A convenient synthesis of 2,3-dihydro-4H-thiopyrano[2,3-b]-, -[2,3-c]-, or -[3,2-c]pyridin-4-ones by the Reaction of the corresponding 1-(Chloropyridinyl) alk-2-en-1-ones with NaSH

Article abstract of DOI:10.1002/hlca.201200543

2,3-Dihydro-4H-thiopyrano[2,3-b]pyridin-4-ones 4 were prepared by a three-step sequence from commercially available 2-chloropyridine (1). Thus, successive treatment of 1 with ⁱPr₂NLi (LDA) and α,β-unsaturated aldehydes gave 1-(2-chloropyridin-3-yl)alk-2-en-1-ols 2, which were oxidized with MnO₂ to 1-(2-chloropyridin-3-yl)alk-2- en-1-ones 3. The reactions of 3 with NaSH×n H₂O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3-dihydro-4H-thiopyrano[2,3-c]pyridin-4-ones 8 and 2,3-dihydro-4H-thiopyrano[3,2-c]pyridin-4-ones 12 were obtained starting from 3-chloropyridine (5) and 4-chloropyridine (9), respectively. Copyright

Full text of DOI:10.1002/hlca.201200543

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Helvetica Chimica Acta – Vol. 96 (2013)
A Convenient Synthesis of 2,3-Dihydro-4H-thiopyrano[2,3-b]-, -[2,3-c]-, or
-[3,2-c]pyridin-4-ones by the Reaction of the Corresponding 1-
(Chloropyridinyl)alk-2-en-1-ones with NaSH
by Kazuhiro Kobayashi* and Ayumi Imaoka
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81(857)315263; e-mail: kkoba@chem.tottori-u.ac.jp)
2,3-Dihydro-4H-thiopyrano[2,3-b]pyridin-4-ones 4 were prepared by a three-step sequence from
i
commercially available 2-chloropyridine (1). Thus, successive treatment of 1 with Pr2NLi (LDA) and
a,b-unsaturated aldehydes gave 1-(2-chloropyridin-3-yl)alk-2-en-1-ols 2, which were oxidized with MnO2
to 1-(2-chloropyridin-3-yl)alk-2-en-1-ones 3. The reactions of 3 with NaSH · n H2O proceeded smoothly
at 08 in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3-dihydro-4H-thiopyrano[2,3-
c]pyridin-4-ones 8 and 2,3-dihydro-4H-thiopyrano[3,2-c]pyridin-4-ones 12 were obtained starting from
3-chloropyridine (5) and 4-chloropyridine (9), respectively.
Introduction. – Recently, significant attention has been focused on 2,3-dihydro-4H-
thiopyrano[2,3-b]pyridin-4-one derivatives, as some of them have been used for the
synthesis of more complex fused heterocycles [1], and a number of derivatives with this
skeleton have been reported to exhibit biological activities [2]. Da Settimo et al. have
demonstrated that 2,3-dihydro-4H-thiopyrano[2,3-b]pyridin-4-one can be prepared
from 2-sulfanylpyridine-3-carboxylic acid and 3-bromopropanoic acid [3]. A similar
synthesis of 2,3-dihydro-4H-thiopyrano[3,2-c]pyridin-4-one using 4-sulfanylpyridine-
3-carboxylic acid has been also reported by Gaillard et al. [4]. However, there have
been so far no reports on the general synthesis of these thiopyrano-pyridinone
derivatives including 2,3-dihydro-4H-thiopyrano[2,3-c]pyridin-4-ones. Hence, we de-
cided to develop a general method applicable to the preparation of these three
thiopyranopyridinone derivatives starting with readily available compounds, and we
report herein the results of our investigation, which provide facile entry to 2-substituted
derivatives.
Results and Discussion. – The three-step preparation of 2,3-dihydro-4H-thiopyr-
ano[2,3-b]pyridin-4-ones 4 was achieved according to the procedure outlined in
Scheme 1. Commercially available 2-chloropyridine (1) was first lithiated with iPr2NLi
(LDA) in THF at ꢀ 788 as described by Gribble and Saulnier [5] to generate 2-chloro-
3-lithiopyridine, which was then allowed to react with a,b-unsaturated aldehydes. The
highly selective attack of the 2-chloropyridin-3-yl anion on the aldehyde in the 1,2-
addition fashion proceeded cleanly, and 1-(2-chloropyridin-3-yl)alk-2-en-1-ols 2 were
obtained in relatively good yields as compiled in Table 1. Subsequently, these alcohols
were oxidized with MnO2 to give the corresponding 1-(2-chloropyridin-3-yl)alk-2-en-1-
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 96 (2013)
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ones 3 in good-to-excellent yields. Finally, these ketones 3 were treated with NaSH · n
H2O in DMF at 08. Substitution/ring-closing conjugate addition, or conjugate addition/
ring closure via substitution proceeded smoothly even at this temperature, and TLC
analyses confirmed that all starting materials had been consumed within 30 min. Usual
aqueous workup, followed by column chromatography on SiO2, provided good yields
of 2-aryl-2,3-dihydro-4H-thiopyrano[2,3-b]pyridin-4-ones 4 (Entries 1 – 4), while the
yields of the products derived from (E)-but-2-enal and 3-methylbut-2-enal, i.e. 2,3-
dihydro-2-methyl-4H-thiopyrano[2,3-b]pyridin-4-one (4e) and 2,3-dihydro-2,2-dimeth-
yl-4H-thiopyrano[2,3-b]pyridin-4-one (4f), were moderate (Entries 5 and 6, resp.).
These results indicate that substitution of an aromatic group in b-position to the C¼O
group of 3 facilitates the cyclization. It should be noted that trans-2,3-dihydro-3-
methyl-2-phenyl-4H-thiopyrano[2,3-b]pyridin-4-one (4d) was obtained almost exclu-
sively; only a trace amount of its stereoisomer was detected by the 1H-NMR spectrum
of the crude product (Entry 4).
Scheme 1
Table 1. Preparation of 2,3-Dihydro-4H-thiopyrano[2,3-b]pyridin-4-ones 4
Entry
R1R2C¼C(R3)CHO
2
Yielda)
3
Yielda)
4
Yielda)
1
2
3
4
5
6
R1 ¼ Ph, R2 ¼ R3 ¼ H
2a
2b
2c
2d
2e
2f
77
71
71
74
52
73
3a
3b
3c
3d
3e
3f
95
99
88
95
73
67
4a
4b
4c
4d
4e
4f
80
78
78
75
54
55
R1 ¼ 4-ClꢀC6H4, R2 ¼ R3 ¼ H
R1 ¼ 4-MeOꢀC6H4, R2 ¼ R3 ¼ H
R1 ¼ Ph, R2 ¼ H, R3 ¼ Me
R1 ¼ Me, R2 ¼ R3 ¼ H
R1 ¼ R2 ¼ Me, R3 ¼ H
a) Yields of isolated products [%].
