Functionalized sulfur-containing compounds. 13. Synthesis of substituted 3-amino-2-(organylsulfinyl)- and -(organylsulfonyl)thieno[2,3-b]pyridines

Article abstract of DOI:10.1007/s11172-006-0287-y

A method for the synthesis of substituted 3-amino-2-(organylsulfinyl) thieno[2,3-b]pyridines by the Thorpe-Ziegler intramolecular cyclization of substituted 3-cyano-2-[(organyl-sulfinyl)methylthio]pyridines was proposed. 3-Amino-2-(organylsulfonyl)thieno[

Full text of DOI:10.1007/s11172-006-0287-y

Russian Chemical Bulletin, International Edition, Vol. 55, No. 3, pp. 529—534, March, 2006
529
Functionalized sulfurꢀcontaining compounds.
13.* Synthesis of substituted 3ꢀaminoꢀ2ꢀ(organylsulfinyl)ꢀ
and ꢀ(organylsulfonyl)thieno[2,3ꢀb]pyridines
V. E. Kalugin,ꢀ A. M. Shestopalov, and V. P. Litvinov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328. Eꢀmail: vek@gazsvyaz.ru
A method for the synthesis of substituted 3ꢀaminoꢀ2ꢀ(organylsulfinyl)thieno[2,3ꢀb]pyridines
by the Thorpe—Ziegler intramolecular cyclization of substituted 3ꢀcyanoꢀ2ꢀ[(organylꢀ
sulfinyl)methylthio]pyridines was proposed. 3ꢀAminoꢀ2ꢀ(organylsulfonyl)thieno[2,3ꢀb]pyriꢀ
dines were obtained by reactions of substituted 3ꢀcyanopyridineꢀ2ꢀthiones with chloromethyl
organyl sulfones. The reaction intermediates 3ꢀcyanoꢀ2ꢀ[(organylsulfonyl)methylthio]pyridines
were transformed into 3ꢀaminoꢀ2ꢀ(organylsulfonyl)thieno[2,3ꢀb]pyridines.
Key words: intramolecular cyclization, the Thorpe—Ziegler reaction, 3ꢀcyanopyridineꢀ2ꢀ
thiones, chloromethyl organyl sulfides, chloromethyl organyl sulfones, 3ꢀcyanoꢀ2ꢀ[(organylꢀ
sulfinyl)methylthio]pyridines, 3ꢀaminoꢀ2ꢀ(organylsulfinyl)thieno[2,3ꢀb]pyridines, 3ꢀaminoꢀ
2ꢀ(organylsulfonyl)thieno[2,3ꢀb]pyridines.
3ꢀAminothieno[2,3ꢀb]pyridine derivatives are of inꢀ
terest as potential drugs.1—6 They are most commonly
synthesized by alkylation of 3ꢀcyanopyridineꢀ2ꢀthiones
with αꢀhalogenꢀcontaining compounds with an active
methylene group such as αꢀhalo carboxylic acids, esters,
amides, and nitriles and αꢀhalo ketones followed by the
baseꢀcatalyzed Thorpe—Ziegler intramolecular cyclizaꢀ
tion (Scheme 1).7—14 Alkali metal hydroxides or alkoxides
have been usually employed as bases.
group (Z = S(O)R or SO2R) in position 2 have been
documented, although the corresponding alkylated interꢀ
mediates have sufficiently "acidic" protons and could enꢀ
ter into the Thorpe—Ziegler intramolecular cyclization.
For this reason, it was of interest to investigate these
reactions.
The target sulfoxides were obtained by alkylation
of 3ꢀcyanopyridineꢀ2ꢀthiones 1a—c with chloromethyl
organyl sulfides 2a—c followed by oxidation of the deꢀ
rived 3ꢀcyanoꢀ2ꢀ[(organylthio)methylthio]pyridines 3a—h
with H2O2 in acetic acid—chloroform (Scheme 2). In this
case, only one S atom was oxidized to give 3ꢀcyanoꢀ
2ꢀ[(organylsulfinyl)methylthio]pyridines 4a—h.
