Graphene-Catalyzed Direct Friedel-Crafts Alkylation Reactions: Mechanism, Selectivity, and Synthetic Utility

Article abstract of DOI:10.1021/jacs.5b09636

Transition-metal-catalyzed alkylation reactions of arenes have become a central transformation in organic synthesis. Herein, we report the first general strategy for alkylation of arenes with styrenes and alcohols catalyzed by carbon-based materials, exploiting the unique property of graphenes to produce valuable diarylalkane products in high yields and excellent regioselectivity. The protocol is characterized by a wide substrate scope and excellent functional group tolerance. Notably, this process constitutes the first general application of graphenes to promote direct C-C bond formation utilizing polar functional groups anchored on the GO surface, thus opening the door for an array of functional group alkylations using benign and readily available graphene materials. Mechanistic studies suggest that the reaction proceeds via a tandem catalysis mechanism in which both of the coupling partners are activated by interaction with the GO surface.

Full text of DOI:10.1021/jacs.5b09636

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Article
Graphene-Catalyzed Direct Friedel-Crafts Alkylation
Reactions: Mechanism, Selectivity and Synthetic Utility
Feng Hu, Mehulkumar A. Patel, Feixiang Luo, Carol R. Flach,
Richard Mendelsohn, Eric Garfunkel, Huixin He, and Michal Szostak
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b09636 • Publication Date (Web): 23 Oct 2015
Downloaded from http://pubs.acs.org on October 23, 2015
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Graphene-Catalyzed Direct Friedel-Crafts Alkylation Reactions: Mecha-
nism, Selectivity and Synthetic Utility
Feng Hu,† Mehulkumar Patel,† Feixiang Luo,‡ Carol Flach,† Richard Mendelsohn,† Eric Gar-
funkel,‡ Huixin He,* ,† and Michal Szostak*,†
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†Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States
‡
Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Rd, Piscataway, NJ 08854, USA
Supporting Information
been reported;19,20 however, these methods are not general
and suffer from harsh reaction conditions, further limiting
ABSTRACT: Transition-metal-catalyzed alkylation reactions
of arenes have become a central transformation in organic
their substrate scope. Given the importance of alkylarenes in
synthesis. Herein, we report the first general strategy for
chemical and pharmaceutical industry,21 it is clear that there
alkylation of arenes with styrenes and alcohols catalyzed by
is an urgent need for the development of new, direct and
carbon-based materials, exploiting the unique property of
atom-economic strategies for the alkylation reactions of
graphenes to produce valuable diarylalkane products in high
arenes that would additionally meet the principles of green
yields and excellent regioselectivity. The protocol is charac-
terized by a wide substrate scope and excellent functional
chemistry22 to enable practical industrial applications.
group tolerance. Notably, this process constitutes the first
general application of graphenes to promote direct C–C bond
formation utilizing polar functional groups anchored on the
GO surface, thus opening the door for an array of functional
group alkylations using benign and readily available gra-
phene materials. Mechanistic studies suggest that the reac-
tion proceeds via a tandem catalysis mechanism in which
both of the coupling partners are activated by interaction
with the GO surface.
Introduction
Figure 1. Examples of biologically-active diarylmethanes.
Transition-metal-catalyzed alkylation reactions of arenes are
among the most important transformations for the produc-
tion of active pharmaceutical ingredients and fine chemicals
that have been extensively utilized in both academic and
industrial laboratories on multi ton scale annually (Figure 1).1
In particular, direct alkylations utilizing alkenes that proceed
via an overall structural isomerization (hydroalkylation)2 and
reactions involving alcohols as atom-economic electrophilic
coupling partners (Friedel-Crafts reactions)3 represent attrac-
tive processes for direct arene functionalization. Since the
seminal work by Murai,4 remarkable progress has been
achieved in direct ortho-selective C–H functionalization of
arenes5 using alkenes with the key contributions from the
groups of Murai,6 Jun,7 Bergman/Ellman,8 Yu,9 and Nakamu-
ra,10 among others.11 Moreover, elegant Friedel-Crafts-type
alkylations and hydroalkylations of unactivated arenes have
been reported by the groups of Beller,12 Rueping,13 Nigge-
mann,14 and Hall,15 among others.16 Despite these remarkable
advances, however, direct alkylation of arenes on industrial
scale is currently achieved by means of transition metal ca-
talysis,17 which utilizes expensive metals, generates toxic
waste and suffers from limited natural abundance of transi-
tion metals.18 Transition-metal-free procedures have also
Figure 2. (a-c) Graphenes as carbocatalysts. (d) This work:
the first graphene-catalyzed direct alkylation of arenes.
