An efficient and improved method for the synthesis of bis(arylmethylidene) thiopyranones

Article abstract of DOI:10.1055/s-2005-872656

Double crossed aldol condensation of a variety of aromatic aldehydes with tetrahydrothiopyran-4-one in the presence of N-(trimethylsilyl)diethylamine and 5 M lithium perchlorate in diethyl ether at room temperature is described. Excellent yields of 3,5-bi

Full text of DOI:10.1055/s-2005-872656

LETTER
2317
An Efficient and Improved Method for the Synthesis of
Bis(arylmethylidene)thiopyranones
S
M
ynthesis of Bis(arylm
.
ethylidene)th
S
iopyranones aeed Abaee,* Mohammad M. Mojtahedi, M. Mehdi Zahedi
Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
Fax +98(21)88037185; E-mail: abaee@ccerci.ac.ir
Received 27 April 2005
Abstract: Double crossed aldol condensation of a variety of aro-
matic aldehydes with tetrahydrothiopyran-4-one in the presence of
N-(trimethylsilyl)diethylamine and 5 M lithium perchlorate in di-
ethyl ether at room temperature is described. Excellent yields of
3
,5-bis(arylmethylidene)thiopyranones are achieved in a facile one-
pot general procedure.
Key words: 3,5-bis(arylmethylidene)thiopyranones, thiopyrans,
lithium perchlorate, crossed aldol condensation
Scheme 1
We are interested in the development of the chemistry of
thiopyran structures. Substituted derivatives of tetra-
1
In recent years, lithium perchlorate in diethyl ether has
been widely used for various organic transformations.18
We decided to extend our previous experiences on the
hydrothiopyran-4-one (1) are useful synthetic precursors
and direct substitution at different positions of 1 is there-
fore interesting. The substituted products of 1 are attrac-
2
1
9
synthetic applications of iminium salts of aldehydes. In
the present article, a one-pot synthetic pathway for double
condensation of thiopyran 1 with aromatic aldehydes in
the presence of N-(trimethylsilyl)diethylamine and 5 M
lithium perchlorate in diethyl ether solution (LPDE) at
room temperature is described (Scheme 2). To the best of
our knowledge, the present methodology is the most effi-
cient and reliable method for the synthesis of the title
structures.
tive as well since they could be converted via removal of
a sulfur atom to a,b-unsaturated ketones, which are not
easily prepared by direct standard procedures.3 The
strategy to use thiopyran skeletons for the construction of
various synthetic targets is well established and has been
recently demonstrated by Ward et al. for the synthesis of
4
polypropionate building blocks.
The crossed aldol condensation has been employed for the
synthesis of bis(arylmethylidene)cycloalkanones by the
reaction of homocyclic ketones with aromatic aldehydes.5
Many developments have been achieved in recent years to
widen the synthetic scope of bis(arylmethylidene)cycloal-
kanones by optimizing the reaction temperature, reaction
6
time, and product yield. More improvements have been
achieved by application of KF-supported reagents under
7
microwave mediation and ultrasound irradiation. Lewis
8
9
acid catalysis using Yb(OTf) , iodotrimethylsilane,
3
1
0
6b
11
12
TiCl (SO CF ), RuCl , Pd/C–Me SiCl and SmI3,
FeCl3, and InCl3 in ionic liquids are also employed. Scheme 2
3
3
3
3
3
1
3
14
Although similar reactions for some heterocyclic
1
5
16
ketones including those with a thiopyranone structure
Initially, treatment of benzaldehyde with N-(trimethylsi-
lyl)diethylamine in 5 M LPDE at room temperature facil-
itated in situ formation of the corresponding iminium salt
have been reported, lack of a general, efficient, and reli-
able method for the synthesis of the title compounds is ob-
vious. Tetrahydrothiopyran-4-one (1) is a key precursor
for the synthetic preparation of a vast number of thiopyran
structures. Therefore, compound 1 was chosen as the
primary precursor for the synthesis of several benzyl-
idenethiopyranone derivatives (Scheme 1).
2
a, due to the Lewis acidity of the lithium ion and high
18
polarity of the reaction medium. Subsequent addition of
thiopyran 1 to the reaction mixture resulted in the forma-
tion of double crossed aldol condensation product 3a
within a few hours at room temperature. The reaction was
found to be complete in less than two hours and the yield
was 92%. In order to test the chemoselectivity of the reac-
tion, parallel reactions were carried out using thiopyran/
benzaldehyde ratios of 1:1 and 1:2. In both cases the same
1
7
SYNLETT 2005, No. 15, pp 2317–2320
1
9
.0
9
.2
0
0
5
Advanced online publication: 05.08.2005
DOI: 10.1055/s-2005-872656; Art ID: D11405ST
©
Georg Thieme Verlag Stuttgart · New York

