Improving the Dakin reaction by using an ionic liquid solvent

Article abstract of DOI:10.1055/s-2003-40848

The oxidation of aromatic aldehydes to phenols (Dakin reaction) has been demonstrated to proceed readily on both activated and non-activated aldehydes in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMI][PF₆], 1) with high selectivity, easy product separation and excellent chemical yields.

Full text of DOI:10.1055/s-2003-40848

LETTER
1545
Improving the Dakin Reaction by Using an Ionic Liquid Solvent
D
akinRea
o
ctioninan
Ir
g
uid Solvent e L. Zambrano,*a Romano Dortab
a
Departamento de Química, Universidad Simón Bolivar, Valle de Sartenejas, Baruta, Caracas 1080-A, Venezuela
Fax +58(2)129063961; E-mail: jzambrano@usb.ve
b
Centro de Química, Instituto Venezolano de Investigaciones Científicas (I.V.I.C.), Apartado 21827, Caracas 1020-A, Venezuela
Received 26 February 2003
ity of unactivated benzaldehydes. We report here on im-
proving the Dakin reaction by using the ionic liquid
solvent 1-butyl-3-methylimidazolium hexafluorophos-
phate ([BMI][PF6], 1).
Abstract: The oxidation of aromatic aldehydes to phenols (Dakin
reaction) has been demonstrated to proceed readily on both activat-
ed and non-activated aldehydes in the ionic liquid 1-butyl-3-meth-
ylimidazolium hexafluorophosphate ([BMI][PF6], 1) with high
selectivity, easy product separation and excellent chemical yields.
The Dakin oxidation of benzaldehyde (2a) using H2O2
(2.2 equiv)/H3BO3 (5 equiv) in THF has been reported to
give phenol (2b) in 74% yield after 12 h.5 Initial oxida-
tions in the ionic liquid solvent 1 were carried out using
2a in order to establish a valid correlation and to optimize
the reaction (Scheme 2). As shown in Table 1 (entry 1), 5
equivalents of H3BO3 allowed for a rapid (< 1 h) and clean
conversion to phenol (2b, 89% yield). A lower amount of
boric acid proved less efficient in terms of reaction time
(2–10 h) and chemical yield (76–85%, entries 2 and 3). At
the end of the reaction, an organic solvent was added.
Among several organic solvents tested, toluene allowed
for a complete separation of both layers and an optimum
extraction of the phenolic products without detectable
amounts of benzoic acid.
Key words: oxidations, phenols, aldehydes, ionic liquid, Dakin re-
action
The conversion of hydroxy benzaldehydes to phenols us-
ing alkaline hydrogen peroxide (the original Dakin reac-
tion, Scheme 1) represents a highly practical and
economical synthetic method.1 Alkoxy substituted ben-
zaldehydes were also oxidized under acid conditions to af-
ford the corresponding phenols,2 while activated
aldehydes were shown to be oxidized to phenols by arene-
selenic acid/H2O2,3 sodium perborate,4 and sodium per-
carbonate.4 More recently, Junjappa and co-workers have
utilized boric acid/hydrogen peroxyde (H3BO3/H2O2) as
an efficient oxidizing system for the conversion of benzal-
dehydes and acetophenones to phenols.5 On the other
hand, ionic liquids consisting of 1-butyl-3-methylimida-
zolium cations, have emerged as useful reaction media
due to desirable properties such as thermal, chemical and
physical stability, very low volatility, and facile recycling.
OH
CHO
H2O2 / H3BO3 / cat. H+
[BMI][PF6] (1)
2b
2a
Scheme 2 Oxidation of benzaldehyde (2a) in [BMI[PF6] (1)
OH
CHO
H2O2 / NaOH
+ NaO2CH–
Table 1 Dakin Oxidation of Benzaldehyde (2a) Using H3BO3/H2O2
in 1 or THF Under Various Conditions
HO
HO
Scheme 1 The reported Dakin reaction.
Entry
H3BO3
(mmol)
Time (h)
Yield (%)
in 1
Yield (%)
in THF
1
2
3
5
1
2
89
85
76
68
37
31
3
In addition, ionic liquids offer the potential for easy prod-
uct separation owing to their adjustable miscibility with
some organic solvents.6 From a chemical point of view,
ionic liquids were shown to enhance reaction rates in a
range of reactions,7 including acid catalyzed reactions,8
thanks to the stabilization of highly polar transition states.
Therefore, the benefits of running the Dakin reaction in a
liquid ionic reaction medium are potentially twofold:
easy biphasic product separation and an enhanced reactiv-
1.5
10
a General reaction conditions: aldehyde (1.0 mmol), H3BO3 (1.5–5