Recently, tremendous progress has been achieved in the
development of new carbon-based materials as benign,
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Page 2 of 9
Table 1. Optimization of the Reaction Conditionsa
abundant, and readily available catalysts for chemical syn-
thesis (Figure 2).23 Importantly, these carbocatalysts merge
the benefits of green synthesis with heterogenous reaction
conditions, which greatly simplifies work-up conditions and
is particularly attractive from an industrial standpoint.24 The
importance of graphene in nanotechnology, electrochemis-
try, and engineering has been recognized by the 2010 Nobel
Prize.25 In 2010, Bielawski reported the landmark study on
using graphene oxide (GO), a water-soluble form of gra-
phene, as a catalyst for chemoselective oxidation of alcohols
under mild conditions (Figure 2A).26 In 2012, Loh reported
oxidative dimerization of amines using base-acid treated
graphene oxide (ba-GO) (Figure 2B).27 In this study, base
treatment and sequential acidification of functional groups
on GO improved the catalyst efficiency in the oxidation of
amines via radical cations. In 2014, Garcia reported a seminal
study on using graphenes as carbocatalysts for hydrogena-
tion of alkenes (Figure 2C).28 The authors demonstrated the
activation of H2 on the graphene surface, which possibly con-
tains frustrated Lewis acid-base sites. Other studies utilizing
GO as a catalyst for oxidation reactions have been report-
ed.29,30 Collectively, these reports demonstrate that gra-
phene-based materials match or even surpass the efficiency
of transition metal catalysts, while at the same time offering
a unique metal-free catalysis platform that can be rationally
modified by heteroatom doping31 and surface modification,32
which heavily benefits from the natural abundance of car-
bon.33 However, in contrast to the extensive progress in using
graphene-based materials as catalysts for oxidation reac-
tions,23–30 the application of graphenes to promote syntheti-
cally useful C–C bond forming reactions utilizing functional
groups on the graphene surface, including acidic sites, that
employ unactivated coupling partners12–16 are severely under-
developed.30
As part of our interest in carbon-based materials,34 we re-
port herein the first general strategy for alkylation of arenes
with styrenes and alcohols2,3 catalyzed by functionalized gra-
phenes, exploiting the unique property of carbon-based ma-
terials23 to produce valuable diarylalkane products21 in high
yields and excellent regioselectivity. This process constitutes
the first general application of graphenes to promote direct
C–C bond formation, utilizing polar functional groups an-
chored on the GO surface,23–30 which may open the door for
industrial arene alkylation using benign, environmentally-
friendly and readily available graphene materials. The reac-
tion is characterized by mild conditions, wide substrate
scope and excellent functional group tolerance. Mechanistic
studies suggest that the reaction proceeds via a tandem ca-
talysis mechanism,35 in which a discrete carbocation is not
formed,36 and both of the coupling partners are activated by
the interaction with the GO surface.37 Finally, we demon-
strate that another advantage of the carbocatalyzed process
is its orthogonal chemoselectivity to metal-catalyzed alkyla-
tions, which should be of particular value for chemoselective
manipulation of functional groups38 beyond the reaction
described herein.
1
2
3
4
5
6
7
8
en-
try
conv
(%)
yield
(%)
catalyst
solvent
T (°C)
1
2
graphite
h-GO
r-GO
GO
CHCl3
CHCl3
CHCl3
CHCl3
toluene
dioxane
CH3CN
DMF
100
100
100
100
100
100
100
100
100
75
<2
<2
<2
<2
37
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3
>98
>98
>98
>98
28
4
>98
63
5
GO
6
GO
26
7
GO
<2
<2
59
90
<2
88
22
8
GO
19
9
GO
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
>98
>98
<2
10
11
12b
13c
14c,d
15e
GO
GO
50
GO
100
120
120
100
90
GO
93
GO
>98
90
GO
>98
>98
aConditions: 1,3-dimethoxybenzene (3.0 equiv), graphene
(200 wt%), solvent (0.20 M), 25-120 °C. b50 wt%. c20wt%. d1.0
M eArene (1.2 equiv). See SI for full details.
