Acid catalyzed alkylation of phenols with cyclohexene: Comparison between homogeneous and heterogeneous catalysis, influence of cyclohexyl phenyl ether equilibrium and of the substituent on reaction rate and selectivity

Article abstract of DOI:10.1016/j.molcata.2011.12.007

The reactivity of several phenols toward liquid phase alkylation with cyclohexene in the presence of heterogeneous and homogeneous acid catalyst at 358 K is studied. The comparison between Amberlyst 15 and CH₃SO ₃H, as examples of heterogeneous and homogeneous systems, shows a higher activity of the former with different behavior of selectivity between the two systems, anyway, in both systems O-alkylation and ring alkylations occur. A remarkable difference in the selectivity of the ring alkylation between heterogeneous and homogeneous systems is observed: Amberlyst 15 shows a constant ortho/para ratio close to 2, while in the presence of CH₃SO ₃H ortho/para is variable from 3 to 5, suggesting an involvement of the cyclohexyl phenyl ether rearrangement. This is proved also by a direct relationship between the ortho/para ratio and the concentration of the cyclohexyl phenyl ether when CH₃SO₃H is used as a catalyst. The formation of cyclohexyl aryl ethers is reversible; on the contrary, ring alkylation appears irreversible. The reactivity of the dimethylphenols shows a strong influence of the steric hindrance of the substituent on the electrophilic attack of the cyclohexyl cation, which is poorly influenced by the inductive effect of the methyl group.

Full text of DOI:10.1016/j.molcata.2011.12.007

Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
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Acid catalyzed alkylation of phenols with cyclohexene: Comparison between
homogeneous and heterogeneous catalysis, influence of cyclohexyl phenyl ether
equilibrium and of the substituent on reaction rate and selectivity
L. Ronchin∗, A. Vavasori, L. Toniolo
Department of Molecular Science and Nanosystems, University Ca’ Foscari of Venice, Dorsoduro 2137, 30123 Venice, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactivity of several phenols toward liquid phase alkylation with cyclohexene in the presence of
heterogeneous and homogeneous acid catalyst at 358 K is studied. The comparison between Amberlyst
15 and CH3SO3H, as examples of heterogeneous and homogeneous systems, shows a higher activity of
the former with different behavior of selectivity between the two systems, anyway, in both systems
O-alkylation and ring alkylations occur. A remarkable difference in the selectivity of the ring alkyla-
tion between heterogeneous and homogeneous systems is observed: Amberlyst 15 shows a constant
ortho/para ratio close to 2, while in the presence of CH3SO3H ortho/para is variable from 3 to 5, sug-
gesting an involvement of the cyclohexyl phenyl ether rearrangement. This is proved also by a direct
relationship between the ortho/para ratio and the concentration of the cyclohexyl phenyl ether when
CH3SO3H is used as a catalyst. The formation of cyclohexyl aryl ethers is reversible; on the contrary, ring
alkylation appears irreversible. The reactivity of the dimethylphenols shows a strong influence of the
steric hindrance of the substituent on the electrophilic attack of the cyclohexyl cation, which is poorly
influenced by the inductive effect of the methyl group.
Received 1 August 2011
Received in revised form
28 November 2011
Accepted 7 December 2011
Available online 16 December 2011
Keywords:
Acid catalysis
Sulfonated resins
Phenols alkylation
Alkylation selectivity
© 2011 Published by Elsevier B.V.
1. Introduction
process innovation aimed to avoid environmental concerns, ion-
exchange resins appear to be ideal catalysts to convert polluting
Organic industrial processes employ acid catalyzed reactions
such as alkylation, acylation, isomerization, cracking, nitration,
condensation, esterification, etc. The green technologies in order
to replace the traditional polluting mineral acid catalysts with
solid ones are continuously improved [1–6]. Zeolites, acid treated
clays, ion exchange resins and supported acids are investigated by
several researchers for their application in pharmaceutical, per-
fumery, agro-chemicals, dye-stuffs, intermediates and specialty
chemical industries [5–12]. Alkylation reactions in particular are
really important in the industrial synthesis of many large scale
production compounds [11,12].
Alkylation of phenol with cyclohexene has attracted consid-
erable interest because of its industrial and academic relevance
[13–21]. This reaction leads to a variety of products such as
4-cyclohexylphenol, 2-cyclohexylphenol, and cyclohexyl phenyl
ether depending on both the catalyst and the reaction conditions.
