Microwave-Assisted Solvent-Free Synthesis of trans-Cinnamic Acids Using Lithium Chloride as Catalyst

Article abstract of DOI:10.1081/SCC-120027254

A simple and efficient procedure has been developed for the synthesis of trans-cinnamic acids 3 by the condensation of aromatic aldehydes 1 with malonic acid 2 using LiCl as catalyst under solvent-free conditions using microwave irradiation. The products are obtained in excellent yields and in a state of high purity.

Full text of DOI:10.1081/SCC-120027254

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Microwave-Assisted Solvent-Free Synthesis of trans-
Cinnamic Acids Using Lithium Chloride as Catalyst
K. Mogilaiah a & G. Randheer Reddy a
a Department of Chemistry, Kakatiya University, Warangal, 506 009, India
Available online: 18 Oct 2011
To cite this article: K. Mogilaiah & G. Randheer Reddy (2004): Microwave-Assisted Solvent-Free Synthesis of trans-
Cinnamic Acids Using Lithium Chloride as Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:2, 205-210
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 2, pp. 205–210, 2004
Microwave-Assisted Solvent-Free Synthesis
of trans-Cinnamic Acids Using Lithium
Chloride as Catalyst
*
K. Mogilaiah and G. Randheer Reddy
Department of Chemistry, Kakatiya University, Warangal, India
ABSTRACT
A simple and efficient procedure has been developed for the synthesis of
trans-cinnamic acids 3 by the condensation of aromatic aldehydes 1 with
malonic acid 2 using LiCl as catalyst under solvent-free conditions using
microwave irradiation. The products are obtained in excellent yields and
in a state of high purity.
Key Words: trans-Cinnamic acids; Lithium chloride; Microwave-
assisted synthesis; Solvent-free.
Knoevenagel condensation of malonic acid with carbonyl compounds is
an important route for substituted a,b-unsaturated acids and the method of
*
Correspondence: K. Mogilaiah, Department of Chemistry, Kakatiya University,
Warangal, 506 009, India; E-mail: mogilaiah_k@yahoo.co.in.
205
DOI: 10.1081/SCC-120027254
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Mogilaiah and Reddy
choice particularly for cinnamic acids is through Doebner modification.[1]
This involves heating aromatic aldehydes and malonic acid in presence of
excess of basic solvents like pyridine and piperidine to facilitate easy
decarboxylation of initially generated a,b-unsaturated malonic acids which
affords cinnamic acids. There has been a number of reports[2] on the
condensation of carbonyl substrates with a variety of active methylene
compounds using inorganic catalysts, both under conventional as well as
microwave heating conditions. However, application of such nonconventional
methods for the condensation of malonic acid with carbonyl compounds is
scarce.
Microwave-assisted organic synthesis is a new and quickly growing area
in synthetic organic chemistry.[3] This synthetic technique is based on the
empirical observation that some organic reactions proceed much faster and
with higher yields under microwave irradiation compared to conventional
heating. In many cases reactions that normally require many hours at reflux
temperature under classical conditions can be completed within several
minutes or even seconds in a microwave oven, even at comparable reaction
temperatures. Recently, more interest has been focused on “dry media”
synthesis using inorganic solid supports. The coupling of microwave heating
mode with the use of mineral solid support[4] such as alumina, silica and clays
have been allowed the synthesis of several organic compounds with higher
selectivity, yield and purity compared to traditional methods. Our ongoing
program to develop environmentally benign protocols,[5] herein, we wish to
report LiCl catalyzed Doebner modification of the Knoevenagel condensation
for the preparation of cinnamic acids under microwave irradiation using basic
alumina as solid support. To the best of our knowledge, this is the first report
on rapid synthesis of cinnamic acids using LiCl as catalyst under microwave
irradiation.
trans-Cinnamic acids 3 were formed in almost quantitative yield when a
mixture of aromatic aldehyde 1, malonic acid 2 and lithium chloride together
with basic alumina as solid support was subjected to microwave irradiation.
All the reactions were performed in open Erlenmeyer flask in the absence of
any solvent and the irradiations were carried out in pulse of one minute each at
Scheme 1.