coupling of simple arenes with olefins and alcohols. We rec-
ognized that if such a process could be developed, it would
represent a significant advancement in the synthesis of un-
symmetrical diarylalkanes20,21 via
a direct and atom-
economical method22 as well as it would open the door for
numerous related transformations using the carbocatalysis
platform.23–30
We initiated our investigations by screening a range of
conditions for the alkylation of 1,3-dimethoxybenzene14 with
styrene in the presence of various graphene-based materials
(Table 1 and SI). After extensive optimization, we were de-
lighted to find that the proposed alkylation reaction pro-
ceeded in an excellent 98% yield in the presence of GO
(modified Hummers method, 200 wt%)34,39 in CHCl3 at 100 °C
(branched/linear >98:2; mono-/dialkylation >98:2). Interest-
ingly, utilization of other graphene-based materials, such as
microwave-enabled holey-GO (h-GO, which refers to GO
with nanoholes existing in its basal plane),34 and reduced GO
(r-GO) provided inferior results (entries 1-4). As expected, no
reaction was observed using natural flake graphite. However,
to our surprise, h-GO which features similar functionalities
as GO also gave low conversion (vide infra). Extensive opti-
mization of the reaction temperature and solvents indicated
that the reaction ensues at lower temperatures, but the pro-
cess is less efficient (entries 4-11). Other solvents could be
used, but CHCl3 was found to provide the best results in
terms of yield and selectivity. Remarkably, the activator load-
ing could be decreased to 20 wt% with no decrease in the
Results and Discussion
We recently developed a series of novel carbon-based ma-
terials.34 Recognizing the importance of arene alkylation
methodologies,1–18 we questioned whether carbon-based ma-
terials can be employed as benign catalysts to promote the
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reaction efficiency (entries 12-14). The observed turnover
number compares very favorably with the GO-
noteworthy feature of our protocol, including a number of
deactivating substituents (1c-1e)41 and functional groups
poised for further functional group manipulation (1e-f).42
Arenes containing neutral (1b), electron-deficient (1c), halide
(1d-1e) and electron-rich substituents (1f) at the para-
position give the alkylated products in high yields. Efficient
alkylation with indene (1g) and dihydronapthalene (1h) cou-
pling partners demonstrates that the current protocol can be
used to selectively install arenes at the benzylic positions in
cyclic ring systems. Disubstituted olefins serve as efficient
coupling partners (1i). Moreover, we were pleased to find
that the reaction is not limited to styrenyl olefins as nor-
bornene underwent coupling to deliver the alkylated product
in high yield (1j).43 We note, however, that terminal aliphatic
alkenes are quantitatively recovered from the reaction (vide
infra), attesting to the high chemoselectivity of the current
protocol.38
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3
4
5
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7
8
Table 2. Olefin Scope in the GO-Catalyzed Alkylation
of Arenesa
yiel regiose-
entry
1
1
olefin
product
d
(%)
lectivity
(%)
9
1a
98
98
9:1
10
11
12
13
14
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22
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2
1b
>20:1
Next, we explored the scope of the arene coupling partner
using styrene as a standard olefin (Table 3). As shown, the
nucleophile scope is also very broad. As expected, a variety of
electron-rich arenes, such as 1,4-dimethoxybenzene (2b),
1,3,5-trimethoxybenzene (2c), and anisole (2d) furnished the
desired products in excellent yields. It is worthwhile to note
that the use of these nucleophiles provides an efficient route
to methoxy-substituted unsymmetrical diarylmethanes
which constitute the core of diverse bioactive natural prod-
ucts.44 Naphthalenes can be coupled in excellent regioselec-
tivity (2e). Furthermore, steric-hindrance on the arene com-
ponent is well-tolerated (2f). The synthetic utility of our pro-
tocol is further highlighted by the coupling of heteroaro-
matic rings relevant in pharmaceutical and materials indus-
try (2g-h).45 Moreover, high yields are achieved in the alkyla-
tion of functionalized aromatic rings featuring aryl bromides
poised for cross-coupling functionalization (2i),42 and even
non-activated substrates, such as mesitylene (2j).12 High
yields and excellent regioselectivity are noteworthy features
of our protocol and compare favorably with metal-catalyzed
arene alkylations.12–16 Notably, the products feature unsym-
metrical diarylalkane motifs that have found numerous ap-
plications as drug pharmacophores.21
3
1c
99
98
12:1
9:1
4
1d
5
1e
1f
65
60
10:1
Me
Ar
6
>20:1
MeO
7
1g
51
15:1
8
1h
88
>20:1
Ar
Me
Table 3. Arene Scope in the GO-Catalyzed Alkylation
of Arenesa
9
1i
1j
62
81
>20:1
3:1
10
yiel regiose-
entry
2
arene
product
d
(%)
lectivity
(%)
aConditions: olefin (1.0 equiv), 1,3-dimethoxybenzene (3.0
equiv), GO (200 wt%), CHCl3 (0.20 M), 100 °C. See SI for full
details.
