An improved synthesis of (E)-cinnamic acid derivatives via the Claisen-Schmidt condensation

Article abstract of DOI:10.1081/SCC-120015773

A variety of (E)-cinnamic acid derivatives are prepared in high yields through the Claisen-Schmidt condensation in the presence of sodium metal and a catalytic amount of methanol with toluene employed as the co-solvent.

Full text of DOI:10.1081/SCC-120015773

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An Improved Synthesis of ( E )-Cinnamic Acid
Derivatives via the Claisen–Schmidt Condensation
a
a
a
Masanori Hatsuda , Tooru Kuroda & Masahiko Seki
a
Product and Technology Development Laboratory, Tanabe Seiyaku Co., Ltd., Kashima,
Yodogawa-ku, Osaka, Japan
Version of record first published: 17 Aug 2006.
To cite this article: Masanori Hatsuda, Tooru Kuroda & Masahiko Seki (2003): An Improved Synthesis of ( E )-Cinnamic
Acid Derivatives via the Claisen–Schmidt Condensation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:3, 427-434
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 3, pp. 427–434, 2003
An Improved Synthesis of (E )-Cinnamic Acid
Derivatives via the Claisen–Schmidt Condensation
Masanori Hatsuda, Tooru Kuroda, and Masahiko Seki*
Product and Technology Development Laboratory, Tanabe Seiyaku
Co., Ltd., Kashima, Yodogawa-ku, Osaka, Japan
ABSTRACT
A variety of (E )-cinnamic acid derivatives are prepared in high yields
through the Claisen–Schmidt condensation in the presence of sodium
metal and a catalytic amount of methanol with toluene employed as
the co-solvent.
(E )-Cinnamic acid derivatives 1 have received a considerable atten-
tion because of their significant use as a sunscreen agent in cosmetic skin
[
and hair care formulations and a starting material for biologically
1]
[2]
active compounds. We have recently reported a novel synthesis of
methyl (2R, 3S)-3-(4-methoxyphenyl)glycidate 2, akey intermedi at e for
diltiazem (3) (Sch. 1), through a catalytic asymmetric epoxidation of
*
Correspondence: Masahiko Seki, Product and Technology Development
Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa-ku,
Osaka 532-8505, Japan; E-mail: m-seki@tenabe.co.jp.
4
27
DOI: 10.1081/SCC-120015773
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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28
Hatsuda, Kuroda, and Seki
Scheme 1.
[
2b]
methyl (E )-4-methoxycinnamate 1a (R ¼ 4-methoxyphenyl).
In order
to reduce the cost of raw materials of 3, an economical synthesis of 1a has
been highly desirable.
Several methods have been reported concerning the synthesis of 1,
which involve the Claisen–Schmidt condensation of aldehydes with
[
3]
[4]
acetates, the Knoevenagel reaction of aldehydes with malonic acid,
the Wittig reaction of aldehydes with a phosphorus ylide derived from
[5]
a-bromoacetate, and, as a more recent method, the Heck reaction
[
6]
between aryl halides and acrylates. Considering the cost of the reagents
and ease of operation especially on a practical large-scale preparation,
the synthesis of 1 through the Claisen–Schmidt condensation should be
most promising. Reported herein is an efficient synthesis of 1 through
an optimized Claisen–Schmidt condensation of aldehydes with methyl
acetate.
Our initial study was performed on the synthesis of methyl (E )-4-
methoxycinnamate 1a using the original experimental procedure
[
3a]
described by Claisen.
metal in methyl acetate at 25 C for 17 h afforded 1a in 68% yield
Treatment of p-anisaldehyde with sodium
ꢀ
(
Method A) (Table 1, Entry 1). The procedure has, however, drawbacks
of poor reproducibility as well as the poor yield. Although the use of
[1]
sodium methoxide in place of sodium metal greatly improved the yield
90% yield) (Method B) (Table 1, Entry 2), a large amount of expensive
(
methyl acetate (8.1 equiv.) was necessary because of the poor solubility of
the product 1a. The clever use of sodium metal in combined with a
catalytic amount of ethanol in ethyl acetate permitted an in situ genera-
tion of the alcoholate to afford, when reacted with benzaldehyde, ethyl
[
3b]
(
E )-cinnamate in good yield. The limited use of ethanol was suggested
to prevent the Cannizzarro reaction, i.e., the concomitant formation of

