Metal-free aerobic oxidative esterification of aromatic aldehydes promoted by potassium fluoride (KF)

Article abstract of DOI:10.1002/jccs.201800344

We investigated the oxidative esterification of aldehydes with alcohols/phenols to produce a range of esters. In this approach, we conducted the reaction under metal-free conditions at room temperature. The reactions were promoted by potassium fluoride (KF) as the additive, resulting in the desired product in good to high yields. This procedure was found to be effective for the production of aryl esters, which are challenging in most of the available reports. It is vital for this procedure not to exclude air as the source of oxygen.

Full text of DOI:10.1002/jccs.201800344

Received: 8 September 2018
DOI: 10.1002/jccs.201800344
Revised: 14 May 2019
Accepted: 14 May 2019
C O M M U N I C A T I O N
Metal-free aerobic oxidative esterification of aromatic aldehydes
promoted by potassium fluoride (KF)
Roghaye Soltani | Arash Ghaderi
Department of Chemistry, College of
Sciences, University of Hormozgan, Bandar
Abstract
Abbas, Iran
We investigated the oxidative esterification of aldehydes with alcohols/phenols to
produce a range of esters. In this approach, we conducted the reaction under metal-
free conditions at room temperature. The reactions were promoted by potassium
fluoride (KF) as the additive, resulting in the desired product in good to high
yields. This procedure was found to be effective for the production of aryl esters,
which are challenging in most of the available reports. It is vital for this procedure
not to exclude air as the source of oxygen.
Correspondence
Arash Ghaderi, Department of Chemistry,
College of Sciences, University of
Hormozgan, Bandar Abbas 71961, Iran.
Email: aghaderi@hormozgan.ac.ir
Funding information
University of Hormozgan; Iran National
Science Foundation, Grant/Award Number:
95825781
K E Y W O R D S
metal-free, oxidative esterification, potassium fluoride
iodine-promoted,[17] reactions are also available in the litera-
ture for the conversion of aldehydes into esters. Here, we
1 | INTRODUCTION
report an alternative approach for the conversion of alde-
hydes to esters under metal-free conditions at room
temperature.
Ester functionality occurs abundantly in many synthetic and
natural products.[1] Hence, searching for new synthetic
methods for the interconversion of different functional
groups into esters is highly valued. The traditional methods
for the synthesis of esters are Fischer esterification[2] and
Schotten–Baumann reaction.[3] The former includes an acid-
catalyzed reaction between a carboxylic acid and an alcohol,
while the latter involves the base-catalyzed reaction between
an acid chloride and an alcohol. In addition, Williamson-
type esterification reaction between a carboxylate and an
activated carbon is another classical reaction for the synthe-
sis of esters.[4] As an alternative approach, the direct conver-
sion of aldehydes to esters via the oxidative process have
attracted significant attention.[5] In this methodology, differ-
ent catalysts have been used, such as copper,[6] nickel,[7]
palladium,[8] etc.[9] In addition to the metal-catalyzed reac-
tions, a literature survey shows that this transformation could
be accomplished under metal-free conditions in the presence
of organocatalysts such as N-heterocyclic carbenes
(NHCs),[10] acetone cyanohydrin,[11] N-iodosuccinimide,[12]
trichlorocyanuric acid (TCCA),[13] etc.[14] Furthermore,
cyanide-promoted reactions,[15] along with oxone-[16] and
We began our optimization studies with the reaction of
4-nitrobenzaldehyde and ethanol at room temperature under
air atmosphere (Table 1). Initially, we used 1,8-diazabicyclo
(5.4.0)undec-7-ene (DBU) as the base and N,N-
dimethylformamide (DMF) as the solvent. The reaction
failed under these conditions, and no product was observed
after an 18-hr reaction time (Table 1, entry 1). Changing the
base to CS2CO3 and K3PO4 resulted in the formation of the
desired product in 34 and 56% isolated yields, respectively
(Table 1, entries 2, 3). Recently, Zeng et al. used the fluoride
ion to promote the conversion of amides to esters.[18]
Inspired by this work, we used potassium fluoride (KF) as
the base for our model reaction. Under these conditions, the
desired ester was isolated in 69% yield (Table 1, entry 4).
No product was obtained when changing the solvent to
CH3CN, EtOH, and water (Table 1, entries 5–7). Therefore,
we have selected KF as the best base and DMF as the sol-
vent of choice. We have also checked the effect of the
amount of KF in the reaction. Increasing the amount of KF
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–5.
http://www.jccs.wiley-vch.de
1

