One-pot synthesis of phenacyl esters from acetophenone, [Bmim]Br 3, and potassium salts of carboxylic acids under solvent-free conditions

Article abstract of DOI:10.1080/00397910802431115

One-pot synthesis of phenacyl esters from acetophenone, [Bmim]Br3, and potassium salts of carboxylic acids under solvent-free conditions gave the corresponding phenacyl esters with excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802431115

This article was downloaded by: [University of North Texas]
On: 03 December 2014, At: 22:03
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
One-Pot Synthesis of Phenacyl
Esters from Acetophenone,
[
Bmim]Br , and Potassium
3
Salts of Carboxylic Acids Under
Solvent-Free Conditions
a
a
a
Zhang-Gao Le , Zong-Bo Xie & Jian-Ping Xu
a
Department of Applied Chemistry , East China
Institute of Technology , Fuzhou, China
Published online: 27 Jan 2009.
To cite this article: Zhang-Gao Le , Zong-Bo Xie & Jian-Ping Xu (2009) One-Pot
Synthesis of Phenacyl Esters from Acetophenone, [Bmim]Br , and Potassium Salts
3
of Carboxylic Acids Under Solvent-Free Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:4,
743-747, DOI: 10.1080/00397910802431115
To link to this article: http://dx.doi.org/10.1080/00397910802431115
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

1
Synthetic Communications , 39: 743–747, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802431115
One-Pot Synthesis of Phenacyl Esters from
Acetophenone, [Bmim]Br , and Potassium Salts
3
of Carboxylic Acids Under Solvent-Free
Conditions
Zhang-Gao Le, Zong-Bo Xie, and Jian-Ping Xu
Department of Applied Chemistry, East China Institute of Technology,
Fuzhou, China
3
Abstract: One-pot synthesis of phenacyl esters from acetophenone, [Bmim]Br ,
and potassium salts of carboxylic acids under solvent-free conditions gave the
corresponding phenacyl esters with excellent yields.
Keywords: Aromatics, [Bmim]Br , phenacyl esters
3
INTRODUCTION
Phenacyl esters have been widely used as valuable intermediates because
they are useful photoremovable protecting groups for carboxylic acids in
[1]
organic synthesis and biochemistry. The phenacyl esters are usually pre-
pared by the sodium or potassium salts of acid with a-bromoacetophe-
nones. Some of these methods are limited by low yields, long reaction
times, hydrolysis of the alkylating reagent, or contamination of product
[
2]
[3]
with alkylating reagents. Recently a number of methods have been
[
4]
developed such as phenacyl bromide in b-cyclodextrin, polymer sup-
port, crown ether in conjunction with phase-transfer catalyst (PTC),
[
5]
[3]
[6]
crown ether under reflux conditions, potassium fluoride in glacial
[
7]
[8]
[9]
acetic or in ionic liquids, and a-tosyloxyketones in ionic liquids.
Received May 3, 2008.
Address correspondence to Zhang-Gao Le, Department of Applied
Chemistry, East China Institute of Technology, Fuzhou 344000, China. E-mail:
lezhang_ecit@163.com
7
43

744
Z.-G. Le, Z.-B. Xie, and J.-P. Xu
Scheme 1.
However, in these methods, phenacyl bromide or a-tosyloxyketones is
used, which is synthesized by ketones. Therefore, the development of
a simple, relatively mild, efficient, and environmentally more benign
synthetic method for phenacyl esters using acetophenone and 1-butyl-
3
-methylimidazolium tribromide ([Bmim]Br ) is still urgent.
3
Solvent-free chemical synthesis has recently received much atten-
[
10]
tion. The advantage of this method over conventional reactions is that
it provides greater selectivity, enhanced reaction rates, cleaner products,
and manipulative simplicity and is environmentally benign. In continua-
tion of our ongoing program to develop environmentally benign and new
synthetic methods using ionic liquids as novel promoters and selective
[
11]
reagents, we report here a new and efficient method for the synthesis
of phenacyl esters using 1-butyl-3-methylimidazolium tribromide
([Bmim]Br ) (Scheme 1), a stable liquid, which is readily prepared by
3
reaction of equimolar amounts of 1-butyl-3-methylimidazolium bromide
and bromine. This reagent, which can be stored for several months
without loss of activity, has recently been used for the stereoselective
[
12]
bromination of alkynes, ketones, phenols, and arylamines.
RESULTS AND DISCUSSION
First, we found that the reaction of acetophenone, 1-butyl-3-methylimida-
zolium tribromide ([Bmim]Br ), and potassium acetate could proceed
3
smoothly at room temperature in the presence of Na CO to form the cor-
2
3
responding ester in 86% yield (entry 1). In a similar fashion, a variety of
acetophenones reacted smoothly with potassium salts of carboxylic acids
under these reaction conditions to give the corresponding phenacyl esters.
The results are summarized in Table 1. All the products gave satisfactory
1
mp, IR, and H NMR data that were consistent with the literature data.
As can be seen from Table 1, the reaction is general and applicable to
potassium salts of aliphatic and aromatic carboxylic acids bearing various

