Solid-supported Pt-catalyzed remote C-H etherification of arylamines: A simple and practical approach for the synthesis of aromatic ethers

Article abstract of DOI:10.1016/j.catcom.2019.105722

A simple and practical approach for a direct remote C-H etherification of arylamines with alcohol is developed herein by using a solid-supported Pt catalyst, hence providing a valuable method for the synthesis of aromatic ethers. The catalyst can easily b

Full text of DOI:10.1016/j.catcom.2019.105722

Catalysis Communications 129 (2019) 105722
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Short communication
Solid-supported Pt-catalyzed remote C-H etherification of arylamines: A
simple and practical approach for the synthesis of aromatic ethers
⁎
Junfen Han, Guodong Wang, Jian Sun, Hongshuang Li, Guiyun Duan, Furong Li, Chengcai Xia
Pharmacy College, Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, China
A R T I C L E I N F O
A B S T R A C T
Keywords:
A simple and practical approach for a direct remote C-H etherification of arylamines with alcohol is developed
herein by using a solid-supported Pt catalyst, hence providing a valuable method for the synthesis of aromatic
ethers. The catalyst can easily be recovered from the reaction mixture and reused for six times without apparent
loss of activity. Control experiments suggest that a radical pathway is involved in this transformation.
Solid-supported catalyst
Pt catalyst
Etherification
Arylamines
Aromatic ethers
1
. Introduction
which led researchers to develop more valuable catalytic systems for
remote CeH etherification.
Aromatic ethers are an important class of compounds that widely
In recent years, the development of heterogeneous catalysts for CeH
functionalization is highly desirable because of the potential ad-
vantages such as the easy removal of catalyst from the reaction mixture
and the possibility to reuse the catalysts [23–27]. In particular, the
generation of CeO bond by heterogeneously catalyzed CeH functio-
nalization is increasingly significant. In 2015, the Cohen et al. reported
a CeH bond etherification of benzo[h]quinoline using a metal-organic
framework-supported Pd catalyst [25]. Subsequently, Ellis et al. de-
monstrated a CeH bond etherification of benzo[h]quinoline with a
multiwall carbon nanotube-supported Pd catalyst [26]. These works
prove the feasibility of developing heterogeneous catalytic systems for
the synthesis of aromatic ethers.
exist in pharmaceuticals, natural products and novel materials (Scheme
a) [1–3]. Therefore, there has been an increasingly urgent need for the
1
development of simple and practical approaches for the synthesis of
aromatic ethers. The traditional access to these compounds needs the
utilization of pre-functionalized starting materials, such as aromatic
boric acid or halides, which leads to the generation of stoichiometric
wastes [4,5]. To meet the requirements of step- and atom-economy, a
transition-metal-catalyzed C-H functionalization strategy has recently
been one of the most efficient and straightforward alternatives. In this
strategy, the N-containing directing groups including pyridine, triazole,
nitroso, oxime, cyano, N-methoxy amide, (pyridin-2-yl)isopropyl amine
and 8-aminoquinoline are commonly used to make the formation of the
CeO bond more feasible [6–9].
Recently, our research interests focus on the development of novel
strategies for the modification of arylamines assisted by PA [13,17]. In
addition, we have achieved selective CeH monomethoxylation and
trimethoxylation of 8-aminoquinoline [28]. Depending on this back-
ground, we reported solid-supported platinum-catalyzed remote CeH
etherification of arylamines, providing a simple and practical approach
for the synthesis of aromatic ether (Scheme 1c). To the best of our
knowledge, this methodology has not yet been achieved.
