Synthesis of 3-arylthieno[2,3-b]-, -[2,3-c]- or -[3,2-c]pyridines utilizing an interrupted pummerer reaction

Article abstract of DOI:10.1055/s-0030-1260152

An efficient procedure for the synthesis of three types of thienopyridines has been developed. Thus, 3-(1-arylethenyl)-2-(ethylsulfinyl)pyridines, 4-(1-arylethenyl)-3-(ethylsulfinyl)pyridines, and 3-(1-arylethenyl)-4- (ethylsulfinyl)pyridines, which can be easily prepared from the respective aryl chloropyridinyl ketones in a three-step sequence, undergo an interrupted Pummerer reaction on treatment with excess acetic anhydride at temperatures ranging from 100 to 130 C to give 3-arylthieno[2,3-b]pyridines, 3-aryl-thieno[2,3-c]pyridines, and 3-arylthieno[3,2-c]pyridines, respectively. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1260152

PAPER
2897
Synthesis of 3-Arylthieno[2,3-b]-, -[2,3-c]- or -[3,2-c]pyridines Utilizing an
Interrupted Pummerer Reaction
Synthesis of
T
hien
a
opyridineszuhiro Kobayashi,* Teruhiko Suzuki, Mai Horiuchi, Yasuhiko Shiroyama, Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University,
4-101 Koyama-minami, Tottori 680-8552, Japan
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 20 May 2011; revised 19 June 2011
mercially available 2-chloropyridine and lithium
diisopropylamide, with benzaldehyde followed by oxida-
tion of the resulting alcohol with activated manganese(VI)
oxide.9 We found that the ketone 1a could be prepared di-
Abstract: An efficient procedure for the synthesis of three types of
thienopyridines has been developed. Thus, 3-(1-arylethenyl)-2-
(ethylsulfinyl)pyridines,
4-(1-arylethenyl)-3-(ethylsulfinyl)py-
ridines, and 3-(1-arylethenyl)-4-(ethylsulfinyl)pyridines, which can
be easily prepared from the respective aryl chloropyridinyl ketones rectly by treatment of 2-chloro-3-lithiopyridine with N,N-
in a three-step sequence, undergo an interrupted Pummerer reaction
on treatment with excess acetic anhydride at temperatures ranging
dimethylbenzamide (see experimental section). Ketone
1a was transformed into 2-(ethylsulfinyl)-3-(1-phe-
from 100 to 130 °C to give 3-arylthieno[2,3-b]pyridines, 3-aryl-
nylethenyl)pyridine (4a) (Scheme 1). Thus, substitution
thieno[2,3-c]pyridines, and 3-arylthieno[3,2-c]pyridines, respec-
of the 2-chloro group with sodium ethanethiolate afforded
tively.
[(2-(ethylsulfanyl)pyridin-3-yl]phenylmethanone (2a),
Key words: thieno[2,3-b]pyridines,
thieno[2,3-c]pyridines,
which was allowed to react with methylenetriphenylphos-
phorane to give 2-(ethylsulfanyl)-3-(1-phenylethenyl)py-
ridine (3a); oxidation of this sulfide with sodium
metaperiodate in aqueous methanol gave 4a.
thieno[3,2-c]pyridines, interrupted Pummerer reaction, acetic anhy-
dride
Some derivatives having the thieno[2,3-b]pyridine,
thieno[2,3-c]pyridine, or thieno[3,2-c]pyridine skeleton
have been reported to exhibit various biological activity.1–4
A number of efficient syntheses of thieno[2,3-b]pyridine
derivatives have been reported.1e,g,5 Surprisingly, howev-
er, there have been only a few efficient methods for the
preparation of thieno[2,3-c]- or -[3,2-c]pyridines in the
literature.2e,6 On the other hand, we have recently reported
a synthesis of 3-arylbenzo[b]thiophenes by means of an
interrupted Pummerer reaction of 1-(arylethenyl)-2-(eth-
ylsulfinyl)benzenes.7 Hence, we were interested in devel-
oping a new method applicable to the preparation of all of
these three types of thienopyridine derivatives by apply-
ing this procedure to the respective pyridine substrates.
The results of our study, which provide a convenient and
common approach to these thienopyridines, are reported
here. We found that the interrupted Pummerer reaction of
3-(1-arylethenyl)-2-(ethylsulfinyl)pyridines, 4-(1-aryl-
ethenyl)-3-(ethylsulfinyl)pyridines, and 3-(1-arylethen-
yl)-4-(ethylsulfinyl)pyridines, which could be prepared
from the respective aryl chloropyridinyl ketones in an
easy three-step sequence, gave 3-arylthieno[2,3-b]py-
ridines, 3-arylthieno[2,3-c]pyridines, and 3-aryl-
thieno[3,2-c]pyridines, respectively.
O
O
Ar
Ar
NaSEt
N
Cl
N
SEt
1
2a 77%
a Ar = Ph
2b 79%
2c 76%
2d 81%
2e 83%
b Ar = 4-MeOC6H4
c Ar = 3,4-(MeO)2C6H3
d Ar = 3,4-(CH2OCH2)C6H3
e Ar = thiophen-2-yl
Ar
Ar
Ph3P=CH2
NaIO4
N
SEt
N
S(O)Et
3a 82%
4a 73%
3b 77%
3c 77%
3d 77%
3e 78%
4b 81%
4c 82%
4d 79%
4e 70%
Scheme 1 Preparation of 3-(1-arylethenyl)-2-(ethylsulfinyl)pyri-
dines 4
The precursor 4a was then subjected to treatment with
acetic anhydride under the conditions for the preparation
of 3-arylbenzo[b]thiophenes reported previously by us.7
Thus, 4a was dissolved in excess acetic anhydride and the
solution was heated at 100 °C until complete consumption
of the starting material 4a (TLC analyses). The reaction
was, however, complicated by the competing normal
Pummerer reaction and reduction of the sulfoxide moiety
to give a complex mixture containing the desired 3-phe-
nylthieno[2,3-b]pyridine (5a) (interrupted Pummerer
product, via A), 1-{[3-(1-phenylethenyl)pyridin-2-yl]sul-
fanyl}ethyl acetate (6) (normal Pummerer product, via B),
Our study on the synthesis of thienopyridines began by
preparing (2-chloropyridin-3-yl)phenylmethanone (1a).
This compound has previously been prepared by the reac-
tion of 2-chloro-3-lithiopyridine,8 generated from com-
SYNTHESIS 2011, No. 18, pp 2897–2906
x
x.
x
x
.
2
0
1
1
Advanced online publication: 05.08.2011
DOI: 10.1055/s-0030-1260152; Art ID: F53211SS
© Georg Thieme Verlag Stuttgart · New York

2898
K. Kobayashi et al.
PAPER
Table 1 Acetic Anhydride Mediated Synthesis of Thienopyridines
5, 11, and 16
and 3a (reduction product) (Scheme 2). This disappoint-
ing result may be ascribed to the lower stability of the cat-
ionic intermediate A due to the nitrogen of pyridine ring
compared to the corresponding intermediate for 3-phenyl-
benzo[b]thiophene previously prepared by us.7
Entry
Sulfoxide
4, 10, or 15 (°C)
Temp
Time
(h)
Product
Yielda
(%)
1
2
4a
4b
100
100
110
100
100
120
120
130
120
120
110
120
31
6
5a
5b
13
79
71
76
72
46
40
42
62
63
63
64
Ph
Ph
3
4c
9
5c
S+
Et
Ph
S
N
N
N
N
4
4d
4
5d
5a 13%
A
B
Ph
5
4e
23
24
22
26
10
10
10
28
5e
Ac2O
6
10a
10b
10c
15a
15b
15c
15d
11a
11b
11c
16a
16b
16c
16d
4a
OAc
CH
Me
100 °C
S
S
7
Me
6 46%
8
3a 6%
9
Scheme 2 Products from 2-(ethylsulfinyl)-3-(1-phenylethenyl)py-
ridine (4a)
10
11
12
This result led us to investigate the reaction of the sub-
strate carrying electron-rich (hetero)aryl groups 4b–e. (2-
Chloropyridin-3-yl)(4-methoxyphenyl)methanone (1b)
was prepared as described for the preparation of 1a. How-
ever, this direct approach to aryl(2-chloropyridin-3-
yl)methanones could not be applied to 3,4-dimethoxyphe-
nyl 1c, 3,4-(methylenedioxy)phenyl 1d, and thiophen-2-
yl derivatives 1e. These ketones were prepared by the re-
action of 2-chloro-3-lithiopyridine with the respective al-
dehydes followed by oxidation with manganese(IV)
oxide. Aryl(2-chloropyridin-3-yl)methanones 1b–e were
converted into 4b–e in a manner similar to that for the
preparation of 4a from 1a. All of the reactions proceeded
uneventfully providing the corresponding 3-(1-arylethen-
yl)-2-(ethylsulfinyl)pyridines 4b–e in good yields
(Scheme 1).
a Isolated yields.
In order to examine the generality of the present sequence,
attempts to synthesize 3-arylthieno[2,3-c]pyridines 11
from aryl(3-chloropyridin-4-yl)methanones 7 were car-
ried out (Scheme 4). Three ketones 7a–c were prepared
from commercially available 3-chloropyridine in a man-
ner similar to that described for the preparation of 1 and
transformed into the corresponding 4-(1-arylethenyl)-3-
(ethylsulfinyl)pyridines 10a–c by the same three-step se-
quence used for the preparation of 4. The reactions of 10
with acetic anhydride required higher reaction tempera-
tures and longer reaction times compared to those for the
preparation of 5 from 4, and gave rather complicated mix-
tures of products, from which only moderate yields of the
desired products 11 were obtained (Table 1, entries 6–8).
We reasoned that these somewhat disappointing results
may be ascribed to the lower electron density of 4-(1-
arylethenyl) groups compared to that of 3-(1-arylethenyl)
groups due to conjugation with the pyridine C=N moiety.