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(
E )-Cinnamic Acid Derivatives
429
Table 1. Optimization of the Claisen–Schmidt condensation.
b
AcOMe Toluene
a
(equiv.) (v/w)
T
( C)
t
(h)
Yield
(%)
a
ꢀ
Entry Method
Base (equiv.)
Na(1.0)
NaOMe (1.3)
Na/MeOH (1.3/0.05)
Na/MeOH (1.3/0.2)
1
2
3
4
A
B
C
D
4.8
8.1
4.7
2.2
0
0
0
3.7
25 17
68
90
78
87
50–55
0–5
1
2
c
20–30 20
a
Volume (mL) of toluene per weight (g) of p-anisaldehyde.
Isolated yield.
b
benzylalcohol and benzoic acid from benzaldehyde. The procedure was
applied to the synthesis of 1a using p-anisaldehyde and methyl acetate
(Method C) (Table 1, Entry 3). However, the yield (78%) was not
satisfactory possibly due to the solubility problem of 1a.
We envisioned a possible use of an inexpensive toluene as the
co-solvent for the condensation in order to reduce the amount of methyl
acetate. The reaction was thus conducted by treating p-anisaldehyde with
methyl acetate (2.2 equiv.) in toluene in the presence of sodium metal (1.3
ꢀ
equiv.) and a catalytic amount of methanol (0.2 equiv.) at 30 C for 20 h.
Since partial hydrolysis (ca. 5%) of 1a was accompanied during the
reaction, the reaction mixture was refluxed in sulfuric acid-methanol
for 2 h before the aqueous work-up and crystallization. Through this
treatment, the desired 1a was isolated with high purity and in excellent
yield (87%) (Method D) (Table 1, Entry 4). It should be noted that the
use of toluene as the co-solvent not only reduced the amount of methyl
acetate but also improved the yield of 1a (Table 1, Entry 4 vs. 3). The
present procedure (Method D) is additionally advantageous in that it can
be conducted at ambient temperature without need for strict control of
the reaction temperature as in Method C.
The optimized procedure (Method D) was applied to the reaction of
the other aldehydes with methyl acetate (Table 2). Benzaldehyde deriva-
tives with an electron-donating or an electron-withdrawing group and
2-naphthaldehyde afforded corresponding methyl (E )-cinnamate deriva-

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30
Hatsuda, Kuroda, and Seki
tives 1b–e in high yields (Table 2, Entries 2–5). Heteroaromatic aldehydes
carrying 2-furyl or 2-thienyl group exerted high reactivity toward the
condensation to afford the desired unsaturated esters 1f, g in excellent
yields (Table 2, Entries 6 and 7). A non-enolizable alkyl aldehyde such as
trimethylacetaldehyde as well provided the desired product 1h in
[
7]
satisfactory yield (63%) (Table 2, Entry 8).
In conclusion, an efficient synthetic procedure of methyl (E )-cinna-
mate derivatives was developed by optimizing the reaction conditions for
the Claisen–Schmidt condensation. The use of inexpensive reagents and
mild reaction conditions that are amenable for a large-scale preparation
Table 2. Synthesis of (E )-cinnamic acid derivatives 1a–h viathe improved
Claisen–Schmidt condensation.
a
Entry
1
Aldehyde
Product
Yield (%)
87
2
3
93
89
4
5
78
90
6
7
93
95
63
b
8
a
Isolated yield.
The product was isolated as a carboxylic acid.
b

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(
E )-Cinnamic Acid Derivatives
431
permitted a practical access to the target compounds of recent synthetic
importance.
EXPERIMENTAL
1
13
Melting points are uncorrected. H- and C-NMR spectra(400 an d
00 MHz, respectively) were recorded with tetramethylsilane as an inter-
1
nal standard. Silica gel column chromatography was performed using
Kieselgel 60 (E. Merck). Thin-layer chromatography (TLC) was carried
out on E. Merck 0.25 mm precoated glass-backed plates (60 F254).
Development was accomplished using 5% phosphomolybdic acid in etha-
nol-heat or visualized by UV light where feasible. The solvents and the
reagents were used as received.
Typical Procedures for the Condensation of
Aldehydes with Methyl Acetate
Synthesis of Methyl (E )-4-Methoxycinnamate (1a)
Method A: Sodium metal (1 g, 0.044 mol) was suspended in toluene
(
10 mL), and the mixture was refluxed for 10 min. The solvent was
removed by decantation, and methyl acetate (21 mL) and p-anisaldehyde
5.82 g, 0.043 mol) were added. The mixture was stirred at room tempera-
(
ture for 17 h and acetic acid (0.38 mL) was added dropwise under cooling
with ice-water. To the mixture were added water and AcOEt, and the
organic layer was washed with water, dried (MgSO ), and evaporated.
4
The crystals formed were collected by adding hexane to afford 1a (5.55 g,
68%) as brown crystals.
Method B: To asuspension of sodium methoxide (70.2 g, 1.3 mol) in
methyl acetate (817 mL) was dropwise added p-anisaldehyde (136.2 g,
ꢀ
ꢀ
1
1
3
mol) a t <40 C for 25 min and the mixture was stirred at 50–55 C for
ꢀ
h. The mixture was treated with water (409 mL) at <30 C and stirred at
ꢀ
0 C for 30 min. The organic layer was separated and evaporated. To the
residue was added MeOH (136 mL) and the solvent was removed by
ꢀ
evaporation. The residue dissolved in MeOH (409 mL) at 60 C wa s
ꢀ
cooled down to 55 C and a seed of 1a was added. The mixture was stirred
ꢀ
ꢀ
at 50–55 C for 30 min and cooled down to 10 C for 1 h. The crystals
ꢀ
formed were collected and dried at 50 C for 17 h to afford 1a (173.1 g,
90%) as colorless crystals.

