Solvent-Free Synthesis of Ethyl α-Cyanocinnamates Catalyzed by K 2O-Al2O3 Using Grinding Method

Article abstract of DOI:10.1081/SCC-120028355

K₂O-Al₂O₃ catalyzes the Knoevenagel condensation of ethyl cyanoacetate with aromatic aldehydes, giving ethyl α-cyanocinnamates in 94-98% yield under solvent-free condition by grinding at room temperature.

Full text of DOI:10.1081/SCC-120028355

This article was downloaded by: [North Carolina State University]
On: 17 July 2013, At: 23:16
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Solvent‐Free Synthesis of Ethyl α‐Cyanocinnamates
Catalyzed by K2O–Al2O3 Using Grinding Method
Shu‐Xiang Wang a , Ji‐Tai Li a , Wen‐Zhi Yang a , Ya‐Hui Yin a & Zi‐Hui Xie a
a Department of Chemistry, College of Chemistry and Environmental Science, Hebei
University, Baoding, 071002, P.R. China
Published online: 20 Aug 2006.
To cite this article: ShuXiang Wang , JiTai Li , WenZhi Yang , YaHui Yin & ZiHui Xie (2004) Solvent‐Free Synthesis of Ethyl
α‐Cyanocinnamates Catalyzed by K2O–Al2O3 Using Grinding Method, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 34:5, 829-834, DOI: 10.1081/SCC-120028355
To link to this article: http://dx.doi.org/10.1081/SCC-120028355
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 5, pp. 829–834, 2004
Solvent-Free Synthesis of Ethyl
a-Cyanocinnamates Catalyzed
by K2O–Al2O3 Using
Grinding Method
*
Shu-Xiang Wang, Ji-Tai Li, Wen-Zhi Yang, Ya-Hui Yin,
and Zi-Hui Xie
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, P.R. China
ABSTRACT
K2O–Al2O3 catalyzes the Knoevenagel condensation of ethyl cyanoa-
cetate with aromatic aldehydes, giving ethyl a-cyanocinnamates in
94–98% yield under solvent-free condition by grinding at room
temperature.
Key Words: Knoevenagel condensation; Ethyl a-cyanocinnamates;
Solvent-free; Cyanoacetate; Grinding method.
*
Correspondence: Shu-Xiang Wang, Department of Chemistry, College of Chemistry
and Environmental Science, Hebei University, Baoding 071002, P.R. China; E-mail:
hbdxxbz@mail.hbu.edu.cn.
829
DOI: 10.1081/SCC-120028355
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
830
Wang et al.
All synthetic chemistry will consume of energy and materials. An
environmentally problematic aspect in organic synthetic chemistry is the use
of organic solvents. The solvents have to be produced in another chemical
process, which again consumes energy and resources. During the reaction the
large amount of solvent has to be heated or cooled, and has to be removed after
completion of the reaction from the reaction mixture, a further waste of
energy.
Recently, some solvent-free reaction conditions have been developed for
oxidation,[1] reduction,[2] substitution,[3] condensation[4] and the Michael
addition.[5] And in many cases, these reactions are more efficient and selective
than those executed in the corresponding solutions.[6] And some solvent-free
reactions could be completed by grinding,[4] the procedure are milder reaction
condition, better yield, and easier work-up compared with the classical heating
method.
Ever since its discovery, the Knoevenagel reaction has been widely
utilized in organic synthesis. In the last years, there has been a growing interest
in the Knoevenagel condensation products, because many of them present
significant biological activity.[7]
Usually ethyl a-cyanocinnamates is prepared via the Knoevenagel con-
densation of ethyl cyanoacetate with aromatic aldehydes under homogenous
conditions. The catalysts are ammonia, organic amines and their salts,[6] some
Lewis acids and bases such as ZnCl2,[8] CdI2,[9] MgO, and ZnO[10] have also
been used as catalysts.
In recent years, the application of inorganic supported catalysts in organic
synthesis has rapidly increased,[11] because these reactions often involve
easier work-up procedures than those needed for homogenous methods.
This prompted us to study the possibility of the Knoevenagel condensa-
tion without solvent. In this work, K2O–Al2O3, an inexpensive but efficient
catalyst, has been employed in the Knoevenagel condensations under solvent-
free condition at room temperature by grinding.
Most products described herein were previously prepared and described
in the literature.[11–14] As shown in the Sch. 1 and Table 1, the Knoevenagel
condensation of ethyl cyanoacetate (2) with aromatic aldehydes (1) produces
Scheme 1.

