First highly efficient synthesis of bis(arylmethylidene)pyranones mediated by lithium perchlorate

Article abstract of DOI:10.1080/00397910500334447

A remarkably efficient double-crossed aldol condensation of tetrahydropyran-4-one with a variety of aromatic aldehydes is described at room temperature in the presence of (trimethylsilyl)diethylamine and lithium perchlorate under solvent-free conditions.

Full text of DOI:10.1080/00397910500334447

Synthetic Communicationsw, 36: 199–206, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500334447
First Highly Efficient Synthesis
of bis(Arylmethylidene)pyranones
Mediated by Lithium Perchlorate
M. Saeed Abaee, Mohammad M. Mojtahedi,
M. Mehdi Zahedi, and S. Mohammad Bolourtchian
Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
Abstract: A remarkably efficient double-crossed aldol condensation of tetrahydro-
pyran-4-one with a variety of aromatic aldehydes is described at room temperature
in the presence of (trimethylsilyl)diethylamine and lithium perchlorate under
solvent-free conditions. Excellent yields of 3,5-bis(arylmethylidene)pyranones are
achieved in a facile one-pot general procedure.
Keywords: bis(Arylmethylidene)pyranones, crossed aldol condensation, lithium per-
chlorate, pyrans, solvent-free
Crossed aldol condensation has been employed for the synthesis of bis(aryl-
methylidene)cycloalkanones by the reaction of homocyclic ketones with
aromatic aldehydes.[1] Many developments have been achieved in recent
years to enhance the synthetic scope of bis(arylmethylidene)cycloalkanones
by optimizing the reaction temperature, time, and yields of products.[2]
More improvements have been gained by application of KF-supported
reagents under microwave mediation and ultrasound irradiation.[3] Lewis
acid catalysis using Yb(OTf)3,[4] iodotrimethylsilane,[5] TiCl3(SO3CF3),[6]
RuCl3,[2b] Pd/C-Me3SiCl,[7] and SmI3[8]; InCl3 and FeCl3
in ionic
[9]
[10]
Received in Poland June 26, 2005
Address correspondence to M. Saeed Abaee, Chemistry and Chemical Engineering
Research Center of Iran, P.O. Box 14335-186, Tehran, Iran. Tel.: þ98-21-8036145;
Fax: þ98-21-8037185; E-mail: abaee@ccerci.ac.ir
199

200
M. S. Abaee et al.
liquids are also employed. However, many of these reactions suffer from
drawbacks such as reverse and side reactions or require harsh reaction con-
ditions. In addition, for similar reactions of tetrahydropyran-4-one 1, which
is a key precursor for a vast number of synthetic preparations,[11] there are
only a few preliminary scattered data available[12] and no spectroscopic struc-
tural characterization exists in the literature for 3,5-bisarylmethylidenes of
pyranones. We are interested in the development of the chemistry of hetero-
cyclics.[13] Substituted derivatives of tetrahydropyran-4-one 1 are useful
synthetic precursors and could be transformed to other heterocyclic struc-
tures.[14] Therefore, a mild general protocol for synthesis of the title structures
from ketone 1 is in demand. In recent years, mild Lewis acidic salts such as
lithium perchlorate have been widely used for various organic transform-
ations.[15] We decided to extend our previous experiences on the synthetic
application of iminium salts of aldehydes.[16] In the present article, a one-
pot synthetic pathway for double condensation of pyran 1 with aromatic
aldehydes in the presence of (trimethylsilyl)diethylamine (TMSNEt2) and
lithium perchlorate under solvent-free conditions is reported (Scheme 1).
Initially, treatment of benzaldehyde with TMSNEt2 and anhydrous
lithium perchlorate at room temperature facilitated in situ formation of the
corresponding iminium salt 2a because of the Lewis acidity of lithium ion
and high polarity of the reaction medium.[17] Subsequent addition of pyran
1 to the reaction mixture resulted in the formation of double-crossed aldol con-
densation product 3a at room temperature. The reaction was found to be
complete in about 3 h and the yield was 91% (Table 1, entry 1).
To test the chemoselectivity of the reaction, parallel reactions were
carried out using pyran/benzaldehyde ratios of 1 : 1 and 1 : 2. In both cases
the same product 3a was formed in comparable quantities. Other control
experiments were run to clarify the role of the reactants. A test reaction
conducted in the absence of TMSNEt2 gave no product. Omission of
lithium perchlorate from the reaction medium also led to complete recovery
of the starting materials. The generality of the method was demonstrated by
the synthesis of similar products (3b–h) using other aromatic aldehydes
Scheme 1.