To elucidate the possible pathway for the formation of 4, the reaction of (2-
chloropyridin-3-yl)(phenyl)methanone [6] with NaSH · n H2O under the above-
mentioned conditions was carried out. It resulted in almost quantitative recovery of
the starting materials. The substitution/ring-closing conjugate addition sequence may
be excluded by this result, indicating that the conjugate addition/ring closure via
substitution sequence is favored. Thus, conjugate addition of HSꢀ to the enone moiety
of 3 is followed by intramolecular substitution of the resulting 3-(2-chlorophenyl)-3-

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Helvetica Chimica Acta – Vol. 96 (2013)
oxo-1-phenylpropane-1-thiolate to give 4. The previous reports on the formation of 3-
ethylsulfanyl-1,3-diphenylpropan-1-one by the reaction of 1,3-diphenylprop-2-en-1-
one (chalcone) with EtSH in the presence of a base under mild conditions [7], and the
formation of (2-ethylsulfanylpyridin-3-yl)phenylmethanone by the reaction of (2-
chloropyridin-3-yl)phenylmethanone with EtSNa under mild conditions [6b] may
support the latter sequence.
2,3-Dihydro-4H-thiopyrano[2,3-c]pyridin-4-ones 8 were prepared from 3-chloro-
pyridine (5) and a,b-unsaturated aldehydes, via 1-(3-chloropyridin-4-yl)alk-2-en-1-ols
6 and 1-(3-chloropyridin-4-yl)alk-2-en-1-ones 7, by a procedure analogous to that
applied for the preparation of 4, as shown in Scheme 2. The precursors 6 and 7 were
obtained in excellent yields. Unfortunately, however, the expected cyclization of 7 with
NaSH · n H2O proceeded less smoothly (ca. 1.5 h for complete consumption of the
starting materials) and less cleanly than that of 3, and resulted in the formation of
rather complicated mixtures of products, from which the desired products 8 were
isolated in much lower yields than those of products 4. This may be rationalized by
considering the lower reactivity of the 3-chloro- compared to the 2-chloropyridine ring.
The use of 2 equiv. NaSH · n H2O did not improve the yields.
Scheme 2
By adapting the reaction conditions for the preparation of 4 and 8, 2,3-dihydro-4H-
thiopyrano[3,2-c]pyridin-4-ones 12 were also prepared starting with 4-chloropyridine
(9) as depicted in Scheme 3. A similarly good performance of 1-(4-chloropyridin-3-
yl)alk-2-en-1-ones 11, obtained from the corresponding alcohols 10, in the reaction with
NaSH · n H2O was observed as described for the conversion of 3 into 4, and relatively
good yields of the desired products 12 were accomplished as compiled in Table 2,
indicating that both yields of compounds 10 and 11 are good as well. Again noted is that
trans-2,3-dihydro-3-methyl-2-phenyl-4H-thiopyrano[3,2-c]pyridin-4-one (12d) was al-
so obtained as the practically sole stereoisomer as stated above.
In summary, the methodology described in this work allows very easy access to
substituted 2,3-dihydro-4H-thiopyrano[2,3-b]-, -[2,3-c]-, or -[3,2-c]pyridin-4-ones,
which are difficult to prepare by previous methods, from 2-, 3- or 4-chloropyridines,

Helvetica Chimica Acta – Vol. 96 (2013)
627
Scheme 3
Table 2. Preparation of 2,3-Dihydro-4H-thiopyrano[3,2-c]pyridin-4-ones 12
Entry
R1R2C¼C(R3)CHO
10
Yielda)
11
Yielda)
12
Yielda)
1
2
3
4
5
6
R1 ¼ Ph, R2 ¼ R3 ¼ H
10a
10b
10c
10d
10e
10f
77
75
79
84
71
83
11a
11b
11c
11d
11e
11f
96
91
94
99
99
91
12a
12b
12c
12d
12e
12f
78
75
78
74
52
55
R1 ¼ 4-ClꢀC6H4, R2 ¼ R3 ¼ H
R1 ¼ 4-MeOꢀC6H4, R2 ¼ R3 ¼ H
R1 ¼ Ph, R2 ¼ H, R3 ¼ Me
R1 ¼ Me, R2 ¼ R3 ¼ H
R1 ¼ R2 ¼ Me, R3 ¼ H
a) Yields of isolated products [%].
respectively. This method may also be of value in organic synthesis because of its
simplicity as well as the ready availability of the starting materials.
Experimental Part
General. All of the org. solvents were dried over appropriate drying agents and distilled prior to use.
BuLi was supplied by Asia Lithium Corporation. All chemicals were commercially available. TLC:
Merck silica gel 60 PF254. Column chromatography (CC): Wako Gel C-200E. M.p.: Laboratory Devices
MEL-TEMP II apparatus; uncorrected. IR: PerkinꢀElmer Spectrum 65 FT-IR spectrophotometer; ˜n in
cmꢀ1. 1H- and 13C-NMR: in CDCl3 with Me4Si as an internal reference, with JEOL ECP500 FT NMR or
JEOL LA400 FT NMR spectrometer (at 500 or 400 MHz (1H) and at 125 or 100 MHz (13C), resp.); d in
ppm, J in Hz. EI-MS (70 eV): with JEOL JMS AX505 HA spectrometer; m/z (rel. %).
(2E)-1-(2-Chloropyridin-3-yl)-3-phenylprop-2-en-1-ol (2a; Representative Procedure). To a stirred
i
soln. of LDA (5.0 mmol), generated from Pr2NH and BuLi by the standard method, in THF (6 ml) at
ꢀ 788 was added 2-chloropyridine (1; 0.23 g, 2.0 mmol) dropwise [5]. After 1 h, (E)-3-phenylprop-2-enal
(0.32 g, 2.4 mmol) was added, and stirring was continued for an additional 10 min before sat. aq. NH4Cl
(20 ml) was added. The mixture was warmed to r.t. and extracted with AcOEt (3 ꢁ 15 ml). The combined
extracts were washed with brine (15 ml) and dried (Na2SO4). Evaporation of the solvent gave a residue,
which was purified by CC (SiO2) to give 2a (0.38 g, 77%). Yellow oil. Rf (THF/hexane 1:5) 0.19. IR
(neat): 3349, 1407. 1H-NMR (500 MHz): 2.38 (d, J ¼ 3.4, 1 H); 5.75 (dd, J ¼ 6.3, 3.4, 1 H); 6.29 (dd, J ¼
16.0, 6.3, 1 H); 6.77 (d, J ¼ 16.0, 1 H); 7.24 – 7.33 (m, 4 H); 7.39 (d, J ¼ 7.4, 2 H); 8.01 (dd, J ¼ 8.0, 1.7, 1 H);
8.33 (dd, J ¼ 4.6, 1.7, 1 H). Anal. calc. for C14H12ClNO (245.70): C 68.44, H 4.92, N 5.70; found: C 68.37, H
4.97, N 5.62.

