Oxidative esterification of aldehydes with alcohols and phenols in air

Article abstract of DOI:10.3184/030823410X12670951969185

Nucleophilic carbene-catalysed oxidative esterification of aldehydes with alcohols and phenols without additional oxidant under an air atmosphere has been achieved, which provides a metal-free new methodology for the oxidative esterification of aldehydes.

Full text of DOI:10.3184/030823410X12670951969185

130 RESEARCH PAPER
MARCH, 130–132
JOURNAL OF CHEMICAL RESEARCH 2010
Oxidative esterification of aldehydes with alcohols and phenols in air
Shuanghua Chenga, Jiuxi Chena, Wenxia Gaoa, Huile Jina, Jinchang Dinga,b and Huayue Wua*
aCollege of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. China
bWenzhou Vocational andTechnical College, Wenzhou, 325035, P. R. China
Nucleophilic carbene-catalysed oxidative esterification of aldehydes with alcohols and phenols without additional
oxidant under an air atmosphere has been achieved, which provides a metal-free new methodology for the oxidative
esterification of aldehydes.
Keywords: oxidative esterification, alcohols, phenols, nucleophilic carbene
Direct transformation of aldehydes to esters under mild con-
ditions is an extremely useful conversion in organic synthesis,
particularly in the synthesis of natural products.1–3 Several
conversions using environmentally unacceptable complexes of
different heavy metal oxidants such as rhenium,4 rhodium,5
ruthenium,6 MnO2,7 pyridinium dichromate,8 [IrCl(cod)]29 and
the highly expensive silver10 have been reported. The efficiency
of this protocol has been enhanced by using reagents including
hydrogen peroxide11 as the principal oxidant coupled with
V2O512 and titanosilicates.13 Other oxidative esterification
protocols involved in the presence of chlorites,14 N-
halosuccinimide,15 PhI(OAc)216 and by photochemical17 as well
as electrochemical means.18 Connon and co-workers19 reported
direct oxidative esterification of aldehydes with alcohols in
the presence of a stoichiometric oxidant catalysed by the
N-heterocyclic carbenes (NHCs) from thiazolium salts. Very
recently, Cao and co-workers20 reported that gold supported on
nanocrystalline β-Ga2O was a versatile bifunctional catalyst
for oxidative transforma3tion of aldehydes into esters. However,
most of the methods are associated with some drawbacks,
which include the use of hazardous reagents, drastic reaction
conditions, metal-catalyst and tedious work up procedure.
Moreover, less attention has been paid to the esterification
reaction of aldehydes with phenols. Thus, developing versatile
approaches to the oxidative esterification reaction of aldehydes
with alcohols or phenols is still a highly desired goal in organic
synthesis.
employing the combination of 4a as a precursor of an N-
heterocyclic carbene (NHC) (15 mol %), and Cs2CO (2.0
equiv) in dry cyclohexane at 25 °C in air (Table 1, ent3ry 9).
Encouraged by this result, we further optimised the reaction
conditions using other NHC precursors (Scheme 1). The
Table 1 Screening conditionsa
Entry Catalyst
Base/equiv
Solvent
Yield/%b
1
2
None
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
Cs2CO3 (2)
None
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Toluene
0
0
3
CsF (2)
40
<5
57
51
<5
<5
67
52
50
58
12
15
<5
<5
15
72
80
42
4
Na2CO3 (2)
K2CO3 (2)
NaOH (2)
DABCO(2)
Et3N (2)
Cs CO (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (1)
Cs2CO3 (0.6)
Cs22CO33 (0.2)
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Dioxane
Methanol
THF
DMF
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Cyclohexane
Recently, we reported the palladium-catalysed aromatic
esterification of aldehydes with organoboronic acids and