2
SOLTANI AND GHADERI
TABLE 1 Optimization of the
reaction conditionsa
O
O
H
O
Base
+
OH
O2N
Solvent, rt, air
18 h
O2N
1a
2a
3a
Entry
Base
Solvent
DMF
DMF
DMF
DMF
CH3CN
EtOH
H2O
Yield (%)
1
DBU
Cs2CO3
K3PO4
KF
—
34
56
69
—
—
—
73
87
—
2
3
4
5
KF
6
KF
7
KF
8b
9c
10
KF
DMF
DMF
DMF
KF
NaF
aReaction conditions: 4-nitrobenzaldehyde (0.5 mmol), EtOH (1 mmol), base (1 mmol), solvent (3 mL) at room
temperature.
bKF (2 mmol) was used.
cKF (4 mmol) was used.
to 4 eq. resulted in the desired product with 73% yield
(Table 1, entry 8). Further increase of KF to 8 eq. improved
the yield up to 87% (Table 1, entry 9). To our surprise, the
reaction using NaF instead of KF failed, showing the impor-
tance of the counterion in this reaction (Table 1, entry 10).
This effect is probably due to the higher nucleophilicity of
KF in comparison with NaF. Therefore, these conditions
were considered optimum.
Using these optimized conditions, we prepared a variety
of esters using structurally different alcohols/phenols
(Table 2). As mentioned above, the reaction of
4-nitrobenzaldehyde (1a) with ethanol (2a) proceeded well,
giving the desired product 3a (Figures S1 and S2) with an
87% yield within an 18-hr reaction time (Table 2, entry 1).
Changing the alcohol to tetraethyl orthosilicate resulted in
the decreased yield of the desired product 3a to 34%
(Table 2, entry 2). The corresponding methyl ester 3b
(Figures S3 and S4) was also synthesized in 85% isolated
yields within 16 hr (Table 2, entry 3). The reaction of
4-nitrobenzaldehyde (1a) with isoamyl alcohol (2d) gave the
desired product 3c (Figures S5 and S6) with 83% isolated
yield (Table 2, entry 4). 2-Butanol (2e) was also tested in
this reaction as a secondary alcohol. In this case, 45% of the
product 3d (Figure S7) was isolated from the reaction mix-
ture (Table 2, entry 5). The reaction of 3-nitrobenzaldehyde
with tetraethyl orthosilicate resulted in the formation of the
product 3e (Figure S8) in moderate yield (Table 2, entry 6).
As there are only few reports for the synthesis of aryl esters
from aldehydes,[8,10,19] we decided to apply our system for
the synthesis of aryl esters. For this aim, we used phenol
derivatives as the coupling partners (Table 2, entries 7–11).
Under the optimized conditions, 4-nitrobenzaldehyde
reacted with phenol, giving the corresponding ester 3f
(Figures S9 and S10) with a 64% yield within 21 h (Table 2,
entry 7). Likewise, 4-methoxyphenol was also reactive under
the same conditions, producing 3g (Figures S11 and
S12) with an 86% yield (Table 2, entry 8). Moderate yield of
the product 3h (Figures S13 and S14) was obtained when
using 4-chlorophenol as one of the reactants, leaving the
chloride functionality intact (Table 2, entry 9). The reaction
failed when bulky 1-naphthol or 2-naphthol were used
(Table 2, entries 10, 11).
In order to obtain some information from the reaction
mechanism, we performed the reaction of 4-nitrobenzal-
dehyde with ethanol under inert atmosphere of nitrogen.
Analysis of the reaction mixture after 18 h showed that no
product was formed, and the starting materials remained
intact. This results shows that aerobic oxidation is involved
in this reaction. Hence, we propose the mechanism for the
reaction as depicted in Scheme 1. Fluoride anion attacks the
aldehyde to form intermediate I. Aerobic oxidation of
I produces intermediate II, which converts to the target mol-
ecule in the presence of an alcohol.

