Direct oxidation of aldehydes to methyl esters with urea hydrogen peroxide and p-toluenesulfonyl chloride

Article abstract of DOI:10.2174/1570178614666170918121035

Combination of urea hydrogen peroxide and p-toluenesulfonyl chloride in methanol was proved to be facile and highly efficient for the oxidative methyl esterification of various aldehydes to the corresponding carboxylic methyl esters.

Full text of DOI:10.2174/1570178614666170918121035

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725
Letters in Organic Chemistry, 2017, 14, 725-728
LETTER ARTICLE
ISSN: 1570-1786
eISSN: 1875-6255
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Direct Oxidation of Aldehydes to Methyl Esters with Urea Hydrogen Per-
oxide and p-Toluenesulfonyl Chloride
BENTHAM
S
CIENCE
Deuk Jun Jeong, Su Bin Lee and Jong Chan Lee*
Department of Chemistry, Chung-Ang University, Seoul 06974, Korea
Abstract: Combination of urea hydrogen peroxide and p-toluenesulfonyl chloride in methanol was
proved to be facile and highly efficient for the oxidative methyl esterification of various aldehydes to
the corresponding carboxylic methyl esters.
A R T I C L E H I S T O R Y
Received: June 27, 2017
Revised: July 26, 2017
Accepted: September 01, 2017
DOI:
10.2174/1570178614666170918121035
Keywords: Aldehydes, esters, oxidation, peroxides, p-toluenesulfonyl chloride, organic chemistry.
1. INTRODUCTION
concentrated 50% aqueous H2O2 solution [17] or reagent
combination of iodine-iodobenzenediacetate was reported
earlier [18]. However, these methods also suffered from dis-
advantage like harsh reaction conditions low yield and lim-
ited range of aldehydes. Therefore, the development of effi-
cient oxidative system for the conversion of aldehydes to
methyl esters under safe and environmentally friendly metal-
free conditions would be highly appealing. Urea hydrogen
peroxide (UHP) has received great attention as a safe dry
alternative to aqueous hydrogen peroxide [19]. UHP proved
to be a valuable oxidant in various important organic reac-
tions due to its high thermal stability, ease of handling, and
environmentally benign properties. In the course of our on-
going interest in the development of sustainable and practical
oxidation methodologies, we have found that combination of
UHP and p-toluenesulfonyl chloride (TsCl) in methanol rep-
resents an excellent oxidative system for the conversion of
aldehydes to the corresponding methyl esters. In considera-
tion of environmentally friendly reactions, this protocol is
attractive, because both UHP and TsCl are inexpensive and
avoid the use of the toxic transition-metal complexes. Ini-
tially, we used benzaldehyde as a model substrate and tested
for the direct oxidative esterification of aldehydes to methyl
esters.
Carboxylic acid ester is a very important functionality in
organic chemistry and can be found in the sub-structure of
many natural products, pharmaceuticals, advanced materials,
and fine chemicals [1]. Traditionally, carboxylic acid esters
have been prepared by the nucleophilic substitution reaction
of carboxylic acids or their derivatives with alcohols in the
presence of the various acidic or basic promoters [2]. In re-
cent years, direct oxidative esterification of aldehydes has
gained considerable attention [3]. This protocol usually in-
volved the formation of hemiacetal intermediates by the re-
actions of aldehydes with alcohols and subsequent oxidation
in the presence of various oxidants such as iodine [4], N-
iodosuccinimide [5], pyridinium hydrobromide perbromide
[6], manganese dioxide [7], siloxanes-palladium [8], and
peroxovanadium [9]. However, these methods are generally
associated with certain drawbacks such as harsh reaction
conditions, low yields, long reaction times, and limited range
of applicable aldehydes. In the last decade, much interest has
aroused on the direct esterification of aldehydes using aque-
ous hydrogen peroxide as a main oxidant in combination
with a variety of transition-metal complexes such as V2O5
[10], methyltrioxorhenium [11], titanosilicate [12], iron-
copper oxide [13] and iron perchlorate [14]. Recently,
methyl esterification of aromatic aldehydes with hydrogen
peroxide in combination with metallic Lewis acids such as
calcium chloride [15], magnesium chloride [15] and zinc
bromide [16] has also been reported. However, only a few
methods which involved hemiacetal intermediates have been
known for the direct esterification of aldehydes under metal-
free reaction conditions. For example, the use of highly
CH3OH
60°C
O
O
TsCl
UHP
H OH
CH3
R
O
R
OCH3
R
H
Scheme (1). Conversion of aldehydes to methyl esters.
2. RESULTS AND DISCUSSION
*Address correspondence to this author at the Department of Chemistry,
Chung-Ang University, Seoul 06974, Korea; Tel: +82-2-820-5202;
E-mail: jclee@cau.ac.kr
Treatment of benzaldehyde with UHP (5.0 equiv.) and
TsCl (1.0 equiv.) in 3 mL of methanol for 6 h at 60°C pro-
1875-6255/17 $58.00+.00
© 2017 Bentham Science Publishers

