Hydroarylation of styrenes with electron-rich arenes over acidic ion-exchange resins

Article abstract of DOI:10.1080/00397911.2013.876547

A series of acidic cation-exchange resins were used for the hydroarylation of resorcinol with styrene, in which resin D072 exhibited the excellent catalytic performance in this reaction with 99% conversion of styrene and 90% selectivity of 4-(1-phenylethyl)resorcinol. It was applied to the hydroarylation of various electron-rich arenes with styrenes, and the hydroarylated products were quantitatively obtained. This catalyst could be used for four consecutive runs with slight decrease in activity. The hydroarylation of resorcinol with styrene over resin D072 in a fixed bed was completed effectively with 94% selectivity and 99% conversion, and this green continuous process is potentially applicable to large-scale productions.

Full text of DOI:10.1080/00397911.2013.876547

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Hydroarylation of Styrenes with
Electron-Rich Arenes Over Acidic Ion-
Exchange Resins
Jingyun Wen a , Haofei Qi a , Xiangjin Kong a , Ligong Chen a & Xilong
Yan a
a School of Chemical Engineering and Technology , Tianjin
University , Tianjin , China
Accepted author version posted online: 18 Mar 2014.Published
online: 29 May 2014.
To cite this article: Jingyun Wen , Haofei Qi , Xiangjin Kong , Ligong Chen & Xilong Yan (2014)
Hydroarylation of Styrenes with Electron-Rich Arenes Over Acidic Ion-Exchange Resins, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:13, 1893-1903, DOI: 10.1080/00397911.2013.876547
To link to this article: http://dx.doi.org/10.1080/00397911.2013.876547
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Synthetic Communications1, 44: 1893–1903, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.876547
HYDROARYLATION OF STYRENES WITH ELECTRON-
RICH ARENES OVER ACIDIC ION-EXCHANGE RESINS
Jingyun Wen, Haofei Qi, Xiangjin Kong, Ligong Chen, and
Xilong Yan
School of Chemical Engineering and Technology, Tianjin University,
Tianjin, China
GRAPHICAL ABSTRACT
Abstract A series of acidic cation-exchange resins were used for the hydroarylation of
resorcinol with styrene, in which resin D072 exhibited the excellent catalytic performance
in this reaction with 99% conversion of styrene and 90% selectivity of 4-(1-phenylethyl)
resorcinol. It was applied to the hydroarylation of various electron-rich arenes with
styrenes, and the hydroarylated products were quantitatively obtained. This catalyst could
be used for four consecutive runs with slight decrease in activity. The hydroarylation of
resorcinol with styrene over resin D072 in a fixed bed was completed effectively with 94%
selectivity and 99% conversion, and this green continuous process is potentially applicable
to large-scale productions.
Keywords Acidic cation-exchange resin; fixed-bed reactor; Friedel–Crafts hydroaryla-
tion; green chemistry; heterogeneous catalyst
INTRODUCTION
Friedel–Crafts hydroarylation is one of the most fundamental and useful trans-
formations for carbon–carbon bond formation and is widely applied to the synthesis
of pharmaceuticals, agrochemicals, dyes, and fine and bulk chemicals. Recently,
Lewis acids such as FeCl3,[1] BiCl3,[2] and Bi(OTf)3[3] and Brønsted acids such as sul-
fonic acid,[4] phosphoric acid,[4] or I2[5] have been used to catalyze the hydroarylation
Received September 12, 2013.
Address correspondence to Xilong Yan, School of Chemical Engineering and Technology, Tianjin
University, Tianjin, China. E-mail: yan@tju.edu.cn
Color versions of one or more of the figures in the article can be found online at www.tandfonline.
com/lsyc.
1893

