Synthesis of unsymmetrically substituted triarylaminesviaacceptorless dehydrogenative aromatization using a Pd/C andp-toluenesulfonic acid hybrid relay catalyst

Article abstract of DOI:10.1039/c9sc06442g

An efficient and convenient procedure for synthesizing triarylamines based on a dehydrogenative aromatization strategy has been developed. A hybrid relay catalyst comprising carbon-supported Pd (Pd/C) andp-toluenesulfonic acid (TsOH) was found to be effective for synthesizing a variety of triarylamines bearing different aryl groups starting from arylamines (diarylamines or anilines), using cyclohexanones as the arylation sources under acceptorless conditions with the release of gaseous H₂. The proposed reaction comprises the following relay steps: condensation of arylamines and cyclohexanones to produce imines or enamines, dehydrogenative aromatization of the imines or enamines over Pd nanoparticles (NPs), and elimination of H₂from the Pd NPs. In this study, an interesting finding was obtained indicating that TsOH may promote the dehydrogenation.

Full text of DOI:10.1039/c9sc06442g

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Synthesis of unsymmetrically substituted triarylamines via acDcOeI: 1p0.t10o39r/lCe9SsC0s6442G
dehydrogenative aromatization using a Pd/C and p-toluenesulfonic acid
hybrid relay catalyst
Satoshi Takayama,a Takafumi Yatabe,a Yu Koizumi,a Xiongjie Jin,b Kyoko Nozaki,b Noritaka Mizunoa
and Kazuya Yamaguchi*a
aDepartment of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan. E-mail: kyama@appchem.t.u-ꢀꢁꢂꢃꢁꢄꢅꢆꢄꢇꢈꢉꢊꢋꢅꢌꢍꢊ+81-3-5841-7220
bDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-8656, Japan.
Abstract
An efficient and convenient procedure for synthesizing triarylamines based on a dehydrogenative aromatization
strategy has been developed. A hybrid relay catalyst comprising carbon-supported Pd (Pd/C) and p-
toluenesulfonic acid (TsOH) was found to be effective for synthesizing a variety of triarylamines bearing
different aryl groups starting from arylamines (diarylamines or anilines), using cyclohexanones as the arylation
sources under acceptorless conditions with the release of gaseous H2. The proposed reaction comprises the
following relay steps: condensation of arylamines and cyclohexanones to produce imines or enamines,
dehydrogenative aromatization of the imines or enamines over Pd nanoparticles (NPs), and elimination of H2
from the Pd NPs. In this study, an interesting finding was obtained indicating that TsOH may promote the
dehydrogenation.
Introduction
Triarylamines are an important class of chemicals that are widely used for synthesizing valuable materials
including polymers, pharmaceuticals, dyes, and natural products.1 In addition, they have been utilized as hole
transport materials for organic electroluminescent devices and dye-sensitized solar cells.2 In general,
triarylamines that are effective as hole transport materials often possess three different aryl groups.2 Such
triarylamines have classically been synthesized by a two-step process in which diarylamines are synthesized
first and then coupled with iodobenzenes by the Ullmann reaction.3 In recent years, triarylamine synthesis by the
Buchwald–Hartwig coupling in the presence of homogeneous Pd catalysts with intricately designed ligands has
become mainstream.4 Although various triarylamines can be produced by these synthetic methods, the use of
haloarenes and the formation of metal halide byproducts are inevitable. Therefore, it is very important to develop
new greener methods that can be used to synthesize triarylamines from various starting materials.
Here, we describe a new strategy for synthesizing unsymmetrically substituted triarylamines based on
dehydrogenative aromatization. Dehydrogenative aromatization has recently emerged as an attractive method
for synthesizing various arenes from ubiquitous saturated six-membered carbocyclic compounds.5 Over the past
few years, various kinds of synthetically useful catalytic reactions employing dehydrogenative aromatization
have been developed, which can be used to effectively access phenols,6 aryl ethers,7 N-substituted anilines,8
biaryls,9 and heterocycles10 (Fig. 1a). Recently, Li and co-workers have developed a dearomatization-
rearomatization strategy in which phenol substrates are once dearomatized followed by reacting with
nucleophiles, and then rearomatized to produce various arene products.11 This dearomatization-rearomatization
strategy has a great potential to be able to utilize biomass-derived phenols for organic synthesis, and is expected
to expand in the future.
1

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Fig. 1) is very inefficient. Furthermore, acceptorless dehydrogenation of the corresponding enamines (step 4 in
DOI: 10.1039/C9SC06442G
Fig. 1) is unknown. In fact, when the reaction between 3-methyldiphenylamine (1a) and 4-ethylcyclohexanone
(2a) was carried out using a commercially available carbon-supported Pd (Pd/C) catalyst, the yield of the desired
unsymmetrically substituted triarylamine 3a was quite low (see Table 1, entry 1, and related discussion). To
realize the effective triarylamine production, acceleration of the condensation and/or the successive
dehydrogenation is very important. We hypothesized that suitable acid co-catalysts promote the reaction. To
examine the feasibility of our hypothesis, we investigated the effect of acid co-catalysts thoroughly. As a result,
we found that various triarylamines could be synthesized from an equimolar mixture of diarylamines and
cyclohexanones using a hybrid relay catalyst comprising Pd/C and p-toluenesulfonic acid (TsOH) (Fig. 1c).
Furthermore, one-pot sequential syntheses of unsymmetrically substituted triarylamines from anilines and two
different cyclohexanones were also successful (Fig. 1c). In the proposed one-pot triarylamine synthesis, the
absence of isolation/purification of the diarylamine intermediates reduces time, cost, effort, and waste generation.
Therefore, the present system has the potential to be an environmentally friendly alternative to cross-coupling
reactions using haloarenes. We revealed that triarylamines are produced via direct dehydrogenation of enamine
intermediates, whereas diarylamines from anilines and cyclohexanones are formed via disproportionation of imine
intermediates. It is worth noting that an interesting finding was obtained indicating that TsOH may promote the
dehydrogenation.