catalyzed oxidation of alcohols.26 This is noteworthy as the
latter process utilizes the carbon-based material as an elec-
tron-acceptor rather than proton-donor. Furthermore, high
yield and excellent selectivity was observed with an equimo-
lar ratio of the coupling partners, indicating that olefin
polymerization40 does not compete with arene alkylation
under these conditions (entry 15). In line with the critical role
of carbocatalyst, alkylation products were not detected in the
absence of GO (see SI for additional control experiments).
1
2a
98
98
90
9:1
2
3
2b
2c
-
-
With the optimized conditions in hand, the preparative
scope was next investigated using 1,3-dimethoxybenzene14 as
a standard arene (Table 2). As shown in Table 2, a wide varie-
ty of olefins featuring diverse functional groups can be readi-
ly arylated. Functional group tolerance is a particularly
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metal-free carbocatalyzed alkylation. In addition, our exten-
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2
3
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5
6
7
8
sive purification process excludes the presence of metallic
impurities.34 (2) Surface area analysis of the recovered GO
(methylene blue adsorption method) is calculated to have a
surface area (SA) of 367.29 m2 g-1, indicating an increase of π-
stacking interactions as compared to the parent GO material
(SA of 1371.62 m2 g-1), consistent with partial reduction to
rGO during the reaction.46 (3) UV-Vis experiments with the
GO material used in the alkylation reactions indicated a sig-
nificant increase of near infrared absorption (at 800 nm, re-
covered GO, absorption of 0.3055, c = 20 mg mL-1, ε = 15.3 mL
mg-1 cm-1; GO, absorption of 0.0634, c = 40 mg mL-1; ε = 1.6
mL mg-1 cm-1) (Figure SI-4). Moreover, compared to the GO
starting material, the peak at 236 nm corresponding to the
π−π*C–C transition has been red-shifted (254 nm), further
suggesting recovery of aromatic properties of the GO materi-
al (partial reduction to rGO).47 (4) pH measurements of the
GO material used for the alkylation reactions (pH = 3.91 at
0.29 mg mL-1) and the recovered GO (pH = 3.95 at 0.29 mg
mL-1) indicated the slightly acidic nature of the GO carbocat-
alyst, and no changes in the acidity after the reaction.48 (5)
EDXS analysis (energy-dispersive X-ray spectroscopy) of the
GO material before the reaction showed C/O atomic ratio of
1.95, which increased to C/O atomic ratio of 3.46 after the
reaction, indicating that some oxygen functionalities have
been removed from the GO surface during the reaction (Fig-
ure SI-1). (6) Detailed XPS analysis of the GO material before
the reaction showed C/O atomic ratio of 1.97, which in-
creased to C/O atomic ratio of 2.96 after the reaction (Figure
3 and Figure SI-2). Furthermore, C1s spectrum of the GO
material before and after the reaction indicated a substantial
decrease of C–O/C=O functional groups on the GO surface
(from 49.4% to 40.9%) with a concomitant increase of the
intensity of peaks corresponding to C=C bonds (from 37.0%
to 52.0%). Notably, these changes include loss of C=O and C–
O functions from the GO surface (epoxide, hydroxyl) during
the reaction, as well as the reduction of anhydride and car-
boxylic acid functional groups on the GO surface (from 13.6%
to 7.2%). (7) Film conductivity measurements indicated a
substantial increase in conductivity of GO (below the detec-
tion limit, 8.7 10-3 S m-1, 100 Mꢀ) and recovered GO (3.2 10-2 S
m-1, 27.8 Mꢀ). (8) FTIR measurements were also performed
to analyze the changes in functional groups on the GO sur-
face during the alkylation reactions (Figure SI-3).49 Com-
pared to the GO starting material, the intensity of signals at
1225, 1204 and 1730 cm-1 attributed to C–O (C–OH/C–O–C,
hydroxyl/epoxide) and C=O (carbonyl groups), respectively,
has significantly decreased. Moreover, complete disappear-
ance of signals at 1413 and 1817 cm-1, attributed to carboxylic
acid RCOO-H bending vibrations and anhydride C=O
stretching vibrations, respectively, was observed. The FTIR
spectrum also revealed that the signal at 1633 cm-1, attributed
to the presence of sp2 C=C bonds, has shifted to 1560 cm-1,
further indicating the loss of electron withdrawing functional
groups from the GO surface. Thus, in agreement with other
data, the FTIR spectral information suggests that polar func-
tional groups are removed from the GO surface during the
alkylation reactions. (9) Calculation of the carboxylic acid
content in the GO starting material used for the alkylation
reactions indicated that GO contains 0.66 mol of C/0.34 mol
of O, with 13.6% of C (0.090 mol) in the form of carboxylic
acid functional groups based on the XPS data.50 Moreover,
the GO material recovered after the alkylation reactions con-
4
5
2d
2e
81
71
11:1
>20:1
Me
Ar
Me
HO
9
10
11
12
13
14
15
16
17
18
19
20
21
22
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6
2f
73
-
Me
7
2g
2h
61
>20:1
11:1
8
66
9
2i
2j
78
63
>20:1
10
-
aSee Table 2. See SI for full details.
