Direct alkylation of aromatics using alcohols in the presence of NaHSO 4/SiO2

Article abstract of DOI:10.1016/j.tet.2012.06.063

Simple and efficient procedure for alkylation of aromatics from alcohols in the presence of NaHSO₄/SiO₂ was developed. Various triaryl methanes were obtained in good yields in short reaction time. For instance the reaction of mesitylene with benzhydrol in the presence of NaHSO₄/SiO₂ gave the corresponding triaryl methane in a quantitative yield. NaHSO₄/SiO₂ was regenerated by simple treatment and could be recycled eight times without activity loss.

Full text of DOI:10.1016/j.tet.2012.06.063

Tetrahedron 68 (2012) 7077e7081
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Direct alkylation of aromatics using alcohols in the presence of NaHSO4/SiO2
,
a
b
Yuta Sato a, Tadashi Aoyama a , Toshio Takido , Mitsuo Kodomari
*
a Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
b Department of Bioscience and Engineering, Shibaura Institute of Technology, Fukasaku, Minuma-ku, Saitama 337-8570, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 May 2012
Received in revised form 13 June 2012
Accepted 14 June 2012
Available online 23 June 2012
Simple and efficient procedure for alkylation of aromatics from alcohols in the presence of NaHSO4/SiO2
was developed. Various triaryl methanes were obtained in good yields in short reaction time. For
instance the reaction of mesitylene with benzhydrol in the presence of NaHSO4/SiO2 gave the
corresponding triaryl methane in a quantitative yield. NaHSO4/SiO2 was regenerated by simple treatment
and could be recycled eight times without activity loss.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Alkylation
Aromatics
Supported reagent
Alcohol
1. Introduction
catalysts, decrease of plant corrosion, and environmentally safe
disposal. Many solid acids, therefore, have been developed. Among
Development of an efficient method for alkylation of aromatic
compounds is important in organic synthesis because substituted
aromatics are contained in natural products and used in synthesis
of pharmaceuticals and functional materials. Traditionally,
substituted aromatics have been synthesized by FriedeleCrafts
reaction from alkyl halide and aromatics in the presence of Lewis
acid, which generates a large amount of hydrogen halide. Recently
many efforts have been devoted to development of environmental-
friendly process. For instance, benzyl acetate,1,2 benzyl ether,3 N-
them, reusable inorganic solid-supported acid catalysts have
attracted much attention. Silica gel supported hydrogensulfate
(NaHSO4/SiO2) has been used for many organic reactions. For in-
stance, aryl-14-H-dibenzo [a,j]xanthenes,17 3,4-dihydropyrimidin-
2(1H)-ones,18 and amidoalkyl naphthols19 were synthesized in the
presence of NaHSO4/SiO2, and monoacetylation of unsymmetrical
diols was catalyzed by NaHSO4/SiO2.20 Recently, we reported al-
kylation of b
-dicarbonyls with alcohols using NaHSO4/SiO2.21 We
attempted to expand this alkylation into aromatic compounds. In
this paper, we describe a direct alkylation of aromatics with alco-
hols using NaHSO4/SiO2.
