Functional sulfur-containing compounds : 1114. Study of intramolecular cyclization of 2-organylthio-, 2-organylsulfinyl-, and 2- organylsulfonylnicotinic acid esters and nitriles upon action of a base

Article abstract of DOI:10.1007/s11172-008-0290-6

The Thorpe-Ziegler intramolecular cyclization of 2-RCH₂S-, 2-RCH₂S(O)-, and 2-RCH₂SO₂-substituted nicotinic acid esters and nitriles (R is alkyl, aryl, and 2-thienyl) upon the action of potassium tert-butoxide has been studied. The reaction results in the formation of the corresponding 2-R-substituted 3-aminothieno[2,3-b]pyridines, 3-aminothieno[2,3-b]pyridine 1-oxides, and 3-aminothieno[2,3-b]pyridine 1,1-dioxides with the reaction taking place only in the case if R is aryl or 2-thienyl. Methyl esters of 2-RCH₂S-, 2-RCH₂S(O)-, and 2-RCH₂SO₂-substituted nicotinic acids also undergo the intramolecular cyclization of the Dieckmann type to form the corresponding 2-R-substituted 3-hydroxythieno[2,3-b]pyridines, thieno[2,3-b]pyridin-3(2H)-one 1-oxides, and thieno[2,3-b]pyridin-3(2H)-one 1,1-dioxides. Such a reaction takes place for all the R groups except when R = AlkCH₂S and AlkCH ₂S(O).

Full text of DOI:10.1007/s11172-008-0290-6

Russian Chemical Bulletin, International Edition, Vol. 57, No. 10, pp. 2139—2145, October, 2008
2139
Functional sulfurꢀcontaining compounds
14.* Study of intramolecular cyclization of 2ꢀorganylthioꢀ, 2ꢀorganylsulfinylꢀ,
and 2ꢀorganylsulfonylnicotinic acid esters and nitriles upon action of a base
V. E. Kalugin and A. M. Shestopalov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: vek@gazsvyaz.ru
The Thorpe—Ziegler intramolecular cyclization of 2ꢀRCH2Sꢀ, 2ꢀRCH2S(O)ꢀ, and
2ꢀRCH2SO2ꢀsubstituted nicotinic acid esters and nitriles (R is alkyl, aryl, and 2ꢀthienyl) upon
the action of potassium tertꢀbutoxide has been studied. The reaction results in the formation of
the corresponding 2ꢀRꢀsubstituted 3ꢀaminothieno[2,3ꢀb]pyridines, 3ꢀaminothieno[2,3ꢀb]ꢀ
pyridine 1ꢀoxides, and 3ꢀaminothieno[2,3ꢀb]pyridine 1,1ꢀdioxides with the reaction taking
place only in the case if R is aryl or 2ꢀthienyl. Methyl esters of 2ꢀRCH2Sꢀ, 2ꢀRCH2S(O)ꢀ, and
2ꢀRCH2SO2ꢀsubstituted nicotinic acids also undergo the intramolecular cyclization of the
Dieckmann type to form the corresponding 2ꢀRꢀsubstituted 3ꢀhydroxythieno[2,3ꢀb]pyridines,
thieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1ꢀoxides, and thieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1,1ꢀdioxides.
Such a reaction takes place for all the R groups except when R = AlkCH2S and AlkCH2S(O).
Key words: intramolecular cyclization, the Thorpe—Ziegler reaction, potassium tertꢀbutꢀ
oxide, 3ꢀcyanoꢀ4,6ꢀdimethylpyridineꢀ2ꢀthione, methyl 4,6ꢀdimethylꢀ2ꢀthioxopyridineꢀ3ꢀcarꢀ
boxylate, 4,6ꢀdimethylꢀ2ꢀorganylthioꢀ3ꢀcyanopyridines, 4,6ꢀdimethylꢀ2ꢀorganylsulfinylꢀ
3ꢀcyanopyridines, 4,6ꢀdimethylꢀ2ꢀorganylsulfonylꢀ3ꢀcyanopyridines, 3ꢀaminoꢀ2ꢀ[arylꢀ
(2ꢀthienyl)]thieno[2,3ꢀb]pyridines, 3ꢀaminoꢀ2ꢀ[aryl(2ꢀthienyl)]thieno[2,3ꢀb]pyridine 1ꢀoxides,
3ꢀaminoꢀ2ꢀ[aryl(2ꢀthienyl)]thieno[2,3ꢀb]pyridine 1,1ꢀdioxides, 2ꢀarylꢀ3ꢀhydroxyꢀ4,6ꢀdimethylꢀ
thieno[2,3ꢀb]pyridine, 2ꢀarylꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1ꢀoxides, 2ꢀ[arylꢀ
(butyl)]ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1,1ꢀdioxides.
reaction also takes place. In all the cases considered, the
activating group Z is in the exoꢀcyclic position in the final
products.
3ꢀAminothieno[2,3ꢀb]pyridines are of great practical
interest first of all due to the wide range of their pharmaꢀ
cological activity. This range includes antiinflammatory,2
antidepressant,3 antibacterial,4 antiviral,5,6 and antitumor7
activity. Therefore, a search for new methods of preparaꢀ
tion of these compounds is an actual problem.
One of the most important methods for the synthesis
of such heterocycles is the intramolecular cyclization of
3ꢀcyanoꢀ2ꢀ(organylmethylthio)pyridines by the Thorpe—
Ziegler reaction under the action of bases.
There are reactions of intramolecular cyclization where
the activating group is directly included into the thiophene
ring. Thus, the reaction of 2ꢀ(benzylsulfonyl)benzoic acid
esters with sodium ethoxide or methoxide leads to benzoꢀ
[b]thiophenꢀ3(2H)ꢀone 1,1ꢀdioxide in high yield.16,17
Treatment of 2ꢀ(benzylsulfinyl)ꢀ or 2ꢀ(benzylsulfonyl)ꢀ
benzonitriles with sodium methoxide gives 3ꢀaminobenzoꢀ
[b]thiophene 1ꢀoxide and 3ꢀaminobenzo[b]thiophene
1,1ꢀdioxide, respectively.17 4,6ꢀDimethoxyꢀ and 4,6ꢀdiꢀ
phenoxyꢀ2ꢀ(benzylsulfinyl)ꢀ and 2ꢀ(sulfonyl)benzonitriles
react with sodium methoxide similarly.18 Even correꢀ
sponding sulfides can undergo the intramolecular cyclization
under certain conditions. The reaction of 2ꢀ(4ꢀnitroꢀ
benzylthio)benzoic acid with sodium ethoxide leads to
2ꢀ(4ꢀnitrophenyl)benzo[b]thiophenꢀ3ꢀol,19 whereas the
reaction of 2ꢀ(benzylthio)benzonitrile with potassium
tertꢀbutoxide gives rise to 3ꢀaminobenzo[b]thiophene.17
A method for preparing benzo[b]thiophenes and 3ꢀpheꢀ
nylbenzo[b]thiophenes by the reaction of benzaldehyde
This reaction proceeds if Z is an electronꢀwithdrawing
group, for example, CN, COOR, CONH2, or C(O)R (see
Refs 8—15). Recently, we have shown1 that in the case
when Z is sulfinyl or sulfonyl group, the Thorpe—Ziegler
* For Part 13, see Ref. 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2100—2106, October, 2008.