On the basis of the results in Tables 2-3, we hypothesized
that the alkylation protocol could be extended to alcohols as
coupling partners. Friedel-Crafts alkylation with alcohols is
regarded as one of the current top research priorities due to
beneficial, environmentally-friendly profile of the reaction.22
In the event, we were pleased to find that the coupling of 1,3-
dimethoxybenzene with benzyl alcohols proceeded with ex-
cellent efficiency under our optimized conditions (see SI for
detailed studies), providing alternative disconnection to the
diarylalkane products.
Scheme 1. GO-Catalyzed Direct Friedel-Crafts Alkyla-
tion of Arenes with Alcohols
R
OMe
R
OMe
GO, air
OH
+
CHCl3, 100 °C
OMe
OMe
5a
5b
2a
3t
, R = H, 82%
3a
, R = Me, 95%
, R = H
, R = Me
To confirm the critical role of graphene in this novel alkyl-
ation reaction, extensive characterization of the GO before
and after the reactions (referred to in the section below as
‘GO’ and ‘recovered GO’) were conducted. (1) To determine if
trace quantities of transition metals were involved in these
alkylation reactions, the GO material was analyzed by XPS
(X-ray photoelectron spectroscopy) and AAS (atomic absorp-
tion spectroscopy). XPS analysis indicated less than 50 ppm
of trace metal contaminants (detection limit). AAS analysis
indicated less than 20 ppb of trace metal contaminants (Mn,
Fe, Cu, Cd, Zn, Ni, Pb, Au; detection limit), supporting the
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tains 0.75 mol of C and 0.25 mol of O, with 7.2% of C (0.054
value of -1.79, R2 = 0.79), indicating an increase of regioselec-
1
2
3
4
5
6
7
8
mol) in the form of carboxylic acid functional groups. This
represents a 2.32 mmol g-1 loss of carboxylic acid functional
groups during the catalysis (TON ca. 20 based on the carbox-
ylic acid functional groups), consistent with a proton switch
mechanism on the graphene surface.51 It is worthwhile to
note that the calculated TON corresponds to the quantity of
the catalytically-active functional groups on the material
surface rather than to the overall mass of the graphene cata-
lyst as is the case with the wt% descriptor. Overall, the struc-
tural changes on the GO surface suggest that GO undergoes
partial reduction to rGO during the process, and point to-
wards the importance of oxygen-containing functionalities
anchored on the GO surface (hydroxyl, epoxide and carbox-
ylic acid groups).