sulfonyl aldimines,4 2-substituted-1,3-dicarbonyl compound,5
a,b-
unsaturated ketones,6 and alcohols have been employed as an
alkylating agent for FriedeleCrafts type alkylation. In particular,
FriedeleCrafts alkylation using alcohols has attracted much atten-
tion as an environmental-friendly process, because H2O was
formed as the only byproduct. Recently, alkylation of aromatics
with alcohols using a catalyst such as molybdenum complex/o-
chloranil,7 molybdenum trioxide,8 pentafluorophenyl boronic
acid,9 IreSn complex,10 InCl3$4H2O,11 PTS,12 triflic acid,13
Fe(ClO4)3$H2O,14 calcium-catalyzed15 and iodine16 have been
reported. These reactions, however, need an after-treatment such
as neutralization and extraction in order to separate the catalyst
from the reaction mixture. In eco-friendly chemical processes, it is
highly desirable to replace homogeneous catalysts with heteroge-
neous catalysts. Solid acid catalysts have many advantages such as
easy handling, easy to isolate the products and to separate the
2. Results and discussion
Various Brønsted and Lewis acids and silica gel supported acid
catalysts were used for the reaction of benzhydrol and benzene
(Table 1). Solution of 1a (2 mmol) in benzene (5 mL) was stirred in
the presence of various acid catalysts at 80 ꢀC for 2 h. It was found
that silica sulfuric acid (SSA) was the most active among the acid
catalysts tested, and the corresponding triphenyl methane (3aa)
was yielded in 83% (entry 1). The reaction mixture, however, be-
came acid because of sulfonation of benzene by SSA.22 Thus, neu-
tralization and extraction were needed in order to isolate 3aa from
the reaction mixture. NaHSO4/SiO2 also catalyzed the reaction as
well as SSA, and 3aa was obtained in 73% yield without neutrali-
zation of the reaction mixture (entry 2). When the reaction was
carried out in the presence of finely ground NaHSO4 instead of
NaHSO4/SiO2, the reaction did not proceed (entry 6). The other silica
* Corresponding author. Tel./fax: þ81 3 3259 0818; e-mail address: aoyama.
tadashi@nihon-u.ac.jp (T. Aoyama).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.063

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Y. Sato et al. / Tetrahedron 68 (2012) 7077e7081
Table 1
Table 3
Preparation of triaryl methane using various acid catalysts
Reaction of 1a and 2f under various conditionsa
OMe
OH
Acid
OH
OMe
+
NaHSO4/SiO2
30 °C
80 °C, 2 h
+
1a
2a
3aa
1a
2f
3af
Entry
Acid
Yielda (%)
1
2
3
4
5
6
7
8
9
SSA (1.00 g)
83
73
13
22
70
0
57
32
76
Entry
2f/1a
Cat. (g)
Solv.
Time (h)
Yield of 3afb (%)
NaHSO4/SiO2 (2.1 mmol/g, 1.00 g)
PPA/SiO2 (30 wt %, 1.00 g)
SA/SiO2 (2.1 mmol/g, 1.00 g)
ZnCl2/SiO2 (2.1 mmol/g, 1.00 g)
NaHSO4$H2O (2.1 mmol/g, 0.29 g)
AlCl3 (2.1 mmol, 0.28 g)
1
2
3
4
5
6
1.0
1.5
2.0
1.5
1.5
1.5
1.0
1.0
1.0
0.5
1.0
1.0
Benzene
Benzene
Benzene
Benzene
Toluene
DCE
2.0
0.5
0.5
8.0
0.5
0.5
62
88
91
78
89
84
FeCl3 (2.1 mmol, 0.34 g)
H2SO4 (2.1 mmol, 0.21 g)
a
A mixture of 1a (2 mmol), 2f, and NaHSO4/SiO2 was stirred in solvent (5 mL) at
30 ꢀC.
a
Determined by GLC using n-dodecane as internal standard.
b
Determined by GLC using n-dodecane as internal standard.
gel supported acids, PPA/SiO2 and SA/SiO2, slightly promoted the
reaction and 3aa was obtained in low yields. However, ZnCl2/SiO2
gave 3aa in 70% yield (entries 3e5). In the case of homogeneous
reactions using Lewis and Brønsted acids, 3aa was obtained in
moderate yields after neutralization and extraction (entries 7e9).
The results of the reaction of toluene and xylenes with benz-
hydrol using NaHSO4/SiO2 were shown in Table 2. Both toluene and
1.5 equiv of 2f was used, the reaction was completed in 0.5 h (entry
2). When the other solvents such as toluene and 1,2-dichloroethane
(DCE) were employed, the yield of 3af was the same as benzene
(entries 5 and 6). With a small amount of NaHSO4/SiO2, a long re-
action time was required in order to obtain 3af in good yield (entry
4). These results suggest as below; a small amount of H2O, which
was generated during the course of reaction, is adsorbed on the
surface of NaHSO4/SiO2. Therefore hydrophobic 2f can hardly ap-
proach the NaHSO4/SiO2.
