Coumarin-surfactant modified polyoxometalate catalyzed cross dehydrogenative coupling of benzyl alcohol with the: Para -C-H of unprotected aniline

Article abstract of DOI:10.1039/c8cy01423j

This paper presents a novel method for synthesizing para-aminobenzophenone and its derivatives (p-ABPs) using a coumarin-surfactant modified polyoxometalate as the catalyst. Preliminary mechanistic studies indicate that the reaction has undergone an oxidative cross dehydrogenative coupling process. This method has the advantages of an easy process, a convenient raw material source, safe and green oxidants, and tolerances of several functional groups.

Full text of DOI:10.1039/c8cy01423j

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Coumarin-surfactant modified polyoxometalate catalyzed cross
dehydrogenative coupling of benzyl alcohol with para-C–H of
unprotected aniline
Received 00th January 20xx,
Accepted 00th January 20xx
†
†
a
b
Qian Xu,a Gang Yu,a Min Liu,a Chang Peng,a M. Katherine Banks,b Weijian Xu,* Ruoxi Wu,*
DOI: 10.1039/x0xx00000x
a
Yanbing Lu*
www.rsc.org/
This paper presents a novel method for synthesizing para- ABPs from benzophenone compounds. But Among these
aminobenzophenone and its derivatives (p-ABPs) using synthesis methods, the use of expensive metal catalysts (such
a
coumarin-surfactantmodified polyoxometalate as the catalyst. as Pt or Pd), unsafe/unfriendly oxidant, specific functional
Preliminary mechanistic studies indicate that the reaction has group required reduce the efficiency of the synthesis reaction.
undergone a oxidative cross dehydrogenative coupling process.
Oxidative cross dehydrogenative coupling (CDC) can directly
This method has the advantages of easy process, convenient raw act on the C—H bond, and then prepare the functionalized
material source, safe and green oxidants, and tolerances of substrate without extra reaction steps.14 This provides a new
several functional group.
synthesis
strategy
for
preparing
amino-containing
(POM)
benzophenone
compounds.
Polyoxometalate
Benzophenone is a class of important compounds that widely
used as synthetic perfume, pharmaceutical intermediates,
optical devices and functional polymer materials.1-5 In
particular, the synthesis of higher value-added para-
aminobenzophenone and its derivatives (p-ABPs) can expand
the application of benzophenone due to the reaction diversity
of amino (-NH2).6
compounds are attracting more and more attention in organic
catalytic studies, for their unique structures and properties as
well as their environmental and economical benefits.15-16 In
our previous research, two kinds of coumarin surfactant-
modified
polyoxometallate
(POM)
materials
((Coumarin)3HPMo11VO40 and (Coumarin)4PMo11VO40) were
synthesized and used in the selective catalytic oxidation of
benzyl alcohol (BzOH) to benzaldehyde (BzH).17 Inspired by the
previous work, a series of p-ABPs were prepared from BzOH
and unprotected aniline using (Coumarin)3HPMo11VO40 as a
catalyst. Herein, a new synthesis method of p-ABPs using POM
hybrid material as a catalyst is described. This synthetic route
has the advantages of easily obtainable raw materials, simple
operation, and strong functional group tolerance. Furthermore,
when the oxidant is air, the reaction can still proceed,
compounding the need for green chemistry.
p-ABPs have been synthesized through the traditional
method of Friedel-Crafts acylation for long time. However,
many functional groups are not compatible with the Lewis
acids used in this reaction. Problems concerning
regioselectivity due to -ortho and -para products enhance the
difficulty of separation.7 The Suzuki–Miyaura cross-coupling
reaction is a good method for synthesizing p-ABPs because the
aryl halides and aryl organometallic reagents are coupled with
the catalyst of transition metal using carbon monoxide as the
C1 source.8,9 Another synthetic strategy is to convert the
functional groups on benzophenone to amino, such as nitro
reduction or amination aryl halides using ammonia or
ammonium salts.10-13 However, these two methods are
advantageous to simple structures of aromatic and aliphatic
compounds, but they are not economical for generating p-
Scheme 1 presents the catalyst preparation process. The
novel polyoxometalate-based catalysts was prepared by
modifying Keggin POM H4PMo11VO40 with
a coumarin
surfactant via electrostatic interactions. The results indicate
that the catalyst has large Brunauer-Emmmett-Teller (BET)
specific surface area and pore size, and also indicate that
strong interactions occur between the reactants. These
features facilitate the enrichment and timely diffusion of the
reactants. The process of preparation and characterization of
catalysts were described in our previous reports.17
a.College of Chemistry and Chemical Engineering, Hunan University, Hunan 410082,
P.R. China E-mail address: weijxu@hnu.edu.cn (W. Xu). yanbinglu@hnu.edu.cn (Y.