1894
J. WEN ET AL.
of styrenes for the synthesis of a variety of 1,1-diarylalkanes in good yields. Although
these catalysts work reliably with a variety of substrates, they are accompanied by ser-
ious corrosion of equipment, complicated workup procedures, consumption of large
amount of acids and bases, and large amounts of wastewater, which is unfriendly to
the environment. Furthermore, wastewater treatment is an ongoing and expensive
issue in large-scale chemical processes.
Efforts recently have been made to develop heterogeneous catalysts for this
reaction, for example, KHSO4,[6] 3D nanoporous FeAl-KIT-5,[7] H-b-zeolite,[8]
acidic ionic liquids,[9] ion-containing mesoporous aluminosilicate,[10] aluminum-
exchanged tungstophosphoric acid,[11] molybdenum complexes,[12,13] Ir-Cp
complexes,[14] palladium complex,[15] Amberlyst-15,[16,17] and the like. However,
the disadvantages limit their application in large-scale productions.
Acidic cation-exchange resins have been recognized as very promising
candidates to manage the handicaps of homogeneous catalysts and solid catalysts
as alternatives because of their advantages such as low cost, environmental friendli-
ness, reusability, noncorrosiveness, and excellent physical characteristics including
high surface area, large pore volume, and uniform pore-size distribution. However,
no examples of immobilized resin systems for hydroarylation in a fixed-bed reactor
are found in the literature.
The establishment of a green continuous process for this important reaction
would be desirable. Therefore, we have investigated various cheap and readily
available acidic cation-exchange resins that may prove to be catalytically active in
hydroarylation. It was found that resin D072 exhibited the best catalytic perfor-
mance. Thus, further efforts have been made to it to ensure that it is an efficient cata-
lyst that has potential to be used in a fixed-bed reactor (Scheme 1).
RESULTS AND DISCUSSION
The well-known Friedel–Crafts alkylation is a typical aromatic electrophilic
substitution, in which the formation of carbocation is crucial to this reaction. Tra-
ditional Brønsted acids protonate the alkenes to produce reactive carbocations.
Acidic resins belong to solid Brønsted acids, which can provide Hþ to catalyze the
reaction. Therefore, a number of acidic resins were selected for the model reaction
of resorcinol with styrene in 1,2-dichloroethane (DCE) to give 4-(1-phenylethyl)
resorcinol as the target product (Table 1). The by-product was double-substituted
resorcinol, which was 4.6-di(1-phenylethyl)resorcinol. 4-(1-Phenylethyl)resorcinol
was reported to be one of the most efficient tyrosinase inhibitors, due to its safety
and effectiveness at low concentration, which has the potential to be used as a
whitening cosmetic.[18]
Scheme 1. General hydroarylation of arenes with styrenes.

CONTINUOUS PROCESS FOR HYDROARYLATION
1895
Table 1. Hydroarylation of resorcinol with styrenea
Entry
Resin
Conv. (%)b
Yield (%)c
Sel.d
1
2
D072
NKC-9
D061
99
99
99
98
3
89
84
83
75
3
90:10
85:15
84:16
77:23
3
4
D062
D401
5
6
D114
D113
2
2
—
—
—
—
—
—
7
2
2
8
D151
D152
1
1
9
2
2
10
11
D001-CC
100 ꢀ 7
1
1
1
1
aReaction condition: 15 mmol of resorcinol, 5 mmol of styrene, 30 wt% (based on styrene) of catalyst,
reflux in DCE for 4 h.
bHPLC conversion of styrene.
cHPLC yield of the product.
dSingle=double substituted isomers were determined by 1H NMR and 13C NMR.
It is obvious that resin’s acidity has an important influence on the hydroaryla-
tion. All sulfonic acidic resins such as D072, NKC-9, D061, and D062 can effectively
catalyze this reaction (Table 1, entries 1–4), in which resin D072 exhibited the
excellent catalytic performance in both conversion and selectivity. However, with
Figure 1. Hydroarylation of resorcinol with styrene in the presence of D072.

1896
J. WEN ET AL.
Table 2. Resin D072 catalyzed the reaction of styrene with various aromaticsa
Entry
Arene
Productb
Conv. (%)c
Yield (%)d
Sel.e
1
100
92
60:40
2
3
100
68
83
68:32
84:16
99
4
97
82
85:15
5
100
100
67
25
67:33
25:75
6f
7f
100
12.5
1:7
(Continued )