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(2E)-3-(4-Chlorophenyl)-1-(2-chloropyridin-3-yl)prop-2-en-1-ol (2b). Yellow oil. Rf (AcOEt/hex-
1
ane 1:2) 0.19. IR (neat): 3317, 1407. H-NMR (500 MHz): 2.32 (s, 1 H); 5.75 (d, J ¼ 6.3, 1 H); 6.27 (dd,
J ¼ 16.0, 6.3, 1 H); 6,73 (d, J ¼ 16.0, 1 H); 7.28 (d, J ¼ 8.0, 2 H); 7.31 (d, J ¼ 8.0, 2 H); 7.32 (dd, J ¼ 7.4, 4.6,
1 H); 7.99 (dd, J ¼ 7.4, 1.7, 1 H); 8.34 (dd, J ¼ 4.6, 1.7, 1 H). Anal. calc. for C14H11Cl2NO (280.15): C 60.02,
H 3.96, N 5.00; found: C 59.98, H 4.05, N 4.97.
(2E)-1-(2-Chloropyridin-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-ol (2c). Yellow oil. Rf (AcOEt/
1
hexane 1:2) 0.23. IR (neat): 3342, 1607, 1512, 1407. H-NMR (500 MHz): 2.29 (s, 1 H); 3.80 (s, 3 H);
5.72 (d, J ¼ 6.3, 1 H); 6.14 (dd, J ¼ 15.7, 6.3, 1 H); 6.70 (d, J ¼ 15.7, 1 H); 6.85 (d, J ¼ 8.0, 2 H); 7.31 – 7.32
(m, 3 H); 8.00 (dd, J ¼ 7.4, 1.7, 1 H); 8.32 (dd, J ¼ 4.6, 1.7, 1 H). Anal. calc. for C15H14ClNO2 (275.73): C
65.34, H 5.12, N 5.08; found: C 65.25, H 5.15, N 5.06.
(2E)-1-(2-Chloropyridin-3-yl)-2-methyl-3-phenylprop-2-en-1-ol (2d). Yellow oil. Rf (THF/hexane
1:5) 0.19. IR (neat): 3339, 1407. 1H-NMR (400 MHz): 1.78 (d, J ¼ 1.0, 3 H); 2.26 (d, J ¼ 3.9, 1 H); 5.63 (d,
J ¼ 3.9, 1 H); 6.77 (s, 1 H); 7.22 – 7.36 (m, 6 H); 8.00 (dd, J ¼ 7.3, 2.0, 1 H); 8.35 (dd, J ¼ 4.9, 2.0, 1 H).
Anal. calc. for C15H14ClNO (259.73): C 69.36, H 5.43, N 5.39; found: C 69.19, H 5.50, N 5.38.
(2E)-1-(2-Chloropyridin-3-yl)but-2-en-1-ol (2e). Yellow oil. Rf (AcOEt/hexane 1:3) 0.36. IR (neat):
1
3350, 1408. H-NMR (500 MHz): 1.73 (d, J ¼ 6.8, 3 H); 2.13 (d, J ¼ 3.4, 1 H); 5.50 – 5.52 (m, 1 H); 5.60
(ddd, J ¼ 14.9, 6.9, 1.7, 1 H); 5.85 (dq, J ¼ 14.9, 6.9, 1 H); 7.28 (dd, J ¼ 7.4, 4.6, 1 H); 7.94 (dd, J ¼ 7.4, 1.7,
1 H); 8.30 (d, J ¼ 4.6, 1.7, 1 H). Anal. calc. for C9H10ClNO (183.63): C 58.86, H 5.49, N 7.63; found: C
58.80, H 5.67, N 7.49.
1-(2-Chloropyridin-3-yl)-3-methylbut-2-en-1-ol (2f). Yellow oil. Rf (AcOEt/hexane 1:3) 0.37. IR
(neat): 3350, 1673, 1406. 1H-NMR (500 MHz): 1.76 (d, J ¼ 1.1, 3 H); 1.88 (d, J ¼ 1.7, 3 H); 1.98 (d, J ¼ 2.9,
1 H); 5.20 (ddd, J ¼ 9.2, 1.7, 1.1, 1 H); 5.73 (dd, J ¼ 9.2, 2.9, 1 H); 7.28 (dd, J ¼ 7.4, 4.6, 1 H); 7.99 (dd, J ¼
7.4, 1.7, 1 H); 8.29 (d, J ¼ 4.6, 1.7, 1 H). Anal. calc. for C10H12ClNO (197.66): C 60.76, H 6.12, N 7.09;
found: C 60.64, H 6.20, N 7.05.
(2E)-1-(3-Chloropyridin-4-yl)-3-phenylprop-2-en-1-ol (6a). White solid. M.p. 106 – 1088 (hexane/
Et2O). IR (KBr): 3153, 1647, 1591. 1H-NMR (500 MHz): 2.44 (d, J ¼ 3.4, 1 H); 5.74 (dd, J ¼ 6.3, 3.4, 1 H);
6.26 (dd, J ¼ 16.0, 6.3, 1 H); 6.76 (d, J ¼ 16.0, 1 H); 7.26 (td, J ¼ 7.4, 1.1, 1 H); 7.31 (t, J ¼ 7.4, 2 H); 7.38 (dd,
J ¼ 7.4, 1.1, 2 H); 7.61 (d, J ¼ 4.6, 1 H); 8.52 (d, J ¼ 4.6, 1 H); 8.54 (s, 1 H). Anal. calc. for C14H12ClNO
(245.70): C 68.44, H 4.92, N 5.70; found: C 68.38, H 5.16, N 5.67.
(2E)-1-(3-Chloropyridin-4-yl)-3-(4-methoxyphenyl)prop-2-en-1-ol (6b). Yellow solid. M.p. 123 –
1
1258 (dec.; hexane/Et2O). IR (KBr): 3450, 1607. H-NMR (500 MHz): 2.32 (br. s, 1 H); 3.80 (s, 3 H);
5.70 (d, J ¼ 6.9, 1 H), 6.11 (dd, J ¼ 16.0, 6.9, 1 H); 6.69 (d, J ¼ 16.0, 1 H); 6.85 (d, J ¼ 8.6, 2 H); 7.31 (d, J ¼
8.6, 2 H); 7.61 (d, J ¼ 5.2, 1 H); 8.52 (d, J ¼ 5.2, 1 H); 8.54 (s, 1 H). Anal. calc. for C15H14ClNO2 (275.73):
C 65.34, H 5.12, N 5.08; found: C 65.09, H 5.14, N 5.03.
