Atom-efficient, solvent-free, green synthesis of chalcones by grinding

Article abstract of DOI:10.1080/00397910802664244

An improved Claisen-Schmidt condensation reaction of methyl ketones and aromatic aldehydes can be achieved by grinding at room temperature in the absence of solvents. This process is simple, efficient, economical, and environmentally benign compared to classical reactions.

Full text of DOI:10.1080/00397910802664244

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Atom-Efficient, Solvent-Free,
Green Synthesis of Chalcones
by Grinding
Nora M. Rateb a & Hussein F. Zohdi a
a Department of Chemistry, Faculty of Science, Cairo
University, Giza, Egypt
Available online: 26 Jun 2009
To cite this article: Nora M. Rateb & Hussein F. Zohdi (2009): Atom-Efficient, Solvent-
Free, Green Synthesis of Chalcones by Grinding, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:15,
2789-2794
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Synthetic Communications1, 39: 2789–2794, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802664244
Atom-Efficient, Solvent-Free, Green Synthesis
of Chalcones by Grinding
Nora M. Rateb and Hussein F. Zohdi
Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
Abstract: An improved Claisen–Schmidt condensation reaction of methyl ketones
and aromatic aldehydes can be achieved by grinding at room temperature in the
absence of solvents. This process is simple, efficient, economical, and environmen-
tally benign compared to classical reactions.
Keywords: Chalcones, Claisen–Schmidt condensation, green chemistry, grinding,
solvent-free synthesis
Green chemistry focuses on research that attempts to reduce or eliminate
negative environmental impacts. Green chemistry[1] aims to prevent waste
and generate substances with little or no toxicity to humans and the
environment, thereby maximizing atom economy. This is achieved by
assuring that the final product contains the greatest possible proportion
of the starting materials and avoiding the use of harmful solvents, or even
better, any solvents at all.
Chalcones represent an important class of natural compounds with a
variety of biological activities.[2] Recent studies on biological evaluation
of chalcones revealed some to be antibacterial, antifungal, anticancer,
anti-inflammatory, antitubercular, antihyperglycemic,[3] and antimalarial
agents.[4] Chalcones are very common in natural products chemistry.[5]
Some derivatives are used as sweeteners, drugs, and sunscreen agents.[5]
Chalcones are also well-known intermediates in the synthesis of various
Received October 7, 2008.
Address correspondence to Hussein F. Zohdi, Department of Chemistry,
Faculty of Science, Cairo University, Giza 12613, Egypt. E-mail: zohdi@cu.edu.eg
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N. M. Rateb and H. F. Zohdi
heterocyclic compounds.[6,7] Some halo derivatives of chalcones are use-
ful synthons in the synthesis of a large number of bioactive molecules.[6]
Several methods have been developed for the preparation of chalcone
derivatives. The most common method is the base-catalyzed Claisen–
Schmidt reaction, in which the condensation of a methyl ketone with an
aldehyde is carried out in the presence of aqueous sodium hydroxide.[3,8,9]
Some other derivatives were prepared by condensation in chloroform[10]
in the presence of a catalytic amount of piperidine at 80ꢀC. Also, the
Claisen–Schmidt reaction was improved by using KOH ꢁ Al2O3 as a
catalyst in alcoholic solvent under ultrasound irradiation.[5] In addition,
another method was described for the synthesis of chalcones using
borontrifluoride-etharate as a catalyst at room temperature.[3] However,
in spite of their utility, some methods suffer disadvantages such as long
reaction times (3–4 h) with high probability of side reactions[3] (as
Cannizaro or aldol condensation), small yields, chemical hazards, and
environmental pollution.
Toda et al.[11] has reported that many reactions can be conducted with
good yields by just grinding solids (or liquid and solids) together. Because
green chemistry has attracted great attention in recent years, we report
herein a simple approach for the preparation of chalcone derivatives.
Most chalcones reported herein have been previously prepared using
classical methods. Several chalcones, 3a–q, were prepared (Scheme 1) by
grinding together equivalent amounts of the appropriate methyl ketones
and different aldehydes in the presence of solid sodium hydroxide in a
porcelain mortar under solvent-free conditions. Grinding for about
3–5 min led to a yellow-colored solid mass, which proved to be the target
chalcone. Grinding continued for another 5–10 min. The crude products
were easily separated by washing with cold water and simple Buchner
filtration; final purification was achieved by crystallization from the
appropriate solvents (Table 1).
The method reported here for the synthesis of chalcones is simple
and effective in terms of short reaction time, excellent yields, and the
Scheme 1. 3a–e, R ¼ 2-furyl: 3a, R0 ¼ 2-furyl; 3b, R0 ¼ 2-thienyl; 3c, R0 ¼ C6H5;
3d, R0 ¼ 4-FC6H4; 3e, R0 ¼ 4-CIC6H4. 3f–j, R ¼ phenyl: 3f, R0 ¼ C6H5; 3 g,
R0 ¼ 4-CH3C6H4; 3 h, R0 ¼ 4-FC6H4; 3i, R0 ¼ 4-CIC6H4; 3j, R0 ¼ 2-thienyl. 3k–
o, R ¼ 2-naphthyl: 3k, R0 ¼ C6H5; 31, R0 ¼ 4-CH3C6H4; 3 m, R0 ¼ 4-FC6H4; 3n,
R0 ¼ 4-CIC6H4; 3o, R0 ¼ 2-thienyl. 3p,q, R ¼ 4-CH3C6H4: 3p, R0 ¼ 4-CH3C6H4;
3q, R0 ¼ 4CH3OC6H4.

