A catalytic oxidative esterification of aldehydes using V2O5-H2O2

Article abstract of DOI:10.1021/ol990383+

(equation presented) X=Me, OMe,NO 2,OH, OBn, Cl, Br etc. Aldehydes, in the presence of methanol, undergo oxidative transformation to the corresponding esters upon treatment with catalytic amounts of vanadium pentoxide in combination with oxidant hydrogen peroxide. Mild reaction conditions, shorter reaction times, high efficiencies, cost-effectiveness, and facile isolation of the desired products make the present methodology a practical alternative.

Full text of DOI:10.1021/ol990383+

ORGANIC
LETTERS
2000
Vol. 2, No. 5
577-579
A Catalytic Oxidative Esterification of
Aldehydes Using V O −H O
2 5
2 2
Rangam Gopinath and Bhisma K. Patel*
Department of Chemistry, Indian Institute of Technology, Guwahati-781 001, India
patel@iitg.ernet.in
Received December 2, 1999
ABSTRACT
Aldehydes, in the presence of methanol, undergo oxidative transformation to the corresponding esters upon treatment with catalytic amounts
of vanadium pentoxide in combination with oxidant hydrogen peroxide. Mild reaction conditions, shorter reaction times, high efficiencies,
cost-effectiveness, and facile isolation of the desired products make the present methodology a practical alternative.
Oxidative transformation of aldehydes to esters is often
required, and hence much effort has been devoted to find
newer methods and newer reagents effective for this type of
oxidative transformation.1,2 Catalyst methyltrioxorhe-
nium(VII), with hydrogen peroxide as oxidant, and a
cocatalyst such as bromide or chloride ions is an efficient
combination for the transformation of aldehydes to esters.3
Unfortunately, many of these procedures often require a large
excess of reagents, expensive catalysts, dry solvent, an inert
atmosphere, and photochemical conditions, causing severe
economic problems upon scale-up. Moreover, at times,
poisonous and polluting reagents, mediators, and cocatalysts
are required along with longer reaction times and drastic
reaction conditions. Also these reagents do not always prove
to be satisfactory for specific oxidation of aldehydes in
systems containing deactivating groups and olefinic func-
tions. We have therefore sought to develop a highly facile,
cost-effective, and environmentally friendly catalytic route
for esterification of aldehydes and now report success in this
endeavor.
as oxidant.4 Utilizing the in situ generated active brominating
agent (Br3 ) we have successfully brominated a wide
-
spectrum of organic substrates.5 On the basis of the versatility
of the combination of V2O5-H2O2 as oxidant, we chose to
examine its efficacy in the controlled oxidation of aldehydes
to esters in the presence of an alcohol. In this Letter we report
V2O5-H2O2-mediated oxidative esterification of wide variet-
ies of aldehydes to the corresponding methyl esters with high
yields in a single step. Our method has advantages over
previous methods with respect to environmentally benign
catalyst and reagent, cost-effectiveness, high efficiency, mild
reaction conditions, shorter reaction times, and facile isolation
of required products.
In a typical reaction, to an ice cooled solution of aldehyde
(1 mmol) in methanol (5 mL) containing 70% HClO4 (0.6
mmol) is slowly added a solution of V2O5 (0.04 mmol)
dissolved in H2O2 (4 mmol) ca. 5 °C. The reactiom times
are as shown for each substrate in Table 1.
Mechanistically, it seems plausible that the aldehyde is
oxidized with V2O5-H2O2 to the corresponding acid, which
is esterified immediately with alcohol. However when
benzoic acid is used instead of benzaldehyde (1) under
identical conditions, no methyl benzoate could be obtained.
It is most probable that this oxidation of aldehydes in an
Recently we have reported a method for the oxidative
transformation of tetrabutylammonium bromide to the cor-
responding tribromide (Br3-) using V2O5 as catalyst and H2O2
(1) Larock, R. C. ComprehensiVe Organic Transformation; VCH: New
York, 1989; pp 840-841.
(4) Chaudhuri, M. K.; Khan, A. T.; Patel, B. K.; Dey, D.; Kharmawoph-
lang, W.; Lakshmiprabha, T. R.; Mandal, G. C. Tetrahedron Lett. 1998,
39, 8163-8166.
(5) Bora, U.; Bose, G.; Chaudhuri, M. K.; Dhar, S. S.; Gopinath, R.;
Khan, A. T.; Patel, B. K. Org. Lett. In press.
(2) March, J. AdVanced Organic Chemistry; John Wiley & Sons: New
York, 1992; p 1196.
(3) Espenson, J. H.; Zhu, Z.; Zauche, T. H. J. Org. Chem. 1999, 64,
1191-1196.
10.1021/ol990383+ CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/16/2000