(2E)-1-(3-Chloropyridin-4-yl)but-2-en-1-ol (6c). White solid. M.p. 57 – 598 (hexane). IR (KBr):
3179, 1400. 1H-NMR (500 MHz): 1.72 (d, J ¼ 6.9, 3 H); 2.41 (s, 1 H); 5.50 (d, J ¼ 6.9, 1 H); 5.57 (ddd, J ¼
14.7, 6.9, 1.1, 1 H); 5.85 (dq, J ¼ 14.7, 6.9, 1 H); 7.54 (d, J ¼ 4.6, 1 H); 8.48 (d, J ¼ 4.6, 1 H); 8.50 (s, 1 H).
Anal. calc. for C9H10ClNO (183.63): C 58.86, H 5.49, N 7.63; found: C 58.69, H 5.61, N 7.52.
(2E)-1-(4-Chloropyridin-3-yl)-3-phenylprop-2-en-1-ol (10a). Yellow solid. M.p. 99 – 1018 (hexane/
Et2O). IR (KBr): 3207, 1648, 1579. 1H-NMR (500 MHz): 2.61 (d, J ¼ 2.9, 1 H); 5.79 (dd, J ¼ 6.3, 2.9, 1 H);
6.34 (dd, J ¼ 16.0, 6.3, 1 H); 6.75 (d, J ¼ 16.0, 1 H); 7.26 (t, J ¼ 7.4, 2 H); 7.29 – 7.33 (m, 2 H); 7.38 (dd, J ¼
8.6, 1.7, 2 H); 8.43 (d, J ¼ 5.2, 1 H); 8.83 (s, 1 H). Anal. calc. for C14H12ClNO (245.70): C 68.44, H 4.92, N
5.70; found: C 68.37, H 5.04, N 5.68.
(2E)-3-(4-Chlorophenyl)-1-(4-chloropyridin-3-yl)prop-2-en-1-ol (10b). Pale-yellow solid. M.p. 114 –
1
1168 (hexane/Et2O). IR (KBr): 3390, 1652, 1579. H-NMR (500 MHz): 2.52 (d, J ¼ 3.4, 1 H); 5.80 (dd,
J ¼ 6.3, 3.4, 1 H); 6.32 (dd, J ¼ 15.5, 6.3, 1 H); 6.71 (d, J ¼ 15.5, 1 H); 7.28 (d, J ¼ 8.6, 2 H); 7.30 (d, J ¼ 5.7,
2 H); 7.31 (d, J ¼ 8.6, 1 H); 8.44 (d, J ¼ 5.7, 1 H); 8.82 (s, 1 H). Anal. calc. for C14H11Cl2NO (280.15): C
60.02, H 3.96, N 5.00; found: C 59.87, H 3.76, N 5.97.
(2E)-1-(4-Chloropyridin-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-ol (10c). Pale-yellow solid. M.p.
125 – 1278 (hexane/Et2O). IR (KBr): 3425, 1639, 1606. 1H-NMR (500 MHz): 2.39 (s, 1 H); 3.80 (s,
3 H); 5.76 (d, J ¼ 6.9, 1 H); 6.20 (dd, J ¼ 16.0, 6.9, 1 H); 6.68 (d, J ¼ 16.0, 1 H); 6.85 (d, J ¼ 9.2, 2 H); 7.29
(d, J ¼ 5.7, 1 H); 7.32 (d, J ¼ 9.2, 2 H); 8.43 (d, J ¼ 5.7, 1 H); 8.84 (s, 1 H). Anal. calc. for C15H14ClNO2
(275.73): C 65.34, H 5.12, N 5.08; found: C 65.29, H 5.19, N 5.09.

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(2E)-1-(4-Chloropyridin-3-yl)-2-methyl-3-phenylprop-2-en-1-ol (10d). Pale-yellow solid. M.p. 140 –
1
1428 (hexane). IR (KBr): 3421, 1653, 1579. H-NMR (500 MHz): 1.81 (d, J ¼ 1.1, 3 H); 2.36 (d, J ¼ 3.4,
1 H); 5.68 (d, J ¼ 3.4, 1 H); 6.78 (s, 1 H); 7.22 – 7.36 (m, 6 H); 8.44 (d, J ¼ 5.2, 1 H); 8.84 (s, 1 H). Anal.
calc. for C15H14ClNO (259.73): C 69.36, H 5.43, N 5.39; found: C 69.30, H 5.69, N 5.32.
(2E)-1-(4-Chloropyridin-3-yl)but-2-en-1-ol (10e). Pale-yellow oil. Rf (AcOEt/hexane 1:1) 0.38. IR
(neat): 3233, 1671, 1579. 1H-NMR (500 MHz): 1.73 (dd, J ¼ 6.9, 1.7, 3 H); 2.29 (d, J ¼ 3.4, 1 H); 5.56 (br.
d, J ¼ 6.9, 1 H); 5.67 (ddd, J ¼ 15.5, 6.9, 1.7, 1 H); 5.84 (dq, J ¼ 15.6, 6.9, 1 H); 7.28 (d, J ¼ 5.7, 1 H); 8.40 (d,
J ¼ 5.7, 1 H); 8.76 (s, 1 H). Anal. calc. for C9H10ClNO (183.63): C 58.86, H 5.49, N 7.63; found: C 58.63, H
5.33, N 7.41.
1-(4-Chloropyridin-3-yl)-3-methylbut-2-en-1-ol (10f). Yellow oil. Rf (AcOEt/hexane 1:2) 0.17. IR
(neat): 3330, 1673, 1579. 1H-NMR (500 MHz): 1.76 (s, 3 H); 1.85 (s, 3 H); 2.16 (d, J ¼ 2.9, 1 H); 5.32 (d,
J ¼ 8.8, 1 H); 5.79 (dd, J ¼ 8.8, 2.9, 1 H); 7.26 (d, J ¼ 4.9, 1 H); 8.40 (d, J ¼ 4.9, 1 H); 8.82 (s, 1 H). Anal.
calc. for C10H12ClNO (197.66): C 60.76, H 6.12, N 7.09; found: C 60.65, H 6.39, N 7.09.
(2E)-1-(2-Chloropyridin-3-yl)-3-phenylprop-2-en-1-one (3a; Representative Procedure). A soln. of
2a (0.28 g, 1.1 mmol) in acetone (4 ml) containing MnO2 (1.1 g, 13 mmol) was stirred for 30 min at r.t. The
mixture was filtered, and the filtrate was concentrated by evaporation. The residue was purified by CC
(SiO2) to give 3a (0.26 g, 95%). Pale-yellow oil. Rf (AcOEt/hexane 1:7) 0.13. IR (neat): 1651, 1617, 1397.
1H-NMR (400 MHz): 7.18 (d, J ¼ 15.6, 1 H); 7.37 – 7.50 (m, 4 H); 7.52 (d, 15.6, 1 H); 7.58 (dd, J ¼ 7.8, 2.0,
2 H); 7.84 (dd, J ¼ 7.8, 2.0, 1 H); 8.54 (dd, J ¼ 4.9, 2.0, 1 H). Anal. calc. for C14H10ClNO (243.69): C 69.00,
H 4.14, N 5.75; found: C 69.01, H 4.15, N 5.65.