Since the pioneering investigation of Daugulis et al. [10], picoli-
namide (PA) has become one of the commonly used N-containing di-
recting groups for the modification of arylamines through CeH func-
tionalization [11–20]. By using this strategy, CeC, CeN, and CeS bond
formation has already been into use thus far and has had a major impact
in the area of organic synthesis. By contrast, the use of the CeO bond
formation reaction remains scarce. In 2018, Punniyamurthy et al.
achieved Cu-catalyzed peri CeH etherification of naphthylamine
through the oxidative addition-reductive elimination mechanism
2. Results and discussion
(
Scheme 1b, 1) [21]. Very recently, Zhang et al. reported a homo-
We started the experiment with reaction of amide (1a), with PhI
geneous Pt-catalyzed CeH methoxylation of arylamines through a ra-
dical mechanism (Scheme 1b, 2) [22]. Despite these considerable ad-
vances, the metal catalysts used in these reactions are unrecoverable,
(OAc)
using Pd/SiO
yield (Table 1, entry 1). Subsequently, other catalysts such as Pt/SiO
2
as the oxidant in methanol (MeOH) at room temperature by
2
as a catalyst; the target product 2a was generated in 29%
2
,
⁎
Corresponding author.
E-mail address: xiachc@163.com (C. Xia).
https://doi.org/10.1016/j.catcom.2019.105722
Received 21 January 2019; Received in revised form 4 June 2019; Accepted 5 June 2019
Available online 07 June 2019
1566-7367/ © 2019 Elsevier B.V. All rights reserved.

J. Han, et al.
Catalysis Communications 129 (2019) 105722
Scheme 1. Examples of important aromatic ethers (a); previous works (b); our strategy (c)
Ru/SiO
that, the yield of product 2a was improved to 69% when Pt/SiO
used as the catalyst (Table 1, entry 2). No desirable product was ob-
2
, and Cu/SiO
2
were studied (Table 1, entries 2–4). We found
tried to determine a better directing group for the synthesis of aromatic
ethers (Table 2). Therefore, some aromatic amides, which were syn-
thesized by the amidation of 1-naphthylamine with various aromatic
carboxylic acids, were used as reactants. We found that the substrate
with a PA group could be converted to product 2a in 81% yield, and
substrates with other N-containing directing groups were transformed
into corresponding products (2b–f) in lower yields. In addition, sub-
strates without N-containing directing group (2g and 2h) showed no
reactivity under standard conditions. These results suggested that the N
atom of pyridine moiety played a significant role in this transformation.
Finally, we chose PA as the directing group for this reaction.
2
was
served by adding only SiO powder into the reaction mixture, which
2
indicated that the transition metals played an important role in this
transformation (Table 1, entry 5). Presently, the synthesis of hyperva-
lent iodine reagent has been well studied; it could be generated in situ
from aryl iodide in the presence of an oxidant [29]. Therefore, some
aryl iodides and oxidants were investigated. First, when iodobenzene
was used as the additive, some oxidants such as K
2
S
2
O
8
, meta-chlor-
operbenzoic acid (m-CPBA), t-butylhydroperoxide (TBHP), H
2 2
O
, and
AcOOH were studied, and only m-CPBA and AcOOH could promote the
reaction, resulting in target product 2a in 31% and 59% yield, re-
spectively (Table 1, entries 6–11). After determining the optimal oxi-
dant, we further studied the additives (Table 1, entries 12–16) and
found that higher yield of product 2a was obtained when 1-iodo-4-
methylbenzene was employed as the additive (Table 1, entry 13).
Further studies in reaction temperature and atmosphere did not en-
hance the product yield (Table 1, entries 17 and 18). It is worth noting
Subsequently, a variety of aromatic amides with different sub-
stituent groups were studied (Table 3). Amide derivatives bearing dif-
ferent functional groups could undergo the methoxylation reaction
smoothly, providing corresponding products in moderate to good
yields. The electronic effect has little effect on this reaction; for ex-
ample, compared with halo- and phenyl-substituted amide derivatives
(2k, 2l, 2o, 2p), methyl, methoxyl, and nonsubstituted amide deriva-
tives (2i, 2j, 2m, 2n, 2q) could afford the target products in higher
yields. In addition, the reactivity of phenylamine derivatives (2m–q)
was relatively lower than that of naphthylamine derivatives (2i–l). Si-
milarly, ethoxylation reaction could also be performed efficiently when
that the reaction also proceeds well when PtCl was used as the catalyst.
2
This result proved that Pt was the catalytic species (Table 1, entry 19).