Table 2
a
Reaction of 2 with 1a using NaHSO4/SiO2
The recyclability of the catalyst was examined. When NaHSO4/
SiO2, which was recovered from the reaction mixture was reused
without any treatment for the same reaction, long reaction time
was required in order to obtain 3af in good yield. In contrast, the
same reaction using NaHSO4/SiO2, which was dried at 120 ꢀC for 1 h
under reduced pressure after isolating it from the reaction mixture,
was carried out at 30 ꢀC for 0.5 h to give 3af in good yield. NaHSO4/
SiO2 regenerated by such a manner could be recycled nine times
without activity loss (Table 4).
OH
Ar
NaHSO4/SiO2
0.5 h
+
Ar H
1a
2b-2e
3ab-3ae
Entry
1
2
Temp (ꢀC) Yield of 3b (%)
Selectivityc (o/p)
2b 80
3ab
3ac
3ad
99
98
99
18:82
6:94
Table 4
Reuse of NaHSO4/SiO2 for the synthesis of 3afa
2
3
2c
60
Reuse
NaHSO4/SiO2 (g)
Yield of 3afb (%)
0
2
4
6
7
8
1.00
0.98
0.98
0.97
0.97
0.97
84
83
83
83
82
76
2d 60
a
A mixture of 1a (2 mmol), 2f (3 mmol), and NaHSO4/SiO2 was
stirred in DCE (5 mL) at 30 ꢀC for 0.5 h.
b
4
2e
80
3ae
99
Determined by GLC using n-dodecane as internal standard.
Various aromatic compounds were employed as a substrate for
the reaction with benzhydrol and the results obtained were sum-
marized in Table 5. Mesitylene, o- and m-dimethoxy benzene gave
the corresponding triaryl methanes 3age3ai in good to excellent
yields at 30 ꢀC in 2 h. The yield of 3ai was 71% in 0.5 h (entries 1e3).
In the reaction of p-dimethoxy benzene (2j), a mixture of mono-
and dialkylated products was produced. Dialkylated product 1,4-
bis(benzhydro)-2,5-dimethoxy benzene was formed along with
3aj (48%). When a large excess of 2j (5 mmol) against 1a (1 mmol)
was used, monoalkylated product 3aj was obtained in 75% yield in
1 h (entry 4). Phenol and 2-naphthol also gave the corresponding
triaryl methanes 3al and 3am in good yields, respectively (entries 6
and 7). But 2-naphthalenethiol (2n) did not give the expected
a
A mixture of 1a (2 mmol) and NaHSO4/SiO2 (1.0 g) was stirred in 2a (5 mL) for
0.5 h.
b
c
Isolated yield.
Determined by NMR.
xylenes reacted with benzhydrol to give quantitatively the corre-
sponding triaryl methanes (3abe3ae). Toluene and o-xylene gave
a mixture of o- and p-regioisomer in 18:82 and 6:94 ratio, which
were determined by 1H NMR.