The use of solid acid catalysts appears a suitable alternative to
the usual procedures in homogeneous phase with catalysts such
as AlCl3, BF3, TiCl4, HF. On considering the current effort toward
processes into greener ones [2–6].
In a large number of industrial processes the cation-exchange
resins are used as a catalyst such as in MTBE or TAME synthesis,
the manufacture of alkyl phenols and bisphenol A, the esterifica-
tion of a variety of carboxylic acids, the hydration of alkenes, the
dimerization of isobutene, etc. [4–6,19,22,23].
The mechanism of acid catalyzed alkylation is well known for
a long time and it is widely accepted the carbonium ion attack to
the electronic rich center as the key step of the reaction [24,25].
Cyclohexene in the presence of acid gives the cyclohexyl cation
as a transient species that readily reacts with a nucleophile giving
the corresponding cyclohexyl derivative. The rearrangement to the
more stable methyl cyclopentyl cation occurs only in a negligible
extent since the skeleton rearrangement is slower than the nucle-
ophilic attack, which occurs, for many nucleophiles, at encounter
[26].
The study of Richard and coworkers on the reactivity of phe-
nol as nucleophile toward methyl phenyl carbocation showed that
the relative rates for alkylation of phenol at OH, C-4 and C-2 are
230:20:1, respectively. On the contrary, the alkylation of the corre-
sponding nucleophilic sites of phenoxide ion, which is an encounter
reaction, showed the relative rates of 2:2:1 [27]. Other authors
pointed out that the selectivity toward the ortho position in the
∗
Corresponding author. Fax: +39 0412348517.
E-mail address: ronchin@unive.it (L. Ronchin).
1381-1169/$ – see front matter © 2011 Published by Elsevier B.V.
doi:10.1016/j.molcata.2011.12.007

L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
135
phenol alkylation is favored when the less hindered secondary
carbonium ions are the electrophiles, while tertiary carbocations
give prevalently para alkylation [28,29]. The studies of Sharma and
coworkers, carried out in the early ninety relating the reactivity
of phenol in the presence of sulfonated resins, pointed out that
the ortho–para selectivity in the ring alkylation of phenol is strictly
related to the nature of the olefin employed. In particular, propene
and 1-butene give an ortho–para ratio close to 2, while isobutene,
␣-methyl styrene and diisobutene give almost exclusively para
alkylation [29]. Recently, Bhatt and Patel reported that supported
12-tungstosilicic acid catalyzes only ring cyclohexylation of phenol
giving an ortho–para ratio close to 2 [15]. More recently, Hölderich
and coworkers showed that high para selectivity is obtained in the
alkylation of phenol with isobutene in the presence of catalysts
with Lewis or Brønsted acid sites, indifferently. The selectivity is not
sensible to the type of acid present in the catalyst but the activity
is influenced by the amount and the strength of the sites [30].
The comparison of activity and selectivity between heteroge-
neous and homogeneous BF3/SiO2 and BF3·(H2O)2 catalysts was
studied by Clark and coworkers [21]. They pointed out that cyclo-
hexyl phenyl ether, and cyclohexyl phenols are formed in the
presence of both systems, but only by the homogeneous BF3·(H2O)2
as a catalyst the rearrangement of the ether to alkyl phenols is
observed [21]. Yadav and Kumar have recently studied the kinetics
of phenol cyclohexylation catalyzed by different solid acids, which
catalyze the formation of phenyl cyclohexyl ether and the prod-
ucts of ring alkylation in a ortho–para ratio close to 2 [14]. The
mechanistic aspect of the electrophilic attack to the phenol is inves-
tigated from a theoretical point of view by Tang and coworkers.
These authors suggested that the addition of the sulfonic acid to
the olefins occurs leading to the formation of a sulfonic ester inter-
mediate, which, in turns, reacts with phenol to form the products
of alkylation [31].
reactor. All the operations were carried out into a glove box in order
to minimize catalyst deactivation by air moisture. Small amounts
of the solution were drawn at different times and the samples were
analyzed by GC, and GC–MS using a HP5 capillary column (300 ␮m
i.d. 30 m long, 95% methyl, 5% phenyl silicone phase). The samples
were checked also by HPLC using a Perkin Elmer apparatus and a
Lichrosphere 100 (RP-18, 5 ␮m) column. The first derivative at time
0 of a third order polynomial function, obtained by fitting cyclohex-
ene concentration vs. time at 10% of conversion, gave the initial rate
of reaction.