726 Letters in Organic Chemistry, 2017, Vol. 14, No. 10
Jeong et al.
vided methyl benzoate in 93% yield. When the reaction was
performed using aqueous 35% H2O2 instead of UHP, the
methyl benzoate was obtained in significantly lower yield of
75%. In the absence of TsCl, the reaction failed to give the
desired methyl benzoate. It is thought the actual oxidant
should be p-toluenesulfonyl peroxyacid formed in situ by the
reaction of UHP and TsCl. Until now, only limited examples
of oxidative reactions utilizing sulfonic peroxyacid were
known. For example, polymer supported sulfonic peroxyacid
formed in situ by the reaction of sulfonic acid moiety on the
polymer surface with hydrogen peroxide were applied for the
dihydroxylation of olefins [20] or the oxidation of aldehydes
to carboxylic acids [21]. In addition, resin supported sulfonic
peroxyacid formed in situ by the reaction of perfluorinated
resin with hydrogen peroxide was utilized in direct esterifi-
cation of aldehyde to esters in the presence of magnesium
sulfate for the narrow range of aldehyde substrates [22]. To
the best of our knowledge, there is no precedent for the utili-
zation of organic sulfonic peroxyacid for the effective oxida-
tive esterification of aldehyde. We initially examined the
effect of the variation of alcohols on the present protocol. As
shown in Table 1, various alcohols such as ethanol, n-
propanol, isopropanol, and t-butanol gave the desired prod-
ucts in the range of modest to good yields whereas phenol
gave unreacted benzaldehyde. Methanol gave the highest
yield among all the tested alcohols.
Encouraged by the excellent methyl benzoate formation,
this protocol was explored for the oxidative methyl esterifi-
cation of a variety of aldehydes. It was noted that the present
reaction conditions exhibit excellent reactivity with various
aromatic, aliphatic and heterocyclic aldehydes as shown in
Table 2. In most cases, the oxidation of aldehydes exclu-
sively afforded the corresponding methyl ester in high yield.
Table 1. Influence of different alcohols for the conversion of benzaldehyde to esters using UHP/TsCla.
Entry
Solvent
Time (h)
Yield (%)b
1
2
3
4
5
6
MeOH
Ethanol
6
93
78
10
15
20
20
24
n-propanol
2-Propanol
t-Butanol
Phenol
56
50
15
N.R.c
aReaction conditions: benzaldehyde (1.0 mmol), UHP (4.0 mmol), TsCl (1.0 mmol), alcohol (3 mL), 60°C. bIsolated yield. cNo reaction.
Table 2. Oxidative esterification of aldehydes to methyl esters using UHP/TsCl.
Entry
Substrate
Product
Time (h)
Yield (%)a
O
H
O
O
1
6
93
O
H
O
O
Cl
2
8
84
Cl
O
O
H
H
H
O
O
O
3
4
5
8
8
8
8
93
80
95
88
Cl
Cl
Cl
Br
F
O
O
Cl
Br
Cl
O
Cl
O
O
O
O
H
6
F
(Table 2) Contd….

Direct Oxidation of Aldehydes to Methyl Esters with Urea Hydrogen Peroxide
Letters in Organic Chemistry, 2017, Vol. 14, No. 10 727
Entry
Substrate
Product
Time (h)
Yield (%)a
O
O
H
H
O
O
7
8
98
O2N
O2N
NC
O
H
O
8
8
98
NC
O
O
O
9
8
8
8
88
96
84
O
O
10
11
H
O
O
O
O
O
H
O
O
O
H
O
12
8
80
O
O
O
O
O
O
O
S
O
S
13
14
15
7
4
7
82
86
83
H
O
H
O
O
O
O
O
H
H
O
O
16
8
7
98
76
O
O
17
18
H
O
O
O
8
8
70
75
H
O
O
O
19
H
O
aIsolated yield.
Aromatic aldehydes with electron-donating or electron-
withdrawing groups also provided the corresponding methyl
esters in high yields. Aromatic aldehydes with orto-
substituents also provided the desired methyl carboxylates in
high yields (entries 2, 4, 9 and 11). In addition, the reaction
worked well for 3-phenyl propanal (entry 16). Moreover, an
enal as trans-cinamaldehyde was successfully converted to
the methyl trans-cinnamate under the present reaction condi-
tions in high yield (entry 15).
esterification protocols reported earlier, electron rich aro-
matic aldehydes and heterocyclic aldehydes provided lower
yields [16], hence this method can be served as a viable al-
ternative method.
It is thought that the reaction presumably proceeds
through oxidation of hemiacetal intermediate with p-
toluenesulfonyl peroxyacid similar to that of the peroxide
mediated conversion of alcohol to ester reported previously
[23].
We also attempted direct esterification of cyclic and
acyclic aliphatic aldehydes to give high yields of correspond-
ing methyl esters (entries 17, 18 and 19). In all of the exam-
ined cases, the carboxylic acid by-product had not been de-
tected. In most of the hydrogen peroxide mediated methyl
3. EXPERIMENTAL
A general experimental procedure for the esterification of
aldehydes is as follows: An aldehyde (1 mmol) was reacted

728 Letters in Organic Chemistry, 2017, Vol. 14, No. 10
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with urea hydrogen peroxide (5 mmol) and p-toluenesulfonyl
chloride (1 mmol) in 3 mL of methanol at 60°C for 6-8 h.
After completion of the reaction, the solvent was removed in
vacuo and the residue was dissolved in ethyl acetate (20 ml),
washed with saturated sodium bicarbonate solution (20 ml)
and dried over anhydrous sodium sulfate. After removal of
solvent, the crude product was purified by column chroma-
tography (230-400 mesh silica gel, n-hexane/ethyl acetate =
1/4). Purification of the product with silica gel flash column
chromatography with ethyl acetate: hexane (1:4) eluent
yielded the pure methyl carboxylic ester.
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In conclusion, we have developed a novel and effective
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aldehydes by use of the reagent combination of UHP and
TsCl. This method employs readily available and inexpen-
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CONSENT FOR PUBLICATION
Not applicable.
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CONFLICT OF INTEREST
Karade, N.N.; Budhewar, V.H.; Katkar, A.N.; Tiwari, G.B.
ARKIVOC, 2006, 11, 162-167.
The authors declare no conflict of interest, financial or
otherwise.
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