Efficient synthesis of novel 3-substituted thiopyran-4-ones

Article abstract of DOI:10.1055/s-2007-990806

Synthesis of several 3-substituted thiopyran-4-ones is reported for the first time via aldol condensation of various aromatic aldehydes with dihydrothiopyran-4-one derivatives under very mild conditions using magnesium bromide diethyl etherate and triethy

Full text of DOI:10.1055/s-2007-990806

PAPER
3339
Efficient Synthesis of Novel 3-Substituted Thiopyran-4-ones
S
ynthesis of
N
ovel 3-S
.
ubstituted T
Sa
es eed Abaee,a Mohammad M. Mojtahedi,*a M. Mehdi Zahedi,a Roholah Sharifi,a Hamidreza Khavasib
a
b
Received 15 May 2007; revised 30 July 2007
Dedicated to Professor Dale E. Ward
O
S
O
S
Abstract: Synthesis of several 3-substituted thiopyran-4-ones is re-
ported for the first time via aldol condensation of various aromatic
aldehydes with dihydrothiopyran-4-one derivatives under very mild
conditions using magnesium bromide diethyl etherate and triethyl-
amine. The products were characterized based on spectroscopic and
X-ray diffraction experiments.
R
R
R
2
1
O
X
Key words: thiopyrans, aldol condensation, magnesium bromide
diethyl etherate, heterocycles
S
4: X = H
5: X = Cl
O
S
O
X
Among the various sulfur-containing heterocycles, thio-
pyran structures are of particular importance owing to
their versatility as useful scaffolds to access certain natu-
ral and unnatural products.1 This prominence is usually
furnished by removal of the sulfur atom at the final stage
of multi-step syntheses providing the access to target
structures which are not easily prepared by direct standard
procedures. In this regard, use of thiopyran dienes as ef-
fective surrogates for unreactive cis-dienes in Diels–
Alder reactions2 and construction of polypropionate
building blocks3 via tandem aldol reactions of thiopyra-
none skeleton are successfully demonstrated by Ward et al.
X
R
3a: X = H
3b: X = Cl
6: X = H
7: X = Cl
S
Scheme 1
Cannizzaro reactions,9 aldol condensation,10 a-aminoni-
trile syntheses,11 alcohols protection,12 Knoevenagel con-
densation,13 and nucleophilic ring opening of epoxides.14
In the present study, we would like to introduce an effi-
cient room temperature procedure for aldol condensation
of enones of type 3 with various aldehydes in the presence
of MgBr2·OEt2 and triethylamine.
In the framework of our investigation into developing ef-
ficient synthetic procedures for thiopyran chemistry, we
recently reported the preparation of various bis(arylmeth-
ylidene)thiopyranones 2 via aldol condensation of 1 with
different aldehydes.4 This encouraged us to extend the re-
sults to dihydrothiopyranone system (e.g., 3a,b) in order
to access products of type 4–7 (Scheme 1).5 These prod-
ucts are suitable for further synthetic manipulation to ob-
tain various substituted thiopyran structures and also via a
possible desulfurization they could in principle produce
unsymmetrically substituted bisenones as divinyl ketone
substrates for Nazarov cyclization.6 Bibliographical sur-
veys found only a single related example (4: R = H) which
was prepared using a four-step reaction from the same
starting material 3a after six days and with an overall yield
of ~50%.1d
This chemistry was exploited by evaluating the reaction
between benzaldehyde and enone 3a using various Lewis
acids at room temperature. The best results were obtained
when a solution of the aldehyde and 3a in dichlo-
romethane was treated with MgBr2·OEt2 in the presence
of triethylamine (Table 1, entry 1). As a result, gradual
disappearance of the reactants and formation of a single
product in 87% yield was noticed within 10 hours. The
structure of the product was elucidated based on its spec-
troscopic data. Mass spectrum, elemental analysis, and
NMR studies were all in accordance with 1:1 condensa-
tion of benzaldehyde with 3a. Two diagnostic coupling
constant values (3JH,H = 10.2 Hz and JH,H = 4.1 Hz) at
4
7.82 ppm in the 1H NMR spectrum were indicative of for-
mation of aldol product 6a.