For a reliable comparison of the performances of different cat-
alysts it is essential to known if reaction rate data are affected by
diffusion phenomena. This is verified by studying the influence of
the granulometry and of the catalyst amount on the reaction rate
catalyzed by the most active catalyst (Amberlyst 36) at 373 K. The
experimental evidences suggest that the kinetics is not influenced
by diffusion phenomena, since there are no differences in the ini-
tial rate using resins with different granulometry and the initial
reaction rates are strictly proportional to the catalyst amount. In
addition, the inspection of Carberry and Wheeler-Weisz numbers
shows values lower than 0.1 and 0.4, respectively [33].
3. Results and discussion
3.1. Influence of solvent and catalyst on reaction rate, conversion
and selectivity
Table 1 reports the activity of two sulfonated resins in the alkyla-
tion of phenol. Maximum yield, as reported in Table 1, is comprised
between 20 and 26% at 40–50% of conversion. Despite of Amberlyst
36 promotes a initial rate of reaction higher than that of Amberlyst
15, the latter gives the highest yield in the ether. As a matter of fact,
Amberlyst 36 (5.5 meq. H+ g−1cat) shows a higher activity than the
Amberlyst 15 (4.7 meq. H+ g−1cat), this is likely due to the higher
acid content of the former. In fact, the activities of the two catalysts
are quite similar considering the initial turnover frequency referred
to the whole H+ sites (Table 1). CH3SO3H (in homogeneous phase) is
the least active catalyst and its TOF is 20 times lower than that of the
sulfonic resins, likely due to the higher acidity of the latter [34]. As
a matter of fact, by considering p-toluensulfonic acid as simplified
model for the sulfonic resins, the pKa of the p-toluensulfonic acids is
2.7 pKa units lower than that of methanesulfonic acid (−4.7 and −2,
respectively) [35]. In the presence of AlCl3 the reaction is faster, but
the comparison of the activities of sulfonated resins, methanesul-
fonic acid (protic acids) and AlCl3 (Lewis acid) is cumbersome due to
the different nature of the acid site. It is noticeable that the reactiv-
ity of the ortho and para positions of phenol is not influenced by the
In this paper we study the cyclohexylation of some phenols and
the reactivity of cyclohexyl phenyl ether in the presence of both
CH3SO3H and sulfonic resins. In particular, we investigate the role
of the cyclohexyl phenyl ether on the ortho–para selectivity and the
reactivity of the dimethylphenols in order to account for the steric
hindrance of the methyl groups on the electrophilic attack of the
cyclohexyl cation.
2. Experimental
2.1. Materials
Reagents and solvents were used after purification of the com-
mercially available samples and their purity was checked by the
usual methods (melting point, TLC, HPLC, GC and GC–MS). The sol-
vents were treated in a double bed column, filled with H2SO4/SiO2
and SiO2 to adsorb water and impurities. The residual water content
was checked by HPLC analysis [32]. Commercial catalysts: macro-
reticular sulfonated styrene divinyl benzene resins Amberlyst 15TM
and Amberlyst 36TM (a trade mark of Rohm and Haas) were pur-
chased from Aldrich.
type of sulfonic resins employed. Ortho- and para-positions of the
∼
phenol show similar relative reactivity giving ortho–para ratio
2
=
in either benzene or 1,2-dichloroethane. In contrast, a not negligi-
ble solvent effect seems to be played by nitromethane, since the
initial reaction rates are almost one order of magnitude lower than
those measured in benzene and 1,2-dichloroethane. In addition, the
∼
ortho–para ratio clearly diminishes (o/p 1.5), thus suggesting an
=
influence of the solvent on the electrophilic attack [36].
2.2. Reactions
Despite of the large difference of activity between CH3SO3H and
AlCl3 in homogeneous phase, the reactions show a similar o/p ratio
(4.2 and 4.5), thus suggesting similar relative reaction rate for each
stage in this homogeneous reactions.
