Chemistry Letters Vol.34, No.4 (2005)
577
amount of oligomer 516 which was generated by the addition
of acetophenone to 4 (Entries 8–10). The yields of chalcone 4
were decreased by the formation of polymers for the reactions
of 4-nitrobenzaldehyde with acetophenone (Entries 14–16). In
these cases, the best yields were obtained when PEG400 was
employed (Entries 8 and 14). When CTACl was used as an
additive, yields of 4 were lower compared to those of PEG400
Table 2. Reactions of cycloalkanones with aldehydes 1 in water
a
in the presence of PEG400
Additiveb
Aldehyde 1
Yield/%
Entry Ketone
Time
Ar
(equiv.)
8
9
10 11
1
2c
6
4-MeOC H4
6
A (0.1)
A (1)
3 h
0
40 28
—
—
—
—
—
1 h
0
0
93
3
4-MeC6H4
A (0.1)
A (1)
3 h
0
42 23
4c
5
1 h
0
39
0
90
0
(Entries 10 and 16). For the other examples, chalcones 4 were
yielded in good yields using 0.1 equiv. of PEG400 (Entries 11,
Ph
A (0.1)
30 min
26
(
50:50)d
12, 13, 23, and 24).
To check the reusability of the PEG400-NaOH system, the
6c
A (1)
1 h
0
0
98
0
—
—
7
B (0.1)
30 min
41
(50:50)d
22
filtrate was evaporated and used for the next experiment. This
system was reused without significant loss of activities (Entries
8d
B (1)
30 min
1 h
30
50:50)d
38
22
45
0
0
0
—
—
—
—
(
(
(
18–20).
9
C (0.2)
C (2)
41
50:50)d
Next, the reactions of cycloalkanones with various aromatic
aldehydes were examined. The results are shown in Table 2. We
chose the reaction of cyclohexanone (6) with benzaldehyde (1)
as a model reaction. Intermediate aldol 8 (erythro:threo =
0c
1
2 h
27
50:50)d
11
4-ClC H4
6
A (0.1)
15 min
31
(50:50)d
34 33
,17
4,17
5
(
1
0:50)4 (31%) and (E)-2-benzylidenecyclohexanone (9)
35%) were isolated from the reaction at room temperature for
5 min in EtOH–H2O (1:1). When 0.1 equiv. of PEG400 was
1
1
1
1
1
2c
3c
4c
5c
6c
A (0.1)
A (1)
30 min
20 min
40 min
30 min
15 min
0
0
0
0
0
0
0
0
0
0
90
—
—
—
—
—
90
98
99
97
7
4-MeOC6H4
4-MeC6H4
Ph
A (1)
used, compounds 8 and 9 were obtained in 39 and 26% yields,
respectively (Entry 5). Without PEG400, the reaction proceeded
slowly to give 8 and 9 after 24 h in 43 and 19% yields, respec-
tively. The reaction of 6 with 2 equiv. of benzaldehyde in the
A (1)
4-ClC6H4
A (0.1)
aReagents and conditions: Ketone 10 mmol, 1 10 mmol, NaOH 10 mmol, H2O 2 mL,
room temp. bA, PEG400; B, PEG500DME; C, PEG250DME. c2 equiv. of aldehydes
were used. derythro:threo ratio of compound 8.
presence of 1 equiv. of PEG400 yielded dibenzylidenecyclohex-
anone (10)1
8,19
in 98% yield (Entry 6). The use of 1 equiv. of
methodology for the synthesis of chalcones and 2,6-bis(aryl-
methylidene)cycloalkanones using PEG400. In this convenient
methodology, side reactions were avoided and high yields were
achieved.
PEG500DME did not give 10 but a mixture of 8 (30%) and 9
38%) (Entry 8). When PEG250DME was added instead of
PEG500DME, compounds 8 and 9 were produced more slowly
Entries 9 and 10). The selectivity (50:50), shown by the
(
(
erythro:threo ratio of 8 obtained in the cases of PEG400,
PEG500DME, and PEG250DME, was the same as that in the
conventional solvent, EtOH–H2O (1:1). The reactions of 6 with
References and Notes
1
2
C. P. Mehnert, N. C. Dispenziere, and R. A. Cook, Chem. Commun., 2002, 1610.
S. Chandrasekhar, Ch. Narsihmulu, S. S. Sultana, and N. R. Reddy, Chem.
Commun., 2003, 1716.
