.30 (both br.s, 2 H each, NH2, CONH2); 8.93 (s, 1 H, H(4))
1.13 (s, 6 H, 2 Me); 2.60, 3.14 (both br.s, 2 H, (СH2)2);
7.03, 7.28 (both m, 3 H, Аr); 7.52 (br.s, 2 H, NH2); 7.71 (d, 2 H,
Аr, 3J = 8.1); 9.02 (s, 1 H, H(4)); 9.31 (s, 1 H, NHCO)
1.13 (s, 6 H, 2 Me); 2.58, 3.08 (both br.s, 2 H each, (СH2)2);
7.50, 7.77 (both m, 5 H, Аr); 8.54 (br.s, 2 H, NH2);
9.19 (s, 1 H, H(4))
7f
8
3335, 3235, 3100 (NH2);
1673 (2 C=O)
2225 (CN); 1688 (C=O)
1.15, 1.23 (both s, 3 H each, 2 Me); 2.65 (s, 3 H, SMe);
2
2.96, 3.19 (both d, 2 H, H2С(8), J = 18.0); 4.59
(s, 1 H, H(6)); 8.38 (s, 1 H, H(4))
9a
3420, 3210—3000 (NH, OH);
2223 (CN); 1735,
2.65 (s, 3 H, SMe); 8.33 (s, 1 H, H(4))b
1682 (2 C=O)
9b
9c
9d
3430, 3240—3050 (NH, OH);
2228 (CN); 1708, 1640 (2 C=O)
3395, 3240—3100 (NH, OH);
2227 (CN); 1725, 1690 (2 C=O)
3415, 3270—3100 (NH, OH);
2222 (CN); 1723, 1688 (2 C=O)
4.52 (br.s, 2 H, SCH2); 7.27 (m, 3 H, Аr); 7.42 (m, 2 H, Ar);
8.31 (s, 1 H, H(4))b
1.40 (t, 3 H, SCH2CH3, 3J = 7.4); 3.27 (q, 2 H, SCH2, 3J = 7.4);
8.30 (s, 1 H, H(4))b
3.95 (br.d, 2 H, SCH2, 3J = 7.0); 5.16 (d, 1 H, cisꢀСH2=СH,
3J = 10.0); 5.37 (d, 1 H, transꢀСH2=СH, 3J = 17.5); 5.93
(m, 1 H, СH=СH2); 8.33 (s, 1 H, H(4))b
(to be continued)

Pyridinecarboxylic acids and tetrahydroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1559
Table 2 (continued)
Comꢀ
pound
IR, ν/cm–1
1H NMR, δ (J/Hz)
10a
10b
10c
3435, 3355, 3315—3050
(2 NH2, OH, NH);
1740, 1675, 1648 (3 C=O)
3420, 3340, 3310, 3210—3050
(2 NH, NH2, OH);
1738, 1625 (3 C=O)
3390, 3322, 3210—3060
(NH2, NH, OH);
6.86 (br.s, 2 H, NH2); 7.31, 7.34 (both br.s, 2 H, CONH2);
9.12 (s, 1 H, H(4))b
7.00 (t, 1 H, Ph, 3J = 7.3); 7.25 (dd, 2 H, Ph, 3J = 7.3, 3J = 7.9);
7.64 (m, 4 H, NH2, Ph); 9.18, 9.20 (both s, 1 H each, H(4), CONH)b
7.49 (m, 3 H, Ph); 7.66 (d, 2 H, Ph, 3J = 7.6); 8.51 (br.s,
2 H, NH2); 9.28 (s, 1 H, H(4))b
1725, 1633 (3 C=O)
11
12
3460—3050 (OH); 2227 sh,
2217 (CN); 1740, 1690 (2 C=O)
3420, 3368, 3195—3040
(2 NH, 2 OH); 2230, 2215 sh.