tivity with a faster reaction rate, which may be characteristic
of a diffusion-controlled reaction rate.57 (3) Intermolecular
competition experiments with differently substituted sty-
renes revealed that steric hindrance plays an important role
in these reactions, consistent with coordination to the GO
surface. (4) Intermolecular competition experiments with
benzylic alcohols revealed that 1° alcohols are intrinsically
more reactive substrates than 2° alcohols, which is opposite
to the trend observed in the classical Friedel-Crafts reac-
tions.3 (5) Initial rate measurements revealed that the overall
reaction rate does not change significantly over the course of
the reaction,58 and that benzylic alcohols are coupled prefer-
entially to olefins (1a, vinital = 1.40 x 10-1 mM s-1; 5b, vinital = 8.03
x 10-1 mM s-1), consistent with dispersion kinetics and the
presence of carbinol as an intermediate in the reaction.59 No
intermediates were detected by careful monitoring of the
reaction with either alkene or alcohol coupling partners. (6)
Examination of different leaving groups in the alkylation,
indicates fully chemoselective reaction for the coupling of
alcohol in the presence of acetate, consistent with coordina-
tion to the graphene surface.37 Importantly, this chemoselec-
tivity is opposite from that expected of the classical alkyla-
tions mediated by transition metals,1–16 and should be of par-
ticular value for chemoselective manipulation of alcohols by
carbon-based materials.38
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Based on this consideration, it is reasonable to observe the
low conversion efficiency in the presence of rGO and graph-
ite due to dramatically decreased oxygen-containing func-
tionalities (Table 1).52 On the other hand, holey GO and GO
contain similar functional groups. Besides, it was widely re-
ported that holey graphene materials exhibit much improved
performance compared to its non-holey counterpart.27,34a,53
The existence of nanoholes in the basal plane of holey GO
not only provides a “short-cut” for efficient mass transport,
but also provides more catalytic centers due to increased
edges. Thus, in the beginning we were surprised by the low
conversion when holey GO was used as the catalyst for the
alkylation reaction. However, careful comparison of the de-
tailed XPS and FTIR analysis of GO and h-GO was per-
formed, and we found that holey GO has higher graphitic
carbon (46% vs. 37%) and total C/O ratio (2.38 vs. 1.97) than
GO as described above. The carboxylic acid content in holey
GO is also much higher (23% vs. 13.6%), possibly due to
much larger amount of edges in holey GO, where carboxylic
acid groups are normally located. However, the relative con-
tent of C–O/C=O functional groups is much lower in holey
GO (31% vs. 49%).34a
A proposed mechanism for the alkylation of arenes is pre-
sented in Scheme 1. The mechanistic studies are consistent
with activation of both of the coupling partners by transient
anchoring to the graphene surface.23 The key step involves
activation of the olefin coupling partner by hydration, gener-
ated in situ from the reduction of graphene, and a transition
state in which the arene nucleophile is prepositioned for a
concerted C–C bond forming step60,61 by π-stacking interac-
tions with the carbon-based material to give the alkylated
product and regenerate the catalyst after the release of water.
Single carbon-based material promotes two distinct steps in
the catalytic cycle owing to the presence of polar and aro-
matic functional groups on a single surface. The fact that the
In general, the molecular structure of GO is described as
defect-free graphitic domains (aromatic regions), which are
separated by amorphous-like regions (polar regions), and
sometimes feature nanoholes in its basal plane.47a,54 The high
content of graphitic carbon with low percentage of C–O/C=O
functional groups indicate that holey GO features larger gra-
phitic domains. Therefore, even though larger amounts of
carboxylic acid groups are present on the holey-GO surface,
the spatial arrangement of these functional groups is not
optimal for the catalytic reaction. In contrast, the smaller
aromatic domains and relatively higher density of functional
groups on the GO material as described above appear to be
beneficial to promote the catalytic C–C coupling.34b
C1s Scan
1 m 35.5 s, 400ꢀm, CAE 50.0, 0.10 eV
C1s Scan
1 m 35.5 s, 400ꢀm, CAE 50.0, 0.10 eV
10 Scans,
3.00E+04
10 Scans,
2.60E+04
2.40E+04
2.20E+04
2.00E+04
1.80E+04
1.60E+04
1.40E+04
1.20E+04
1.00E+04
8.00E+03
6.00E+03
4.00E+03
2.00E+03
0.00E+00
2.00E+04
1.00E+04
0.00E+00
298 296 294 292 290 288 286 284 282 280
298 296 294 292 290 288 286 284 282 280
Binding Energy (eV)
Binding Energy (eV)
We conducted additional studies to gain insight into the
mechanism of the alkylation reaction of arenes (Figure 4 and
SI). (1) Hammett study performed using differently substitut-
ed 4-arylalkene electrophiles showed an excellent correlation
(a small ρ+ value of -0.68, R2 = 0.99; ρ value of -1.12, R2 =
0.90),55 indicating build-up of a partial positive charge at the
benzylic carbon in the transition state, which can be com-
pared with a ρ+ value of -5.6 for a classical solvolysis of aryl
tosylates via an SN1 mechanism.56 (2) Moreover, Hammett
correlation obtained by plotting the regioselectivity of alkyla-
tion of 1,3-dimethoxybenzene with 4-substituted styrenes
showed an excellent correlation (ρ+ value of -1.16, R2 = 0.98; ρ
Figure 3. (a) X-ray photoelectron spectroscopy C1s spectrum
of GO. (b) X-ray photoelectron spectroscopy C1s spectrum of
GO after alkylation of 1,3-dimethoxybenzene with styrene.