Scheme 1
The physical characteristics of sulfides 3a—h and sulꢀ
foxides 4a—h are given in Table 1. Their spectroscopic
characteristics are presented in Table 2.
Intramolecular cyclization of sulfoxides 4a—h was carꢀ
ried out by adding a solution of KOH in aqueous methaꢀ
nol to a solution of compound 4 in DMF. 3ꢀAminoꢀ2ꢀ
(organylsulfinyl)thieno[2,3ꢀb]pyridines 5a—h were obꢀ
tained in good yields (see Table 1). The fact of the cyꢀ
clization was proven by IR spectroscopy. The spectra of
the products showed no absorption bands of the cyano
group at 2212—2220 cm–1; instead, absorption bands apꢀ
peared at 3400—3500 cm–1, which is characteristic of an
amino group (Table 3).
Z = COOH, COOR, CONHR, COR, CN
B is the base
We failed to synthesize similar 3ꢀcyanoꢀ2ꢀ[(organylꢀ
sulfonyl)methylthio]pyridines 6 by oxidation of sulfides 3
or sulfoxides 4 because the oxidation also occurred at the
S atom bound to the pyridine ring, giving a mixture of
No examples of the synthesis of 3ꢀaminothieꢀ
no[2,3ꢀb]pyridines containing the sulfinyl or sulfonyl
* For Part 12, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 510—515, March, 2006.
1066ꢀ5285/06/5503ꢀ0529 © 2006 Springer Science+Business Media, Inc.

530
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
Kalugin et al.
Scheme 2
intramolecular cyclization into 3ꢀaminoꢀ2ꢀ(organylꢀ
sulfonyl)thieno[2,3ꢀb]pyridines 8a—f (Scheme 3).
Scheme 3
Compound
R1 R2
R3
R2—R3
Compound
R4
1a, 3a—c,
4a—c, 5a—c
1b, 3d—f,
Me
H
H
Me
2a, 3a,d,g—5a,d,g C8H17
Compound
R1
R2
R3
Compound
R4
—(CH2)4—
2b, 3b,e,h—5b,e,h
Ph
R2—R3
4d—f, 5d—f
1c, 3g,h—5g,h CF3
H
2ꢀthienyl 2c, 3c,f—5c,f
CH2Ph
1d, 8f
8a—c
8d,e
Ph
Me
H
H
H
4ꢀ(MeO)C6H4 7a, 8a,f
Bu
C8H17
Ph
Me
7b, 8b
7c, 8c,d
7d, 8e
—(CH2)4—
products. Because of this, we attempted to obtain sulꢀ
fones 6 by reactions of 3ꢀcyanopyridineꢀ2ꢀthiones 1 with
chloromethyl organyl sulfones 7.
CH2Ph
Insofar as sulfones 7 are poorly reactive, their reacꢀ
tions with pyridinethiones 1 were carried out in DMF at
100—110 °C for several hours in the presence of triethylꢀ
amine. The IR spectra of the products showed no absorpꢀ
tion bands characteristic of the cyano group but contained
bands characteristic of the amino group (see Table 2).
Obviously, intermediate sulfones 6a—f undergo in situ
The reaction of pyridinethione 1a with chloromethyl
octyl sulfoxide 9 under analogous conditions gave a mixꢀ
ture of sulfoxides 4a and 5a (Scheme 4).
The latter result suggests that the sufficiently high acidꢀ
ity of the methylene group in both sulfones 6 and sulfꢀ
oxides 4 allows intramolecular cyclization in the presence
of such a base as triethylamine.