molecular oxygen.21 Here, we report the nucleophilic carbene-
catalysed oxidative esterification reaction of aldehydes with
alcohols and phenols without additional oxidant under an air
atmosphere.
4d
4a
4a
4a
The model reaction of piperonal 1a with methanol was
conducted to screen for optimal reaction conditions. After
careful screening, to our delight, a 67 % yield of methyl
benzo[d][1,3]dioxole-5-carboxylate (3a) was obtained by
a All reactions were run with piperonal (60 mg, 0.4 mmol),
methanol (48 µL, 1.2 mmol), catalyst (15 mol%) and base in
2 mL of dry solvent for 10 h at 25 oC in air.
b Isolated yields.
Scheme 1 Precursors of N-heterocyclic carbene.
* Correspondent. E-mail: huayuewu@wzu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2010 131
selected results, for catalysts, solvents and bases are listed in
Table 1.
On the other hand, the use of other alcohols was investi-
gated. In addition to ethanol, piperonal could be esterified with
pentanol and iso-amyl alcohol (Table 2, entries 2–4). The
secondary alcohol isopropanol also reacted with piperonal to
give the ester 3e in 57% yield (Table 2, entry 5).
Furthermore, the oxidative esterification reactions of
piperonal with the phenols were also investigated under the
same conditions. To our delight, 3m and 3n were obtained in
55% and 53% yields respectively (Scheme 2). This procedure
represents a simple, direct method for the synthesis of aryl
benzoate derivatives.
In summary, we have developed the direct oxidative esterifi-
cation of aldehydes with alcohols and phenols catalysed by
N-heterocyclic carbenes without the additional oxidant at
ambient temperature under an air atmosphere. Investigations
on the application of the protocol are currently underway in
our laboratory.
Reaction with 4d as catalyst provided the corresponding
methylester in 15% yield and 4b and 4c proved nearly inactive
(Table 1, entries 15–17), so it was known to us that 4a was the
most active catalyst among those above (Table 1, entry 9).
Among the screened solvents, toluene, methanol, dioxane,
THF and DMF afforded products in 52%, 58%, 50%, 12% and
15% yields respectively (Table 1, entries 10–14). However, the
reaction with cyclohexane as solvent gave product in 67%
yield (Table 1, entry 9). Among Na2CO3, K CO3, NaOH, CsF,
Cs2CO3 and DABCO, Cs CO is the best 2base, but reaction
with NEt3 as base could ha2rdly3provide the corresponding ester
(entries 3–9). Subsequently, we examined the effect of the
amount of base for the esterification reaction (Table 1, entries
18–20), and reaction with 0.6 equiv of Cs2CO as base pro-
vided the product in 80% yield. So we adopted 3the conditions
with 4a (15 mol %), and Cs2CO3 (0.6 equiv.) at 25 °C in air in
the present protocol.
Experimental
Chemicals and solvents were either used as purchased or purified
by standard techniques. IR spectra were recorded on a Bruker-
EQUINOX55 spectrometer. NMR spectroscopy was performed on a
Bruker-300 spectrometer or Bruker-500 spectrometer using CDCl3 as
the solvent with tetramethylsilane (TMS) as an internal standard at
room temperature. Chemical shifts are given in δ relative to TMS,
the coupling constants J are given in Hz. Mass spectra (MS) was mea-
sured with a Thermo Finnigan LCQ-Advantage. Elemental analyses
were carried out using a Carlo-Erba EA1112 instrument. Column
chromatography was performed using EM Silica gel 60 (300–400
mesh).
With the optimised conditions in hand, the reactions of
different aldehydes with methanol were examined (Table 2).
A series of substituted aromatic aldehydes with electron-
donating or electron-withdrawing groups attached to the
aromatic ring were investigated. Aldehydes with electron-