1066ꢀ5285/08/5710ꢀ2139 © 2008 Springer Science+Business Media, Inc.

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Kalugin and Shestopalov
and benzophenone 2ꢀnitro derivatives with benzyl merꢀ
captanes in the presence of potash in dimethylformamide
has been suggested.20 In the course of this reaction, the
initially formed 2ꢀbenzylthio derivatives undergo the
intramolecular cyclization to form the corresponding
benzo[b]thiophenes. However, such a reaction proceeds
under very drastic conditions.
6a—c, and 3ꢀaminoꢀ2ꢀarylthieno[2,3ꢀb]pyridine 1,1ꢀdiꢀ
oxides 7a,b, respectively, in high yields (Scheme 2).
Scheme 2
The reaction of 3ꢀcyanoꢀ2ꢀ(2ꢀnitrophenylmethylthio)ꢀ
pyridines in the presence of potassium hydroxide in
dimethylformamide is the only example of obtaining
3ꢀaminoꢀ2ꢀarylthieno[2,3ꢀb]pyridines.21
It seemed reasonable to systematically study this
method of construction of a thiophene ring for the synꢀ
thesis of thieno[2,3ꢀb]pyridines, which allows one to obꢀ
tain earlier unavailable derivatives of such heterocycles.
3ꢀCyanoꢀ4,6ꢀdimethylpyridineꢀ2ꢀthione and methyl
4,6ꢀdimethylꢀ2ꢀthioxopyridineꢀ3ꢀcarboxylate were used
as the starting pyridineꢀ2ꢀthiones, that allowed us to obꢀ
tain two series of thieno[2,3ꢀb]pyridine derivatives. Alkyl,
benzyl, and 2ꢀthienylmethyl groups were used as the
organyl group.
Nicotinonitrile derivatives 2—4 were obtained by the
alkylation of 3ꢀcyanoꢀ4,6ꢀdimethylpyridineꢀ2ꢀthione (1)
with organyl halides with subsequent oxidation of sulfides
2a—e obtained to sulfoxides 3a—e and sulfones 4a—d
(Scheme 1).
X = S (2a—c, 5a—c), S=O (3a—c, 6a—c), SO2 (4a,b, 7a,b)
R = Ph (a), 4ꢀClC H (b), 2ꢀthienyl (c)
6
4
Sulfides 2d,e, sulfoxides 3d,e, and sulfones 4c,d, where
RCH2 = CH3 or C4H9, do not give the corresponding
thienopyridines even under reflux for three hours. In this
case, their partial decomposition is observed.
The fact that such a feature is observed irrespective of
the oxidation state of the sulfur atom, apparently, can be
explained by stabilization of the carbanion formed during
the reaction by the benzyl system.
Methyl nicotinate derivatives 9—11 were obtained
from methyl 4,6ꢀdimethylꢀ2ꢀthioxopyridineꢀ3ꢀcarboxyꢀ
late 8 similarly to this scheme (Scheme 3).
Scheme 1
Scheme 3
2, 3: R = Ph (a), 4ꢀClC H (b), 2ꢀthienyl (c), H (d), C H (e);
6
4
3 7
4: R = Ph (a), 4ꢀClC H (b), H (c), C H (d)
R = Ph (a), 4ꢀClC6H4 (b), C3H7 (c)
6
4
3 7
In the course of the reaction of compounds 9—11 with
potassium tertꢀbutoxide, the same picture is observed,
which was found for nitriles 2—4. Thus, benzylꢀsubstiꢀ
tuted sulfides 9a,b, sulfoxides 10a,b, and sulfones 11a,b,
where R is aryl, afford the corresponding thieno[2,3ꢀb]ꢀ
Treatment of sulfides 2a—c, sulfoxides 3a—c, and sulꢀ
fones 4a,b with potassium tertꢀbutoxide in tertꢀbutanol
through the intramolecular cyclization finally leads to
3ꢀaminoꢀ2ꢀ[aryl(thienyl)]thieno[2,3ꢀb]pyridines 5a—c,
3ꢀaminoꢀ2ꢀ[aryl(thienyl)]thieno[2,3ꢀb]pyridine 1ꢀoxides

2ꢀAryl(thienyl, butyl)thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2141
pyridine derivatives 12—14. However, the structure of the
final products depends on the oxidation state of the sulfur
atom. If during the cyclization of sulfides 9a,b, 2ꢀarylꢀ3ꢀ
hydroxyꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridines 12a,b are
formed, then the intramolecular cyclization of sulfoxides
10a,b and sulfones 11a,b gives 2ꢀarylꢀ4,6ꢀdimethylthienoꢀ
[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1ꢀoxides 13a,b and 2ꢀarylꢀ4,6ꢀ
dimethylthieno[2,3ꢀb]ꢀpyridinꢀ3(2H)ꢀone 1,1ꢀdioxides
14a,b, respectively, as the final products (Scheme 4).
4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate 11c with potassium
tertꢀbutoxide results in the intramolecular cyclization to
the corresponding 4,6ꢀdimethylꢀ2ꢀpropylthieno[2,3ꢀb]ꢀ
pyridinꢀ3(2H)ꢀone 1,1ꢀdioxide 14c in good yield.
In conclusion, the method studied allows us to obtain
in high yield earlier unavailable thieno[2,3ꢀb]pyridines,
thieno[2,3ꢀb]pyridine 1ꢀoxides, and thieno[2,3ꢀb]pyridine
1,1ꢀdioxides containing 2ꢀaryl, 2ꢀthienyl, and even 2ꢀalkyl
group.
Experimental
Scheme 4
IR spectra were recorded on a Specord M82 instrument in
1
KBr pellets for solid compounds and for neat liquids. H NMR
spectra were recorded on a Bruker AM 300 spectrometer (300 MHz)
in DMSOꢀd6.
4,6ꢀDimethylꢀsubstituted 3ꢀcyanopyridines 2a—e (general
procedure). Powdered KOH (0.6 g, 11 mmol) was added to a
suspension of 3ꢀcyanoꢀ4,6ꢀdimethylpyridineꢀ2ꢀthione (1)22
(1.64 g, 10 mmol) in MeOH (15 mL) and the reaction mixture
was stirred under heating until pyridinethione 1 was completely
dissolved. Then, a halide (10 mmol) was added, the mixture was
refluxed for 30 min, cooled to room temperature, diluted with
water (100 mL), and the substance was extracted with CHCl3.