The reactions and the kinetic runs were performed in a
stirred glass reactor thermostatted by
a circulation bath at
358 K, containing weighed samples of solvent, reagents and cat-
alyst at autogenous solvent pressure (122 and 158 kPa for 1,2
dichloroethane and benzene, respectively). In a typical experiment
10 mL of solution containing 10 mmol of phenol, 10 mmol of cyclo-
hexene plus 5 mmol of methylcyclohexane as internal standard and
the desired amount of catalyst (100–500 mg) were placed in the
The concentration–time profiles reported in Figs. 1–3, relative to
the reactions in the presence of Amberlyst 15, CH3SO3H and AlCl3,
respectively, show different trends. Fig. 1 reports the reaction cat-
alyzed by Amberlyst 15. It appears that cyclohexyl phenyl ether is
a transient species, which is almost completely consumed at the
end of the reaction. On the contrary, the formation of cyclohexyl,

136
L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
Table 1
Alkylation of phenol: selectivity after 240 min of reaction at 358 K. Run conditions: phenol 1.1 mol L−1, cyclohexene 1.1 mol L−1, catalyst 400 mg, reaction volume 10 mL.
a
Catalyst
Conv. (%) r0
TOFb Ether maximum
yield (%)
Selectivityc (%)
o/p
2-Cyclohexyl phenol 4-Cyclohexyl phenol Dicyclohexyl phenols Cyclohexyl cyclohexene Ratio
Benzene
Amb.15
Amb. 36
42
48
15
18
5.3
5.8
25
23
29
38
16
21
13
14
15
18
1.9
1.9
1,2-Dichloroethane
Amb.15
Amb.36
51
64
18
22
3.5
58
6.8
6.9
0.34
7.7
26
23
17
15
29
31
10
5
14
16
2.4
1.1
15
18
2.3
4.6
12
15
2
2.0
1.9
4.2
4.5
CH3SO3Hd 21
d,e
AlCl3
44
1
Nitromethane
Amb.15
Amb.36
16
19
3.8
6.0
0.81
1.1
10
10
24
24
16
16
Traces
Traces
Traces
Traces
1.5
1.5
(105 mol L−1 s−1 gcat−1).
a
b
c
Initial turnover frequency (104 s−1
)
Products in trace amount, as the isomers of alkylated the cyclohexyl ether, has been neglected.
Homogeneous reactions.
T 288 K, AlCl3 1 mmol.
d
e
1.2
di-cyclohexyl phenols increases monotonically during the reac-
tion course. Formation of di-cyclohexyl phenols is observed also
at very low conversion, because of alkyl phenols are highly acti-
vated toward the electrophilic attack [37]. Under the conditions
used the main side reaction is cyclohexene dimerization, whose
product (cyclohexylcyclohexene) shows an almost linear mono-
tonic increase during reaction course. It is noteworthy that dimer
formation is strongly inhibited using nitromethane as the solvent,
suggesting an inhibiting effect of the solvent on the formation of
the electrophile [36].
Fig. 2 shows the reaction profile in the presence of CH3SO3H:
the reaction is almost ten time slower than that in the presence
of Amberlyst 15 as a catalyst (Table 1) and after 20 h of reaction
all the products are still increasing, while the formation of di-
cylohexyl phenols is negligible. The concentration–time profile of
phenol cyclohexylation catalyzed by AlCl3 (Fig. 3) evidences a fast
reaction also at 288 K (almost twice of that measured in the pres-
ence of Amberlyst 15 at 358 K) but the reaction completely stops
after 55 min, with a modest conversion and with a noticeable loss
of the mass balance. Such a behavior suggests a fast catalyst deac-
tivation due to the formation of heavy pitch, which is confirmed by
HPLC analysis.
cyclohexycyclohexene
di-cyclohexylphenol
cyclohexene
phenol
cyclohexyl phenyl ether
2-cyclohexylphenol
4-cyclohexylphenol
0.06
0.04
0.02
0.00
1.0
0.8
0.6
0.4
0.2
0.0
0
200
400
600
800 1000 1200
0
200
400
600
800
1000 1200
time (miinutes)
Fig. 1. Reaction profile of alkylation of phenol at 358 K catalyzed by Amberlyst
36. Run conditions: phenol 1.1 mol L−1, cyclohexene 1.2 mol L−1, catalyst 400 mg,
solvent 1,2-dichloroethane, reaction volume 10 mL.
1.0
0.8
0.6
0.020
2-cyclohexyphenol
1.0
cyclohexene
cyclohexyl phenyl ether
2-cyclohexylphenol
4-cyclohexylphenol
cyclohexylcyclohexene
4-cyclohexylphenol
0.015
cyclohexylcyclohexene
di-alkykphenol
0.4
0.010
0.8
0.005
0.000
0.2
0.1
0.0
0
50
100
150
200
1000 1200
0.6
cyclohexene
cyclohexyl phenyl ether
0.15
0.10
0.05
0.00
0
100
200
1100
1200
0
50
100
150
200
250
1000
1200
time (minutes)
time (minutes)
Fig. 2. Reaction profile of alkylation of phenol at 358 K catalyzed by methanesul-
fonic acid. Run conditions: phenol 1 mol L−1, cyclohexene 1 mol L−1, catalyst 400 mg,
solvent 1,2-dichloroethane, reaction volume 10 mL.