Results and discussion
Reaction between 3-methyldiphenylamine and 4-ethylcyclohexanone
We conducted the reaction between 3-methyldiphenylamine (1a) and 4-ethylcyclohexanone (2a) under various
conditions. Initially, the reaction between 1a and 2a in mesitylene at 160 °C was carried out in the presence of
Pd/C without any co-catalysts. However, the yield of and selectivity to the desired unsymmetrically substituted
triarylamine 3a were unsatisfactory (Table 1, entry 1). We concluded that the condensation between 1a and 2a
did not proceed well, and in order to solve the problem, we performed the reaction in the presence of various
acid or base co-catalysts. As a result, TsOH was identified as a suitable acid co-catalyst. In the presence of Pd/C
(2 mol%) and TsOH (10 mol%), the reaction gave the desired triarylamine 3a in 85% yield after 2 h, and side
products such as the reductive amination product 4a and 4-ethylphenol (5a) were hardly detected (Table 1,
entry 2). It should be noted that the reaction proceeded efficiently with an equimolar mixture of 1a and 2a. It
was confirmed by volumetric measurement and mass spectrometry (MS) analysis of the evolved gas that
approximately two equivalents of H2 gas with respect to 3a were produced during the reaction. Other Brønsted
acid co-catalysts, such as benzoic acid (PhCOOH), trifluoroacetic acid (CF3COOH), and methanesulfonic acid
(CH3SO3H), were less effective (Table 1, entries 3–5). The relatively high solubility of TsOH in mesitylene
compared with the other Brønsted acid co-catalysts tested is considered to be one reason for the effectiveness
of TsOH. For the reaction between 1a and 2a, Lewis acid co-catalysts were ineffective (Table 1, entries 6–10).
Conversely, the direct dehydrogenation of 2a was conspicuously promoted in the presence of base co-catalysts
(especially K2CO3), resulting in the undesirable formation of phenol 5a as the major product (Table 1, entries 11
and 12).15
The choice of support was very significant, and the effect of TsOH was most noticeable when using Pd/C
(Table 1, entry 2). We prepared several supported Pd catalysts using various oxide or hydroxide supports
ꢡꢟꢄꢩꢑꢓꢕꢕꢁꢂꢋꢤꢃ ꢑꢓꢕꢕꢁꢂꢋ = TiO2, Al2O3, CeO2, or Mg6Al2(OH)16CO3‧4H2O (LDH)) and performed the reaction
between 1a and 2a using these catalysts. Although the Pd content and average particle sizes of the Pd NPs in
the Pd/support catalysts were almost the same as those in Pd/C (Fig. S1, Table S1, ESI†), the catalytic
3

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performance of all other Pd/support catalysts was greatly inferior to that of Pd/C (Table 1, entries 13–16). Thus,
DOI: 10.1039/C9SC06442G
it is presumed that the promotion effect of TsOH cannot be fully exhibited when using Pd/support because of
its adsorption on the basic sites of the oxide or hydroxide surface. In particular, when a strong basic support
(LDH) was used, the desired 3a was not produced at all, and the corresponding phenol 5a was obtained as the
major product (Table 1, entry 16).15 Therefore, the use of basic supports is inappropriate for this reaction.
Among the solvents examined, mesitylene yielded the best results (Table S2, entry 1, ESI†), and decane and
diethyleneglycol dimethyl ether (diglyme) also afforded 3a in good yields (Table S2, entries 2 and 3, ESI†). On
the other hand, highly polar solvents such as N,N-dimethylacetamide and N-methylpyrrolidone were not effective
(Table S2, entries 4 and 5, ESI†). When the reaction temperature was examined in the range 130 °C–160 °C, it
was found that the reaction progressed more efficiently as the temperature increased (Table S3, ESI†).
Table 1 Screening of catalysts and co-catalystsa
1a
catalyst
+
mesitylene, 160oC
Ar (1 atm), 2 h
5a
4a
3a
2a
Yield (%)
Entry
Catalyst
Co-catalysts
3a
6
4a
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
13
31
5a
4
1
Pd/C
w/o
2
Pd/C
Pd/C
TsOH
85
7
<1
5
3
PhCOOH
CF3COOH
CH3SO3H
Ti(OiPr)4
Al(OiPr)3
ZnCl2
4
Pd/C
13
20
8
4
5
Pd/C
<1
3
6
Pd/C
7
Pd/C
5
6
8
Pd/C
<1
6
<1
<1
1
9
Pd/C
B(C6F5)3
Sc(O3SCF3)3
Na2CO3
K2CO3
TsOH
10
11
12
13
14
15
16
17
18
19
Pd/C
1
Pd/C
2
7
Pd/C
1
69
<1
<1
1
Pd/TiO2
Pd/Al2O3
Pd/CeO2
Pd/LDH
Ru/C
Rh/C
Pt/C
54
4
TsOH
TsOH
11
<1
3
TsOH
9
TsOH
<1
<1
<1
TsOH
54
39
TsOH
aReaction conditions: Catalyst (metal: 2 mol%), additive (10 mol%), 1a (0.5 mmol), 2a
(0.5 mol%), mesitylene (2 mL), Ar (1 atm), temperature 160 °C, and time 2 h. Yields were
determined by GC and are relative to 1a.
We also examined the reaction between 1a and 2a using supported metal catalysts other than Pd. In the
4

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presence of Ru/C, the reaction hardly proceeded (Table 1, entry 17). Conducting the reaction DinOIt:h1e0.1p0r3e9s/Ce9nScCe06o4f42G
Rh/C or Pt/C afforded 3a in moderate yields along with significant amounts of the reductive amination product
4a (Table 1, entries 18 and 19). Therefore, Pd/C was determined to be the best catalyst for this reaction.
Hereafter, we mainly used the most effective Pd/C and TsOH hybrid relay catalyst under the aforementioned
optimized conditions for further detailed investigations.
To establish whether the observed catalysis of the synthesis of 3a from 1a and 2a occurred heterogeneously
on Pd/C or was a result of the presence of leached Pd species in the reaction solution, the Pd/C catalyst was
removed by hot filtration 1 h after the reaction was started, and the reaction was restarted with the filtrate under
the same conditions. As shown in Fig. S2, ESI†, the production of 3a immediately ceased upon the removal of
Pd/C. Additionally, after the reaction, the filtrate was analyzed using inductively coupled plasma atomic
emission spectroscopy (ICP-AES), and it was found that Pd species were barely detectable (less than 0.09% of
Pd used for the reaction). Consequently, it was concluded that the observed catalysis of the reaction was truly
heterogeneous.16 Furthermore, the Pd/C retrieved after the reaction could be reused for the reaction between 1a
and 2aꢒꢃꢋꢆꢁꢓꢈꢆꢃꢋꢆꢅꢃꢐꢊꢋꢊꢙꢇꢋꢌꢐꢃꢕꢅꢂꢔꢁꢂꢎꢊꢉꢐꢅꢃꢑꢙꢌꢈꢆꢋꢙꢇꢃꢄꢅꢐꢙꢌꢉꢅꢄꢤ a yield of 72% for 3a was obtained with a reused
Pd/C catalyst (Fig. S3, ESI†).
