Ionic liquids as solvent for efficient esterification of carboxylic acids with alkyl halides

Article abstract of DOI:10.3906/kim-0904-39

The selective esterification of carboxylic acid derivatives with a variety of alkyl halides was carried out using ionic liquid as solvent in the presence of triethylamine. The reaction was found to proceed under relatively mild conditions with excellent conversions (up to 99%) and selectivities. The ionic liquid was recycled and reused. TUeBITAK.

Full text of DOI:10.3906/kim-0904-39

Turk J Chem
34 (2010) , 187 – 191.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0904-39
Ionic liquids as solvent for efficient esterification of
carboxylic acids with alkyl halides
1,∗
1
2
¨
˙
Yetkin GOK , Bu¨lent ALICI , Engin C¸ ETINKAYA
1
1
˙
¨
˙
¨
¨
˘
Ismail OZDEMIR and Ozlem OZEROGLU
1
˙
Ino¨nu¨ University, Faculty Science and Arts, Chemistry Department,
44280 Malatya-TURKEY
e-mail: ygok@inonu.edu.tr
2
˙
Chemistry Department, Ege University, 35100 Bornova, Izmir-TURKEY
Received 27.04.2009
The selective esterification of carboxylic acid derivatives with a variety of alkyl halides was carried out
using ionic liquid as solvent in the presence of triethylamine. The reaction was found to proceed under
relatively mild conditions with excellent conversions (up to 99%) and selectivities. The ionic liquid was
recycled and reused.
Key Words: Ionic liquids, green solvent, esterification, imidazolidine, catalyst.
Introduction
Esterification of carboxylic acids is one of the most important reactions in organic synthesis, and more environ-
mentally benign alternative approaches to those currently used by the chemical industry are in great demand.1,2
Conventional esterification is conducted with excess carboxylic acids (or alcohols) against a counterpart in the
presence of an acid catalyst, or with stoichiometric dehydrating reagents or activated carboxylic acid deriva-
tives. The use of excess substrates wastes these compounds, and the use of stoichiometric dehydrating reagents
or activated carboxylic acid derivatives produces significant amounts of byproducts from the reagents. Salts
of the carboxylic acids may also be converted into esters by heating them with alkyl halides. This reaction is
most successful with primary halides, but secondary and tertiary halides given ester with olefin as a byproduct
by loss of hydrogen halide from the alkyl halide. The contamination of crude products with excess substrates
or byproducts requires substantial materials, energy, and time for the purification of ester. Recently, efforts
∗Corresponding author
187

¨
Ionic liquids as solvent for efficient esterification of..., Y. GOK, et al.,
have been made in order to replace the conventional methods and to develop clean catalytic methods such as
supported sulfuric acid or solid superacid and by carrying out the reaction in ionic liquids for the syntheses of
organic esters.3−16
Ecological and economic problems impose more severe requirements on the application of alternative
solvents in technology and large scale organic synthesis.17 An ideal solvent should be nonvolatile and low-
toxic, highly resistant to chemical agents and temperature, and reusable. Ionic liquids have been described
as one of the most promising new reaction media and meet the above requirements to a considerable extent.
Unique properties, such as high thermal stability, negligible vapor pressure, easy handling, and the ability to
dissolve both organic and inorganic compounds contribute to their increasing applications. On the other hand,
immiscibility of ionic liquids with a number of organic solvents provides a solution for biphasic separation of the
desired products. To date, ionic liquids have been successfully applied to effect a wide series of organic reactions,
such as carbonylation, etherification, reduction of aldehydes and ketones, rearrangements, cycloaddition, and
polymerization. Herein, we report our results about the use of the ionic liquid (IL, 1-butyl-3-methyl-4,5-
dihydroimidazolinium hexafluorophosphate) as reaction medium to carry out esterification of carboxylic acids
by reacting with alkyl halides.18−23
N
+
PF6
N
IL
Experimental
Manipulations were prepared with standard Schlenk techniques under an inert atmosphere of nitrogen with
previously dried solvents. The IL was prepared with known methods.24 Flash chromatography; Merck silica
gel (230-400 mesh) eluent ethylacetate/hexane (1:5). 1 H-NMR (300 MHz) and 13 C-NMR (75.5 MHz) spectra
were recorded using a Bruker AM 300 WB FT spectrometer with chemical shifts referenced to residual solvent
CDCl3 . Microanalyses were performed by the IBTAM-Malatya analysis center.
General Procedure for the Esterification Reaction
Into a vial was loaded the carboxylic acid derivatives (1.00 mmol), the alkyl halides (1.00 mmol), ionic liquid
(2 mL) and triethylamine (1.00 mmol). The mixture was stirred at 60 or 90 ◦ C for 1 h. Formation of a white
solid, presumably Et3 N.HX, is a useful indication of the reaction progress. After 1 h heating, the mixture was
cooled to room temperature. The product was extracted with ethyl acetate (3 × 10 mL). The crude product
was finally purified by flash chromatography on silica gel with EtOAc/hexane (1/5 v/v) as eluent.
The IL was easily recycled. After the reaction, with the mixture decanted, the rest of the viscous IL
was thoroughly washed with EtOAc (2 × 10 mL) and reused after drying in a vacuum (0.01 Torr, 25 ◦ C). The
188

