Molecular iodine in ionic liquid: A green catalytic system for esterification and transesterification

Article abstract of DOI:10.1080/00397910903161660

Esterification of carboxylic acids and transesterification of-ketoesters with alcohols have been developed using a catalytic amount of iodine in polyethylene glycol (PEG) ionic liquid (IL 1000) to afford the corresponding esters in good yields. By simple separation of the ionic-liquid phase containing the iodine, the system of I2/IL 1000 can be reused several times. Copyright

Full text of DOI:10.1080/00397910903161660

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Molecular Iodine in Ionic Liquid: A Green
Catalytic System for Esterification and
Transesterification
a
a
Yiming Ren & Chun Cai
a
Chemical Engineering College, Nanjing University of Science and
Technology, Nanjing, China
Version of record first published: 06 May 2010
To cite this article: Yiming Ren & Chun Cai (2010): Molecular Iodine in Ionic Liquid: A Green Catalytic
System for Esterification and Transesterification, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 40:11, 1670-1676
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1
Synthetic Communications , 40: 1670–1676, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903161660
MOLECULAR IODINE IN IONIC LIQUID: A GREEN
CATALYTIC SYSTEM FOR ESTERIFICATION AND
TRANSESTERIFICATION
Yiming Ren and Chun Cai
Chemical Engineering College, Nanjing University of Science and
Technology, Nanjing, China
Esterification of carboxylic acids and transesterification of b-ketoesters with alcohols have
been developed using a catalytic amount of iodine in polyethylene glycol (PEG) ionic liquid
(IL 1000) to afford the corresponding esters in good yields. By simple separation of the
ionic-liquid phase containing the iodine, the system of I /IL 1000 can be reused several times.
2
Keywords: Esterification; ionic liquid; molecular iodine; transesterification
INTRODUCTION
Esterification of carboxylic acids and transesterification of esters with alcohols
play important roles in the production of organic esters, especially for some important
[
1–3]
products and intermediates in the laboratory and industry.
fication of carboxylic acids is a common and useful method for protecting carboxyl
In addition, the esteri-
[
4,5]
[6,7]
groups.
[
acids,
A number of procedures catalyzed by a variety of protic acids,
[10,11]
Lewis
have been
8,9]
[12,13]
[14]
solid catalysts,
ionic liquids (ILs),
and enzymes
reported in the literature. However, many of these catalysts are expensive, difficult
to prepare, toxic, and unsuitable for acid-sensitive functional groups or require longer
reaction times and large amounts of solid supports, which would eventually result in
the generation of a large amount of toxic waste.
Recently, the use of molecular iodine has drawn considerable attention because
it is an inexpensive, nontoxic, readily available catalyst for various organic transfor-
mations that affords the corresponding products in excellent yields with high selec-
tivity. The mild Lewis acidity associated with iodine enhances its use in organic
synthesis for several organic transformations that use stoichiometric levels to
catalytic amounts. Owing to numerous advantages associated with this ecofriendly
element, iodine has been explored as a powerful catalyst for various organic transfor-
[
15–22]
mations.
for esterification and transesterification reaction with good yields.
Previously, molecular iodine had been explored as a powerful catalyst
[
23–27]
However, the
reuse of iodine is difficult because it has good solubility in most organic solvents and
Received March 30, 2009.
Address correspondence to Chun Cai, Chemical Engineering College, Nanjing University of
Science and Technology, Nanjing 210094, China. E-mail: c.cai@mail.njust.edu.cn
1
670

