Oxidative esterification of benzaldehyde and deactivated aromatic aldehydes with N-bromosuccinimide-pyridine

Article abstract of DOI:10.1080/00397911.2011.572219

(Chemical Equation Presented) Whereas the oxidative esterification of benzaldehyde to methyl benzoate with N-bromosuccinimide (NBS)-pyridine requires dark conditions and 5 equivalents each of NBS and K₂CO₃ and gave only moderate yield (52%) of the product (McDonald et al. J. Org. Chem. 1989, 54, 1213), simple change of base to pyridine gave the desired product in 83% gas chromatographic yield with only 1 equivalent each of NBS and pyridine. Moreover, the reaction could be conducted without exclusion of light. Aromatic aldehydes bearing electron-withdrawing substituents at meta/para position yielded the corresponding methyl esters in still better yields. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.572219

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Oxidative Esterification of Benzaldehyde
and Deactivated Aromatic Aldehydes
with N-Bromosuccinimide-pyridine
a
a
Manoj K. Agrawal , Subbarayappa Adimurthy & Pushpito K. Ghosh
a
a
Central Salt and Marine Chemicals Research Institute, Council
of Scientific and Industrial Research, Gijubhai Badheka Marg,
Bhavnagar, Gujarat, India
Accepted author version posted online: 02 Jan 2012.Version of
record first published: 29 May 2012.
To cite this article: Manoj K. Agrawal , Subbarayappa Adimurthy & Pushpito K. Ghosh (2012):
Oxidative Esterification of Benzaldehyde and Deactivated Aromatic Aldehydes with N-
Bromosuccinimide-pyridine, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:19, 2931-2936
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1
Synthetic Communications , 42: 2931–2936, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.572219
OXIDATIVE ESTERIFICATION OF BENZALDEHYDE
AND DEACTIVATED AROMATIC ALDEHYDES WITH
N-BROMOSUCCINIMIDE-PYRIDINE
Manoj K. Agrawal, Subbarayappa Adimurthy, and
Pushpito K. Ghosh
Central Salt and Marine Chemicals Research Institute, Council of Scientific
and Industrial Research, Gijubhai Badheka Marg, Bhavnagar, Gujarat, India
GRAPHICAL ABSTRACT
Abstract Whereas the oxidative esterification of benzaldehyde to methyl benzoate with
N-bromosuccinimide (NBS)-pyridine requires dark conditions and 5 equivalents each of
2 3
NBS and K CO and gave only moderate yield (52%) of the product (McDonald et al.
J. Org. Chem. 1989, 54, 1213), simple change of base to pyridine gave the desired product
in 83% gas chromatographic yield with only 1 equivalent each of NBS and pyridine. More-
over, the reaction could be conducted without exclusion of light. Aromatic aldehydes bear-
ing electron-withdrawing substituents at meta=para position yielded the corresponding
methyl esters in still better yields.
Supplemental materials are available for this article. Go to the publisher’s online edition
1
of Synthetic Communications to view the free supplemental file.
Keywords Benzaldehydes; esterification; methyl benzoates; NBS; oxidation
INTRODUCTION
Direct esterification of aldehydes is a useful reaction as it combines two steps
[
1]
into one. Several reagents are reported for this reaction in the literature. Lerebours
[
and Wolf employed siloxane for oxidative esterification of aldehydes. Phthalalde-
2]
[
3]
hyde was converted to lactone using disodium tetracarbonyl ferrate [Na Fe(CO) ],
4
2
[
4]
[5]
Cp ZrH , and CaO, and epoxyaldehydes were converted into b-hydroxyesters by
2
2
employing substituted thiazolidium salt and diisopropylethylamine (DIPEA) as a
Received December 24, 2010.
Address correspondence to Pushpito K. Ghosh, Central Salt and Marine Chemicals Research
Institute, G. B. Marg, Bhavnagar, Gujarat 364 002, India. E-mail: pkghosh@csmcri.org
2
931