The extract was dried with MgSO4, the solvent was evaporated,
and the residue was subjected to chromatography on silica gel.
The eluent was CHCl3—hexane, 3 : 2. The eluate was concenꢀ
trated and the substances were crystallized from appropriate
solvent to obtain compounds 2a—e.
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ[(phenylmethyl)thio]pyridine (2a),
the yield was 92%, m.p. 88—90 °C (CHCl3—hexane). Found
(%): C, 70.68; H, 5.62; S, 12.42. C15H14N2S. Calculated (%):
1
C, 70.83; H, 5.55; S, 12.60. IR, ν/cm–1: 2224 (CN). H NMR,
δ: 2.37 (s, 3 H, CH3); 2.50 (s, 3 H, CH3); 4.50 (s, 2 H, CH2S);
7.08 (s, 1 H, H(5) pyridine); 7.27 (m, 3 H, Ph); 7.42 (m, 2 H, Ph).
2ꢀ{[(4ꢀChlorophenyl)methyl]thio}ꢀ3ꢀcyanoꢀ4,6ꢀdimethylꢀ
pyridine (2b), the yield was 93%, m.p. 143—144 °C (CHCl3—
hexane). Found (%): C, 62.49; H, 4.61; Cl, 12.13; S, 10.98.
C15H13ClN2S. Calculated (%): C, 62.39; H, 4.54; Cl, 12.28; S,
11.10. IR, ν/cm–1: 2220 (CN). 1H NMR, δ: 2.40 (s, 3 H, CH3);
2.52 (s, 3 H, CH3); 4.50 (s, 2 H, CH2S); 7.10 (s, 1 H, H(5)
pyridine); 7.33 (d, 2 H, aryl, J = 8.5 Hz); 7.47 (d, 2 H, aryl,
J = 8.5 Hz).
R = Ph (a), 4ꢀClꢀC6H4 (b), Pr (c)
Compounds 13a,b and 14a,b possess typical acidic
properties and react even with NaHCO3 giving the correꢀ
sponding salts.
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ[(2ꢀthienylmethyl)thio]pyridine (2c),
the yield was 82%, m.p. 111—113 °C (CHCl3—hexane). Found
(%): C, 58.40; H, 4.18; S, 26.18. C12H10N2S2. Calculated (%):
1
C, 58.51; H, 4.09; S, 26.03. IR, ν/cm–1: 2220 (CN). H NMR,
We studied reaction of sulfide 9c, sulfoxide 10c, and
sulfone 11c with potassium tertꢀbutoxide and found that
the oxidation state of the sulfur atom considerably affects
result of the reaction. Thus, during the reaction of methyl
2ꢀ(butylthio)ꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate 9c with
potassium tertꢀbutoxide, no considerable changes are obꢀ
served and the starting substance can be recovered from
the reaction mixture. The reaction of methyl 2ꢀ(butylꢀ
sulfinyl)ꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate 10c with
potassium tertꢀbutoxide leads to decomposition of this
compound and to formation of a complex mixture of
substances. The reaction of methyl 2ꢀ(butylsulfonyl)ꢀ
δ: 2.40 (s, 3 H, CH3); 2.57 (s, 3 H, CH3); 4.74 (s, 2 H, CH2S);
6.90 (m, 1 H, H(3) thiophene); 7.08 (m, 1 H, H(4) thiophene);
7.10 (s, 1 H, H(5) pyridine); 7.35 (d, 1 H, H(5) thienyl, J = 5 Hz).
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀmethylthiopyridine (2d), the yield
was 89%, m.p. 88—90 °C (diethyl ether—hexane). Found (%):
C, 61.03; H, 5,57; S, 18.22. C9H10N2S. Calculated (%): C,
1
60.64; H, 5.65; S, 17.99. IR, ν/cm–1: 2220 (CN). H NMR, δ:
2.38 (s, 3 H, CH3); 2.48 (s, 3 H, CH3); 2.57 (s, 3 H, CH3S); 7.06
(s, 1 H, H(5) pyridine).
2ꢀButylthioꢀ3ꢀcyanoꢀ4,6ꢀdimethylpyridine (2e), the yield was
92%, m.p. 34.5—35.5 °C (diethyl ether—hexane). Found (%):
C, 65.61; H, 7.47; S, 14.38. C12H16N2S. Calculated (%): C, 65.42;

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Kalugin and Shestopalov
H, 7.32; S, 14.55. IR, ν/cm–1: 2222 (CN). 1H NMR, δ: 0.93 (t,
3 H, CH3, J = 7.3 Hz); 1.42 (m, 2 H, CH2); 1.63 (m, 2 H, CH2);
2.40 (s, 3 H, CH3); 2.48 (s, 3 H, CH3); 3.23 (t, 2 H, CH2S,
J = 7.3 Hz); 7.08 (s, 1 H, H(5) pyridine).
dried with MgSO4, concentrated, and the substances were crysꢀ
tallized from appropriate solvent to obtain compounds 4a—d.
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ[(phenylmethyl)sulfonyl]pyridine
(4a), the yield was 78%, m.p. 193—195 °C (chloroform—methꢀ
anol). Found (%): C, 63.06; H, 5.05; S, 11.08. C15H14N2O2S.
Calculated (%): C, 62.92; H, 4.93; S, 11.20. IR, ν/cm–1: 2232
(CN), 1320, 1132 (SO2). H NMR, δ: 2.50 (s, 3 H, CH3); 2.64
(s, 3 H, CH3); 4.95 (s, 2 H, CH2SO2); 7.32 (m, 5 H, Ph), 7.73
(s, 1 H, H(5) pyridine).
2ꢀ{[(4ꢀChlorophenyl)methyl]sulfonyl}ꢀ3ꢀcyanoꢀ4,6ꢀdimethylꢀ
pyridine (4b), the yield was 75%, m.p. 195—196 °C (chloroform—
methanol). Found (%): C, 55.98; H, 4.16; Cl, 11.23; S, 10.12.
C15H13ClN2O2S. Calculated (%): C, 56.16; H, 4.08; Cl, 11.05;
S, 9.99. IR, ν/cm–1: 2232 (CN), 1316, 1130 (SO2). 1H NMR, δ:
2.53 (s, 3 H, CH3); 2.66 (s, 3 H, CH3); 5.00 (s, 2 H, CH2SO2);
7.34 (d, 2 H, aryl, J = 9 Hz); 7.42 (d, 2 H, aryl, J = 9 Hz); 7.74
(s, 1 H, H(5) pyridine).