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N. M. Rateb and H. F. Zohdi
formation of one product as measured by thin-layer chromatography
(TLC). It is also consistent with the green chemistry approach because
it does not need heating or microwave irradiation. It occurs at room
temperature and is completely free from organic solvents during
both the reaction and separation of the product (except for
recrystallization).
EXPERIMENTAL
Melting points were measured on an Electrothermal melting-point appa-
ratus and are uncorrected. Infrared (IR) spectra were recorded on a
Shimadzu Fourier transform (FT)–IR 8101 PC IR spectrophotometer.
Mass spectra were measured on a GCMS-QP1000 EX spectrometer at
70 eV. Elemental analyses were carried out at the Microanalytical Center
of Cairo University.
General Procedure
A mixture of the appropriate methyl ketones 1 (5 mmol), aromatic
aldehyde 2 (5 mmol), and sodium hydroxide (7 mmol) was thoroughly
ground with a pestle in an open mortar at room temperature for
2–3 min until the mixture turned into a melt. The initial syrupy reac-
tion mixture solidified within 3–5 min. Grinding continued for
5–10 min more, and the reaction was monitored by TLC. The solid
was washed with cold water to remove the sodium hydroxide and
recrystallized from the appropriate solvent to give the corresponding
chalcone derivatives. The yields and melting points are reported in
Table 1.
Spectral and Analytical Data of Some Compounds
Compound 3j: mp 49–52ꢀC; MS: m=z ¼ 214. Anal. calcd. C13H10OS: C,
72.87; H, 4.70; S, 14.96. Found: C, 72.77; H, 4.79; S, 15.11. IR (KBr):
t=cmꢂ1 1651 (CO).
Compound 3 m: mp 110–113ꢀC; MS: m=z ¼ 276. Anal. calcd.
C19H13FO: C, 82.59; H, 4.74. Found: C, 82.55; H, 4.62. IR (KBr):
t=cmꢂ1 1662 (CO).
Compound 3o: mp 80–82ꢀC; MS: m=z ¼ 264. Anal. calcd. C17H12OS:
C, 77.24; H, 4.58; S, 12.13. Found: C, 77.30; H, 4.49; S, 12.0. IR (KBr):
t=cmꢂ1 1654 (CO).

Green Synthesis of Chalcones
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