Fig. 3. Reaction profile of alkylation of phenol catalyzed by AlCl3 at 288 K. Run
conditions: phenol 1 mol L−1, cyclohexene 1 mol L−1, catalyst 140 mg, solvent 1,2-
dichloroethane, reaction volume 10 mL.

L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
137
0.20
5
4
3
2
0.10
2-cyclohexylphenol
4-cyclohexylphenol
di-alkylphenols
0.08
0.06
0.04
0.02
0.00
0.15
0.10
0.05
0.00
CH3SO3H
Amberlyst 15
AlCl3
0
200
1000
1200
cyclohexene
phenol
cyclohexyl phenyl ether
cyclohexylcyclohexene
0
100
200
1000 1100 1200 1300
time (minutes)
Fig. 6. Reactivity of cyclohexyl phenyl ether. Run conditions: T 358 K Amberlyst 15,
400 mg, solvent 1,2-dichloroethane, reaction volume 10 mL.
0
20
40
60
80
100
conversion (%)
the cyclohexyl phenyl ether toward ortho and para selectivity. Such
a behavior suggests that, in the presence of Amberlyst 15, the ortho
and para selectivity is mainly influenced by the mesomeric effect
of the hydroxyl group [37–39]. Besides the reaction catalyzed by
AlCl3 shows a small increase of the ortho/para ratio vs. cyclohexyl
phenyl ether concentration, but with a neat prevalence of the ortho
isomer. The reasons of such a behavior are not clear and at least
two effects may concur to give this result: the ether rearrangement
and a specific interaction between phenol and AlCl3, as suggested
by Sartori and coworkers [40].
Fig. 4. Comparison of ortho/para ratio vs. conversion in the cyclohexylation of phe-
nol in the presence of liquid and solid acid catalysts. Run conditions: cyclohexene
and phenol 1 mol L−1, Amberlyst 15 and CH3SO3H 1.8 meq H+, AlCl3 10 mmol, solvent
1,2-dichloroethane, reaction volume 10 mL T 358 K.
In Fig. 4 the trend of the ortho–para ratio vs. conversion for
each catalyst is reported. Employing Amberlyst 15 as a catalyst
ortho–para ratio remains practically constant (1.9–2.1), whereas,
in the presence of CH3SO3H, monotonically increases from 2.4 to
4.2 as the conversion increases. Also in the presence of AlCl3, the
ortho–para ratio vs. conversion increases from 4.1 to 4.5. These evi-
dences suggest a different nature in the formation of the ortho and
para isomers as the catalyst nature change. This is confirmed by
the trends of the ortho–para ratio vs. cyclohexyl phenyl ether con-
centration reported in Fig. 5. Clearly, there is a linear relationship
between the ether concentration and the formation of the ortho iso-
mer in the presence of CH3SO3H, thus suggesting the involvement
of the cyclohexyl phenyl ether in the formation of the ortho isomer,
likely via rearrangement [37,38]. On the contrary, in the presence of
Amberlyst 15, there is a very small influence of the concentration of
3.2. Reactivity of cyclohexyl phenyl ether
The reactivity of cyclohexyl phenyl ether, in presence of acid
catalysts, is reported in Figs. 6–8 and in Table 2. Fig. 6 shows the
concentration–time profile of the reaction catalyzed by Amberlyst
15: cyclohexene reaches a maximum after 2 h of reaction, and then
it decreases to complete consumption. At the same time, phenol
concentration reaches to a maximum and subsequently dimin-
ishes smoothly (almost to a plateau). As a matter of fact, phenol
is less converted than cyclohexene because all reactions, such as
alkylation, dialkylation and cyclohexene dimerization, concur to
consume cyclohexene. The initial reaction rate of ether decom-
position is comparable to that of the phenol cyclohexylation and
5.5
o/p CH3SO3H
5.0
o/p Amberlyst 15
o/p AlCl3
4.5
0.20
4.0
3.5
3.0
2.5
2.0
0.15
cyclohexene
phenol
cyclohexyl phenyl ether
2-cyclohexyl phenol
4-cyclohexyl phenol
0.10
0.05
0.00
0.00
0.05
0.10
0.15
0.20
0.25
0.30
cylohexyl phenyl ether (mol L-1)
0
50
100
150
200
250
time (minutes)
Fig. 5. Comparison of ortho/para ratio vs. cyclohexyl phenyl ether concentration
in the cyclohexylation of phenol in the presence of liquid and solid acid catalysts.
