Non-catalytic anti-Markovnikov phenol alkylation with supercritical water

Article abstract of DOI:10.1246/cl.2006.716

The anti-Markovnikov alkylation of phenol with tert-butyl alcohol could be achieved without catalyst in supercritical water at 673 K. The dehydration of tert-butyl alcohol gave isobutene and was followed by the reaction with phenol to form 2-isobutylphenol as an anti-Markovnikov product, 2-tert-butylphenol and 4-tert-butylphenol. The hydroxy group probably participated in the anti-Markovnikov alkylation and the increase in water density enhanced the formation of 2-isobutylphenol as well as 4-tert-butylphenol. Copyright

Full text of DOI:10.1246/cl.2006.716

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Chemistry Letters Vol.35, No.7 (2006)
Non-catalytic Anti-Markovnikov Phenol Alkylation with Supercritical Water
Ã
Takafumi Sato, Yasuyoshi Ishiyama, and Naotsugu Itoh
Department of Applied Chemistry, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585
(Received April 6, 2006; CL-060409; E-mail: itoh-n@cc.utsunomiya-u.ac.jp)
The anti-Markovnikov alkylation of phenol with tert-butyl
water were loaded into the reactor after purging the reactor with
argon. This amount of water corresponded to water densities be-
tween 0 and 0.5 g/cm . After the reaction, liquid products were
alcohol could be achieved without catalyst in supercritical water
at 673 K. The dehydration of tert-butyl alcohol gave isobutene
and was followed by the reaction with phenol to form 2-isobutyl-
phenol as an anti-Markovnikov product, 2-tert-butylphenol and
-tert-butylphenol. The hydroxy group probably participated
in the anti-Markovnikov alkylation and the increase in water
density enhanced the formation of 2-isobutylphenol as well as
3
recovered with acetone and both qualitative and quantitative
analyses of the products were performed with GC-MS with an
internal standard. For some cases, we conducted experiments
by using the reactors equipped with a high pressure valve to
analyze gas products. For these cases, the gas products were
analyzed by GC-TCD. Product yield was defined on a tert-butyl
alcohol loaded basis, as: yield [%] = (moles of carbon atom
of the alkyl side chain attached to the benzene ring)/(moles of
carbon in tert-butyl alcohol loaded) Â 100.
4
4
-tert-butylphenol.
The Friedel–Crafts alkylation is one of the most important
reactions to produce alkyl aromatics in the chemical industry.
This reaction usually proceeds with strong acids under water-
free condition, thus considerable waste treatments and highly
closed systems are required. The chemistry of typical Friedel–
Crafts reaction, which is governed by the carbocation, leads to
regioselectivity for the alkyl side chain of aromatics and depends
on the stability of the carbocation intermediates (Makovnikov
rule). Therefore, it is difficult to synthesize lower branched
alkylphenols because highly branched carbocation is favored.
Catalysis with metal complexes is one of the methods to achieve
Figure 1 shows the yields of the main products in the alkyla-
tion of phenol with tert-butyl alcohol in water at 673 K and
3
0.5 g/cm of water density. The liquid products were 2-isobutyl-
phenol, 2-tert-butylphenol, and 4-tert-butylphenol. The 2-iso-
propylphenol was a minor product and its yield was below
1.1%. In some cases, several other small peaks such as butyl
phenyl ether, 2-propylphenol were identified in the GC analysis,
however, the yields of these compounds were trace (below
0.1%). We conducted the experiments for gas analysis for some
3
runs at 80 min reaction time at 673 K and 0.5 g/cm water den-
1
anti-Markovnikov alkylation. On the other hand, in the alkyla-
sity. For this case, almost all gas products were isobutene, whose
molar proportion to other gases was 90.4%. The proportion of
isobutane and propane was 6.6 and 2.4%, respectively. Propyl-
ene, methane, carbon dioxide, and hydrogen were formed below
1%. The yield of isobutene shown in Figure 1 was estimated
from carbon balance and included other gases as well.
From the results in Figure 1, we propose the main reaction
pathway. In Figure 1, the yield of tert-butyl alcohol (1) rapidly
decreased with reaction time and the yield of isobutene (2) in-
tion of phenol, the hydroxy group of phenol strongly activates
the ring substituents at both the ortho- and para-positions. Var-
ious catalysis can change the ratio of ortho- and para-orientation
2
–5
for alkylation of phenol. Solid catalysis of alkylation of phe-
6
nol in supercritical carbon dioxide and non-catalytic reaction in
7
supercritical alcohols give alkylphenols.
In high temperature water including the supercritical region
(Tc = 647 K, Pc = 22.1 MPa), water acts as a solvent and many