(2 CN); 1715, 1653 (4 C=O)
3.58—4.10 (m, 4 H, SCH2, CH2I); 5.43 (m, 1 H, H(3));
8.33 (s, 1 H, H(7))c
8.00 (s, 2 H, 2 H(4)); 10.87 (br.s, 2 H, 2 NHCO);
13.93 (br.s, 2 H, 2 COOH)
a No signal for the SH group appears because of deuterium exchange.
b No signals for the COOH and NH groups appear because of deuterium exchange.
c No signal for the COOH group appears because of deuterium exchange.
H, 7.07; N, 5.76. C15H17NO2. Calculated (%): C, 74.05;
H, 7.04; N, 5.76. 1H NMR, δ: 1.06 (s, 6 H, 2 Me); 2.30, 2.38
(both br.s, 2 H each, (CH2)2); 7.17—7.41 (m, 5 H, Ph); 8.48
The structures of products 3, 4, and 6—12 were deꢀ
termined from the data of physicochemical studies (see
Experimental and Table 2).
3
(d, 2 H, CH=, J = 13.7 Hz); 12.75 (d, 1 H, NH).
5ꢀAnilinomethylideneꢀ2,2ꢀdimethylꢀ1,3ꢀdioxaneꢀ4,6ꢀdione
(1c). Yield 92%, m.p. 156—157 °C. Found (%): C, 63.19;
H, 5.32; N, 5.66. C13H13NO4. Calculated (%): C, 63.15;
H, 5.30; N, 5.67. H NMR, δ: 1.70 (s, 6 H, 2 Me); 7.19—7.51
(m, 5 H, Ph); 8.58 (d, 2 H, CH=, 3J = 14.7 Hz); 11.27
(d, 1 H, NH).
Cyanothioxohexahydroquinolinones 3a,b and dihydropyridineꢀ
carboxylic acid 4 (general procedure). Potassium hydroxide
(11.2 g, 0.2 mol) was added to a vigorously stirred suspension
of a 1,3ꢀdicarbonyl compound (1a—c) (0.1 mol) and cyanoꢀ
thioacetamide (2) (10.01 g, 0.1 mol) in 100 mL of EtOH. After
24 h, the reaction mixture was acidified with conc. HCl to
pH 5 and kept for 3 h. The precipitate that formed was filtered
off and washed successively with water and EtOH.
Experimental
1
1
H NMR spectra were recorded on Gemini 200 (200 MHz),
Bruker DRXꢀ500 (500 MHz) (for 3b), and Bruker AMꢀ300
(300 MHz) (for 4) instruments in DMSOꢀd6 with Me4Si as the
internal standard. IR spectra were recorded in Nujol on an
IKSꢀ29 spectrophotometer. Elemental analysis for C, H, and
N was performed on a Perkin—Elmer C,H,Nꢀanalyzer. The
course of the reaction was monitored and the purity of the
compounds synthesized was checked by TLC on Silufol UVꢀ254
plates in acetone—hexane (3 : 5); spots were visualized with
iodine vapors. Melting points were determined on a Kofler
microscope stage.
Anilinomethylidene derivatives of 1,3ꢀdicarbonyl compounds
1a—c (general procedure). A mixture of a 1,3ꢀdicarbonyl comꢀ
pound (0.1 mol), triethyl orthoformate (21.6 mL, 0.13 mol),
and freshly distilled aniline (9.1 mL, 0.1 mol) was refluxed with
vigorous stirring for 5 min and distillation of volatile products
to afford a syrupy reaction mass. It was diluted with 30 mL of
EtOH and refluxed for an additional 3 min. Then it was cooled
with stirring to ∼20 °C and diluted with water to 100 mL. After
2 h, the product was filtered off and washed with water, twice
with 60% EtOH, and with hexane.
3ꢀCyanoꢀ2ꢀthioxoꢀ1,2,5,6,7,8ꢀhexahydroquinolinꢀ5ꢀone
(3a). Yield 80%, m.p. >300 °C (from AcOH—DMF, 1 : 1).
Found (%): C, 58.92; H, 4.01; N, 13.89. C10H8N2OS. Calcuꢀ
lated (%): C, 58.81; H, 3.95; N, 13.72.