Run conditions: cyclohexene and phenol 1 mol L−1, Amberlyst 15, 400 mg, CH3SO3H
1.8 meq H+ and AlCl3 1 mmol, solvent 1,2-dichloroethane, reaction volume 10 mL T
358 K.
Fig. 7. Reactivity of cyclohexyl phenyl ether. Run conditions: cyclohexyl phenyl
ether 0.21 mol L−1, T 358 K, CH3SO3H 180 mg, solvent 1,2-dichloroethane, reaction
volume 10 mL.

138
L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
Table 2
Reactivity of cyclohexyl phenyl ether: selectivity after 240 min of reaction at 358 K. Run conditions: cyclohexyl phenyl ether 0.2 mol L−1, solvent 1,2-dichloroethane, reaction
volume 10 mL.
a
Catalyst
Conv. (%)
r0
Selectivity (%)
o/p
2-Cyclohexyl phenol
4-Cyclohexyl Phenol
Dicyclohexyl phenols
18
Traces
22
Ratio
Amberlyst 15b
CH3SO3Hc
AlCl3
92
85
74
10
40
75
10
4
19
33
0.9
3.4
3.3
4.2
5.6
d
a
(105 mol L−1 s−1 g−1cat).
Amberlyst 15, 400 mg.
CH3SO3H 180 mg.
T 288 K, AlCl3 0.2 mmol.
b
c
d
considering the whole reaction steps, ring alkylations are likely the
slower stage, thus allowing accumulation of phenol and cyclohex-
ene. In the presence of CH3SO3H (Fig. 7) the reverse etherification
occurs with an initial reaction rate 4 times higher than when
Amberlyst 15 is used as a catalyst, and after 50 min of reaction
75% of cyclohexyl phenyl ether is converted to cyclohexene and
phenol in 95% of overall selectivity. In fact, CH3SO3H as a catalyst
does not give ring alkylation products in high yields, but allows fast
decomposition of the ether. Fig. 8 shows the concentration–time
profile of the reactivity of the cyclohexyl phenyl ether at 288 K, in
the presence of AlCl3, the initial reaction rate is much higher than
in the presence of Amberlyst 15 (7 times) but it does not reach com-
pleteness probably because of catalyst poisoning, in agreement to
what found in phenol alkylation. In this case, the concentration of
cyclohexene is negligible with respect to that of phenol, due to a
fast formation of cyclohexene oligomerization products, which are
probably one of the reasons of catalyst deactivation.
The ortho/para selectivity (see Table 2) with different catalysts
after 4 h of reaction is in the range 3.3–5.6, and, as expected, the
ether favors the ortho-selectivity. Apparently, the trends of the o/p
ratio vs. ether conversion, showed in Fig. 9, are not in agreement
with those found in the phenol cyclohexylation (Fig. 5), because
both AlCl3 and CH3SO3H show a constant o/p ratio (5.3, 4.3, respec-
tively), while in the presence of Amberlyst 15 the o/p ratio decreases
from 4.2 to 2.7. Despite of the complexity of the reaction it is clear
that cyclohexyl phenyl ether is involved in the selectivity of the
ortho and para isomers of the alkylated phenols, but further inves-
tigations needs to highlight such a behavior.
3.3. Reactivity of dimethylphenols and 2,4,6-trimethylphenol
Further insight on the reactivity of the cyclohexyl cation as elec-
trophile toward phenols may be gained by studying the reactivity
of dimethylphenols and of the 2,4,6-trimethylphenol, in order to
test the influence of the methyl substituent both for its induc-
tive effect as well as for the steric hindrance. In Figs. 10 and 11,
the concentration–time profile of the cyclohexylation of the 2,3-
dimethylphenol catalyzed by both Amberlyst 15 and CH3SO3H are
shown. The general trend observed in this case is similar for all
phenols, thus suggesting the involvement of a same reaction path.