One-Pot Synthesis of Phenacyl Esters
745
Table 1. Synthesis of phenacyl esters from acetophenone, [Bmim]Br
a
potassium salts of carboxylic acids under solvent-free conditions
3
, and
b
Product t Yield (%) Mp ( C) Lit. mp ( C)
ꢀ
ꢀ
Entry
Ar
R
[
[
8]
8]
1
2
3
4
5
6
7
8
9
0
1
2
3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH
CH
Ph
4-BrPh
4-NO Ph
4-MeOPh
2-MeOPh
2-MePh
2-OHPh
Ph
3
2a
2b
2c
2d
2e
2f
86
85
86
83
80
85
82
81
84
85
81
83
82
50
26
119
84
49–50
25–26
3
CH
2
[
[
8]
9]
119–120
[
84
9]
2
124–125 123–124
[
9]
133–134 134
[
62
137
7]
2g
2h
2i
62
136–137
109–110
[
[
9]
8]
109
118–119 118
109–110 110–111
[
9]
1
1
1
1
4-ClPh
4-MeOPh Ph
4-NO Ph Ph
2-Furyl Ph
2j
[
[
9]
9]
2k
2l
2
142
74
141–142
[
73
9]
2m
a
All reactions were run with acetophenone (2 mmol), [Bmim]Br3 (2 mmol),
Na CO (1.1 mmol), and potassium salts of carboxylic acids (2.4 mmol) at rt.
2
3
b
Isolated yield.
groups such as bromo, methyl, hydroxy, methoxy, and nitro groups (entries
1
–9) and to several substituted acetophenones containing different substi-
tutes, such as chloro, methoxy, and nitro (entries 10–12). On the basis of
these results, we exploited our method to 2-furyl ethanone. We found that
the synthesis of 2-benzoyloxy-1-(2-furyl)ethanone can also be performed
with high yield (entry 13). The experimental procedure is very simple and
convenient. All of the tested reactions could complete within 30 min.
In conclusion, we have demonstrated the synthesis of phenacyl esters
from acetophenone, [Bmim]Br , and potassium salts of carboxylic acids
3
under solvent-free conditions in the presence of Na CO , a simple,
2
3
efficient method. The present method has many obvious advantages
compared to those reported in the literature, including avoiding use of
toxic solvent or catalyst, environmental friendliness, simplicity of metho-
dology, ease of product isolation, and higher yield.
EXPERIMENTAL
Materials
Melting points were determined on a digital melting-point apparatus
and were not corrected. Infrared spectra were recorded on a Vector 22

746
Z.-G. Le, Z.-B. Xie, and J.-P. Xu
(Bruker). Nuclear magnetic resonance spectra were recorded on an
Avance DMX 400 (Bruker) spectrometer. The ionic liquids [Bmim]Br
3
[
12c]
was synthesized according to reported procedures.
commercially available and were used without further purification.
All materials are
General Procedure for Synthesis of Phenacyl Esters
[
Bmim]Br (2 mmol) was very slowly added (1 drop per 5 s) to acetophe-
3
none (2 mmol) with continuous stirring for 5 min at room temperature.
Then Na CO (1.1 mmol) and potassium salt (2.4 mmol) were added,
and the mixture was stirred at room temperature for 30 min. After the
2
3
reaction completed, the reaction mixture was extracted with Et O, the
2
ethereal layer was concentrated by rotary evaporator, and the crude pro-
duct was purified by the preparative thin-layer chromatography (TLC)
on silica gel using a mixture of petroleum ether and EtOAc as developer
to give the corresponding pure product of phenacyl ester.
ACKNOWLEDGMENTS
This work was financially supported by the National Science Foundation
(
(
20862001), the Key Project of the Chinese Ministry of Education
206075), the Science Foundation of JiangXi Province (0620001), the
Science and Technology Foundation of the Education Department of
JiangXi Province ([2006]207), and the Doctor Foundation of the East
Institute of Technology.
REFERENCES
1
. (a) Soural, M.; Hlav ꢀa cˇ , J.; Hradil, P.; Fry ꢁs ov ꢀa , I.; Hajd u´ ch, M.; Bertolasi, V.;
Malo nˇ , M. Synthesis and cytotoxic activity of substituted 2-phenyl-3-
hydroxy-4(1H)-quinolinones-7-carboxylic acids and their phenacyl erters.
Eur. J. Med. Chem. 2006, 41, 467; (b) Sheehan, J. C.; Umezawa, K. Phenacyl
photosensitive blocking groups. J. Org. Chem. 1973, 38, 3771; (c) Taylor-
Papadimitriou, J.; Yovanidis, C.; Paganou, A.; Zervas, L. New methods in
peptide synthesis, part V: On a- and c-diphenyl-methyl and phenacyl esters
of L-glutamic acid. J. Chem. Soc. C 1967, 1830.
2
3
4
. Shriner, R. L.; Fuson, R. C.; Curtin, D. Y. The Systematic Identification of
Organic Compounds, 5th ed.; Wiley: New York, 1964; p. 235.
. Jagdale, S. J.; Patil, V. S.; Salunkhe, M. M. Synthesis of phenacyl esters by
using PTC and dibenzo-[18]-crown-6. Synth. Commun. 1996, 26, 1747.
. Narender, M.; Reddy, M. S.; Kumar, V. P.; Rao, K. R. Organic reaction in
water: Synthesis of phenacyl esters from phenacyl bromide and potassium