IODINE-CATALYZED ESTERIFICATION
1671
Scheme 1. PEG ionic liquids.
Scheme 2. Iodine-catalyzed esterification in IL 1000.
Scheme 3. Iodine-catalyzed transesterification in IL 1000.
easy sublimation at high temperature. Recently, we reported a facile method for
[
28]
recovery and reuse of iodine by polyethylene glycol (PEG) ionic liquid. The PEG
ILs (Scheme 1) and toluene have the advantages of both homogeneous and hetero-
geneous phases at different temperatures (biphasic conditions at lower temperatures
and monophasic at higher temperatures) with the ease of product as well as catalyst
separation. Here, we report our successful approach for transesterification and direct
esterification using a catalytic amount of iodine in the PEG IL (Schemes 2 and 3).
RESULTS AND DISCUSSION
First, the reaction of acrylic with methanol was explored to search for the
optimal conditions, such as the amount of catalysts and the reaction temperature
(Table 1). The reaction temperature had a great influence on the reaction. A poor
yield was obtained when the reaction proceeded at room temperature (Table 1,
entry 1). Increasing the reaction temperature could remarkably enhance both reaction
yield and rate, perhaps because the IL and toluene formed a homogeneous phase at
high temperature. The results showed that an appreciable amount of I was 3 mol% to
2
acrylic (Table 1, entry 7). A longer reaction time was necessary and less yield was
obtained with less I . An increase in the amount of I did not lead to an improvement
2
2
in yield (Table 1, entry 6). However, in the absence of iodine, few products were
synthesized (Table 1, entry 10). The reaction was also explored in several PEG ILs
(Table 1, entry 7); the results showed that all the PEG ILs had good yields for the
reaction. However, IL 1000 and toluene have both homogeneous and heterogeneous
phases at different temperatures, and the system of IL 1000=toluene change to two
phases is faster than other PEG ionic liquids system at room temperature.

1672
Y. REN AND C. CAI
Table 1. Studies on the reaction of acrylic with methanol in IL 1000
ꢀ
a
Entry
I
2
(mol%)
T ( C)
Yield (%)
1
2
3
4
5
6
3
3
3
3
3
4
3
r.t.
70
12
51
59
72
83
91
80
90
100
110
110
b
7
90, 89, 87, 85
c
8
8
d
9
0
e
8
9
8
9
2
1
0
110
110
110
73
44
1
0
Trace
a
b
c
Isolated yields.
The system of I
2
=IL 1000 was run for four consecutive cycles.
IL 400 was used.
d
IL 2000 was used.
IL 4000 was used.
e
Under the optimized reaction conditions, we investigated the reaction of
carboxylic acids with various alcohols (Table 2). Both aromatic and aliphatic alco-
hols reacted efficiently with carboxylic acids promoted by I in IL 1000. Table 2
2
shows how the aromatic alcohols, with different substituents such as chloro, nitro,
methoxy, and methyl, were converted to the corresponding esters in excellent yields.
However, aromatic alcohols with electron-donating groups gave the corresponding
Table 2. Direct esterification of carboxylic acids with alcohols using iodine as
a
catalyst in IL 1000
b
Entry
Carboxylic acid
Alcohol
Yield (%)
1
2
3
4
5
6
7
8
9
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
COOH
COOH
COOH
COOH
COOH
COOH
COOH
COOH
COOH
COOH
C
6
H
5
CH
2
OH
CH OH
CH OH
OH
CH OH
CHOH
85
91
2-MeC
4-MeOC
2-ClC
3-NO
(CH
CH
c-C
n-C
t-C
CH
n-C
(CH
6
H
4
2
6
H
4
2
92
6
H
4
CH
2
82
80
2
C
H
6 4
2
3
)
2
90
92
3
OH
6
H11OH
90
94
4
H
9
OH
OH
1
1
1
1
1
1
1
0
1
2
3
4
5
6
4
H
9
61
91
n-C10H
21COOH
3
OH
C
C
2
H
H
5
COOH
COOH
9
H
19OH
CHOH
93
90
2
5
3
)
2
n-C
8
H
17COOH
COOH
COOH
CH
CH
CH
3
OH
OH
OH
91
Trace
Trace
C
4-NO
6
H
5
3
3
2
C
6
H
4
a
b
All reactions were carried out with 3 mol% of iodine in refluxing toluene for 6 h.
Isolated yields.