3ꢀCyanoꢀ7,7ꢀdimethylꢀ2ꢀthioxoꢀ1,2,5,6,7,8ꢀhexahydroꢀ
quinolinꢀ5ꢀone (3b). Yield 82%, m.p. >300 °C (from
AcOH—DMF, 1 : 1). Found (%): C, 62.19; H, 5.27; N, 12.18.
C12H12N2OS. Calculated (%): C, 62.04; H, 5.21; N, 12.06.
5ꢀCyanoꢀ6ꢀmercaptoꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarboxyꢀ
lic acid (4). Yield 64%, decomp. 340—345 °C (from water).
Found (%): C, 43.02; H, 2.08; N, 14.41. C7H4N2O3S. Calcuꢀ
lated (%): C, 42.85; H, 2.06; N, 14.28.
2ꢀAnilinomethylidenecyclohexaneꢀ1,3ꢀdione (1a). Yield 70%,
m.p. 122—123 °C. Found (%): C, 72.56; H, 6.11; N, 6.50.
C
13H13NO2. Calculated (%): C, 72.54; H, 6.09; N, 6.51.
Tetrahydroquinolinones 6a—d (general procedure). A 10%
aqueous solution of KOH (2.5 mL, 4.5 mmol) was added to a
suspension of thiones 3a,b (4.5 mmol) in 25 mL of EtOH. The
reaction mixture was heated with stirring to 50 °C (until the
starting reagent was dissolved) and filtered into a solution of an
alkyl halide (5a—c) (4.5 mmol) in 10 mL of EtOH. After 12 h,
1H NMR, δ: 1.95 (m, 2 H, C(5)H2); 2.45 (m, 4 H, C(4)H2,
C(6)H2); 7.21—7.41 (m, 5 H, Ph); 8.49 (d, 1 H, CH=, 3J =
13.3 Hz); 12.76 (d, 1 H, NH).
2ꢀAnilinomethylideneꢀ5,5ꢀdimethylcyclohexaneꢀ1,3ꢀdione
(1b). Yield 89%, m.p. 137—138 °C. Found (%): C, 74.09;

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Dotsenko et al.
the reaction mixture was diluted with 15 mL of water, and the
solid precipitate that formed was filtered off and washed with
50% EtOH.
3ꢀCyanoꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetrahydroquinolinꢀ5ꢀone
(6a). Yield 70%, m.p. 136—138 °C (from EtOH). Found (%):
C, 60.75; H, 4.66; N, 12.94. C11H10N2OS. Calculated (%):
C, 60.53; H, 4.62; N, 12.83.
in 10 mL of MeOH was slowly added dropwise. The reaction
mixture was stirred for an additional 30 min and diluted
with water. The precipitate that formed was filtered off
and washed with 50% EtOH to give compound 8 (3.32 g,
60%), m.p. 149—150 °C (from EtOH). Found (%): C, 47.95;
H, 4.07; N, 8.59. C13H13BrN2OS. Calculated (%): C, 48.01;
H, 4.03; N, 8.61.
3ꢀCyanoꢀ7,7ꢀdimethylꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetrahydroꢀ
quinolinꢀ5ꢀone (6b). Yield 78%, m.p. 154—156 °C (from
MeOH). Found (%): C, 63.50; H, 5.82; N, 11.43. C13H14N2OS.
Calculated (%): C, 63.39; H, 5.73; N, 11.37.
2ꢀBenzylthioꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ5,6,7,8ꢀtetrahydroꢀ
quinolinꢀ5ꢀone (6c). Yield 81%, m.p. 132—134 °C (from
MeOH—water, 4 : 1). Found (%): C, 70.89; H, 5.68; N, 8.82.
C19H18N2OS. Calculated (%): C, 70.78; H, 5.63; N, 8.69.
3ꢀCyanoꢀ2ꢀethylthioꢀ7,7ꢀdimethylꢀ5,6,7,8ꢀtetrahydroꢀ
quinolinꢀ5ꢀone (6d). Yield 70%, m.p. 105—106 °C (from
MeOH—water, 4 : 1). Found (%): C, 64,68; H, 6.23; N, 10.86.