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Microwave-Assisted Solvent-Free Synthesis of trans-Cinnamic Acids
207
700 watts (with 2 minutes interval for cooling), which enables easy monitoring
of the course of the reaction by TLC. Temperature of the reaction mass
reached a maximum of 115–1258C at the end of each irradiation and the
conversion was completed within a short irradiation time of 3–8 minutes. This
transformation is very clean and all the cinnamic acids thus obtained were
practically pure. It is interesting to note that this reaction did not proceed at all
when performed without LiCl. When we extended this protocol for aromatic
ketones no condensation product could be obtained.
In conclusion, the microwave assisted Doebner modification of the
Knoevenagel condensation catalyzed by LiCl presented in this paper is a
quick, clean and convenient method for the preparation of cinnamic acids in
near quantitative yields. Other merits like simple work-up and isolation
method, high purity of the product which does not require any further
purification, use of inexpensive catalyst, makes this procedure environmen-
tally friendly and attractive alternative to currently available methods.
EXPERIMENTAL
All melting points are uncorrected. IR spectra in KBr were recorded on a
Perkin–Elmer spectrum BX series FT-IR spectrophotometer, 1H NMR
spectra on a Varian Gemini 200 MHz spectrometer using TMS as an internal
standard and mass spectra (EI) on a Jeol JMS D-300 spectrometer. Analytical
TLC was performed on Merk 60F-254 silica gel plates. Irradiation was carried
out in a domestic microwave oven (BPL 800 G, 2450 MHz).
General Procedure
A mixture of aromatic aldehyde 1 (0.01 mol), malonic acid 2 (0.01 mol)
and lithium chloride (0.01 mol) was transferred into a 100 mL Erlenmeyer
flask. To this basic alumina (3 g) was added and properly mixed with the help
of glass rod, till free flowing powder was obtained. This powder is then
irradiated in a domestic microwave oven (700 watts) for the specific period of
time as indicated in Table 1. After completion of the reaction (monitored by
TLC), the contents of the flask was cooled to room temperature and treated
with methanol (30 mL). The methanol solution was poured into ice cold water
(50 mL), the precipitated solid was filtered, and dried under vacuum to afford
pure cinnamic acid 3. All the compounds prepared were characterized by IR,
1H NMR and MS spectroscopy and finally by comparison with authentic
samples.[6]

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Mogilaiah and Reddy
Table 1. Microwave-assisted preparation of trans-cinnamic acids 3.
Time
(min)
Yield
(%)
M.P.
(8C)
M.P. (lit.[6]
)
Compound
Ar
(8C)
3a
3b
3c
3d
3e
3f
C6H5
6
6
6
5
6
5
8
5
7
6
96
98
98
96
97
93
94
97
95
95
134
197
133
198
4-CH3C6H4
4-CH3OC6H4
2-ClC6H4
171
172
208–209
248
198
208–210
248–250
197
4-ClC6H4
3-O2NC6H4
4-O2NC6H4
4-HOC6H4
3g
3h
3i
285–286
214
286
214–215
233–235
181–183
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
232–234
180–182
3j
3k
3l
6
3
98
97
239
238
145–146
145–148
The IR, 1H NMR and mass spectral data of the products (3a–3l) are given
below:
Compound 3a. IR (KBr) 3027–2520, 1686, 1630, 1450, 1312, 1222,
1075, 980 cm21; 1H NMR (CDCl3, 200 MHz) d 7.75 (1H, d, J ¼ 15.9 Hz, 3-
H), 7.70–7.18 (SH, m, Ar-H), 6.41 (1H, d, J ¼ 15.9 Hz, 2-H); EIMS m/z 148
(Mþ).
Compound 3b. IR (KBr) 2921–2550, 1682, 1620, 1423, 1312, 1223,
1080, 988 cm21; 1H NMR (CDCl3, 200 MHz) d 7.62 (1H, d, J ¼ 15.9 Hz, 3-
H), 7.40–7.36 (4H, m, Ar-H), 6.22 (1H, d, J ¼ 15.9 Hz, 2-H), 2.35 (3H, s,
CH3); EIMS m/z 162 (Mþ).
Compound 3c. IR (KBr) 2845–2500, 1685, 1625, 1445, 1315, 1215,
1
1095, 975 cm21; H NMR (CDCl3, 200 MHz) d 7.65 (1H, d, J ¼ 15.9, 3-H),
7.44–6.92 (4H, m, Ar-H), 6.31 (1H, d, J ¼ 15.9, 2-H), 3.85 (3H, s, OCH3);
EIMS m/z 178 (Mþ).
Compound 3d. IR (KBr) 2925–2510, 1690, 1623, 1424, 1318, 1227,
1039, 984 cm21; 1H NMR (CDCl3, 200 MHz) d 7.58 (1H, d, J ¼ 16 Hz, 3-H),
7.32–7.10 (4H, m, Ar-H), 6.32 (1H, d, J ¼ 16 Hz, 2-H); EIMS m/z 182 (Mþ).
Compound 3e. IR (KBr) 2964–2500, 1707, 1632, 1427, 1306, 1231,
1085, 985 cm21; 1H NMR (CDCl3, 200 MHz) d 7.83 (1H, d, J ¼ 16 Hz, 3-H),
7.51–7.18 (4H, m, Ar-H), 6.56 (1H, d, J ¼ 16 Hz, 2-H), EIMS m/z 182 (Mþ).