2932
M. K. AGRAWAL, S. ADIMURTHY, AND P. K. GHOSH
[
catalyst. N-Heterocyclic carbenes (NHC) derived from benzimidazolium or
6]
[7]
[
8]
triazolium salts are used as catalysts for generating saturated esters from a,b-
unsaturated aldehydes using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and t-
BuOK=DIPEA, respectively, as bases. The disproportionation reaction of two mole-
cules of an aldehyde to form ester, catalyzed by Al(OiPr) or boric acid, is the
3
[9]
well-known Tischenko reaction.
Several other methods have been developed under acidic, neutral, and basic
[
10]
[11]
[12]
conditions. KHSO (oxone),
nate,
sodium metaperiodate,
perborate,
and m-chloroperbenzoic acid (MCPBA)
effective under acidic conditions. In a few reports, the acid used along with oxidizing
percarbo-
5
[
12]
[13]
[14]
hydrogen peroxide,
are
[
12,13]
agent was HClO , the latter itself being a powerful oxidizing agent.
4
[15]
Iodobenzenediacetate=I2
Reactions have also been carried out under basic conditions.
conditions, was found to be a promising reagent, yielding methyl benzoate in 89%
is a reagent operating under neutral conditions.
[
16,17]
NIS, under dark
[
17]
yield with 2.5 mol equivalents each of the reagent and K CO base.
2
The reagent
3
was also versatile, and a variety of substrates underwent the desired transformation.
The reaction with N-bromosuccinimide (NBS) instead of N-iodosuccinimide (NIS)
met with limited success, and only 52% of methyl benzoate was obtained even with
[
17]
fivefold excess of the reagent.
NIS also. We were motivated to reinvestigate the reaction with NBS, particularly
Dark conditions were necessary as in the case of
[
18]
in view of its clean and cost-effective synthesis with ‘‘green bromine.’’
RESULTS AND DISCUSSION
When employing 5 mol equivalents each of NBS and K CO per mole benzal-
2
3
[17]
dehyde, as reported by McDonald et al., no reaction was observed under normal
ambient conditions. However, after covering the reactor with black cloth, methyl
benzoate was obtained in 62% GC yield, which is close to the value of 52% reported
by the authors. Recognizing that the need for dark conditions emanates from the
generation of HBr, it was felt that homogeneous reaction conditions might be better
suited for efficient trapping of the acid during the reaction. If the base could enhance
the nucleophilicity of the carbonyl oxygen, that may further facilitate the reaction.
After evaluating several bases, pyridine was identified as the best choice in view of
its resistance to oxidation and electrophilic substitution. Methyl benzoate was
obtained in 83% yield (GC-MS area%) with only 1 mol equivalent each of NBS
and pyridine (entry 1, Table 1). The reaction was attempted with other alcohols also
(Table S1, supporting information). Conversions were low with ethanol and n-pro-
panol, but the desired esters were obtained cleanly. Other alcohols predominantly
gave undesired products. Further experiments were conducted with methanol only.
When oxidative esterification was attempted with electron-rich substituted ben-
zaldehydes, ring bromination occurred as a competing reaction as reported for oxi-
[19]
dation reactions with NBS.
For example, 4-methyl benzaldehyde gave only 55%
conversion, with 24% yield of desired methyl ester along with bromo-substituted side
products (entry 2, Table 1). 4-Methoxybenzaldehyde showed ca. 70% conversion
with only 29% yield of the desired ester (entry 3, Table 1). We next studied deacti-
vated benzaldehyde derivatives. 4-Nitrobenzaldehyde gave 93% GC yield of ester
with 100% selectivity (entry 4, Table 1). This reaction was equally effective with

OXIDATIVE ESTERIFICATION
2933
Table 1. Oxidative esterification of various aldehydes using NBS–pyridine
Substrate–
NBS–
Pyridine
a
Conversion Yield Selectivity
b
Time
(h)
Entry
Substrate
Ester
(%)
(%)
(%)
1
6
1:1:1
1:1:1
1:1:1
83
55
70
83
24
29
100
44
2
3
.5
3
4
4
6
41
1:1:1
1:1:1
93
85
93
85
100
100
5
6
4
4
6
1:1:1
1:1:1
32
87
32
85
100
98
7
8
9
4
9
9
1:1:1
1:4:4
1:4:4
70
100
100
48
100
100
69
100
100
1
1
0
1
7
1:2:1
100
100
100
a
b
Conversion based on area % by GC-MS (see the Supplementary Material).
Yield of desired product based on area % by GC-MS.
NBS prepared using ‘‘green bromine’’ (2:1 bromide=bromate) obtained from the
[
18]
intermediate of liquid bromine manufacture.
That is, liquid bromine can be
eliminated altogether from the product life cycle. 3-Nitrobenzaldehyde and 2-nitro-
benzaldehyde were converted in 85% and 32% yields, respectively, with 100% selec-
tivity in both cases (entries 5 and 6, Table 1). In 3-chloro benzaldehyde and 2-chloro
benzaldehyde, the conversions were 87% and 70%, respectively, while the corre-
sponding values for selectivity were 98% and 69% (entries 7 and 8, Table 1). In
the latter case, the starting material was partly in the form of acetal.
Phthalaldehyde derivatives were also studied. With 4 mol equivalents of the
reagent, the conversion and selectivity were 100% in both 4-phthalaldehyde and
3-phthalaldehyde (entries 9 and 10, Table 1). (Although not shown in the table,
when 2 mol equivalents of reagent was employed, 4-phthalaldehyde gave 71% diester