IODINE-CATALYZED ESTERIFICATION
1673
Table 3. Transesterification of b-ketoesters with alcohols using iodine as catalyst in
IL 1000
a
b
Entry
b-Ketoester
Alcohol
Yield (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
n-C
(CH
n-C
s-C
t-C
3
H
7
OH
70
68
80
76
51
71
80
75
81
53
70
72
3
)
2
CHOH
4
H
9
OH
OH
4
H
9
4
H
9
OH
11OH
17OH
c-C
n-C
6
H
8
H
6 5 2
C H CH OH
n-C
t-C
c-C
4
H
9
OH
OH
1
1
1
0
1
2
4 9
H
6
H11OH
C
6
H
5
CH OH
2
a
b
All reactions were carried out with 3 mol% of iodine in refluxing toluene for 6 h.
Isolated yields.
products in better yields than those with electron-withdrawing groups. The reaction
of t-BuOH under the same conditions gave only the corresponding ester in moderate
yield (Table 2, entry 10). We next examine the transesterification of b-ketoesters
with various alcohols with I =IL 1000 (Table 3). Table 3 showed that the various
2
b-ketoesters were gained in good yields. Similarly, the reaction of t-BuOH under
the same conditions gave only the corresponding esters in moderate yields because
of the steric hindrance of t-BuOH (Table 3, entries 5 and 10). However, in cases
where a carboxylic acid group is directly attached to an aromatic ring, such as
benzoic acid (Table 2, entries 15 and 16), there was almost no reaction.
The recycling performance of iodine in the IL 1000 was investigated in the
reaction of acrylic acid and methanol. The data listed in Table 1 showed that
I2=IL 1000 could be reused four times with satisfying results.
In conclusion, we have developed a simple, inexpensive, and effective method
for the esterification and transesterification using a catalytic amount of iodine in IL.
The advantages of the present reaction are the elimination of metals and toxic
reagents, operational simplicity, and good yields of products. Moreover, the simple
experimental procedure, combined with ease of recovery and reuse of iodine, is
expected to contribute to the development of a green strategy for the other
iodine-catalyzed reaction. Further studies on the reuse of iodine are now in progress.
EXPERIMENTAL
Infrared (IR) spectra were recorded on a Bomem MB154S infrared analyzer.
H NMR were recorded with Bruker Advance RX300. Electrospray ionization–mass
1
spectrometry (ESI-MS) results were recorded on a Themo Finningan Trace TSQ.
Reagents were obtained from commercial sources. Commercially available reagents
were used without further purification. Products are all known compounds and were
identified by comparing of their physical and spectra data with those reported in the
literature.