(2E)-3-(4-Chlorophenyl)-1-(2-chloropyridin-3-yl)prop-2-en-1-one (3b). Yellow solid. M.p. 149 –
1
1518 (hexane). IR (KBr): 1668, 1603, 1390. H-NMR (500 MHz): 7.15 (d, J ¼ 16.0, 1 H); 7.38 – 7.41 (m,
3 H); 7.48 (d, 16.0, 1 H); 7.52 (d, J ¼ 8.0, 2 H); 7.84 (dd, J ¼ 7.4, 1.7, 1 H); 8.54 (dd, J ¼ 4.7, 1.7, 1 H). Anal.
calc. for C14H9Cl2NO (278.13): C 60.46, H 3.26, N 5.04; found: C 60.28, H 3.50, N 4.96.
(2E)-1-(2-Chloropyridin-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (3c). Yellow solid. M.p. 114 –
1
1168 (hexane). IR (KBr): 1655, 1595, 1396. H-NMR (500 MHz): 3.86 (s, 3 H); 6.93 (d, J ¼ 9.2, 2 H);
7.04 (d, J ¼ 16.0, 1 H); 7.37 (dd, J ¼ 7.4, 5.2, 1 H); 7.45 (d, J ¼ 16.0, 1 H); 7.54 (d, J ¼ 9.2, 2 H); 7.82 (dd, J ¼
7.4, 1.7, 1 H); 8.52 (dd, J ¼ 5.2, 1.7, 1 H). Anal. calc. for C15H12ClNO2 (273.71): C 65.82, H 4.42, N 5.12;
found: C 65.72, H 4.42, N 5.09.
(2E)-1-(2-Chloropyridin-3-yl)-2-methyl-3-phenylprop-2-en-1-one (3d). Pale-yellow solid. M.p. 120 –
1
1228 (hexane). IR (KBr): 1646, 1619, 1396. H-NMR (500 MHz): 2.27 (d, J ¼ 1.1, 3 H); 7.09 (q, J ¼ 1.1,
1 H); 7.35 – 7.43 (m, 6 H); 7.70 (dd, J ¼ 7.4, 1.7, 1 H); 8.51 (dd, J ¼ 5.1, 1.7, 1 H). Anal. calc. for
C15H12ClNO2 (257.71): C 69.91, H 4.69, N 5.43; found: C 69.66, H 4.70, N 5.46.
(2E)-1-(2-Chloropyridin-3-yl)but-2-en-1-one (3e). Pale-yellow oil. Rf (AcOEt/hexane 1:7) 0.23. IR
(neat): 1660, 1622, 1397. 1H-NMR (500 MHz): 1.99 (dd, J ¼ 6.9, 1.7, 3 H); 6.53 (dq, J ¼ 16.2, 1.7, 1 H); 6.78
(dq, J ¼ 16.2, 6.9, 1 H); 7.33 (dd, J ¼ 7.4, 5.2, 1 H); 7.71 (dd, J ¼ 7.4, 1.7, 1 H); 8.49 (dd, J ¼ 5.2, 1.7, 1 H).
Anal. calc. for C9H8ClNO (181.62): C 59.52, H 4.44, N 7.71; found: C 59.48, H 4.48, N 7.47.
1-(2-Chloropyridin-3-yl)-3-methylbut-2-en-1-one (3f). Pale-yellow oil. Rf (AcOEt/hexane 1:3) 0.39.
1
IR (neat): 1671, 1609, 1396. H-NMR (400 MHz): 2.02 (d, J ¼ 1.0, 3 H); 2.27 (s, 3 H); 6.48 (q, J ¼ 1.0,
1 H); 7.32 (dd, J ¼ 7.3, 4.9, 1 H); 7.79 (dd, J ¼ 7.3, 2.0, 1 H); 8.46 (dd, J ¼ 4.9, 2.0, 1 H). Anal. calc. for
C10H10ClNO (195.65): C 61.39, H 5.15, N 7.16; found: C 61.20, H 5.06, N 7.07.
(2E)-1-(3-Chloropyridin-4-yl)-3-phenylprop-2-en-1-one (7a). Pale-yellow solid. M.p. 96 – 988 (hex-
ane). IR (KBr) 1651, 1619. 1H-NMR (500 MHz): 7.07 (d, J ¼ 16.0, 1 H); 7.35 (d, J ¼ 4.6, 1 H); 7.41 – 7.46
(m, 4 H); 7.57 (dd, J ¼ 7.4, 1.7, 2 H); 8.63 (d, J ¼ 4.6, 1 H); 8.72 (s, 1 H). Anal. calc. for C14H10ClNO
(243.69): C 69.00, H 4.14, N 5.75; found: C 68.90, H 4.23, N 5.53.
(2E)-1-(3-Chloropyridin-4-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (7b). Yellow solid. M.p. 109 –
1
1118 (hexane). IR (KBr): 1634, 1623, 1603. H-NMR (400 MHz): 3.86 (s, 3 H); 6.93 (d, J ¼ 8.8, 2 H);
6.94 (d, J ¼ 16.6, 1 H); 7.34 (d, J ¼ 4.9, 1 H); 7.37 (d, J ¼ 16.6, 1 H); 7.53 (d, J ¼ 8.8, 2 H); 8.62 (d, J ¼ 4.9,
1 H); 8.71 (s, 1 H). Anal. calc. for C15H12ClNO2 (273.71): C 65.82, H 4.42, N 5.12; found: C 65.71, H 4.51,
N 4.92.
(2E)-1-(3-Chloropyridin-4-yl)but-2-en-1-one (7c). Pale-yellow oil. Rf (AcOEt/hexane 1:3) 0.30. IR
1
(neat): 1663, 1638, 1622. H-NMR (500 MHz): 2.00 (dd, J ¼ 6.9, 1.1, 3 H); 6.45 (dd, J ¼ 15.5, 1.1, 1 H);

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6.72 (dq, J ¼ 15.5, 6.9, 1 H); 7.23 (d, J ¼ 5.2, 1 H); 8.57 (d, J ¼ 5.2, 1 H); 8.67 (s, 1 H). Anal. calc. for
C9H8ClNO (181.62): C 59.52, H 4.44, N 7.71; found: C 59.43, H 4.49, N 7.60.
(2E)-1-(4-Chloropyridin-3-yl)-3-phenylprop-2-en-1-one (11a). This compound was rather unstable,
so it had to be used in the next step as soon as possible after isolation. Pale-yellow oil. Rf (AcOEt/hexane
1:3) 0.40. IR (neat): 1642, 1620. 1H-NMR (500 MHz): 7.15 (d, J ¼ 16.0, 1 H); 7.42 – 7.45 (m, 4 H); 7.50 (d,
J ¼ 16.0, 1 H); 7.59 (dd, J ¼ 8.0, 1.7, 2 H); 8.62 (d, J ¼ 5.2, 1 H); 8.71 (s, 1 H).