organic reactions have been shown to proceed without cata-
lyst.8 Chandler et al.
–12
13,14
reported that alkylation of phenol
1
00
with propan-2-ol and tert-butyl alcohol proceeded without cata-
lyst in high temperature water at 548 K and the alkyl side chain
of products were followed by Friedel–Crafts alkylation rule. For
the alkylation of phenol, we have found that the highly ortho
2
5
0
0
0
OH
1
1
0,11
selective alkylation of phenol with propan-2-ol
and regio-
OH
1
2
selective alkylation of phenol with propionaldehyde occurs in
supercritical water.
2
1
OH
In this study, we conducted the alkylation of phenol with
tert-butyl alcohol in sub- and supercritical water at 673 K with-
out catalyst. We show that alkylphenol whose alkyl side chain
being anti-Markovnikov type can be formed without catalyst
and the orientation for ortho- and para-position can be control-
led with water density in supercritical water.
5
3
4
0
0
OH
0
20 40 60 80 100
Reaction Time / min
Experiments were conducted in stainless 316 tube-bomb
3
reactors (6 cm ) with a forced convection oven at 673 K. The
phenol and tert-butyl alcohol was purchased from Wako Pure
Chemical Industries, Ltd., and their purities were both >99%.
For the reaction of tert-butyl alcohol with phenol, 0.002 mol of
tert-butyl alcohol and 0.010 mol of phenol and from 0 to 3 g of
Figure 1. Yield of (+) isobutene (2), ( ) 2-isobutylphenol (3),
) 2-tert-butylphenol (4), ( ) 4-tert-butylphenol (5) for reac-
(
tion of phenol with tert-butyl alcohol ( ) at 0.5 g/cm of water
density and 673 K.
3
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.7 (2006)
717
Table 1. Effect of water density on the alkylation of phenol
with tert-butyl alcohol for 80 min at 673 K, [tert-butyl alcohol]0
bulk proton concentration. As a result, the alkylation occurred
mainly at the ortho position and 2-tert-butylphenol preferred
to form in lower water density region. In the high water density
region, the yield of 4-tert-butylphenol was larger than that of
2-tert-butylphenol because the steric hindrance of tert-butyl
group was probably high.
=
0.33 mol/L, [phenol]0 = 1.65 mol/L
Yield/%
Water
density
À3
Sum of 3,
4, 5
1
3
4
5
/
g cm
On the other hand, the yield of 2-isobutylphenol was lower
3
0
103.0
18.9
8.9
9.1
7.2
3.4
2.8
10.1
9.7
1.1
4.9
1.5
3.8
3.2
0.0
0.0
2.9
9.6
4.5
7.7
14.5
23.1
34.8
than 3.4% below 0.2 g/cm of water density, increased to 10% at
3
0
0
0
0
.2
.3
.4
.5
3
0
of water density. Sato et al.
.3 g/cm of water density and was attained 13.4% at 0.5 g/cm
1
1,12
reported that the hydroxy group
participated in the alkylation of phenol to form a carbon–carbon
bond between carbon of aromatic ring and the alkene (OH-cata-
lyzed reaction). In the case of phenol alkylation in supercritical
water, alkylation proceeds through both typical Friedel–Crafts
alkylation and above OH-catalyzed alkylation. The reaction field
of OH-catalyzed reaction seemed to be limited around ortho-
position of hydroxy group, which causes no formation of 4-
isobutylphenol. The increase in water density influenced the sol-
vation around OH group of phenol and enhanced OH-catalyzed
13.4
18.2
creased corresponding to the decrease of tert-butyl alcohol. Xu
et al.15 reported that tert-butyl alcohol decomposed to isobutene
without catalyst in high temperature water and acid accelerated
the dehydration. In supercritical water, the higher temperatures
used probably caused rapid dehydration of tert-butyl alcohol to
isobutene. After that, the alkylation of phenol with isobutene
proceeded to form 4-tert-butylphenol (5), 2-isobutylphenol (3),
and 2-tert-butylphenol (4) whose yields were in this order. At
1
1
reaction to form anti-Markovnikov alkylphenol.
1
1
40 min of reaction time, the yield of 2-isobutylphenol was
2.6% as the same level at 80 min (not shown), which indicates
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7
8
9
3
to 0.4 g/cm . The higher dissociation constant of phenol makes
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3
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4
.9% between 0 and 0.5 g/cm of water density and that of 4-
tert-butylphenol greatly increased with increasing water density
up to 18.2%. In the typical Friedel–Crafts alkylation, the tert-
butyl positive ion attacks both ortho- and para-position of
hydroxy group and the structure of the alkyl side chain becomes
highly branched according to Markovnikov rule. The increase of
water density promotes typical Friedel–Crafts alkylation by the
increase in proton concentration. In water, the solvation of water
molecules around the hydroxy group of phenol occurs.1 There-
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7
Published on the web (Advance View) May 30, 2006; doi:10.1246/cl.2006.716