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Journal of the American Chemical Society
Page 6 of 9
result in further enhancement of selectivity and catalytic
activity of carbon-based materials. Further mechanistic stud-
Hammett Plot
Plot of Alkylation Selectivity vs. σ+
MeO
0.5
0.4
0.3
0.2
0.1
0.0
ꢁ0.1
ꢁ0.2
MeO
y = ꢁ1.117x + 0.058, R2 = 0.903 (σ)
y = ꢁ1.793x + 0.285, R2 = 0.792 (σ)
y = ꢁ1.160x + 0.048, R2 = 0.982 (σ+
1.0
0.8
0.6
0.4
0.2
0.0
ꢁ0.2
1
2
3
4
5
6
7
y = ꢁ0.681x ꢁ 0.079, R2 = 0.994 (σ+
)
)
ies and the extension to a wide variety of π-systems are un-
derway in our laboratories, and these results will be reported
shortly.62
Me
Me
F
F
Cl
Cl
ASSOCIATED CONTENT
Supporting Information
ꢁ0.8
ꢁ0.6
ꢁ0.4
σ+
ꢁ0.2
0.0
0.2
ꢁ0.8
ꢁ0.6
ꢁ0.4
σ+
ꢁ0.2
0.0
0.2
Characterization of catalysts, elemental analysis, experi-
mental procedures and compound characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
8
9
Figure 4. (a) Plot of log k vs. σ+ for the alkylation of 1,3-
dimethoxybenzene with styrene. (b) Plot of log s (s = selec-
tivity) vs. σ+ for the alkylation of 1,3-dimethoxybenzene with
styrene. [olefin] = 0.20 M. [arene] = 0.60 M. [GO] = 40
mg/mL. T = 100 °C.
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AUTHOR INFORMATION
Corresponding Author
michal.szostak@rutgers.edu
huixinhe@ rutgers.edu
chemical structures including the spatial arrangement of
functional groups on GO surfaces exert significant impact on
the catalytic efficiency soundly supports this hypothesis. In
this scenario, olefin hydration appears to be a kinetically
relevant step in the reaction. An alternative mechanism, in-
volving arene addition to the carbocation cannot be exclud-
ed; however, this mechanism is less likely based on the rela-
tive reactivity data. A possible mechanism when alcohols are
used as substrates involves activation of the alcohol by a
transient coordination to the carbocatalyst surface to give a
stabilized cation. This mechanism is supported by the rela-
tive reactivity in the alkylation using benzylic alcohols and
olefins, as well as by the relative reactivity of 1° and 2° alco-
hols observed in the mechanistic studies. Further studies to
elucidate the mechanism are ongoing.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support was provided by Rutgers University and
the National Science Foundation (CBET 1438493). The Bruker
500 MHz spectrometer used in this study was supported by
the NSF-MRI grant (CHE-1229030).
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R1
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R
Me
Ar1
[GO]
Ar1
Ar2
ꢁH2O
[GO]
H
O
[GO]
R1
Ar1
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O
Me
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[GO]
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Ar1
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Ar2
H
Conclusions
In conclusion, we have developed a highly efficient alkyla-
tion of arenes to give valuable diarylmethanes catalyzed by
graphenes. Our data show that graphenes in the absence of
any transition metals are effective and general catalysts for
the formation of C–C bonds via a novel catalysis mechanism,
in which activation of both coupling partners is possible ow-
ing to the presence of polar and aromatic functional groups
on the graphene surface. Considering the importance of
Friedel-Crafts alkylation reactions as well as a wide variety of
coupling manifolds for arene functionalization, our study
provides a conceptual framework for the use of GO-based
materials for large scale industrial catalysis. Notably, our
study shows that reactions catalyzed by graphene oxide dis-
play orthogonal regio- and chemoselectivity to transition
metals, which allows to distinguish between functional
groups with similar reactivity. We expect that doping with
heteroatoms and control of the polar sites on the surface will
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