In recent years, magnesium bromide diethyl etherate
(MgBr2·OEt2) has found many applications as a mild
Lewis acid to ease up various synthetic organic transfor-
mations.7 In this context, we have demonstrated the use-
fulness of MgBr2·OEt2 in Diels–Alder cycloadditions,8
The same mixture gave no product in the absence of
MgBr2·OEt2 illustrating the promoting effect of the cata-
lyst. Alternatively, omission of triethylamine led to the
formation of small amount of 6a and nearly quantitative
recovery of the starting materials. By using this proce-
dure, a variety of different aldehydes were treated under
the same conditions to evaluate the generality of the pro-
cess. Thus, when electron-releasing-substituted (entries
SYNTHESIS 2007, No. 21, pp 3339–3344
x
x.
x
x
.
2
0
0
7
Advanced online publication: 21.09.2007
DOI: 10.1055/s-2007-990806; Art ID: T08407SS
© Georg Thieme Verlag Stuttgart · New York

3340
M. S. Abaee et al.
PAPER
2,3) and electron-withdrawing-substituted aldehydes (en- indicate the formation of 6c which seems to result from
tries 4–6) were subjected to react with 3a, formation of structure 4c via a hydrogen atom rearrangement.
more than 80% of single products 6b–f in each case was
observed within 10–12 hours. Similarly, furfural and
thiophene-2-carbaldehyde behaved equally well and, as
To illustrate the further generality of this method, we next
employed these results for similar reactions of enone 3b.
This substrate for which we developed a new facile syn-
thetic procedure in our laboratories is suitable for further
the consequence of their reaction with 3a, products 6g,h
were formed (entries 7,8).15 All products were character-
manipulation and substitution reactions at the thiopyran
ized by their IR, 1H NMR, 13C NMR, and mass spectra and
ring because of the chlorine substituent. Scheme 2 sum-
marizes the pathway for direct preparation of 3b from 3a
their purity were confirmed by elemental analyses.
In order to verify the proposed structures, a single crystal and synthesis of 7a–d in 80–88% yield via MgBr2·OEt2-
of 6c was prepared and analyzed by X-ray crystallograph- mediated reactions of 3b with four different aldehydes.15
ic experiments.16 The results, depicted in Figure 1, clearly
Table 1 MgBr2·OEt2-Mediated Aldol Condensation of 3a with Various Aromatic Aldehydes
O
O
MgBr2⋅OEt2, Et3N
RCHO, CH2Cl2, r.t.
R
S
10–12 h
S
3a
6a–h
Entry
1
Aldehyde
Product
Yield (%)a
87
O
benzaldehyde
6a
6b
6c
S
O
2
3
4
4-methylbenzaldehyde
4-methoxybenzaldehyde
83
82
80
S
O
S
OMe
O
4-chlorobenzaldehyde
6d
6e
S
Cl
Cl
O
5
2,6-dichlorobenzaldehyde
83
S
Cl
O
6
7
4-bromobenzaldehyde
thiophene-2-carbaldehyde
furfural
6f
82
86
85
S
Br
O
S
6g
6h
S
O
O
8
S
a Isolated yield.
Synthesis 2007, No. 21, 3339–3344 © Thieme Stuttgart · New York

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Synthesis of Novel 3-Substituted Thiopyran-4-ones
3341
MgBr2
MgBr2
O
S
O
Et3N
S
a
b
RCHO
Br
Br
O
Mg
O
OH
O
R
R
Figure 1 Crystal structure of 6c. Displacement ellipsoids at 50%
probability level.
c
d
S
S
O
O
O
S
O
S
R
R
S
S
4
6
3a
1
Scheme 3 Proposed mechanism for the formation of 6/7.
a
b
c
Table 2 MgBr2·OEt2 Mediated Aldol Condensation of 3a or 3b
with Various Aromatic Aldehydes at 0 °C
O
S
O
S
O
O
Cl
Cl
R
X
X
MgBr2⋅OEt2, Et3N
R
3b
5
RCHO, CH2Cl2, 0 °C
S
S
7a: R = C6H5; 80%
3a or 3b
4 or 5
O
7b: R = 4-MeC6H4; 82%
7c: R = 4-MeOC6H4; 88%
7d: R = 4-ClC6H4; 85%
Cl
X
H
H
H
H
Cl
H
R
Product
4b
Yield (%)
R
4-MeC6H4
75
73
76
80
77
79
S
4-MeOC6H4
4-ClC6H4
4c
Scheme 2 Reagents and conditions: (a) NCS (2 equiv), CCl4,
70%;17 (b) NCS, pyridine, CH2Cl2, 92%; (c) MgBr2·OEt2, Et3N,
CH2Cl2, r.t., 10–12 h.