Lu)
b.Zachry Department of Civil Engineering, Texas A&M University, College Station, TX
77843, United States E-mail address: wur@tamu.edu (R. Wu).
These authors contributed equally to this work.
†
† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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A
convert to the target product (3a) through a Friedel-Crafts
process.18-22 However, to verify the actual mechanism and
process, a type of radical scavenger (butylated hydroxytoluene
(BHT) or 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), or 1,1-
Diphenylethylene) was dropped into the reaction, under the
same reaction conditions, and then no 3a was detected, as
shown in Scheme 2 (eqn 2-4). The GC-MS data show that the
Scheme 1. Illustration for preparing a net-like trap POM-
based amphiphilic catalyst and its possible reaction
mechanism.
reaction product was intermediate
A. The reaction did not
proceed further to generate the corresponding 3a. The
reaction mechanism is not a Friedel-Crafts process but a free
radical control process. The reaction 1-4 also show that the
oxidation of BzOH to BzH was not a free radical reaction. It also
confirmed the previous hypothesis that BzOH was rapidly
Our previous researches show that the rapid oxidation of
BzOH to BzH can be done in 90 minutes without producing the
by-product benzoic acid. The conversion of BzOH and the
selectivity of BzH are close to 100 percent with the use of
oxidized to BzH, and then BzH reacted with aniline to form A.
(Coumarin)3HPMo11VO40
as
a
catalyst.17
Similarly,
The eqn 5-6 further prove that the oxidation of BzOH to BzH is
one step in the reaction, and the catalyst not only participates
in the oxidation of BzOH to BzH, but also determines the next
(Coumarin)3HPMo11VO40 also shows the best catalytic effect
among different catalysts in the synthesis of p-
aminobenzophenone, as in Tab 1. These results indicate that
the catalytic active center is H4PMo11VO40 and the oxygen
molecule is an oxidant. The (Coumarin)3HPMo11VO40 has
better catalytic effect than the unmodified H4PMo11VO40. A
possible explanation is that the structural characteristics of
large specific surface area, pore size, and π-π* conjugate effect
with the reactant and result the enrichment of reactants.
reaction process. Furthermore, the reaction intermediate
A
synthesized by literature can react with aniline to get 3a in the
action of catalyst, and the 3a can’t be obtained without
catalyst.23 Combining the previous reaction results, it can be
shown that the catalyst not only catalyzes the oxidation of
BzOH to BzH, but also participates in the formation of a free
radical. Summarizing the related literature, aniline can donate
one electron in oxidation under the presence of catalyst, and
lose one proton to obtain a highly active aniline radical, shown
Tab. 1. The reaction yield of different catalysts with different
oxidants investigateda.
in Scheme 3B and 3C 24
. Therefore, this explains why 3a cannot
catalyst
oxidant yield(%)b
be obtained in the BHT or TEMPO presence cases,, or in the
NO
O2
O2
O2
O2
O2
ND
trace
78
absence of catalyst.
O
H4PMo11VO40
NH2
OH
(Coumarin)3HPMo11VO40
(Coumarin)4PMo11VO40
Coumarin-surfactant
Standard condition
+
(1-4)
NH2
20
1a
2a
3a
ND
trace
ND
ND
42
(1) No free radical scavenger, 73% yield
(2) 2 equiv TEMPO, ND
(3) 2 equiv BHT, ND
(4) 2 equiv 1,1-Diphenylethylene, ND
O
Coumarin-surfactant + H4PMo11VO40 O2
No catalyst
O2
N2
O
(Coumarin)3HPMo11VO40
(Coumarin)3HPMo11VO40
aReaction conditions: catalyst
NH2
Standard condition
H
+
air
(5-6)
(7-8)
NH2
3
mg (1.1
µmol), O2,
L (0.2 mmol),
2a
3a
(5) 3 mg catalyst, 70% yield
(6) without catalyst, ND
DMSO/CH3Cl ( V/V: 1:1 ) (0.5 mL), BzOH 21
aniline 54
µ
µ
not dectected.
