Esterification of carboxylic acids with boron trichloride

Article abstract of DOI:10.1016/S0040-4039(01)00602-5

Treatment of carboxylic acids with boron trichloride followed by addition of alcohol provides the carboxylic ester. This esterification, following BCl₃ ether or ester O-C cleavage reaction conditions, proceeds cleanly in good yields with most substrates. Cleavage of benzyl esters with boron trichloride then treating with methanol affords the methyl ester.

Full text of DOI:10.1016/S0040-4039(01)00602-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3959–3961
Esterification of carboxylic acids with boron trichloride
Christopher A. Dyke and Thomas A. Bryson*
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA
Received 16 March 2001; revised 9 April 2001; accepted 11 April 2001
Abstract—Treatment of carboxylic acids with boron trichloride followed by addition of alcohol provides the carboxylic ester. This
esterification, following BCl ether or ester OꢀC cleavage reaction conditions, proceeds cleanly in good yields with most substrates.
3
Cleavage of benzyl esters with boron trichloride then treating with methanol affords the methyl ester. © 2001 Published by
Elsevier Science Ltd.
Esterification of carboxylic acids using protic and Lewis
acids is a common, fundamental process in organic
of boron trichloride. Consequently, when the amount
of boron trichloride is reduced, the yields are also
reduced. It appears that competition for trichloro-
borane by multiple Lewis base sites is overcome by
1
–3
synthesis.
Likewise, Lewis acids are employed to
2,4–7
cleave some esters as well as ethers.
Under the
reaction conditions for O-debenzylation, we find that
carboxylic acids also undergo esterification. Treatment
of the benzyl ether 1 with boron trichloride and then
addition of an excess of BCl , which results in increased
3
yields of the respective ether. In the case of phenolic
acids 4b and 4c, which have two Lewis base sites,
increasing the number of equivalents does not result in
increased yields of ester. In all other cases, acids 4d–g
with multiple Lewis base sites, including the pyridyl
acid 4g, excess reagent affords good yields of ester
5d–g. It is noteworthy that with 1–3 equiv. of BCl3,
m-methoxy acid 4e forms ester 5e in low yield and there
is also considerable methyl ether cleavage. The ratio of
the resultant ether 5e to methyl 3-hydroxybenzoate (6)
is approximately 1.5:1.
5
quenching with methanol does not produce the
olefinic-acid 3, but yields the enol-ester 2. Quenching
with water, however, does produce the seco-acid 3
(
Scheme 1). We report herein an efficient, versatile
method for the esterification of carboxylic acids.
It is our observation that carboxylic acids, in general,
form the methyl ester (Table 1) in good yield when 1–4
equiv. of boron trichloride are employed. Trichlorobo-
rane (1 equiv.) with simple acids, phenylacetic acid (4a)
for example, forms the ester in good yield. The esterifi-
cation of cinnamic and aryl acids requires a large excess
Cleavage of hindered methyl ethers is efficient with
8,9
boron trichloride, and although not hindered, the
O
OMe
OH
2) MeOH
O
1
) BCl3
OH
2
3
(1)
OBn
O
CH Cl2
2
1
2
) H O
2
OH
OH
Scheme 1.
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00602-5

3
960
C. A. Dyke, T. A. Bryson / Tetrahedron Letters 42 (2001) 3959–3961
Table 1. Reaction of carboxylic acids 4a–g with boron
trichloride
proximity of the ether and acid groups in 4e may be
responsible for the competing pathways. When 4 equiv.
are used, methyl ether cleavage is no longer observed
and yields increase dramatically. We speculate that with
4
equiv. of BCl , both the acid and ether are associated
3
with boron-minimizing interaction, and the cleavage is
no longer a competing reaction.
Substitution of other alcohols for methanol (Table 2)
10
also results in esterification, however, as the bulk of
the alcohol increases the yield decreases. Primary alco-
hols form esters in good yield. Secondary and tertiary
alcohols form esters, but the yields are not as high.
Though it is not very efficient, tert-butyl alcohol
affords the tert-butyl ester 8d. Interestingly, the same
7
reagent, boron trichloride, which cleaves benzyl esters,
also forms benzyl ester 8e.
Within the context of benzyl ester cleavage, benzyl ester
8
e is cleaved with boron trichloride then quenched with
methanol to yield the methyl ester 8a (Scheme 2). This
is a high-yielding transformation that is more versatile
than simple esterification where concentration and
removal of the undesired alcohol drives the equilibrium
to the desired ester.
The tandem OꢀC bond cleavage and ester formation
also forms amide 9 by using the same protocol but with
ammonia quench instead of alcohol. This latter process
and the formation of other acid derivatives is under
investigation.
In summary, the ether and ester cleaving property of
5,7
boron trichloride is harnessed as a simple, generally
efficient method for esterification. In addition, both
cleavage and ester formation is effected sequentially in
a one-pot process.
Table 2. Esterification of carboxylic acid 7 with varying alcohols
Entry
Alcohol
R
Yield (%)
a
b
c
d
e
MeOH
EtOH
i-PrOH
t-BuOH
BnOH
Me
Et
i-Pr
t-Bu
Bn
97
60
36
25
51
O
C
O
1
) BCl , CH Cl
3
2
2
Br
Br
C
(4)
OBn
OCH3
2
) MeOH
8e
8a
83%
Scheme 2. pseudo-Transesterification of benzyl ester 8e.

C. A. Dyke, T. A. Bryson / Tetrahedron Letters 42 (2001) 3959–3961
3961
O
O
1
) BCl , CH Cl
OH
OBn 2) NH3
3 2 2
NH2
OH
(5)
1
9
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