4d
4-BrC6H4
4f
4-MeOC6H4
2,4,6-(MeO)3C6H2
5c
Based on the observed results, a mechanistic pathway can
be proposed through which products of type 4 (5) are
formed and then isomerized in situ to their respective
compounds of type 6 (7) (Scheme 3). Apparently, 4 (5) is
primarily formed as a result of Lewis acid mediated aldol
condensation of 3a (3b) with aldehydes. Under the condi-
tions, 4 (5) is then conveniently isomerized to 6 (7) due to
arriving at a more thermodynamically stable aromatic
structure. To support this hypothesis, we attempted to sup-
press the rearrangement process and stop the reaction at
aldol condensation step by altering the reaction condi-
tions. Consequently, when the same reactions were con-
ducted at lower temperature, products 4,5 were formed in
73–80% yields within 6 hours of reaction time (Table 2)
while the rest of the starting aldehydes remained unreact-
ed. These products isomerized to their corresponding
compounds of type 6,7 when left in solution for few days.
In the presence of MgBr2·OEt2/triethylamine or under re-
fluxing conditions, the rearrangement took place in short-
er time periods.
4i
In summary, we have disclosed here the first general pro-
cedure for the synthesis of the title compounds under very
mild conditions using MgBr2·OEt2 and triethylamine. The
generality of this versatile reaction and formation of sin-
gle products in high yields make this method an attractive
addition to the present thiopyran chemistry archive. At-
tempts at desulfurization of the products are also under-
way.
Reactions were monitored by TLC using silica gel coated plates and
EtOAc–hexane solutions as the mobile phase. Melting points are
uncorrected. FT-IR spectra were recorded using KBr disks on a
Bruker Vector-22 IR spectrometer and absorptions are reported as
wave numbers (cm–1). 1H NMR and 13C NMR spectra were obtained
on a FT-NMR Bruker Ultra ShieldTM (500 MHz) instrument as
CDCl3 solutions and the chemical shifts are expressed as d units
with Me4Si as the internal standard. Mass spectra were obtained on
Synthesis 2007, No. 21, 3339–3344 © Thieme Stuttgart · New York

3342
M. S. Abaee et al.
PAPER
a Finnigan Mat 8430 apparatus at an ionization potential of 70 eV.
Elemental analyses were performed using a Thermo Finnigan Flash
EA 1112 instrument. Compound 3a was prepared using available
methods.18 All other reagents were purchased from commercial
sources and were freshly used after being purified by standard pro-
cedures.
13C NMR (CDCl3): d = 179.7, 158.8, 144.3, 137.1, 133.9, 131.1,
130.9, 130.3, 114.6, 55.7, 36.8.
MS (70 eV): m/z = 232 (M+), 217, 171, 131, 115.
Anal. Calcd for C13H12O2S: C, 67.21; H, 5.21. Found: C, 67.28; H,
5.62.
3-(4-Chlorobenzyl)-4H-thiopyran-4-one (6d)
Pale yellow crystals; yield: 80%; mp 63–65 °C.
IR (KBr): 3000, 1602, 1489 cm–1.
1H NMR (CDCl3): d = 7.76 (dd, J = 4.1, 10.2 Hz, 1 H), 7.32–7.30
(m, 3 H), 7.20 (d, J = 8.3 Hz, 2 H), 7.08 (d, J = 10.2 Hz, 1 H), 3.89
(s, 2 H).
13C NMR (CDCl3): d = 179.4, 143.3, 137.4, 137.0, 134.3, 132.9,
131.3, 130.9, 129.3, 37.2.
