A practical Knoevenagel condensation catalyzed by PEG400 and anhydrous K2CO3 without solvent

Article abstract of DOI:10.1081/SCC-200026650

Knoevenagel condensation of aromatic aldehydes with active methylene compounds under solvent-free conditions to synthesize arylidene compounds in good to excellent yields using powdered anhydrous K₂CO₃ and PEG400 as catalysts has bee

Full text of DOI:10.1081/SCC-200026650

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A Practical Knoevenagel
Condensation Catalyzed by
PEG400 and Anhydrous K CO
2
3
Without Solvent
a
a
b
Yu‐Qing Cao , Zhi Dai , Rui Zhang & Bao‐Hua
a
Chen
a
College of Chemistry and Environmental Science,
Hebei University, P.R. China
b
Hebei Changtian Pharma, Baoding, P.R. China
Version of record first published: 06 Jan 2011
To cite this article: Yu‐Qing Cao, Zhi Dai, Rui Zhang & Bao‐Hua Chen (2004): A
Practical Knoevenagel Condensation Catalyzed by PEG400 and Anhydrous K CO3
2
Without Solvent, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:16, 2965-2971
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 16, pp. 2965–2971, 2004
A Practical Knoevenagel Condensation
Catalyzed by PEG400 and Anhydrous
K CO Without Solvent
2
3
1,*
1
Yu-Qing Cao, Zhi Dai, Rui Zhang, and Bao-Hua Chen
2
1
1
College of Chemistry and Environmental Science,
Hebei University, P.R. China
2
Hebei Changtian Pharma, Baoding, P.R. China
ABSTRACT
Knoevenagel condensation of aromatic aldehydes with active methylene
compounds under solvent-free conditions to synthesize arylidene com-
pounds in good to excellent yields using powdered anhydrous K
and PEG400 as catalysts has been described.
2 3
CO
Key Words: Aromatic aldehydes; Methylene compounds; PEG400;
Solvent-free.
*
Correspondence: Yu-Qing Cao, College of Chemistry and Environmental Science,
Hebei University, P.R. China; E-mail: chemistry_hbu@yahoo.com.
2
965
DOI: 10.1081/SCC-200026650
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2
966
Cao et al.
INTRODUCTION
Developing green chemistry is one of the most important purposes of
organic synthesis at present. Organic synthesis in the absence of solvent is a
powerful tool for the generation of structurally diverse molecules, due to
their special selectivity, the ease of set-up and work-up, arousing great inter-
[
1–3]
est.
Moreover, solvent-free reactions sometimes are faster, taking just a
few minutes rather than hours to complete because the reactants are close
contact with each other. This aspect, coupled with the lower overall costs of
running a reaction without solvent and no specially needed equipment,
could become a decisive factor in industry.
Polyethylene glycols (PEGs) havebeenwidelyusedasPTC inmanyorganic
[
4,5]
reactions
availability. IthasbeenprovedthatPEGsincorporating 7–9unitsaremoreeffec-
owing to their stability, low cost, environment-friendly, and easy
þ
þ
[6]
tiveincatalyzingthereactionsinwhichK orNa saltsparticipate. Especially,
due to their liquid property and the two hydroxy groups, PEG 400–600 was more
suitable for liquid–liquid or solid–liquid phase solvent-free organic reactions.
[
7,8]
As a continuance of our study,
PEGs as PTC in condensation catalyzed by alkali without solvent.
we take a primary investigation on using
Knoevenagel condensation of carbonyl compounds with active methylene
compounds is one of the most important methods for the preparation of sub-
[
9–11]
stituted alkenes.
ditions carried out by microwave irradiation and by grinding has rapidly
Recently, Knoevenagel reaction under solvent-free con-
[
12–14]
increased.
But microwave irradiation process is difficult to apply in
the industrial process until now and the grinding reaction is only suitable to
some active solid reactants. We wish to report a convenient preparation of
some arylidene derivatives by Knoevenagel condensation of aromatic alde-
hydes with active methylene compounds under solvent-free conditions using
PEG400 and K CO as catalysts (Sch. 1). The results are listed in Table 1.
2
3
RESULTS AND DISCUSSION
Anhydrous K CO was more satisfied to obtain excellent yield in short
time than other inorganic alkalies. KOH and NaOH were too strong bases
2
3
Scheme 1.

Knoevenagel Condensation
2967

2
968
Cao et al.

Knoevenagel Condensation
2969
to result in more by-products. KF and AcONa cannot catalyze effectively this
reaction under the same conditions. Low yield was obtained and long reaction
time is needed using MgO and CaO as base catalysts. Using K CO , KOH,
2
3
KF, and MgO as catalyst for the condensation of benzaldehyde with ethyl
cyanoacetate, a yield of 84%, 46%, 51%, and 55% was, respectively, obtained
under the same reaction conditions. The appreciable amount of PEG400 was
between 3 and 5 mol% to aromatic aldehydes. A longer reaction time will be
necessary and lower yield obtained with less PEG. The more amount
of PEG400 employed, the more products would be lost during the cause of
washing with water.
From Table 1, it was shown that the condensation of aldehydes with elec-
tron withdrawing groups such as –Cl and –NO in the aromatic ring, with
2
active methylene compounds can be carried out in relatively shorter time
and higher yield than with electron donating groups such as –N(CH ) and
3
2
–
OCH . A longer reaction time was necessary for the reactants with –OH
3
owing to –OH can partly react with alkali to form salt and the reaction
resulted in high melting point of the product. The rate would slow down
along with increasing amount of the high melting point of products, so a
high reaction temperature was needed. However, higher temperature will
result in low yield especially for the products containing group –OH and
ester bond due to the oxidation and hydrolysis of some reactant and product
by water generating in reaction. But when nitromethane and nitroethane as
active methylene compounds, arylidene compounds cannot be obtained
under this condition.
In summary, this method was safe, environment-friendly, and working-up
easily. The distinct advantages of this process lie in being easily practiced in
industry without needing special equipment.
EXPERIMENTAL
TLC was GF254 thin layer chromatography with petroleum ether/diethyl
ether (2/1) used as eluent. All the reagents and aromatic aldehydes were
obtained from commercial suppliers and were not purified. Melting points
were determined on a microscopy apparatus and uncorrected.
General Procedure
A mixture of aromatic aldehyde 2 (0.1 mol), active methylene compound
(0.1 mol), anhydrous K CO (0.02 mol), and PEG-400 (1.5 mL) were taken
2 3
1
into a 50 mL three-necked, round-bottomed flask equipped with mechanical

2
970
Cao et al.
stirrer and drying tube filled with KOH. The reaction was processed with
vigorous stirring and heating at assigned temperature. The completion of
the reaction was monitored by TLC. The reaction mixture was cooled to
room temperature and treated with cool water (acidifying needed for the
products with –OH). The product was filtered, dried, recrystallized from
1
ethanol, and identified by comparison of physical data and H NMR and IR
spectra with those described in the literatures.
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Received in Japan February 23, 2004