The reaction using anisole (2f) as a substrate did not need large
excess amount of 2f over 1a. For instance, the reaction of 1a
(2 mmol) and 2f (2 mmol) gave 3af in 62% yield along with 2% of o-
substituted product at 30 ꢀC for 2 h (Table 3, entry 1). When

Y. Sato et al. / Tetrahedron 68 (2012) 7077e7081
7079
Table 5
Reaction of 1a and 2a
Ar
OH
NaHSO4/SiO2
+
Ar H
DCE
R
R
2g-2u
3
1a: R = H
1b: R = OMe
1c: R = Cl
Entry
1
1
2
Temp (ꢀC) Time (h) Yield of 3b (%)
Entry
9
1
2
Temp (ꢀC) Time (h) Yield of 3b (%)
OMe
SMe
1a
2g
30
2.0
2.0
3ag
3ah
98
97
1a
2o
2p
30
30
0.5
0.5
3ao
3ap
99
84
OMe
OMe
2
3
1a
1a
2h 30
10
11
1a
1a
OMe
OMe
OMe
O
2i
2j
30
30
0.5
3ai
71
2q
30
0.5
3aq
88
2.0
1.0
48c
S
Br
4
5
1a
1a
3aj
12
13
1a
1a
2r
2s
30
30
0.5
0.5
3ar
3as
90
90
75c,d
OMe
OMe
S
2k
21
30
30
0.5
3ak
84
MeO
OMe
OH
H
N
6
7
1a
1a
0.5
0.5
3al
75c
99
14
15
1a
1b
2t
2f
60
30
1.0
0.5
3at
3bf
59
44
OMe
Cl
OH
SH
2m 30
3am
8
1a
2n 30
0.5
3an
0 (91)e
16
1c
2u 130
2.0
3cu
28f
a
A mixture of 1 (2 mmol), 2 (3 mmol), and NaHSO4/SiO2 (1.00 g) was stirred in DCE.
Isolated yield.
Determined by GLC using dodecane as internal standard.
Compound 2j (5 mmol) was used.
The number in parenthesis was shown a yield of benzhydryl-2-naphtyl sulfide (4).
A mixture of 1a (2 mmol), 2u (5 mL), and NaHSO4/SiO2 (1.00 g) was used.
b
c
d
e
f
compound. Reaction of 2n with 1a afforded benzhydryl naphthyl
sulfide in 91% yield (entry 8). 2-Methoxy naphthalene (2o) affor-
ded 1-benzhydryl-2-methoxy naphthalene quantitatively. In con-
trast, 2-methylthio naphthalene (2p) gave a mixture of regioisomer
of benzhydryl-2-methylthio naphthalene in 84% yield (entries 9
and 10). Some heterocyclic compounds, 2-methylfuran, 2-
bromothiophene, benzothiophene, and indole, were also
employed as a substrate for this reaction (entries 11e14). Indole
required higher reaction temperature and longer reaction time than
the other heterocyclic compounds. Compound 3at was obtained in
moderate yield when the reaction of 2t with 1a was carried out at
60 ꢀC for 1 h. In the reaction using indole, it is considered that the
activity of NaHSO4/SiO2 decreases due to an adsorption of 2t onto
NaHSO4/SiO2. To prove this, a slurry of 2t (3 mmol) and NaHSO4/
SiO2 (1.0 g) in DCE was stirred at 60 ꢀC. After 1 h, the mixture was
filtered to remove NaHSO4/SiO2. Compound 2t (1.9 mmol) was in
the filtrate. Thus, it was found that 1.1 mmol of 2t was adsorbed
onto NaHSO4/SiO2.

7080
Y. Sato et al. / Tetrahedron 68 (2012) 7077e7081
The results of the alkylation 2h using a series of alcohols were
compounds 3fhe3hh along with small amount of disubstituted
products (entries 5e7). Reaction of 2h with benzyl alcohol (1i) gave
a mixture of regioisomers 3ih and 3ih0 in 19% and 47% yields (entry
8). In the case of allylic alcohols, sec-allylic alcohols 1j and 1k gave
3jh and 3kh in an almost quantitative yield without allyl rear-
rangement, respectively. On the other hand, primary allylic alcohols
1l and 1m were less reactive than sec-allylic alcohols, 1l gave 3lh in
40% yield and the reaction with 1m did not proceed (entries 9e12).