In agreement with that observed for the phenol the activity of the
Amberlyst 15 is, in any case, higher than that of CH3SO3H (Table 3),
which is likely due to the superior protonation ability of the solid
acid with respect to the liquid one [34,35]. The activity of 3,5-
dimethyl phenol and 2,6-dimethyl phenol are lower than that of
neat phenol (Table 1), the phenomenon may be ascribed to the
steric hindrance of the substituents, which slow down the elec-
trophilic attack [37,38]. Such an effect is more pronounced on the
initial reaction rate of the 2,6-isomer than the 3,5-one. The small
increase of the reaction rate of the 2,3-dimethyl-phenol cyclo-
hexylation with respect to that of neat phenol may be due to the
inductive effect of methyl groups, even though the steric hindrance
may play a non-negligible effect. In fact, the initial reaction rate
of 2,4-dimethyl-phenol is equivalent to that of phenol, the rea-
son of this behavior is not clear, but it might be ascribed to the
6
5
4
0.20
cyclohexyl phenyl ether
cyclohexene
phenol
2-cyclohexyl phenol
4-cyclohexyl phenol
0.15
3
0.10
0.05
0.00
o/p Amberlyst 15
o/p CH3SO3H
o/p AlCl3
2
20
40
60
80
100
conversion (%)
0
50
100
150
200
250
Fig. 9. Comparison of ortho/para ratio vs. conversion in the cyclohexylation of
phenol and in the rearrangement of cyclohexyl phenyl ether. Run conditions: cyclo-
hexene and phenol 1 mol L−1, Amberlyst 15, CH3SO3H 1.8 meq H+ and AlCl3 1 mmol
as catalysts, solvent 1,2-dichloroethane, reaction volume 10 mL T 358 K. Cyclohexyl
phenyl ether rearrangement are carried out with the same run conditions except
time (minutes)
Fig. 8. Reactivity of cyclohexyl phenyl ether. Run conditions: cyclohexyl phenyl
ether 0.21 mol L−1, T 358 K, AlCl3 1 mmol, solvent 1,2-dichloroethane, reaction vol-
ume 10 mL.
the initial concentration of 0.2 mol L−1
.

L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
139
Table 3
Alkylation of dimethylphenols and 2,4,6-trimethylphenol: selectivity after 240 min of reaction at 358 K. Run conditions: dimethylphenols 1.2 mol L−1, cyclohexene 1.1 mol L−1
Amberlyst 15, 400 mg or CH3SO3H 180 mg, solvent 1,2-dichloroethane, reaction volume 10 mL.
,
a
Catalyst
Conv. (%)
r0
Selectivity (%)
Ether
2-Cyclohexyl DMPb
3-Cyclohexyl DMPb
4-Cyclohexyl DMPb
Cyclohexyl
cyclohexene
2,6-Dimethylphenol
Amberlyst 15
CH3SO3H
15
7.2
2.6
0.9
26
18
–
–
5
11
15
16
13
55
3,5-Dimethylphenol
Amberlyst 15
CH3SO3H
35
14
16
4.1
24
29
27
14
–
–
5
0.1
10
13
2,3-Dimethylphenol
Amberlyst 15
CH3SO3H
95
13
44
3.1
4
18
38
19
5
–
12
5
4
55
2,4-Dimethylphenol
Amberlyst 15
CH3SO3H
80
12
30
2.1
10
12
42
10
10c
2c
–
–
5
62
2,5-Dimethylphenol
Amberlyst 15
CH3SO3H
57
16
14
1.5
16
16
16
9
–
–
16
4
2
15
2,4,6-Trimethylphenol
Amberlyst 15c
1
5
0.2
0.6
–
–
–
–
–
–
–
–
50
50
CH3SO3Hc
(105 mol L−1 s−1 gcat−1).
DMP = dimethylphenol.
a
b
c
Between the two possible isomer (in 3 or 5 position) it has not verified what is formed, but the 5 isomer is more plausible, due to the lower steric hindrance of the 5
position.
d
Large part of the products are peach, formation of traces of the ether and the m-isomer has been observed after 20 h of reaction.
simultaneous presence of two contrary effects: the steric hindrance
and the inductive effect of the methyl groups. The reactivity of 2,5-
dimethyl-phenol is clearly influenced by the steric hindrance of
the methyl groups, in particular the one in 2-positions slows down
the attack of the cyclohexyl cation toward the hydroxyl group,
while that in 5-position simultaneously hampers the attack to both
ortho and para positions. As a matter of fact, 2,4,6-trimethyl-phenol
shows a negligible reactivity toward electrophilic attack, thus sug-
gesting the cyclohexyl cation is greatly influenced by the steric
hindrance both on the attack to the hydroxyl group and to the
phenyl ring.
