Improved solvent-free Dakin oxidation protocol

Article abstract of DOI:10.1080/00397910701820673

A solvent-free Dakin reaction with mCPBA was accomplished with various aromatic aldehydes, resulting in an easy and improved methodology for the preparation of corresponding phenols. 3,4-Methylenedioxyphenol, 3,4-dimethoxyphenol, 4-methoxyphenol, 4-chlorophenol, and other functionalized phenols were obtained in high yields from the corresponding aromatic aldehydes in a few minutes. This new methodology represents an efficient alternative for this important synthetic conversion. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701820673

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Improved Solvent‐Free Dakin Oxidation
Protocol
Emerson Teixeira da Silva a b , Celso Amorim Câmara c , O. A. C. Antunes a b
, Eliezer J. Barreiro d & Carlos A. M. Fraga d
a Chemistry Institute, Federal University of Rio de Janeiro, Cidade
Universitária, Rio de Janeiro, Brazil
b Nortec Química, Duque de Caxias, Brazil
c Chemistry Department, Rural Federal University of Pernambuco, Recife,
Brazil
d Laboratório de Avaliação e Síntese de Substâncias Bioativas, Federal
University of Rio de Janeiro, Faculty of Pharmacy, Rio de Janeiro, Brazil
Version of record first published: 15 Feb 2008.
To cite this article: Emerson Teixeira da Silva, Celso Amorim Câmara, O. A. C. Antunes, Eliezer J. Barreiro
& Carlos A. M. Fraga (2008): Improved Solvent‐Free Dakin Oxidation Protocol, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:5, 784-788
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Synthetic Communicationsw, 38: 784–788, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701820673
Improved Solvent-Free Dakin Oxidation
Protocol
3
Emerson Teixeira da Silva,1,2 Celso Amorim Camara,
ˆ
O. A. C. Antunes,1,2 Eliezer J. Barreiro,4 and Carlos A. M.
Fraga4
1Chemistry Institute, Federal University of Rio de Janeiro, Cidade
´
Universitaria, Rio de Janeiro, Brazil
´
2
Nortec Quımica, Duque de Caxias, Brazil
3Chemistry Department, Rural Federal University of Pernambuco,
Recife, Brazil
´ ´ ˆ
Laboratorio de Avaliac¸a˜o e Sıntese de Substancias Bioativas, Federal
4
University of Rio de Janeiro, Faculty of Pharmacy, Rio de Janeiro, Brazil
Abstract: A solvent-free Dakin reaction with mCPBA was accomplished with various
aromatic aldehydes, resulting in an easy and improved methodology for the preparation
of corresponding phenols. 3,4-Methylenedioxyphenol, 3,4-dimethoxyphenol, 4-meth-
oxyphenol, 4-chlorophenol, and other functionalized phenols were obtained in high
yields from the corresponding aromatic aldehydes in a few minutes. This new method-
ology represents an efficient alternative for this important synthetic conversion.
Keywords: Dakin reaction, mCPBA, solvent-free, synthesis of phenols
The Dakin reaction formally consists of the conversion of hydroxybenzalde-
hydes into phenols, by using alkaline hydrogen peroxide (Scheme 1).[1]
Phenols are suitable intermediates for many purposes and have proved to be
useful in the synthesis of several biologically active compounds.[2]
Received in the USA September 5, 2007
Address correspondence to Carlos A. M. Fraga, Laboratorio de Avaliac¸a˜o e Sıntese
´
´
ˆ
de Substancias Bioativas, Federal University of Rio de Janeiro, Faculty of Pharmacy,
Rio de Janeiro, RJ, Brazil. E-mail: cmfraga@pharma.ufrj.br
784