As expected, the interrupted Pummerer reaction of 4b–e
proved to proceed relatively cleanly on treatment with
acetic anhydride at 100–110 °C to give, after simply re-
moving acetic anhydride under reduced pressure followed
by purification by preparative TLC or column chromatog-
raphy on silica gel, the desired corresponding 3-aryl-
thieno[2,3-b]pyridines 5b–e (Scheme 3). The yields of the
products were fair-to-good as summarized in Table 1 (en-
tries 2–5). As can be seen from entry 5, this transforma-
tion also works well with thiophen-2-yl precursor 4e to
afford the corresponding product, 3-(thiophen-2-
yl)thieno[2,3-b]pyridine (5e), in a yield almost equivalent
to those of 5b–d, though a considerably extended reaction
time was needed.
The present sequence could also be applied to the synthe-
sis of 3-arylthieno[3,2-c]pyridines 16 (Scheme 5). Four
aryl(4-chloropyridin-3-yl)methanones 12a–d were easily
prepared from commercially available 4-chloropyridine
as described for the preparation of 1 and 7, and the con-
version of 12a–d into 3-(1-arylethenyl)-4-(ethylsulfi-
nyl)pyridines 15a–d was carried out as described above.
These four sulfoxides 15a–d were then exposed to treat-
ment with acetic anhydride at the temperatures indicated
in Table 1, which were slightly higher than those for the
preparation of 5 and slightly lower than those for the prep-
aration of 11. The desired 3-arylthieno[3,2-c]pyridines
16a–d were obtained in acceptable yields (Table 1, entries
9–12). Thiophen-2-yl substrate 15d reacted sluggishly
Ar
Ac2O, 100–110 °C
4b–e
S
N
5
Scheme 3 Preparation of 3-arylthieno[2,3-b]pyridines 5
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

PAPER
Synthesis of Thienopyridines
2899
ods.2e,6 (ii) The precursors for the last step of the present
sequence can be easily prepared from commercially avail-
able and inexpensive chloropyridines using conventional
organic reactions. (iii) The last step of the present synthe-
sis can be operated easily.
O
O
Ar
SEt
Ar
NaSEt
N
N
Cl
7
8a 85%
8b 85%
8c 98%
a Ar = 4-MeOC6H4
b Ar = 3,4-(CH2OCH2)C6H3
c Ar = thiophen-2-yl
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were de-
termined as with a Shimadzu FTIR-8300 spectrophotometer. The
1H NMR spectra were recorded in CDCl3 using TMS as an internal
reference with a Jeol ECP500 FT NMR spectrometer operating at
500 MHz. The 13C NMR spectra were determined in CDCl3 using
TMS as an internal reference with a Jeol ECP500 FT NMR spec-
trometer operating at 125 MHz. Low-resolution MS spectra (EI, 70
eV) were measured by a Jeol JMS AX505 HA spectrometer. TLC
was carried out on a Merck Kieselgel 60 PF254. Column chromatog-
raphy was performed using Wako Gel C-200E. All of the organic
solvents used in this study were dried over appropriate drying
agents and distilled prior to use. 4-Methoxy-N,N-dimethylbenza-
mide was prepared by a previously reported procedure.10 All other
chemicals used in this study were commercially available.
Ar
Ar
Ph3P=CH2
NaIO4
N
N
SEt
S(O)Et
9a 86%
9b 70%
9c 81%
10a 82%
10b 70%
10c 75%
Ar
Ac2O, 120–130 ºC
N
S
11
Scheme 4 Preparation of 3-arylthieno[2,3-c]pyridines 11
Aryl(2-chloropyridin-3-yl)methanones 1a,b, (3-Chloropyridin-
4-yl)(4-methoxyphenyl)methanone (7a), and (4-Chloropyridin-
3-yl)(4-methoxyphenyl)methanone (12a)
These compounds were prepared by treating 2-chloro-3-lithiopyri-
dine, 3-chloro-4-lithiopyridine, or 4-chloro-3-lithiopyridine with
appropriate N,N-dimethylbenzamides in THF at –78 °C under the
same conditions for the reaction of these chlorolithiopyridine with
benzaldehydes.8
with acetic anhydride to complete the reaction in a much
longer reaction time comparable to that of 5e (entry 12).
However, the yield of the corresponding product 16d was
nearly equal to those of the other products 16a–c.
O
O
N
Ar
NaSEt
N
Ar
SEt
(2-Chloropyridin-3-yl)phenylmethanone (1a)9
Cl
Yellow oil; yield: 66%; Rf = 0.26 (THF–hexane, 1:4). The spectral
data (IR and 1H NMR) were identical to those reported previously.9
12
a Ar = 4-MeOC6H4
b Ar = 3,4-(MeO)2C6H3
c Ar = 3,4-(CH2OCH2)C6H3
d Ar = thiophen-2-yl
13a 95%
13b 85%
13c 82%
13d 90%
(2-Chloropyridin-3-yl)(4-methoxyphenyl)methanone (1b)
Yellow solid; yield: 56%; mp 75–77 °C (Et2O).
IR (KBr): 1641 cm–1.
Ar
Ar
1H NMR: d = 3.89 (s, 3 H), 6.96 (d, J = 9.2 Hz, 2 H), 7.38 (dd,
J = 7.3, 5.0 Hz, 1 H), 7.72 (dd, J = 7.3, 1.8 Hz, 1 H), 7.78 (d, J = 9.2
Hz, 2 H), 8.54 (dd, J = 5.0, 1.8 Hz, 1 H).
Ph3P=CH2
N
NaIO4
N
SEt
S(O)Et
Anal. Calcd for C13H10ClNO2: C, 63.04; H, 4.07; N, 5.66. Found: C,
62.96; H, 4.33; N, 5.49.
14a 92%
15a 63%
14b 93%
14c 83%
14d 77%
15b 73%
15c 60%
15d 68%
(3-Chloropyridin-4-yl)(4-methoxyphenyl)methanone (7a)
White solid; yield: 70%; mp 94–97 °C (hexane–Et2O).
Ar
Ac2O, 110–120 °C
IR (KBr): 1655 cm–1.
N
1H NMR: d = 3.90 (s, 3 H), 6.97 (d, J = 9.2 Hz, 2 H), 7.27 (d, J = 5.0
Hz, 1 H), 7.77 (d, J = 9.2 Hz, 2 H), 8.62 (d, J = 5.0 Hz, 1 H), 8.71
(s, 1 H).
S
16
Scheme 5 Preparation of 3-arylthieno[3,2-c]pyridines 16
Anal. Calcd for C13H10ClNO2: C, 63.04; H, 4.07; N, 5.66. Found: C,
62.96; H, 4.09; N, 5.49.
In conclusion, we have developed a convenient procedure
for the synthesis of three types of 3-arylthienopyridines
(4-Chloropyridin-3-yl)(4-methoxyphenyl)methanone (12a)
utilizing an interrupted Pummerer reaction of the respec- Yellow solid; yield: 56%; mp 86–89 °C (hexane–Et2O).
IR (KBr): 1649 cm–1.
tive (1-arylethenyl)(ethylsulfinyl)pyridines. Although the
3-substituents in the products are limited to electron-rich
aryl groups, the present method may find value in organic
synthesis because of its notable advantages: (i) Thienopy-
ridines synthesized in the present study, especially 3-
arylthieno[2,3-c]pyridines and 3-arylthieno[3,2-c]py-
ridines, are very difficult to prepare by previous meth-
1H NMR: d = 3.90 (s, 3 H), 6.97 (d, J = 9.2 Hz, 2 H), 7.44 (d, J = 5.5
Hz, 1 H), 7.79 (d, J = 9.2 Hz, 2 H), 8.58 (s, 1 H), 8.62 (d, J = 5.5 Hz,
1 H).
Anal. Calcd for C13H10ClNO2: C, 63.04; H, 4.07; N, 5.66. Found: C,
62.97; H, 4.28; N, 5.37.
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

2900
K. Kobayashi et al.
PAPER
Aryl(2-chloropyridin-3-yl)methanones 1c–e, Aryl(3-chloropy-
ridin-4-yl)methanones 7b,c, and Aryl(4-chloropyridin-3-
yl)methanones 12
These compounds were prepared by treating 2-chloro-2-lithiopyri-
dine with appropriate aldehydes in THF at –78 °C,8 followed by ox-
idation of the resulting alcohols with MnO2 under the reported
conditions.9
IR (neat): 1647, 1609 cm–1.
1H NMR: d = 7.16 (dd, J = 5.0, 3.7 Hz, 1 H), 7.38 (dd, J = 7.3, 4.6
Hz, 1 H), 7.43 (dd, J = 3.7, 0.9 Hz, 1 H), 7.80 (dd, J = 7.3, 1.8 Hz,
1 H), 7.82 (dd, J = 5.0, 0.9 Hz, 1 H), 8.56 (dd, J = 4.6, 1.8 Hz, 1 H).
Anal. Calcd for C10H6ClNOS: C, 53.70; H, 2.70; N, 6.26. Found: C,
53.83; H, 2.70; N, 6.19.
(1,3-Benzodioxol-5-yl)(3-chloropyridin-4-yl)methanol
White solid; yield: 67%; mp 168–171 °C (hexane–CH2Cl2).
IR (KBr): 3154 cm–1.
(2-Chloropyridin-3-yl)(3,4-dimethoxyphenyl)methanol
Yellow oil; yield: 60%; Rf = 0.19 (THF–hexane, 1:2).
IR (neat): 3381, 1604 cm–1.
1H NMR: d = 2.36 (d, J = 3.2 Hz, 1 H), 5.94 (d, J = 1.4 Hz, 1 H),
5.96 (d, J = 1.4 Hz, 1 H), 6.02 (d, J = 3.2 Hz, 1 H), 6.77 (d, J = 7.8
Hz, 1 H), 6.82 (d, J = 1.4 Hz, 1 H), 6.86 (dd, J = 7.8, 1.4 Hz, 1 H),
7.68 (d, J = 5.0 Hz, 1 H), 8.50 (s, 1 H), 8.54 (d, J = 5.0 Hz, 1 H).