ORDER
REPRINTS
Solvent-Free Synthesis of Ethyl a-Cyanocinnamates
831
Table 1. The condensation of aromatic aldehydes 1a–1l with ethyl cyanoacetate 2.
Reaction Reaction
time temperature Yielda
Entry
Ar
(min)
(8C)
(%)
m.p. (8C) (Lit)
a
C6H5
90
90
90
120
90
90
90
30
30
8
23
26
27
60
25
25
25
27
26
28
21
25
24
20
23
20
22
27
94
95
93
83
0
50–51 (49–51[11]
)
ab
ac
ad
ae
af
ag
b
c
0
0
97
4-ClC6H4
3-ClC6H4
3-NO2C6H4
91–92 (90–91[13]
)
97 102–103 (100–102.5[13]
)
d
e
98 136–137 (134–136[13]
96 172–173 (172–173[11]
)
)
4-NO2C6H4
4-CH3C6H4
12
25
50
40
180
25
188
10
f
97
95
94–95 (94–95[11]
83–84 (80–84[12]
)
)
g
4-CH3OC6H4
3,4-(CH2O2)C6H3
3-OCH3-4-HOC6H3
4-(CH3)2NC6H4
4-HOC6H5
h
i
98 106–107 (106–107[14]
97 111–112 (111–112[11]
97 126–127 (124–126[11]
96 171–172 (176–177[11]
)
)
)
)
j
k
l
C6H5CH55CH
98 107–108 (116[12]
)
aIsolated yield based on the aldehyde.
bOn 0.1 mol scale, K2O–Al2O3 20 g.
cRecycled K2O–Al2O3 as catalyst.
dReaction at 608C for 2 hr using EtOH as solvent.
eKNO3 as catalyst.
fAl2O3 (neutral) as catalyst.
gKNO3 deposit on Al2O3 (neutral) as catalyst.
ethyl a-cyanocinnamates (3) in high yield. Some reactions (b–h, j and l) are
completed in relative short time (8–50 min). The a,b-unsaturated aromatic
aldehyde (1l) gave the corresponding E-isomer olefin; no Michael-type
addition product was obtained. Condensation of aldehydes (1i and 1k) with 2
was slow probably due to the acidity of hydroxyl group in the benzene ring.
The results in Table 1 indicate that K2O–Al2O3 is an effective catalyst.
The yield of product 3ac is excellent by using recycled K2O–Al2O3 (see entry
af). KNO3, neutral Al2O3, and KNO3 deposit on neutral Al2O3 did not catalyze
the reaction (see entries ae, af and ag).
In summary, we have found a practical Knoevenagel condensation pro-
cedure for the synthesis of ethyl a-cyanocinnamates catalyzed by K2O–Al2O3

ORDER
REPRINTS
832
Wang et al.
in the absence of solvent at room temperature by using a grinding method.
Compared with the classical heating method, the main advantages of the
procedure are milder reaction condition, better yield, and easier work-up.
EXPERIMENTAL
Liquid aldehydes 1 were purified by distillation. Melting points were
uncorrected. IR spectra were recorded on a Bio-Rad FTS-40 spectrometer
1
(KBr). H NMR spectra were measured on a Bruker AC-80 (80 MHz), TMS
used as internal standard and CDCl3 as solvent.
Preparation and Activation of the Catalyst of K2O–Al2O3
A solution of 13 g KNO3 in 50 mL water, and 37 g neutral Al2O3 (Tianjin
No. 3 Chemical Reagent Factory, China, 0.154 mm) was added to a 250 mL
flask. The mixture was stirred in presence of air at 508C for 0.5 hr. Water was
evaporated at 508C under reduced pressure (2.7 kPa) on a rotary evaporator.
The resulting free flowing powder was added to a crucible and heated in muffle
furnace at 5008C for 3 hr.
General Procedure
Aldehyde 1 (1 mmol), ethyl cyanoacetate 2 (119 mg, 1.05 mmol) and
K2O–Al2O3 (200 mg) were added to a mortar. The mixture was grounded with
a pestle at room temperature for 5 min, and laid up at room temperature till the
aldehyde was disappeared (TLC). After completion, 10 mL dichloromethane
was added to the reaction mixture; the catalyst was removed by filtration and
washed with dichloromethane (3 ꢀ 5 mL). Then the solvent was evaporated at
308C under reduced pressure (27 kPa) on a rotary evaporator to give solid,
which was washed with 5% aqueous ethanol. The pure product was obtained
by recrystallization from 50% aqueous ethanol. The authenticity of the
products was established by comparing their melting points.
ACKNOWLEDGMENT
The Office of Education of Hebei Province, China (2001104) supported
the project.