Table 1. Reaction of pyran 1 with aromatic aldehydes in the presence of LiClO4 and TMSNEt2
Melting point (8C)
Yielda
(%)
Entry
1
Aldehyde
Product
Found
Reported
91
179–181
170–172
185–187[12a]
2
86
175–177[12a]
3
4
86
87
180–182
168–170
110[12b]
—
(continued)

Table 1. Continued
Melting point (8C)
Found Reported
Yielda
(%)
Entry
5
Aldehyde
Product
88
91
85
90
192–194
170–172
195–197
206–208
—
—
—
—
6
7
8
aIsolated yields.

Synthesis of bis(Arylmethylidene)pyranones
203
under the same conditions. All reactions proceeded rapidly at room
temperature and complete conversions were observed in less than 3 h. The
results are summarized in Table 1. Under present conditions, a sole product
is formed in each reaction and no other product normally observed under
classical aldol reactions is detected. The present one-pot protocol involves
mild reaction conditions, great efficiency, short reaction times, high product
yields, and use of inexpensive commercially available materials.
In conclusion, we have presented the first general and efficient synthetic
protocol for the preparation of 3,5-bis(arylmethylidene)pyranones at room
temperature. The generality of this versatile reaction makes it an attractive
addition to the present literature of pyrans chemistry. We are currently
exploring the feasibility of converting these products to other heterocyclic
systems. Extension of the results to the synthesis of bisarylmethylidenes of
other heterocyclic ketones is also underway. Caution: Although we did not
have any accidents using lithium perchlorate (LiClO4), it is advisable to dry
lithium perchlorate in a hood behind a laboratory shield.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded using KBr disks on a
Bruker Vector-22 infrared spectrometer. 1H NMR and 13C NMR spectra were
obtained on a Bruker AC 80-MHz instrument as CDCl3 solutions using TMS
as internal standard reference. Reagents were purchased from commercial
sources. Aldehydes were redistilled or recrystallized before use.
Typical Procedure for the Preparation
of bis(Arylmethylidene)pyranones
Pyranone 1 (1 mmol) was added to the mixture of the aldehyde (2 mmol),
LiClO4 (1 mmol), and TMSNEt2 (2 mmol), and the mixture was stirred at
room temperature. Reactions were monitored by TLC. After about 3 h, the
reactions were complete and the products precipitated out. The precipitates
were washed by 0.5 M of hydrochloric acid solution and brine. The precipi-
tates were recrystalized by means of ethyl acetate. Isolated yields of
products were 85–91%.
(3Z,5Z)-3,5-Dibenzylidene-tetrahydropyran-4-one (3a). Yellow crystals
were obtained in 91% yield, mp 179–1818C (reported mp 185–1878C)[12a]
;
IR (KBr, cm21) 1668, 1610, 1581; 1H NMR (CDCl3) d 4.87 (d, 4H,
J ¼ 2 Hz), 7.20–7.45 (m, 10H), 7.78 (t, 2H, J ¼ 2 Hz); 13C NMR (CDCl3):
d 68.6, 128.6, 129.3, 130.4, 133.2, 134.8, 136.4, 185.5; MS (70 eV) m/z
(%) 276 (Mþ), 144, 131, 115. Calcd. for C19H16O2: C, 82.6; H, 5.8. Found:
C, 82.2; H, 5.8.