1H NMR: d = 2.43 (d, J = 3.7 Hz, 1 H), 3.86 (s, 3 H), 3.87 (s, 3 H),
6.10 (d, J = 3.7 Hz, 1 H), 6.82–6.94 (m, 3 H), 7.31 (dd, J = 7.8, 4.6
Hz, 1 H), 8.01 (dd, J = 7.8, 1.8 Hz, 1 H), 8.32 (dd, J = 4.6, 1.8 Hz,
1 H).
Anal. Calcd for C13H10ClNO3: C, 59.22; H, 3.82; N, 5.31. Found: C,
58.94; H, 3.54; N, 5.13.
Anal. Calcd for C14H14ClNO3: C, 60.11; H, 5.04; N, 5.01. Found: C,
59.95; H, 5.23; N, 4.76.
(1,3-Benzodioxol-5-yl)(3-chloropyridin-4-yl)methanone (7b)
Yellow oil; yield: 67%; Rf = 0.40 (EtOAc–hexane, 1:3).
IR (neat): 1667, 1603 cm–1.
(2-Chloropyridin-3-yl)(3,4-dimethoxyphenyl)methanone (1c)
White solid; yield: 57%; mp 185–187 °C (hexane–CH2Cl2).
IR (KBr): 1655 cm–1.
1H NMR: d = 6.10 (s, 2 H), 6.85 (d, J = 8.2 Hz, 1 H), 7.23 (dd,
J = 8.2, 1.4 Hz, 1 H), 7.26 (d, J = 4.6 Hz, 1 H), 7.38 (d, J = 1.8 Hz,
1 H), 8.62 (d, J = 4.6 Hz, 1 H), 8.70 (s, 1 H).
1H NMR: d = 3.96 (s, 6 H), 6.86 (d, J = 7.8 Hz, 1 H), 7.19 (dd,
J = 7.3, 1.8 Hz, 1 H), 7.38 (dd, J = 7.3, 5.0 Hz, 1 H), 7.58 (d, J = 2.3
Hz, 1 H), 7.72 (dd, J = 7.8, 2.3 Hz, 1 H), 8.54 (dd, J = 5.0, 1.8 Hz,
1 H).
Anal. Calcd for C13H8ClNO3: C, 59.67; H, 3.08; N, 5.35. Found: C,
59.78; H, 3.19; N, 5.09.
Anal. Calcd for C14H12ClNO3: C, 60.55; H, 4.36; N, 5.04. Found: C,
60.71; H, 4.60; N, 4.90.
(3-Chloropyridin-4-yl)(thiophen-2-yl)methanol
White solid; yield: 72%; mp 116–118 °C (hexane–Et2O).
IR (KBr): 3106 cm–1.
1H NMR: d = 2.77 (d, J = 3.9 Hz, 1 H), 6.37 (d, J = 3.9 Hz, 1 H),
6.92–7.00 (m, 2 H), 7.31 (dd, J = 4.9, 1.4 Hz, 1 H), 7.72 (d, J = 4.9
Hz, 1 H), 8.52 (s, 1 H), 8.55 (d, J = 4.9 Hz, 1 H).
(1,3-Benzodioxol-5-yl)(2-chloropyridin-3-yl)methanol
White solid; yield: 68%; mp 113–115 °C (THF).
IR (KBr): 3343 cm–1.
1H NMR: d = 2.35 (d, J = 3.2 Hz, 1 H), 5.95 (d, J = 1.4 Hz, 1 H),
5.96 (d, J = 1.4 Hz, 1 H), 6.05 (d, J = 3.2 Hz, 1 H), 6.78 (d, J = 8.2
Hz, 1 H), 6.83 (d, J = 1.8 Hz, 1 H), 6.87 (dd, J = 8.2, 1.8 Hz, 1 H),
7.31 (dd, J = 7.8, 4.6 Hz, 1 H), 8.04 (dd, J = 7.8, 1.8 Hz, 1 H), 8.32
(dd, J = 4.6, 1.8 Hz, 1 H).
Anal. Calcd for C10H8ClNOS: C, 53.22; H, 3.57; N, 6.21. Found: C,
53.28; H, 3.75; N, 6.04.
(3-Chloropyridin-4-yl)(thiophen-2-yl)methanone (7c)
Yellow oil; yield: 66%; Rf = 0.44 (EtOAc–hexane, 1:2).
IR (neat): 1651 cm–1.
1H NMR: d = 7.17 (dd, J = 4.6, 3.6 Hz, 1 H), 7.35 (d, J = 5.0 Hz, 1
H), 7.42 (dd, J = 3.6, 1.4 Hz, 1 H), 7.84 (dd, J = 4.6, 1.4 Hz, 1 H),
8.64 (d, J = 5.0 Hz, 1 H), 8.74 (s, 1 H).
Anal. Calcd for C13H10ClNO3: C, 59.22; H, 3.82; N, 5.31. Found: C,
58.94; H, 3.85; N, 5.23.
(1,3-Benzodioxol-5-yl)(2-chloropyridin-3-yl)methanone (1d)
Yellow oil; yield: 62%; Rf = 0.32 (THF–hexane, 1:2).
IR (neat): 1661, 1603 cm–1.
1H NMR: d = 6.09 (s, 2 H), 6.85 (d, J = 8.2 Hz, 1 H), 7.26 (dd,
J = 8.2, 1.8 Hz, 1 H), 7.37 (dd, J = 7.3, 4.6 Hz, 1 H), 7.39 (d, J = 1.8
Hz, 1 H), 7.71 (dd, J = 7.3, 1.8 Hz, 1 H), 8.54 (dd, J = 4.6, 1.8 Hz,
1 H).
Anal. Calcd for C10H6ClNOS: C, 53.70; H, 2.70; N, 6.26. Found: C,
53.54; H, 2.75; N, 6.04.
(4-Chloropyridin-3-yl)(3,4-dimethoxyphenyl)methanol
White solid; yield: 62%; mp 108–111 °C (hexane–Et2O).
IR (KBr): 3133 cm–1.
Anal. Calcd for C13H8ClNO3: C, 59.67; H, 3.08; N, 5.35. Found: C,
59.53; H, 3.29; N, 5.07.
1H NMR: d = 2.51 (d, J = 3.7 Hz, 1 H), 3.86 (s, 3 H), 3.87 (s, 3 H),
6.15 (d, J = 3.7 Hz, 1 H), 6.83 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.2,
1.8 Hz, 1 H), 6.94 (d, J = 1.8 Hz, 1 H), 7.28 (d, J = 5.5 Hz, 1 H),
8.43 (d, J = 5.5 Hz, 1 H), 8.88 (s, 1 H).
(2-Chloropyridin-3-yl)(thiophen-2-yl)methanol
Pale-yellow oil; yield: 56%; Rf = 0.33 (THF–hexane, 1:3).
IR (neat): 3334 cm–1.
1H NMR: d = 2.67 (d, J = 3.7 Hz, 1 H), 6.39 (d, J = 3.7 Hz, 1 H),
6.95–6.97 (m, 2 H), 7.29 (dd, J = 5.0, 1.4 Hz, 1 H), 7.33 (dd, J = 7.3,
4.6 Hz, 1 H), 8.10 (dd, J = 7.3, 1.8 Hz, 1 H), 8.35 (dd, J = 4.6, 1.8
Hz, 1 H).
Anal. Calcd for C14H14ClNO3: C, 60.11; H, 5.04; N, 5.01. Found: C,
60.01; H, 5.13; N, 5.05.
(4-Chloropyridin-3-yl)(3,4-dimethoxyphenyl)methanone (12b)
White solid; yield: 72%; mp 173–176 °C (hexane–Et2O).
IR (KBr): 1651 cm–1.
Anal. Calcd for C10H8ClNOS: C, 53.22; H, 3.57; N, 6.21. Found: C,
53.13; H, 3.75; N, 6.09.
1H NMR: d = 3.96 (s, 6 H), 6.87 (d, J = 8.7 Hz, 1 H), 7.21 (dd,
J = 8.7, 2.3 Hz, 1 H), 7.45 (d, J = 5.5 Hz, 1 H), 7.58 (d, J = 2.3 Hz,
1 H), 8.59 (s, 1 H), 8.63 (d, J = 5.5 Hz, 1 H).
(2-Chloropyridin-3-yl)(thiophen-2-yl)methanone (1e)
Yellow oil; yield: 70%; Rf = 0.24 (THF–hexane, 2:5).
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

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Synthesis of Thienopyridines
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Anal. Calcd for C14H12ClNO3: C, 60.55; H, 4.36; N, 5.04. Found: C,
60.57; H, 4.41; N, 4.81.
1H NMR: d = 1.31 (t, J = 7.3 Hz, 3 H), 3.18 (q, J = 7.3 Hz, 2 H),
3.88 (s, 3 H), 6.94 (d, J = 8.7 Hz, 2 H), 7.06 (dd, J = 7.3, 4.6 Hz, 1
H), 7.56 (dd, J = 7.3, 1.4 Hz, 1 H), 7.77 (d, J = 8.7 Hz, 2 H), 8.54
(dd, J = 4.6, 1.4 Hz, 1 H).
(1,3-Benzodioxol-5-yl)(4-chloropyridin-3-yl)methanol
Pale-yellow solid; yield: 60%; mp 126–128 °C (hexane–CH2Cl2).
IR (KBr): 3177 cm–1.
Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12. Found: C,
65.79; H, 5.43; N, 5.02.
1H NMR: d = 2.59 (d, J = 3.7 Hz, 1 H), 5.95 (d, J = 1.4 Hz, 1 H),
5.96 (d, J = 1.4 Hz, 1 H), 6.11 (d, J = 3.7 Hz, 1 H), 6.78 (d, J = 8.2
Hz, 1 H), 6.86–6.88 (m, 2 H), 7.27 (d, J = 5.0 Hz, 1 H), 8.42 (d,
J = 5.0 Hz, 1 H), 8.87 (s, 1 H).
[2-(Ethylsulfanyl)pyridin-3-yl](3,4-dimethoxyphenyl)metha-
none (2c)
White solid; mp 101–103 °C (hexane–Et2O).
IR (KBr): 1645 cm–1.