CONTINUOUS PROCESS FOR HYDROARYLATION
1897
Sel.e
—
Table 2. Continued
Entry
Arene
Productb
—
Conv. (%)c
Yield (%)d
8
100
0
9
—
0
—
—
aReaction conditions: 15 mmol arene, 5 mmol (substituted) styrene, 30 wt% D072, reflux in DCE, 4 h.
bMain product.
cHPLC conversion of styrene.
dHPLC yield of products.
eMain product: other isomers.
fThe selectivity was detected by 1H NMR.
carboxylic resins as catalysts, nearly no alkylated product was detected, due to their
poor protonation ability (Table 1, entries 5–11).
D072 is sulfonic resin with the appearance of light camel in color and spherical
particles, its surface area is 77 m2=g, the pore volume is 0.27 mL=g, the concentration
of Hþ is greater than 4.8 mmol=g, and the average pore size is 56 nm. All these para-
meters make it appropriate for the catalyst of the hydroarylation.
The effect of dosages of D072 was investigated, as shown in Figure 1. With the
increase of the catalyst’s dosage from 5 to 30 wt%, the conversion of styrene increased
from 75% to 99% and the selectivity for the target product remained unchanged. With
30 wt% of D072, significant conversion and selectivity could result. Therefore, 30 wt%
of D072 was used in this reaction.
To explore the scope and limitations of this reaction, various aromatic com-
pounds were employed as the substrate to react with styrene. Under the optimized
condition styrene almost fully reacted with the electron-rich arenes to give the corre-
sponding alkylated products (Table 2, entries 1–5); however, arenes with weaker
electron-donating groups were ineffective (Table 2, entries 6–8) because most of styr-
ene reacted itself to afford the alkylated styrene and few desirable products were
obtained. Furthermore, perhaps the basic group of aniline blocked acidic centers of
the resin, and neither the desired product nor alkylated styrene were obtained
(Table 2, entry 9).
Then, para-chloro, bromo, methyl, and tert-butyl substituted styrenes were
examined, and all of them reacted well as hydroarylation reagents to give the corre-
sponding products with satisfactory yield and selectivity (Table 3, entries 1–9).
Additionally, take hydroarylation of styrenes with pyrocatechol for example, and
the ratio of 4-substituted isomer with 3-substituted isomer was different (Table 3,
entries 2, 4, 6, 8; Table 2, entry 4). This may depend on the stability of carbocation.
The introduction of electron-donating group to the benzene ring could enhance the

1898
J. WEN ET AL.
Table 3. Resin D072 catalyzed the reaction of styrenes with various aromaticsa
Entry
Arene
Productb
Conv. (%)c
Yield (%)d
Sel.e
1
100
91
67:33
2
3
4
5
100
100
100
96
90
93
81
95
90:10
93:7
81:19
>99:1
6
7
100
94
99
94:6
99
100
(Continued )

CONTINUOUS PROCESS FOR HYDROARYLATION
1899
Table 3. Continued
Entry
8
Arene
Productb
Conv. (%)c
Yield (%)d
Sel.e
100
83
83:17
9
100
96
96:4
aReaction conditions: 15 mmol arene, 5 mmol (substituted) styrene, 30 wt% D072, reflux in DCE for 4 h.
bMain product.
cHPLC conversion of styrene.
dHPLC yield of products.
eMain product : other isomers.
Scheme 2. Stability of the carbocations.
stability of the carbocation: the greater the stability, the better the selectivity.
However, the introduction of electron-withdrawing group could reduce the stability
of the carbocation. Therefore the stability of these carbocations is shown in
Scheme 2. The experimental results demonstrated the selectivity of these target
products was consistent with the stability of carbocations.
Next, the reusability of resin D072 was investigated in the model reaction of
resorcinol with styrene. After each run, the catalyst was filtered from the reaction mix-
ture and reused for four runs without any activation. As shown in Table 4, the activity
remained unchanged in the first three runs, but in the fourth cycle, the activity of the
reused catalyst started declining while the conversion remained high. The catalyst
(fresh and reused) has been characterized by using scanning electron microscopy
(SEM) analysis; after the first run, the morphology of the catalyst was same with
the fresh (Figs. 2a and 2b). When the catalyst was used for four runs (Figs. 2c and
2d), the morphology almost had no changes, and the number and size of protuber-
ances on the wrinkles seemed unchanged. This indicated that the catalyst was
chemically stable.
Finally, the implementation of the resin in a continuous system is the ultimate
goal of large-scale application. Hence, we integrated the loaded resin D072 beads in
a fixed catalyst bed, which was then continuously fed with a preheated solution of