Table 1. Physical characteristics of compounds 3—5 and 8
Compound
Molecular
formula
Found
Calculated
M.p./°C
Yield (%)
(%)
S
C
H
N
3a
3b
3c
3d
C17H26N2S2
C15H14N2S2
C16H16N2S2
C19H28N2S2
63.19
63.31
63.04
62.90
63.81
63.97
65.32
65.47
8.22
8.13
4.87
4.93
5.32
5.37
8.14
8.10
20.02
19.88
22.23
22.39
21.43
21.34
18.54
18.40
8.60
8.69
9.69
9.78
9.38
9.32
7.98
8.04
Oil
62—64
Oil
85
87
84
84
32—34
(to be continued)

2ꢀ[Organylsulfinyl(sulfonyl)]thienopyridines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
531
Table 1 (continued)
Compound
Molecular
formula
Found
Calculated
M.p./°C
Yield (%)
(%)
S
C
H
N
3e
3f
C17H16N2S2
65.20
65.35
66.41
66.22
54.26
54.03
52.73
52.93
60.50
60.32
59.37
59.58
60.55
60.73
62.44
62.60
62.25
62.17
63.04
63.13
52.36
52.15
50.81
50.93
60.18
60.32
59.70
59.58
60.88
60.73
62.84
62.60
62.39
62.17
63.05
63.13
52.31
52.15
51.07
50.93
52.45
52.32
57.41
57.59
56.74
56.58
59.44
59.28
60.18
60.31
63.47
63.69
5.11
5.16
5.63
5.56
5.25
5.21
2.65
2.71
7.80
7.74
4.62
4.67
5.02
5.10
7.70
7.74
4.96
4.91
5.34
5.30
5.10
5.03
2.56
2.61
7.68
7.74
4.64
4.67
5.16
5.10
7.81
7.74
5.00
4.91
5.32
5.30
5.07
5.03
2.65
2.61
6.12
6.08
7.35
7.39
4.48
4.43
4.62
4.68
5.00
5.06
5.38
5.34
20.66
20.52
19.50
19.64
21.70
21.63
23.70
23.55
18.76
18.94
21.34
21.20
20.22
20.26
17.75
17.59
19.46
19.52
18.86
18.72
20.68
20.88
22.62
22.66
18.88
18.94
21.13
21.20
20.11
20.26
17.38
17.59
19.56
19.52
18.86
18.72
20.92
20.88
22.74
22.66
21.33
21.49
18.01
18.09
20.21
20.14
18.48
18.62
18.04
17.89
14.28
14.17
9.03
8.97
8.50
8.58
6.20
6.30
6.95
6.86
8.25
8.28
9.22
9.26
8.76
8.85
7.61
7.68
8.60
8.53
8.12
8.18
6.03
6.08
6.67
6.60
8.37
8.28
9.30
9.26
8.93
8.85
7.63
7.68
8.45
8.53
8.22
8.18
6.01
6.08
6.53
6.60
9.48
9.39
8.02
7.90
8.63
8.80
8.18
8.13
7.90
7.81
6.24
6.19
86—87
Oil
83
86
83
85
93
90
88
90
92
90
90
93
80
82
80
78
82
83
74
78
72
74
68
70
72
65
C
18Н18N2S2
3g
3h
4a
4b
4c
4d
4e
4f
C20H23F3N2S3
C18H11F3N2S3
C17H26N2OS2
C15H14N2OS2
C16H16N2OS2
C19H28N2OS2
C17H16N2OS2
C18H18N2OS2
77—78
123—125
Oil
162—164
124—126
76—78
184—186
172—174
123—125
172—174
66—68
4g
4h
5a
5b
5c
5d
5e
5f
C20H23F3N2OS3
C18H11F3N2OS3
C17H26N2OS2
C15H14N2OS2
C16H16N2OS2
C19H28N2OS2
C17H16N2OS2
C18H18N2OS2
130—133
137—139
103—106
164—166
172—174
86—88
5g
5h
8a
8b
8c
8d
8e
8f
C20H23F3N2OS3
C18H11F3N2OS3
C13H18N2O2S2
171—173
105—107
113—114
197—199
198—200
201—203
124—126
C
17H26N2O2S2
C15H14N2O2S2
C17H16N2O2S2
C
18H18N2O2S2
C24H24N2O3S2

532
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
Kalugin et al.