1H NMR: d = 1.32 (t, J = 7.3 Hz, 3 H), 3.19 (q, J = 7.3 Hz, 2 H),
3.949 (s, 3 H), 3.954 (s, 3 H), 6.86 (d, J = 8.2 Hz, 1 H), 7.08 (dd,
J = 7.3, 5.0 Hz, 1 H), 7.25 (dd, J = 7.3, 1.8 Hz, 1 H), 7.54 (s, 1 H),
7.57 (d, J = 7.3 Hz, 1 H), 8.56 (d, J = 5.0, 1.8 Hz, 1 H).
Anal. Calcd for C13H10ClNO3: C, 59.22; H, 3.82; N, 5.31. Found: C,
59.16; H, 3.89; N, 5.19.
(1,3-Benzodioxol-5-yl)(4-chloropyridin-3-yl)methanone (12c)
Yellow oil; yield: 57%; Rf = 0.43 (THF–hexane, 1:2).
IR (neat): 1661, 1603 cm–1.
Anal. Calcd for C16H17NO3S: C, 63.34; H, 5.65; N, 4.62. Found: C,
63.28; H, 5.79; N, 4.89.
1H NMR: d = 6.09 (s, 2 H), 8.85 (d, J = 8.2 Hz, 1 H), 7.27 (dd,
J = 8.2, 1.8 Hz, 1 H), 7.40 (d, J = 1.8 Hz, 1 H), 7.43 (d, J = 5.5 Hz,
1 H), 8.57 (s, 1 H), 8.62 (d, J = 5.5 Hz, 1 H).
(1,3-Benzodioxol-5-yl)[2-(ethylsulfanyl)pyridin-3-yl]metha-
none (2d)
Yellow oil; Rf = 0.42 (Et2O–hexane, 1:1).
IR (neat): 1651, 1603 cm–1.
Anal. Calcd for C13H8ClNO3: C, 59.67; H, 3.08; N, 5.35. Found: C,
59.37; H, 3.19; N, 5.27.
(4-Chloropyridin-3-yl)(thiophen-2-yl)methanol
Pale-yellow solid; yield: 78%; mp 104–106 °C (hexane–Et2O).
IR (KBr): 3300 cm–1.
1H NMR: d = 2.86 (d, J = 4.1 Hz, 1 H), 6.43 (d, J = 4.1 Hz, 1 H),
6.95–6.97 (m, 2 H), 7.29–7.31 (m, 2 H), 8.45 (d, J = 5.5 Hz, 1 H),
8.92 (s, 1 H).
1H NMR: d = 1.32 (t, J = 7.3 Hz, 3 H), 3.19 (q, J = 7.3 Hz, 2 H),
6.08 (s, 2 H), 6.84 (d, J = 8.2 Hz, 1 H), 7.07 (dd, J = 7.3, 4.6 Hz, 1
H), 7.29 (dd, J = 8.2, 1.8 Hz, 1 H), 7.37 (d, J = 1.8 Hz, 1 H), 7.55
(dd, J = 7.3, 1.8 Hz, 1 H), 8.55 (dd, J = 4.6, 1.8 Hz, 1 H).
Anal. Calcd for C15H13NO3S: C, 62.70; H, 4.56; N, 4.87. Found: C,
62.81; H, 4.50; N, 4.70.
Anal. Calcd for C10H8ClNOS: C, 53.22; H, 3.57; N, 6.21. Found: C,
53.04; H, 3.68; N, 6.07.
[2-(Ethylsulfanyl)pyridin-3-yl](thiophen-2-yl)methanone (2e)
Yellow oil; Rf = 0.52 (Et2O–hexane, 1:1).
IR (neat): 1651 cm–1.
(4-Chloropyridin-3-yl)(thiophen-2-yl)methanone (12d)
Yellow oil; yield: 56%; Rf = 0.57 (EtOAc–hexane, 1:1).
IR (neat): 1648 cm–1.
1H NMR: d = 7.17 (dd, J = 5.0, 3.7 Hz, 1 H), 7.45–7.47 (m, 2 H),
7.83 (dd, J = 5.0, 1.4 Hz, 1 H), 8.64 (d, J = 5.5 Hz, 1 H), 8.69 (s, 1
1H NMR: d = 1.33 (t, J = 7.3 Hz, 3 H), 3.20 (q, J = 7.3 Hz, 2 H),
7.08 (dd, J = 7.3, 5.0 Hz, 1 H), 7.14 (dd, J = 5.0, 4.1 Hz, 1 H), 7.48
(dd, J = 4.1, 1.8 Hz, 1 H), 7.73 (dd, J = 7.3, 1.4 Hz, 1 H), 7.76 (dd,
J = 5.0, 1.4 Hz, 1 H), 8.57 (dd, J = 5.0, 1.8 Hz, 1 H).
Anal. Calcd for C12H11NOS2: C, 57.80; H, 4.45; N, 5.62. Found: C,
57.80; H, 4.48; N, 5.61.
H).
Anal. Calcd for C10H6ClNOS: C, 53.70; H, 2.70; N, 6.26. Found: C,
53.53; H, 2.89; N, 6.04.
[3-(Ethylsulfanyl)pyridin-4-yl](4-methoxyphenyl)methanone
(8a)
3-Aroyl-2-(ethylsulfanyl)pyridines 2, 4-Aroyl-3-(ethylsulfa-
nyl)pyridines 8, and 3-Aroyl-4-(ethylsulfanyl)pyridines 13
These compounds were prepared by treating 1, 7, and 12 with
NaSEt, generated from EtSH and NaH, in DMF at 0 °C under the
conditions reported previously.7
Yellow oil; Rf = 0.35 (THF–hexane, 1:2).
IR (neat): 1661 cm–1.
1H NMR: d = 1.24 (t, J = 7.3 Hz, 3 H), 2.91 (q, J = 7.3 Hz, 2 H),
3.89 (s, 3 H), 6.95 (d, J = 9.2 Hz, 2 H), 7.19 (d, J = 4.6 Hz, 1 H),
7.75 (d, J = 9.2 Hz, 2 H), 8.56 (d, J = 4.6 Hz, 1 H), 8.73 (s, 1 H).
[2-(Ethylsulfanyl)pyridin-3-yl]phenylmethanone (2a)
Pale-yellow solid; mp 61–62 °C (hexane).
IR (KBr): 1649 cm–1.
Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12. Found: C,
65.88; H, 5.54; N, 5.04.
(1,3-Benzodioxol-5-yl)[3-(ethylsulfanyl)pyridin-4-yl]metha-
none (8b)
Yellow oil; Rf = 0.37 (THF–hexane, 1:3).
IR (neat): 1661 cm–1.
1H NMR: d = 1.33 (t, J = 7.3 Hz, 3 H), 3.20 (q, J = 7.3 Hz, 2 H),
7.07 (dd, J = 7.3, 4.6 Hz, 1 H), 7.49 (dd, J = 7.8, 7.3 Hz, 2 H), 7.61
(tt, J = 7.3, 1.4 Hz, 1 H), 7.62 (dd, J = 7.3, 1.8 Hz, 1 H), 7.78 (dd,
J = 7.8, 1.4 Hz, 2 H), 8.57 (dd, J = 4.6, 1.8 Hz, 1 H).
Anal. Calcd for C14H13NOS: C, 69.11; H, 5.39; N, 5.76. Found: C,
68.92; H, 5.32; N, 5.71.
1H NMR: d = 1.24 (t, J = 7.3 Hz, 3 H), 2.91 (q, J = 7.3 Hz, 2 H),
6.09 (s, 2 H), 6.83 (d, J = 8.2 Hz, 1 H), 7.18 (dd, J = 4.6 Hz, 1 H),
7.21 (dd, J = 8.2, 1.4 Hz, 1 H), 7.38 (d, J = 1.4 Hz, 1 H), 8.56 (d,
J = 4.6 Hz, 1 H), 8.72 (s, 1 H).
[2-(Ethylsulfanyl)pyridin-3-yl](4-methoxyphenyl)methanone
(2b)
Anal. Calcd for C15H13NO3S: C, 62.70; H, 4.56; N, 4.87. Found: C,
62.50; H, 4.78; N, 4.83.
Yellow oil; Rf = 0.29 (THF–hexane, 1:4).
IR (neat): 1651 cm–1.
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K. Kobayashi et al.
PAPER
[3-(Ethylsulfanyl)pyridin-4-yl](thiophen-2-yl)methanone (8c)
Yellow oil; Rf = 0.43 (THF–hexane, 1:2).
IR (neat): 1645 cm–1.
1H NMR: d = 1.27 (t, J = 7.3 Hz, 3 H), 2.96 (q, J = 7.3 Hz, 2 H),
7.15 (dd, J = 5.0, 3.6 Hz, 1 H), 7.31 (d, J = 5.0 Hz, 1 H), 7.40 (dd,
J = 3.6, 0.9 Hz, 1 H), 7.80 (dd, J = 5.0, 0.9 Hz, 1 H), 8.57 (d, J = 5.0
Hz, 1 H), 8.75 (s, 1 H).
1H NMR: d = 1.27 (t, J = 7.3 Hz, 3 H), 3.10 (q, J = 7.3 Hz, 2 H),
5.34 (s, 1 H), 6.86 (d, J = 0.9 Hz, 1 H), 7.02 (dd, J = 7.3, 5.0 Hz, 1
H), 7.26–7.33 (m, 5 H), 7.37 (dd, J = 7.3, 1.8 Hz, 1 H), 8.44 (dd,
J = 5.0, 1.8 Hz, 1 H).
Anal. Calcd for C15H15NS: C, 74.65; H, 6.26; N, 5.80. Found: C,
74.50; H, 6.29; N, 5.71.
2-(Ethylsulfanyl)-3-[1-(4-methoxyphenyl)ethenyl]pyridine (3b)
Pale-yellow oil; Rf = 0.60 (THF–hexane, 1:5).
IR (neat): 1605 cm–1.
Anal. Calcd for C12H11NOS2: C, 57.80; H, 4.45; N, 5.62. Found: C,
58.01; H, 4.54; N, 5.43.