1900
J. WEN ET AL.
Table 4. Reuse of resin D072a
Run
Conv. (%)b
Yield (%)c
Sel.d
1
2
3
4
99
85
86:14
88:12
88:12
84:16
99
99
99
87
87
83
aReaction condition: 15 mmol of resorcinol, 5 mmol of styrene, 30 wt% (based on
styrene) of catalyst, reflux in DCE for 4 h.
bHPLC conversion of styrene.
cHPLC yields of product.
dSingle=double substituted isomer were determined by 1H NMR and 13C NMR.
Figure 2. SEM images of resin D072 before (a) and after (b) the first run and before (c) and after (d) the
fourth run.
resorcinol and styrene in DCE. Unlike batch conditions, the temperature should not
be too high due to vaporization of solvent in continuously conditions. Thus most
resorcinol was absorbed in resin and styrene flowed out with solvent; therefore,
the desirable product was not detected in the outcoming flow. Then, the reaction
temperature was set to 72 ꢁC; surprisingly, styrene almost fully reacted, and the out-
coming flow was monitored by HPLC for 9 h and samples were taken at intervals. As
shown in Table 5, resin D072 showed good activity and selectivity in the fixed bed.
To our delight, the selectivity (up to 94%) of the catalyst was significantly improved
compared to the batch conditions. This was a tandem reaction; it was inevitable to

CONTINUOUS PROCESS FOR HYDROARYLATION
1901
Table 5. Continuous flow conditionsa
Time (h)
Conv. (%)b
Yield (%)c
Sel.d
3
4
5
6
7
8
9
99
99
99
99
99
99
99
93
93
93
92
93
92
93
94:6
94:6
94:6
93:7
94:6
93:7
94:6
aReaction conditions: flow rate 0.3 mL=min, temperature 72 ꢁC.
bHPLC conversion of styrene.
cHPLC yields of product 1.
dSingle=double substituted isomer were determined by 1H NMR and 13C NMR.
produce the double substituted by-product. In batch conditions, the dosage of the
catalyst was less than that of continuous conditions, and therefore the reaction time
was much longer, which could promote the occurrence of further alkylation of the
product. Compared with the batch conditions, as the product continuously flowed
out of the fixed-bed reactor, the product’s retention time in the reactor was much
shorter. This made it difficult to be further alkylated, and therefore the selectivity
for the product was greater.
To explore the general applicability of the established continuous conditions,
greater concentrations of the mixture of phenol (14.1 g, 0.15 mol) and styrene
(5.2 g, 0.05 mol) in DCE (174 mL) were constantly fed to the fixed-bed reactor at a
rate of 0.3 mL=min. The outgoing flow was monitored by HPLC, styrene reacted
adequately with phenol, and the ratio of p-substituted isomer with o-substituted iso-
mer was 1:1, which was different from the batch conditions. The yield of the overall
single-substituted products was 90%, similar to that with batch conditions.
CONCLUSION
In summary, we have developed a simple and efficient method for hydroaryla-
tion of various electron-rich arenes and styrenes with promising yields using resin
D072 as a green and heterogeneous catalyst. The catalyst is commercially available,
inexpensive, and reusable, and it has been successfully applied to the continuous
flow conditions with greater selectivity than batch conditions. This green continuous
process is potentially applicable to large-scale productions.
EXPERIMENTAL
General Procedure for the Hydroarylation
Batch conditions. Styrene (5 mmol, 0.52 g) was added to a mixture of resorci-
nol (15 mmol, 1.65 g) and resin (0.156 g, 30 wt%) in 10 mL of DCE, and the solution
was stirred under reflux for 4 h. After the completion, the mixture was allowed to cool
down to ambient temperature, and the catalyst was separated by filtration. The
organic layer was washed with water (10 mL ꢀ 3) to remove the unreacted resorcinol,

1902
J. WEN ET AL.
then dried with anhydrous magnesium sulfate, and concentrated under vacuum to
give the viscous dark yellow oil. The residue was purified by flash chromatography
(silica, eluant: petroleum=ethyl acetate=methanol) to get pure single-substituted
and double-substituted products respectively.
Continuous conditions. A preheated solution of resorcinol (15 mmol) and
styrene (5 mmol) in DCE (150 mL) was fed continuously with a syringe pump (flow
rate 0.3 mL=min) over a catalyst bed consisting of 40 mL D072; the reaction tempera-
ture was 72 ꢁC. The outlet of the reactor was sampled at intervals. The crude mixtures
were directly analyzed by HPLC. The more detailed HPLC analysis conditions
and spectroscopic data of the new compounds are provided in the Supplementary
Information.
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
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