After determining the optimal reaction conditions, we subsequently
2

J. Han, et al.
Catalysis Communications 129 (2019) 105722
Table 1
a
Screening of reaction conditions .
Entry
Catalyst
Pd/SiO
Additive
Oxidant
Yield [%]b
1
2
3
4
5
6
7
8
9
2
2
–
–
–
–
–
–
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
PhI(OAc)
–
2
2
2
2
2
29
Pt/SiO
69
Ru/SiO
2
2
trace
trace
0
Cu/SiO
SiO
2
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
Pt/SiO
2
0
2
2
2
2
2
2
2
2
2
2
2
2
C
C
C
C
C
C
6
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
I
I
I
I
I
K
2
S
2
O
8
trace
31
m-CPBA
TBHP
trace
trace
59
10
11
12
13
14
15
16
17
18
19
2 2
H O
AcOOH
AcOOH
AcOOH
AcOOH
AcOOH
AcOOH
AcOOH
AcOOH
AcOOH
F
5
I
22
4-Me-C
6
H
4
I
81
4-Br-C
4-F-C
6
H
H
4
I
65
6
4
I
43
4-MeO-C
6
H
4
I
I
70
c
d
4-Me-C
4-Me-C
4-Me-C
6
6
6
H
H
H
4
4
4
79
I
I
80
PtCl
2
82
a
b
c
Reaction conditions: 1a (0.2 mmol), catalyst (loading 1 mol%), additive (0.2 equiv.), oxidant (2 equiv.), MeOH (1 mL), stirred at room temperature for 12 h.
Isolated yields.
d
Stirred at 70 °C. Under N
2
atmosphere.
Table 2
a
Investigation of the directing group .
a
Reaction conditions: 1 (0.2 mmol), Pt/SiO
2
(loading 1 mol%), 4-Me-C
H
6 4
I (0.2 equiv.), AcOOH (2 equiv.), CH OH (1 mL), stirred at room temperature for 12 h,
3
isolated yields. b gram-scale synthesis (5 mmol of 1a was used).
methanol (CH
3
OH) was replaced by ethanol (CH
3
CH
2
OH), giving the
generated in 82% yield, highlighting that this method is a useful tool for
the synthesis of deuterated compounds, which is common in new
pharmaceuticals. Unfortunately, the reaction could not occur when
corresponding products (2r–w) in moderate to good yields. When
deuterated methanol was employed as the solvent, product 2× was
3

J. Han, et al.
Catalysis Communications 129 (2019) 105722
Table 3
a
Substrate scope .
a
Reaction conditions: 1 (0.2 mmol), Pt/SiO
2
(loading 1 mol%), 4-Me-C
6 4
H I (0.2 equiv.), AcOOH (2 equiv.), ROH (1 mL), stirred at room temperature for 12 h, isolated
b
yields. Stirred at 70 °C.
isopropanol ((CH
3
)
2
CHOH), hexafluoroisopropanol ((CF
3
)
2
CHOH), or
if TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) (Scheme 3b) or DPE
(1,1-diphenyl ethylene) (Scheme 3c) was used as the radical inhibitor.
Furthermore, adduct (II) was detected by high-resolution mass spec-
trometry (HRMS). These results suggest that a radical pathway is in-
volved in the reaction. The kinetic isotope effect experiment was also
performed; the low ratio (k = 1.14) indicated that the OeH bond
cleavage process was not the rate-determining step (see Supporting
Information, Scheme S1). In addition, the reaction with the solution
after hot filtration at approximately 50% yield essentially stopped,
strongly suggesting that the active catalytic species exist in the het-
erogeneous substance (Fig. S1) [30]. This conclusion is strengthened by
the Hg(0) poisoning test (Scheme 3d). After this, the reaction kinetics
were measured. It was observed that similar plots were obtained for the
reactions under different stirring speeds (Fig. S2).
phenol (PhOH) was used as the solvent and reactant. We suspected that
the large steric hindrance of these reactants prevented this transfor-
mation.