Triarylamine synthesis from diarylamines and cyclohexanones
Under the optimized reaction conditions described above using Pd/C and TsOH, we next examined the scope of
suitable substrates for the proposed triarylamine synthesis from diarylamines and cyclohexanones. The
substrates used in this study are shown in Fig. 2. As summarized in Fig. 3, various kinds of substrate
combinations were converted into the corresponding unsymmetrically substituted triarylamines in moderate-to-
high yields. These reactions (except for the synthesis of 3c and 3g) efficiently proceeded using equimolar
mixtures of diarylamines and cyclohexanones. The desired triarylamine products were readily isolated by simple
column chromatography on silica gel.
Diarylamines
1a
1b
1c
1d
Cyclohexanones
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
Anilines
6d
6a
6b
6c
Fig. 2 Substrates used in this study.
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DOI: 10.1039/C9SC06442G
Pd/C, TsOH
+
mesitylene, 160 oC, Ar (1 atm)
1
2
3
3a (1a+2a, 2 h)
85% (70%)
3b (1a+2b, 2 h)
80% (70%)
3c (1a+2c, 6 h)
3d (1a+2d, 2 h)
73% (76%)
3e (1a+2e, 2 h)
78% (66%)
1%
3f (1a+2f, 2 h)
84% (84%)
3h (1a+2h, 2 h)
31% (32%)
3i (1a+2i, 2 h)
54% (58%)
3j (1b+2a, 2 h)
67% (63%)
3g (1a+2g, 2 h)
2%a
3m (1a+2j,b 18 h)
(51%)
3k (1c+2a, 4 h)
73% (76%)
3l (1d+2a, 6 h)
62% (62%)
Fig. 3 Substrate scope of the proposed triarylamine synthesis from diarylamines and cyclohexanones using a
Pd/C and TsOH hybrid relay catalyst. Reaction conditions: Pd/C (2 mol%), TsOH (10 mol%), 1 (0.5 mmol), 2
(0.5 mmol), mesitylene (2 mL), Ar (1 atm), and temperature 160 °C. Yields are relative to 1. GC yields and
isolated yields (values in parentheses) are shown. In all cases, phenol side products 5 were hardly detected.
b
aElimination of the methoxy group occurred during the reaction, giving 3e as the major product (35%). 1a
(1.0 mmol), 2j (0.5 mmol).
Cyclohexanone (2e) and its derivatives with alkyl groups at the 3- or 4-position (2a, 2b, and 2d) smoothly
reacted with diarylamine 1a, affording the corresponding triarylamine derivatives in high yields (3a, 3b, 3d,
and 3e). Unfortunately, the use of 2-methylcyclohexanone (2cꢣꢃꢊꢑꢃꢋꢆꢅꢃꢊꢂꢇꢙꢊꢋꢌꢁꢉꢃꢑꢁꢓꢂꢐꢅꢃꢚꢊꢑꢃꢄꢌꢔꢔꢌꢐꢓꢙꢋꢤꢃꢔꢁꢂꢃꢋꢆꢅꢃ
reaction between 1a and 2c, the desired triarylamine 3c was hardly produced. We speculated that if there is a
substituent at the 2-position, the steric hindrance of the cyclohexene ring to be dehydrogenated will increase,
thus impeding the access of the enamine intermediate to the Pd NP surface. However, if a substituent is
introduced at the 2-position of aniline in advance, it is possible to synthesize triarylamines bearing a substituent
at the 2-position such as 3c, as discussed in more detail later.
By using tetrahydronaphthalenone (2f), it was possible to introduce a naphthalene skeleton into the
diarylamine (3f). When using 4-methoxycyclohexanone (2g) as the arylation source, an undesirable elimination
of the methoxy group occurred during the aromatization step, giving 3e as the major product. In order to
synthesize triarylamines bearing a methoxy group such as 3g, it is indispensable to introduce the methoxy group
into the aniline in advance, as discussed in more detail later. Cyclohexanones bearing an amide (2h) or an ester
group (2i) were tested with the proposed system, affording the corresponding triarylamines in moderate yields
6

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(3h and 3i). Diphenylamine (1b) and naphthylphenylamines (1c and 1d) also worked well asDrOeIa: 1c0t.i1o03n9/pCa9rStCn0e6r4s42G
of 2a, affording the corresponding triarylamines in good yields (3j, 3k, and 3l). It is noteworthy that TPD (3m),
which is a highly valuable hole transport material for organic electroluminescent devices,2 was readily
synthesized from 1a and bis(4-cyclohexanone) 2j (1a:2j = 2:1) utilizing the proposed method.
One-pot triarylamine synthesis from anilines and two different cyclohexanones
In this section, we describe our attempts to develop a one-pot triarylamine synthesis from anilines and two
different cyclohexanones. As discussed in the previous section, it was found that various triarylamines can be
synthesized from diarylamines and cyclohexanones using a Pd/C and TsOH hybrid relay catalyst. Therefore, we
first investigated whether the hybrid relay catalyst could be applied to selective diarylamine synthesis (1a) from
3-methylaniline (6a) and cyclohexanone (2e) under the optimized conditions for triarylamine synthesis from
diarylamines and cyclohexanones. As shown in Fig. 4, in the presence of Pd/C and TsOH, an equimolar mixture
of 6a and 2e selectively converted to the desired diarylamine 1a in 82% yield without formation of the reductive
amination product N-cyclohexylaniline 7a as well as triarylamine 3e. Under these conditions, 2e (arylation
source) was not present during the reaction because the consecutive reaction of condensation between 6a and
2e and disproportionation of the corresponding imine (8e) was completed immediately (within a few minutes)
after the reaction started, as mentioned later in detail. Therefore, even if the reactions between anilines and
cyclohexanones are carried out under the same conditions as used for triarylamine synthesis, diarylamines are
selectively obtained without producing triarylamines because there are no arylation sources. This facilitates a
very simple one-pot triarylamine synthesis, i.e., after completion of the first reaction between an aniline and a
cyclohexanone, it is only necessary to add a cyclohexanone as the second arylation source without isolation of
the diarylamine intermediate or changing any reaction conditions, which reduces time, cost, effort, and waste
generation.
The effect of TsOH on the reaction between 6a and 2e was crucial. When using Pd/C and TsOH, the reaction
exclusively yielded 1a after 18 h. On the other hand, in the absence of TsOH, the desired diarylamine 1a was
only obtained in 48% yield together with the formation of 7a in 41% yield under the same conditions (Fig. 4).
Therefore, in the reaction between 6a and 2e, TsOH likely promotes the condensation to some extent but is
considered to be more important in promoting the Pd-catalyzed dehydrogenative aromatization of 7a to 1a, as
discussed later.