[4-(Ethylsulfanyl)pyridin-3-yl](4-methoxyphenyl)methanone
(13a)
Yellow oil; Rf = 0.50 (THF–hexane, 1:2).
IR (neat): 1651 cm–1.
1H NMR: d = 1.37 (t, J = 7.3 Hz, 3 H), 2.98 (q, J = 7.3 Hz, 2 H),
3.90 (s, 3 H), 6.96 (d, J = 8.7 Hz, 2 H), 7.27 (d, J = 5.5 Hz, 1 H),
7.81 (d, J = 8.7 Hz, 2 H), 8.50 (s, 1 H), 8.51 (d, J = 5.5 Hz, 1 H).
1H NMR: d = 1.28 (t, J = 7.3 Hz, 3 H), 3.10 (q, J = 7.3 Hz, 2 H),
3.80 (s, 3 H), 5.21 (d, J = 0.9 Hz, 1 H), 5.76 (d, J = 0.9 Hz, 1 H),
6.84 (d, J = 9.2 Hz, 2 H), 7.02 (dd, J = 7.3, 5.0 Hz, 1 H), 7.21 (d,
J = 9.2 Hz, 2 H), 7.37 (dd, J = 7.3, 1.8 Hz, 1 H), 8.43 (dd, J = 5.0,
1.8 Hz, 1 H).
Anal. Calcd for C16H17NOS: C, 70.81; H, 6.31; N, 5.16. Found: C,
70.80; H, 6.32; N, 5.19.
Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12. Found: C,
65.72; H, 5.59; N, 5.04.
2-(Ethylsulfanyl)-3-[1-(3,4-dimethoxyphenyl)ethenyl]pyridine
(3c)
Colorless oil; Rf = 0.45 (EtOAc–hexane, 1:5).
IR (neat): 1601 cm–1.
(3,4-Dimethoxyphenyl)[4-(ethylsulfanyl)pyridin-3-yl]metha-
none (13b)
White solid; mp 107–109 °C (hexane–Et2O).
IR (KBr): 1636 cm–1.
1H NMR: d = 1.37 (t, J = 7.3 Hz, 3 H), 2.99 (q, J = 7.3 Hz, 2 H),
3.955 (s, 3 H), 3.964 (s, 3 H), 6.87 (d, J = 8.7 Hz, 1 H), 7.27 (d,
J = 5.5 Hz, 1 H), 7.29 (dd, J = 8.7, 1.8 Hz, 1 H), 7.55 (d, J = 1.8 Hz,
1 H), 8.51 (s, 1 H), 8.52 (d, J = 5.5 Hz, 1 H).
1H NMR: d = 1.28 (t, J = 7.3 Hz, 3 H), 3.12 (q, J = 7.3 Hz, 2 H),
3.85 (s, 3 H), 3.87 (s, 3 H), 5.24 (s, 1 H), 5.78 (s, 1 H), 6.72 (dd,
J = 8.2, 1.4 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.91 (d, J = 1.4 Hz,
1 H), 7.03 (dd, J = 7.3, 5.0 Hz, 1 H), 7.38 (dd, J = 7.3, 1.4 Hz, 1 H),
8.44 (dd, J = 5.0, 1.4 Hz, 1 H).
Anal. Calcd for C17H19NO2S: C, 67.74; H, 6.35; N, 4.65. Found: C,
67.48; H, 6.19; N, 4.89.
Anal. Calcd for C16H17NO3S: C, 63.34; H, 5.65; N, 4.62. Found: C,
63.27; H, 5.67; N, 4.61.
3-[1-(1,3-Benzodioxol-5-yl)ethenyl]-2-(ethylsulfanyl)pyridine
(3d)
(1,3-Benzodioxol-5-yl)[4-(ethylsulfanyl)pyridin-3-yl]metha-
none (13c)
Yellow oil; Rf = 0.33 (Et2O–hexane, 1:4).
White solid; mp 63–64 °C (hexane–Et2O).
IR (KBr): 1601 cm–1.
1H NMR: d = 1.28 (t, J = 7.3 Hz, 3 H), 3.11 (q, J = 7.3 Hz, 2 H),
5.22 (s, 1 H), 5.74 (s, 1 H), 5.96 (s, 2 H), 6.68 (dd, J = 8.2, 1.8 Hz,
1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 1.8 Hz, 1 H), 7.02 (dd,
J = 7.3, 5.0 Hz, 1 H), 7.36 (dd, J = 7.3, 1.8 Hz, 1 H), 8.43 (dd,
J = 5.0, 1.8 Hz, 1 H).
IR (neat): 1645 cm–1.
1H NMR: d = 1.36 (t, J = 7.3 Hz, 3 H), 2.98 (q, J = 7.3 Hz, 2 H),
6.08 (s, 2 H), 6.85 (d, J = 8.2 Hz, 1 H), 7.26 (d, J = 5.5 Hz, 1 H),
7.31 (dd, J = 8.2, 1.4 Hz, 1 H), 7.38 (d, J = 1.4 Hz, 1 H), 8.49 (s, 1
H), 8.51 (d, J = 5.5 Hz, 1 H).
Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found: C,
67.21; H, 5.31; N, 4.62.
Anal. Calcd for C15H13NO3S: C, 62.70; H, 4.56; N, 4.87. Found: C,
62.91; H, 4.80; N, 4.82.
2-(Ethylsulfanyl)-3-[1-(thiophen-2-yl)ethenyl]pyridine (3e)
Pale-yellow oil; Rf = 0.47 °C6H6–hexane, 1:5).
IR (neat): 1608 cm–1.
1H NMR: d = 1.30 (t, J = 7.3 Hz, 3 H), 3.14 (q, J = 7.3 Hz, 2 H),
5.18 (s, 1 H), 5.83 (s, 1 H), 6.68 (dd, J = 3.7, 0.9 Hz, 1 H), 6.93 (dd,
J = 5.0, 3.7 Hz, 1 H), 7.03 (dd, J = 7.3, 5.0 Hz, 1 H), 7.22 (d, J = 5.0
Hz, 1 H), 7.42 (dd, J = 7.3, 1.8 Hz, 1 H), 8.45 (dd, J = 5.0, 1.8 Hz,
1 H).
[4-(Ethylsulfanyl)pyridin-3-yl](thiophen-2-yl)methanone (13d)
Yellow oil; Rf = 0.50 (THF–hexane, 1:1).
IR (neat): 1634 cm–1.
1H NMR: d = 1.38 (t, J = 7.3 Hz, 3 H), 3.00 (q, J = 7.3 Hz, 2 H),
7.17 (dd, J = 5.0, 3.7 Hz, 1 H), 7.28 (d, J = 5.5 Hz, 1 H), 7.55 (dd,
J = 3.7, 0.9 Hz, 1 H), 7.79 (dd, J = 5.0, 0.9 Hz, 1 H), 8.53 (d, J = 5.5
Hz, 1 H), 8.70 (s, 1 H).
Anal. Calcd for C12H11NOS2: C, 57.80; H, 4.45; N, 5.62. Found: C,
57.79; H, 4.29; N, 5.61.
Anal. Calcd for C13H13NS2: C, 63.12; H, 5.30; N, 5.66. Found: C,
63.02; H, 5.41; N, 5.88.
3-(1-Arylethenyl)-2-(ethylsulfanyl)pyridines 3, 4-(1-Arylethe-
nyl)-3-(ethylsulfanyl)pyridines 9, and 3-(1-Arylethenyl)-4-(eth-
ylsulfanyl)pyridines 14
3-(Ethylsulfanyl)-4-[1-(4-methoxyphenyl)ethenyl]pyridine (9a)
Colorless crystals; mp 49–51 °C (hexane).
IR (KBr): 1605 cm–1.
1H NMR: d = 1.22 (t, J = 7.3 Hz, 3 H), 2.87 (q, J = 7.3 Hz, 2 H),
3.80 (s, 3 H), 5.18 (s, 1 H), 5.76 (s, 1 H), 6.84 (d., J = 8.7 Hz, 2 H),
7.13 (d, J = 5.0 Hz, 1 H), 7.17 (d, J = 8.7 Hz, 2 H), 8.42 (d, J = 5.0
Hz, 1 H), 8.55 (s, 1 H).
These compounds were prepared by treating 2, 8, and 13 with
Ph3P=CH2 in THF at 0 °C under conditions reported previously.11
2-(Ethylsulfanyl)-3-(1-phenylethenyl)pyridine (3a)
Pale-yellow oil; Rf = 0.62 (THF–hexane, 1:4).
IR (neat): 1615 cm–1.
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Synthesis of Thienopyridines
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Anal. Calcd for C16H17NOS: C, 70.81; H, 6.31; N, 5.16. Found: C,
70.79; H, 6.60; N, 5.18.
1H NMR: d = 1.32 (t, J = 7.3 Hz, 3 H), 2.93 (q, J = 7.3 Hz, 2 H),
5.17 (s, 1 H), 5.86 (s, 1 H), 6.68 (d, J = 3.7 Hz, 1 H), 6.93 (dd,
J = 5.0, 3.7 Hz, 1 H), 7.14 (d, J = 5.5 Hz, 1 H), 7.23 (d, J = 5.0 Hz,
1 H), 8.23 (s, 1 H), 8.44 (d, J = 5.5 Hz, 1 H).
4-[1-(1,3-Benzodioxol-5-yl)ethenyl]-3-(ethylsulfanyl)pyridine
(9b)
Anal. Calcd for C13H13NS2: C, 63.12; H, 5.30; N, 5.66. Found: C,
63.07; H, 5.41; N, 5.54.
Pale-yellow oil; Rf = 0.38 (EtOAc–hexane, 1:5).
IR (neat): 1602 cm–1.
3-(1-Arylethenyl)-2-(ethylsulfinyl)pyridines 4, 4-(1-Arylethe-
nyl)-3-(ethylsulfinyl)pyridines 10, and 3-(1-Arylethenyl)-4-(eth-
ylsulfinyl)pyridines 15
1H NMR: d = 1.24 (t, J = 7.3 Hz, 3 H), 2.89 (q, J = 7.3 Hz, 2 H),
5.18 (s, 1 H), 5.74 (s, 1 H), 5.97 (s, 2 H), 6.61 (dd, J = 8.2, 1.8 Hz,
1 H), 6.72 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 1.8 Hz, 1 H), 7.12 (d,
J = 5.0 Hz, 1 H), 8.42 (d, J = 5.0 Hz, 1 H), 8.54 (s, 1 H).
