Convenient preparation of tert-butyl esters

Article abstract of DOI:10.1016/j.tetlet.2006.03.005

A general method is presented for the preparation of tert-butyl esters by the gentle warming of the carboxylic acid in the presence of excess of tert-butyl acetoacetate and a catalytic amount of acid. This method generates only low pressures, and is there

Full text of DOI:10.1016/j.tetlet.2006.03.005

Tetrahedron Letters 47 (2006) 3065–3066
Convenient preparation of tert-butyl esters
*
Douglass F. Taber, David A. Gerstenhaber and Xia Zhao
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
Received 19 September 2005; revised 28 February 2006; accepted 1 March 2006
Available online 20 March 2006
Abstract—A general method is presented for the preparation of tert-butyl esters by the gentle warming of the carboxylic acid in the
presence of excess of tert-butyl acetoacetate and a catalytic amount of acid. This method generates only low pressures, and is there-
fore suitable for laboratory scale pressure glassware.
Ó 2006 Elsevier Ltd. All rights reserved.
We present here a convenient method (Scheme 1) for the
preparation of tert-butyl esters through the in situ gen-
eration of isobutylene from tert-butyl acetoacetate using
catalytic sulfuric acid in the presence of carboxylic acid.
alcohol as the isobutylene source with catalysis by acid
and heat to form the desired esters. Such processes
4
5
Table 1. Preparation of tert-butyl esters using tert-butyl acetoacetate
Several methods for the preparation of tert-butyl esters
from carboxylic acids have been developed. These reac-
tions can be separated into two classes. The first are
methods that use irreversible reagents such as alkyl
halides, S-pyridyl-thiolates in the presence of CuBr2,
tert-butyl 2,2,2-trichloroacetimidate, N,N-dimethyl-
formamide-di-tert-butyl acetal or EDCI/DMAP/tert-
Entry
#
Starting
material
Product
%
Reaction
Yield notes
O
O
1
82
2 4
H SO ,
24 h, rt
OH
O
1
butanol. We find these methods to be undesirable
1a
3a
because they require reagents that are too expensive
for general use in large-scale work.
2
,3
O
O
2
3
OH
O
O
90
91
H
2
SO
4
,
O
O
1b
3ba
48 h, 50 °C
The second class of approaches employ isobutylene.
This gaseous reagent is volatile and its use can generate
high pressures, making use of isobutylene as a reagent in
the laboratory problematic. Recent work has been direc-
ted toward the alleviation of some of these issues by gen-
erating isobutylene in situ. These methods use tert-butyl
O
O
O
OH
H
2
4
SO ,
48 h, rt
3cb
1c
O
O
OH
4
5
95
91
H
2
SO
4
,
O
O
4
8 h, rt
O
O
3dc
1
d
O
2
OH
O
cat. H SO
O
O
2
4
rt
1
a
3a
OH
O
2
4 h
2 4
H SO ,
8
h, 50 °C
Scheme 1.
3ed
1
e
a
b
c
Refs. 2a,4a,4b.
Ref. 3b.
Refs. 3a,3b.
Ref. 1e.
Keywords: tert-Butyl esters; Isobutylene; tert-Butyl acetoacetate.
*
Corresponding author. Tel.: +1 302 831 2433; fax: +1 302 831
335; e-mail: taberdf@udel.edu
d
6
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.005