ꢀ
ꢁ
Pd/C
mesitylene, 160 oC
Ar (1 atm), 18 h
6a
2e
+
1a
7a
3e
with TsOH
w/o TsOH
82%
48%
<1%
41%
<1%
<1%
Fig. 4 Effect of TsOH on the reaction between 3-methylaniline (6a) and cyclohexanone (2e). Reaction
conditions: Pd/C (2 mol%), TsOH (10 mol%), 6a (0.5 mmol), 2e (0.5 mmol), mesitylene (2 mL), Ar (1 atm),
temperature 160 °C, and time 18 h. Yields are relative to 6a and were determined by GC.
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Several results of the proposed one-pot triarylamine synthesis are summarized in Fig. 5D. OWI:e10s.1u0c39c/eCs9sSfCu0l6l4y42G
synthesized triarylamines with alkyl substituents at the 3- or 4-position of the phenyl rings in good yields (3a,
3b, and 3d). These triarylamines could be synthesized even if the order in which the aryl groups are introduced
is changedꢤꢃꢔꢁꢂꢃꢅꢦꢊꢎꢕꢙꢅꢒꢃ3a was obtained in 65% yield using 2a as the first arylation source (18 h) and 2e as the
second arylation source (4 h) under the conditions in Fig. 5. Regarding the synthesis of triarylamines bearing
substituents at the 2-position of the phenyl rings, which was impossible in the previous section, for example, by
starting from 2-methylaniline (6b) and sequentially introducing aryl groups into it, the desired triarylamine 3c
was synthesized in high yield using the developed one-pot synthesis. The new one-pot synthesis was also
effective at introducing substituents that ꢋꢅꢉꢄꢃꢋꢁꢃꢠꢅꢃꢅꢙꢌꢎꢌꢉꢊꢋꢅꢄꢃꢌꢉꢋꢁꢃꢋꢆꢅꢃꢊꢉꢌꢙꢌꢉꢅꢃꢑꢓꢠꢑꢋꢂꢊꢋꢅꢃꢌꢉꢃꢊꢄꢍꢊꢉꢐꢅꢤꢃfor example,
triarylamine 3g, which could not be successfully synthesized using 4-methoxycyclohexanone (2g) as the
arylation source, was obtained in high yield by utilizing 4-methoxyaniline (6c) as the starting material and 2e
and 2b as the arylation sources. A triarylamine bearing a fluoro group (3n) was also synthesized.
first step
second step
2
2
Pd/C, TsOH
mesitylene, 160 oC
Ar (1 atm)
Pd/C, TsOH
mesitylene, 160 oC
Ar (1 atm)
6
3
3c (6b+2e+2ba)
79% (62%)
3b (6a+2e+2b)
3a (6a+2e+2a)
81%
84%
ꢂ
ꢁ
ꢃꢄ
3d (6a+2d+2e)
3g (6c+2e+2b)
86% (74%)
3n (6d+2e+2a)
65%
63%
Fig. 5 Substrate scope of the proposed one-pot triarylamine synthesis from anilines and two different
cyclohexanones using a Pd/C and TsOH hybrid relay catalyst. Reaction conditions: (first step) Pd/C (2 mol%),
TsOH (10 mol%), 6 (0.5 mmol), 2 (0.5 mmol), mesitylene (2 mL), Ar (1 atm), temperature 160 °C, and time
18 h. (second step) After the first step, 2 (0.55 mmol) was added to the reaction mixture, and the reaction was
continued for further 2 h under the same conditions. Yields are relative to 6. GC yields and isolated yields
(values in parentheses) are shown. In all cases, phenol side products 5 were hardly detected. a8 h for the second
step.
Reaction pathways
In this section, the reaction pathways of the proposed triarylamine synthesis are discussed in detail. To begin
