Bismuth(III) chloride-mediated, efficient, solvent-free, mwi-enhanced doebner condensation for the synthesis of (E)-cinnamic acids

Article abstract of DOI:10.1080/00397910903162833

A bismuth(III) chloride-mediated green process for the production of (E)-cinnamic acid derivatives using microwave irradiation under solvent-free conditions is described. The (E)-cinnamic acids are obtained in excellent yields. This protocol is green because it employs an established environmentally benign procedure, microwave irradiation. Solvent vapor pollution is not there because it is solvent free, and bismuth(III) chloride is an established nontoxic catalyst. Copyright

Full text of DOI:10.1080/00397910903162833

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Bismuth(III) Chloride–Mediated, Efficient,
Solvent-Free, MWI-Enhanced Doebner
Condensation for the Synthesis of (E)-
Cinnamic Acids
Suresh a , Dhruva Kumar a & Jagir S. Sandhu a
a Department of Chemistry , Punjabi University , Patiala, Punjab,
India
Published online: 08 Jun 2010.
To cite this article: Suresh , Dhruva Kumar & Jagir S. Sandhu (2010) Bismuth(III) Chloride–Mediated,
Efficient, Solvent-Free, MWI-Enhanced Doebner Condensation for the Synthesis of (E)-Cinnamic Acids,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:13, 1915-1919, DOI: 10.1080/00397910903162833
To link to this article: http://dx.doi.org/10.1080/00397910903162833
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Synthetic Communications1, 40: 1915–1919, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903162833
BISMUTH(III) CHLORIDE–MEDIATED, EFFICIENT,
SOLVENT-FREE, MWI-ENHANCED DOEBNER
CONDENSATION FOR THE SYNTHESIS OF
(E)-CINNAMIC ACIDS
Suresh, Dhruva Kumar, and Jagir S. Sandhu
Department of Chemistry, Punjabi University, Patiala, Punjab, India
A bismuth(III) chloride–mediated green process for the production of (E)-cinnamic acid
derivatives using microwave irradiation under solvent-free conditions is described. The
(E)-cinnamic acids are obtained in excellent yields. This protocol is green because it
employs an established environmentally benign procedure, microwave irradiation. Solvent
vapor pollution is not there because it is solvent free, and bismuth(III) chloride is an
established nontoxic catalyst.
Keywords: Bismuth(III) chloride; (E)-cinnamic acids; MWI; solvent free
INTRODUCTION
trans-Cinnamic acids are of current interest because they are useful synthons in
organic chemistry and for several industrial products. Notably these are required in
the production of cosmetics and hair protection agents.[1,2] Because of these signifi-
cant uses in industry as well as organic synthesis, there has been considerable interest
for developing facile efficient processes for their production. The previous proce-
dures employed conventional heating, catalysts such as pyridine and piperidine,[3]
and organic bases. Organic bases are established carcinogenic materials and have
been replaced by several inorganic salts.[4] Several methods have been reported for
synthesis of cinnamic acids, which involve the Claisen–Schmidt condensation of
aldehydes with acetates,[5] the Knoevenagel reaction of aldehydes with malonic
acid,[6] the Wittig reaction of aldehydes with a phosphorus ylide derived from
a-bromoacetate,[7] and more recently the Heck reaction between aryl halides and
acrylates.[8] Evidently, these procedures are not facile and cheap. Considering the
cost of the reagents and ease of operation, especially on a practical, large-scale prep-
aration, herein we report the time-effective synthesis of cinnamic acids in excellent
yield by Doebner condensation of aryl aldehydes and malonic acid. We and others[9]
have been developing bismuth(III) chloride as an efficient nontoxic catalyst in
organic synthesis. Guided by the nontoxic behavior of this salt and our requirement
Received May 15, 2009.
Address correspondence to Jagir S. Sandhu, Department of Chemistry, Punjabi University, Patiala,
Patiala 147 002, Punjab, India. E-mail: j_sandhu2002@yahoo.com
1915

1916
SURESH, D. KUMAR, AND J. S. SANDHU
Scheme 1. Doebner condensation of aryl aldehydes and malonic acid.
for trans-cinnamic acids (we needed this material in the development of enaminone
chemistry of uracils),[10] we disclose an efficient protocol for the production of
(E)-cinnamic acids through Doebner modification as shown in Scheme 1.
RESULTS AND DISCUSSION
We initiated our investigation with pilot experiments using 5 mol% BiCl3 in
condensation of anisaldehyde (5 mmol) and malonic (5.05 mmol) without solvent
under microwaves, which proceed smoothly in a short time, but the obtained yields
of trans-cinnamic acids were not excellent. To optimize the yields, we performed
experiments to quantify the catalyst and established 10 mol% BiCl3 catalyst as
enough to have the optimum yields. In a typical procedure, aryl aldehydes, malonic
acid, and BiCl3 (1:1.1:0.1) were mixed properly and treated under microwave
irradiation (MWI) using solvent-free conditions (for times, see Table 1) to obtain
trans-cinnamic acids 3a in 98% yields. To check the efficacy and applicability of this
catalyst, we could successfully obtain a range of desired products in 89–98% yields
(Table 1) in 3–8 min. Catalyst more than 5 mol% (up to 10 mol%) did not
effect any drastic change in reaction time and yields. Electron-withdrawing and
Table 1. BiCl3-catalyzed synthesis of (E)-cinnamic acids
Entry
R1
R2
R3
Producta
Time (min)
Yield (%)b
Mp (lit.[11]) (ꢀC)
1
2
H
MeO
H
H
H
H
H
Cl
H
H
H
Cl
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3
98
97
95
97
94
92
89
90
94
89
93
90
91
132 (133)
170–171 (172)
4
3
H
5
209–210 (208–210)
196–197 (197)
4
Me
Cl
H
3.5
6
5
H
249–251 (248–250)
196–197 (197)
6
H
Cl
NO2
H
7.5
6.5
7
7
3g
3h
3i
232–233 (233–235)
286 (286)
8
NO2
OH
H
H
9
H
5
213–215 (214–215)
198 (197–198)
166–168 (168)
10
11
12
13
OH
MeO
MeO
H
3k
3l
6.5
5
OH
Meo
Me2N
3m
3n
4
181–182 (181–183)
215–216 (216)
8
aThe products were characterized by comparison of their melting points and spectral (IR, 1H NMR)
data with those of authentic samples.
bIsolated yields after recrystallization.