mmol), H2O2 (2.0 mmol), H2SO4 (0.1 mmol) in [BMI][PF6] (1) or
THF at 25 °C.
Using the best conditions reported in Table 1 (entry 1), the
Dakin reaction in 1 was explored on several activated and
non-activated aromatic aldehydes. The results are summa-
rized in Table 2. All reactions were carried out using 5
equivalents of boric acid in about 1 mL of 1. However, ex-
periments run on activated substrates with a lower amount
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Art Id.1437-2096,E;2003,0,10,1545,1546,ftx,en;S01903ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1546
J. L. Zambrano, R. Dorta
LETTER
of boric acid (3 equiv) gave similar chemical yields and der mild conditions with the additional benefit of easy
reaction times (Table 2, entries 1 and 2). The oxidation of product separation. This work shows that ionic liquids
2-hydroxy-1-naphthaldehyde (5a) and piperonal (6a) in 1 such as 1 provide an ideal environment for Dakin-type
gave the corresponding phenols 5b and 6b in 76% and reactions. We believe that the liquid ionic solvent 1 effec-
78% yields, respectively (Table 2, entries 3 and 4). Since tively activates substrates and/or stabilizes ionic interme-
the oxidations of both substrates were highly exothermic, diates in Dakin type reactions.
they had to be run at 0 °C. Finally, the Dakin oxidation of
p-chlorobenzaldehyde (7a) in 1 proceeded smoothly at
room temperature to afford phenol 7b after 12 h in 65%
Acknowledgement
We thank the NMR Laboratory at the Chemistry Department (Uni-
versidad Simón Bolivar).
yield as the only isolated product (Table 2, entry 5). The
corresponding carboxylic acid was not observed. In com-
parison, the oxidation of 7a using H2O2/H3BO3 in THF as
reported by Junjappa and co-workers5 proceeds at 60 °C
to give 7b in 60% and p-chlorobenzoic acid in 30%
yield.9,10
References
(1) Dakin, H. D. Org. Synth., Coll. Vol. 1; Wiley: New York,
1941, 149.
In summary, we have demonstrated that aromatic alde-
hydes can be effectively and selectively converted to their
corresponding phenolic products in the ionic liquid 1 un-
(2) Matsumoto, M.; Kobayashi, H.; Hotta, Y. J. Org. Chem.
1984, 49, 4740.
(3) Syper, L. Synthesis 1989, 167.
(4) McKillop, A.; Sanderson, W. R. Tetrahedron 1995, 51,
6145.
(5) Roy, A.; Reddy, K. R.; Mohanta, P. K.; Ila, H.; Junjappa, H.
Synth. Commun. 1999, 29, 3781.
Table 2 Dakin Oxidation of Aldehydes 3a–7a Using H3BO3/H2O2
in 1a
(6) For a recent review, see: Olivier-Bourbigou, H.; Magna, L.
J. Mol. Cat. A: Chem. 2002, 182-183, 419.
(7) Varma, R. S.; Namboodivi, V. V. Chem. Commun. 2001,
643.
(8) Howart, J.; Hanlon, K.; Fayne, D.; McCormac, P.
Tetrahedron Lett. 1997, 38, 3097.
(9) CAS #: 2b [108-95-2], 3b [106-44-5], 4b [150-76-5], 5b
[574-00-5], 6b [533-31-3], 7b [106-48-9].
(10) Typical Procedure: To a solution of the aromatic aldehyde
(1 mmol) in [BMI][PF6] (1, 1 mL) was added boric acid
(3–5 mmol) with stirring, followed by sulfuric acid (0.1
mmol) and a solution of hydrogen peroxide (35%, 2 mmol).
The resulting reaction mixture was stirred for 1–2 h at room
temperature and then toluene (2 mL) was added. The two-
phase liquid mixture was stirred and then allowed to stand.
The toluene phase (upper phase) was decanted off and the
ionic phase was extracted with a second portion of toluene (2
mL). The combined toluene layers were dried (MgSO4) and
then evaporated to give a yellowish solid. This solid was
redissolved in CH2Cl2, filtered through a pad of silica gel
(eluted with hexane/ethyl acetate 10:1), and dried in vacuo to
afford a white-yellowish solid in 65–89% yield. The product
was analyzed by 1H NMR or GC-MS.
Entry Aldehyde
Product
Yield
(%)
1
2
3
4
5
p-methyl benzaldehyde
(3a)
p-cresol (3b)
82 (79)b
84 (81)b
76c
p-methoxy benzaldehyde p-methoxy phenol
(4a) (4b)
2-hydroxy-1-naphthalde- 1,2-naphthalenediol
hyde (5a)
(5b)
piperonal (6a)
3,4-methylenedioxy 78c
phenol (6b)
p-chloro benzaldedyde
(7a)
p-chloro phenol (7b) 65
a General reaction conditions: aldehyde (1.0 mmol), H3BO3 (5
mmol), H2O2 (2.0 mmol), H2SO4 (0.1 mmol) in [BMI][PF6] (1)
at 25 °C.
b Experiments run with 3 equivalents of H3BO3.
c Experiments run at 0 °C.
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