Then, gram-scale synthesis was performed, resulting in the final
product 2a in 73% yield (Table 2). This result demonstrated that this
method has potential application prospect in organic synthesis. Fur-
thermore, the application value of the solid-supported Pt catalyst was
emphasized by its facile recovery and reuse after the reaction. Even
after performing six times of recycling experiments, the catalytic ac-
tivity of the solid-supported Pt catalyst remained stable (Scheme 2).
The reaction mechanism was subsequently investigated (Scheme 3).
First, some analogues (1n–p) of substrate 1a were employed as the
starting material. However, no product was obtained. This result fur-
ther indicated that the N of pyridine and amide group with free NH was
indispensable in this reaction (Scheme 3a). The reaction was suppressed
Finally, a possible mechanism for the reaction of solid-supported Pt-
catalyzed remote CeH etherification of arylamines was proposed
4

J. Han, et al.
Catalysis Communications 129 (2019) 105722
Scheme 2. Recycling and reuse of the catalyst Pt/SiO
2
Scheme 4. Plausible mechanism
Scheme 3. Investigation of the mechanism
5

J. Han, et al.
Catalysis Communications 129 (2019) 105722
pressure. Product 2 was purified by flash column chromatography using
II
(
Scheme 4) [16–20,22]. First, substrate 1a coordinated with Pt /SiO
2
to form complex (A) in the presence of AcOOH. Subsequently, complex
PE/EtOAc as an eluent.
(
A) was converted to complex (B) through the single-electron transfer
process between amide and the solid-supported Pt catalyst. Further,
methoxyl radical (C) was generated from methanol in the presence of
the in situ-formed hypervalent iodine reagent, which attacked complex
4.4. General procedure for the gram-scale synthesis of product 2a
Amide 1 (5 mmol), Pt/SiO
2
(loading 1 mol%), 4-Me-C
6
H I (0.2
4
(
B) to produce complex (D). After the generation of complex (E)
equiv.), AcOOH (2 equiv.), and ROH (20 mL) were added into a reac-
tion flask. The mixture was then stirred for 12 h at room temperature.
After the conversion was completed, the catalyst was filtered off and the
filtrate was poured into water (50 mL), extracted with EtOAc
through deprotonation of complex (D), the final product 2a was ob-
tained through a metal dissociation process.
3
. Conclusion
(25 mL × 3), and dried with Na
2
SO , and the solvent was removed
4
under reduced pressure. Product 2a was purified by flash column
In summary, we have demonstrated a solid-supported Pt-catalyzed
chromatography using PE/EtOAc as an eluent.
strategy for direct remote CeH etherification of arylamines by using
alcohol as an alkoxy source, thereby producing desirable products in
moderate to good yields. This methodology provided a useful tool for
the efficient synthesis of aromatic ethers. Control experiments sug-
gested that there was a radical pathway underlying this reaction.
4.5. Catalyst recycling experiment
Amide 1a (0.2 mmol), Pt/SiO
2
(loading 1 mol%), 4-Me-C
6
H
4
I (0.2
equiv.), AcOOH (2 equiv.), and CH
3
OH (1 mL) were added into a re-
action tube. The mixture was then stirred for 12 h at room temperature.
After conversion was completed, the catalyst was filtered off, washed
with ethyl acetate and water twice, and then dried for 12 h at 65 °C.
Then, the catalyst was reused for the subsequent reaction.
4
. Experimental section
4.1. General information
All the chemicals were obtained commercially and used without any
4.6. General procedure for radical suppression experiment
prior purification. All products were isolated by short-column chro-
matography on a silica gel (200–300 mesh) using petroleum ether
Following the synthetic procedure for product 2a, the reaction of
1
13
(
60–90 °C) and ethyl acetate. H and C NMR spectra were recorded
amide 1a (0.2 mmol) was performed in the presence of Pt/SiO (loading
2
using a Bruker Advance 500 spectrometer at ambient temperature, with
1 mol%), 4-Me-C
6
H
4
I (0.2 equiv.), AcOOH (2 equiv.), and TEMPO or
CDCl
3
as the solvent and tetramethylsilane as the internal standard.