(2E)-3-(4-Chlorophenyl)-1-(4-chloropyridin-3-yl)prop-2-en-1-one (11b). White solid. M.p. 114 –
1168 (dec.; hexane/Et2O). IR (KBr): 1670, 1630, 1605. 1H-NMR (500 MHz): 7.13 (d, J ¼ 16.0, 1 H);
7.40 (d, J ¼ 8.6, 2 H); 7.44 (d, J ¼ 5.2, 1 H); 7.48 (d, J ¼ 16.0, 1 H); 7.52 (d, J ¼ 8.6, 2 H); 8.62 (d, J ¼ 5.2,
1 H); 8.70 (s, 1 H). Anal. calc. for C14H9Cl2NO (278.13): C 60.46, H 3.26, N 5.04; found: C 60.36, H 3.20, N
4.87.
(2E)-1-(4-Chloropyridin-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (11c). Pale-yellow solid. M.p.
114 – 1168 (hexane). IR (KBr): 1655, 1594. 1H-NMR (500 MHz): 3.86 (s, 3 H); 6.94 (d, J ¼ 9.2, 2 H); 7.02
(d, J ¼ 15.5, 1 H); 7.43 (d, J ¼ 5.2, 1 H); 7.45 (d, J ¼ 15.5, 1 H); 7.54 (d, J ¼ 9.2, 2 H); 8.60 (d, J ¼ 5.2, 1 H);
8.68 (s, 1 H). Anal. calc. for C15H12ClNO2 (273.71): C 65.82, H 4.42, N 5.12; found: C 65.71, H 4.28, N 5.01.
(2E)-1-(4-Chloropyridin-3-yl)-2-methyl-3-phenylprop-2-en-1-one (11d). Pale-yellow oil. Rf (AcOEt/
hexane 1:3) 0.33. IR (neat): 1658, 1619. 1H-NMR (500 MHz): 2.27 (d, J ¼ 1.1, 3 H); 7.11 (q, J ¼ 1.1, 1 H);
7.35 – 7.43 (m, 6 H); 8.57 (s, 1 H); 8.60 (d, J ¼ 5.2, 1 H). Anal. calc. for C15H12ClNO (257.71): C 69.91, H
4.69, N 5.43; found: C 69.85, H 4.72, N 5.31.
(2E)-1-(4-Chloropyridin-3-yl)but-2-en-1-one (11e). Pale-yellow oil. Rf (AcOEt/hexane 1:2) 0.38. IR
(neat): 1659, 1622. 1H-NMR (500 MHz): 2.00 (dd, J ¼ 6.9, 1.1, 3 H); 6.53 (dq, J ¼ 15.5, 1.1, 1 H); 6.78 (dq,
J ¼ 15.5 6.9, 1 H); 7.39 (d, J ¼ 5.2, 1 H); 8.57 (d, J ¼ 5.2, 1 H); 8.58 (s, 1 H). Anal. calc. for C9H8ClNO
(181.62): C 59.52, H 4.44, N 7.71; found: C 59.42, H 4.50, N 7.67.
1-(4-Chloropyridin-3-yl)-3-methylbut-2-en-1-one (11f). Pale-yellow oil. Rf (AcOEt/hexane 1:1) 0.40.
IR (neat): 1669, 1610. 1H-NMR (500 MHz): 2.03 (s, 3 H); 2.28 (s, 3 H); 6.47 (s, 1 H); 7.36 (d, J ¼ 5.2, 1 H);
8.54 (d, J ¼ 5.2, 1 H); 8.67 (s, 1 H). Anal. calc. for C10H10ClNO (195.65): C 61.39, H 5.15, N 7.16; found: C
61.26, H 5.17, N 7.07.
2,3-Dihydro-2-phenyl-4H-thiopyrano[2,3-b]pyridin-4-one (4a; Representative Procedure). A mix-
ture of 3a (0.17 g, 0.70 mmol) in DMF (3 ml) containing NaSH · n H2O (70% as NaSH; 62 mg,
0.77 mmol) was stirred at 08 until disappearance of the starting material had been confirmed by TLC
analyses (SiO2; within 30 min, ca. 1.5 h for 8). Sat. aq. NH4Cl (10 ml) was added, and the mixture was
extracted with AcOEt (3 ꢁ 10 ml). The combined extracts were washed with brine (10 ml), dried
(Na2SO4), and concentrated by evaporation. The residue was purified by CC (SiO2) to give 4a (0.13 g,
80%). Yellow oil. Rf (THF/hexane 1:5) 0.43. IR (neat): 1684, 1396. 1H-NMR (500 MHz): 3.23 (dd, J ¼
16.0, 2.9, 1 H); 3.35 (dd, J ¼ 16.0, 12.6, 1 H); 4.78 (dd, J ¼ 12.6, 2.9, 1 H); 7.17 (dd, J ¼ 7.4, 4.6, 1 H); 7.34 –
7.46 (m, 5 H); 8.35 (dd, J ¼ 7.4, 1.7, 1 H); 8.58 (dd, J ¼ 4.6, 1.7, 1 H). 13C-NMR (100 MHz): 44.07; 45.77;
120.22; 126.88; 127.45; 128.61; 129.10; 136.55; 137.77; 153.88; 164.06; 193.95. EI-MS: 241 (100, Mþ). Anal.
calc. for C14H11NOS (241.31): C 69.68, H 4.59, N 5.80; found: C 69.62, H 4.54, N 5.71.
2-(4-Chlorophenyl)-2,3-dihydro-4H-thiopyrano[2,3-b]pyridin-4-one (4b). Yellow solid. M.p. 108 –
1
1108 (hexane). IR (KBr): 1683, 1396. H-NMR (500 MHz): 3.21 (dd, J ¼ 16.0, 2.9, 1 H); 3.30 (dd, J ¼
16.0, 12.6, 1 H); 4.75 (dd, J ¼ 12.6, 2.9, 1 H); 7.17 (dd, J ¼ 8.0, 4.6, 1 H); 7.37 (d, J ¼ 9.2, 2 H); 7.38 (d,
J ¼ 9.2, 2 H); 8.34 (dd, J ¼ 8.0, 2.3, 1 H); 8.58 (dd, J ¼ 4.6, 2.3, 1 H). 13C-NMR (100 MHz): 43.33; 45.59;
120.40; 126.85; 128.82; 129.31; 134.50; 136.26; 136.61; 153.96; 163.60; 193.56. EI-MS: 275 (100, Mþ).
Anal. calc. for C14H10ClNOS (275.75): C 60.98, H 3.66, N 5.08; found: C 60.73, H 3.62, N 5.14.