BiCl3-CATALYZED SYNTHESIS OF (E)-CINNAMIC ACIDS
1917
electron-donating substituents on aryl aldehydes did not affect product yields and
reaction rate; clearly the catalyst was effective over a wide range of aryl aldehydes.
CONCLUSION
In summary, the present method employing BiCl3 is a mild, efficient, and envir-
onmentally benign protocol for the synthesis of (E)-cinnamic acids. Products are
obtained in excellent yields in short reaction times. The factor in favor of the present
protocol is that the catalyst used is a cheap, well-known, and nontoxic inorganic salt.
Operational simplicity and easy workup are the other attractive features of this
procedure. These features place this protocol superior to the existing ones. During
aqueous workup, no hazardous, unsafe, or corrosive by-products were formed, as
is the case with strong, metallic, conventional Lewis acids.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
Reagent-grade chemicals were purchased from a commercial source and used
without further purification. Infrared (IR) spectra were recorded in KBr discs on
a Perkin-Elmer 240C analyzer. 1H NMR spectra were recorded on a Varian Gemini
300-MHz spectrometer using trimethylsilane (TMS) as internal standard. The
progress of the reaction was monitored by thin-layer chromatography (TLC) using
silica gel G (Merck).
General Procedure for Preparation of trans-Cinnamic Acids
Aryl aldehydes (10 mmol), malonic acid (10 mmol), and BiCl3 (0.1 mmol) were
mixed for 3–4 min in an Erlenmeyer flask. This reaction mixture was treated with
MWI for the times given in Table 1 using solvent-free conditions. After completion
of the reaction (monitored via TLC), the crude product was cooled, washed with
water, and filtered, then recrystallized from ethanol.
Representative Spectral Data
Compound 3a. 1H NMR (CDCl3) d 7.70 (d, J ¼ 16.0 Hz, 1H), 7.55–7.48
(m, 2H), 7.45–7.34 (m, 3H), 6.44 (d, J ¼ 16.0 Hz, 1H), 3.81 (s, 3H); 13C NMR
(CDCl3) d 167.8 (s), 145.3 (d), 134.8 (s), 130.7 (d), 129.3 (d), 128.5 (d), 118.2 (d),
52.1 (q); IR (KBr) 1720, 1638, 981, 769 cmꢁ1; MS m=z 162 (Mþ).
Compound 3b. 1H NMR (CDCl3) d 7.65 (d, J ¼ 16.0 Hz, 1H), 7.49–7.45
(m, 2H), 6.92–6.88 (m, 2H), 6.31 (d, J ¼ 16.0 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H);
13C NMR (CDCl3) d 168.1 (s), 161.8 (s), 144.9 (d), 130.1 (d), 127.5 (s), 115.7 (d),
114.7 (d), 55.7 (q), 51.9 (q); IR (KBr) 1718, 1639, 1604, 985, 839, 824 cmꢁ1; MS
m=z 192 (Mþ).
Compound 3c. 1H NMR (CDCl3) d 7.64 (d, J ¼ 16.0 Hz, 1H), 7.46
(dd, 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, 1H),
3.81 (s, 3H); 13C NMR (CDCl3) d 167.6 (s), 143.8 (d), 136.6 (s), 133.3 (s), 129.6

1918
SURESH, D. KUMAR, AND J. S. SANDHU
(d), 129.6 (d), 118.8 (d), 52.2 (q); IR (KBr) 1710, 1635, 1006, 82 cmꢁ1; MS m=z
196 (Mþ).
Compound 3d. 1H NMR (CDCl3) d 7.67 (d, J ¼ 16.0 Hz, 1H), 7.42
(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), 3.80 (s,
3H), 2.37 (s, 3H); 13C NMR (CDCl3) d 167.6 (s), 144.9 (d), 140.7 (s), 130.7 (s),
129.6 (d), 128.1 (d), 116.7 (d), 51.6 (q), 21.5 (q); IR (KBr) 1712, 1634, 818 cmꢁ1
MS m=z 176 (Mþ).
;
ACKNOWLEDGMENTS
The authors are thankful to the Council of Scientific and Industrial Research,
New Delhi, India, for financial assistance and to the Indian National Science
Academy, New Delhi, India, for additional financial support for this research
project.
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