An efficient homogeneous gold(I) catalyst for N-alkylation of amines with alcohols by hydrogen autotransfer

Article abstract of DOI:10.1016/j.tet.2014.10.007

A new and highly efficient homogeneous [Ph₃PAuCl]/AgOTf catalytic system was developed in N-alkylation reaction of primary amines with alcohols through a hydrogen autotransfer process. This Au(I) catalytic system shows excellent selectivity for mono-alkylation of primary amines with benzyl alcohol under moderate temperature of 100 °C (only secondary amines as product). The possible mechanism of this hydrogen autotransfer reaction with the catalytic system was proposed.

Full text of DOI:10.1016/j.tet.2014.10.007

Tetrahedron 70 (2014) 8829e8835
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient homogeneous gold(I) catalyst for N-alkylation of amines
with alcohols by hydrogen autotransfer
*
Hongwei Yang, Rongfang Mao, Cuicui Luo, Chunxu Lu, Guangbin Cheng
School of Chemical Engineering, Nanjing University of Science and Technology, Xiaolingwei 200, Nanjing, Jiangsu, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 April 2014
Received in revised form 25 September 2014
Accepted 4 October 2014
Available online 13 October 2014
A new and highly efficient homogeneous [Ph3PAuCl]/AgOTf catalytic system was developed in N-alkyl-
ation reaction of primary amines with alcohols through a hydrogen autotransfer process. This Au(I)
catalytic system shows excellent selectivity for mono-alkylation of primary amines with benzyl alcohol
under moderate temperature of 100 ꢀC (only secondary amines as product). The possible mechanism of
this hydrogen autotransfer reaction with the catalytic system was proposed.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Gold
Homogeneous catalysis
Hydrogen autotransfer
N-alkylation
1. Introduction
transition metals.10 Although these catalysts exhibited good activity
in transfer hydrogenation reactions, they also have some disad-
Amines play an important role in organic synthesis due to their
wide use as synthetic intermediates for the production of phar-
macophores, fine chemicals, agrochemicals, bioactive compounds,
polymers, and dyes.1 With the rapid development of green syn-
thetic chemistry, synthesis of amines from alcohols as green re-
agents have attracted considerable interests.2 However, this
process has been largely restricted to multistep synthesis due to the
weak activity of the hydroxyl group. Thus the hydroxyl group was
generally transformed into a more reactive substituent, such as
halide, carbonyl group, and then afford the corresponding amine
product by N-alkylation of alkyl halides1d,3 and reductive amina-
tion of carbonyl compounds,4 respectively (Scheme 1, pathway 1
and 2). In addition, these organic transformations inevitably lead to
stoichiometric amounts of waste salt (pathway 1) or low selectivity
for mono-alkylation (pathway 2) of primary amines.1a,5
Recently the direct catalytic N-alkylation of amines with alco-
hols, commonly known as ‘the borrowing hydrogen’ or hydrogen
autotransfer reactions,6 has received considerable attention. This
attention arises from its one-step process and environmentally
friendly byproduct (only H2O as a byproduct) (Scheme 1, pathway
3). Several attempts have been carried out to perform this trans-
formation catalyzed by transition-metal complexes, including
complexes of iridium,7 rhodium,8 ruthenium,7a,9 and other
vantages. For example, amine alkylation reactions with Ruthenium
and Rhodium complexes as catalysts require high reaction tem-
perature (>150 ꢀC).11 Ag/Al2O3 as a heterogeneous catalyst shows
poor selectivity for mono-alkylation of primary amines with benzyl
alcohol.12 Thus, the development of an efficient, alternative cata-
lytic system for N-alkylation of amines with alcohols is highly
desirable.
Gold-catalyzed organic transformations13 have received con-
siderable attention in organic synthesis since Bond et al.14 reported
the hydrogenation of olefins over supported gold catalysts in 1973.
In comparison with other transition-metal catalysts, investigations
of gold-catalyzed transfer hydrogenation were very scarce. There
have been a few successful attempts for heterogeneous gold cata-
lyst, showing excellent activity for N-alkylation of amines with
alcohols.1a However, homogeneous gold catalyst for this hydrogen
autotransfer reaction was scarcely reported. Herein we report
a successful example of homogeneous gold(I) complex catalyzing
the hydrogen autotransfer of amines with alcohols under relatively
mild conditions.
2. Results and discussion
2.1. N-alkylation of aniline with benzyl alcohol: optimization
of the reaction conditions
Our investigation started with the reaction of aniline (1a) with
benzyl alcohol (2a) using a catalyst system consisting of Ph3PAuCl
* Corresponding author. Fax: þ86 (25)84303286; e-mail address: gcheng@mail.
njust.edu.cn (G. Cheng).
http://dx.doi.org/10.1016/j.tet.2014.10.007
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