Table 2. Spectroscopic characteristics of compounds 3—5 and 8
Comꢀ
pound
IR (KBr),
ν/cm–1
1H NMR
δ (J/Hz)
3a
3b
3c
3d
2216 (CN)
2212 (CN)
2216 (CN)
2222 (CN)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42, 1.71 (both m, 2 H each, СН2); 2.45, 2.53
(both s, 3 H each, Me); 2.62 (m, 2 H, СH2S); 4.45 (s, 2 H, СH2S); 6.82 (s, 1 H, Н(5) pyridine)
2.45, 2.53 (both s, 3 H each, Me); 4.76 (s, 2 H, СH2S); 6.82 (s, 1 H, Н(5) pyridine); 7.35 (m, 3 H,
Ph); 7.50 (m, 2 H, Ph)
2.45, 2.55 (both s, 3 H each, Me); 3.72 (m, 2 H, СH2Ph); 4.47 (s, 2 H, СH2S); 6.82 (s, 1 H,
Н(5) pyridine); 7.25 (m, 5 H, Ph)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42 (m, 2 H, CH2); 1.78 (m, 6 H, СН2);
2.56 (m, 2 H, СH2S); 2.70 (t, 3 H, Me, J = 7.5); 2.85 (t, 3 H, Me, J = 7.5); 4.45 (s, 2 H,
СH2S); 7.80 (s, 1 H, Н(4) pyridine)
3e
3f
2222 (CN)
2224 (CN)
2228 (CN)
1.78 (m, 4 H, 2 СН2); 2.68, 2.85 (both t, 3 H each, Me, J = 7.5); 4.80 (s, 2 H, СH2S); 7.30 (m, 3 H,
Ph); 7.45 (m, 2 H, Ph); 7.80 (s, 1 H, Н(4) pyridine)
1.80 (m, 4 H, 2СН2); 2.71, 2.85 (both t, 3 H each, Me, J = 7.5); 3.73 (m, 2 H, СH2Ph); 4.47 (s, 2 H,
СH2S); 7.25 (m, 5 H, Ph); 7.82 (s, 1 H, Н(4) pyridine)
3g
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42, 1.71 (both m, 2 H each, СН2); 2.58 (m, 2 H,
СH2S); 4.50 (s, 2 H, СH2S); 7.20 (t, 1 H, Н(4) thiophene, J = 5.5); 7.50 (d, 1 H,
Н(3) thiophene, J = 5.5); 7.65 (d, 1 H, Н(5) thiophene, J = 5.5); 7.84 (s, 1 H, Н(5) pyridine)
3h
4a
2228 (CN)
4.86 (s, 2 H, СH2S); 7.20 (t, 1 H, Н(4) thiophene, J = 5.5); 7.30 (m, 3 H, Ph); 7.50 (m, 3 H, Ph,
Н(3) thiophene, J = 5.5); 7.68 (d, 1 H, Н(5) thiophene, J = 5.5); 7.87 (s, 1 H, Н(5) pyridine)
2216 (CN);
1030 (SO)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42, 1.72 (both m, 2 H each, СН2); 2.45, 2.55
(both s, 3 H each, Me); 2.92 (m, 2 H, СH2SO); 4.38, 4.64 (both d, 1 H each, СH2SO, J = 13);
6.82 (s, 1 H, Н(5) pyridine)
4b
4c
4d
2220 (CN);
1036 (SO)
2.40, 2.50 (both s, 3 H each, Me); 4.77, 4.90 (both d, 1 H each, СH2SO, J = 15); 7.08 (s, 1 H,
Н(5) pyridine); 7.50 (m, 3 H, Ph); 7.68 (m, 2 H, Ph)
2216 (CN);
1052 (SO)
2.45, 2.55 (both s, 3 H each, Me); 4.07 (d, 1 H, СH2SO, J = 13); 4.28 (m, 2 H, СH2Ph);
4.70 (d, 1 H, СH2SO, J = 13); 6.82 (s, 1 H, Н(5) pyridine); 7.30 (m, 5 H, Ph)
2222 (CN),