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Microwave-Assisted Solvent-Free Synthesis of trans-Cinnamic Acids
209
Compound 3f. IR (KBr) 3010–2510, 1690, 1620, 1417, 1306, 1224,
1050, 989 cm21; 1H NMR (CDCl3, 200 MHz) d 8.42 (1H, s, Ar-H), 7.75 (1H,
d, J ¼ 15.9 Hz, 3-H), 8.18–7.75 (3H, m, Ar-H), 6.55 (H, d, J ¼ 15.9 Hz, 2-H);
EIMS m/z 193 (Mþ).
Compound 3g. IR (KBr) 2928–2520, 1690, 1631, 1429, 1349, 1228,
1115, 987 cm21; 1H NMR (CDCl3 200 MHz) d 7.82 (1H, d, J ¼ 16 Hz), 8.30–
7.96 (4H, m, Ar-H), 6.62 (1H, d, J ¼ 16 Hz); EIMS m/z 193 (Mþ).
Compound 3h. IR (KBr) 3402, 3010–2720, 1683, 1620, 1438, 1330,
1236, 1095, 980 cm21; 1H NMR (CDCl3, 200 MHz) d 7.43 (1H, d, J ¼ 16 Hz,
3-H), 7.23–6.75 (4H, m, Ar-H), 6.26 (1H, d, J ¼ 16 Hz, 2-H), 3.58 (1H, brs,
OH); EIMS m/z 164 (Mþ).
Compound 3i. IR (KBr) 2920–2550, 1695, 1641, 1437, 1320, 1224,
1
1090, 978 cm21; H NMR (CDCl3, 200 MHz) d 7.70 (1H, d, J ¼ 15.9 Hz,
3-H), 7.52–7.15 (3H, m, Ar-H), 6.25 (1H, d, J ¼ 15.9 Hz, 2-H); EIMS m/z
216 (Mþ).
Compound 3j. IR (KBr) 2910–2520, 1684, 1620, 1440, 1310, 1220,
1
1080, 982 cm21; H NMR (CDCl3, 200 MHz) d 7.76 (1H, d, J ¼ 15.9 Hz,
3-H), 7.18–6.90 (3H, m, Ar-H), 6.35 (1H, d, J ¼ 15.9 Hz, 2-H); 3.87 (6H, s,
2 Â OCH3); EIMS m/z 208 (Mþ).
Compound 3k. IR (KBr) 2920–2500, 1694, 1626, 1422, 1318, 1251,
1
1102, 982 cm21; H NMR (CDCl3, 200 MHz) d 7.58 (1H, d, J ¼ 15.9 Hz,
3-H), 6.96–6.76 (3H, m, Ar-H), 6.35 (1H, d, J ¼ 15.9 Hz, 2-H), 590 (2H, s,
OCH2O); EIMS m/z 192 (Mþ).
Compound 3l. IR (KBr) 2925–2520, 1677, 1615, 1440, 1307, 1244,
1075, 973 cm21; 1H NMR (CDCl3, 200 MHz) d 7.81 (1H, d, J ¼ 16 Hz, 3-H),
7.38–7.10 (3H, m, Ar-H), 6.20 (1H, d, J ¼ 16 Hz, 2-H); EIMS m/z 154 (Mþ).
ACKNOWLEDGMENT
The authors are grateful to the Director, Indian Institute of Chemical
1
Technology, Hyderabad, India for providing H NMR spectra.
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Received in India July 4, 2003

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