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Hatsuda, Kuroda, and Seki
Method C: Sodium metal (2.9 g, 0.126 mol) cut in small pieces was
suspended in xylene (40 mL), and the mixture was heated until sodium
had melted. The mixture was cooled to room temperature and stirring
was continued until the sodium had solidified in very fine particles. The
solvent was removed by decantation, and methyl acetate (37.4 mL,
0.47 mol) and methanol (0.21 mL, 5.2 mmol) were added. To a stirred
suspension of the mixture was added p-anisaldehyde (13.6 g, 0.1 mol)
ꢀ
ꢀ
for 2 h at 0–5 C. After the mixture was stirred at 0–5 C for 2 h, the
mixture was treated carefully with AcOH (9 mL) and water (50 mL).
The resulting mixture was extracted with AcOEt (50 mL Â 2), dried
(
(
MgSO ) and evaporated. The residue was dissolved in methanol
4
24 mL) under reflux, and water (10 mL) was added dropwise to the
ꢀ
mixture. Then the mixture was gradually cooled down to 15 C and stirred
ꢀ
a t 15C for 1 h. The crystals formed were collected, washed with a mixed
ꢀ
solvent of methanol and water (MeOH/H O ¼ 7:3) and dried at 50 C for
2
1
3 h to afford 1a (15.1 g, 78%) as slightly yellow crystals.
Method D: To amixture of meth an ol (0.64 g, 0.020 mol) an d methyl
acetate (16.3 g, 0.22 mol) was added sodium metal (2.9 g, 0.126 mol) cut in
ꢀ
small pieces under stirring at 25 C. After adding p-anisaldehyde (13.6 g,
ꢀ
0
.1 mol) in toluene (50 mL) to the mixture at 30–35 C for 0.5 h, the
ꢀ
mixture was stirred at 30 C for 20 h. The mixture was treated with metha-
nol (40 mL) and sulfuric acid (18.6 g, 0.19 mol) and refluxed for 2 h. After
the solvent was partially evaporated (ca. 30 mL), the mixture was washed
with water (50 mL), dried (MgSO ) and evaporated. The residue was
4
dissolved in methanol (24 mL) under reflux, and water (10 mL) was
added dropwise to the mixture. Then the mixture was gradually cooled
ꢀ
ꢀ
down to 15 C and stirred at 15 C for 1 h. The crystals formed were
collected, washed with a mixed solvent of methanol and water
ꢀ
(
MeOH/H O ¼ 7:3) and dried at 50 C for 17 h to afford 1a (16.9 g,
2
ꢀ
[5b]
ꢀ
1
88–89 C); H-NMR
8
7%) as colorless crystals. M.p. 87–88 C (Lit.
(
2
(
CDCl ) ꢀ 7.65 (d, J ¼ 16.0 Hz, 1H), 7.49–7.45 (m, 2H), 6.92–6.88 (m,
3
1
3
H), 6.31 (d, J ¼ 16.0 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H); C-NMR
CDCl ) ꢀ 168.1 (s), 161.8 (s), 144.9 (d), 130.1 (d), 127.5 (s), 115.7 (d),
3
1
8
14.7 (d), 55.7 (q), 51.9 (q); IR (KBr) 1718, 1639, 1604, 985, 839,
À1
þ
24 cm ; MS m/z 192 (M ).
The compounds 1b–g were prepared according to method D.
ꢀ
[8]
Methyl (E )-cinnamate (1b): Yield 93%; m.p. 34–36 C (Lit.
ꢀ
1
3
2
4–35 C); H-NMR (CDCl ) ꢀ 7.70 (d, J ¼ 16.0 Hz, 1H), 7.55–7.48 (m,
3
1
3
H), 7.45–7.34 (m, 3H), 6.44 (d, J ¼ 16.0 Hz, 1H), 3.81 (s, 3H); C-NMR
(
CDCl ) ꢀ 167.8 (s), 145.3 (d), 134.8 (s), 130.7 (d), 129.3 (d), 128.5 (d),
3
À1 þ
18.2 (d), 52.1 (q); IR (KBr) 1720, 1638, 981, 769 cm ; MS m/z 162 (M ).
1