1032 (SO)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42 (m, 2 H, CH2); 1.78 (m, 6 H, СН2);
2.70, 2.85 (both t, 2 H each, CH2, J = 7.5); 2.92 (m, 2 H, СH2SO); 4.40, 4.64 (both d, 1 H each,
СH2SO, J = 14); 7.82 (s, 1 H, Н(4) pyridine)
4e
4f
2224 (CN),
1036 (SO)
1.82 (m, 4 H, 2 СН2); 2.85, 2.95 (both t, 2 H each, CH2, J = 7.5); 4.75, 4.90 (both d, 1 H each,
СH2SO, J = 15); 7.45 (m, 3 H, Ph); 7.65 (m, 2 H, Ph) 7.72 (s, 1 H, Н(4) pyridine)
2220 (CN),
1042 (SO)
1.85 (m, 4 H, 2 СН2); 2.88, 2.98 (both t, 2 H each, CH2, J = 7.5); 4.03 (d, 1 H, СH2SO, J = 13);
4.30 (m, 2 H, СH2Ph); 4.70 (d, 1 H, СH2SO, J = 13); 7.30 (m, 5 H, Ph); 7.70 (s, 1 H,
Н(4) pyridine)
4g
2230 (CN);
1036 (SO)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42 (m, 2 H, CH2); 1.71 (m, 2 H, СН2);
2.92 (m, 2 H, СH2SO); 4.43, 4.58 (both d, 1 H each, СH2SO, J = 13); 7.20 (t, 1 H, Н(4) thiophene,
J = 5.5); 7.50 (d, 1 H, Н(3) thiophene, J = 5.5), 7.68 (d, 1 H, Н(5) thiophene, J = 5.5);
7.84 (s, 1 H, Н(5) pyridine)
4h
5a
2228 (CN);
1044 (SO)
4.75, 4.92 (both d, 1 H each, СH2SO, J = 15); 7.23 (t, 1 H, Н(4) thiophene, J = 5.5); 7.50 (d, 1 H,
Н(3) thiophene, J = 5.5); 7.70 (d, 1 H, Н(5) thiophene, J = 5.5); 7.84 (s, 1 H, Н(5) pyridine)
3384, 3326,
3228 (NH2);
1016 (S=O)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42, 1.71 (both m, 2 H each, СН2); 2.55,
2.70 (both s, 3 H each, Me); 3.15 (m, 2 H, СH2SO); 5.10 (s, 2 H, NH2); 6.85 (s, 1 H,
Н(5) pyridine)
5b
5c
3424, 3388,
3212 (NH2);
1016 (S=O)
2.53, 2.70 (both s, 3 H each, Me); 5.23 (s, 2 H, NH2); 6.77 (s, 1 H); 7.45 (m, 3 H, Ph); 7.70 (m,
2 H, Ph)
3390, 3328,
3220 (NH2);
1012 (S=O)
2.50, 2.67 (both s, 3 H each, Me); 4.32 (m, 2 H, СН2Ph); 5.20 (s, 2 H, NH2); 6.90 (s, 1 H,
Н(5) pyridine); 7.30 (m, 5 H, Ph)
(to be continued)

2ꢀ[Organylsulfinyl(sulfonyl)]thienopyridines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
533
Table 2 (continued)
Comꢀ
pound
IR (KBr),
ν/cm–1
1H NMR
δ (J/Hz)
5d
3420, 3396,
3308, 3212
(NH2);
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4CH2); 1.42, 1.71 (both m, 2 H each, СН2); 1.87 (m, 4 H,
2 СН2); 2.85, 2.98 (both t, 2 H each, CH2, J = 7.5); 3.15 (m, 2 H, СH2SO); 4.57 (s, 2 H, NH2);
7.50 (s, 1 H, Н(4) pyridine)
1016 (S=O)
5e
5f
3380, 3328,
3224 (NH2);
1016 (S=O)
1.87 (m, 4 H, 2 СН2); 2.86, 2.95 (both t, 2 H each, CH2, J = 7.5); 5.00 (s, 2 H, NH2); 7.50 (m, 4 H,