2ꢀ(Organylsulfinyl)ꢀsubstituted 3ꢀcyanoꢀ4,6ꢀdimethylpyriꢀ
dines 3a—e (general procedure). Hydrogen peroxide (30% aq.,
1.2 mL, 12 mmol) was added to a suspension of compound
2a—e (10 mmol) in AcOH (20 mL). The reaction mixture was
stirred for 80 min at 65 °C, cooled to room temperature, and
CHCl3 (20 mL) was added to it. Acetic acid was neutralized by
addition of aq. Na2CO3, the organic layer was separated, the
aqueous layer was twice extracted with CHCl3. The combined
extracts were dried with MgSO4 and concentrated and the residue
was subjected to chromatography on silica gel. Eluent was
CHCl3, CHCl3—acetone, 4 : 1. The eluate was concentrated,
the substances were crystallized from acetone—diethyl ether to
obtain compounds 3a—e.
1
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ[(phenylmethyl)sulfinyl]pyridine
(3a), the yield was 68%, m.p. 172—174 °C. Found (%): C,
66.77; H, 5.14; S, 12.04. C15H14N2OS. Calculated (%): C, 66.64;
H, 5.22; S, 11.86 IR, ν/cm–1: 2228 (CN), 1064 (SO). 1H NMR,
δ: 2.42 (s, 3 H, CH3); 2.61 (s, 3 H, CH3); 4.36 (d, 1 H, CH2SO,
J = 13 Hz); 4.44 (d, 1 H, CH2SO, J = 13 Hz); 7.08 (m, 2 H, Ph);
7.30 (m, 3 H, Ph); 7.54 (s, 1 H, H(5) pyridine).
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ(methylsulfonyl)pyridine (4c), the
yield was 81%, m.p. 111—112 °C (methanol). Found (%): C,
51.30; H, 4.88; S, 15.17. C9H10N2O2S. Calculated (%): C, 51.41;
H, 4.79; S, 15.25. IR, ν/cm–1: 2238 (CN), 1320, 1130 (SO2).
1H NMR, δ: 2.57 (s, 3 H, CH3); 2.61 (s, 3 H, CH3); 3.43 (s, 3 H,
CH3SO2); 7.74 (s, 1 H, H(5) pyridine).
2ꢀ(Butylsulfonyl)ꢀ3ꢀcyanoꢀ4,6ꢀdimethylpyridine (4d), the
yield was 72%, m.p. 59—60 °C (methanol). Found (%):
C, 57.02; H, 6.51; S, 12.55. C12H16N2O2S. Calculated (%): C,
57.12; H, 6.39; S, 12.71. IR, ν/cm–1: 2236 (CN), 1320, 1128
(SO2). 1H NMR, δ: 0.90 (t, 3 H, CH3, J = 7.5 Hz); 1.42 (m, 2 H,
CH2); 1.65 (m, 2 H, CH2); 2.57 (s, 3 H, CH3); 2.61 (s, 3 H, CH3);
3.60 (t, 2 H, CH2SO2, J = 7.3 Hz); 7.74 (s, 1 H, H(5) pyridine).
2ꢀAryl(2ꢀthienyl)ꢀsubstituted 3ꢀaminoꢀ4,6ꢀdimethylthienoꢀ
[2,3ꢀb]pyridines 5a—c (general procedure). Potassium tertꢀbutꢀ
oxide (1.12 g, 10 mmol) was added to a solution of sulfide 2a—c
(10 mmol) in tertꢀbutanol (20 mL) at 50 °C with stirring. The
reaction mixture was stirred for 30 min, cooled, and poured into
water (100 mL). The substance was extracted with CHCl3. The
extract was dried with MgSO4 and concentrated and the residue
was subjected to chromatography on silica gel. Eluent was CHCl3.
After evaporation of the solvent, the substances were crystallized
from appropriate solvent to obtain compounds 5a—c.
3ꢀAminoꢀ4,6ꢀdimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridine (5a),
the yield was 75%, m.p. 74—76 °C (acetone—hexane). Found
(%): C, 70.65; H, 5.47; S, 12.81. C15H14N2S. Calculated (%):
C, 70.83; H, 5.55; S, 12.60. IR, ν/cm–1: 3418, 3364 (NH). 1H NMR,
δ: 2.50 (s, 3 H, CH3); 2.76 (s, 3 H, CH3); 4.83 (s, 2 H, NH2);
7.00 (s, 1 H, H(5) thieno[2,3ꢀb]pyridine); 7.32 (t, 1 H, Ph,
J = 8 Hz); 7.48 (t, 2 H, Ph, J = 8 Hz); 7.57 (d, 2 H, Ph, J = 8 Hz).
3ꢀAminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyriꢀ
dine (5b), the yield was 72%, m.p. 197—198 °C (acetone—
hexane). Found (%): C, 62.23; H, 4.67; Cl, 12.42; S, 11.22.
C15H13ClN2S. Calculated (%): C, 62.39; H, 4.54; Cl, 12.28; S,
11.10. IR, ν/cm–1: 3436, 3336 (NH). 1H NMR, δ: 2.50 (s, 3 H,
CH3); 2.76 (s, 3 H, CH3); 4.95 (s, 2 H, NH2); 6.98 (s, 1 H, H(5)
thieno[2,3ꢀb]pyridine); 7.50 (d, 2 H, aryl, J = 8.5 Hz); 7.57 (d,
2 H, aryl, J = 8.5 Hz).
2ꢀ[(4ꢀChlorophenyl)methyl]sulfinylꢀ3ꢀcyanoꢀ4,6ꢀdimethylꢀ
pyridine (3b), the yield was 65%, m.p. 126—128 °C. Found (%):
C, 59.18; H, 4.22; Cl, 11.85; S, 10.72. C15H13ClN2OS. Calcuꢀ
lated (%): C, 59.11; H, 4.30; Cl, 11.63; S, 10.52. IR, ν/cm–1
:
2232 (CN), 1068 (SO). 1H NMR, δ: 2.42 (s, 3 H, CH3); 2.61 (s,
3 H, CH3); 4.37 (d, 1 H, CH2SO, J = 13 Hz); 4.48 (d, 1 H,
CH2SO, J = 13 Hz); 7.10 (d, 2 H, aryl, J = 8.5 Hz); 7.34 (d, 2 H,
aryl, J = 8.5 Hz); 7.56 (s, 1 H, H(5) pyridine).