SOLTANI AND GHADERI
3
TABLE 2 Reaction of 4-nitrobenzaldehde with different alcoholsa
O
H
O
KF
OR
O2N
ROH
+
O2N
DMF, air, rt
1
2
3
Entry
Aromatic aldehydes
Alkoxy/phenoxy source
Product
Time (hr)
Isolated yield (%)
1
18
87
O
H
O
OH
2a
O
O
O2N
O2N
O2N
1a
3a
3a
2
3
4
5
Si(OEt)4
18
16
18
20
34
85
83
45
O
H
O
2b
O2N
1a
CH3OH
2c
O
H
O
O
O2N
O2N
1a
3b
O
H
O
OH
O
2d
O2N
O2N
1a
3c
O
H
OH
O
O
2e
O2N
O2N
1a
3d
6
Si(OEt)4
18
40
O
H
O
2b
O
NO2
NO2
1b
3e
7
8
21
19
64
86
O
H
OH
O
O
2f
O2N
O2N
1a
3f
O
H
O
O
O
HO
O
2g
O2N
O2N
1a
3g

4
SOLTANI AND GHADERI
TABLE 2 (Continued)
O
O
H
KF
OR
O2N
ROH
+
O2N
DMF, air, rt
1
2
3
Entry
Aromatic aldehydes
Alkoxy/phenoxy source
Product
Time (hr)
Isolated yield (%)
9
24
45
O
Cl
Cl
O
H
HO
O
2h
O2N
O2N
1a
3h
10
11
24
24
Trace
Trace
O
O
OH
O
H
H
O
O2N
O2N
2i
1a
1a
3i
OH
O
2j
O2N
O
O2N
3j
aReaction conditions: 4-nitrobenzaldehyde (0.5 mmol), alcohol/phenol (1 mmol), KF (4 mmol), DMF (3 mL) at rt.
O
K
F
O
H
O
O
Metal-free
aerobic oxidation
H
KF
ROH
-HF
OR
F
O2N
O2N
O2N
O2N
I
II
SCHEME 1 Plausible pathway for the aerobic oxidation of aldehydes promoted by KF
ORCID
2 | CONCLUSIONS
Arash Ghaderi https://orcid.org/0000-0002-2215-9261
In conclusion, we have reported an effective procedure for the
synthesis of esters under metal-free conditions at room tem-
perature. In this approach, KF has been used as the key addi-
tive for the reaction to proceed. Utilizing the optimized
conditions, different alkoxide sources, including a 2ꢀ alcohol,
Si(OEt)4, and phenol derivatives, were successfully used to
produce a range of esters. Mechanistic studies showed that the
oxygen of atmosphere is necessary for the reaction, and the
aerobic oxidation is included in the reaction pathway.
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The authors are thankful to Iran National Science Founda-
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Hormozgan research council for the financial support.

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SUPPORTING INFORMATION
Additional supporting information may be found online in
the Supporting Information section at the end of this article.
How to cite this article: Soltani R, Ghaderi A.
Metal-free aerobic oxidative esterification of aromatic
aldehydes promoted by potassium fluoride (KF). J
Chin Chem Soc. 2019;1–5. https://doi.org/10.1002/
jccs.201800344