with, the first step involving the reaction between anilines and cyclohexanones (steps 1 and 2 in Fig. 1c) was
examined. As can be seen from the time course of the reaction between 6a and 2e in the presence of Pd/C and
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ꢞꢑꢪꢛꢃꢡꢀꢌꢈꢗ ꢳꢊꢣꢒꢃꢋꢆꢅꢑꢅꢃꢑꢓꢠꢑꢋꢂꢊꢋꢅꢑꢃꢚꢅꢂꢅꢃꢐꢁꢎꢕꢙꢅꢋꢅꢙꢇꢃꢐꢁꢉꢑꢓꢎꢅꢄꢃꢌꢎꢎꢅꢄꢌꢊꢋꢅꢙꢇꢃꢊꢔꢋꢅꢂꢃꢋꢆꢅꢃꢑꢋꢊꢂꢋꢃꢁꢔDꢃꢋOꢆI:ꢅ1ꢃ0ꢂ.ꢅ10ꢊ3ꢐ9ꢋ/ꢌCꢁ9ꢉSꢃCꢊ0ꢉ64ꢄ4ꢃ2G
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ꢄꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃ ꢡꢄꢋꢣꢃ ꢌꢉꢃ ꢆꢌꢈꢆꢃ ꢇꢌꢅꢙꢄꢃ ꢓꢉꢄꢅꢂꢃ ꢋꢆꢅꢃ ꢑꢊꢎꢅꢃ ꢐꢁꢉꢄꢌꢋꢌꢁꢉꢑꢃ ꢌꢉꢃ ꢋꢆꢅꢃ ꢕꢂꢅꢑꢅꢉꢐꢅꢃ ꢁꢔꢃ ꢟꢄꢩꢴꢃ ꢊꢉꢄꢃꢞꢑꢪꢛꢃ ꢡꢀꢌꢈꢗ ꢵꢊꢣꢗꢃ
ꢟꢂꢅꢍꢌꢁꢓꢑꢙꢇꢒꢃꢚꢅꢃꢆꢊꢍꢅꢃꢂꢅꢕꢁꢂꢋꢅꢄꢃꢋꢆꢊꢋꢃꢐꢝꢐꢇꢐꢙꢁꢆꢅꢦꢇꢙꢌꢄꢅꢉꢅꢠꢅꢉꢏꢅꢉꢊꢎꢌꢉꢅꢃꢡꢌꢎꢌꢉꢅꢃꢇꢋꢣꢃꢚꢊꢑꢃꢑꢎꢁꢁꢋꢆꢙꢇꢃꢐꢁꢉꢍꢅꢂꢋꢅꢄꢃꢋꢁꢃꢊꢃꢥꢶꢜꢃ
ꢎꢌꢦꢋꢓꢂꢅꢃꢁꢔꢃꢄꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃꢊꢉꢄꢃꢐꢝꢐꢇꢐꢙꢁꢆꢅꢦꢇꢙꢊꢉꢌꢙꢌꢉꢅꢃꢓꢉꢄꢅꢂꢃꢑꢌꢎꢌꢙꢊꢂꢃꢊꢐꢐꢅꢕꢋꢁꢂꢙꢅꢑꢑꢃꢐꢁꢉꢄꢌꢋꢌꢁꢉꢑꢃꢌꢉꢃꢋꢆꢅꢃꢕꢂꢅꢑꢅꢉꢐꢅꢃꢁꢔꢃꢟꢄꢝ
ꢠꢊꢑꢅꢄꢃꢢꢟꢃꢐꢊꢋꢊꢙꢇꢑꢋꢑꢗꢥꢜꢅꢃꢴꢁꢉꢑꢌꢄꢅꢂꢌꢉꢈꢃꢋꢆꢅꢃꢕꢂꢅꢑꢅꢉꢋꢃꢅꢦꢕꢅꢂꢌꢎꢅꢉꢋꢊꢙꢃꢂꢅꢑꢓꢙꢋꢑꢃꢊꢉꢄꢃꢋꢆꢁꢑꢅꢃꢁꢔꢃꢁꢓꢂꢃꢕꢂꢅꢍꢌꢁꢓꢑꢃꢑꢋꢓꢄꢌꢅꢑꢒꢃꢌꢋꢃꢐꢊꢉꢃꢠꢅꢃ
ꢐꢁꢉꢐꢙꢓꢄꢅꢄꢃꢋꢆꢊꢋꢃꢄꢌꢊꢂꢇꢙꢊꢎꢌꢉꢅꢃꢄꢅꢃꢚꢊꢑꢃꢕꢂꢁꢄꢓꢐꢅꢄꢃꢎꢏꢅꢃꢋꢆꢅꢃꢄꢌꢑꢕꢂꢁꢕꢁꢂꢋꢌꢁꢉꢊꢋꢌꢁꢉꢃꢁꢔꢃꢋꢆꢅꢃꢌꢎꢌꢉꢅꢃꢌꢉꢋꢅꢂꢎꢅꢄꢌꢊꢋꢅꢃꢡꢔꢁꢂꢎꢅꢄꢃꢎꢏꢅꢃ
ꢋꢆꢅꢃꢐꢁꢉꢄꢅꢉꢑꢊꢋꢌꢁꢉꢃꢁꢔꢃꢈꢅꢃꢊꢉꢄꢃꢉꢊꢣꢃꢊꢉꢄꢃꢋꢆꢊꢋꢃꢋꢆꢅꢃꢄꢌꢑꢕꢂꢁꢕꢁꢂꢋꢌꢁꢉꢊꢋꢌꢁꢉꢃꢁꢔꢃꢇꢅꢃꢚꢊꢑꢃꢎꢓꢐꢆꢃꢔꢊꢑꢋꢅꢂꢃꢋꢆꢊꢉꢃꢋꢆꢅꢃꢄꢅꢆꢇꢄꢂꢁꢈꢅꢉꢊꢋꢌꢁꢉꢃ
ꢁꢔꢃꢆꢅꢃꢡꢀꢌꢈꢗ ꢳꢠꢣꢗ
ꢀꢁꢂꢃ ꢈ ꢡꢊꢣꢃꢞꢌꢎꢅꢃꢐꢁꢓꢂꢑꢅꢃꢔꢁꢂꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢠꢅꢋꢚꢅꢅꢉꢃꢰꢝꢎꢅꢋꢆꢇꢙꢊꢉꢌꢙꢌꢉꢅꢃꢡꢈꢅꢣꢃꢊꢉꢄꢃꢐꢇꢐꢙꢁꢆꢅꢦꢊꢉꢁꢉꢅꢃꢡꢉꢊꢣꢃꢊꢉꢄꢃꢡꢠꢣꢃꢕꢙꢊꢓꢑꢌꢠꢙꢅꢃ
ꢂꢅꢊꢐꢋꢌꢁꢉꢃ ꢕꢊꢋꢆꢚꢊꢇꢗꢃ ꢷꢅꢊꢐꢋꢌꢁꢉꢃ ꢐꢁꢉꢄꢌꢋꢌꢁꢉꢑꢶꢃ ꢟꢄꢩꢴꢃ ꢡꢜ ꢎꢁꢙꢭꢣꢒꢃ ꢞꢑꢪꢛꢃ ꢡꢥꢸ ꢎꢁꢙꢭꢣꢒꢃ ꢈꢅꢃ ꢡꢸꢗꢹ ꢎꢎꢁꢙꢣꢒꢃ ꢉꢊꢃ ꢡꢸꢗꢹ ꢎꢎꢁꢙꢣꢒꢃ
ꢎꢅꢑꢌꢋꢇꢙꢅꢉꢅꢃꢡꢜ ꢎꢺꢣꢒꢃꢧꢂꢃꢡꢥ ꢊꢋꢎꢣꢒꢃꢊꢉꢄꢃꢋꢅꢎꢕꢅꢂꢊꢋꢓꢂꢅꢃꢥꢳꢸ ꢻꢴꢗ
9

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DOI: 10.1039/C9SC06442G
7b
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Fig. 7 Time courses for the dehydrogenative aromatization of N-cyclohexylaniline (7b) (a) with TsOH or (b)
without TsOH. Reaction conditions: Pd/C (Pd: 2 mol%), TsOH (0 or 10 mol%), 7b (0.5 mmol), mesitylene
(2 mL), 160°C, Ar (1 atm).
The positive effect of TsOH on the dehydrogenation of 7b to 1b was confirmed as follows. The reaction
profiles for the Pd/C-catalyzed dehydrogenation of 7b clearly revealed that the dehydrogenation rate increased
in the presence of TsOH (Fig. 7). Consequently, we conclude that TsOH promotes the rate-limiting amine
dehydrogenation. In acceptorless alcohol dehydrogenation using several metal complexes, it has been reported
that the activation energies of H2 liberation are relatively large and that the key to lowering them is to efficiently
transfer H+ to metal hydride species.17 Therefore, we propose that one possible explanation for the role of TsOH
on amine dehydrogenation is promoting H2 liberation via the reaction between TsOH (H+) and the hydride
species generated on the Pd surface.