2,3-Dihydro-2-(4-methoxyphenyl)-4H-thiopyrano[2,3-b]pyridin-4-one (4c). Yellow solid. M.p. 104 –
1068 (hexane/Et2O). IR (KBr): 1683, 1395. 1H-NMR (500 MHz): 3.20 (dd, J ¼ 16.0, 2.9, 1 H); 3.31 (dd,
J ¼ 16.0, 13.2, 1 H); 3.82 (s, 3 H); 4.73 (dd, J ¼ 13.2, 2.9, 1 H); 6.92 (d, J ¼ 9.2, 2 H); 7.15 (dd, J ¼ 8.0, 5.2,
1 H); 7.36 (d, J ¼ 9.2, 2 H); 8.33 (dd, J ¼ 8.0, 2.3, 1 H); 8.57 (dd, J ¼ 5.2, 2.3, 1 H). 13C-NMR (100 MHz):
43.50; 45.99; 55.30; 114.42; 120.15; 128.64; 129.66; 136.54; 136.57; 153.86; 159.68; 164.20; 194.18. EI-MS:
271 (100, Mþ). Anal. calc. for C15H13NO2S (271.33): C 66.40, H 4.83, N 5.16; found: C 66.34, H 4.85, N
5.03.
trans-2,3-Dihydro-3-methyl-2-phenyl-4H-thiopyrano[2,3-b]pyridin-4-one (4d). Pale-yellow oil. Rf
1
(AcOEt/hexane 1 :5) 0.34. IR (neat): 1683, 1398. H-NMR (500 MHz): 1.12 (d, J ¼ 6.9, 3 H); 3.24 –

Helvetica Chimica Acta – Vol. 96 (2013)
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3.31 (m, 1 H); 4.42 (d, J ¼ 12.0, 1 H); 7.15 (dd, J ¼ 8.0, 4.6, 1 H); 7.33 – 7.44 (m, 5 H); 8.30 (dd, J ¼ 8.0, 1.7,
1 H); 8.56 (dd, J ¼ 4.6, 1.7, 1 H). 13C-NMR (100 MHz): 12.86; 47.65; 50.34; 120.10; 126.67; 128.24; 128.55;
129.05; 136.96; 137.32; 153.70; 163.03; 196.14. EI-MS: 255 (100, Mþ). Anal. calc. for C15H13NOS (255.33):
C 70.56, H 5.13, N 5.49; found: C 70.39, H 5.27, N 5.26.
2,3-Dihydro-2-methyl-4H-thiopyrano[2,3-b]pyridin-4-one (4e). White solid. M.p. 64 – 668 (hexane).
IR (KBr): 1683, 1399. 1H-NMR (500 MHz): 1.49 (d, J ¼ 6.9, 3 H); 2.81 (dd, J ¼ 16.0, 11.5, 1 H); 3.05 (dd,
J ¼ 16.0, 3.4, 1 H); 3.65 – 3.72 (m, 1 H); 7.13 (dd, J ¼ 8.0, 4.6, 1 H); 8.29 (dd, J ¼ 8.0, 2.3, 1 H); 8.55 (dd,
J ¼ 4.6, 2.3, 1 H). 13C-NMR (125 MHz): 20.38; 35.02; 46.68; 119.97; 126.84; 136.32; 153.75; 163.90; 194.33.
EI-MS: 179 (100, Mþ). Anal. calc. for C9H9NOS (179.24): C 60.31, H 5.06, N 7.81; found: C 60.05, H 4.94,
N 7.85.
2,3-Dihydro-2,2-dimethyl-4H-thiopyrano[2,3-b]pyridin-4-one (4f). White solid. M.p. 76 – 798 (hex-
ane). IR (KBr): 1685, 1396. 1H-NMR (500 MHz): 1.51 (s, 6 H); 2.91 (s, 2 H); 7.13 (dd, J ¼ 8.0, 4.6, 1 H);
8.30 (dd, J ¼ 8.0, 1.7, 1 H); 8.57 (dd, J ¼ 4.6, 1.7, 1 H). 13C-NMR (125 MHz): 28.74; 43.73; 52.96; 119.78;
126.16; 136.10; 154.00; 163.79; 194.66. EI-MS: 193 (100, Mþ). Anal. calc. for C10H11NOS (193.27): C
62.15, H 5.74, N 7.25; found: C 61.95, H 5.74, N 7.04.
2,3-Dihydro-2-phenyl-4H-thiopyrano[2,3-c]pyridin-4-one (8a). Yellow solid. M.p. 155 – 1568 (hex-
1
ane/Et2O). IR (KBr): 1688. H-NMR (500 MHz): 3.26 (dd, J ¼ 16.6, 2.9, 1 H); 3.36 (dd, J ¼ 16.6, 13.1,
1 H); 4.75 (dd, J ¼ 13.1, 2.9, 1 H); 7.35 – 7.44 (m, 5 H); 7.86 (d, J ¼ 5.2, 1 H); 8.49 (d, J ¼ 5.2, 1 H); 8.65 (s,
1 H). 13C-NMR (125 MHz): 45.54; 46.46; 120.68; 127.36; 128.80; 129.13; 135.05; 137.20; 137.63; 146.37;
149.31; 193.80. EI-MS: 241 (100, Mþ). Anal. calc. for C14H11NOS (241.31): C 69.68, H 4.59, N 5.80; found:
C 69.68, H 4.75, N 5.78.
2,3-Dihydro-2-(4-methoxyphenyl)-4H-thiopyrano[2,3-c]pyridin-4-one (8b). Yellow solid. M.p. 131 –
1338 (hexane). IR (KBr): 1685, 1613. 1H-NMR (400 MHz): 3.23 (dd, J ¼ 16.6, 2.9, 1 H); 3.33 (dd, J ¼ 16.6,
13.2, 1 H); 3.82 (s, 3 H); 4.71 (dd, J ¼ 13.2, 2.9, 1 H); 6.92 (d, J ¼ 8.3, 2 H); 7.35 (d, J ¼ 8.3, 2 H); 7.86 (d,
J ¼ 4.9, 1 H); 8.48 (d, J ¼ 4.9, 1 H); 8.64 (s, 1 H). 13C-NMR (125 MHz): 45.01; 46.68; 55.32; 114.43; 120.67;
128.56; 129.59; 135.05; 137.38; 146.29; 149.29; 159.80; 194.01. EI-MS: 271 (100, Mþ). Anal. calc. for
C15H13NO2S (271.33): C 66.40, H 4.83, N 5.16; found: C 66.30, H 5.05, N 5.10.
2,3-Dihydro-2-methyl-4H-thiopyrano[2,3-c]pyridin-4-one (8c). Pale-yellow oil. Rf (AcOEt/hexane
1:3) 0.33. IR (neat): 1694. 1H-NMR (500 MHz): 1.49 (d, J ¼ 6.9, 3 H); 2.81 (dd, J ¼ 16.6, 11.5, 1 H); 3.07
(dd, J ¼ 16.6, 2.9, 1 H); 3.65 – 3.72 (m, 1 H); 7.80 (d, J ¼ 5.2, 1 H); 8.44 (d, J ¼ 5.2, 1 H); 8.62 (s, 1 H).