Ph, Н(4) pyridine); 7.93 (m, 2 H, Ph)
3464, 3296
(NH2);
1.90 (m, 4 H, 2 СН2); 2.90, 2.98 (both t, 2 H each, CH2, J = 7.5); 4.37 (s, 2 H, СН2Ph);
4.57 (s, 2 H, NH2); 7.22 (m, 5 H, Ph); 7.45 (s, 1 H, Н(4) pyridine)
1008 (S=O)
5g
5h
8a
8b
8c
8d
8e
8f
3504, 3320
(NH2);
1024 (S=O)
0.87 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2); 1.42, 1.71 (both m, 2 H each, СН2);
3.20 (m, 2 H, СH2SO); 5.25 (s, 2 H, NH2); 7.20 (t, 1 H, Н(4) thiophene, J = 5.5); 7.50 (d, 1 H,
Н(3) thiophene, J = 5.5); 7.74 (d, 1 H, Н(5) thiophene, J = 5.5); 7.90 (s, 1 H, Н(5) pyridine)
3496, 3304
(NH2);
1020 (S=O)
5.40 (s, 2 H, NH2); 7.20 (t, 1 H, Н(4) thiophene, J = 5.5); 7.50 (m, 4 H, Ph, Н(3) thiophene);
7.70 (m, 2 H, Ph); 7.74 (d, 1 H, Н(5) thiophene, J = 5.5); 7.86 (s, 1 H, Н(5) pyridine)
3492, 3380
0.93 (t, 3 H, Me, J = 7.0); 1.42, 1.85 (both m, 2 H each, СН2); 2.55, 2.70 (both s, 3 H each, Me);
(NH2); 1276, 3.22 (m, 2 H, СH2SO2); 5.15 (s, 2 H, NH2); 6.87 (s, 1 H, Н(5) pyridine)
1144 (SO2)
3494, 3380
0.87 (t, 3 H, Me, J = 7.0); 1.30 (m, 8 H, 4 CH2); 1.42, 1.70 (both m, 2 H each, СН2); 2.55, 2.70
(NH2); 1276, (both s, 3 H each, Me); 3.20 (m, 2 H, СH2SO2); 5.07 (s, 2 H, NH2); 6.87 (s, 1 H, Н(5) pyridine)
1140 (SO2)
3500, 3384
(NH2); 1300, Ph); 8.00 (m, 2 H, Ph)
1148 (SO2)
2.55, 2.70 (both s, 3 H each, Me); 5.40 (s, 2 H, NH2); 6.85 (s, 1 H, Н(5) pyridine); 7.50 (m, 3 H,
3448, 3284
1.85 (m, 4 H, 2 СН2); 2.88, 2.95 (both t, 2 H each, CH2, J = 7.5); 5.60 (s, 2 H, NH2); 7.50 (s, 1 H,
(NH2); 1304, Н(4) pyridine); 7.55 (m, 3 H, Ph); 7.93 (m, 2 H, Ph)
1140 (SO2)
3448, 3304
1.90 (m, 4 H, 2СН2); 2.88, 2.98 (both t, 2 H each, CH2, J = 7.5); 4.40 (s, 2 H, СН2Ph);
(NH2); 1300, 4.92 (s, 2 H, NH2); 7.25 (m, 5 H, Ph); 7.48 (s, 1 H, Н(4) pyridine)
1140 (SO2)
3476, 3372
(NH2); 1300, 5.10 (s, 2 H, NH2); 7.10 (d, 2 H, J = 5.5); 7.60 (m, 5 H, Ph); 7.80 (s, 1 H, Н(5) pyridine);
1116 (SO2) 7.90 (d, 2 H, J = 5.5)
0.92 (t, 3 H, Me, J = 7.0); 1.41, 1.85 (both m, 2 H each, СН2); 3.85 (s, 3 H, MeО);
Scheme 4
Experimental
IR spectra were recorded on a PerkinꢀElmerꢀ577 instrument
(chloroform or Nujol). 1H NMR spectra were recorded on a
Bruker WMꢀ250 instrument (250 MHz) in DMSOꢀd6.
Compounds 1a (see Ref. 7), 1b (see Ref. 14), 1c (see Ref. 15),
and 1d (see Ref. 10) were prepared according to known proꢀ
cedures.
