Phosphomolybdic acid as a bifunctional catalyst for Friedel–Crafts type dehydrative coupling reaction

Article abstract of DOI:10.1002/aoc.4450

Phosphomolybdic acid (H₃PMo₁₂O₄₀) was found to be a bifunctional catalyst for C─C bond formation via the dehydrative reaction of diarylmethanols with various nucleophiles, including 2-naphthols, indoles, benzofuran and ben

Full text of DOI:10.1002/aoc.4450

Received: 9 April 2018
DOI: 10.1002/aoc.4450
Revised: 7 May 2018
Accepted: 14 May 2018
C O M M U N I C A T I O N
Phosphomolybdic acid as a bifunctional catalyst for
Friedel–Crafts type dehydrative coupling reaction
Guo‐Ping Yang1,2 | Dilireba Dilixiati1 | Tao Yang1 | Dong Liu1 | Bing Yu3
| Chang‐Wen Hu1
1 Beijing Institute of Technology, Key
Phosphomolybdic acid (H3PMo12O40) was found to be a bifunctional catalyst
Laboratory of Cluster Science of Ministry
of Education, Beijing Key Laboratory of
Photoelectronic/Electrophotonic, School
of Chemistry and Chemical Engineering,
Beijing 100081, People's Republic of China
for C─C bond formation via the dehydrative reaction of diarylmethanols with
various nucleophiles, including 2‐naphthols, indoles, benzofuran and
benzothiophene. The protons in the catalyst might play a critical role in the
activation of alcohol, while the polyanion was advantageous for stabilizing
the carbocation species. The cooperative catalytic system showed its own
merits, such as high reaction rate, low catalyst loading, mild conditions, excel-
lent yields (up to 99%) and good functional group compatibility.
2 China Academy of Engineering Physics,
People's Republic of China
3 Zhengzhou University, College of
Chemistry and Molecular Engineering,
Zhengzhou 450001, Henan Province,
People's Republic of China
KEYWORDS
Correspondence
alcohols, cooperative effect, dehydrative coupling, polyoxometalates
Bing Yu, College of Chemistry and
Molecular Engineering, Zhengzhou
University, Zhengzhou 450001, Henan
Province, China.
Email: bingyu@zzu.edu.cn
Chang‐Wen Hu, School of Chemistry and
Chemical Engineering, Beijing Institute of
Technology, Beijing 100081, China.
Email: cwhu@bit.edu.cn
Funding information
National Natural Science Foundation of
China, Grant/Award Numbers: 21501010
and 21671019; 973 Program, Grant/Award
Number: 2014CB932103; the 111 Project,
Grant/Award Number: B07012
1 | INTRODUCTION
is formally generated as the sole by‐product,[2] which
makes dehydrative coupling cleaner than the conven-
The construction of C─C bonds plays an important role
in organic synthesis. As a consequence, a variety of strat-
egies including transition‐metal‐catalyzed cross‐coupling,
C─H bond functionalization, photocatalysis, oxidative
cross‐coupling and Friedel–Crafts type dehydrative cou-
pling have been developed for C─C bond formation.[1]
Particularly, in Friedel–Crafts type dehydrative coupling
the direct use of aryl alcohols as an economic alternative
to C─X species has attracted increasing attention due to
their availability and lower toxicity. Importantly, water
tional Friedel–Crafts reaction.
In 1986, Uemura and co‐workers reported the first
Friedel–Crafts alkylation of alcohols with arenes using
TeCl4 as catalyst.[3] Subsequently, Sc (OTf)3 and Mo
[4]
[5]
(CO)6 were applied as catalysts for the reaction of free
alcohols. Since then, enormous efforts have been devoted
to the development of new synthetic methods for the
direct substitution of π‐activated alcohols.[6] In recent
years, plenty of systems, including metal triflates (e.g.
Hf, Sc, Ya and La),[7] NbCl5,[8] I2,[9] surfactant‐type
Appl Organometal Chem. 2018;e4450.
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YANG ET AL.
Brønsted acid/H2O,[10] Amberlyst‐15,[11] C6F5B(OH)2,[12]
on these results, we envisaged that the in situ generated
cation could be attacked by suitable external nucleophiles.
In the work reported herein, phosphomolybdic acid
(H3PMo12O40) was found to be a single‐component bifunc-
tional catalyst in the Friedel–Crafts type dehydrative cou-
pling reaction of diarylmethanols with 2‐naphthols,
indoles, benzofuran and benzothiophene under mild con-
ditions (Scheme 1).
FeCl3,[13] NaHSO4/SiO2
and SnBr4,[15] have been
[14]
reported. Very recently, the group of Moran[16] reported
that 1,1,1,3,3,3‐hexafluoro‐2‐propanol as a hydrogen‐
bond acceptor with strong Brønsted acid TfOH was an
efficient catalytic system for dehydrative Friedel–Crafts
reactions. However, most of those reported methods
necessitate the use of halogenated reagents, caustic acids
or hash reaction conditions (e.g. elevated temperature for
extended periods of time), thus limiting their applicability.
Therefore, a halogen‐free, nontoxic and easy‐to‐handle
catalyst is very important for both Friedel–Crafts type
dehydrative coupling reaction improvement and green
catalyst design.
The inexpensive polyoxometalates (POMs) have
shown broad activities in green chemistry.[17] Particularly,
a Keggin‐type POM exhibited potential for dehydrative
reactions of benzylic alcohols and various nucleophiles
for the construction of C─C/N bonds.[18] In our previous
work,[19] the inexpensive H3PMo12O40/propylene carbon-
ate was found to be a unique and efficient catalytic system
for the carbohydroxylation of terminal alkynes with ben-
zylic alcohols under mild conditions. In these protocols,
the key intermediate, benzyl cation, was generated after
protonation of the benzylic alcohol by the POM. Based
2 | RESULTS AND DISCUSSION
To optimize the reaction conditions, diphenylmethanol
(1a) and 2‐naphthol (2a) were chosen as model com-
pounds for the reaction (Table 1). The experiment without
catalyst provided only 4% yield of the desired compound 3a
in dichloroethane (DCE) at room temperature for 1 h
(entry 1). Product 3a was obtained in yields of 84, 68 and
88% when the Keggin‐type POMs H3PW12O40, H4SiW12O40
and H3PMo12O40 were applied as catalysts, respectively
(entries 2–4). Therefore, H3PMo12O40 was employed as
catalyst for the screening of solvents. It was found that
the solvent has a marked impact on the efficiency of the
reaction. The reaction in MeCN gave the highest selectivity
and yield towards product 3a (entry 5). Reactions in other
solvents, e.g. toluene, cyclohexane and tetrahydrofuran
(THF), gave 3a in good yields but lower selectivities
(entries 6–8). When the reaction was conducted in
water, a yield of 3a of only 21% was obtained (entry 9).
Notably, the reaction time can be shortened to 20 min,
and the excellent yield and selectivity of 3a were retained
SCHEME 1 Friedel–Crafts type dehydrative coupling reaction
TABLE 1 Effects of catalyst and various solvents on the reactionsa
Entry
Solvent
Conv. of 1a (%)
Yield (%)b
1c
2d
3e
4
DCE
7
4
DCE
85
99
99
99
99
93
99
23
99
84
68
88
99
94
68
53
21
99
DCE
DCE
5
MeCN
Toluene
Cyclohexane
THF
6
7
8
9
10f
H2O
MeCN
aReaction conditions: diphenylmethanol (0.2 mmol), 2‐naphthol (0.22 mmol), H3PMo12O40 (3 mol%), solvent (1 ml), r.t., 1 h. bYields determined by GC with
biphenyl as the internal standard. The main by‐product is benzhydrol ether. cWithout catalyst. dH3PW12O40 (3 mol%) as catalyst. eH4SiW12O40 (3 mol%) as
f
catalyst. Reaction time: 20 min.