ORDER
REPRINTS
Solvent-Free Synthesis of Ethyl a-Cyanocinnamates
833
REFERENCES
1. Rasmussen, M.O.; Axelsson, O.; Tanner, D. A practical procedure for the
solid-phase synthesis of racemic 2,20-dihydroxy-1,10-binaphthyl. Syn.
Commun. 1997, 27, 4027–4030.
2. Mehta, G.; Khan, F.A.; Lakshmi, K.A. Modification of p-face selectivity
of 7-norbornenones during reduction in b-cyclodextrin and solid state.
Tetrahedron Lett. 1992, 33, 7977–7980.
3. Smricina, M.; Vyskocil, S.; Hanus, V.; Polasek, M.; Langer, V. The
SN2 reaction in the solid state. An unusual, BAl2 aminolysis of an ester
group in crystalline (+)-2-amino-20-hydroxy-30-(methoxycarbonyl)-1,10-
binaphthyl elucidated by x-ray diffraction and isotopic labeling, new
experimental evidence for linearity in SN2 substitution. J. Am. Chem.
Soc. 1996, 118, 487–489.
4. (a) Ren, Z.J.; Cao, W.G.; Tong, W.Q. The knoevenagel condensation
reaction of aromatic aldehydes with malononitrile by grinding in the
absence of solvents and catalyst. Syn. Commun. 2002, 32 (22),
3475–3479; (b) Geng, L.J.; Wang, S.X.; Li, J.T.; Liu, C.H. Preparation
of derivatives of 5-arylidene babituric acid by grinding method. Youji
Huaxue (Chinese J. Org. Chem.) 2002, 22 (12), 1047–1049.
5. (a) Satish, B.; Panneerselvam, K.; Zacharias, D.; Desiraju, G.R.
Intramolecular Michael-type addition in the solid state. J. Chem. Perkin
Trans 2 1995, 325–328; (b) Li, X.L.; Wang, Y.M.; Matsuura, T.;
Meng, J.B. The solid-state Michael addition of indole to 4-arylidene-3-
methyl-5-pyrazolones. J. Heterocycl. Chem. 1999, 36 (3), 697–701.
6. Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chemical Reviews
2000, 100, 1025–1074.
7. Bose, D.S.; Narsaiah, A.V. An efficient benzyltriethylammonium chloride
catalyzed preparation of electrophilic alkenes: a practical synthesis of
trimethoprim. J. Chem. Research (S) 2001, 36–38.
8. Rao, P.S.; Venkataratnam, R.V. Zinc chloride as a new catalyst for
knoevenagel condensation. Tetrahedron Lett. 1991, 32 (41), 5821–5822.
9. Prajapati, D.; Sandhu, J.S. Cadmium iodide as a new catalyst for
knoevenagel condensations. J. Chem. Soc. Perkin Trans 1 1993,
739–740.
10. Moison, H.; Texier-Boullet, F.; Foucaud, A. Knoevenagel, Wittig and
Wittig–Horner reactions in the presence of magnesium oxide or zinc
oxide. Tetrahedron 1987, 43, 537–542.
11. Dai, G.; Shi, D.; Zhou, L. Knoevenagel condensation catalyzed by
potassium fluoride/alumina. Yingyong Huaxue (Chinese J. Appl. Chem.)
1995, 12 (3), 104; Chem. Abstr. 1996, 125, 33274v.

ORDER
REPRINTS
834
Wang et al.
12. Ren, Z.J.; Cao, L.; Zhou, H.B.; Jiang, E. The study of knoevenagel
condensation and solvent effect without catalyst. Youji Huaxue (Chinese
J. Org. Chem.) 1996, 16, 48–52; Chem. Abstr. 1996, 124, 316680s.
13. Li, J.T.; Li, T.S.; Li, L.J.; Cheng, X. Synthesis of ethyl a-cyano-
cinnamates under ultrasound irradiation. Ultrason. Sonochem. 1999, 6 (4),
199–201; Chem. Abstr. 1999, 131, 351056j.
14. Popp, F.D. Synthesis of 3-hydroxypridines I: condensation of aromatic
aldehydes with ethyl cyanoacetate. J. Org. Chem. 1960, 25, 646–647.
Received in the USA September 3, 2003

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request Permission/
Order Reprints" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
Fair Use in the Classroom.
(AAP) website for guidelines on
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our
Website
User Agreement for more details.
Request Permission/Order Reprints
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120028355