Chloromethyl organyl sulfides 2a—c and chloromethyl
organyl sulfones 7a—d were prepared as described earlier.16
3ꢀCyanoꢀ2ꢀ[(organylthio)methylthio]pyridines 3a—h (general
procedure). Triethylamine (15 mmol) was added to a solution
of 3ꢀcyanopyridineꢀ2ꢀthione 1 (10 mmol) and chloromethyl
organyl sulfide 2 (10 mmol) in dry acetonitrile (15 mL). The
reaction mixture was refluxed for 20 min, cooled, and diluted
with ether (40 mL). The precipitate that formed was filtered off,
the filtrate was concentrated under reduced pressure, and the
residue was chromatographed on silica gel with hexane—benꢀ

534
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
Kalugin et al.
zene (8 : 1) as an eluent. The eluate was concentrated and the
residue was crystallized from acetone—methanol.
2. G. Wagner, H. Vieweg, S. Leistner, N. Boehm, U. Krasselt,
V. Hanfeld, J. Prantz, and R. Grupe, Pharmazie, 1990,
45, 102.
3. A. Rumler, V. Hagen, and A. Hagen, Pharmazie, 1990,
45, 657.
4. F. Guerrera, L. Saferno, M. C. Sarva, and M. A. Siracussa,
Farmaco, 1993, 48, 1725.
5. V. P. Litvinov, L. A. Rodinovskaya, Yu. A. Sharanin,
A. M. Shestopalov, and A. Senning, Sulfur Rep., 1992, 13,
155 pp.W
6. V. P. Litvinov, V. V. Dotsenko, and S. G. Krivokolysko,
Khimiya tienopiridinov i rodstvennykh sistem [The Chemistry
of Thienopyridines and Related Systems], Nauka, Moscow,
2005, 410 pp. (in Russian).
7. K. Gewald, M. Hentschel, and U. Illgen, J. Pract. Chem.,
1974, 316, 1030.
8. F. Guerrera, M. A. Siracussa, and B. Tornetta, Farmaco,
Ed. Sci., 1976, 31, 21.
9. A. Krause, Z. Bomica, A. M. Shestopalov, L. A.
Rodinovskaya, and J. Pelczer, Khim. Geterotsikl.
Soedin., 1981, 377 [Chem. Heterocycl. Comp., 1981 (Engl.
Transl.)].
3ꢀCyanoꢀ2ꢀ[(organylsulfinyl)methylthio]pyridines 4a—h (genꢀ
eral procedure). Acetic acid (10 mL) and 30% H2O2 (0.6 mL,
6 mmol) were added to a solution of sulfide 3 (5 mmol) in
chloroform (10 mL). The reaction mixture was kept at 30—35 °C
for 30 min and neutralized in a separatory funnel with a solution
of Na2CO3. Organic material from the aqueous layer was exꢀ
tracted with chloroform. The combined extract was dried over
MgSO4, the solvent was removed in vacuo, and the residue was
crystallized from ether.
3ꢀAminoꢀ2ꢀ(organylsulfinyl)thieno[2,3ꢀb]pyridines 5a—h
(general procedure). A solution of KOH (3 mmol) in a mixture
of water (2 mL) and methanol (10 mL) was added to a solution
of sulfoxide 4 (5 mmol) in DMF (10—20 mL). The reaction
mixture was kept at 35—40 °C for 30 min and cooled. If a preꢀ
cipitate formed, it was filtered off and washed with methanol; if
no precipitate formed, the reaction mixture was poured into a
separatory funnel with water (100 mL) and the product was
extracted with chloroform. The combined extract was dried over
MgSO4, the solvent was removed in vacuo, and the residue was
crystallized from ether.
3ꢀAminoꢀ2ꢀ(organylsulfonyl)thieno[2,3ꢀb]pyridines 8a—f
(general procedure). A solution of 3ꢀcyanopyridineꢀ2ꢀthione 1
(5 mmol), chloromethyl organyl sulfone 7 (5 mmol), and triꢀ
ethylamine (8 mmol) in DMF (5 mL) was kept at 100—110 °C
for 7 h, cooled, and worked up as described for compounds 5.