5-Chloro-2,3-dihydrothiopyran-4-one (3b)
To a solution of ketone 3a (3.4 g, 30 mmol) and pyridine (2.5 mL,
30 mmol) in CH2Cl2 (100 mL) at 0 °C was added N-chlorosuccin-
imide portionwise (4.2 mg, 31 mmol) and the mixture was stirred at
r.t. for 4 h until TLC monitoring showed complete disappearance of
the starting ketone. The mixture was concentrated under reduced
pressure and the product was extracted with Et2O (3 × 50 mL) from
the black precipitate. Product 3b was obtained after removal of Et2O
on a rotary evaporator; oil; yield: 3.8 g (85%).
MS (70 eV): m/z = 236 (M+), 201, 184, 168, 149, 115.
1H NMR (CDCl3): d = 7.49 (s, 1 H), 2.92–2.81 (m, 2 H), 3.30–3.09
(m, 2 H).
Anal. Calcd for C12H9ClOS: C, 60.89; H, 3.83. Found: C, 60.64; H,
3.76.
13C NMR (CDCl3): d = 186.4, 142.3, 123.5, 33.4, 27.2.
MS (70 eV): m/z = 148 (M+), 120, 92.
3-(2,6-Dichlorobenzyl)-4H-thiopyran-4-one (6e)
Pale yellow crystals; yield: 83%; mp 126–127 °C.
IR (KBr): 3021, 1597, 1434 cm–1.
1H NMR (CDCl3): d = 7.79 (dd, J = 4.1, 10.2 Hz, 1 H), 7.39 (d,
J = 8.1 Hz, 2 H), 7.23 (t, J = 8.1 Hz, 1 H), 7.12 (d, J = 10.2 Hz, 2
H), 6.90 (d, J = 4.1 Hz, 1 H), 4.26 (s, 2 H).
13C NMR (CDCl3): d = 179.3, 139.8, 137.3, 136.9, 134.7, 132.1,
130.6, 129.3, 128.9, 33.0.
MS (70 eV): m/z = 270 (M+), 235, 200, 171.
3-Substituted Thiopyran-4-ones 6 and 7; General Procedure
Ketone 3a (or 3b) (3 mmol) was added to the mixture of the alde-
hyde (3.3 mmol), MgBr2·OEt2 (775 mg, 3 mmol), and Et3N (364
mg, 3.6 mmol) in CH2Cl2 (10 mL) and the mixture was stirred at r.t.
for 10–12 h until TLC showed complete disappearance of the start-
ing ketone. The mixture was diluted with CH2Cl2 (10 mL) and the
organic layer was washed with H2O (3 × 10 mL). The organic layer
was dried (Na2SO4) and concentrated under reduced pressure. The
product was separated by column chromatography using hexane–
EtOAc (3:2) as the eluent and recrystallized from EtOAc.
Anal. Calcd for C12H8Cl2OS: C, 53.15; H, 2.97. Found: C, 53.23; H,
2.85.
3-Benzyl-4H-thiopyran-4-one (6a)
Pale yellow crystals; yield: 87%; mp 73–75 °C.
IR (KBr): 3026, 1600, 1224 cm–1.
3-(4-Bromobenzyl)-4H-thiopyran-4-one (6f)
Pale yellow crystals; yield: 82%; mp 76–78 °C.
1H NMR (CDCl3): d = 7.82 (dd, J = 4.1, 10.2 Hz, 1 H), 7.36–7.33
IR (KBr): 3038, 1599, 1226 cm–1.
(m, 3 H), 7.28–7.23 (m, 3 H), 7.18 (d, J = 10.2 Hz, 1 H), 3.92 (s, 2
1H NMR (CDCl3): d = 7.73 (dd, J = 4.1, 10.2 Hz, 1 H), 7.42 (d,
J = 8.3 Hz, 2 H), 7.32 (d, J = 4.1 Hz, 1 H), 7.12 (d, J = 8.3 Hz, 2 H),
7.03 (d, J = 10.2 Hz, 1 H), 3.85 (s, 2 H).
13C NMR (CDCl3): d = 179.3, 143.1, 137.7, 137.4, 134.4, 132.2,
131.6, 130.9, 121.0, 37.2.