2
equiv. of the other aromatic aldehydes 1 using 1 equiv. of
PEG400 completed within 1 h to give 10 in excellent yields
Entries 2 and 4). In the case of 4-chlorobenzaldehyde, 0.1
3
4
5
6
7
8
9
1
B. M. Choudary, K. Jyothi, S. Madhi, and M. L. Kantam, Synlett, 2004, 231.
F. Toda, K. Tanaka, and K. Hamai, J. Chem. Soc., Perkin Trans. 1, 1990, 3207.
S. Iimura, K. Manabe, and S. Kobayashi, J. Org. Chem., 68, 8723 (2003).
V. Dryanska and C. Ivanov, Tetrahedron Lett., 41, 3519 (1975).
M. Zeheng, L. Wang, J. Shao, and Q. Zhong, Synth. Commun., 27, 351 (1997).
J. Deli, T. Lorand, D. Szabo, and A. Foldesi, Pharmazie, 39, 539 (1984).
F. Fringuelli, G. Pani, O. Piermatti, and F. Pizzo, Tetrahedron, 50, 11499 (1994).
Z. Zhang, Y.-W. Dong, and G.-W. Wang, Chem. Lett., 32, 966 (2003).
(
equiv. of PEG400 was sufficient for the exclusive production
of 10 (Entry 12). For the reactions of 6 with 4-nitrobenzalde-
hyde, only polymeric materials were obtained. This method
was further applied to the condensation of cyclopentanone (7)
with various aldehydes. Bis(arylmethylidene)cyclopentanones
0
11 K. Tanemura, T. Suzuki, Y. Nishida, K. Satsumabayashi, and T. Horaguchi,
Synth. Commun., in press.
1
2
3
For condensation of arylacetonitriles with aromatic aldehydes in toluene, see:
B. Zupancic and M. Kokalj, Synthesis, 1981, 913.
ˇ ˇ
A typical procedure is as follows: to a mixture of ketone 2 (1.2 g, 10 mol), NaOH
(11) were isolated in excellent yields (Entries 13–16).
1
O
O
OH
Ar
O
O
(400 mg, 10 mmol), and PEG400 (400 mg, 1 mmol) in water (2 mL) was added
aldehyde 1 (1.2 g, 10 mmol). After stirring at room temperature for 1 h, the mix-
ture was poured into water (25 mL). The solid product was collected by filtration,
washed with water, and dried to give 4 (2.2 g, 97%). Recrystallizaion from EtOH
gave higher purity of the product (Table 1, Entry 11).
Ar
Ar
Ar
n
n
n
n
1
4
G. Powers, D. S. Casebier, D. Fokas, W. J. Ryan, J. R. Troth, and D. L. Coffen,
Tetrahedron, 54, 4085 (1998).
15 K. Watanabe and A. Imazawa, Bull. Chem. Soc. Jpn., 55, 3208 (1982).
6
7
n = 1
n = 0
8 n = 1
9 n = 1
10 n = 1
11 n = 0
ꢁ
1
6
Compound 5: mp 92–93 C; IR (KBr) 3064, 2900, 2836, 1682, 1598, 1516, 1238,
ꢂ1
In fact, the products can be isolated in practically pure form
1
1
036, 816, 760 cm ; H NMR (500 MHz, CDCl3): ꢀ 3.31 (2H, dd, J ¼ 16:5 and
simply by filtration. If the products were liquid, lathering was not
observed in the extraction with EtOAc. On the other hand, phase
separation is often difficult because of lathering when surfactants
such as CTACl were employed. PEG400 is a cheap and relative-
ly safe compound compared to surfactants or other phase transfer
catalysts [LD50 (rats) of PEG400 = 30 mL/kg].20 In addition,
PEG400 possesses low vapor pressure. These facts indicate that
PEG400 is a highly suitable additive.
7.0 Hz), 3.46 (2H, dd, J ¼ 16:5 and 7.0 Hz), 3.74 (3H, s), 4.02 (1H, t, J ¼ 7:0
Hz), 6.80 (2H, d, J ¼ 8:5 Hz), 7.19 (2H, d, J ¼ 8:5 Hz), 7.43 (4H, dd, J ¼ 8:0
13
and 8.0 Hz), 7.52 (2H, dd, J ¼ 8:0 and 1.0 Hz) and 7.93–7.95 (4H, m); C NMR
(
125 MHz, CDCl3): ꢀ 36.5, 45.1, 55.2, 114.0, 128.1, 128.4, 128.6, 133.0, 135.8,
136.9, 158.2, 198.7. Anal. Calcd for C24H22O3: C, 80.4; H, 6.2%. Found: C,
0.1; H, 6.3%.
8
1
7
H. O. House, D. S. Crumrine, A. Y. Teranishi, and H. D. Olmstead, J. Am. Chem.
Soc., 95, 3310 (1973).
18
19
20
N. Iranpoor and F. Kazemi, Tetrahedron, 54, 9475 (1998).
Y. Zhu and Y. Pan, Chem. Lett., 33, 668 (2004).
‘‘Merck Index,’’ 12th ed., ed. by S. Budavari, Merck & Co., New Jersey
(1996), p 7733.
In conclusion, we constituted an environmentary friendly
Published on the web (Advance View) March 19, 2005; DOI 10.1246/cl.2005.576