Solvent-Free Dakin Oxidation
785
Scheme 1. Original Dakin reaction.
Although there are several different methodologies focusing on the prep-
aration of phenols from benzaldehydes,[3] we exploited the Dakin reaction
during our research program for the synthesis and evaluation of new
bioactive compounds.[4] In the course of these studies, we discovered that
the reaction mentioned previously could be optimized by mixing net
mCPBA and the corresponding benzaldehydes, resulting in shorter reaction
times and easier workup.
It is now well established that some organic reactions can occur efficiently
in the solid state,[5] resulting in environmentally friendly synthetic products.
In this context, we herein report an efficient and unprecedented solid-
state oxidation of activated and nonactivated aromatic aldehydes using
mCPBA.
Previous studies carried out by Varma and Naicker[3f] described a solid-
state procedure using an urea–hydrogen peroxide adduct useful only for
activated hydroxylated benzaldehydes in glass tubes at high temperature.
Using our protocol (Table 1), various nonactivated benzaldehydes could be
converted to the corresponding phenols with remarkable reduction of
reaction time and high yield, in comparison with other previously reported
procedures in solution.[3] Simply mixing together the aromatic aldehyde and
mCPBA by using a pestle in a mortar results in a pasty mass and after few
minutes yields the desired phenol derivative, which was easily isolated after
a sequence of alkaline hydrolysis with a 10% aqueous sodium hydroxide.
The results obtained are displayed in Table 1. Remarkably this procedure
does not show a preference for an electron-rich substrate (entries 1–5), so
other substrates could be oxidized as well (entries 6–10).
To show the benefits of our protocol, we followed the oxidative procedure
described by Nam and co-workers,[2] employing H2O2 in MeOH and catalytic
H2SO4 at room temperature to obtain 3,4-methylenedioxyphenol (entry 1),
3,4-dimethoxyphenol (entry 2), 4-methoxyphenol (entry 3), and 4-chlorophe-
nol (entry 6) in comparable yields after 48 h. By applying our procedure, we
can prepare them in approximately, 10 min. When exploiting another proce-
dure,[3g] sesamol, 4-methoxyphenol and 4-chlorophenol were obtained from
the corresponding benzaldehydes, after 2 h and in lower yield, by treatment
with 1-butyl-3-methylimidazoliumhexafluorophosphate in the presence of
H3BO3/H2SO4 as a catalyst.
In summary, the present article discloses an efficient solid-state procedure
for the preparation of various functionalized phenols, which in comparison

786
E. T. da Silva et al.
Table 1. Oxidation of aromatic aldehydes using mCPBA solvent-free procedure
Yielda
(%)
Entry
1
Starting material
Product
Microanalysis datab
95
Anal. calcd. for C7H6O3:
C, 60.87; H, 4.38; found:
C, 60.67; H, 4.35.
2
90
Anal. calcd. for
C8H10O3: C, 62.33; H,
6.54; found: C, 62.08; H,
6.49.
3
4
5
87
85
85
Anal. calcd. for C7H8O2:
C, 67.73; H, 6.50; found:
C, 67.59; H, 6.43.
Anal. calcd. for C7H8O2:
C, 67.73; H, 6.50; found:
C, 67.66; H, 6.39.
Anal. calcd. for
C14H14O3: C, 73.03; H,
6.13; found: C, 72.75; H,
6.12.
6
7
81
80
84
65
78
Anal. calcd. for
C6H5ClO: C, 56.06; H,
3.92; found: C, 55.88; H,
3.87.
Anal. calcd. for
C6H5ClO: C, 56.06; H,
3.92; found: C, 55.93; H,
3.83.
8
Anal. calcd. for
C6H5FO: C, 64.28; H,
4.50; found: C, 63.99; H,
4.47.
9
Anal. calcd. for
C6H5BrO: C, 41.65; H,
2.91; found: C, 41.57; H,
2.90.
10
Anal. calcd. for C10H8O:
C, 83.31; H, 5.59; found:
C, 83.20; H, 5.48.
aThe yield refers to isolated product, after 10 min of reaction, including oxidation
and hydrolysis.
bMicroanalyses were obtained with a Perkin-Elmer 240 analyzer, using a
Perkin-Elmer AD-4 balance.

Solvent-Free Dakin Oxidation
787
with previous reports appears to be a superior alternative in terms of shorter
reaction time, cleaner product formation, and easier workup.
GENERAL PROCEDURE
A combination of 0.5 mmol of the appropriate aromatic aldehyde and 1.5 eq.
of solid mCPBA (ꢀ55%) were mixed with a pestle in a fume cupboard. The
solids immediately melt and in some cases moderate evolution of heat was
observed. After 5 min, thin-layer chromatographic (TLC) inspection
indicated the end of the reaction. At this point, 5 mL of a 10% aqueous
sodium hydroxide solution was added and mixed until complete dissolution.
After an additional 5 min of stirring and washing with diethyl ether
(2 Â 10 mL), the pH of the aqueous phase was adjusted to 6–7 and the
mixture was extracted with CH2Cl2 (3 Â 20 mL). The organic extracts were
combined, dried over anhydrous sodium sulfate, filtered, and evaporated to
1
furnish the corresponding pure phenols, which were analyzed by H NMR
and gas chromatography coupled to mass spectrometry (GC-MS) and
compared with authentic samples, showing a high degree of purity.
1
Example (entry 1): mp 60–628C (lit. 64–658C); H NMR (200 MHz,
CDCl3) 6.65 (d, J ¼ 8.33 Hz, 1H); 6.43 (d, J ¼ 2.47, 1H); 6.25 (dd,
J ¼ 8.33 and 2.56 Hz, 1H); 5.9 (s, 2H); 5.46 (br, 1H, OH).
ACKNOWLEDGMENTS
´
Thanks are due to Conselho Nacional de Desenrolvimento Cientıfico e
Tecnologico (CNPq, BR) and Fundac¸a˜o Carlos Chagas Filho de Amparo a
´
Pesquisa do Estado do Rio de Janeiro (FAPERJ, BR) for financial support
and fellowships.
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