YANG ET AL.
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(entry 10). These results encouraged us to evaluate the
amount of H3PMo12O40 employed. As shown in Figure 1,
when 2.5 mol% of H3PMo12O40 was used, excellent selec-
tivity of 1a and yield of 3a were achieved.
Having established a standard set of reaction condi-
tions, we surveyed the substrate scope of this dehydrative
coupling reaction at room temperature. As listed in
Table 2, both electron‐rich and electron‐deficient
diphenylmethanols showed high reactivities with 2‐
naphthol (2a), affording the corresponding products
3a–e in excellent yields (90–99%). Additionally, the reac-
tions of Br‐substituted naphthols, e.g. 6‐bromo‐2‐naphthol
and 7‐bromo‐2‐naphthol, with electron‐rich and electron‐
deficient diphenylmethanols also provide the C─C bond
formation products 3f–m in excellent yields (90–96%).
Furthermore, the application of 2‐methoxynaphthalene
as substrate also gave the desired products 3n–q in high
yields (91–95%).
In order to further demonstrate the generality of our
catalytic system, a variety of commercially available het-
erocycles such as indole, benzofuran and benzothiophene
were used as nucleophiles for the reaction with
diphenylmethanols. As presented in Table 3, indoles and
various diarylmethanols could be converted into the corre-
sponding products 5a–c in good yields (90–97%) at an ele-
vated reaction temperature (60 °C) in DCE. Moreover,
benzofuran and benzothiophene also proved to be efficient
substrates for the dehydrative reaction affording the corre-
sponding 2‐functionalized products 5e–j in high yields
(90–96%).
To gain a deeper insight into the role of the POM
catalyst in this process, we performed a series of control
experiments, with the results summarized in Table 4.
The reaction of 1a and 2a without any catalyst at room
temperature for 20 min did not give the product 3a
FIGURE 1 Effects of catalyst loading for the reaction in MeCN
(1 ml) at room temperature for 20 min
TABLE 2 Reaction of diarylmethanols with 2‐naphthol derivativesa
aReaction conditions: 1 (0.6 mmol), 2 (1.1 equiv.), H3PMo12O40 (2.5 mol%) and MeCN (3 ml) as solvent, r.t., 30 min. Isolated yields based on 1 are given.
bReaction time: 20 min.