H).
13C NMR (CDCl3): d = 179.4, 143.7, 143.6, 138.3, 135.2, 130.5,
130.0, 129.2, 127.2, 37.6.
MS (70 eV): m/z = 202 (M+), 185, 169, 141, 115.
MS (70 eV): m/z = 281 (M+), 265, 200, 184, 115.
Anal. Calcd for C12H10OS: C, 71.25; H, 4.98. Found: C, 71.32; H,
4.89.
Anal. Calcd for C12H9BrOS: C, 51.26; H, 3.23. Found: C, 51.34; H,
3.51.
3-(4-Methylbenzyl)-4H-thiopyran-4-one (6b)
Pale yellow crystals; yield: 83%; mp 71–73 °C.
IR (KBr): 3022, 1596, 1224 cm–1.
3-(Thien-2-ylmethyl)-4H-thiopyran-4-one (6g)
Pale yellow crystals; yield: 86%; mp 58–60 °C.
1H NMR (CDCl3): d = 7.71 (dd, J = 4.1, 10.2 Hz, 1 H), 7.26 (d,
J = 4.1 Hz, 1 H), 7.17–7.11 (m, 4 H), 7.04 (d, J = 10.2 Hz, 1 H),
3.87 (s, 2 H), 2.34 (s, 3 H).
13C NMR (CDCl3): d = 179.6, 144.0, 137.3, 136.6, 135.3, 134.2,
130.8, 129.9, 129.8, 37.2, 21.5.
IR (KBr): 3034, 1599, 1252 cm–1.
1H NMR (CDCl3): d = 7.87 (dd, J = 4.1, 10.2 Hz, 1 H), 7.55 (d,
J = 4.1 Hz, 1 H), 7.28 (d, J = 10.2 Hz, 1 H), 7.26 (d, J = 5 Hz, 1 H),
7.03 (dd, J = 3, 5 Hz, 1 H), 6.96 (d, J = 3 Hz, 1 H), 4.17 (s, 2 H).
13C NMR (CDCl3): d = 179.1, 142.8, 140.3, 137.5, 134.5, 130.8,
127.6, 127.2, 125.1, 31.7.
MS (70 eV): m/z = 216 (M+), 201, 161, 129, 115.
MS (70 eV): m/z = 208 (M+), 175, 121, 97.
Anal. Calcd for C13H12OS: C, 72.19; H, 5.59. Found: C, 72.22; H,
5.71.
Anal. Calcd for C10H8OS2: C, 57.66; H, 3.87. Found: C, 57.45; H,
3.77.
3-(4-Methoxybenzyl)-4H-thiopyran-4-one (6c)
Pale yellow crystals; yield: 82%; mp 115–117 °C.
IR (KBr): 3032, 1597, 1246 cm–1.
3-(Fur-2-ylmethyl)-4H-thiopyran-4-one (6h)
Oil; yield: 85%.
1H NMR (CDCl3): d = 7.77 (dd, J = 4.1, 10.1 Hz, 1 H), 7.26 (d,
J = 4.1 Hz, 1 H), 7.18 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 10.1 Hz, 1
H), 7.91 (d, J = 8.5 Hz, 2 H), 3.88 (s, 2 H), 3.84 (s, 3 H).
IR (KBr): 3029, 1606, 1226 cm–1.
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Synthesis of Novel 3-Substituted Thiopyran-4-ones
3343
1H NMR (CDCl3): d = 7.72 (dd, J = 4, 10.2 Hz, 1 H), 7.39 (d, J = 4
Hz, 1 H), 7.32 (s, 1 H), 6.99 (d, J = 10.2 Hz, 1 H), 6.29 (s, 1 H), 6.14
(d, J = 2.5 Hz, 1 H), 3.89 (s, 2 H).
13C NMR (CDCl3): d = 179.1, 151.8, 142.4, 140.6, 137.6, 134.5,
130.7, 111.0, 108.4, 30.0.
h. The organic layer was washed with H2O (3 × 10 mL), dried
(Na2SO4), and concentrated under reduced pressure. The product
was separated by column chromatography using hexane–EtOAc
(3:2) as the eluent and recrystallized from EtOAc.