10

Page 11 of 16
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DOI: 10.1039/C9SC06442G
ꢀꢁꢂꢃ ꢇ ꢡꢊꢣꢃꢞꢌꢎꢅꢃꢐꢁꢓꢂꢑꢅꢃꢔꢁꢂꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢠꢅꢋꢚꢅꢅꢉꢃꢰꢝꢎꢅꢋꢆꢇꢙꢄꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃꢡꢄꢅꢣꢃꢊꢉꢄꢃꢱꢝꢅꢋꢆꢇꢙꢐꢇꢐꢙꢁꢆꢅꢦꢊꢉꢁꢉꢅꢃꢡꢉꢅꢣꢃ
ꢊꢉꢄꢃꢡꢠꢣꢃꢕꢙꢊꢓꢑꢌꢠꢙꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢕꢊꢋꢆꢚꢊꢇꢗꢃꢷꢅꢊꢐꢋꢌꢁꢉꢃꢐꢁꢉꢄꢌꢋꢌꢁꢉꢑꢶꢃꢟꢄꢩꢴꢃꢡꢜ ꢎꢁꢙꢭꢣꢒꢃꢞꢑꢪꢛꢃꢡꢥꢸ ꢎꢁꢙꢭꢣꢒꢃꢄꢅꢃꢡꢸꢗꢹ ꢎꢎꢁꢙꢣꢒꢃꢉꢅꢃ
ꢡꢸꢗꢹ ꢎꢎꢁꢙꢣꢒꢃꢎꢅꢑꢌꢋꢇꢙꢅꢉꢅꢃꢡꢜ ꢎꢺꢣꢒꢃꢧꢂꢃꢡꢥ ꢊꢋꢎꢣꢒꢃꢊꢉꢄꢃꢋꢅꢎꢕꢅꢂꢊꢋꢓꢂꢅꢃꢥꢳꢸ ꢻꢴꢗ
ꢢꢅꢦꢋꢒꢃꢋꢆꢅꢃꢑꢅꢐꢁꢉꢄꢃꢑꢋꢅꢕꢃꢁꢔꢃꢋꢆꢅꢃꢑꢇꢉꢋꢆꢅꢑꢌꢑꢃꢌꢉꢍꢁꢙꢍꢌꢉꢈꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢠꢅꢋꢚꢅꢅꢉꢃꢄꢌꢊꢂꢇꢙꢊꢎꢌꢉꢅꢑꢃꢊꢉꢄꢃꢐꢇꢐꢙꢁꢆꢅꢦꢊꢉꢁꢉꢅꢑꢃ
ꢡꢑꢋꢅꢕꢑ ꢰꢃꢊꢉꢄꢃꢱꢃꢌꢉꢃꢀꢌꢈꢗ ꢥꢐꢣꢃꢚꢊꢑꢃꢅꢦꢊꢎꢌꢉꢅꢄꢗꢃꢀꢌꢈꢗ ꢼꢊꢃꢑꢆꢁꢚꢑꢃꢋꢆꢅꢃꢋꢌꢎꢅꢃꢐꢁꢓꢂꢑꢅꢃꢔꢁꢂꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢠꢅꢋꢚꢅꢅꢉꢃꢄꢌꢊꢂꢇꢙꢊꢎꢌꢉꢅꢃꢄꢅꢃ
ꢊꢉꢄꢃꢐꢇꢐꢙꢁꢆꢅꢦꢊꢉꢁꢉꢅꢃꢉꢅꢗꢃꢞꢆꢅꢃꢂꢅꢄꢓꢐꢋꢌꢍꢅꢃꢊꢎꢌꢉꢊꢋꢌꢁꢉꢃꢕꢂꢁꢄꢓꢐꢋꢃꢌꢅꢃꢊꢉꢄꢃꢋꢆꢅꢃꢐꢁꢂꢂꢅꢑꢕꢁꢉꢄꢌꢉꢈꢃꢅꢉꢊꢎꢌꢉꢅꢃꢍꢅꢃꢚꢅꢂꢅꢃꢉꢁꢋꢃꢄꢅꢋꢅꢐꢋꢅꢄꢃ
ꢄꢓꢂꢌꢉꢈꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢗꢃꢘꢉꢃꢊꢄꢄꢌꢋꢌꢁꢉꢒꢃꢉꢁꢃꢋꢂꢊꢐꢅꢑꢃꢁꢔꢃꢕꢊꢂꢋꢌꢊꢙꢙꢇꢃꢄꢅꢊꢂꢁꢎꢊꢋꢌꢏꢅꢄꢃꢔꢁꢂꢎꢑꢃꢁꢔꢃꢄꢅꢃꢚꢅꢂꢅꢃꢊꢙꢑꢁꢃꢄꢅꢋꢅꢐꢋꢅꢄꢃꢄꢓꢂꢌꢉꢈꢃꢋꢆꢅꢃ
ꢂꢅꢊꢐꢋꢌꢁꢉꢗꢥꢼꢒꢥꢽꢃ
ꢾꢅꢃ
ꢑꢅꢕꢊꢂꢊꢋꢅꢙꢇꢃ
ꢑꢇꢉꢋꢆꢅꢑꢌꢏꢅꢄꢃ
ꢐꢝꢐꢇꢐꢙꢁꢆꢅꢦꢇꢙꢄꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃ
ꢡꢌꢋꢣꢃ
ꢊꢉꢄꢃ
ꢐꢝꢡꢥꢝ
ꢐꢇꢐꢙꢁꢆꢅꢦꢅꢉꢇꢙꢣꢄꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃ ꢡꢍꢋꢣꢃ ꢊꢉꢄꢃ ꢕꢅꢂꢔꢁꢂꢎꢅꢄꢃ ꢋꢆꢅꢑꢅꢃ ꢂꢅꢊꢐꢋꢌꢁꢉꢑꢃ ꢓꢉꢄꢅꢂꢃ ꢋꢆꢅꢃ ꢑꢊꢎꢅꢃ ꢐꢁꢉꢄꢌꢋꢌꢁꢉꢑꢗꢃ ꢛꢁꢚꢅꢍꢅꢂꢒꢃ ꢋꢆꢅꢃ
ꢔꢁꢂꢎꢊꢋꢌꢁꢉꢃꢁꢔꢃꢋꢂꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃꢚꢊꢑꢃꢉꢁꢋꢃꢁꢠꢑꢅꢂꢍꢅꢄꢃꢚꢆꢅꢉꢃꢓꢑꢌꢉꢈꢃꢌꢋꢃꢊꢑꢃꢋꢆꢅꢃꢑꢓꢠꢑꢋꢂꢊꢋꢅꢗꢃꢧꢑꢃꢔꢁꢂꢃꢋꢆꢅꢃꢂꢅꢊꢐꢋꢌꢁꢉꢃꢁꢔꢃꢍꢋꢒꢃꢊꢙꢋꢆꢁꢓꢈꢆꢃ
ꢋꢆꢅꢃꢆꢇꢄꢂꢁꢙꢇꢑꢌꢑꢃꢁꢔꢃꢍꢋꢃꢌꢉꢌꢋꢌꢊꢙꢙꢇꢃꢕꢂꢁꢈꢂꢅꢑꢑꢅꢄꢃꢋꢁꢃꢔꢁꢂꢎꢃꢄꢋꢃꢊꢉꢄꢃꢉꢊꢒꢃꢋꢂꢌꢕꢆꢅꢉꢇꢙꢊꢎꢌꢉꢅꢃꢡꢎꢏꢣꢃꢚꢊꢑꢃꢔꢌꢉꢊꢙꢙꢇꢃꢁꢠꢋꢊꢌꢉꢅꢄꢃꢌꢉꢃꢈꢁꢁꢄꢃ
ꢇꢌꢅꢙꢄꢃꢡꢀꢌꢈꢗ ꢽꢣꢗꢃꢞꢆꢅꢂꢅꢔꢁꢂꢅꢒꢃꢅꢉꢊꢎꢌꢉꢅꢑꢃꢊꢂꢅꢃꢕꢂꢁꢠꢊꢠꢙꢇꢃꢋꢆꢅꢃꢌꢉꢋꢅꢂꢎꢅꢄꢌꢊꢋꢅꢑꢃꢁꢔꢃꢋꢂꢌꢊꢂꢇꢙꢊꢎꢌꢉꢅꢑꢃꢌꢉꢃꢋꢆꢌꢑꢃꢑꢇꢉꢋꢆꢅꢑꢌꢑꢒꢃꢠꢓꢋꢃꢌꢋꢃꢌꢑꢃ
ꢐꢁꢉꢑꢌꢄꢅꢂꢅꢄꢃꢋꢆꢊꢋꢃꢋꢂꢌꢊꢂꢇꢙꢊꢎꢌꢉꢅꢑꢃꢊꢂꢅꢃꢔꢁꢂꢎꢅꢄꢃꢠꢇꢃꢄꢌꢂꢅꢐꢋꢃꢄꢅꢆꢇꢄꢂꢁꢈꢅꢉꢊꢋꢌꢁꢉꢃꢂꢊꢋꢆꢅꢂꢃꢋꢆꢊꢉꢃꢄꢌꢑꢕꢂꢁꢕꢁꢂꢋꢌꢁꢉꢊꢋꢌꢁꢉꢒꢃꢓꢉꢙꢌꢯꢅꢃꢋꢆꢅꢃ
ꢂꢅꢊꢐꢋꢌꢁꢉꢃꢌꢉꢃꢋꢆꢅꢃꢔꢌꢂꢑꢋꢃꢑꢋꢅꢕꢃꢡꢀꢌꢈꢗ ꢼꢠꢣꢗꢃꢿꢌꢉꢐꢅꢃꢍꢅꢃꢚꢊꢑꢃꢉꢁꢋꢃꢁꢠꢑꢅꢂꢍꢅꢄꢃꢊꢋꢃꢊꢉꢇꢃꢋꢌꢎꢅꢃꢡꢀꢌꢈꢗ ꢼꢊꢣꢒꢃꢌꢋꢃꢌꢑꢃꢕꢂꢅꢑꢓꢎꢅꢄꢃꢋꢆꢊꢋꢃꢋꢆꢅꢃꢄꢌꢂꢅꢐꢋꢃ
ꢄꢅꢆꢇꢄꢂꢁꢈꢅꢉꢊꢋꢌꢁꢉꢃꢔꢂꢁꢎꢃꢍꢅꢃꢋꢁꢃꢎꢅꢃꢌꢑꢃꢍꢅꢂꢇꢃꢔꢊꢑꢋꢗꢃꢧꢋꢃꢕꢂꢅꢑꢅꢉꢋꢒꢃꢊꢙꢋꢆꢁꢓꢈꢆꢃꢋꢆꢅꢂꢅꢃꢌꢑꢃꢉꢁꢋꢃꢅꢉꢁꢓꢈꢆꢃꢅꢦꢕꢅꢂꢌꢎꢅꢉꢋꢊꢙꢃꢅꢍꢌꢄꢅꢉꢐꢅꢒꢃꢌꢋꢃ
ꢑꢅꢅꢎꢑꢃꢕꢁꢑꢑꢌꢠꢙꢅꢃꢋꢆꢊꢋꢃꢞꢑꢪꢛꢃꢊꢐꢐꢅꢙꢅꢂꢊꢋꢅꢑꢃꢋꢆꢌꢑꢃꢄꢅꢆꢇꢄꢂꢁꢈꢅꢉꢊꢋꢌꢁꢉꢗ
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DOI: 10.1039/C9SC06442G
1b
3o
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50
4b
1b
2b
3o
4b
0
0
0.5
1
Time (h)
1.5
2