1674
Y. REN AND C. CAI
Typical Procedure for the Synthesis of IL 1000
Methylsulfonyl chloride (10 mL) was added to a solution of PEG 1000
60 mmol) and triethylamine (120 mmol) in toluene (200 mL) within 30 min under
(
a nitrogen atmosphere. The mixture was stirred at room temperature. After 3 h,
the mixture was filtered. The filtrate was added to 1-methylimidazol (120 mmol),
ꢀ
and the mixture was stirred at 86 C for 17 h. After the reaction, the IL layer was
separated and washed with petroleum ether (3 ꢁ 10 mL). Evaporation of solvent
1
under reduced pressure gave the desired pure product IL 1000 in 80% yield. H
NMR (500 MHz, CDCl , d): 2.85 (s, 6H, 2OSO CH ), 3.70–3.76 [m, 97H,
3
2
3
(
2
M
OCH CH ) ], 3.82 (s, 6H, 2NCH ), 7.52 (s, 2H, 2CH), 7.59 (s, 2H, 2CH), 8.81 (s,
þþ
2
2 n
3
þþ
H, 2CH); ESI-MS: 448.17, M =2, n ¼ 16), 470.20, M =2, n ¼ 17, 492.20,
þþ þþ þþ þþ
=2, n ¼ 18, 514.27, M =2, n ¼ 19, 558.27, M =2, n ¼ 21, 580.30, M =2,
þþ þþ þþ
n ¼ 22, 602.33, M =2, n ¼ 23, 624.36, M =2, n ¼ 24, 646.36, M =2, n ¼ 25,
þþ
þþ
þþ
6
68.37, M =2, n ¼ 26, 690.43, M =2, n ¼ 27, 712.43, M =2, n ¼ 28, 153.07
ꢂ1
(100); IR (KBr, cm ): 3447, 3153, 2985, 1447, 1352, 1205, 1117, 1060, 858, 587.
General Procedure for Esterification
I2 (0.06 mmol) was added to a solution of carboxylic acid (2 mmol), alcohol
1 mL), and toluene (1.5 mL) in IL 1000 (1 mL). The mixture was refluxed for the
(
specified time and monitored by thin-layer chromatography (TLC). After the reac-
tion, the mixture was cooled to room temperature, and the upper toluene containing
the expected product was separated by decantation. The toluene was evaporated,
and the pure products were obtained via purification through column chromato-
graphy. The bottom phase was the IL containing the iodine and the produced water.
The system of I =IL 1000 was reused after removal of the water under reduced
2
pressure.
General Procedure for Transesterification
I2 (0.06 mmol) was added to a solution of b-ketoester (2 mmol), alcohol
2.5 mmol), and toluene (1.5 mL) in IL 1000 (1 mL). The mixture was refluxed for
(
the specified time and monitored by TLC or gas chromatography (GC). After the
reaction, the mixture was cooled to room temperature, and the upper toluene
containing the expected product was separated by decantation. The toluene was
evaporated, and the pure products were obtained via purification through column
chromatography. The bottom phase was the IL containing the iodine. The system
of I =IL 1000 was reused in subsequent runs without further purification.
2
REFERENCES
1. Otera, J. Esterification; Wiley-VCH: Weinheim, 2003.
2. Otera, J. Esterification. Chem. Rev. 1993, 93, 1449–1470.
3. Larock, R. C. Comprehensive Organic Transformations, 2nd ed.; VCH: New York, 1999;
pp. 1932–1941.