DPE (2 equiv.) in CH
3
OH (1 mL) for 12 h at room temperature.
TEM tests were performed using a JEOL transmission electron micro-
scope. Elemental information was recorded by X-ray photoelectron
4.7. General procedure for mercury poisoning experiment
spectroscopy (XPS). The Pt content of Pt/SiO was determined using an
2
inductively coupled plasma optical emission spectrometer (ICP-OES)
Following the synthetic procedure for product 2a, the reaction of
(
(
Shimadzu, OPTIMA 2100 DV). Analytical thin-layer chromatography
TLC) was performed using Merck precoated TLC (silica gel 60 F254
amide 1a (0.2 mmol) was performed in the presence of Pt/SiO (loading
2
)
1 mol%), 4-Me-C
6
H I (0.2 equiv.), AcOOH (2 equiv.), and mercury
4
plates.
(60 mg) in CH OH (1 mL) for 12 h at room temperature.
3
4.2. Catalyst preparation and characterization
Acknowledgments
The Pt/SiO catalyst was prepared according to a modified litera-
2
This work was supported by the Shandong Provincial Natural
Science Foundation (ZR2017LB006) and Science Foundation of
Educational Commission of Shandong Province of China (J17KA248).
ture procedure [31,32]. H PtCl ·6H O (85 mg) was dissolved in dis-
2
6
2
tilled water (5 mL) under ultrasonication for 15 min in a beaker. A
homogeneous solution was obtained. Then, other reagents such as
ethanol (20 mL) and tetraethyl orthosilicate (20.8 g) were added to the
solution under vigorous stirring. Then, the mixture was stirred at 338 K
until a solid gel was obtained. After aging at room temperature for 12 h,
the obtained xerogel was dried at 343 K for 6 h, 373 K for 6 h, and 393 K
for 4 h. Finally, the catalyst precursor was calcined at 673 K in air for
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.catcom.2019.105722.
4
h to obtain the final catalyst. Pd/SiO
2
, Ru/SiO
2
, and Cu/SiO
2
were
References
also prepared in the same way as that for Pt/SiO
2
. The Pt/SiO
2
catalyst
was characterized before and after the reaction by Brunauer–-
[1] S. Enthaler, A. Company, Chem. Soc. Rev. 40 (2011) 4912.
[
[
[
[
2] S. Ohkawa, K. Fukatsu, S. Miki, T. Hashimoto, J. Sakamoto, T. Doi, Y. Nagai,
T. Aono, J. Med. Chem. 40 (1997) 559.
Emmett–Teller (BET) surface area analysis (Table S1). The dispersion of
the Pt/SiO catalyst before and after the reaction was observed by
2
3] R. Takise, R. Isshiki, K. Muto, K. Itami, J. Yamaguchi, J. Am. Chem. Soc. 139 (2017)
3340.
transmission scanning electron microscopy (TEM) (Fig. S3), where no
significant changes were observed. The Pt content was found to be
4] C. Sambiagio, S.P. Marsden, A.J. Blackera, P.C. McGowan, Chem. Soc. Rev. 43
(
2014) 3525.
0
.5%, which was determined using an ICP-OES. XPS showed that Pt
5] J.F. Hartwig, Nature 455 (2008) 314.
nanoparticles existed as PtO on the SiO
2
support (Fig. S4) [33–35].
[6] Z. Chen, B. Wang, J. Zhang, W. Yu, Z. Liu, Y. Zhang, Org. Chem. Front. 2 (2015)
1
107.
[
[
[
7] L. Ackermann, Chem. Rev. 111 (2011) 1315.
4
.3. General procedure for the synthesis of product 2
8] P.B. Arockiam, C. Bruneau, P.H. Dixneuf, Chem. Rev. 112 (2012) 5879.
9] T.W. Lyons, M.S. Sanford, Chem. Rev. 110 (2010) 1147.
Amide 1 (0.2 mmol), Pt/SiO
2
(loading 1 mol%), 4-Me-C
6
H
4
I (0.2
[10] V.G. Zaitsev, D. Shabashov, O. Daugulis, J. Am. Chem. Soc. 127 (2005) 13154.