L (0.6 mmol), 150 °C, 12 h. Isolated yieldsb. ND =
O
NH2
Ph
Standard condition
N
+
NH2
2a
3a
Further, using (Coumarin)3HPMo11VO40 as a catalyst, the
effects of different solvents, reactant ratio, reaction
temperature, and catalyst content on the reaction were
studied, and the optimal reaction conditions were selected, as
shown in electronic supplementary information (ESI).
(7) 3mg catalyst, 68% yield.
(8) without catalyst, ND
Scheme 2 Mechanistic investigations.
Based on the description of previous studies, one possible
reaction mechanism was proposed, as shown in Scheme 3
First, BzOH 1a is oxidized to BzH, and then reacts with aniline
2a to get the imine intermediate . At the same time, the
.
Comparing the processes of selective oxidation of BzOH and
the synthesis of p-aminobenzophenone, it can be found that a
higher efficiency of BzOH oxidation is correlated with a higher
yield of p-aminobenzophenone. A simple hypothesis can be
made that the oxidation of benzyl alcohol to BzH is an
A
reaction is triggered by the transfer of a single electron from
aniline 2a to Vv, which is the catalytic activity center and
generated by VIV under the oxidation of O2. The formed cation
important
process
during
the
synthesis
of
p-
radical
radical
B tends to lose one proton to form a cyclohexadienyl
aminobenzophenone. The reaction mechanism was initially
considered as that the BzOH was rapidly oxidized to BzH, and
C
, and
C
is captured by
A
to form the deliver
, then E
intermediate
D
.
D
captures H to form a more stable
E
then the BzH react with aniline rapidly to form
a
undergoes dehydrogenation and hydrolysis to give the product
benzylideneaniline intermediate A, and then the intermediate
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.
The aniline formed during the process of hydrolysis can easily trap the reactants with a benzene ring (such as BzOH
continue to participate in the reaction. In order to further and aniline) due to the π-π* conjugate effects between
verify this reaction mechanism, the reaction product of eqn 1 reactants and catalyst. In this way, the catalyst also shows the
was detected by GC-MS. The results show that the main effect of enriching the reactants, and further improves the
product is 3a, and intermediates
A and E were detected, as catalytic effect of the reaction. It is worth mentioning that
shown in ESI. The results of GC-MS further confirm the when the oxidant is replaced by air, although the reaction yield
feasibility of the proposed reaction mechanism.
decreases, the reaction can still proceed, as shown in Tab 1.
In summary, a POM-based catalyst (Coumarin)3HPMo11VO40,
is prepared and used for synthesis of p-ABPs. The mechanism
studies show that this reaction has a cross dehydrogenative
coupling process between BzOH and aniline. This synthesis
strategy provides a new idea for the synthesis of compounds
containing amino functional groups. Further, this synthesis
method does not require protections of highly reactive amino
groups during the reaction, and the synthesis of p-ABPs
compounds increases the possibility of other modification
because of the presence of amino groups.
Scheme 3 Proposed mechanism.
The authors acknowledge the financial support from the Qatar
National Research Fund, Grant Number NPRP8-1292-2-548.
As shown in Scheme 4, a series of p-ABPs were synthesized
with the presence of (Coumarin)3HPMo11VO40, using several
benzyl alcohol and aniline derivatives. The products were then
1
characterized by H NMR, 13C NMR, and 19F NMR, as shown in
Conflicts of interest
the ESI. Unlike other 3a derivatives, compounds 3o and 3u
have larger benzene ring conjugation structures. The amino
group in the compound 3o and 3u can be further modified,
which may be useful in UV absorbers, curing agents, or other
optical devices.25
There are no conflicts to declare.
Notes and references
1.