In the reaction using tert-alcohols such as tert-butanol (1n) and
triphenyl methanol (1o), a long reaction time (8e16 h) and a high
temperature were required in order to obtain 3nh and 3oh in good
yield (entries 13 and 14). However, the reaction of 2f with 1o did not
give tetra-aryl methane 3of under the same conditions. Compound
summarized in Table 6. Compound 1b was converted completely in
0.5 h and 3bh was obtained in 63% yield along with small amount of
di(4-methoxyphenyl) ketone and di(4-methoxyphenyl) methane
(entry 1). On the other hand,1c needed higher reaction temperature
and longer reaction time (60 ꢀC, 3 h) than 1b in order to obtain 3ch
in excellent yield (entry 2). The reaction using 1d proceeded
smoothly at 60 ꢀC to give 3dh quantitatively in 0.5 h (entry 3). The
reaction
using
a
,a
0-diphenyl-1,4-benzene-dimethanol
(1e)
(1 mmol) needed a large amount of solvent DCE because 1 mmol of
1e did not dissolve completely in 5 mL of DCE. When the reaction
was carried out in 10 mL of DCE at 80 ꢀC, 3eh was yielded in 77%
(entry 4). 1-Phenylethanols (1fe1h) afforded the expected
Table 6
Reaction of 1 and 2ha
OMe
OMe
OMe
OMe
NaHSO4/SiO2
+
R OH
DCE
R
3
1
2h
Entry
1
1
Temp (ꢀC) Time (h) Yield of 3b (%)
Entry
8d
1
Temp (ꢀC) Time (h) Yield of 3b (%)
OH
OH
(3-)3ih
(4-)3ih0
19
47
1b 30
0.5
3bh
63
1i
80
7
Ph OH
OH
MeO
OMe
Cl
2
3
1c 60
3
3ch
3dh
94
99
9
1j
30
30
0.5
0.5
3jh
99
92
Ph
Ph
Cl
OH
Ph
OH
1d 60
0.5
10
1k
3kh
Ph
Cl
OH
Ph
4
5
6
7
1e 80
1f 60
1g 30
1h 80
0.5
0.5
0.5
2.5
3eh
3fh
3gh
3hh
77c
82
77
86
11
12
13
1l
30
0.5
3lh
40
0
Ph
OH
Ph
OH
OH
1m 80
1
3mh
3nh
OH
Ph
OH
OH
1n
80
8
70
OH
OH
14
15
1o
1p
80
30
16
3oh
3ph
88
38
Ph Ph
Ph
Cl
OH
0.5
a
A mixture of 1 (2 mmol), 2h (3 mmol), and NaHSO4/SiO2 (1.00 g) was stirred in DCE.
Isolated yield.
A mixture of 1 (1 mmol), 2h (3 mmol), NaHSO4/SiO2 (1.00 g) and DCE (10 mL) was used.
Determined by GLC using dodecane as internal standard.
b
c
d

Y. Sato et al. / Tetrahedron 68 (2012) 7077e7081
7081
3of was obtained in 87% yield when the reaction was carried out
using 10 equiv of 2f against 1o (Scheme 1).
OMe
OMe
OH
Ph Ph
Ph
1o
2 mmol
NaHSO4/SiO2
When 1,2,3,4-tetrahydro-1-naphthol (1p) was used as an alky-
lating agent for the reaction of 2h, 3ph was produced in 38% yield
along with unexpected product 5 (entry 15 and Scheme 2). When
2 mmol of 1p was stirred in DCE in the presence of NaHSO4/SiO2 at
30 ꢀC for 0.5 h, 5 was produced in 57% yield along with 6 (26%)
(Scheme 3, (Eq. 1)). Compound 5 was also formed by dimerization
of 6. When a mixture of 6 and NaHSO4/SiO2 was stirred at 30 ꢀC for
0.5 h in DCE, 5 was obtained in 85% yield. Reaction of 6 with 1p
using NaHSO4/SiO2 gave 5 in 81% yield (Scheme 3, (Eqs. 2 and 3)).
We interested in this direct coupling of alkene and alcohol. 1a also
reacted with 6 under the same conditions to give 7 in 72% yield
(Scheme 3, (Eq. 4)). These reactions are now under investigations.