[
[
[
11] G. Rouquet, N. Chatani, Angew. Chem. Int. Ed. 52 (2013) 11726.
12] O. Daugulis, J. Roane, L.D. Tran, Acc. Chem. Res. 48 (2015) 1053.
13] C. Xia, K. Wang, G. Wang, G. Duan, Org. Biomol. Chem. 16 (2018) 2214.
equiv.), AcOOH (2 equiv.), and ROH (1 mL) were added into a reaction
tube. The mixture was then stirred for 12 h at room temperature. After
the conversion was completed, the catalyst was filtered off and the
filtrate was poured into water (5 mL), extracted with EtOAc (5 mL × 3),
[14] J. Xu, K. Cheng, C. Shen, R. Bai, Y. Xie, P. Zhang, ChemCatChem 10 (2018) 965.
[
[
15] J. Xu, L. Qiao, J. Shen, K. Chai, C. Shen, P. Zhang, Org. Lett. 19 (2017) 5661.
16] J. Xu, K. Du, J. Shen, C. Shen, K. Chai, P. Zhang, ChemCatChem 10 (2018) 3675.
and dried with Na
2
SO , and the solvent was removed under reduced
4
6

J. Han, et al.
Catalysis Communications 129 (2019) 105722
[
17] G. You, K. Wang, X. Wang, G. Wang, J. Sun, G. Duan, C. Xia, Org. Lett. 20 (2018)
(2015) 5772.
4
005.
[28] G. Wang, J. Han, K. Wang, H. Li, G. Duan, C. Xia, F. Li, Catal. Commun. 114
(2018) 37.
[
[
[
[
[
[
[
18] S. Liang, M. Bolte, G. Manolikakes, Chem. Eur. J. 23 (2017) 96.
19] J.-M. Li, Y.-H. Wang, Y. Yu, R.-B. Wu, J. Weng, G. Lu, ACS Catal. 7 (2017) 2661.
20] H. Zhu, S. Sun, H. Qiao, F. Yang, J. Kang, Y. Wu, Y. Wu, Org. Lett. 20 (2018) 620.
21] S. Roy, S. Pradhan, T. Punniyamurthy, Chem. Commun. 54 (2018) 3899.
22] J. Shen, J. Xu, H. Cai, C. Shen, P. Zhang, Org. Biomol. Chem. 17 (2019) 490.
23] L. Liu, A. Corma, Chem. Rev. 118 (2018) 4981.
[29] X. Wang, J. Gallardo-Donaire, R. Martin, Angew. Chem. Int. Ed. 53 (2014) 11084.
[30] R.H. Crabtree, Chem. Rev. 112 (2012) 1536.
[31] Y. Zhu, F. Zaera, Catal. Sci. Technol. 4 (2014) 955.
[32] R.-P. Ye, L. Lin, C.-Q. Liu, C.-C. Chen, Y.-G. Yao, ChemCatChem 9 (2017) 4587.
[33] S. Oh, S. Back, W.H. Doh, S.Y. Moon, J. Kim, Y. Jung, J.Y. Park, RSC Adv. 7 (2017)
45003.
24] S. Santoro, S.I. Kozhushkov, L. Ackermann, L. Vaccaro, Green Chem. 18 (2016)
3
471.
[34] D. Miller, H.S. Casalongue, H. Bluhm, H. Ogasawara, A. Nilsson, S. Kaya, J. Am.
Chem. Soc. 136 (2014) 6340.
[
[
25] H. Fei, S.M. Cohen, J. Am. Chem. Soc. 137 (2015) 2191.
26] S. Korwar, K. Brinkley, A.R. Siamaki, B.F. Gupton, K.C. Ellis, Org. Lett. 17 (2015)
[35] L. Deng, H. Miura, T. Shishido, S. Hosokawa, K. Teramura, T. Tanaka, Chem.
Commun. 53 (2017) 6937.
1
782.
[
27] S. Vásquez-Céspedes, A. Ferry, L. Candish, F. Glorius, Angew. Chem. Int. Ed. 54
7