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ[(2ꢀthienylmethyl)sulfinyl]pyridine
(3c), the yield was 60%, m.p. 161—162 °C. Found (%): C, 55.08;
H, 4.01; S, 24.27. C12H10N2OS2. Calculated (%): C, 54.94; H,
3.84; S, 24.44. IR, ν/cm–1: 2228 (CN), 1064 (SO). 1H NMR, δ:
2.44 (s, 3 H, CH3); 2.62 (s, 3 H, CH3); 4.62 (d, 1 H, CH2SO,
J = 13 Hz); 4.72 (d, 1 H, CH2SO, J = 13 Hz); 6.87 (d, 1 H, H(3)
thiophene, J = 4 Hz); 6.98 (m, 1 H, H(4) thiophene); 7.46 (d,
1 H, H(5) thiophene, J = 5 Hz); 7.56 (s, 1 H, H(5) pyridine).
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ(methylsulfinyl)pyridine (3d), the
yield was 60%, m.p. 103—105 °C. Found (%): C, 55.41; H, 5.26;
S, 16.33. C9H10N2OS. Calculated (%): C, 55.65; H, 5.19; S,
16.50. IR, ν/cm–1: 2228 (CN), 1040 (SO). 1H NMR, δ: 2.53
(s, 3 H, CH3); 2.60 (s, 3 H, CH3); 2.90 (s, 3 H, CH3SO); 7.58 (s,
1 H, H(5) pyridine).
2ꢀ(Butylsulfinyl)ꢀ3ꢀcyanoꢀ4,6ꢀdimethylpyridine (3e), the yield
was 63%, m.p. 88—89 °C. Found (%): C, 61.16; H, 6.97; S,
13.41. C12H16N2OS. Calculated (%): C, 60.99; H, 6.82; S, 13.57.
1
IR, ν/cm–1: 2232 (CN), 1048 (SO). H NMR, δ: 0.93 (t, 3 H,
CH3, J = 7.3 Hz); 1.42 (m, 2 H, CH2); 1.63 (m, 2 H, CH2); 2.52
(s, 3 H, CH3); 2.58 (s, 3 H, CH3); 3.08 (t, 2 H, CH2SO, J = 7.5 Hz);
7.56 (s, 1 H, H(5) pyridine).
2ꢀ(Organylsulfonyl)ꢀsubstituted 3ꢀcyanoꢀ4,6ꢀdimethylpyriꢀ
dines 4a—d (general procedure). Powdered KMnO4, (1.26 g, 8 mmol)
was added to a solution or suspension of sulfide 2a,b,d,e (5 mmol)
in AcOH (20 mL) with stirring, keeping the temperature within
20—25 °C. The reaction mixture was stirred for another 40 min,
discolored by addition of aq. Na2SO3, and poured into a
separation funnel with water (100 mL). The substance was
extracted with CHCl3. The extract was washed with aq. NaHCO3,
3ꢀAminoꢀ4,6ꢀdimethylꢀ2ꢀ(2ꢀthienyl)thieno[2,3ꢀb]pyridine
(5c), the yield was 70%, m.p. 144—146 °C (acetone—hexane).
Found (%): C, 58.63; H, 4.13; S, 26.18. C12H10N2S2. Calculated
(%): C, 58.51; H, 4.09; S, 26.03. IR, ν/cm–1: 3428, 3348 (NH).
1H NMR, δ: 2.48 (s, 3 H, CH3); 2.75 (s, 3 H, CH3); 5.00 (s, 2 H,
NH2); 7.00 (s, 1 H, H(5) thieno[2,3ꢀb]pyridine); 7.18 (t, 1 H,

2ꢀAryl(thienyl, butyl)thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2143
H(3) thiophene, J = 4 Hz); 7.27 (d, 1 H, H(4) thiophene,
J = 4 Hz); 7.58 (d, 1 H, H(5) thiophene, J = 5 Hz).
temperature for 16 h. Then, MeOH (20 mL) and AcOH (1.5 mL)
were added to the reaction mixture followed by keeping for 2 h
at –15 °C. The substance precipitated was filtered off and washed
with cold MeOH to obtain ester 8 (9 g, 78%), m.p. 187—189 °C
(acetone—hexane). Found (%): C, 54.68; H, 5.70; S, 16.41.
C9H11NO2S. Calculated (%): C, 54.80; H, 5.62; S, 16.25.
Methyl 2ꢀorganylthioꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylates
9a—c (general procedure). Halide (12 mmol) was added to a
solution of thione 8 (1.97 g, 10 mmol) and triethylamine (1.4 g,
14 mmol) in CHCl3 (10 mL). The reaction mixture was refluxed
for 1 h, the solvent was evaporated in vacuo, and the residue was
subjected to chromatography on silica gel. Eluent was hexane—
CHCl3, 1 : 1. The eluate was concentrated, the substance
obtained was dried in vacuo or crystallized from appropriate
solvent.
2ꢀAryl(2ꢀthienyl)ꢀsubstituted 3ꢀaminoꢀ4,6ꢀdimethylthienoꢀ
[2,3ꢀb]pyridine 1ꢀoxides 6a—c (general procedure). Potassium
tertꢀbutoxide (1.12 g, 10 mmol) was added to a solution of
sulfoxide 3a—c (10 mmol) in tertꢀbutanol (25 mL) at 50 °C and
with stirring. The reaction mixture was stirred for 10 min, cooled,
and poured into water (100 mL). After several hours, the
substance was filtered off, dried in air, and crystallized from
appropriate solvent to obtain compounds 6a—c.
3ꢀAminoꢀ4,6ꢀdimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridine 1ꢀoxide
(6a), the yield was 80%, m.p. 202—204 °C (DMF—MeOH).
Found (%): C, 66.73; H, 5.30; S, 11.75. C15H14N2OS. Calculated
(%): C, 66.64; H, 5.22; S, 11.86. IR, ν/cm–1: 3412 (NH), 1012
1
(SO). H NMR, δ: 2.54 (s, 3 H, CH3); 2.70 (s, 3 H, CH3); 6.05
(s, 2 H, NH2); 7.30 (m, 2 H, Ph); 7.50 (m, 3 H, Ph); 7.60 (s,
1 H, H(5) thieno[2,3ꢀb]pyridine).
Methyl 4,6ꢀdimethylꢀ2ꢀ[(phenylmethyl)thio]pyridineꢀ3ꢀcarꢀ
boxylate (9a), the yield was 92%, oil. Found (%): C, 66.72; H,
6.03; S, 11.22. C16H17NO2S. Calculated (%): C, 66.87; H, 5.96;
S, 11.16. IR, ν/cm–1: 1732 (CO). 1H NMR, δ: 2.22 (s, 3 H,
CH3); 2.45 (s, 3 H, CH3); 3.81 (s, 3 H, COOCH3); 4.40 (s, 2 H,
CH2S); 6.95 (s, 1 H, H(5) pyridine); 7.25 (m, 3 H, Ph); 7.38 (d,
2 H, Ph, J = 7.5 Hz).
3ꢀAminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyriꢀ
dine 1ꢀoxide (6b), the yield was 82%, m.p. 220—222 °C (decomp.)
