Efficient synthesis of deoxybenzoins from chalcones

Article abstract of DOI:10.1080/00397910601130967

β-Ketoaldehydes derived from chalcone epoxides by Lewis acid-catalyzed rearrangement underwent smooth deformylation when refluxed in tetrahydrofuran (THF) in the presence of ethylenediamine, affording deoxybenzoins in excellent yields. The method is general and useful for the preparation of deoxybenzoins with a variety of substitution patterns. Copyright Taylor & Francis Group, LLC.

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Efficient Synthesis of Deoxybenzoins from
Chalcones
Paulson Mathew a , Daliya Mathew a & C. V. Asokan a
a School of Chemical Sciences, Mahatma Gandhi University, Kottayam,
Kerala, India
Published online: 10 Mar 2007.
To cite this article: Paulson Mathew , Daliya Mathew & C. V. Asokan (2007): Efficient Synthesis of
Deoxybenzoins from Chalcones, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 37:5, 661-665
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Synthetic Communicationsw, 37: 661–665, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601130967
Efficient Synthesis of Deoxybenzoins
from Chalcones
Paulson Mathew, Daliya Mathew, and C. V. Asokan
School of Chemical Sciences, Mahatma Gandhi University, Kottayam,
Kerala, India
Abstract: b-Ketoaldehydes derived from chalcone epoxides by Lewis acid–catalyzed
rearrangement underwent smooth deformylation when refluxed in tetrahydrofuran
(THF) in the presence of ethylenediamine, affording deoxybenzoins in excellent
yields. The method is general and useful for the preparation of deoxybenzoins with a
variety of substitution patterns.
Keywords: chalcones, epoxides, deoxybenzoins, deformylation, rearrangement
Deoxybenzoins are useful precursors for the synthesis of various carbo-
cycles,[1] heterocycles,[2] and a variety of natural products having aryl substi-
tuents.[3] They are usually prepared by Friedel–Crafts acylation reaction[4]
of electron-rich aromatic compounds with aryl acetic acids/chlorides or by
selective deoxygenation of benzoins. Although the former is useful only for
electron-rich substrates, the latter usually affords symmetrical deoxybenzoins.
Other methods[5] reported for the synthesis of deoxybenzoins are designed for
specific targets and use less common substrates and reagents. We have
recently reported the synthesis of bioactive 3,4-diaryl pyrrole containing
marine natural products lamellarin O and lukianol A from the ketene-N,S-
acetals derived from commercially available deoxybenzoins.[6] In continu-
ation of an ongoing project to develop newer methods for lamellarin
alkaloids[7] and related natural products by our well-established procedure,
Received October 8, 2005
Address correspondence to C. V. Asokan, School of Chemical Sciences, Mahatma
Gandhi University, Kottayam, Kerala 686 650, India. E-mail: asokancv@yahoo.com
661

662
P. Mathew, D. Mathew, and C. V. Asokan
we needed a simple and efficient method for the preparation of deoxybenzoins
with various substitution patterns.
Chalcones, prepared by the condensation of substituted benzaldehydes
and acetophenones, are useful synthons for various transformations. Though
the formation of b-ketoaldehydes by the Lewis acid–catalyzed rearrangement
of chalcone epoxides has been known for a long time,[8] the synthetic potential
of these aldehydes have not been extensively explored. In our procedure, the
.
b-ketoaldehydes generated by the BF3 Et2O-catalyzed rearrangement of
chalcone epoxides were deformylated by treatment with ethylenediamine to
afford the corresponding deoxybenzoins.
In an attempt to construct 3,4-diarylpyrrole-2-carboxylates, we treated the
b-ketoaldehyde 2a with ethyl glycinate in ethanol in the presence of triethyl-
amine. This reaction led to moderate yields of enaminoketone along with
small amounts of deoxybenzoin 3a. We envisioned that treatment of b-ketoal-
dehydes 2a with appropriate nucleophiles would afford a convenient route to
deoxybenzoins. When the b-ketoaldehyde 2a was treated with ethylene-
diamine in tetrahydroferan (THF), the reaction proceeded with complete
deformylation within 4 h. Substituted chalcones were prepared by the conden-
sation of different benzaldehydes with acetophenones using aqueous sodium
hydroxide in 95% ethanol. The chalcones in the methanol–THF (1:1)
mixture were transformed into the corresponding epoxides 1 using alkaline
hydrogen peroxide.[9] The aldehydes 2 were generated in good yields by
treating an ice-cooled solution of the epoxides 1 in dichloromethane with
[10]
.
BF3 Et2O.
The crude aldehydes 2 were directly used for the subsequent reaction.
When the aldehydes 2 were refluxed in the presence of 1 equivalent of
ethylene diamine in THF for 3–5 h, deformylation takes place, affording
the deoxybenzoins 3 in excellent yields (Scheme 1). A wide range of structu-
rally varied b-ketoaldehydes was subjected to deformylation by this procedure
to provide the corresponding deoxybenzoins (Table 1).
Thus, we have developed a straightforward and simple method for the
reparation of deoxybenzoins starting from readily available and inexpensive
chalcone epoxides. The reagents used are common and less expensive. The
reaction is general and a variety of substituted deoxybenzoins were
synthesized.
Scheme 1.

Deoxybenzoins from Chalcones
663
Table 1. Deoxybenzoins prepared
Time
(h)
Yield
(%)
Entry
Product
R1
R2
1
2
3a
3b
3c
3d
3e
3f
H
H
H
H
H
4
4
4
4
5
4
4
5
5
5
3
4
3
3
93
84
90
88
78
88
84
90
85
87
92
82
86
85
OCH3
Br
Cl
3
4
5
OCH3
Br
Cl
OCH3
OCH3
OCH3
N(CH3)2
N(CH3)2
N(CH3)2
Cl
6
7
3g
3h
3i
8
H
9
OCH3
Cl
10
11
12
13
14
3j
3k
3l
H
OCH3
Br
Cl
Cl
Cl
3m
3n
Cl
EXPERIMENTAL
General Procedure for the Synthesis of 3-Oxo-2,3-diphenyl
Propanal 2
To an ice-cooled solution of chalcone epoxide 1 (10 mmol) in dichloro-
methane (30 mL), borontrifluoride ethyrate (10 mmol) was added dropwise
over a period of 10 min and stirred for 2 h. The reaction was then quenched
with 5% aqueous NaHCO3 solution (50 mL) and extracted using chloroform
(2 Â 50 mL). The organic layer was washed with water (2 Â 50 mL) and
dried over anhydrous Na2SO4. Evaporation of the solvent afforded the
aldehydes 2 in nearly quantitative yields. This was used for the next step
without further purification.
General Procedure for the Synthesis of 1,2-Diphenyl-1-ethanone 3
To the crude aldehyde 2 (10 mmol) in THF (50 mL), ethylenediamine
(10 mmol) was added and refluxed for 3–5 h. When the reaction was
complete (as monitored by thin-layer chromatography), the mixture was
cooled and poured into ice water (50 mL), extracted using chloroform
(2 Â 50 mL), and dried (Na2SO4). The solvent was evaporated, and the
crude product was purified by passing through a short column of silica gel
using hexane.

664
P. Mathew, D. Mathew, and C. V. Asokan
ACKNOWLEDGMENTS
This work was supported by Kerala State Council of Science, Technology, and
Environment and Council of Scientific and Industrial Research, New Delhi
[Project No. 01(1954)/04/EMR-II]. We thank Madurai Kamaraj University,
Madurai, for providing spectral and analytical data. P. M. thanks the Uni-
versity Grants Commission for assistance under the Faculty Improvement
Program.
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