Zinc-catalyzed oxidative esterification of aromatic aldehydes

Article abstract of DOI:10.1016/j.tetlet.2012.04.111

A general and efficient protocol for the oxidative esterification of aldehydes has been developed. By using 10 mol % of ZnBr₂ and 4 equiv of H₂O₂, 21 examples of esters were produced in good to excellent yields. Both electron-donating and electron-withdrawing functional groups are tolerable under our reaction conditions.

Full text of DOI:10.1016/j.tetlet.2012.04.111

Tetrahedron Letters 53 (2012) 3397–3399
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Zinc-catalyzed oxidative esterification of aromatic aldehydes
⇑
Xiao-Feng Wu
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou, Zhejiang Province 310018, People’s Republic of China
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A general and efficient protocol for the oxidative esterification of aldehydes has been developed. By using
Received 29 March 2012
Revised 20 April 2012
Accepted 24 April 2012
Available online 1 May 2012
1
2 2 2
0 mol % of ZnBr and 4 equiv of H O , 21 examples of esters were produced in good to excellent yields.
Both electron-donating and electron-withdrawing functional groups are tolerable under our reaction
conditions.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Zinc catalyst
Aldehyde
Ester
Oxidation
2 2
H O
The application of zinc salts as catalysts in organic synthesis has
Here, we wish to report an efficient zinc-catalyzed oxidative
esterification of aromatic aldehydes. H as green oxidant was ap-
plied in this reaction which generates water as the only by-prod-
uct. With 10 mol % of ZnBr and 4 equiv of H , 21 examples of
esters were produced in 60–95% of yields.
Initially, the reaction of benzaldehyde (1 mmol) in methanol
(2 mL) was carried out with ZnCl (10 mol %; anhydrous) as the
pre-catalyst and H (2 mmol) as the oxidant. To our delight,
1
attracted a lot of attention during the last decade. Because of their
inexpensiveness, abundance, and low toxicity, zinc salts have been
tested and used in organic synthesis and also been used to take the
place of expensive and toxic metals in some reactions. Thus the
group of Enthaler has developed a series of novel methodologies
2 2
O
2
2 2
O
1o–t
for the transformation of primary amides into nitriles,
which
2
was reported with palladium catalyst before.2
2 2
O
Carboxylic acid derivatives constitute integral parts of poly-
mers, pharmaceuticals, and agrochemicals, as well as building
blocks for organic synthesis and natural products. Typically, they
38% of the desired ester was formed with 50% conversion of benz-
aldehyde (Table 1, entry 1). Benzoic acid and (dimethoxymeth-
yl)benzene were also detected as by-products in the reaction.
Because of the low conversion, we decided to increase the amount
are prepared from the corresponding acid, activated ester, or acid
3
halide in stoichiometric reactions with
O
nucleophiles. An
of oxidant used. With 4 mmol of H
improved to 60% with 82% conversion (Table 1, entry 2). Then we
started to check the influence of different zinc salts, ZnBr gave
70% of methyl benzoate and 43% of the product was produced with
Zn(OTf) as the pre-catalyst (Table 1, entries 3 and 4). But to our
surprise, no ester was formed by using Zn(CN) and Zn(OAc) as
2 2
O , the yield of the ester was
interesting and more direct manner is the oxidative esterification
4
of the readily available aldehydes with alcohols. But these poten-
2
tially valuable procedures require the use of stoichiometric heavy-
metal oxidants or expensive transition metal catalysts.5 Recently,
the group of Darcel reported a general and efficient iron-catalyzed
2
2
2
oxidative esterification of aldehydes.6 Fe(ClO
)
3
ÁxH
O was used as
the pre-catalysts (Table 1, entries 5 and 6). Some other cheap met-
als were also tested, such as, calcium salts, manganese salts, mag-
nesium salts, and also lithium chloride. Their chloride salts
resulted in 56–60% yields of the desired ester with good conver-
sion, but non-chloride salts did not give any product (Table 1, en-
4
2
the pre-catalyst, both aromatic and aliphatic aldehydes can be
transformed into esters in good to excellent yields. But the pres-
ence of perchlorate counterion is potentially explosive, especially
7
in the case of lithium cation. Taking the development of environ-
mental benign methodologies into consideration; it will be
extremely interesting for synthetic chemists to develop a cheap
metal-catalyzed oxidative esterification of aldehydes with green
oxidants.
2
tries 7–14). Based on these results, ZnBr was chosen as the pre-
catalyst for further optimization. The yield of the ester decreased
to 35% by using 1 mL of methanol as the solvent (Table 1, entry
15). In contrast, 89% of methyl benzoate and 99% of conversion
was achieved with 4 mL of methanol as the solvent (Table 1, entry
1
6). No ester was formed in the absence of catalyst, but only
⇑
Tel.: +49 381 1281 343.
E-mail address: xiao-feng.wu@catalysis.de
benzoic acid was detected (Table 1, entry 17). Because of the
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.111