Table 1. Oxidative Esterificationa of Aldehydes to Corresponding Methyl Esters with V2O5-H2O2
substrate
time/h
productc
yield (%)d
ester (%)d,e
benzaldehyde (1)
3.0
0.75
0.5
7.5
5.0
2.5
3.0
6.0
5.0
5.5
0.5b
5.0
2.0
2.0b
methyl benzoate
100
100
100
93
100
100
100
83
100
96
100
100
91
100
100
100
97
100
100
100
100
100
m-bromobenzaldehyde (2)
p-methylbenzaldehyde (3)
o-hydroxybenzaldehyde (4)
o-methoxybenzaldehyde (5)
p-hydroxybenzaldehyde (6)
p-methoxybenzaldehyde (7)
4-hydroxy-3-methoxybenzaldehyde (8)
3,4-dimethoxybenzaldehyde (9)
p-chlorobenzaldehyde (10)
p-nitrobenzaldehyde (11)
p-benzyloxybenzaldehyde (12)
2-furaldehyde (13)
methyl m-bromobenzoate
methyl p-methylbenzoate
methyl o-hydroxybenzoate
methyl o-methoxybenzoate
methyl p-hydroxybenzoate
methyl p-methoxybenzoate
methyl 4-hydroxy-3-methoxybenzoate
methyl 3,4-dimethoxybenzoate
methyl p-chlorobenzoate
methyl p-nitrobenzoate
85
100
100
100
100
95
methyl p-benzyloxybenzoate (15)
methyl 2-furoate
methyl cinnamate
cinnamaldehyde (14)
a Reactions were monitored by TLC, GC. b The reaction was performed at reflux temperature after addition of the reagent under ice-cooled conditions.
1
c Confirmed by comparison with IR and H NMR of the authentic sample. d Determined by GC. e The balance is the carboxylic acid.
alcoholic medium proceeds through a hemiacetal (X1) f
vanadium hemiacetal intermediate (X3) f ester, as indicated
in Scheme 1.
substituted alcohol has been observed with other oxidizing
2
agents such as CrO3 and NIS.7
Under these conditions activated, deactivated, conjugated,
and hindered aldehydes can all be oxidized to the corre-
sponding methyl esters in excellent yields. Typically, a
V2O5-H2O2-catalyzed reaction of benzaldehyde (1) with
methanol gave methyl benzoate in quantitative yield. Under
similar experimental conditions, m-bromobenzaldehyde (2)
and p-methylbenzaldehyde (3) produced the corresponding
methyl esters, methyl m-bromobenzoate and methyl p-
methylbenzoate, respectively, in very high yields in a short
time. The reaction of aromatic aldehydes with o-substituted
compounds such as o-hydroxybenzaldehyde (4) and o-
methoxybenzaldehyde (5) to yield esters is more sluggish,
as compared to the corresponding p-substituted substrates
p-hydroxybenzaldehyde (6) and p-methoxybenzaldehyde (7).
This could be attributed to an unfavorable equilibrium to
hemiacetal due to steric strain as proposed in Scheme 1.
Steric interaction could also be responsible for the slow
reaction rate of trisubstituted aldehydes such as 4-hydroxy-
3-methoxybenzaldehyde (8) and 3,4-dimethoxybenzaldehyde
(9). Aromatic aldehydes substituted with electron-withdraw-
ing groups at the p-position such as p-chlorobenzaldehyde
(10) and p-nitrobenzaldehyde (11) react slowly. Only 10%
conversion to methyl p-nitrobenzoate is observed in 5 h for
the deactivated substrate (11), under the reaction conditions.
However, refluxing the reaction in a water bath can accelerate
the reaction rate as demonstrated in the case of p-nitro-
benzaldehyde (11). Importantly, no other side products are
obtained during reflux. Substrate p-benzyloxybenzaldehyde
(12) reacts slowly to give methyl p-benzyloxybenzoate (15)8
in quantitative yield.
Scheme 1. Proposed Mechanism of Esterification
Aldehyde under acidic conditions reacts with alcohol to
form hemiacetal (X1). It is envisaged that the initially formed
hemiacetal (X1) reacts with peracid (X2), which results from
the addition of H2O2 to vanadium(V) oxide to form a
vanadium hemiacetal type intermediate (X3).6 The conjugate
base of the peracid (X3) is an excellent leaving group for
nucleophilic displacement.6 Subsequent elimination produced
the desired product and releases the catalyst. We believe that
formation of the hemiacetal intermediate (X1) is necessary.
In the absence of alcohol, aldehydes are rapidly oxidized to
their corresponding acids. The success of the reaction is
dependent upon the selective oxidation of the hemiacetal
hydroxy moiety (X1) in the presence of a much higher
concentration of alcohol. Selective oxidation of a more
(7) McDonald, C.; Holcomb, H.; Kennedy, K.; Kirkpatrick, E.; Leathers,
T.; Vanemon, P. J. Org. Chem. 1989, 54, 1213-1215.
(8) Selected data for methyl p-benzyloxybenzoate (15): mp 95-96 °C;
IR (KBr) 2950, 1716, 1608, 1511, 1460, 1439, 1393, 1321, 1280, 1255,
1
(6) Freeman, F. Organic Synthesis by Oxidation with Metal Compounds;
Mijs W. J., De Jonge, C. H. R. I., Eds.; Plenum Press: New York, 1986;
Chapter 1, pp 2.
1173, 1116, 1009, 855, 773, 748, 702 cm-1; H NMR (400 MHz, CDCl3)
δ 3.88 (s, 3H, -OCH3), 5.12 (s, 2H, ArCH2), 6.99 (d, J ) 9 Hz, 2H, ArH),
7.30-7.45 (m, 5H, ArH), 7.99 (d, J ) 9 Hz, 2H, ArH).
578
Org. Lett., Vol. 2, No. 5, 2000