13C-NMR (125 MHz): 20.38; 36.62; 47.51; 120.49; 134.97; 136.98; 146.05; 149.55; 193.96. EI-MS: 179 (100,
Mþ). Anal. calc. for C9H9NOS (179.24): C 60.31, H 5.06, N 7.81; found: C 60.22, H 5.10, N 7.75.
2,3-Dihydro-2-phenyl-4H-thiopyrano[3,2-c]pyridin-4-one (12a). Yellow oil. Rf (AcOEt/hexane, 1:3)
0.33. IR (neat): 1686. 1H-NMR (500 MHz): 3.21 (dd, J ¼ 16.6, 2.9, 1 H); 3.33 (dd, J ¼ 16.6, 13.2, 1 H); 4.78
(dd, J ¼ 13.2, 2.9, 1 H); 7.19 (d, J ¼ 4.6, 1 H); 7.35 – 7.44 (m, 5 H); 8.46 (d, J ¼ 4.6, 1 H); 9.18 (s, 1 H).
13C-NMR (125 MHz): 45.33; 46.01; 121.28; 125.28; 127.38; 128.86; 129.18; 137.38; 150.39; 152.08; 152.27;
193.45. EI-MS: 241 (100, Mþ). Anal. calc. for C14H11NOS (241.31): C 69.68, H 4.59, N 5.80; found: C
69.43, H 4.83, N 5.81.
2-(4-Chlorophenyl)-2,3-dihydro-4H-thiopyrano[3,2-c]pyridin-4-one (12b). Yellow solid. M.p. 147 –
1
1498 (hexane). IR (KBr): 1691. H-NMR (500 MHz): 3.19 (dd, J ¼ 16.0, 2.9, 1 H); 3.29 (dd, J ¼ 16.0,
12.6, 1 H); 4.75 (dd, J ¼ 12.6, 2.9, 1 H); 7.19 (d, J ¼ 5.2, 1 H); 7.35 (d, J ¼ 8.6, 2 H); 7.38 (d, J ¼ 8.6, 2 H);
8.47 (d, J ¼ 5.2, 1 H); 9.17 (s, 1 H). 13C-NMR (125 MHz): 44.62; 45.86; 121.26; 125.19; 128.75; 129.40;
134.78; 135.89; 150.42; 151.78; 152.21; 193.01. EI-MS: 275 (100, Mþ). Anal. calc. for C14H10ClNOS
(275.75): C 60.98, H 3.66, N 5.08; found: C 60.99, H 3.69, N 5.02.
2,3-Dihydro-2-(4-methoxyphenyl)-4H-thiopyrano[3,2-c]pyridin-4-one (12c). Yellow solid. M.p.
130 – 1328 (hexane). IR (KBr): 1685, 1610. 1H-NMR (400 MHz): 3.19 (dd, J ¼ 16.0, 2.9, 1 H); 3.31 (dd,
J ¼ 16.0, 12.7, 1 H); 3.83 (s, 3 H); 4.74 (dd, J ¼ 12.7, 2.9, 1 H); 6.92 (d, J ¼ 8.8, 2 H); 7.18 (d, J ¼ 5.4, 1 H);
7.33 (d, J ¼ 8.8, 2 H); 8.46 (d, J ¼ 5.4, 1 H); 9.17 (s, 1 H). 13C-NMR (125 MHz): 44.78; 46.23; 55.30;
114.48; 121.22; 125.28; 128.59; 129.31; 150.37; 152.03; 152.43; 159.84; 193.67. EI-MS: 271 (100, Mþ). Anal.
calc. for C15H13NO2S (271.33): C 66.40, H 4.83, N 5.16; found: C 66.30, H 4.83, N 5.11.
trans-2,3-Dihydro-3-methyl-2-phenyl-4H-thiopyrano[3,2-c]pyridin-4-one (12d). Pale-yellow solid.
M.p. 160 – 1628 (hexane/Et2O). IR (KBr): 1678. 1H-NMR (500 MHz): 1.12 (d, J ¼ 6.9, 3 H); 3.29 (dq, J ¼
12.0, 6.9, 1 H); 4.43 (d, J ¼ 12.0, 1 H); 7.12 (d, J ¼ 5.2, 1 H); 7.32 – 7.42 (m, 5 H); 8.44 (d, J ¼ 5.2, 1 H); 9.13

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(s, 1 H). 13C-NMR (125 MHz): 12.62; 47.90; 51.38; 120.71; 125.12; 128.14; 128.78; 129.13; 137.00; 150.67;
151.34; 151.83; 195.66. EI-MS: 255 (100, Mþ). Anal. calc. for C15H13NOS (255.33): C 70.56, H 5.13, N 5.49;
found: C 70.46, H 5.28, N 5.57.
2,3-Dihydro-2-methyl-4H-thiopyrano[3,2-c]pyridin-4-one (12e). Pale-yellow oil. Rf (AcOEt/hexane
1:2) 0.38. IR (neat): 1686. 1H-NMR (500 MHz): 1.48 (d, J ¼ 6.9, 3 H); 2.78 (dd, J ¼ 16.0, 10.9, 1 H); 3.04
(dd, J ¼ 16.0, 2.9, 1 H); 3.66 – 3.73 (m, 1 H); 7.16 (d, J ¼ 5.2, 1 H); 8.42 (d, J ¼ 5.2, 1 H); 9.11 (s, 1 H).
13C-NMR (125 MHz): 20.36; 36.40; 46.94; 121.61; 125.25; 150.11; 151.87; 152.07; 193.63. EI-MS: 179 (100,
Mþ). Anal. calc. for C9H9NOS (179.24): C 60.31, H 5.06, N 7.81; found: C 60.15, H 5.05, N 7.73.
2,3-Dihydro-2,2-dimethyl-4H-thiopyrano[3,2-c]pyridin-4-one (12f). Pale-yellow oil. Rf (AcOEt/
hexane 1:2) 0.30. IR (neat): 1686. 1H-NMR (500 MHz): 1.50 (s, 6 H); 2.89 (s, 2 H); 7.14 (d, J ¼ 5.2, 1 H);
8.44 (d, J ¼ 5.2, 1 H); 9.13 (s, 1 H). 13C-NMR (125 MHz): 28.61; 45.43; 53.15; 121.70; 124.56; 149.88;
151.70; 152.06; 194.03. EI-MS: 193 (100, Mþ). Anal. calc. for C10H11NOS (193.27): C 62.15, H 5.74, N 7.25;
found: C 62.16, H 5.70, N 7.11.
We thank Mrs. Miyuki Tanmatsu of our university for recording mass spectra and performing
combustion analyses.
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Received September 26, 2012