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YANG ET AL.
TABLE 3 Reaction of diarylmethanols with benzoheterocycle
compoundsa
FIGURE 2 1H NMR spectra in CD3CN (0.5 ml): (a) 1a
(0.1 mmol); (b) H3PMo12O40 (0.0025 mmol); (c) mixture of 1a
(0.1 mmol) and H3PMo12O40 (0.0025 mmol) at room temperature
Based on the results discussed above and those of
EI‐MS study, a tentative reaction pathway is proposed
(Scheme 2). Under the catalytic conditions, the alcohol
1a is quickly converted into the corresponding ether
6, which proved to be a reversible process from a
time‐course investigation.[19a] Compound 1a can be
directly protonated by the POM catalyst affording the
intermediate 7. After dehydration of 7, the carbocation
species 8, stabilized by the polyanion[20] (denoted as
[PMoO]), is generated. Subsequently, the desired product
3 is obtained via nucleophilic attack at 8, followed by
proton transfer.
aReaction conditions: 1 (0.6 mmol), 4 (1.1 equiv.), H3PMo12O40 (2.5 mol%),
DCE (3 ml) as solvent, 60 °C, 1 h. Isolated yields based on 1 are given.
(entry 1). Both Brønsted acid p‐TsOH ⋅H2O and the
polyanion salt Na3PMo12O40 ⋅12H2O showed good cata-
lytic activities for the model reaction under identical
conditions, giving the product 3a in 51 and 39% yields,
respectively (entries 2 and 3). These results indicated that
both protons and polyanion in H3PMo12O40 are critical
for the catalytic performance.
Furthermore, the interaction between POM catalyst
and alcohol 1a in CD3CN was monitored using 1H
NMR spectroscopy (Figure 2). Fast proton exchange
(denoted as asterisk) was observed between 1a and
H3PMo12O40 at room temperature. Moreover, 1a was
rapidly converted into benzhydrol ether catalyzed by
H3PMo12O40 (Figure 2c), which was consistent with the
reaction monitored using GC–MS. These results suggested
that the interaction between 1a and H3PMo12O40 was fast
and efficient.
SCHEME
polyanion)
2
Proposed reaction mechanism ([PMoO]
=
TABLE 4 Control experimentsa
Entry
Catalyst (mol%)
Yield (%)b
1
2
3
—
0
p‐TsOH ⋅H2O (7.5)
51
39
Na3PMo12O40 ⋅12H2O (2.5)
aReaction conditions: to a reaction vial, 1a (0.2 mmol), 2a (0.22 mmol), catalyst and MeCN (1 ml) were added and stirred at room temperature for 20 min. After
reaction, the mixture was analyzed by GC. bYields determined by GC with biphenyl as internal standard.

YANG ET AL.
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3 | CONCLUSIONS
In summary, we have reported an efficient bifunctional
H3PMo12O40 catalyst for C─C bond construction
from diarylmethanols and various nucleophiles by
Friedel–Crafts dehydrative reaction under very mild
conditions. In this bifunctional catalyst, the protons in
POM might play a critical role in the activation of alcohol,
while the polyanion was advantageous for stabilizing
the carbocation species. Given the cooperative effect, the
one‐component bifunctional H3PMo12O40 catalyst appears
as a promising new material for future application as a
green acidic catalyst for organic synthesis.
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4 | EXPERIMENTAL
Typical procedure for the POM‐catalyzed dehydrative
reaction was as follows. To a 4 ml reaction vial,
diphenylmethanol (0.2 mmol), 2‐naphthol (0.22 mmol),
H3PMo12O40 (2.5 mol%) and MeCN or DCE (1 ml) were
added. Then the reaction was carried out in screw cap vials
with a Teflon seal at room temperature (or 60 °C) for the
desired time. After completion of the reaction, the mixture
was purified by column chromatography (petroleum
ether–EtOAc) to afford the desired product (see the
Supporting Information).
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ACKNOWLEDGMENTS
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We thank the National Natural Science Foundation of
China (21501010, 21671019), 973 Program (2014CB932103)
and the 111 Project (B07012) for financial support.
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ORCID
[13] H. Li, W. Li, W. Liu, Z. He, Z. Li, Angew. Chem. Int. Ed. 2011,
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Bing Yu http://orcid.org/0000-0002-2423-1212
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How to cite this article: Yang G‐P, Dilixiati D,
Yang T, Liu D, Yu B, Hu C‐W. Phosphomolybdic
acid as a bifunctional catalyst for Friedel–Crafts
type dehydrative coupling reaction. Appl
Organometal Chem. 2018;e4450. https://doi.org/
10.1002/aoc.4450
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.