Pyridinecarboxylic acids 9a—d and 10a—c (general proceꢀ
dure). A 10% aqueous solution of KOH (2.97 mL, 5.3 mmol)
was added to a stirred suspension of acid 4 (0.5 g, 2.6 mmol) in
10 mL of 50% aqueous ethanol. The reaction mixture was
dissolved by heating and filtered into a solution of an alkyl
halide (5a—g) (2.6 mmol) in 5 mL of EtOH. The resulting
solution was refluxed for 5 min, left for 48 h, and acidified with
conc. HCl to pH 5. After 3 h, the precipitate that formed was
filtered off and washed with 50% EtOH.
5ꢀCyanoꢀ6ꢀmethylthioꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarꢀ
boxylic acid (9a). Yield 76%, m.p. 246—247 °C (from MeOH).
Found (%): C, 45.84; H, 2.89; N, 13.36. C8H6N2O3S. Calcuꢀ
lated (%): C, 45.71; H, 2.88; N, 13.33.
C
14H16N2OS. Calculated (%): C, 64.59; H, 6.19; N, 10.76.
3ꢀAminotetrahydrothieno[2,3ꢀb]quinolinꢀ5ꢀones 7a—f (genꢀ
eral procedure). A 10% aqueous solution of KOH (2.8 mL,
5 mmol) was added to a stirred suspension of thiones 3a,b
(4.5 mmol) in 8 mL of DMF. The reaction mixture was brought
to boiling and filtered into a solution of an alkyl halide (5d—f)
(4.5 mmol) in 5 mL of DMF. The reaction mixture was
stirred for 2 h, left for 24 h, and brought to boiling. Then a
10% aqueous solution of KOH (2.8 mL, 5 mmol) was added,
and refluxing was continued for an additional 3 min. After 4 h,
the precipitate that formed was filtered off and washed
with EtOH.
3 ꢀ A m i n o ꢀ 2 ꢀ c a r b a m o y l ꢀ 5 , 6 , 7 , 8 ꢀ t e t r a h y d r o t h i e ꢀ
no[2,3ꢀb]quinolinꢀ5ꢀone (7a). Yield 85%, decomp. 320 °C (from
AcOH—DMF, 3 : 1). Found (%): C, 55.28; H, 4.27; N, 16.15.
C12H11N3O2S. Calculated (%): C, 55.16; H, 4.24; N, 16.08.
3ꢀAminoꢀ2ꢀ(Nꢀphenylcarbamoyl)ꢀ5,6,7,8ꢀtetrahydroꢀ
thieno[2,3ꢀb]quinolinꢀ5ꢀone (7b). Yield 75%, m.p. 291—292 °C
(from AcOH—DMF, 4 : 1). Found (%): C, 64.19; H, 4.53;
N, 12.54. C18H15N3O2S. Calculated (%): C, 64.08; H, 4.48;
N, 12.45.
3ꢀAminoꢀ2ꢀbenzoylꢀ5,6,7,8ꢀtetrahydrothieno[2,3ꢀb]quinolinꢀ
5ꢀone (7c). Yield 83%, m.p. 263—264 °C (from AcOH).
Found (%): C, 67.04; H, 4.45; N, 8.66. C18H14N2O2S. Calcuꢀ
lated (%): C, 67.06; H, 4.38; N, 8.69.
3ꢀAminoꢀ2ꢀcarbamoylꢀ7,7ꢀdimethylꢀ5,6,7,8ꢀtetrahydroꢀ
thieno[2,3ꢀb]quinolinꢀ5ꢀone (7d). Yield 78%, m.p. 278—280 °C
(from AcOH—DMF, 3 : 1). Found (%): C, 58.22; H, 5.30;
N, 14.61. C14H15N3O2S. Calculated (%): C, 58.11; H, 5.23;
N, 14.52.
3ꢀAminoꢀ7,7ꢀdimethylꢀ2ꢀ(Nꢀphenylcarbamoyl)ꢀ5,6,7,8ꢀ
tetrahydrothieno[2,3ꢀb]quinolinꢀ5ꢀone (7e). Yield 75%, m.p.