These compounds were prepared by treating 3, 9, and 14 with
NaIO4 in aq MeOH at r.t.7
Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found: C,
67.28; H 5.45; N, 4.89.
2-(Ethylsulfinyl)-3-(1-phenylethenyl)pyridine (4a)
Pale-yellow oil; Rf = 0.36 (THF–hexane, 4:1).
IR (neat): 1614, 1045 cm–1.
3-(Ethylsulfanyl)-4-[1-(thiophen-2-yl)ethenyl]pyridine (9c)
Pale-yellow oil; Rf = 0.50 (EtOAc–hexane, 1:2).
1H NMR: d = 1.11 (t, J = 7.3 Hz, 3 H), 2.74–2.81 (m, 1 H), 2.92–
2.99 (m, 1 H), 5.36 (s, 1 H), 5.93 (s, 1 H), 7.22–7.24 (m, 2 H), 7.33–
7.35 (m, 3 H), 7.46 (dd, J = 7.8, 4.6 Hz, 1 H), 7.67 (dd, J = 7.8, 1.8
Hz, 1 H), 8.82 (dd, J = 4.6, 1.8 Hz, 1 H).
IR (neat): 1607 cm–1.
1H NMR: d = 1.25 (t, J = 7.3 Hz, 3 H), 2.91 (q, J = 7.3 Hz, 2 H),
5.12 (s, 1 H), 5.82 (s, 1 H), 6.62 (dd, J = 3.6, 1.4 Hz, 1 H), 6.92 (dd,
J = 5.1, 3.6 Hz, 1 H), 7.17 (dd, J = 5.1, 0.7 Hz, 1 H), 7.23 (dd,
J = 5.1, 1.4 Hz, 1 H), 8.44 (d, J = 5.1 Hz, 1 H), 8.59 (s, 1 H).
Anal. Calcd for C15H15NOS: C, 70.01; H, 5.87; N, 5.44. Found: C,
69.75; H, 5.81; N, 5.30.
Anal. Calcd for C13H13NS2: C, 63.12; H, 5.30; N, 5.66. Found: C,
63.05; H, 5.41; N, 5.65.
2-(Ethylsulfinyl)-3-[1-(4-methoxyphenyl)ethenyl]pyridine (4b)
Pale-yellow oil; Rf = 0.51 (THF–hexane, 5:1).
IR (neat): 1607, 1028 cm–1.
1H NMR: d = 1.13 (t, J = 7.3 Hz, 3 H), 2.77–2.84 (m, 1 H), 2.93–
3.00 (m, 1 H), 3.81 (s, 3 H), 5.23 (s, 1 H), 5.83 (s, 1 H), 6.85 (d,
J = 8.7 Hz, 2 H), 7.16 (d, J = 8.7 Hz, 2 H), 7.45 (dd, J = 7.8, 4.6 Hz,
1 H), 7.66 (dd, J = 7.8, 1.8 Hz, 1 H), 8.82 (dd, J = 4.6, 1.8 Hz, 1 H).
4-(Ethylsulfanyl)-3-[1-(4-methoxyphenyl)ethenyl]pyridine
(14a)
Colorless oil; Rf = 0.59 (EtOAc–hexane, 1:2).
IR (neat): 1605 cm–1.
1H NMR: d = 1.29 (t, J = 7.3 Hz, 3 H), 2.89 (q, J = 7.3 Hz, 2 H),
3.81 (s, 3 H), 5.22 (s, 1 H), 5.78 (s, 1 H), 6.84 (d, J = 8.7 Hz, 2 H),
7.11 (d, J = 5.5 Hz, 1 H), 7.21 (d, J = 8.7 Hz, 2 H), 8.29 (s, 1 H),
8.42 (d, J = 5.5 Hz, 1 H).
Anal. Calcd for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C,
66.71; H, 6.01; N, 4.66.
Anal. Calcd for C16H17NOS: C, 70.81; H, 6.31; N, 5.16. Found: C,
70.69; H, 6.19; N, 5.10.
2-(Ethylsulfinyl)-3-[1-(3,4-dimethoxyphenyl)ethenyl]pyridine
(4c)
Colorless oil; Rf = 0.45 (EtOAc–hexane, 5:1).
IR (neat): 1601, 1022 cm–1.
3-[1-(3,4-Dimethoxyphenyl)ethenyl]-4-(ethylsulfanyl)pyridine
(14b)
Colorless oil; Rf = 0.28 (EtOAc–hexane, 1:10).
IR (neat): 1601 cm–1.
1H NMR: d = 1.30 (t, J = 7.3 Hz, 3 H), 2.90 (q, J = 7.3 Hz, 2 H),
3.85 (s, 3 H), 3.88 (s, 3 H), 5.24 (s, 1 H), 5.79 (s, 1 H), 6.72 (dd,
J = 8.2, 1.8 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.90 (d, J = 1.8 Hz,
1 H), 7.12 (d, J = 5.5 Hz, 1 H), 8.31 (s, 1 H), 8.43 (d, J = 5.5 Hz, 1
H).
1H NMR: d = 1.13 (t, J = 7.3 Hz, 3 H), 2.79–2.88 (m, 1 H), 2.95–
3.03 (m, 1 H), 3.86 (s, 3 H), 3.88 (s, 3 H), 5.25 (s, 1 H), 5.84 (s, 1
H), 6.61 (dd, J = 8.0, 2.2 Hz, 1 H), 6.78 (d, J = 8.0 Hz, 1 H), 6.88
(d, J = 2.2 Hz, 1 H), 7.46 (dd, J = 7.6, 4.8 Hz, 1 H), 7.66 (dd,
J = 7.6, 1.8 Hz, 1 H), 8.82 (dd, J = 4.8, 1.8 Hz, 1 H).
Anal. Calcd for C17H19NO3S: C, 64.33; H, 6.03; N, 4.41. Found: C,
64.21; H, 6.01; N, 4.36.
Anal. Calcd for C17H19NO2S: C, 67.74; H, 6.35; N, 4.65. Found: C,
67.68; H, 6.42; N, 4.77.
3-[1-(1,3-Benzodioxol-5-yl)ethenyl]-2-(ethylsulfinyl)pyridine
(4d)
Pale-yellow oil; Rf = 0.19 (THF–hexane, 2:1).
IR (neat): 1603, 1038 cm–1.
3-[1-(1,3-Benzodioxol-5-yl)ethenyl]-4-(ethylsulfanyl)pyridine
(14c)
Pale-yellow oil; Rf = 0.47 (EtOAc–hexane, 1:2).
IR (neat): 1603 cm–1.
1H NMR: d = 1.31 (t, J = 7.3 Hz, 3 H), 2.90 (q, J = 7.3 Hz, 2 H),
5.22 (s, 1 H), 5.75 (s, 1 H), 5.96 (s, 2 H), 6.68 (dd, J = 8.2, 1.4 Hz,
1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 1.4 Hz, 1 H), 7.11 (d,
J = 5.5 Hz, 1 H), 8.28 (s, 1 H), 8.42 (d, J = 5.5 Hz, 1 H).
1H NMR: d = 1.14 (t, J = 7.3 Hz, 3 H), 2.80–2.87 (m, 1 H), 2.95–
3.02 (m, 1 H), 5.24 (s, 1 H), 5.81 (s, 1 H), 5.99 (s, 2 H), 6.57 (dd,
J = 8.2, 1.8 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 1.8 Hz,
1 H), 7.45 (dd, J = 7.8, 4.6 Hz, 1 H), 7.65 (dd, J = 7.8, 1.8 Hz, 1 H),
8.82 (dd, J = 4.6, 1.8 Hz, 1 H).
Anal. Calcd for C16H15NO3S: C, 63.77; H, 5.02; N, 4.65. Found: C,
63.70; H, 5.00; N, 4.54.
Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found: C,
67.16; H 5.40; N, 4.65.
2-(Ethylsulfinyl)-3-[1-(thiophen-2-yl)ethenyl]pyridine (4e)
Yellow oil; Rf = 0.38 (THF–hexane, 4:1).
IR (neat): 1607, 1045 cm–1.
1H NMR: d = 1.14 (t, J = 7.3 Hz, 3 H), 2.85–2.94 (m, 1 H), 2.97–
3.05 (m, 1 H), 5.18 (s, 1 H), 5.87 (s, 1 H), 6.62 (dd, J = 3.6, 1.1 Hz,
4-(Ethylsulfanyl)-3-[1-(thiophen-2-yl)ethenyl]pyridine (14d)
Yellow oil; Rf = 0.49 (EtOAc–hexane, 1:1).
IR (neat): 1604 cm–1.
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

2904
K. Kobayashi et al.
PAPER
3-[1-(1,3-Benzodioxol-5-yl)ethenyl]-4-(ethylsulfinyl)pyridine
1 H), 6.93 (dd, J = 4.7, 3.6 Hz, 1 H), 7.26 (dd, J = 4.7, 1.1 Hz, 1 H),
7.44 (dd, J = 7.7, 4.7 Hz, 1 H), 7.69 (dd, J = 7.7, 1.5 Hz, 1 H), 8.82
(dd, J = 4.7, 1.5 Hz, 1 H).
(15c)
Pale-yellow oil; Rf = 0.21 (EtOAc–hexane, 1:2).
Anal. Calcd for C13H13NOS2: C, 59.28; H, 4.98; N, 5.32. Found: C,
59.25; H, 4.93; N, 5.34.
IR (neat): 1603, 1032 cm–1.
1H NMR: d = 1.10 (t, J = 7.3 Hz, 3 H), 2.54–2.62 (m, 1 H), 2.79–
2.86 (m, 1 H), 5.32 (s, 1 H), 5.75 (s, 1 H), 6.00 (s, 2 H), 6.61 (d,
J = 8.2 Hz, 1 H), 6.74–6.76 (m, 2 H), 7.93 (d, J = 5.0 Hz, 1 H), 8.56
(s, 1 H), 8.84 (d, J = 5.0 Hz, 1 H).