(Z)-3-(4-Methylbenzylidene)-2,3-dihydrothiopyran-4-one (4b)
Yellow crystals; yield: 75%; mp 98–101 °C.
MS (70 eV): m/z = 192 (M+), 163, 115.
IR (KBr): 1603, 1399 cm–1.
Anal. Calcd for C10H8O2S: C, 62.48; H, 4.19. Found: C, 62.52; H,
4.23.
1H NMR (CDCl3): d = 7.64 (s, 1 H), 7.53 (d, J = 10.1 Hz, 1 H), 7.29
(d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.36 (d, J = 10.1 Hz,
1 H), 4.17 (s, 2 H), 2.43 (s, 3 H).
13C NMR (CDCl3): d = 186.3, 145.9, 139.5, 138.4, 132.3, 130.9,
129.9, 129.8, 125.3, 30.0, 21.8.
3-Benzyl-5-chloro-4H-thiopyran-4-one (7a)
Pale yellow crystals; yield: 80%; mp 75–77 °C.
IR (KBr): 3024, 1604, 1311 cm–1.
1H NMR (CDCl3): d = 7.95 (d, J = 3.9 Hz, 1 H), 7.35–7.30 (m, 3 H),
7.25–7.22 (m, 3 H), 3.92 (s, 2 H).
MS (70 eV): m/z = 216 (M+), 201, 128, 115.
Anal. Calcd for C13H12OS: C, 72.19; H, 5.59. Found: C, 72.25; H,
5.66.
13C NMR (CDCl3): d = 173.9, 143.4, 138.3, 134.0, 133.8, 133.5,
129.9, 129.2, 127.2, 38.3.
MS (70 eV): m/z = 236 (M+), 219, 200, 184, 115.
(Z)-3-(4-Methoxybenzylidene)-2,3-dihydrothiopyran-4-one (4c)
Yellow crystals; yield: 73%; mp 89–90 °C.
IR (KBr): 1589, 1431 cm–1.
Anal. Calcd for C12H9ClOS: C, 60.89; H, 3.83. Found: C, 60.34; H,
3.87.
1H NMR (CDCl3): d = 7.60 (s, 1 H), 7.51 (d, J = 10.1 Hz, 1 H), 7.34
(d, J = 8.5 Hz, 2 H), 6.97 (d, J = 8.5 Hz, 2 H), 6.34 (d, J = 10.1 Hz,
1 H), 4.17 (s, 2 H), 3.87 (s, 3 H).
13C NMR (CDCl3): d = 186.3, 160.5, 145.5, 138.2, 131.6, 129.7,
127.6, 125.4, 114.7, 55.8, 30.0.
3-Chloro-5-(4-methylbenzyl)-4H-thiopyran-4-one (7b)
Pale yellow crystals; yield: 82%; mp 79–81 °C.
IR (KBr): 3024, 1613, 1260 cm–1.
1H NMR (CDCl3): d = 7.97 (d, J = 3.9 Hz, 1 H), 7.31 (d, J = 3.9 Hz,
1 H), 7.17 (m, 4 H), 3.92 (s, 2 H), 2.36 (s, 3 H).
13C NMR (CDCl3): d = 174.0, 143.9, 136.9, 135.0, 134.1, 133.4,
133.1, 130.0, 129.9, 37.9, 21.5.
MS (70 eV): m/z = 232 (M+), 217, 146, 115.
Anal. Calcd for C13H12O2S: C, 67.21; H, 5.21. Found: C, 67.18; H,
5.35.
MS (70 eV): m/z = 250 (M+), 217, 201, 184, 115.
(Z)-3-(4-Chlorobenzylidene)-2,3-dihydrothiopyran-4-one (4d)
Yellow crystals; yield: 76%; mp 73–75 °C.
IR (KBr): 1604, 1487 cm–1.
1H NMR (CDCl3) d = 7.58 (s, 1 H), 7.55 (d, J = 10.1, 1 H), 7.43 (d,
J = 8.4 Hz, 2 H), 7.31 (d, J = 8.4 Hz, 2 H), 6.36 (d, J = 10.1, 1 H),
4.10 (s, 2 H).