270—272 °C (from EtOH—Me2CO, 1 : 1). Found (%): C, 65.82;
H, 5.29; N, 11.62. C20H19N3O2S. Calculated (%): C, 65.73;
H, 5.24; N, 11.50.
3ꢀAminoꢀ2ꢀbenzoylꢀ7,7ꢀdimethylꢀ5,6,7,8ꢀtetrahydroꢀ
thieno[2,3ꢀb]quinolinꢀ5ꢀone (7f). Yield 80%, m.p. 232—234 °C
(from AcOH). Found (%): C, 68.69; H, 5.24; N, 8.10.
C20H18N2O2S. Calculated (%): C, 68.55; H, 5.18; N, 7.99.
6ꢀBromoꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetraꢀ
hydroquinolinꢀ5ꢀone (8). A suspension of quinolinone 6b (4.19 g,
17 mmol) in 50 mL of anhydrous MeOH was heated with
stirring to 50 °C, and then a solution of Br2 (0.87 mL, 17 mmol)
6ꢀBenzylthioꢀ5ꢀcyanoꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarboxyꢀ
lic acid (9b). Yield 73%, m.p. 215—216 °C (from MeOH—water,
3 : 1). Found (%): C, 58.84; H, 3.53; N, 9.90. C14H10N2O3S.
Calculated (%): C, 58.73; H, 3.52; N, 9.78.
5ꢀCyanoꢀ6ꢀethylthioꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarboxylic
acid (9c). Yield 70%, m.p. 229—231 °C (from MeOH—water,
3 : 1). Found (%): C, 48.33; H, 3.64; N, 12.57. C9H8N2O3S.
Calculated (%): C, 48.21; H, 3.60; N, 12.49.
6ꢀAllylthioꢀ5ꢀcyanoꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarboxylic
acid (9d). Yield 75%, m.p. 182—185 °C (from MeOH—water,
3 : 1). Found (%): C, 50.99; H, 3.44; N, 11.89. C10H8N2O3S.
Calculated (%): C, 50.84; H, 3.41; N, 11.86.
3ꢀAminoꢀ2ꢀcarbamoylꢀ6ꢀoxoꢀ6,7ꢀdihydrothieno[2,3ꢀb]pyriꢀ
dineꢀ5ꢀcarboxylic acid (10a). Yield 66%, m.p. >300 °C (from
AcOH—DMF, 1 : 1). Found (%): C, 42.78; H, 2.80; N, 16.65.
C9H7N3O4S. Calculated (%): C, 42.69; H, 2.79; N, 16.59.
3ꢀAminoꢀ6ꢀoxoꢀ2ꢀ(Nꢀphenylcarbamoyl)ꢀ6,7ꢀdihydroꢀ
thieno[2,3ꢀb]pyridineꢀ5ꢀcarboxylic acid (10b). Yield 66%,
decomp. 300—303 °C (from AcOH—DMF, 1 : 1). Found (%):
C, 54.83; H, 3.40; N, 12.81. C15H11N3O4S. Calculated (%):
C, 54.71; H, 3.37; N, 12.76.
3ꢀAminoꢀ2ꢀbenzoylꢀ6ꢀoxoꢀ6,7ꢀdihydrothieno[2,3ꢀb]pyridineꢀ
5ꢀcarboxylic acid (10c). Yield 50%, m.p. 327—329 °C (from
AcOH). Found (%): C, 57.45; H, 3.24; N, 8.99. C15H10N2O4S.
Calculated (%): C, 57.32; H, 3.21; N, 8.91.
8ꢀCyanoꢀ3ꢀiodomethylꢀ5ꢀoxoꢀ2,3,4,5ꢀtetrahydrothiazoꢀ
lo[3,2ꢀa]pyridineꢀ6ꢀcarboxylic acid (11). A solution of I2 (0.43 g,
1.7 mmol) in 30 mL of EtOH was added to a solution of
compound 9d (0.4 g, 1.7 mmol) in 20 mL of EtOH. The reacꢀ
tion mixture was refluxed for 5 min and then stirred at 50 °C
for 6 h. After 4 days, the crystalline precipitate that formed
was filtered off. The yield of acid 11 was 0.55 g (90%),
m.p. 226—228 °C (from Me2CO). Found (%): C, 33.21;
H, 1.96; N, 7.76. C10H7IN2O3S. Calculated (%): C, 33.17;
H, 1.95; N, 7.74.