3066
D. F. Taber et al. / Tetrahedron Letters 47 (2006) 3065–3066
require a method for driving the reaction to completion
by removal of water.
1977, 42, 1286; (b) Kim, S.; Lee, S. I. J. Org. Chem. 1984,
9, 1712; (c) Dhaon, M. K.; Olsen, R. K.; Ramasamy, K. J.
Org. Chem. 1982, 47, 1962; (d) Armstrong, A.; Bracken-
ridge, I.; Jackson, R. F. W.; Kirk, J. M. Tetrahedron Lett.
4
We envisioned using tert-butyl acetoacetate as the
source of isobutylene since it could offer several advan-
tages. This procedure does not call for the use of expen-
sive reagents, the handling of gaseous isobutylene, or
harsh conditions. Further, the only byproducts would
1
988, 29, 2483; (e) Ravi, B.; Mereyala, H. B. Tetrahedron
Lett. 1989, 30, 6089; (f) Widmer, U. Synthesis 1983, 2,
35.
1
2
. For procedures for the acid catalyzed esterification with
isobutylene, see: (a) Altschul, R. J. Am. Chem. Soc. 1948,
70, 2604; (b) Altschul, R. J. Am. Chem. Soc. 1946, 68,
2569.
3. tert-Butyl esters can also be formed by the exchange of
methyl esters with tert-butyl acetate. For descriptions of
these reactions, see: (a) Stanton, M. G.; Gagne, M. R. J.
Org. Chem. 1997, 62, 8240; (b) Stanton, M. G.; Allen, C. B.;
Kissling, R. M.; Lincoln, A. L.; Gagne, M. R. J. Am. Chem.
Soc. 1998, 120, 5981.
be acetone and CO , so it would not be necessary to
2
remove water in order to drive the reaction to acceptable
conversions.
Our initial target for optimization was compound 1a.
We examined several acids including sulfuric acid,
methanesulfonic acid and p-toluenesulfonic acid as
potential catalysts. We found that sulfuric acid gave us
the highest conversions. Using excess of tert-butyl aceto-
acetate and catalytic amounts of sulfuric acid at room
temperature, we were able to obtain the desired tert-
butyl esters, across a range of substrates, in acceptable
yields (Table 1).
4
. For esterifications using the in situ generation of isobutyl-
ene, see: (a) Karmakar, D.; Das, P. J. Synth. Commun.
2
001, 31, 535; (b) Wright, S. W.; Hagemon, D. L.; Wright,
A. S.; McClure, L. D. Tetrahedron Lett. 1997, 38, 7345.
5. Representative procedure for the preparation of esters:
Carboxylic acid 1a (0.49 g, 2.48 mmol, 1 mol equiv), 0.02 g
(
0.20 mmol, 0.08 mol equiv) of concd H
2 4
SO , and 2.62 g
(
16.24 mmol, 6.5 mol equiv) of tert-butyl acetoacetate were
We believe that the procedure outlined here is a
convenient and scalable method for the conversion of
preparative quantities of carboxylic acids to their corres-
ponding tert-butyl esters.
charged to a 15 mL glass pressure tube equipped with a
threaded Teflon plug. The reaction was sealed and held at rt
for 24 h. After 24 h, the reaction vessel was cooled in a dry/
ice acetone bath to reduce any pressure that might have
been generated during the reaction. Once the contents were
frozen, the cap was cautiously removed. The contents
were transferred to a separatory funnel and partitioned
between ether and, sequentially, 1.25% aqueous NaOH and
Acknowledgments
We would like to thank Hercules Incorporated for
financial support for this work. We express our appreci-
ation to Ernest Laletas, Audrey K. Showalter and Joan
B. Updyke for NMR spectroscopy and special thanks to
Kyle J. Bottorff and George A. Lock for many helpful
discussions.
2 4
saturated brine. The organic extract was dried (Na SO )
and concentrated. The NaOH phase was acidified and
extracted with ether to recover 0.10 g (80% conversion) of
unreacted acid. The yellow oily organic residue was
chromatographed to give 0.42 g (82% yield) of 3a as a
clear oil. TLC R
cm ) 2978 (s), 1705 (s), 1597 (m), 1475 (m); H NMR
f
= 0.29 (EtOAc/hexanes, 5:95). IR (neat,
À1
1
(
400 MHz, CDCl
J = 1.5, 7.5 Hz 1H), 7.7 (dd, J = 1.4, 7.6 Hz 1H); C NMR
300 MHz, CDCl ) d: 130.7, 130.5, 129.7, 128.7, 128.0,
3
) d: 1.2 (s, 9H), 7.3 (m, 7H), 7.5 (qd,
13
References and notes
(
3
1
. (a) Wang, S.-S.; Gisin, B. F.; Winter, D. P.; Makofske, R.;
127.1, 127.0, 27.6; HRMS calcd for C17
H O (M+Na)
18 2
Kulesha, I. D.; Tzougraki, C.; Meienhofer, J. J. Org. Chem.
277.1204, found 277.1417.