2934
M. K. AGRAWAL, S. ADIMURTHY, AND P. K. GHOSH
Scheme 1. Probable mechanism for oxidative esterification of aldehydes.
and 26% monoester, whereas the corresponding values with 3-phthalaldehyde were
2% and 35%, respectively). When 2-picolinaldehyde was subjected to oxidative
6
esterification with 2 mole equivalents of NBS and 1 mol equivalent of pyridine, com-
plete conversion with 100% selectivity was found (entry 11, Table 1).
It is assumed that the oxidative esterification process involves intermediate for-
1
mation of hemiacetal. The H NMR spectrum of 4-nitrobenzaldehyde in CD OD
3
showed that the free- and hemiacetal forms of the aldehyde were present in 1:3 ratio
(Fig. S1, supporting information) and the ratio remained unchanged in the presence
of pyridine (Fig. S2, supporting information). Because aromatic rings bearing
electron-withdrawing groups would make the methine H more acidic (Scheme 1),
the facile reaction with nitrobenzaldehyde and other deactivated aldehydes can be
rationalized.
In conclusion, NBS–pyridine is shown to be a useful reagent combination for
the conversion of benzaldehyde and deactivated aromatic aldehydes to the corre-
sponding methyl esters. However, the reagent is less suitable for aliphatic and acti-
vated aromatic aldehydes. In these cases, NIS-K CO and other reagents may be
2
3
more appropriate.
EXPERIMENTAL
NMR spectra of synthesized esters (Table 1) were recorded on a model DPX300
Bruker FT-NMR instrument. Fourier transform–infrared (FT-IR) spectra were
recorded on a Perkin-Elmer GX-2000 spectrometer. All products from Table 2 are
analyzed by gas chromatography–mass spectrometry (GC-MS) using, Shimadzu
GC-MS-QP2010. Analytical thin-layer chromatography (TLC) was performed on
an Aluchrosep silica-gel 60=UV254 plate. Products were purified by column chroma-
tography using 100 to 200-mesh silica gel. All reactions were carried out under ambi-
ent conditions with magnetic stirring, and yield refers to GC-MS area% yield.
Representative Procedure for the Oxidative Esterification of
Aldehyde
4
-Nitrobenzaldehyde (500 mg, 3.311 mmol), pyridine (261 mg, 3.311 mmol),
and methanol (10 mL) were taken together in a 50-mL round-bottom flask and stir-
red for 5 min with a magnetic stirrer at room temperature. NBS (590 mg,
3
.311 mmol) was added gradually over a period of 2 h under vigorous stirring. The

OXIDATIVE ESTERIFICATION
2935
reaction was terminated after 6 h (TLC), and the solvent was stripped off under
reduced pressure. The residue was shaken with 10 mL of water and extracted into
CH Cl (25 mL ꢀ 3). The combined organic layers were washed with 1 M HCl to
2
2
remove all traces of pyridine. It was dried over anhydrous Na SO and concentrated
2
4
under reduced pressure. Analysis of the crude product by GC-MS showed 93%
desired ester. The crude product thus obtained was purified on a silica-gel column
to afford the pure methyl 4-nitrobenzoate (533 mg, 2.94 mmol, 89%). Spectroscopic
1
data of the product was in good agreement with reported data. H NMR (CDCl ):
3
(
d) ¼ 3.91 (s, 3 H, CH ), 8.18 (d, 2 H, J ¼ 6.0 Hz, CH), 8.21 (d, 2 H, J ¼ 6.0 Hz, CH)
3
3
1
3
ppm; C NMR (CDCl ) (d) ¼ 52.8, 122.5, 130.7, 145.0 (Quat-C), 150.5 (Quat-C),
1
1
1
65.1 (Quat-C) ppm; (
(KBr) 3113, 3079, 3003, 2957, 1956, 1727, 1525, 1347,
max
ꢁ
1
280, 1204, 1103, 1058, 988, 955, 719, 502 cm ; MS (EI, 70 eV) m=z: 181.00 (calc),
þ
81.06 (M ) (obsd).
Supplementary Material
Analytical data, NMR spectra, and GC-MS spectra of synthesized compounds
are provided in the Supporting Information, available online.
ACKNOWLEDGMENTS
We are grateful to P. Paul for generous assistance in analysis and to H.
Brahmbhatt and J. K. Mohan for GC-MS, V. Agrawal for IR, and H. Bhatt
for NMR data. M. K. A. thanks the University Grants Commission (UGC),
New Delhi, for the award of a UGC-NET fellowship, and P. K. G thanks the
Council for Scientific and Industrial Research for supporting this work as part
of a laboratory project.
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