6,6´ꢀDithiobis(5ꢀcyanoꢀ2ꢀoxoꢀ1,2ꢀdihydropyridineꢀ3ꢀcarꢀ
boxylic acid) (12). A 10% aqueous solution of KOH (2.97 mL,
5.3 mmol) was added to a stirred suspension of acid 4 (0.5 g,
2.6 mmol) in 10 mL of 50% EtOH. The reaction mixture was
brought to boiling, filtered into a solution of 35% H2O2 (0.5 mL,
5.3 mmol), left at ∼20 °C for 24 h, and acidified with conc. HCl

Pyridinecarboxylic acids and tetrahydroquinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1561
to pH 5. After 3 h, the precipitate that formed was filtered off
and washed with water and EtOH. The yield of disulfide 12 was
52%, decomp. temp. 340 °C. Found (%): C, 43.13; H, 1.56;
N, 14.40. C14H6N4O6S2. Calculated (%): C, 43.08; H, 1.55;
N, 14.35.
References
1. V. P. Litvinov, Ya. Yu. Yakunin, and V. D. Dyachenko,
Khim. Geterotsikl. Soedin., 2001, 41 [Chem. Heterocycl.
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Xꢀray diffraction analysis of compound 11 was carried out
for a single crystal 0.17×0.31×0.47 mm at ∼20 °C on an
EnrafꢀNonius CAD4 automated fourꢀcircle diffractometer
(MoKα radiation, 2θ/ω = 1.2, θmax = 24°; 0 ≤ h ≤ 6, –10 ≤ k ≤ 10,
–13 ≤ l ≤ 13). The set of 2396 collected reflections included
1818 independent ones (Rint = 0.011). The crystals of comꢀ
pound 11 are triclinic, a = 5.786(4) Å, b = 9.157(3) Å, c =
11.801(4) Å, α = 104.36(3)°, β = 95.18(4)°, γ = 104.40(5)°, V =
2. V. P. Litvinov, S. G. Krivokolysko, and V. D. Dyachenko,
Khim. Geterotsikl. Soedin., 1999, 579 [Chem. Heterocycl.
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A. G. Orpen, and R. Tailor, J. Chem. Soc., Perkin Trans. 2,
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organicheskikh soedinenii kisloroda i sery v gazovoi faze [Moꢀ
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578.9(5) Å3, M = 362.14, Z = 2, dcalc = 2.10 g cm–3, µ =
–
29.3 cm–1, F(000) = 347, space group P1. The structure was
solved by the direct method and refined by the leastꢀsquares
method in the anisotropic fullꢀmatrix approximation with the
CRYSTALS program package.9 The refinement was performed
for 1532 reflections with I > 3(I ) (the number of the refined
parameters was 158, and the number of reflections per paramꢀ
eter was 9.7). All H atoms were located from the difference
electronꢀdensity map and refined with fixed coordinates and
thermal parameters (except for the H(2) atom involved in hyꢀ
drogen bonding, which was refined isotropically). Refinement
with the use of the Chebyshev weight scheme10 (scheme paꢀ
rameters were 1.03, –0.56, 0.39, and –0.42) gave final discrepꢀ
ancy factors R = 0.038 and RW = 0.038; GOF = 1.124. Tables
of nonhydrogen atom coordinates have been deposited with the
Cambridge Crystallographic Database.
9. D. J. Watkin, C. K. Prout, J. R. Carruthers, and P. W.
Betteridge, CRYSTALS, Issue 10, University of Oxford, Oxꢀ
ford, 1996.
10. J. R. Carruthers and D. J. Watkin, Acta Crystallogr., Sect. A,
1979, 35, 698.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
32063).
Received July 19, 2001;
in revised form December 14, 2001