The influence of the methyl groups on the ring alkylation selec-
tivity is strictly related to the position of the substituent rather than
their inductive effect. For instance, 3,5- and 2,3-dimethylphenol
show, in the presence of Amberlyst 15 as a catalyst, an ortho–para
ratio of 5.4 and 3.2, respectively. As a matter of fact, such a behavior
suggests that the relative reactivity of the para positions of these
compounds is about 3 times lower than the ortho ones. The compar-
ison of these results with the almost equal relative reactivity of the
ortho and para positions, observed in the cyclohexylation of phe-
nol in the presence of Amberlyst 15 as a catalyst, suggests a strong
effect of the steric hindrance of the methyl groups on the selectiv-
O
t
s
y
l
a
t
a
c
d
i
c
a
+
OH
isomers
Cy
isomers
OH
Cy
+
+
Cy
acid catalyst
OH
OCy
OH
+
acid catalyst
n
Scheme 1. Reaction paths for phenol cyclohexylation and for the cyclohexene oligomerization.

140
L. Ronchin et al. / Journal of Molecular Catalysis A: Chemical 355 (2012) 134–141
3.4. Reaction path proposed for the reactions
1.0
0.8
0.6
0.4
0.2
0.0
cylohexene
Alkylation, etherification and olefin oligomerization are the
reactions between phenols and cyclohexene observed in the pres-
ence of acid catalysts. All the experimental evidences suggest the
reaction path depicted in Scheme 1. There are three parallel and two
consecutive acid catalyzed reactions. In particular, the formation
of cyclohexyl phenyl ether is reversible (also the formation of the
aliphatic ether is reversible [41]), while ring alkylation of phenol,
cyclohexene oligomerization cyclohexyl phenyl ether rearrange-
ment and alkylphenols isomerization are practically irreversible
[39].
cyclohexyl phenyl ether
2-cyclohexyphenol
4-cyclohexyphenol
4. Conclusions
The reaction between phenol and cyclohexene occurs via a com-
plex path, which is characterized by the formation of the cyclohexyl
phenyl ether as reversible intermediate and its complete conver-
sion to the products of ring alkylation at the end of the reaction,
whenever catalyst deactivation does not occur. The reactions of O-
alkylation, ring alkylation, ether rearrangement and cyclohexene
oligomerization occur simultaneously, but the latter is practically
negligible by selecting the proper solvent or carrying out the reac-
tion in excess of phenols. In the presence of Amberlyst 15 and
36 resins the selectivity of ring alkylation of phenol seems to be
driven by the typical ortho/para orienting effect of the hydroxyl
group. On the contrary, a specific action of homogeneous systems
(CH3SO3H and AlCl3) toward formation of the ortho isomers has
been observed, but it is not clear what is the reason of such a behav-
ior. The electrophilic attack of the cyclohexyl cation is strongly
influenced by the steric hindrance of the methyl group as a matter
of fact, the alkylation of 2,4,6-trimethylphenol practically does not
occur, and the activation, due to the inductive effect to the con-
tiguous positions of the methyl group, is negligible compared to
the deactivation induced by the steric hindrance.
0
50
100
150
200
250
300
time (minutes)
Fig. 10. Reactivity of 2,3-dimethyl phenol. Run conditions: T 358 K, solvent 1,2-
dichloroethane, Amberlyst 15, 400 mg, reaction volume 10 mL.
ity. Further support to this is the equal reactivity of the ortho and
para positions of the 2,5-dimethylphenol. In this case, it is likely
that the methyl in 5-position has the same effect on the reactivity
of the ortho and para position with the consequent equal relative
reactivity.
When CH3SO3H is used the ortho selectivity increases as
already observed for phenol. For instance, cyclohexylation of
3,5-dimethylphenol catalyzed by CH3SO3H shows an very high
ortho–para ratio (o/p = 140) and in any case, for each phenol with
unsubstituted ortho and para position, there is a neat increase
of the ortho selectivity in the presence of CH3SO3H compared to
Amberlyst 15. Such a behavior is not straightforward, since it is
not clear what are the reasons of such a specific ortho direct-
ing action of the CH3SO3H, however, either the mechanism via
cyclohexyl phenyl ether rearrangement [37–39], or that via a
methanesulfonic–phenol complex [40] can be responsible for this
behavior.
Acknowledgments
Financial support by Ca’ Foscari University of Venice is gratefully
acknowledged (Ateneo fund 2009). A thank to Dr. Davide Montin
for some preliminary experiments carried out during his degree in
Industrial Chemistry. Finally, a special thank to Mr. Claudio Tortato
for the helpful discussions.
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