2
318
M. S. Abaee et al.
LETTER
Table 1 Reactions of Thiopyran 1 with Aromatic Aldehydes in the Presence of TMSNEt2a and LPDE
Entry
1
Aldehyde
Product
Yield (%)b
92
3a
3b
3c
3d
3e
2
3
4
5
96
94
97
92
6
7
8
3f
94
95
95
3g
3h
a
N-(Trimethylsilyl)diethylamine.
Isolated yields.
b
product 3a was formed in comparable quantities. Other tive addition to the present literature. We are currently ex-
control experiments were carried out to clarify the role of ploring the scope of this protocol to enhance the existing
the reactants. A test reaction conducted in the absence of synthetic methodologies for similar homocyclic systems.
N-(trimethylsilyl)diethylamine, gave no product. Omis- The application of the results to other heterocyclic homo-
sion of lithium perchlorate from the reaction medium also logues is underway.
led to complete recovery of the starting materials. The
generality of the method was demonstrated by the synthe-
sis of similar products (3b–h) using other aromatic alde-
hydes under the same conditions. All reactions proceeded were obtained on a Bruker AC 80 MHz instrument as CDCl solu-
Melting points are uncorrected. IR spectra were recorded using KBr
disks on a Bruker Vector-22 infrared spectrometer. NMR spectra
3
rapidly at room temperature and complete conversions tions using TMS as the internal standard reference. Mass spectra
were obtained on a Sinnigan Mat 8430 apparatus. Compound 1 was
were observed in less than two hours (Table 1). Under the
2
0
prepared using available methods. Solvents and reagents were
purchased from commercial sources. Aldehydes were redistilled or
recrystallized before use. Caution: Although we did not have any
present conditions, all reactions proceeded cleanly and no
other products, which are normally observed under classi-
cal conditions, are detected. The present one-pot protocol
has the advantages of mild reaction conditions, great effi-
ciency, short reaction times, high product yields, and use
accidents using lithium perchlorate (LiClO ), it is advisable to dry
4
lithium perchlorate in a hood behind a Lab shield.
of inexpensive commercially available materials. In con- Bis(arylmethylidene)thiopyranones; Typical Procedure
A mixture of the aldehyde (2 mmol) and a Et O (1.5 mL) solution
of 5 M LPDE and N-(trimethylsilyl)diethylamine (3 mmol) was
stirred at r.t. under an inert atmosphere for 10 min. To this mixture
was added thiopyranone 1 (1 mmol) and stirring continued under
clusion, we have presented a novel, reliable, and efficient
general synthetic protocol for the preparation of 3,5-
bis(arylmethylidene)thiopyranones at room temperature.
The generality of this versatile reaction makes it an attrac-
2
Synlett 2005, No. 15, 2317–2320 © Thieme Stuttgart · New York