donating groups such as piperonal 1a and p-methylbenzalde-
hyde 1b provided the corresponding methyl ester in 80 % and
75% yields respectively (Table 2, entries 1 and 6). Electron-
withdrawing substituents on the aromatic ring of aldehyde
decrease the yields, 1c–h (Table 2, entries 7–12). Moreover,
o-nitrobenzaldehyde 1f (Table 2, entry 10) provided the
corresponding product 3j in 34% yield, which is lower than
m-substituted (40 %, Table 2, entry 11) and p-substituted (51%,
Table 2, entry 12) analogues which may be partly due to a
steric hindrance effect.
General procedure
A Schlenk reaction tube was charged with aldehyde (0.4 mmol), 4a
(20.6 mg, 15 mol %), Cs2CO3 (78 mg, 0.6 equiv), alcohol (1.2 mmol)
and 2 mL of dry cyclohexane in an air atmosphere, then the mixture
was stirred for 10 hours at room temperature. After completion of the
reaction, as indicated by TLC, the reaction mixture was extracted with
ethyl acetate (3×10 mL), concentrated under reduced pressure and the
residue was purified by flash column chromatography on silica gel to
give the desired product 3. The physical and spectroscpic data of the
compounds 3a–n are as follows.
Table 2 Esterification reactions of aldehydes with alcoholsa
Methyl benzo[d][1,3]dioxole-5-carboxylate (3a)22: 1H NMR
(CDCl3, 300 MHz): δ 3.80 (s, 3H), 5.96 (s, 2H), 6.74–7.59 (m, 3H);
13C NMR (CDCl3, 75 MHz): δ 52.2, 101.9, 108.1, 109.7, 124.3, 125.5,
147.9, 151.7, 166.6.
Methyl benzo[d][1,3]dioxole-5-carboxylate (3b)23: 1H NMR
(CDCl3, 300 MHz): δ 1.37 (t, J = 7.1 Hz, 3H), 4.33 (q, J = 7.1 Hz, 2H),
6.02 (s, 2H), 6.81–7.67 (m, 3H); 13C NMR (CDCl3, 75 MHz): δ 14.3,
61.0, 101.9, 108.0, 109.6, 124.7, 125.4, 147.8, 151.6, 166.1.
Pentyl benzo[d][1,3]dioxole-5-carboxylate (3c)24: 1H NMR (CDCl ,
300 MHz): δ 0.88–0.95 (m, 3H), 1.34–1.44 (m, 4H), 1.70–1.737
(m, 2H), 4.27 (t, J = 6.7 Hz, 2H), 6.03 (s, 2H), 6.82–7.67 (m, 3H);
13C NMR (CDCl , 75 MHz): δ 14.1, 22.5, 28.4, 28.6, 65.2, 101.9,
108.1, 109.6, 1243.7, 125.4, 147.8, 151.6, 166.2.
Entry Ar
R
Product Yield/%b
1
2
3,4-(OCH2O)-C6H3 1a CH
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
68
50
52
57
75
59
70
51
34
40
51
1a
CH3CH2
3
1a
CH33(CH2)
(CH ) CH4(CH2)2
(CH33)22CH
CH
4
1a
5
1a
6
p-MeC6H4 1b
p-ClC6H4 1c
p-BrC H 1d
2,4-Cl6C4H 1e
o-NO22C66H43 1f
m-NO2C6H 1g
p-NO2C6H441h
7
CH3
8
CH3
Isopentyl benzo[d][1,3]dioxole-5-carboxylate (3d)25: 1H NMR
(CDCl3, 300 MHz): δ 0.95–0.98 (m, 6H), 1.60–1.67 (m, 3H), 4.28–
4.33 (m, 2H), 6.02 (s, 2H), 6.81–7.66 (m, 3H); 13C NMR (CDCl3,
75 MHz): δ 22.7, 25.4, 37.6, 63.7, 101.9, 108.1, 109.6, 124.7, 125.4,
147.8, 151.6, 166.2.
9
CH3
10
11
12
CH3
3j
3k
3l
CH3
CH33
Isopropyl benzo[d][1,3]dioxole-5-carboxylate (3e)26: 1H NMR
(CDCl3, 300 MHz): δ 1.28 (d, J = 6.24 Hz, 6H), 5.10–5.18 (m, 1H),
5.95 (s, 2H), 6.75–7.59 (m, 3H); 13C NMR (CDCl , 125 MHz): δ 22.0,
68.2, 101.7, 107.9, 109.5, 125.0, 125.2, 147.6, 1531.4, 165.5.
a All reactions were run with alcohols (1.2 mmol), aldehydes
(0.4 mmol), 4a (20.6 mg, 15 mol %) and Cs2CO (78 mg, 0.6
equiv) in 2 mL of dry cyclohexane for 10 hours at325 °C in air.
b Isolated yields.
Scheme 2 Reactions of piperonal with phenols.

132 JOURNAL OF CHEMICAL RESEARCH 2010
Methyl 4-methylbenzoate (3f)23: 1H NMR (CDCl3, 300 MHz):
δ 2.33 (s, 3H), 3.82 (s, 3H), 7.15–7.19 (m, 2H), 7.84–7.87 (m, 2H);
13C NMR (CDCl3, 75 MHz): δ 21.6, 51.9, 127.4, 129.0, 129.6, 143.5,
167.2.
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Electronic Supplementary Information
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Received 30 December 2009; accepted 14 February 2010
Paper 100937 doi: 10.3184/030823410X12670951969185
Published online: 22 March 2010

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