204
M. S. Abaee et al.
(3b).
(3Z,5Z)-3,5-bis(4-Methoxybenzylidene)-tetrahydropyran-4-one
Yellow crystals were obtained in 86% yield, mp 170–1728C (reported mp
175–1778C)[12a]; IR (KBr, cm21) 1593, 1560, 1508; 1H NMR (CDCl3)
d 3.78 (s, 6H), 4.87 (d, 4H, J ¼ 2 Hz), 6.86 (d, 4H, J ¼ 9 Hz), 7.23 (d, 4H,
J ¼ 9 Hz), 7.72 (t, 2H, J ¼ 2 Hz); 13C NMR (CDCl3) d 55.4, 68.6, 114.2,
127.6, 131.5, 132.4, 135.6, 160.6, 185.4; MS (70 eV) m/z (%) 336 (Mþ),
305, 146, 131. Calcd. for C21H20O4: C, 75.0; H, 6.0. Found: C, 74.5; H, 6.0.
(3Z,5Z)-3,5-bis(4-Methylbenzylidene)-tetrahydropyran-4-one (3c). Yellow
crystals were obtained in 86% yield, mp 180–1828C (reported mp
1
1108C)[12b]; IR (KBr, cm21) 1665, 1605, 1508, 1266; H NMR (CDCl3)
d 2.32 (s, 6H), 4.87 (d, 4H, J ¼ 2 Hz), 7.16 (s, 8 H), 7.75 (t, 2H, J ¼ 2 Hz);
13C NMR (CDCl3) d 21.4, 68.6, 129.4, 130.7, 132.0, 132.4, 136.2, 139.7,
185.5; MS (70 eV) m/z (%) 304 (Mþ), 289, 130, 115. Calcd. for C21H20O2:
C, 82.9; H, 6.6. Found: C, 82.5; H, 6.6.
(3Z,5Z)-3,5-bis(4-Chlorobenzylidene)-tetrahydropyran-4-one (3d). Yellow
crystals were obtained in 87% yield, mp 168–1708C; IR (KBr, cm21) 1671,
1
1612, 1559, 1263, 1090; H NMR (CDCl3): d 4.80 (d, 4H, J ¼ 2 Hz), 7.25
(d, 4H, J ¼ 7 Hz), 7.40 (d, 4H, J ¼ 7 Hz), 7.70 (t, 2H, J ¼ 2 Hz); 13C NMR
(CDCl3) d 68.2, 128.0, 128.8, 131.4, 133.1, 133.3, 135.0, 188.4; MS (70 eV)
m/z (%) 344 (Mþ), 253, 141, 115. Calcd. for C19H14Cl2O2: C, 66.1; H, 4.1.
Found: C, 64.9; H, 4.3.
(3Z,5Z)-Tetrahydro-3,5-bis[(pyridine-3-yl)methylene]pyran-4-one (3e).
Yellow crystals were obtained in 88% yield, mp 192–1948C; IR (KBr,
1
cm21) 1672, 1616, 1272; H NMR (CDCl3) d 4.86 (d, 4H, J ¼ 2 Hz), 7.18–
7.70 (m, 8H), 8.50 (br s, 2H), 13C NMR (CDCl3) d 68.2, 123.4, 130.4,
132.8, 134.6, 136.9, 149.9, 150.9, 187.0; MS (70 eV) m/z (%) 278 (Mþ),
117, 90.
(3Z,5Z)-3,5-bis[(Furan-2-yl)methylene]-tetrahydropyran-4-one
(3f).
Yellow crystals were obtained in 91% yield, mp 170–1728C; IR (KBr,
1
cm21) 1665, 1268, 756; H NMR (CDCl3) d 4.97 (d, 4H, J ¼ 2 Hz), 6.57–
6.45 (m, 4H), 7.35–7.52 (m, 4H); 13C NMR (CDCl3) d 68.4, 112.6, 117.4,
121.1, 130.1, 145.5, 151.8, 187.0; MS (70 eV) m/z (%) 256 (Mþ), 134,
115, 106, 78.
(3Z,5Z)-Tetrahydro-3,5-bis[(thiophen-2-yl)methylene]pyran-4-one (3 g).
Yellow crystals were obtained in 85% yield, mp 195–1978C; IR (KBr,
1
cm21) 1662, 1592, 1186; H NMR (CDCl3): 4.90 (d, 4H, J ¼ 2 Hz), 7.00–
7.50 (m, 6H), 7.87 (br s, 2H); 13C NMR (CDCl3) d 68.3, 127.9, 128.2,
130.9, 133.3, 138.3, 184.2; MS (70 eV) m/z (%) 288 (Mþ), 260, 122.
Calcd. for C15H12O2S2: C, 62.5; H, 4.2. Found: C, 52.0; H, 4.3.
(3Z,5Z)-Tetrahydro-3,5-bis[(E)-3-phenylallylidene]tetrahydropyran-4-one
(3 h). Orange crystals were obtained in 90% yield, mp 206–2088C; IR (KBr,
1
cm21) 1734, 1660, 1587, 1216; H NMR (CDCl3) d 4.77 (d, 4H, J ¼ 2 Hz),

Synthesis of bis(Arylmethylidene)pyranones
205
6.80–7.80 (m, 16H); 13C NMR (CDCl3) d 67.3, 122.0, 127.4, 127.9, 128.2,
132.2, 134.8, 137.4, 142.6, 187.2; MS (70 eV) m/z (%) 328 (Mþ), 209,
141, 128, 115. Calcd. for C23H20O2: C, 84.1; H, 6.1. Found: C, 83.6; H, 6.1.
ACKNOWLEDGMENT
Partial financial support by the Ministry of Science, Research, and Technology
of Iran is greatly appreciated. B. Mohebali is also acknowledged for conduct-
ing NMR experiments.
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