IODINE-CATALYZED ESTERIFICATION
1675
4
5
6
7
8
9
. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley: New York, 1999; pp. 269–453.
. Haslam, E. Recent developments in methods for the esterification and protection of the
carboxyl group. Tetrahedron 1980, 36, 2409.
. Rehberg, C. E.; Fischer, C. H. Preparation and properties of the n-alkyl acrylates. J. Am.
Chem. Soc. 1944, 66, 1203.
. Wang, B.; Ming, Y. L.; Shuan, S. J. Ionic liquid-regulated sulfamic acid: Chemoselective
catalyst for the transesterification of b-ketoesters. Tetrahedron Lett. 2003, 44, 5037.
. Ranu, B. C.; Dutta, P.; Sarkar, A. A simple and efficient procedure for transesterification
catalyzed by indium triiodide. J. Org. Chem. 1998, 63, 6027.
. Barbosa, S. L.; Dabdoub, M. J.; Hurtado, G. R.; Klein, S. I.; Baroni, A. C. M.; Cunha, C.
Solvent-free esterification reactions using Lewis acids in solid-phase catalysis. Appl. Catal.
A 2006, 313, 146.
1
1
1
1
1
1
0. Madje, B. R.; Patil, P. T.; Shindalkar, S. S.; Benjamin, S. B.; Shingare, M. S.; Dongare,
M. K. Facile transesterification of b-ketoesters under solvent-free condition using borate
zirconia solid acid catalyst. Catal. Commun. 2004, 5, 353.
1. Bhagiyalakshmi, M.; Priya, S. V.; Mabel, J. H.; Palanichamy, M.; Murugesan, V. Effect
of hydrophobic and hydrophilic properties of solid acid catalysts on the esterification of
maleic anhydride with ethanol. Catal. Commun. 2008, 9, 2007.
2. Gui, J.; Cong, X.; Liu, D.; Zhang, X.; Hu, Z.; Sun, Z. Novel Brønsted acidic ionic
liquid as efficient and reusable catalyst system for esterification. Catal. Commun.
2
3. Li, X.; Eli, W.; Li, G. Solvent-free synthesis of benzoic esters and benzyl esters in
004, 5, 473.
novel Brønsted acidic ionic liquids under microwave irradiation. Catal. Commun. 2008,
9, 2264.
4. Cordova, A.; Janda, K. D. A highly chemo- and stereoselective synthesis of b-keto
esters via a polymer-supported lipase-catalyzed transesterfication. J. Org. Chem. 2001,
66, 1906.
5. Bandgar, B. P.; Shaikh, K. A. Molecular iodine–catalyzed efficient and highly
rapid synthesis of bis(indolyl)methanes under mild conditions. Tetrahedron Lett. 2003,
44, 1959.
1
1
1
1
2
2
2
6. Saeeng, R.; Sirion, U.; Sahakitpichan, P.; Isobe, M. Iodine catalyzes C-glycosidation of
D-glucal with silylacetylene. Tetrahedron Lett. 2003, 44, 6211.
7. Phukan, P. Iodine as a very powerful catalyst for three-component synthesis of protected
homoallylic amines. J. Org. Chem. 2004, 69, 4005.
8. Phukan, P. Iodine as an extremely powerful catalyst for the acetylation of alcohols under
solvent-free conditions. Tetrahedron Lett. 2004, 45, 4785.
9. Banik, B. K.; Fernandez, M.; Alvarez, C. Iodine-catalyzed highly efficient Michael
reaction of indoles under solvent-free condition. Tetrahedron Lett. 2005, 46, 2479.
0. Ishihara, M.; Togo, H. An efficient preparation of 2-imidazolines and imidazoles
from aldehydes with molecular iodine and (diacetoxyiodo)benzene. Synlett 2006, 227.
1. Das, B.; Chowdhury, N.; Damodar, K. Iodine-catalyzed efficient conjugate addition
of pyrroles to a,b-unsaturated ketones. Tetrahedron Lett. 2007, 48, 2867.
2. Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M. L.; Ke, J. K.; Chan, P. W. H. Iodine-
catalyzed allylation of 1,3-dicarbonyl compounds with allylic alcohols at room tempera-
ture. Tetrahedron Lett. 2008, 49, 122.
2
2
3. Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B. A mild and efficient method
for esterification and transesterification catalyzed by iodine. Tetrahedron Lett. 2002,
43, 879.
4. Chavan, S. P.; Shivasankar, K.; Sivappa, R.; Kale, R. Zinc-mediated transesterification of
b-ketoesters and coumarin synthesis. Tetrahedron Lett. 2002, 43, 8583.

1676
Y. REN AND C. CAI
2
5. Chavan, S. P.; Kale, R. R.; Shivasankar, K.; Chandake, S. I.; Benjamin, S. B. A simple
and efficent method for transesterification of b-ketoesters catalysed by iodine. Synthesis
003, 2695.
2
2
6. Bosco, J. W. J.; Agrahari, A.; Saikia, A. K. Molecular iodine–catalyzed selective
acetylation of alcohols with vinyl acetate. Tetrahedron Lett. 2006, 47, 4065.
7. Ahmed, N.; Lier, J. E. Molecular iodine in isopropenyl acetate (IPA): A highly efficient
catalyst for the acetylation of alcohols, amines, and phenols under solvent-free conditions.
Tetrahedron Lett. 2006, 47, 5345.
2
28. Ren, Y. M.; Cai, C. A green procedure for the protection of carbonyl compounds
catalyzed by iodine in ionic liquid. Tetrahedron Lett. 2008, 49, 7110.