P. Gautam, M. Dhiman, V. Polshettiwar and B. M.
Bhanage, Green Chem., 2016, 18, 5890-5899.
M. Krause, H. Frederiksen, K. Sundberg, F. S. Jørgensen, L.
N. Jensen, P. Nørgaard, C. Jørgensen, P. Ertberg, A. Juul
and K. T. Drzewiecki, Environ. Int., 2017, 110, 51-60.
M. Aydin, G. Temel, D. K. Balta and N. Arsu, Polym. Bull.,
2015, 72, 309-322.
2.
3.
4.
5.
L. Cheng and W. Shi, Prog. Org. Coat., 2011, 71, 355-361.
R. B. Lal, H. W. Zhang, W. S. Wang, M. D. Aggarwal, H. W.
H. Lee and B. G. Penn, J. Crys. Growth., 1997, 174, 393-
397.
6.
M. Liu, X. Chen, T. Chen, Q. Xu and S. F. Yin, Org. Biomol.
Chem., 2017, 15, 9845-9854.
7.
8.
P. H. Gore, Chem. Rev., 1955, 55, 229-281.
P. Gautam and B. M. Bhanage, Cheminform, 2015, 80,
7810-7815.
9.
P. Gautam and B. M. Bhanage, J. Org. Chem., 2015, 80,
7810-7815.
10.
11.
12.
13.
J. P, M. K, L. Z, F. X, U. A, S. Y and L. W, J. Am. Chem. Soc.,
2017, 139, 12234-12242.
S. M. Kelly and B. H. Lipshutz, Cheminform, 2014, 45, 98-
101.
C. Thomas, M. Wu and K. L. Billingsley, Cheminform, 2016,
81, 330.
R. A. Green and J. F. Hartwig, Angew. Chem. Int. Ed., 2015,
54, 3768-3772.
C. J. Li, Accounts of Chemical Research, 2009, 42, 335-344.
I. V. Kozhevnikov, Chem. Rev., 1998, 98, 171-198.
A. M. Khenkin, I. Efremenko, J. M. Martin and R.
Neumann, J. Am. Chem. Soc., 2013, 135, 19304-19310.
Q. Xu, S. Li, M. Katherine Banks, W. Xu and R. Wu, Catal.
Commun., 2018, 114, 24-27.
aReaction conditions:
1 (0.4 mmol), 2 (1 mmol), cat (0.02 mmol)
in DMSO/CH3Cl (1 mL, V/V=1:1) within 8 h. Isolated yields.
Scheme 4 Scope of benzyl alcohol and aniline derivatives.a
In the process of designing catalyst, the coumarin surfactant
with rigid conjugated structure was introduced into the POMs.
Unlike other small molecule and flexible chain surfactants, the
coumarin surfactant cannot enter the empty space of the
POMs easily. Therefore, the modified catalyst has a larger
specific surface and pore size compared to other POM hybrids
with flexible chain surfactants. This catalyst structure can
14.
15.
16.
17.
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18.
19.
20.
M. Tamura and K. Tomishige, Angew. Chem., 2015, 54,
864-867.
L. Geng, J. Song, Y. Zhou, Y. Xie, J. Huang, W. Zhang, L.
Peng and G. Liu, Chem. Commun., 2016, 52, 13495-13498.
X. Wu, Q. Gao, X. Geng, J. Zhang, Y. Wu and A. Wu, Org.
Lett., 2016, 18, 2507.
21.
22.
Y. Chen and Z. Xie, Chin. J. Org. Chem., 2012, 32, 462-471.
Q. Kang, A. Zhuoan Zhao and S. L. You, J. Am. Chem. Soc.,
2007, 129, 1484-1485.
23.
E. Balint, A. Tajti, A. adam, I. Csontos, K. Karaghiosoff, M.
Czugler, P. abranyi-Balogh and G. Keglevich, Beilstein J.
Org. Chem., 2017, 13, 76-86.
24.
25.
X. Ji, D. Li, X. Zhou, H. Huang and G.-J. Deng, Green Chem.,
2017, 19, 619-622.
Z. Li, B. Wu, G. Su and G. Huang, J. Crys. Growth., 1997,
171, 506-511.
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