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Chemistry Letters Vol.32, No.1 (2003)
Alkylation of Phenols by Oxidation-Reduction Condensation
Using 2,6-Dimethyl-1,4-benzoquinone and Alkoxydiphenylphosphine
Taichi Shintou, Wataru Kikuchi, and Teruaki MukaiyamaÃ
The Kitasato Institute, Center for Basic Research, TCI, 6-15-5, Toshima, Kita-ku, Tokyo 114-0003
(Received September 19, 2002; CL-020809)
Various alkyl phenyl ethers were obtained in high yields by
dimethyl-1,4-benzoquinone was studied and the corresponding
phenyl alkyl ethers were obtained in good yields under mild
conditions.
way of oxidation-reduction condensation where alkoxydiphenyl-
phosphine, prepared easily from chlorodiphenylphosphine and
corresponding alcohols, was treated with various phenols in the
co-existence of 2,6-dimethyl-1,4-benzoquinone(DMBQ) under
mild conditions.
In the first place, benzylation of phenol with 1.1 equivalent of
Ph2POBn was tried by using 1.0 equivalent of 1,4-benzoquinone
in dichloromethane, and the desired product was obtained in 49%
yield within 0.5 h (Table 1, entry 1). When DMBQ was used
under the above conditions, the benzyl phenyl ether was obtained
in 85% yield (entry 2). On the other hand, the yield lowered to
75% when phenol, 1.1 equivalent of DMBQ and 1.1 equivalent of
Ph2POBn were allowed to react in dichloromethane at 0 ꢀC and
stirred for additional 0.5 h at room temperature (entry 3). After
screening the reaction conditions, it was found that the desired
product was obtained in 92% yield under the above conditions
when 1.5 equivalent of Ph2POBn was used (entries 3–5).
The fundamental concept of oxidation-reduction condensa-
tion is to perform dehydration condensation by removing H2O in
elements of 2[H] and [O] with the use of weak reductant-oxidant
combination.1 The strong point of this concept is that the reaction
is carried out under mild and neutral conditions without having
any assistance of acids or bases. In our previous communication,
the high-yielding preparation of various carboxylic benzyl esters
was performed by way of a new-type oxidation-reduction
condensation
that
used
benzyloxydiphenylphosphine
Table 1. Benzylation of phenol with Ph2POBn and quinones
(Ph2POBn),2 carboxylic acids and 2,6-dimethyl-1,4-benzo-
quinone under mild conditions.3 In the above reaction, Ph2POBn
was assumed to initially react with DMBQ to form an adduct,
which then transformed to the phosphonium carboxylate by the
interaction with carboxylic acid. Intramolecular attack of the
carboxylate anion to the benzylic carbon of the salt afforded the
corresponding carboxylic acid ester along with diphenylphos-
phiric acid 4-hydroxy-3,5-dimethylphenyl ester. Since benzyl-
oxydiphenylphosphine was used in the above reaction, only
carboxylic acid benzyl esters resulted.
In this new-type oxidation-reduction condensation, alkoxyl
group was introduced to the phosphorus in advance, and the
reaction completed through the steps in which tetra-valent
phosphorus of the intermediate phosphonium salt was converted
to so-called penta-valent phosphorus while negatively charged
oxygen of adduct 1 (Scheme 1) captured one hydrogen atom
synchronously. In order to extend the scope of this type of
condensation reaction, a similar oxidation-reduction condensa-
tion using several alkoxydiphenylphosphines, phenols and 2,6-
Ph2POBn
Quinone (1.0 equiv.)
OH
OBn
CH2Cl2, rt, 0.5 h
Entry
Ph2POBn/equiv.
Quinone
Yield/%
1
2
3
4
5
1.1
1.1
1.1
1.2
1.5
1,4-benzoquinone
DMBQa
DMBQ
49
85
72b
85
DMBQ
DMBQ
92
aDMBQ(2,6-dimethyl-1,4-benzoquinone). bTo a mixture of
phenol and 2,6-dimethyl-1,4-benzoquinone was added a
Ph2POBn in CH2Cl2 at 0 ꢀC and then reacted for 0.5 h at room
temperature.
Next, benzylation of various phenols with Ph2POBn and
DMBQ was tried (Table 2). As a result, the corresponding benzyl
phenols were obtained in good yields under mild conditions.
A proposed reaction mechanism is shown in Scheme 1:
Ph2POBn initially reacted with DMBQ to form adduct 1, which
then transformed to the phosphonium phenolate 2 by the
interaction with phenol. Intramolecular attack of the phenolate
anion to the benzylic carbon of the salt 2 afforded the
corresponding benzyl ether along with diphenylphosphinic acid
4-hydroxy-3,5-dimethylphenyl ester 3.
Ph
O
Ph
Ph2POBn
P
Ph
O
O
H OPh
O
O
1
In the present reaction of using phenols, the corresponding
benzyl phenols were obtained in good yields under mild
conditions which accompanied the by-product 4 formed probably
by the competitive reaction between the two moles of initially
formed 1 having phenolic nature (Scheme 2).
Ph
OPh
O
O
Ph
Ph
O
Ph
P
PhOBn
+
P
OH
Ph
O
OH
Alkylations of phenol and p-nitrophenol with several
alkoxydiphenylphosphine and DMBQ were tried (Table 3) and
the corresponding alkyl phenyl ethers were obtained in good
3
2
Scheme 1.
Copyright Ó 2003 The Chemical Society of Japan