3-(Ethylsulfinyl)-4-[1-(4-methoxyphenyl)ethenyl]pyridine (10a)
Colorless oil; Rf = 0.43 (THF–hexane, 2:1).
IR (neat): 1607, 1045 cm–1.
1H NMR: d = 1.14 (t, J = 7.3 Hz, 3 H), 2.59–2.67 (m, 1 H), 2.75–
2.82 (m, 1 H), 3.82 (s, 3 H), 5.27 (s, 1 H), 5.77 (s, 1 H), 6.86 (d,
J = 8.7 Hz, 2 H), 7.13 (d, J = 8.7 Hz, 2 H), 7.23 (d, J = 5.0 Hz, 1 H),
8.75 (d, J = 5.0 Hz, 1 H), 9.13 (s, 1 H).
Anal. Calcd for C16H15NO3S: C, 63.77; H, 5.02; N, 4.65. Found: C,
63.55; H, 5.18; N, 4.62.
4-(Ethylsulfinyl)-3-[2-(thiophen-2-yl)ethenyl]pyridine (15d)
Yellow oil; Rf = 0.22 (EtOAc–hexane, 1:1).
Anal. Calcd for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C,
66.61; H, 6.01; N, 5.02.
IR (neat): 1605, 1062 cm–1.
1H NMR: d = 1.11 (t, J = 7.3 Hz, 3 H), 2.58–2.65 (m, 1 H), 2.84–
2.91 (m, 1 H), 5.26 (s, 1 H), 5.86 (s, 1 H), 6.70 (dd, J = 3.7, 0.9 Hz,
1 H), 6.96 (dd, J = 5.0, 3.7 Hz, 1 H), 7.30 (dd, J = 5.0, 0.9 Hz, 1 H),
7.96 (d, J = 5.0 Hz, 1 H), 8.59 (s, 1 H), 8.86 (d, J = 5.0 Hz, 1 H).
4-[1-(1,3-Benzodioxol-5-yl)ethenyl]-3-(ethylsulfinyl)pyridine
(10b)
Yellow oil; Rf = 0.36 (EtOAc–hexane, 3:1).
IR (neat): 1603, 1040 cm–1.
1H NMR: d = 1.16 (t, J = 7.3 Hz, 3 H), 2.61–2.69 (m, 1 H), 2.78–
2.85 (m, 1 H), 5.28 (s, 1 H), 5.75 (s, 1 H), 6.00 (s, 2 H), 6.59 (dd,
J = 8.2, 1.8 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 1.8 Hz,
1 H), 7.23 (d, J = 5.0 Hz, 1 H), 8.76 (d, J = 5.0 Hz, 1 H), 9.13 (s, 1
H).
Anal. Calcd for C13H13NOS2: C, 59.28; H, 4.98; N, 5.32. Found: C,
59.03; H, 4.86; N, 5.37.
3-Arylthienopyridines 5, 11, and 16; General Procedure
A soln of 4, 10, or 15 (1.0 mmol) in Ac2O (2 mL) was heated at 100–
130 °C under stirring until the starting material had disappeared. Af-
ter removal of excess Ac2O under reduced pressure, the residue was
purified by preparative TLC or column chromatography (silica gel),
or recrystallization to afford product(s).
Anal. Calcd for C16H15NO3S: C, 63.77; H, 5.02; N, 4.65. Found: C,
63.49; H, 5.09; N, 4.43.
3-Phenylthieno[2,3-b]pyridine (5a)11
This compound was obtained in 13% yield along with 1-{[3-(1-phe-
nylethenyl)pyridin-2-yl]sulfanyl}ethyl acetate (6) (46%) and 3a
(6%).
4-[1-(Thiophen-2-yl)ethenyl]-3-(ethylsulfinyl)pyridine (10c)
Yellow oil; Rf = 0.28 (EtOAc–hexane, 4:1).
IR (neat): 1607, 1045 cm–1.
1H NMR: d = 1.17 (t, J = 7.3 Hz, 3 H), 2.64–2.72 (m, 1 H), 2.83–
2.90 (m, 1 H), 5.23 (s, 1 H), 5.84 (s, 1 H), 6.67 (d, J = 2.7 Hz, 1 H),
6.96 (dd, J = 5.0, 1.4 Hz, 1 H), 7.26–7.31 (m, 2 H), 8.78 (d, J = 4.6
Hz, 1 H), 9.16 (s, 1 H).
Thieno[2,3-b]pyridine 5a
Rf = 0.25 (THF–hexane, 1:20).
The spectral (IR, 1H and 13C NMR) of this product were identical to
those reported previously.11
Anal. Calcd for C13H13NOS2: C, 59.28; H, 4.98; N, 5.32. Found: C,
59.06; H, 4.84; N, 5.48.
Acetate 6
Pale yellow oil; Rf = 0.25 (THF–hexane, 1:20).
IR (neat): 1744, 1616 cm–1.
1H NMR: d = 1.60 (d, J = 6.9 Hz, 3 H), 1.99 (s, 3 H), 5.33 (s, 1 H),
5.87 (s, 1 H), 6.94 (q, J = 6.9 Hz, 1 H), 7.07 (dd, J = 7.3, 5.0 Hz, 1
H), 7.26 (dd, J = 7.8, 1.8 Hz, 2 H), 7.29–7.33 (m, 3 H), 7.40 (dd,
J = 7.3, 1.8 Hz, 1 H), 8.44 (dd, J = 5.0, 1.8 Hz, 1 H).
4-(Ethylsulfinyl)-3-[1-(4-methoxyphenyl)ethenyl]pyridine (15a)
Yellow oil; Rf = 0.28 (EtOAc–hexane, 2:1).
IR (neat): 1607, 1030 cm–1.
1H NMR: d = 1.81 (t, J = 7.3 Hz, 3 H), 2.53–2.60 (m, 1 H), 2.77–
2.84 (m, 1 H), 3.82 (s, 3 H), 5.31 (s, 1 H), 5.77 (s, 1 H), 6.86 (d,
J = 9.2 Hz, 2 H), 7.15 (d, J = 9.2 Hz, 2 H), 7.93 (dd, J = 5.0, 0.9 Hz,
1 H), 8.57 (s, 1 H), 8.84 (d, J = 5.0 Hz, 1 H).
Anal. Calcd for C17H17NO2S: C, 68.20; H, 5.72; N, 4.68. Found: C,
68.12; H, 5.92; N, 4.42.
Anal. Calcd for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C,
66.74; H, 6.04; N, 4.92.
3-(4-Methoxyphenyl)thieno[2,3-b]pyridine (5b)
Pale-yellow solid; mp 95–97 °C (Et2O).
IR (KBr): 3101, 1521, 1241, 1035 cm–1.
1H NMR: d = 3.88 (s, 3 H), 7.03 (d, J = 8.7 Hz, 2 H), 7.33 (dd,
J = 8.2, 4.6 Hz, 1 H), 7.43 (s, 1 H), 7.49 (d, J = 8.7 Hz, 2 H), 8.16
(dd, J = 8.2, 1.4 Hz, 1 H), 8.61 (dd, J = 4.6, 1.4 Hz, 1 H).
13C NMR: d = 55.4, 114.4, 119.3, 122.4, 127.8, 129.5, 130.5, 131.4,
135.3, 146.6, 159.4, 162.5.
MS: m/z = 241 (100%, [M+]).
3-[1-(3,4-Dimethoxyphenyl)ethenyl]-4-(ethylsulfinyl)pyridine
(15b)
Pale-yellow oil; Rf = 0.44 (EtOAc–hexane, 5:1).
IR (neat): 1601, 1024 cm–1.
1H NMR: d = 1.09 (t, J = 7.3 Hz, 3 H), 2.54–2.61 (m, 1 H), 2.77–
2.85 (m, 1 H), 3.84 (s, 3 H), 3.89 (s, 3 H), 5.33 (s, 1 H), 5.79 (s, 1
H), 6.68 (dd, J = 8.2, 2.3 Hz, 1 H), 6.79–6.81 (m, 2 H), 7.94 (d,
J = 5.0 Hz, 1 H), 8.58 (s, 1 H), 8.84 (d, J = 5.0 Hz, 1 H).
Anal. Calcd for C17H19NO3S: C, 64.33; H, 6.03; N, 4.41. Found: C,
64.09; H, 6.07; N, 4.29.
Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80. Found: C,
69.61; H, 4.74; N, 5.59.
3-(3,4-Dimethoxyphenyl)thieno[2,3-b]pyridine (5c)
Pale-yellow solid; mp 104–106 °C (hexane–CH2Cl2).
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

PAPER
Synthesis of Thienopyridines
3-(Thiophen-2-yl)thieno[2,3-c]pyridine (11c)
2905
IR (KBr): 3068, 1605, 1524, 1261, 1022 cm–1.
Pale-yellow oil; Rf = 0.26 (EtOAc–hexane, 1:5).
IR (neat): 3084, 1578, 1275, 1031 cm–1.
1H NMR: d = 7.18 (dd, J = 5.0, 3.6 Hz, 1 H), 7.36 (dd, J = 3.6, 1.4
Hz, 1 H), 7.41 (d, J = 5.0, 1.4 Hz, 1 H), 7.75 (s, 1 H), 7.99 (dd,
J = 5.0, 0.9 Hz, 1 H), 8.58 (d, J = 5.0 Hz, 1 H), 9.18 (d, J = 0.9 Hz,
1 H).
1H NMR: d = 3.94 (s, 3 H), 3.96 (s, 3 H), 7.00 (d, J = 8.2 Hz, 1 H),
7.06 (d, J = 1.8 Hz, 1 H), 7.11 (dd, J = 8.2, 1.8 Hz, 1 H), 7.34 (dd,
J = 7.8, 4.6 Hz, 1 H), 7.46 (s, 1 H), 8.18 (dd, J = 7.8, 1.4 Hz, 1 H),
8.61 (dd, J = 4.6, 1.4 Hz, 1 H).