3
398
X.-F. Wu / Tetrahedron Letters 53 (2012) 3397–3399
Table 1
Table 2 (continued)
a
Oxidative esterification of benzaldehyde
Entry
Aldehyde
Esters
Yieldb (%)
83
CHO
CHO
CO Me
CHO [M] 10 mol%, H O2
CO Me
2
2
2
CO H
2
1
0
1
Cl
Br
Cl
Br
MeOH, RT, air
1
mmol
CO Me
2
1
88
61
Entry Metal salt
10 mol %)
H
2
O
2
Conv.b
(%)
Yieldb
(%)
Select.
(%)
(
(equiv)
CHO
CO Me
2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
ZnCl
ZnCl
2
2
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
50
82
90
77
50
68
48
30
45
60
85
72
82
80
96
99
15
38
60
70
43
0
76
73
78
56
0
0
0
0
0
1
1
2
3
2
O N
O N
2
2
ZnBr
Zn(OTf)
Zn(OAc)
Zn(CN)
Mn(OAc)
Ca(OH)
Ca(OAc)
Mg(OAc)
MgCl
MnCl
2
2
65
90
CHO
CO
Me
2
O
S
O
S
2
2
0
0
0
0
3
14
15
CHO
CO Me
2
2
2
CHO
CO Me
2
1
1
1
1
1
1
1
1
2
Á4H
2
O
0
0
60
88
84
75
2
60
57
57
56
35
89
70
79
69
70
36
90
0
CHO
CHO
CHO
CHO
CHO
CHO
CO Et
2
2
CaCl
LiCl
2
16
17
18
19
c
CO Pr
ZnBr
ZnBr
/
2
2
d
2
0
CO iPr
2
a
Catalyst (10 mol %), benzaldehyde (1 mmol), MeOH (2 mL), H
water), rt, air, 16 h.
Conversion and yield were determined by GC using hexadecane as the internal
standard based on benzaldehyde.
2 2
O (30 % in
b
CO
CH
CF
2
2
3
80
89
c
MeOH (1 mL).
MeOH (4 mL).
d
CO nBu
2
c
2
0
1
85
CO nPent
2
2
86
Table 2
a
Zinc-catalyzed oxidative esterification of aldehydes
a
ZnBr
2
(10 mol %), aldehydes (1 mmol), ROH (4 mL),
H
2
O
2
(30 % in water,
4
mmol), rt, air, 16 h (reaction time is not optimized).
ZnBr (10 mol%)
CHO
2
CO R'
b
2
Yield was determined by GC using hexadecane as the internal standard based
on aldehyde.
H O (4 mmol)
2
2
c
Isolated yield.
R
R'OH (4 mL)
RT, 16 h
R
Entry
1
Aldehyde
Esters
Yieldb (%)
2 2
decomposition of H O , we need an excess amount in order to have
satisfied conversion. With 4 ml of MeOH to dilute the reaction
solution, the direct oxidation of aldehyde can be suppressed in
some distance. But the activation of aldehyde with zinc salt is still
valid. We did not see the influence of air in our reaction system;
the reaction can still happen if we do the reaction under argon
CHO
CO Me
2
89
95
CHO
CHO
CO Me
2
c
2
3
4
90
CO Me
90
atmosphere.
2
c
81
With the best reaction conditions in our hand,8 we decided to
test the generality and efficiency of this methodology. As shown
in Table 2, para-, meta-, and ortho-substituted benzaldehydes re-
acted with methanol under standard reaction conditions with
81–95% of yields (Table 2, entries 2–4). Naphthyl substitution
can also be tolerated, and resulted in 88% of the corresponding
ester (Table 2, entry 5). In addition, phenyl, methoxy-, and phen-
oxy-decorated benzaldehydes can be transformed into the desired
esters in 85–93% of yields (Table 2, entries 6–8). Besides the men-
tioned electron-donating functional groups, electron-withdrawing
CHO
CO Me
2
81
88
CHO
CO Me
2
5
CHO
CO Me
2
6
7
8
9
85
Ph
Ph
CHO
CHO
CO Me
92
2
substitutions can also be tolerated. F-, Cl-, Br-, and NO
methyl esters were synthesized from their parent aldehydes in
1–88% of yields (Table 2, entries 9–12). Moreover, heterocyclic
and ,b-unsaturated aldehydes can also be applied as substrates
and gave the desired products in moderate to excellent yields
60–90%; Table 2, entries 13–15). But aliphatic aldehydes like
2
-substituted
c
8
1
MeO
PhO
F
MeO
PhO
F
6
CO Me
93
2
c
a
8
0
(
CHO
CO Me
2
cyclohexanecarbaldehyde and pentanal did not give any desired
esters under our standard reaction conditions.
80

X.-F. Wu / Tetrahedron Letters 53 (2012) 3397–3399
3399
Besides methanol, the other low boiling point alcohols were
also tested (Table 2, entries 16–21). Ethanol, propanol, and even
pentanol were all successfully reacted with benzaldehyde and gave
the corresponding esters in 75–88% of yields. When we carried out
the reaction of benzaldehyde with phenol or tert-butanol, only
benzoic acid was formed under our conditions.
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In conclusion, a general and efficient protocol for oxidative
esterification of aldehydes has been developed. By using 10 mol %
of ZnBr and 4 equiv of H O , 21 examples of different esters were
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2
(10 mol %), and a
stirring bar was added. Then H (4 mmol; 30% aq) was added slowly to the
2 2
O
(
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ethyl acetate (3 mL) were injected, a part of the solution was taken for GC and
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