13C NMR (CDCl3): d = 186.1, 146.2, 136.9, 135.2, 133.6, 132.2,
131.1, 129.5, 125.2, 29.9.
Anal. Calcd for C13H11ClOS: C, 62.27; H, 4.42. Found: C, 62.21; H,
4.45.
3-Chloro-5-(4-methoxybenzyl)-4H-thiopyran-4-one (7c)
Pale yellow crystals; yield: 88%; mp 88–89 °C.
1H NMR (CDCl3): d = 7.98 (d, J = 3.8 Hz, 1 H), 7.29 (d, J = 3.8 Hz,
1 H), 7.18 (d, J = 8.4 Hz, 2 H), 6.90 (d, J = 8.4 Hz, 2 H), 3.92 (s, 2
H), 3.83 (s, 3 H).
13C NMR (CDCl3): d = 174.1, 158.9, 144.0, 134.1, 133.6, 133.1,
131.1, 130.0, 114.7, 55.7, 37.5.
MS (70 eV): m/z = 236 (M+), 201, 149, 115.
Anal. Calcd for C12H9ClOS: C, 60.89; H, 3.83. Found: C, 60.80; H,
3.89.
MS (70 eV): m/z = 266 (M+), 251, 235, 187, 145, 115.
Anal. Calcd for C13H11ClO2S: C, 58.54; H, 4.16. Found: C, 58.60;
H, 4.22.
(Z)-3-(4-Bromobenzylidene)-2,3-dihydrothiopyran-4-one (4f)
Yellow crystals; yield: 80%; mp 101–103 °C.
IR (KBr): 1599, 1478 cm–1.
1H NMR (CDCl3): d = 7.59 (s, 1 H), 7.56 (d, J = 10.1, 1 H), 7.54 (d,
J = 8.1 Hz, 2 H), 7.23 (d, J = 8.1 Hz, 2 H), 6.35 (d, J = 10.1, 1 H),
4.09 (s, 2 H).
13C NMR (CDCl3): d = 186.1, 146.2, 136.9, 134.1, 132.4, 131.3,
128.1, 125.2, 123.5, 29.9.
MS (70 eV): m/z = 280 (M+), 201, 173, 115.
3-Chloro-5-(4-chlorobenzyl)-4H-thiopyran-4-one (7d)
Pale yellow crystals; yield: 85%; mp 76–78 °C.
IR (KBr): 3027, 1709, 1600, 1229 cm–1.
1H NMR (CDCl3): d = 7.99 (d, J = 3.9 Hz, 1 H), 7.38 (d, J = 3.9 Hz,
1 H), 7.30 (d, J = 8.3 Hz, 2 H), 7.20 (d, J = 8.3 Hz, 2 H), 3.93 (s, 2
H).
13C NMR (CDCl3): d = 173.9, 143.0, 136.7, 134.3, 133.7, 133.5,
133.1, 131.3, 129.3, 37.8.
Anal. Calcd for C12H9BrOS: C, 51.26; H, 3.23. Found: C, 51.45; H,
3.52.
MS (70 eV): m/z = 271 (M+), 263, 235, 199, 171, 115.
Anal. Calcd for C12H8Cl2OS: C, 53.15; H, 2.97. Found: C, 53.19; H,
3.11.
(Z)-5-Chloro-3-(4-methoxybenzylidene)-2,3-dihydrothiopyran-
4-one (5c)
Yellow crystals; yield: 77%; mp 69–71 °C.
IR (KBr): 1655, 1462 cm–1.
1H NMR (CDCl3): d = 7.68 (s, 1 H), 7.67 (s, 1 H), 7.35 (d, J = 8.6
Hz, 2 H), 6.98 (d, J = 8.6 Hz, 2 H), 4.20 (s, 3 H), 3.88 (s, 2 H).
3-Substituted 2,3-Dihydrothiopyran-4-ones 4 and 5; General
Procedure
Ketone 3a (or 3b) (3 mmol) was added to an ice-cooled mixture of
the aldehyde (3.3 mmol), MgBr2·OEt2 (3 mmol), and Et3N (3.6
mmol) in CH2Cl2 (10 mL) and the mixture was stirred at 0 °C for 6
Synthesis 2007, No. 21, 3339–3344 © Thieme Stuttgart · New York

3344
M. S. Abaee et al.
PAPER
(4) Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M. Synlett
13C NMR (CDCl3): d = 180.4, 160.8, 141.5, 140.1, 131.7, 129.3,
127.2, 125.5, 114.8, 55.8, 30.1.