13C NMR: d = 56.02, 56.04, 111.6, 111.7, 119.4, 120.8, 122.6,
128.6, 130.5, 131.4, 135.5, 146.7, 149.0, 149.3, 162.5.
MS: m/z = 271 (100%, [M+]).
13C NMR: d = 117.2, 125.5, 125.6, 127.8, 128.7, 130.3, 135.8,
137.2, 142.6, 143.6, 145.2.
Anal. Calcd for C15H13NO2S: C, 66.40; H, 4.83; N, 5.16. Found: C,
66.56; H, 5.07; N, 5.05.
MS: m/z = 217 (100%, [M+]).
Anal. Calcd for C11H7NS2: C, 60.80; H, 3.25; N, 6.45. Found: C,
60.80; H, 3.18; N, 6.50.
3-(1,3-Benzodioxol-5-yl)thieno[2,3-b]pyridine (5d)
White solid; mp 121–124 °C (hexane–Et2O).
IR (KBr): 3101, 1518, 1236, 1031 cm–1.
3-(4-Methoxyphenyl)thieno[3,2-c]pyridine (16a)
White solid; mp 102–105 °C (hexane–CH2Cl2).
IR (KBr): 3084, 1611, 1497, 1250, 1030 cm–1.
1H NMR: d = 3.88 (s, 3 H), 7.04 (d, J = 8.7 Hz, 2 H), 7.35 (s, 1 H),
7.53 (d, J = 8.7 Hz, 2 H), 7.83 (dd, J = 5.4, 0.9 Hz, 1 H), 8.49 (d,
J = 5.4 Hz, 1 H), 9.19 (s, 1 H).
1H NMR: d = 6.04 (s, 2 H), 6.94 (d, J = 8.2 Hz, 1 H), 7.02–7.03 (m,
2 H), 7.34 (dd, J = 8.2, 4.6 Hz, 1 H), 7.43 (s, 1 H), 8.17 (dd, J = 8.2,
1.4 Hz, 1 H), 8.61 (dd, J = 4.6, 1.4 Hz, 1 H).
13C NMR: d = 101.3, 108.7, 108.8, 119.4, 121.9, 122.8, 129.2,
130.4, 131.2, 135.2, 146.7, 147.4, 148.1, 162.4.
MS: m/z = 255 (100%, [M+]).
13C NMR: d = 55.4, 114.4, 117.6, 122.9, 127.0, 129.7, 134.2, 137.2,
142.6, 145.5, 148.1, 159.6.
Anal. Calcd for C14H9NO2S: C, 65.87; H, 3.55; N, 5.49. Found: C,
65.79; H, 3.56; N, 5.31.
MS: m/z = 241 (100%, [M+]).
Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80. Found: C,
69.51; H, 4.73; N, 5.89.
3-(Thiophen-2-yl)thieno[2,3-b]pyridine (5e)
Yellow oil; Rf = 0.35 (THF–hexane, 1:50).
IR (neat): 3113, 1519, 1238, 1028 cm–1.
3-(3,4-Dimethoxyphenyl)thieno[3,2-c]pyridine (16b)
White solid; mp 142–144 °C (hexane–CH2Cl2).
IR (KBr): 3092, 1501, 1234, 1032 cm–1.
1H NMR: d = 3.95 (s, 3 H), 3.97 (s, 3 H), 7.02 (d, J = 8.2 Hz, 1 H),
7.12 (d, J = 1.8 Hz, 1 H), 7.17 (dd, J = 8.2, 1.8 Hz, 1 H), 7.39 (s, 1
H), 7.85 (d, J = 5.5 Hz, 1 H), 8.51 (d, J = 5.5 Hz, 1 H), 9.22 (s, 1 H).
1H NMR: d = 7.17 (d, J = 5.1, 3.7 Hz, 1 H), 7.32 (dd, J = 3.7, 1.4
Hz, 1 H), 7.36–7.39 (m, 2 H), 7.60 (s, 1 H), 8.38 (dd, J = 8.4, 1.4
Hz, 1 H), 8.62 (dd, J = 4.5, 1.4 Hz, 1 H).
13C NMR: d = 119.7, 123.7, 125.17, 125.22, 127.8, 128.4, 130.7,
130.8, 136.8, 147.0, 162.3.
MS: m/z = 217 (100%, [M+]).
13C NMR: d = 56.0 (2 C), 111.5, 111.8, 117.6, 121.1, 123.1, 127.3,
134.2, 137.4, 142.7, 145.6, 148.2, 149.1, 149.2.
Anal. Calcd for C11H7NS2: C, 60.80; H, 3.25; N, 6.45. Found: C,
60.69; H, 3.39; N, 6.40.
MS: m/z = 271 (100%, [M+]).
Anal. Calcd for C15H13NO2S: C, 66.40; H, 4.83; N, 5.16. Found: C,
66.33; H, 5.01; N, 5.17.
3-(4-Methoxyphenyl)thieno[2,3-c]pyridine (11a)
Pale-yellow solid; mp 78.5–81 °C (hexane–Et2O).
IR (KBr): 3088, 1612, 1491, 1248, 1030 cm–1.
3-(1,3-Benzodioxol-5-yl)thieno[3,2-c]pyridine (16c)
Colorless crystals; mp 119–121 °C (hexane–Et2O).
IR (KBr): 3094, 1489, 1248, 1047 cm–1.
1H NMR: d = 6.06 (s, 2 H), 6.95 (d, J = 7.3 Hz, 1 H), 7.07 (s, 1 H),
7.08 (d, J = 7.8 Hz, 1 H), 7.36 (s, 1 H), 7.83 (d, J = 5.5 Hz, 1 H),
8.50 (d, J = 5.5 Hz, 1 H), 9.19 (s, 1 H).
1H NMR: d = 3.88 (s, 3 H), 7.04 (d, J = 8.7 Hz, 2 H), 7.50 (d, J = 8.7
Hz, 2 H), 7.78 (dd, J = 6.0, 0.9 Hz, 1 H), 7.60 (s, 1 H), 8.53 (d,
J = 6.0 Hz, 1 H), 9.18 (d, J = 0.9 Hz, 1 H).
13C NMR: d = 55.3, 114.4, 117.1, 127.0, 127.6, 129.6, 137.2, 137.3,
143.2, 143.2, 145.2, 159.5.
MS: m/z = 241 (100%, [M+]).
13C NMR: d = 101.4, 108.8, 109.1, 117.6, 122.3, 123.3, 128.4,
134.1, 137.3, 142.8, 145.5, 147.7, 148.1, 148.2.
Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80. Found: C,
69.91; H, 4.51; N, 6.01.
MS: m/z = 255 (100%, [M+]).
Anal. Calcd for C14H9NO2S: C, 65.87; H, 3.55; N, 5.49. Found: C,
65.82; H, 3.72; N, 5.30.
3-(1,3-Benzodioxol-5-yl)thieno[2,3-c]pyridine (11b)
Pale-yellow solid; mp 134–136 °C (hexane–CH2Cl2).
IR (KBr): 3091, 1487, 1248, 1030 cm–1.
3-(Thiophen-2-yl)thieno[3,2-c]pyridine (16d)
Yellow oil; Rf = 0.50 (EtOAc–hexane, 1:2).
IR (neat): 3088, 1574, 1435, 1281 cm–1.
1H NMR: d = 7.20 (dd, J = 5.0, 3.7 Hz, 1 H), 7.39–7.42 (m, 2 H),
7.54 (s, 1 H), 7.84 (dd, J = 5.5, 0.9 Hz, 1 H), 8.53 (d, J = 5.5 Hz, 1
H), 9.42 (s, 1 H).
1H NMR: d = 6.05 (s, 2 H), 6.95 (d, J = 8.7 Hz, 1 H), 7.03–7.05 (m,
2 H), 7.60 (s, 1 H), 7.79 (dd, J = 5.5, 0.9 Hz, 1 H), 8.53 (d, J = 5.5
Hz, 1 H), 9.18 (s, 1 H).
13C NMR: d = 101.3, 108.8, 108.9, 117.1, 122.1, 128.0, 128.4,
137.2, 137.3, 143.1, 143.3, 145.2, 147.6, 148.1.
MS: m/z = 255 (100%, [M+]).
13C NMR: d = 117.7, 124.2, 125.6, 125.8, 127.9, 130.2, 133.5,
135.7, 142.6, 145.3, 148.3.
Anal. Calcd for C14H9NO2S: C, 65.87; H, 3.55; N, 5.49. Found: C,
65.83; H, 3.62; N, 5.40.
MS: m/z = 217 (100%, [M+]).
Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York

2906
K. Kobayashi et al.
PAPER
Anal. Calcd for C11H7NS2: C, 60.80; H, 3.25; N, 6.45. Found: C,
60.78; H, 3.16; N, 6.28.
Quinn, C.; Salmeron, J.-A.; Wishart, N.; Woller, K.; Zu, Z.
Bioorg. Med. Chem. Lett. 2008, 18, 4952. (d) Cusack, K.;
Allen, H.; Bischoff, A.; Clabbers, A.; Dixon, R.; Fix-
Stenzel, S.; Friedman, M.; Gaumont, Y.; George, D.;
Gordon, T.; Grongsaard, P.; Janssen, B.; Jia, Y.; Moskey,
M.; Quinn, C.; Salmeron, A.; Thomas, C.; Wallace, G.;
Wishart, N.; Yu, Z. Bioorg. Med. Chem. Lett. 2009, 19,
1722. (e) Zhao, L.; Zhang, Y.; Dai, C.; Guzi, T.; Wiswell,
D.; Seghezzi, W.; Parry, D.; Fischmann, T.; Siddiqui, M. A.
Bioorg. Med. Chem. Lett. 2010, 20, 7216. (f) See also ref.
1a.
Acknowledgement
Determination of mass spectra and performance of combustion ana-
lyses by Mrs. Miyuki Tanmatsu of this university are gratefully
acknowledged.
References
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Synthesis 2011, No. 18, 2897–2906 © Thieme Stuttgart · New York