LETTER
Synthesis of Bis(arylmethylidene)thiopyranones
2319
the same conditions and the course of the reaction was monitored by
TLC experiments. At the end of the reaction the product precipitat-
ed out at once due to the relative non-polarity of the product in the
polar reaction medium. The reaction mixture was diluted with
CH Cl , washed with 0.5 M HCl solution, and the organic layer was
(3Z,5Z)-3,5-Bis[(furan-2-yl)methylene]tetrahydrothiopyran-4-
one (3f)
Yellow crystals; yield: 94%; mp 155–157 °C.
IR (KBr): 1648, 1471, 1284, 747 cm–1.
2
2
1
H NMR (CDCl ): d = 4.04 (s, 4 H), 6.40–6.58 (m, 4 H), 7.35–7.49
dried over Na SO . Evaporation of the solvent led to crystallization
3
2
4
(
m, 4 H).
of the products which were further recrystallized from EtOAc. The
structure and geometry of the products were determined by their
physical and spectroscopic specifications and compared to those
13
C NMR (CDCl ): d = 29.7, 112.3, 117.4, 122.6, 129.9, 144.9,
3
1
52.0, 187.6.
1
6
available in the literature.
+
MS (70 eV): m/z (%) = 272 (M ), 244, 137, 106.
(
3Z,5Z)-3,5-Dibenzylidenetetrahydrothiopyran-4-one (3a)
(
3Z,5Z)-Tetrahydro-3,5-bis[(thiophen-2-yl)methylene]thio-
Yellow crystals; yield: 92%; mp 142–144 °C.
pyran-4-one (3g)
Yellow crystals; yield: 95%; mp 155–157 °C.
IR (KBr): 1646, 1582, 1281 cm–1.
–
1
IR (KBr): 1599, 1444, 1269 cm .
1
H NMR (CDCl ): d = 3.84 (s, 4 H), 7.30 (s, 10 H), 7.72 (s, 2 H).
3
1
3
C NMR (CDCl ): d = 30.0, 128.4, 128.7, 129.8, 133.7, 134.9,
1
3
H NMR (CDCl ): d = 3.90 (s, 4 H), 7.00–7.50 (m, 6 H), 7.86 (s, 2
3
1
36.6, 188.6.
H).
+
MS (70 eV): m/z (%) = 292 (M ), 147, 115.
13
C NMR (CDCl ): d = 29.5, 127.6, 129.4, 133.2, 138.3, 187.0.
3
+
MS (70 eV): m/z (%) = 304 (M ), 153, 122, 121.
(
3Z,5Z)-3,5-Bis(4-methoxybenzylidene)tetrahydrothiopyran-4-
one (3b)
(
3Z,5Z)-Tetrahydro-3,5-bis[(pyridine-3-yl)methylene]thio-
Yellow crystals; yield: 96%; mp 174–176 °C.
pyran-4-one (3h)
Yellow crystals; yield: 95%; mp 186–188 °C.
IR (KBr): 1723, 1557, 1273 cm–1.
–
1
IR (KBr) 1654, 1592, 1505, 1252 cm .
1
H NMR (CDCl ): d = 3.76 (s, 6 H), 3.80 (s, 4 H), 6.85 (d, 4 H,
3
J = 10 Hz), 7.30 (d, 4 H, J = 10 Hz), 7.66 (s 2 H).
1
H NMR (CDCl ): d = 3.78 (s, 4 H), 7.10–7.60 (m, 8 H), 8.51 (s, 2
3
1
3
C NMR (CDCl ): d = 30.2, 55.3, 114.1, 127.5, 131.9, 136.1, 160.2,
3
H).
1
85.4.
1
3
C NMR (CDCl ): d = 29.7, 123.2, 130.7, 133.0, 136.0, 136.6,
3
+
MS (70 eV): m/z (%) = 352 (M ), 278, 146, 103.
1
49.4, 150.3, 185.0.
+
MS (70 eV): m/z (%) = 294 (M ), 148, 117, 84.
(
3Z,5Z)-3,5-Bis(4-methylbenzylidene)tetrahydrothiopyran-4-
one (3c)
Yellow crystals; yield: 94% yield; mp 186–188 °C.
Acknowledgment
–
1
IR (KBr): 1657, 1595, 1275 cm .
Partial financial support by the Ministry of Science, Research,
and Technology of Iran is greatly appreciated. B. Mohebali is
acknowledged for conducting NMR experiments.
1
H NMR (CDCl ): d = 2.31 (s, 6 H), 3.84 (s, 4 H), 7.20–7.45 (m, 8
3
H), 7.68 (s 2 H).
1
3
C NMR (CDCl ): d = 21.4, 30.1, 129.1, 129.9, 132.4, 133.3, 136.8,
3
1
39.2, 185.5.
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MS (70 eV): m/z (%) = 320 (M ), 305, 147, 130, 115.
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