+
DCE
80°C, 16h
Ph Ph
Ph
2f
20 mmol
3of
Y.= 87 %
Scheme 1.
OMe
OMe
Conclusion
+
+
1p
2h
In conclusion, we developed a simple and efficient procedure for
alkylation of aromatics with alcohols using NaHSO4/SiO2 and various
triaryl methanes were prepared. NaHSO4/SiO2 was easily recovered
from the reaction mixture and regenerated by simple treatment and
could be reused more than eight times without activity loss.
5
3ph
Scheme 2.
Supplementary data
1H NMR, 13C NMR, MS, IR, and elemental analysis are available.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2012.06.063.
NaHSO4/SiO2
+
1p
(1)
5
57 %
DCE
30 °C, 0.5 h
6
26 %
References and notes
1. Mertins, K.; Iovel, I.; Kischel, J.; Zapf, A.; Beller, M. Adv. Synth. Catal. 2006, 348, 691.
2. Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed. 2005,
44, 3913.
3. Wang, B.; Xiang,S.; Sun,Z.; Guan, Z.; Hu, P.;Zhao, K.TetrahedronLett. 2008, 49, 4310.
4. Thirupathi, P.; Kim, S. S. J. Org. Chem. 2010, 75, 5240.
5. Li, H.; Li, W.; Liu, W.; He, Z.; Li, Z. Angew. Chem., Int. Ed. 2011, 50, 2975.
6. Kumar, A. V.; Rao, K. A. Tetrahedron Lett. 2011, 52, 5188.
7. Yamamoto, Y.; Itonaga, K. Chem.dEur. J. 2008, 14, 10705.
8. Wang, F.; Ueda, W. Chem.dEur. J. 2009, 15, 742.
9. McCubbin, J. A.; Krokhin, O. V. Tetrahedron Lett. 2010, 51, 2447.
10. Roy, S.; Podder, S.; Choudhury, J. J. Chem. Sci. 2008, 120, 429.
11. Sun, H.; Li, B.; Chen, S.; Li, J.; Hua, R. Tetrahedron 2007, 63, 10185.
12. Sanz, R.; Martinez, A.; Miguel, D.; Alvarez-Guiterrez, J. M.; Rodriguez, F. Adv.
Synth. Catal. 2006, 348, 1841.
NaHSO4/SiO2
(2)
(3)
DCE
30 °C, 0.5 h
6
5
85 %
NaHSO4/SiO2
+
1p
1a
5
DCE
80 °C, 1 h
81 %
6
13. Bras, J. L.; Muzart, J. Tetrahedron 2007, 63, 7942.
14. Thirupathi, P.; Kim, S. S. Tetrahedron 2010, 66, 2995.
15. Niggemann, M.; Meel, M. J. Angew. Chem., Int. Ed. 2010, 49, 3684.
16. Sun, G.; Wang, Z. Tetrahedron Lett. 2008, 49, 4929.
17. Rostamizadeh, S.; Shadjou, N.; Amani, A. M.; Balalaie, S. Chin. Chem. Lett. 2008,
19, 1151.
18. Chari, M. A.; Syamasundar, K. J. Mol. Catal. A. Chem. 2004, 221, 137.
19. Shaterian, H. R.; Yarahmadi, H.; Ghashang, M. Turk. J. Chem. 2009, 33, 449.
20. Breton, G. W. J. Org. Chem. 1997, 62, 8952.
Ph
Ph
NaHSO4/SiO2
+
(4)
DCE
30 °C, 0.5 h
6
7
72 %
21. Aoyama, T.; Miyota, S.; Takido, T.; Kodomari, M. Synlett 2011, 2971.
22. Hajipour, A. R.; Mirjalili, B. B. F.; Zarei, A.; Khazdooz, L.; Ruoho, A. E. Tetrahedron
Lett. 2004, 45, 6607.
Scheme 3.