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(
E )-Cinnamic Acid Derivatives
433
ꢀ
Methyl (E )-4-methylcinnamate (1c): Yield 89%; m.p. 56–58 C
ꢀ
[5b]
Lit.
1
(
(
56–57 C); H-NMR (CDCl ) ꢀ 7.67 (d, J ¼ 16.0 Hz, 1H), 7.42
3
d, J ¼ 8.1 Hz, 2H), 7.19 (d, J ¼ 8.0 Hz, 2H), 6.40 (d, J ¼ 16.0 Hz, 1H),
1
3
3
.80 (s, 3H), 2.37 (s, 3H); C-NMR (CDCl ) ꢀ 167.6 (s), 144.9 (d), 140.7
3
(
1
s), 130.7 (s), 129.6 (d), 128.1 (d), 116.7 (d), 51.6 (q), 21.5 (q); IR (KBr)
À1
þ
712, 1634, 818 cm ; MS m/z 176 (M ).
Methyl (E )-4-chlorocinnamate (1d): Yield 78%; m.p. 74–76 C (Lit.
ꢀ
[5b]
ꢀ
1
7
3–75 C); H-NMR (CDCl ) ꢀ 7.64 (d, J ¼ 16.0 Hz, 1H), 7.46 (dd,
3
J ¼ 6.4, 2.1 Hz, 2H), 7.35 (dd, J ¼ 6.4, 1.9 Hz, 2H), 6.41 (d, J ¼ 16.0 Hz,
1
3
1
1
1
H), 3.81 (s, 3H); C-NMR (CDCl ) ꢀ 167.6 (s), 143.8 (d), 136.6 (s),
3
33.3 (s), 129.6 (d), 129.6 (d), 118.8 (d), 52.2 (q); IR (KBr) 1710, 1635,
À1
þ
006, 821 cm ; MS m/z 196 (M ).
Methyl (E )-2-(2-naphthyl)propenoate (1e): Yield 90%; m.p. 91–92 C
ꢀ
[9]
ꢀ
Lit. 91–92 C); H-NMR (CDCl ) ꢀ 7.93 (s, 1H), 7.88–7.82 (m, 4H),
3
1
(
7
1
1
1
8
.66 (dd, J ¼ 1.7, 8.6 Hz, 1H), 7.52–7.50 (m, 2H), 6.55 (d, J ¼ 16.0 Hz,
1
3
H), 3.83 (s, 3H); C-NMR (CDCl ) ꢀ 167.9 (s), 145.3 (d), 134.6 (s),
3
33.7 (s), 132.3 (s), 130.4 (d), 129.1 (d), 129.0 (d), 128.2 (d), 127.6 (d),
27.1 (d), 123. 9 (d), 118.3 (d), 52.1 (q); IR (KBr) 1736, 1716, 1649, 984,
À1
þ
26 cm ; MS m/z 212 (M ).
Methyl (E )-2-(2-fulyl)propenoate (1f ) : Yield 93%; oil; H-NMR
CDCl ) ꢀ 7.48 (d, J ¼ 1.7 Hz, 1H), 7.44 (d J ¼ 15.8 Hz, 1H), 6.61 (d,
[
10]
1
(
3
J ¼ 3.3 Hz, 1H), 6.47 (dd, J ¼ 1.9, 3.4 Hz, 1H), 6.32 (d, J ¼ 15.6 Hz,
1
3
1
1
1
H), 3.79 (s, 3H); C-NMR (CDCl ) ꢀ167.9 (s), 151.3 (s), 145.1 (d),
3
31.6 (d), 115.8 (d), 115.2 (d), 112.7 (d), 52.0 (q); IR (KBr) 1718, 1642,
À1
þ
018, 764 cm ; MS m/z 152 (M ).
Methyl (E )-2-(2-thienyl)propenoate (1g): Yield 95%; 47–48 C (Lit.
ꢀ
[9]
ꢀ
1
4
0–41 C); H-NMR (CDCl ) ꢀ 7.79 (d, J ¼ 15.7 Hz, 1H), 7.37
3
(
6
d, J ¼ 4.3 Hz, 1H), 7.26–7.25 (m, 1H), 7.05 (dd, J ¼ 3.7, 5.1 Hz, 1H),
1
3
.24 (d, J ¼ 15.7 Hz, 1H), 3.79 (s, 3H); C-NMR (CDCl ) ꢀ 167.7 (s),
3
1
39.9 (s), 137.7 (d), 131.3 (d), 128.8 (d), 128.5 (d), 116.9 (d), 52.1 (q); IR
À1
þ
(
KBr) 1711, 1627, 992, 856, 839, 708 cm ; MS m/z 168 (M ).
E )-4,4-Dimethyl-2-pentenoic acid (1h): To asolution of meth an ol
(
0.64 g, 0.020 mol) and methyl acetate (16.3 g, 0.22 mol) was added
(
ꢀ
sodium metal (2.9 g, 0.126 mol) cut in small pieces under stirring at 25 C.
After adding trimethylacetaldehyde (8.6 g, 0.1 mol) in toluene (50 mL)
ꢀ
ꢀ
to the mixture at 30–35 C for 0.5 h, the mixture was stirred at 30 C for
0 h. The mixture was treated with methanol (40 mL) and 5 N aq. NaOH
40 mL, 0.2 mol) and stirred overnight. After the solvent was evaporated,
2
(
the residue was acidified to pH 1 with 10% aq. HCl and then extracted with
AcOEt (50 mL). The extract was dried (MgSO ) and evaporated. The
4
residue was chromatographed on silica gel (hexane/AcOEt ¼ 4:1) to