(DMF—MeOH). Found (%): C, 59.02; H, 4.38; S, 11.70.
C15H13ClN2OS. Calculated (%): C, 59.11; H, 4.30; Cl, 11.63;
1
S, 10.52. IR, ν/cm–1: 3412 (NH), 1012 (SO). H NMR, δ: 2.53
(s, 3 H, CH3); 2.70 (s, 3 H, CH3); 6.23 (s, 2 H, NH2); 7.30 (s,
1 H, H(5) thieno[2,3ꢀb]pyridine); 7.50 (d, 2 H, aryl, J = 7.5 Hz);
7.58 (d, 2 H, aryl, J = 7.5 Hz).
Methyl 2ꢀ{[(4ꢀchlorophenyl)methyl]thio}ꢀ4,6ꢀdimethylpyriꢀ
dineꢀ3ꢀcarboxylate (9b), the yield was 90%, m.p. 43—44 °C
(hexane). Found (%): C, 59.87; H, 5.07; Cl, 11.14; S, 10.06.
C16H16ClNO2S. Calculated (%): C, 59.72; H, 5.01; Cl, 11.02;
S, 9.96. IR, ν/cm–1: 1700 (CO). 1H NMR, δ: 2.20 (s, 3 H,
CH3); 2.45 (s, 3 H, CH3); 3.81 (s, 3 H, COOCH3); 4.36 (s,
2 H, CH2S); 6.93 (s, 1 H, H(5) pyridine); 7.30 (d, 2 H, aryl,
J = 8.0 Hz); 7.38 (d, 2 H, aryl, J = 8.0 Hz).
3ꢀAminoꢀ4,6ꢀdimethylꢀ2ꢀ(2ꢀthienyl)thieno[2,3ꢀb]pyridine
1ꢀoxide (6c), the yield was 68%, m.p. 214—216 °C (decomp.)
(DMF—MeOH). Found (%): C, 54.76; H, 3.96; S, 24.61.
C12H10N2OS2. Calculated (%): C, 54.94; H, 3.84; S, 24.44.
1
IR, ν/cm–1: 3492, 3308 (NH), 1020 (SO). H NMR, δ: 2.53 (s,
3 H, CH3); 2.70 (s, 3 H, CH3); 6.23 (s, 2 H, NH2); 7.18 (t, 1 H,
H(3) thiophene, J = 4 Hz); 7.27 (d, 1 H, H(4) thiophene,
J = 4 Hz); 7.30 (s, 1 H, H(5) thieno[2,3ꢀb]pyridine); 7.58 (d,
1 H, H(5) thiophene, J = 5 Hz).
2ꢀArylꢀsubstituted 3ꢀaminoꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyriꢀ
dine 1,1ꢀdioxides 7a,b (general procedure). Potassium tertꢀbutꢀ
oxide (1.12 g, 10 mmol) was added to a solution of sulfone 4a,b
(10 mmol) in tertꢀbutanol (40 mL) at 50 °C and with stirring.
The reaction mixture was stirred for 10 min followed by addition
of MeOH (100 mL), and placed into a refrigerator. After several
hours, the substance precipitated was filtered off and washed
with cold MeOH.
Methyl 2ꢀbutylthioꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate (9c),
the yield was 90%, oil, Found (%): C, 61.80; H, 7.62; S, 12.72.
C13H19NO2S. Calculated (%): C, 61.63; H, 7.56; S, 12.65. IR,
ν/cm–1: 1736 (CO). 1H NMR, δ: 0.88 (s, 3 H, CH3, J = 7.5 Hz);
1.42 (m, 2 H, CH2); 1.63 (m, 2 H, CH2); 2.20 (s, 3 H, CH3);
2.40 (s, 3 H, CH3); 3.10 (t, 2 H, CH2S, J = 7.5 Hz); 3.83 (s, 3 H,
COOCH3); 6.90 (s, 1 H, H(5) pyridine).
Methyl 2ꢀorganylsulfinylꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate
10a—c (general procedure). Hydrogen peroxide (30% aq., 0.5 mL,
5 mmol) was added to a solution of 9a—c (4 mmol) in AcOH
(10 mL). The reaction mixture was heated for 30 min at 60 °C
and cooled to room temperature followed by addition of CHCl3
(15 mL). Acetic acid was neutralized by aq. Na2CO3. Comꢀ
pounds 10a—c were isolated as described for sulfoxides 3.
Methyl 4,6ꢀdimethylꢀ2ꢀ[(phenylmethyl)sulfinyl]pyridineꢀ
3ꢀcarboxylates (10a), the yield was 80%, m.p. 102.5—103.5 °C
(acetone—hexane). Found (%): C, 63.51; H, 5.79; S, 10.37.
C16H17NO3S. Calculated (%): C, 63.35; H, 5.65; S, 10.57. IR,
ν/cm–1: 1732 (CO), 1064 (SO). 1H NMR, δ: 2.30 (s, 3 H, CH3);
2.52 (s, 3 H, CH3); 4.27 (d, 1 H, CH2SO, J = 13 Hz); 4.36 (d,
1 H, CH2SO, J = 13 Hz); 7.20 (m, 2 H, Ph); 7.33 (m, 3 H, Ph);
7.38 (s, 1 H, H(5) pyridine).
Methyl 2ꢀ{[(4ꢀchlorophenyl)methyl]sulfinyl}ꢀ4,6ꢀdimethylꢀ
pyridineꢀ3ꢀcarboxylate (10b), the yield was 85%, 110—112 °C
(acetone—hexane). Found (%): C, 56.76; H, 4.71; Cl, 10.62;
S, 9.60. C16H16ClNO3S. Calculated (%): C, 56.89; H, 4.77; Cl,
10.49; S, 9.49. IR, ν/cm–1: 1732 (CO), 1060 (SO). 1H NMR, δ:
2.28 (s, 3 H, CH3); 2.50 (s, 3 H, CH3); 3.77 (s, 3 H, COOCH3);
4.28 (d, 1 H, CH2SO, J = 13 Hz); 4.40 (d, 1 H, CH2SO, J = 13 Hz);
7.16 (d, 2 H, aryl, J = 7.5 Hz); 7.35 (d, 2 H, aryl, J = 7.5 Hz);
7.38 (s, 1 H, H(5) pyridine).
3ꢀAminoꢀ4,6ꢀdimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridine 1,1ꢀdiꢀ
oxide (7a), the yield was 92%, m.p. 292—294 °C (DMF—MeOH).