Principles of oxidative transformation can also be extended
to heterocyclic aldehydes as well. Thus, 2-furaldehyde (13)
could be smoothly converted to methyl 2-furoate in quantita-
tive yield. The efficacy of the methodology is further
demonstrated by esterification of unsaturated aldehyde such
as cinnamaldehyde (14). Longer reaction times under the
given conditions (30% in 7 h) can be due to an unfavorable
equilibrium in hemiacetal formation, due to disruption of
conjugation. Here again, refluxing the reaction mixture in a
water bath can enhance the reaction rate and improve the
yield (95% in 2 h).
highly efficient method for the synthesis of esters from
corresponding aldehydes under mild conditions. We have
enough evidence that the methodology may work equally
well for the synthesis of other esters. The reagent is cheap
and nontoxic, and the inorganic salts are removed easily.
Although the literature enumerates a number of procedures
for conversion of aldehydes to esters, the simplicity, envi-
ronmental acceptability, and inexpensiveness of our proce-
dure makes it a practical alternative. Its synthetic application
to other esters and detailed reaction mechanism are currently
under investigation and will be reported in due course.
A minor amount of carboxylic acids is also obtained for
substrates 2, 5, and 9. The esters formed do not hydrolyze
under the reaction conditions to acids; thus the minor
amounts of acids obtained are due to the overoxidation of
aldehydes.
Acknowledgment. R.G. acknowledges the financial sup-
port and B.K.P acknowledges the partial support of this
research from the institute. We thank Professor M. K.
Chaudhuri for helpful discussions.
In the above systems, H2O2 does not bring about esteri-
fication without the catalyst (V2O5) and the catalyst alone
fails to bring about esterification. The reactions can be carried
out even in the absence of any external acid, but reactions
are rather sluggish. It may be mentioned here that analogous
to methyltrioxorhenium(VII) mediated esterification,3 addi-
tion of a catalytic amount of bromide ion greatly enhances
the rate, the details of which will be reported subsequently.
In conclusion, the present method represents a simple, yet
Supporting Information Available: Detailed experi-
mental procedures for esterification of p-hydroxy benzalde-
hyde (6) to methyl p-hydroxybenzoate and p-nitrobenzalde-
hyde (11) to methyl p-nitrobenzoate and their characterization
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL990383+
Org. Lett., Vol. 2, No. 5, 2000
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