Sulfones 8a—f were purified by crystallization from methanol or
ethanol.
Chloromethyl octyl sulfoxide (9). A solution of monoꢀ
peroxyphthalic acid (3.65 g, 20 mmol) in ether (50 mL) was
added at –15 to –10 °C to a stirred solution of chloromethyl
octyl sulfide (3.9 g, 20 mmol) in anhydrous ether (100 mL). The
reaction mixture was stirred at this temperature for 30 min,
allowed to warm to 0 °C, and treated with a solution of Na2CO3.
The organic phase was dried over MgSO4 and concentrated. The
residue was crystallized from ether—hexane. The yield of comꢀ
pound 9 was 3.6 g, m.p. 43 °C. Found (%): C, 51.44; H, 9.15;
S, 15.10; Cl, 16.70. C9H19ClO5. Calculated (%): C, 51.29;
H, 9.09; S, 15.21; Cl, 16.82.
Reaction of 3ꢀcyanoꢀ4,6ꢀdimethylpyridineꢀ2ꢀthione (1a) with
chloromethyl octyl sulfoxide (9). A solution of compound 1a
(0.82 g, 5 mmol), sulfoxide 9 (1.05 g, 5 mmol), and triethylꢀ
amine (8 mmol) in DMF (7 mL) was kept at 100—110 °C for
7 h and worked up as described for compounds 5. The residue
was chromatographed on silica gel with chloroform—acetone
(10 : 1) as an eluent to give sulfoxide 4a (1 g) and thienopyriꢀ
dine 5a (0.55 g).
10. Yu. A. Sharanin, A. M. Shestopalov, and V. K.
Promonenkov, Zh. Org. Khim., 1984, 20, 2012 [J. Org. Chem.
USSR, 1984, 20 (Engl. Transl.)].
11. V. P. Litvinov, Yu. A. Sharanin, L. A. Rodinovskaya,
A. M. Shestopalov, V. Yu. Mortikov, and V. K.
Promonenkov, Izv. Akad. Nauk SSSR, Ser. Khim., 1984,
2760 [Bull. Acad. Sci USSR, Div. Chem. Sci., 1984, 33, 2528
(Engl. Transl.)].
12. V. P. Litvinov, E. E. Apenova, Yu. A. Sharanin, V. N.
Nesterov, V. E. Shklover, and Yu. T. Struchkov, Izv. Akad.
Nauk SSSR, Ser. Khim., 1986, 145 [Bull. Acad. Sci USSR,
Div. Chem. Sci., 1986, 35, 131 (Engl. Transl.)].
13. L. A. Rodinovskaya, Yu. A. Sharanin, A. M. Shestopalov,
and V. P. Litvinov, Khim. Geterotsikl. Soedin., 1988, 805
[Chem. Heterocycl. Comp., 1988 (Engl. Transl.)].
14. L. A. Rodinovskaya, E. V. Belukhina, A. M. Shestopalov,
and V. P. Litvinov, Izv. Akad. Nauk, Ser. Khim., 1994, 489
[Russ. Chem. Bull., 1994, 43, 449 (Engl. Transl.)].
15. L. A. Rodinovskaya, Yu. A. Sharanin, V. P. Litvinov, A. M.
Shestopalov, V. K. Promonenkov, B. M. Zolotarev, and
V. Yu. Mortikov, Zh. Org. Khim., 1985, 21, 2439 [J. Org.
Chem. USSR, 1985, 21 (Engl. Transl.)].
16. A. R. Derzhinskii, V. E. Kalugin, and E. N. Prilezhaeva,
Izv. Akad. Nauk SSSR, Ser. Khim., 1982, 1375
[Bull. Acad. Sci USSR, Div. Chem. Sci., 1982, 31 (Engl.
Transl.)].
References
1. V. E. Kalugin and V. P. Litvinov, Izv. Akad. Nauk, Ser. Khim.,
2000, 881 [Russ. Chem. Bull., 2000, 49, 879 (Engl. Transl.)].
Received 20 January 2006;
in revised form 23 March 2006