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34
Hatsuda, Kuroda, and Seki
ꢀ
[11]
afford 1h (8.0 g, 63%) as colorless crystals. M.p. 61–62 C (Lit.
ꢀ
1
6
2–62.5 C); H-NMR (CDCl ) ꢀ 7.09 (d, J ¼ 15.8 Hz, 1H), 5.75 (d,
3
1
3
J ¼ 15.9 Hz, 1H), 1.10 (s, 9H); C-NMR (CDCl ) ꢀ 173.2 (s), 162.3 (d),
3
À1
116.5 (d), 34.3 (s), 28.9 (q); IR (KBr) 1693, 1651, 994, 923, 878 cm ; MS
m/z 128 (M ).
þ
REFERENCES
1
2
. Thoemel, F.; Hoffmann, W.; Degner, D. Use of Etherified
p-Hydroxycinnamic Acid Esters as Sunscreens. Eur. Pat. Appl. EP
4,976, February 3, 1982.
. (a) Gou, D.-M.; Liu, Y.-C.; Chen, C.-S. J. Org. Chem. 1993, 58 (5),
287–1289; (b) Seki, M.; Furutani, T.; Imashiro, R.; Kuroda, T.;
4
1
Yamanaka, T.; Harada, N.; Arakawa, H.; Kusama, M.;
Hashiyama, T. Tetrahedron Lett. in press.
. (a) Claisen, L. Chem. Ber. 1890, 23, 976–978; (b) Marvel, C.S.;
3
King, W.O. Org. Synth. Coll. 1941, 1, 252–254.
4
5
. Johnson, A.L. J. Org. Chem. 1976, 41 (8), 1320–1324.
. (a) Patil, V.J.; Mavers, U. Tetrahedron Lett. 1996, 37 (8),
1
2
281–1284; (b) Schiemenz, G.P.; Thobe, J. Chem. Ber. 1966, 99 (8),
663–2668.
6
. For arecent ex am ple, see: Gruber, A.S.; Pozebon, D.; Monteiro,
A.L.; Dupont, J. Tetrahedron Lett. 2001, 42 (42), 7345–7348 and
references therein.
7
. Because of the problem of a low boiling point of the methyl ester
ꢀ
[5a]
b.p. ¼ 160–162 ), the product was isolated as an carboxylic acid.
(
8. Staab, H.A.; Mannschreck, A. Chem. Ber. 1962, 95 (5), 1284–1297.
. Heck, R.F. J. Am. Chem. Soc. 1968, 90 (20), 5518–5526.
9
1
1
0. Rodriguez, J.; Waegell, B. Synthesis 1988, (7), 534–535.
1. Larock, R.C. J. Org. Chem. 1975, 40 (22), 3237–3242.
Received in Japan October 15, 2001