Use of diethoxymethane as a solvent for phase-transfer esterification of carboxylic acids

Article abstract of DOI:10.1080/00397911.2010.547647

The esterification of carboxylic acids with selected primary alkyl halides in diethoxymethane (DEM) utilizing solid-liquid phase-transfer catalysis has been studied. The use of DEM as the solvent simplifies the process in that a single solvent can be used for both reaction and workup.

Full text of DOI:10.1080/00397911.2010.547647

This article was downloaded by: [University of Western Ontario]
On: 08 November 2012, At: 04:42
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
Use of Diethoxymethane as a Solvent
for Phase-Transfer Esterification of
Carboxylic Acids
a
M. Todd Coleman
a
FutureFuel Chemical Company, Batesville, Arkansas, USA
Accepted author version posted online: 07 Dec 2011.Version of
record first published: 26 Mar 2012.
To cite this article: M. Todd Coleman (2012): Use of Diethoxymethane as a Solvent for Phase-Transfer
Esterification of Carboxylic Acids, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:13, 1911-1913
To link to this article: http://dx.doi.org/10.1080/00397911.2010.547647
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
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.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

1
Synthetic Communications , 42: 1911–1913, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.547647
USE OF DIETHOXYMETHANE AS A SOLVENT
FOR PHASE-TRANSFER ESTERIFICATION OF
CARBOXYLIC ACIDS
M. Todd Coleman
FutureFuel Chemical Company, Batesville, Arkansas, USA
GRAPHICAL ABSTRACT
Abstract The esterification of carboxylic acids with selected primary alkyl halides in
diethoxymethane (DEM) utilizing solid–liquid phase-transfer catalysis has been studied.
The use of DEM as the solvent simplifies the process in that a single solvent can be used
for both reaction and workup.
Keywords Diethoxymethane; esterification; phase-transfer catalysis
INTRODUCTION
It has previously been reported that diethoxymethane (DEM) is a good solvent
[
1]
for the O-alkylation of phenols using phase-transfer catalysis conditions. The
properties of DEM make it a strong candidate for other phase-transfer catalysis
reactions. DEM is stable to basic reaction conditions and also has limited water solu-
bility (4.2%), thus eliminating the need for an extraction solvent. Its high boiling
ꢀ
point (88 C) makes it versatile over a wide range of reaction temperatures. The
use of DEM as a solvent for the esterification of carboxylic acids using
phase-transfer catalysis has been studied and is the subject of this communication.
The classical method used to prepare esters from carboxylic acids is the use of
alcohols in the presence of a strong acid catalyst (Fischer esterification). When com-
pounds other than methyl and ethyl esters are desired, alternative routes are some-
times required because of the cost or stability of the alcohol. One alternative method
utilizes a phase-transfer catalyst generated in situ from an alkyl halide and an amine
in 2-butanone as the solvent. The reactions in this study were carried out in a Parr
[2]
reactor under pressure. Dichloromethane is also a popular solvent for esterification
[
3]
as has been reported for the preparation of glycidate esters and benzyl benzoate.
A
Received November 30, 2010.
Address correspondence to M. Todd Coleman, FutureFuel Chemical Co., 2800 Gap Road,
Batesville, AR 72501, USA. E-mail: toddcoleman@ffcmail.com
1
911

1912
M. T. COLEMAN
method to prepare substituted benzyl phenylacetate esters, key intermediates in the
synthesis of cephalosporin and oxa-b-lactam antibiotics, under solid–liquid phase
[
4]
transfer conditions has also been reported. Key elements of this patented process
are the use of a solvent that does not dissolve the carboxylate salt while dissolving
the alkyl halide. Solvents utilized were ketones, esters, or nitriles, with acetone being
the preferred solvent. The workup described in this reference requires the removal
of the initial solvent followed by use of an extraction solvent. These conditions have
thus been modified to determine if DEM is suitable for solid–liquid phase-transfer
catalyzed reactions.
ESTERIFICATION OF CARBOXYLIC ACIDS
The esterification of various carboxylic acids has been evaluated in DEM using
several primary alkyl halides under solid–liquid phase-transfer catalysis (Table 1).
The general procedure consists of dissolving the carboxylic acid (0.1 mol) in DEM
(
0
150 mL). Potassium carbonate (9.2 g, 0.067 mol), potassium iodide (4.2 g,
.025 mol), tetrabutylammonium bromide (0.2 g, 0.0006 mol), and the alkyl halide
ꢀ
(0.11 mol) were added. The slurry was heated to reflux (80–85 C) and held for 6 h.
After cooling to <50 C, the mass was diluted with water (100 mL) to dissolve salts,
ꢀ
and the layers were separated. The top organic phase was washed with a saturated
NaHCO solution (50 mL) followed by a saturated NaCl solution (50 mL). After
3
drying over Na SO and concentration by rotary evaporation, the crude product
2
4
was purified by short-path distillation and analyzed by NMR.
Table 1. Esterification of acids using DEM as solid–liquid phase-transfer catalysis reaction solvent
Entry
R
1
R
2
X
Yield
1
2
3
4
5
6
7
8
9
Benzyl
Phenyl
Benzyl
Benzyl
Benzyl
Butyl
Butyl
Allyl
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
81
78
82
82
73
30
18
89
72
Cyclohexyl
Benzyl
Cyclohexyl
Benzyl
Cyclohexyl
Allyl
Benzyl
Butyl
C
C
7
7
H
H
15
15
10
Benzyl
Cl
57
1
1
2
1
Benzyl
Benzyl
Cl
Cl
31
82

ESTERIFICATION IN DIETHOXYMETHANE
1913
Yields were generally good for all cases studied. Esterification of unsaturated
acids did not result in yields as good as aromatic or saturated acids, with acrylic acid
and cinnamic acid resulting in poor yields. Crotonic acid, however, provided a yield
similar to the aromatic and saturated acids. Use of allyl chloride as the electrophile
resulted in poor yield of allyl esters. It was suspected that the reduced product yield
could be due to the low boiling point of allyl chloride. However, a lower reaction
temperature did not result in an improvement in yield.
DEM did provide an advantage in product isolation. Because DEM has low
solubility in water, an extraction solvent was not required. Isolation involved merely
adding water to dissolve salts, decantation, and distillation of the DEM to give crude
products, which were purified by short-path distillation.
CONCLUSION
DEM has been demonstrated to be an excellent solvent for the esterification of
carboxylic acids using solid–liquid phase-transfer catalysis. Yields are generally good
and product workup is greatly simplified. The evaluation of DEM as a solvent for
other types of phase-transfer catalysis reactions is being further evaluated in these
laboratories.
ACKNOWLEDGMENTS
The author thanks Louise Sandefur, Dimmick Bymaster, and Tim Oster for
helpful comments on this manuscript. The author also thanks the FutureFuel
Chemical Company Analytical Department for NMR and GC support.
REFERENCES
1
2
. Coleman, M. T.; LeBlanc, G. Org. Process Res. Dev. 2010, 14(3), 732–736.
. Hennis, H. E.; Easterly, J. P.; Collins, L. R.; Thompson, L. R. Ind. Eng. Chem. Prod. Res.
Dev. 1967, 6(3), 193–195.
3. (a) Petit, Y.; Larcheveque, M. Org. Synth. 1998, 75, 37; (b) Yang, H.-M.; Lin, C-L. J. Mol.
Cat. A: Chem. 2003, 206(1–2), 67–76.
4
. Green, J. M.; Bunnell, C. A. Synthesis of substituted benzyl ethers. US Patent 4334079
(
CAN 97:144590), November 3, 1980.