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Ionic liquids as solvent for efficient esterification of..., Y. GOK, et al.,
Table. Esterification of carboxylic acids with alkyl halides in ionic liquid.a
O
C
O
C
IL
NEt3
+
R'-X
R
OR'
R
OH
Entry
RCO2H
R’X
Yield(%)b
no reaction c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
no reaction c
no reaction d
ButBr
COOH
98
99
C6H5CH2Cl
2,4,6-(CH3)3C6H2CH2Cl
(CH3)2CHBr
BrCH2CH2CH2Br
BrCH2CH2CH2CH2Br
99
99e
98
99
99
99
94
99e
88
97e
99
99
99
99e
99
ButBr
O2N
COOH
C6H5CH2Cl
2,4,6-(CH3)3C6H2CH2Cl
(CH3)2CHBr
H2N
COOH
H3CCH2CH2CH2Br
(CH3)2CHBr
15
16
ButBr
CH=CHCOOH
C6H5CH2Cl
17
18
19
20
21
22
2,4,6-(CH3)3C6H2CH2Cl
(CH3)2CHBr
Cl
CH=CHCOOH
COOH
ButBr
C6H5CH2Cl
99
(CH3)2CHBr
98e
HOOC
26
27
28
29
30
31
32
ButBr
92
C6H5CH2Cl
98f
(CH3)2CHBr
ButBr
99e,f
98f
HO2CCO2H
HO2C(CH2)2CO2H
HO2C(CHOH)2CO2H
HOCH2CO2H
ButBr
ButBr
ButBr
99f
99f
87
COOH
OH
33
ButBr
99
aAt 60 or 90 °C in IL; at 1 h; IL/acid = 5; RX/acid = 1; NEt3/acid = 1. bIsolated yield. cIn the presence of THF or toluene instead of ionic
liquid and NH4F as catalyst. d In the absence NEt3. eAt 60 °C. fDi alkylation; 2 h.
189

¨
Ionic liquids as solvent for efficient esterification of..., Y. GOK, et al.,
IL was utilized repeatedly more than 3 times in the esterification of benzoic acids with alkyl halides with the
conversions being unchanged.
Results and discussion
Esterification reactions of carboxylic acids with primary and secondary alkyl halides in the presence of triethy-
lamine were carried out in IL. The results are listed in Table. Excellent yields and perfect selectivity were
obtained in all cases. Olefins were not detected as elimination products from the secondary alkyl halides. Since
the products were weakly soluble in the ionic liquid, they were easily separated by simple extraction with ether
and purified by flash chromatography on silica gel with the eluent system of ethylacetate/hexane (1:5). The
structure of the esters obtained was confirmed by NMR. As shown in Table, in the absence of the IL or NEt3
as reaction medium or as base, respectively, reactions do not proceed (Entries 1-3). The ratio NEt3 /acid is 1.
The results in Table show that the esterification of aromatic, aliphatic, and α,β-unsaturated acids with
the halides was satisfactory. The hydroxy group of aromatic acid (Entry 33) and aliphatic acids (Entries 31-32)
did not take part in the esterification. In the reaction of p-phthalic, oxalic, and succinic acid monoesterification
products were detected (Entries 26-30). However, the monoester/diester ratio depends on the reaction time. It
is worth noting that dibromides gave the desired diesters in high yields (Entries 8, 9).
Conclusion
We have demonstrated that the ionic liquid (IL) can be successfully used for esterification reactions involving
carboxylic acids and a variety of alkyl halides in the presence of weak base NEt3 . The reaction was found to
proceed with high conversions in relatively short reaction times and at lower temperatures. The process is also
significant from the view point of pollution control since the ILs can be recycled.
Acknowledgments
¨
˙
We thank the Scientific and Technological Research Council of Turkey (TUBITAK) (107T419).
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