Fig. 9 Time course for the reaction of N-(1-cyclohexenyl)diphenylamine (9b). Reaction conditions: Pd/C
(2 mol%), TsOH (10 mol%), 9b (0.4 mmol), mesitylene (1.6 mL), 160°C, Ar (1 atm).
Here arises a question why the tertiary amine N-cyclohexyldiphenylamine (4b) did not undergo
dehydrogenation while the secondary amine N-cyclohexylaniline (7b) was dehydrogenated to 1b in Fig. 7. In
the first step reaction, since imines (8) function as good hydrogen acceptors, it appears that diarylamines (1)
and N-cyclohexylanilines (7) are formed by disproportionation (Fig. 6b). Thereafter, the dehydrogenations of 7
produce 8, and eventually, 1 become the major products (Fig. 6b). In contrast, in the second step reaction,
enamines (9) do not act as hydrogen acceptors, so it appears that triarylamines (3) are formed by direct
dehydrogenation (Fig. 8b). We consider that this difference arises because of a steric reasonꢤ the unsaturated
bond in 8 can access the Pd NP surface but that in bulkier 9 is considered difficult. The lack of progress in the
dehydrogenation of 4b is also considered to be caused by a similar steric reason. However, it may be also
possible that 4b contained two aryl groups that the lone pair in nitrogen is very well delocalized to the aryl
groups, causing the Pd cannot efficiently coordinate to the nitrogen to furnish the desired dehydrogenation
process. To clarify this possibility, we separately synthesized N,N-dicyclohexylaniline and performed the
reaction under the conditions described in Fig. 10 using Pd/C and TsOH. The reaction progressed marginally,
affording 4b in 14% yield. In this case, triphenylamine was not detected. Therefore, it may be concluded that
the reason for no reaction of 4b is due to not only the steric reason but also the effect of its lone pair
delocalization. We also found during this work that when the Pd/C and TsOH hybrid relay catalyst was used,
the dehydrogenative aromatization of several tertiary amines, such as N,N-dimethylcyclohexylamine (10a) and
N,N-diethylcyclohexylamine (10b), which are less sterically crowded around the N positions or smaller
delocalization effect than N-cyclohexyldiphenylamine and N,N-dicyclohexylaniline, proceeded effectively,
giving the corresponding anilines (Fig. 10). To the best of our knowledge, this is the first report of
dehydrogenative aromatization of tertiary amines.