One-Pot Synthesis of Phenacyl Esters
747
salts of aromatic acids in the presence of b-cyclodextrin. Synth. Commun.
005, 35, 1681.
. (a) Thorat, M.; Mane, R.; Jagdale, M.; Salunkhe, M. Synthesis of phenacyl
2
5
esters via polymer supported reagents. Org. Prep. Proced. Int. 1986, 18,
203; (b) Du, L. H.; Zhang, S. J.; Wang, Y. G. Phenacyl esters as a new photo-
cleavable linker in liquid-phase chemistry. Tetrahedron Lett. 2005, 46, 3399.
. Durst, H. D. Crown ether catalysis: ‘‘Naked’’ anions as reactive intermediates
in the synthesis of phenacyl esters. Tetrahedron Lett. 1974, 15, 2421.
. Clark, J. H.; Miller, J. M. Hydrogen bonding in organic synthesis, V:
Potassium flouride in carboxylic acids as an alternative to crown ether with
acid salts in the preparation of phenacyl esters. Tetrahedron Lett. 1977, 18,
6
7
599.
8
9
. Hu, Y.; Chen, J.; Le, Z. G.; Chen, Z. C.; Zheng, Q. G. Organic reactions in
ionic liquids: An efficient method for the synthesis of phenacyl esters by reac-
tion of carboxylic acids with a-bromoacetophenone promoted by potassium
fluoride. Chin. Chem. Lett. 2005, 16, 903.
. Liu, Z.; Chen, Z. C.; Zheng, Q. G. Organic reactions in ionic liquids: Ionic
liquid–accelerated nucleophilic substitution reaction of a-tosyloxyketones
with potassium salts of aromatic acids. Synthesis 2004, 33.
1
0. Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chem. Rev. 2000, 100,
025.
1
1. (a) Le, Z. G.; Xie, Z. B.; Ying, M. Ionic liquid–promoted ring-closure reac-
tion between 1,4-dihydroxyanthraquinone and diamines. Molecules 2006,
1
11(6), 464; (b) Le, Z. G.; Xu, J. P.; Rao, H. Y.; Ying, M. One-pot synthesis
of 2-aminobenzothiazoles using a new reagent of [Bmim]Br in [Bmim]BF .
3
4
J. Heterocycl. Chem. 2006, 43, 1123; (c) Le, Z. G.; Chen, Z. C.; Hu, Y.;
Zheng, Q. G. Organic reactions in ionic liquids: Ionic liquid–promoted effi-
cient synthesis of N-alkyl and N-arylimides. Synthesis 2004, 995; (d) Le, Z.
G.; Chen, Z. C.; Hu, Y.; Zheng, Q. G. Organic reaction in ionic liquids:
N-alkylation of phthalimide and several nitrogen heterocycles. Synthesis
2004, 208; (e) Le, Z. G.; Chen, Z. C.; Hu, Y.; Zheng, Q. G. Organic reactions
in ionic liquids: Organic reactions in ionic liquids: A simple highly regioselec-
tive or regiospecific substitutions of benzotriazole. Heterocycles 2004, 63,
1077.
1
2. (a) Chiappe, C.; Conte, V.; Pieraccini, D. Bromination of alkynes in ionic
liquids—A kinetic investigation. Eur. J. Org. Chem. 2002, 2831; (b) Le, Z.
G.; Chen, Z. C.; Hu, Y. (Bmim)Br3 as a new reagent for regioselective
mono-bromination of phenols and several activated aromatics under
solvent-free conditions. Chin. J. Chem. 2005, 23, 1537; (c) Le, Z. G.; Chen,
Z. C.; Hu, Y.; Zheng, Q. G. [Bmim]Br as a new reagent for regioselective
3
mono-bromination of arylamines with under solvent-free conditions. Synth-
esis 2004, 17, 2809.