2005, 2317.
(5) This type of aldol condensation followed by hydrogen atom
rearrangement has precedence in heterocyclic and for 2,3-
dihydropyridin-4(1H)-one systems as previously reported:
Kitagawa, H.; Kumura, K.; Atsumi, K. Chem. Lett. 2006,
712.
(6) (a) Ulrich, E. A.; Batson, W. A.; Tius, M. A. Synthesis 2006,
2139. (b) Grant, G. T. N.; West, F. G. J. Am. Chem. Soc.
2006, 128, 9348. (c) Douelle, F.; Tal, L.; Greaney, M. F.
Chem. Commun. 2005, 660. (d) Wang, Y.; Schill, B. D.;
Arif, A. M.; West, F. G. Org. Lett. 2003, 5, 2747.
(7) Tipparaju, S. K. Synlett 2004, 912; and references cited
therein.
(8) Ward, D. E.; Abaee, M. S. Org. Lett. 2000, 2, 3937.
(9) Abaee, M. S.; Sharifi, R.; Mojtahedi, M. M. Org. Lett. 2005,
7, 5893.
(10) Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M.; Sharifi, R.
Heteroat. Chem. 2007, 18, 44.
MS (70 eV): m/z = 266 (M+), 251, 235, 131, 103.
Anal. Calcd for C13H11ClO2S: C, 58.54; H, 4.16. Found: C, 58.63;
H, 4.18.
(Z)-3-(2,4,6-Trimethoxybenzylidene)-2,3-dihydrothiopyran-4-
one (4i)
Yellow crystals; yield: 79%; mp 93–95 °C.
IR (KBr): 1586, 1473 cm–1.
1H NMR (CDCl3): d = 7.49 (s, 1 H), 7.47 (d, J = 10.2 Hz, 1 H), 6.32
(d, J = 10.2 Hz, 1 H), 6.18 (s, 2 H), 3.88 (s, 3 H), 3.84 (s, 6 H), 3.81
(s, 2 H).
13C NMR (CDCl3): d = 186.0, 162.8, 159.3, 146.0, 131.3, 131.0,
125.2, 105.9, 90.9, 56.1, 55.8, 32.2. MS (70 eV): m/z = 292 (M+),
261, 191, 167.
Anal. Calcd for C15H16O4S: C, 61.62; H, 5.52. Found: C, 61.70; H,
5.47.
(11) Mojtahedi, M. M.; Abaee, M. S.; Abbasi, H. Can. J. Chem.
2006, 84, 429.
(12) Mojtahedi, M. M.; Abbasi, H.; Abaee, M. S. J. Mol. Catal.
A: Chem. 2006, 250, 6.
(13) Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M.;
Khanalizadeh, G. ARKIVOC 2006, (xv), 48.
(14) (a) Mojtahedi, M. M.; Abaee, M. S.; Bolourtchian, M.;
Abbasi, H. Phosphorus, Sulfur and Silicon 2007, 182, 905.
(b) Mojtahedi, M. M.; Abaee, M. S.; Hamidi, V. Catal.
Commun. 2007, 8, 1671.
Acknowledgment
Partial financial support of this work by the Ministry of Science,
Research, and Technology of Iran is gratefully acknowledged.
References
(15) The reaction is limited to aldehydes with no a-hydrogen.
Under the conditions, aliphatic aldehydes undergo self
condensation and the starting ketone remains intact.
(16) Crystallographic data for 6c have been deposited with the
Cambridge Crystallographic Data Center as supplementary
publication no. CCDC-627143. Copies of these data can be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [Fax: +44(1223)336033; E-
mail: deposit@ccdc.cam.ac.uk or via www.ccdc.cam.ac.uk/
conts/retrieving.html].
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Synthesis 2007, No. 21, 3339–3344 © Thieme Stuttgart · New York