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DOI: 10.1039/C9SC06442G
ꢁ
ꢁ
10a
11a (79%)
Pd/C, TsOH
mesitylene, 160 oC
Ar (1 atm), 2 h
10b
11b (69%)
Fig. 10 Dehydrogenative aromatization of N,N-dimethylcyclohexylamine (10a) and N,N-diethylcyclohexylamine
(10b). Reaction conditions: Pd/C (2 mol%), TsOH (10 mol%), 10 (0.5 mmol), mesitylene (2 mL), Ar (1 atm),
temperature 160 °C, and time 2 h. Yields are relative to 10 and determined by GC.
Conclusion
We have successfully developed efficient catalytic procedures for synthesizing triarylamines via acceptorless
dehydrogenative aromatization. In the presence of a Pd/C and TsOH hybrid relay catalyst, various types of
structurally diverse unsymmetrically substituted triarylamines could be synthesized starting from diarylamines
and cyclohexanones. Moreover, a one-pot sequential triarylamine synthesis from anilines and two different
cyclohexanones was also successful. Owing to their practical and environmentally benign nature, we hope that
the catalytic transformations developed in this study will find wide applications in the synthesis of arylamine
derivatives and related compounds. The discovery that this type of dehydrogenation is promoted in the presence
of a suitable Brønsted acid co-catalyst is also very interesting and can be expected to apply to a variety of related
functional transformations, which may be exploited in future synthetic schemes.
Experimental section
Instruments and reagents
Gas chromatography (GC) analyses were performed using a Shimadzu GC-2014 equipped with a flame
ionization detector using an InertCap5 capillary column. GC-MS spectra were recorded using a Shimadzu
GCMS-QP2010 equipped with an InertCap5 capillary column at an ionization voltage of 70 eV. Liquid-state
1
13
nuclear magnetic resonance (NMR) spectra were recorded using a JEOL JNM-ECA-500. H and C NMR
spectra were measured at 500.2 and 125.8 MHz, respectively, using tetramethylsilane as an internal standard
(δ = 0 ppm). ICP-AES analyses were performed using a Shimadzu ICPS-8100. Transmission electron
microscopy observations were performed using a JEOL JEM-2000EX. Column chromatography on silica gel
was performed using a Biotage Isolera system. Elemental analyses for C, H, and N were performed using an
Elementar vario MICRO cube. Pd/C (Lot. No. 217-024030, 217-172450, N.E. CHEMCAT), Ru/C (Lot No. 417-
020160, N.E. CHEMCAT), Rh/C (Lot. No. MCM7367, FUJIFILM Wako Pure Chemical), and Pt/C (Lot No.
117-061210, N.E. CHEMCAT) were commercially available. Al2O3 (KHS-24, Sumitomo Chemical), TiO2 (ST-
01, Ishihara Sangyo Kaisya), CeO2 (544841-25G, Aldrich), ZrO2 (37022, Nacalai Tesque), and
Mg6Al2(OH)16CO3‧4H2O (LDH, Tomita Pharmaceutical Co., Ltd.) were commercially available. Pd/support
catalysts were prepared according to a literature procedure.20 Substrates (except for 4b and 9b) and solvents
were obtained from TCI, Aldrich, Kanto Chemical, FUJIFILM Wako Pure Chemical (reagent grade), or Combi-
blocks, and purified prior to use, if necessary.21 Compounds 4b and 9b were synthesized according to a literature
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DOI: 10.1039/C9SC06442G
procedure.22 N,N-Dicyclohexylaniline was synthesized according to a literature procedure.23
Catalytic reactions
Catalytic reactions were typically carried out according to the following procedure. Pd/C (2 mol%), TsOH
(10 mol%), diarylamine (1, 0.5 mmol), cyclohexanone (2, 0.5 mmol), n-hexadecane (0.1 mmol, internal
standard), mesitylene (2 mL), and a Teflon-coated magnetic stir bar were successively placed into a ~20 mL
Schlenk flask reactor, and then the mixture was stirred at 160 °C under Ar (1 atm). Substrate conversions and
product yields were periodically monitored by GC analysis. For the isolation of the products, the internal
standard was not used. After the reaction, the catalyst was removed by simple filtration and the filtrate was
concentrated by evaporation of the mesitylene solvent. The crude product was subjected to column
chromatography on silica gel (typically using hexane and toluene as an eluent), yielding the pure triarylamine
product. The products were identified by GC-MS, NMR (1H and 13C), and/or elemental analyses. Detection of
H2 in the gas phase was carried out by GC-MS analysis. Quantification of the H2 formed was achieved by
measurement of the volume of evolved gas.
Acknowledgments
We thank Dr. Kento Taniguchi for his help with preliminary experiments. This work was supported in part by
JSPS KAKENHI Grant No. 15H05797 in “Precisely Designed Catalysts with Customized Scaffolding” and
19H02509.
Notes and references
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13 Shi and co-workers recently reported an efficient triarylamine synthesis form nitrobenzenes and
cyclohexanones (8 equivalents with respect to nitrobenzenes) using Pd NPs on N/O-doped carbon.
However, in their system, triarylamines with three different aryl groups cannot be synthesized. See: S. Pang,
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14 Although Li and co-workers recently reported the synthesis of triphenylamine from diphenylamine and 2-
cyclohexen-1-one using O2 as the oxidant, the yield of triphenylamine was low (33%), and the substrate
15

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scope was not mentioned. See: A. Dominguez-Huerta, I. Perepichka and C.-J. Li, ChemSusChem, V2ie0w1A9rt,ic1le2O,nline
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2999.
15 We have recently reported that base co-catalysts efficiently promote the Pd NP-catalyzed dehydrogenation
of cyclohexanones to phenols. See references 6d and 12b.
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18 We consider that the most important role of TsOH in this triarylamine synthesis is to promote
dehydrogenation. In addition, TsOH is also considered to help on the condensation between diarylamines
and cyclohexanones. One referee pointed out that it may be also possible that TsOH could partially
protonate the diarylamines, and that protonated species would be possible to be reduced to partially
dearomatized forms, e.g., some kinds of N-cyclohexylaniline type species, possessing stronger
nucleophilicities than diarylamines.19 However, as mentioned above, such dearomatized forms were not
detected at all during the reaction between 1a and 2a. If such dearomatized forms are the real nucleophiles,
N-cyclohexyldiphenylamines should be formed. However, the corresponding N-cyclohexyldiphenylamine
4a was not detected during the reaction between 1a and 2a, as shown in Fig. 8a. In addition, starting from
N-cyclohexyldiphenylamine 4b, the corresponding triarylamine was not produced at all in the present
system. These results suggest that the role of TsOH pointed out by the referee is less likely to be present.
19 Z. Wang, H. Zemg and C.-J. Li, Org. Lett., 2019, 21, 2302.
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23 C. R. Johnson, M. I. Ansari and A. Coop, ACS Omega, 2018, 3, 10886.
16