Found (%): C, 63.03; H, 5.01; S, 11.33. C15H14N2O2S. Calcuꢀ
lated (%): C, 62.92; H, 4.93; S, 11.20. IR, ν/cm–1: 3508, 3408
1
(NH), 1268, 1136 (SO2). H NMR, δ: 2.56 (s, 3 H, CH3); 2.73
(s, 3 H, CH3); 6.37 (s, 2 H, NH2); 7.37 (s, 1 H, H(5) thieno[2,3ꢀb]ꢀ
pyridine); 7.42 (m, 1 H, Ph); 7.55 (m, 4 H, Ph),
3ꢀAminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyriꢀ
dine 1,1ꢀdioxide (7b), the yield was 94%, m.p. 272—274 °C
(DMF—MeOH). Found (%): C, 56.22; H, 4.11; Cl, 10.96; S,
9.92. C15H13ClN2O2S. Calculated (%): C, 56.16; H, 4.08; Cl,
11.05; S, 9.99. IR, ν/cm–1: 3468, 3356 (NH), 1260, 1132 (SO2).
1H NMR, δ: 2.55 (s, 3 H, CH3); 2.71 (s, 3 H, CH3); 6.55 (s, 2 H,
NH2); 7.40 (s, 1 H, H(5) thieno[2,3ꢀb]pyridine); 7.60 (s, 4 H, aryl).
Methyl 4,6ꢀdimethylꢀ2ꢀthioxopyridineꢀ3ꢀcarboxylate (8) was
obtained similarly to ethyl 4,6ꢀdimethylꢀ2ꢀthioxopyridineꢀ
3ꢀcarboxylate.23 A mixture of methoxycarbonylthioacetamide24
(7.8 g, 0.058 mol), acetylacetone (11.7 g, 0.117 mol), and
triethylamine (2 g) was heated for 5 h at 50 °C and kept at room

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Kalugin and Shestopalov
Methyl 2ꢀ(butylsulfinyl)ꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate
(10c), the yield was 82%, oil. Found (%): C, 58.13; H, 7.04; S,
11.73. C13H19NO3S. Calculated (%): C, 57.97; H, 7.11; S, 11.90.
IR, ν/cm–1: 1736 (CO), 1044 (SO). 1H NMR, δ: 0.88 (s, 3 H,
CH3, J = 7.5 Hz); 1.42 (m, 2 H, CH2); 1.63 (m, 2 H, CH2);
2.30 (s, 3 H, CH3); 2.60 (s, 3 H, CH3); 3.00 (t, 2 H, CH2S,
J = 7.5 Hz); 3.83 (s, 3 H, COOCH3); 7.36 (s, 1 H, H(5) pyridine).
Methyl 2ꢀorganylsulfonylꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxyꢀ
lates 11a—c (general procedure). Powdered KMnO4 (1 g, 6.3 mmol)
was added to a solution of 9a—c (4 mmol) in AcOH (15 mL)
with such a rate that to keep the temperature within 20—25 °C.
The reaction mixture was stirred for another 30 min and treated
as described for sulfones 4 to obtain compounds 11a—c.
Methyl 4,6ꢀdimethylꢀ2ꢀ(phenylmethylsulfonyl)pyridineꢀ
3ꢀcarboxylate (11a), the yield was 85%, m.p. 111—112 °C
(CHCl3—hexane). Found (%): C, 60.28; H, 5.46; S, 10.11.
C16H17NO4S. Calculated (%): C, 60.17; H, 5.37; S, 10.04.
IR, ν/cm–1: 1740 (CO), 1320, 1148 (SO2). 1H NMR, δ: 2.25 (s,
3 H, CH3); 2.58 (s, 3 H, CH3); 3.77 (s, 3 H, COOCH3); 4.82
(s, 2 H, CH2SO2); 7.26 (m, 2 H, Ph); 7.33 (m, 3 H, Ph); 7.57 (s,
1 H, H(5) pyridine).
Methyl 2ꢀ{[(4ꢀchlorophenyl)methyl]sulfonyl}ꢀ4,6ꢀdimethylꢀ
pyridineꢀ3ꢀcarboxylate (11b), the yield was 83%, m.p. 131—132
°C (CHCl3—hexane). Found (%): C, 54.19; H, 4.63; Cl, 10.12;
S, 9.15. C16H16ClNO4S. Calculated (%): C, 54.31; H, 4.56; Cl,
10.02; S, 9.06. IR, ν/cm–1: 1736 (CO), 1320, 1140 (SO2). 1H NMR,
δ: 2.28 (s, 3 H, CH3); 2.50 (s, 3 H, CH3); 3.77 (s, 3 H, COOCH3);
4.85 (s, 2 H, CH2SO2); 7.26 (d, 2 H, aryl, J = 7.5 Hz); 7.40 (d,
2 H, aryl, J = 7.5 Hz); 7.58 (s, 1 H, H(5) pyridine).
Methyl 2ꢀ(butylsulfonyl)ꢀ4,6ꢀdimethylpyridineꢀ3ꢀcarboxylate
(11c), the yield was 80%, oil. Found (%): C, 54.88; H, 6.65; S,
11.31. C13H19NO4S. Calculated (%): C, 54.72; H, 6.71; S, 11.24.
IR, ν/cm–1: 1744 (CO), 1320, 1140 (SO2). 1H NMR, δ: 0.88 (t,
3 H, CH3, J = 6.5 Hz); 1.42 (m, 2 H, CH2); 1.63 (m, 2 H, CH2);
2.30 (s, 3 H, CH3); 2.55 (s, 3 H, CH3); 3.43 (t, 2 H, CH2SO2,
J = 7.5 Hz); 3.83 (s, 3 H, COOCH3); 7.58 (s, 1 H, H(5) pyridine).
2ꢀArylꢀ3ꢀhydroxyꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridines 12a,b
(general procedure). Potassium tertꢀbutoxide (0.7 g, 6 mmol) was
added to a solution of compound 9a,b (4 mmol) in tertꢀbutanol
(12 mL) at 50 °C with stirring. The reaction mixture was stirred
for 1 h, cooled, and diluted with water (50 mL) followed by
addition of AcOH (0.5 g). The substance was extracted with
CHCl3, the extract was dried with MgSO4 and concentrated,
and the residue was subjected to chromatography on silica gel.
Eluent was CHCl3—hexane, 3 : 1. The eluate was concentrated
and the substances were crystallized from appropriate solvent to
obtain compounds 12a,b.
pyridine); 7.52 (d, 2 H, aryl, J = 7.5 Hz); 7.78 (d, 2 H, aryl,
J = 7.5 Hz); 9.42 (br.s, 1 H, OH).
2ꢀArylꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone 1ꢀoxides
13a,b (general procedure). Potassium tertꢀbutoxide (0.7 g, 6 mmol)
was added to a solution of compound 10a,b (4 mmol) in
tertꢀbutanol (12 mL) at 50 °C with stirring. The reaction mixture
was stirred for 30 min, cooled, and diluted with water (50 mL)
followed by addition of AcOH (0.5 g). The substance was
extracted with CHCl3. The extract was dried with MgSO4,
concentrated, and compounds 13a,b were crystallized from
appropriate solvent.
4,6ꢀDimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone
1ꢀoxide (13a), the yield was 62%, m.p. 126—129 °C (acetone—
diethyl ether). Found (%): C, 66.51; H, 4.88; S, 11.90. C15H13NO2S.
Calculated (%): C, 66.40; H, 4.83; S, 11.82. IR, ν/cm–1: 1712
(C=O), 1048 (SO). 1H NMR, δ: 2.65 (s, 3 H, CH3); 2.70 (s,
3 H, CH3); 5.52 (s, 0.5 H, CHSO); 5.74 (s, 0.5 H, CHSO); 7.25
(m, 1 H, Ph); 7.42 (m, 4 H, Ph); 7.62 (s, 1 H, H(5) thienoꢀ
[2,3ꢀb]pyridine).
2ꢀ(4ꢀChlorophenyl)ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀ
one 1ꢀoxide (13b), the yield was 61%, m.p. 141—144 °C (acetone—
diethyl ether). Found (%): C, 58.81; H, 4.02; Cl, 11.70; S,
10.57. C15H12ClNO2S. Calculated (%): C, 58.92; H, 3.96; Cl,
11.59; S, 10.48. IR, ν/cm–1: 1704 (C=O), 1044 (SO). 1H NMR,
δ: 2.63 (s, 3 H, CH3); 2.70 (s, 3 H, CH3); 5.58 (s, 0.5 H, CHSO);
5.77 (s, 0.5 H, CHSO); 7.28 (d, 1 H, aryl, J = 7.5 Hz); 7.50 (m,
3 H, aryl); 7.60 (s, 1 H, H(5) thieno[2,3ꢀb]pyridine).
2ꢀOrganylꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone
1,1ꢀdioxides 14a—c (general procedure). Potassium tertꢀbutoxide
(0.7 g, 6 mmol) was added to a solution of compound 11a—c
(4 mmol) in tertꢀbutanol (18 mL) at 50 °C with stirring. The
reaction mixture was stirred for 20 min, cooled, and treated as
described for compounds 13a,b to obtain compounds 14a—c.
4,6ꢀDimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone
1,1ꢀdioxide (14a), the yield was 75%, m.p. 185—188 °C (acetone—
hexane). Found (%): C, 62.78; H, 4.61; S, 10.03. C15H13NO3S.
Calculated (%): C, 62.70; H, 4.56; S, 9.96. IR, ν/cm–1: 1720
(C=O), 1320, 1132 (SO2). 1H NMR, δ: 2.70 (s, 6 H, CH3); 6.08
(s, 1 H, CHSO2); 7.23 (m, 2 H, Ph); 7.47 (m, 3 H, Ph); 7.74 (s,
1 H, H(5) thieno[2,3ꢀb]pyridine).
2ꢀ(4ꢀChlorophenyl)ꢀ4,6ꢀdimethylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀ
one 1,1ꢀdioxide (14b), the yield was 70%, m.p. 177—178 °C
(acetone—hexane). Found (%): C, 55.83; H, 3.69; Cl, 10.91;
S, 9.86. C15H12ClNO3S. Calculated (%): C, 55.99; H, 3.76; Cl,
11.02; S, 9.96. IR, ν/cm–1: 1716 (C=O), 1340, 1132 (SO2).
1H NMR, δ: 2.70 (s, 6 H, CH3); 6.12 (s, 1 H, CHSO2); 7.38 (d,
2 H, aryl, J = 7.5 Hz); 7.54 (d, 2 H, aryl, J = 7.5 Hz); 7.75 (s,
1 H, H (5) thieno[2,3ꢀb]pyridine).
4,6ꢀDimethylꢀ2ꢀpropylthieno[2,3ꢀb]pyridinꢀ3(2H)ꢀone
1,1ꢀdioxide (14c), the yield was 68%, m.p. 98.5—100 °C
(acetone—hexane). Found (%): C, 56.77; H, 5.93; S, 12.52.
C12H15NO3S. Calculated (%): C, 56.90; H, 5.97; S, 12.66. IR,
ν/cm–1: 1716 (C=O), 1316, 1140 (SO2). 1H NMR, δ: 0.97 (t,
3 H, CH3, J = 7.5 Hz); 1.62 (m, 2 H, CH2); 1.87 (m, 1 H, CH2);
2.03 (m, 1 H, CH2); 2.62 (s, 3 H, CH3); 2.67 (s, 3 H, CH3); 4.47
(dd, 1 H, CHSO2, J1 = 12 Hz, J2 = 4 Hz); 7.65 (s, 1 H, H(5)
thieno[2,3ꢀb]pyridine).
3ꢀHydroxyꢀ4,6ꢀdimethylꢀ2ꢀphenylthieno[2,3ꢀb]pyridine (12a),
the yield was 54%, m.p. 156—158 °C (acetone—hexane). Found
(%): C, 70.48; H, 5.08; S, 12.68. C15H13NOS. Calculated (%):
C, 70.56; H, 5.13; S, 12.56. IR, ν/cm–1: 3450—3300 (OH).
1H NMR, δ: 2.50 (s, 3 H, CH3); 2.70 (s, 3 H, CH3); 7.04 (s, 1 H,
H(5) thieno[2,3ꢀb]pyridine); 7.23 (t, 1 H, Ph, J = 7.5 Hz); 7.46
(t, 2 H, Ph, J = 7.5 Hz); 7.74 (d, 2 H, Ph, J = 7.5 Hz); 9.40 (br.s,
1 H, OH).
2ꢀ(4ꢀChlorophenyl)ꢀ3ꢀhydroxyꢀ4,6ꢀdimethylthieno[2,3ꢀb]ꢀ
pyridine (12b), the yield was 51%, m.p. 152—154 °C (acetone—
hexane). Found (%): C, 62.02; H, 4.23; Cl, 12.05; S, 10.90.
C15H12ClNOS. Calculated (%): C, 62.17; H, 4.17; Cl, 12.23;
S, 11.06. IR, ν/cm–1: 3450—3300 (OH). 1H NMR, δ: 2.50 (s,
3 H, CH3); 2.70 (s, 3 H, CH3); 7.05 (s, 1 H, H(5) thieno[2,3ꢀb]ꢀ
This work was partially financially supported by
the Russian Academy of Sciences (Program of RAS,
Pꢀ8, 2008).

2ꢀAryl(thienyl, butyl)thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 10, October, 2008
2145
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Received October 24, 2007;
in revised form January 23, 2008