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H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
Scheme 1. Strategies for synthesis of amine with alcohol-based.
(5 mol %), t-BuOK (1.0 equiv), and 1,4-dioxane (2 mL) at 100 ꢀC for
48 h. The desired product 3aa could be obtained in 25% yield (Table
1, entry 1). Addition of additive was studied to improve the catalyst
activity. The yield was not obviously changed by the addition of
Cs2CO3 in a ratio of 1:1 with Ph3PAuCl (Table 1, entry 2), whereas
catalytic activity was considerably promoted by the addition of
AgOTf (Table 1, entry 3, 48% yield). AgOTf alone showed lower re-
activity with 14% yield (Table 1, entry 4). Thus the combination of
Ph3PAuCl and AgOTf was more efficient to this reaction, which
could be ascribed to the major reactive role of Ph3PAuOTf, gener-
ated from Ph3PAuCl and AgOTf.15 Decreasing temperature would
result in a reduction of catalytic activity of Au(I). No desired product
was obtained at 60 ꢀC (Table 1, entry 5), and the yield was only 9%
when reaction temperature increases to 80 ꢀC (Table 1, entry 6). In
order to optimize the reaction condition, the catalyst loading was
screened from 3 mol % to 15 mol %. The results indicated that yield
of 3aa was enhancing with an increased amount of catalyst. The
yield of 3aa was only 37% (Table 1, entry 7) when the catalyst
loading was 3 mol %. By further increasing the catalyst loading to
10 mol %, the yield of 3aa was improved dramatically, and reached
78% (Table 1, entries 8 and 9). But the yield was increased by only 4%
when the catalyst amount was increased from 10 to 15 mol % (Table
1, entries 9e11). So 10 mol % was chosen as the optimized catalyst
loading in consideration of economical efficiency and effectiveness.
In addition, the addition of the base was assumed to further facil-
itate the initial alcohol dehydrogenation. The influence of the base
was also investigated, such as NaOH, KOH, K2CO3, and K3PO4$3H2O
(Table 1, entries 12e15). But these bases couldn’t afford the desired
product in higher yield than that of t-BuOK. Investigations into the
optimum solvent for this reaction suggested that 1,4-dioxane is the
best choice (Table 1, entries 9, 16e19). Various other solvents such
as PhCH3, THF, MeCN, ClCH2CH2Cl show low catalytic activities and
afford no more than 18% yield of product.
2.2. N-alkylation of various amines with benzyl alcohol
With the optimized conditions established, we investigated the
generality of aniline derivatives with benzyl alcohol (2a) in Au(I)
catalytic system (Table 2). Electron-donating substituents have
a positive effect on the reactivity of anilines with benzyl alcohol.
Anilines substituted with electron-donating group eCH3 at the
ortho, para position, eOCH3 at the para position give high yields of
corresponding mono-alkylation of primary aromatic amines (Table
2, entries 1e3). The substituted anilines bearing electron-
withdrawing substituents were smoothly alkylated with 1a in
moderate to good yields (Table 2, entries 4e7). It is noteworthy that
halo-substituted anilines show good reactivity in the reaction while
a small amount of N-benzylaniline (3aa) as a dehalogenation
byproduct was obtained. The generation of dehalogenation
byproduct could be accounted for the catalytic reduction of the
desired product 3 with the intermediate AueH species. However,
no reaction was observed if anilines bearing strong electron-
withdrawing substituents such as eNO2, eOCCH3 or eF3C were
used as substrates (Table 2, entry 8). Unexpectedly, N-phenyl-
acetamide as substrate afford 63% yield of N-benzylaniline (entry
9), which could be caused by the hydrolysis of acetanilide in the
alkaline solution. Hetero-amine and naphthylamine also show
good reactivity in this reaction and give good yields (Table 2, entries
10, 11).
Table 1
Optimization of the reaction conditions of gold(I) complex catalyzed N-alkylation of
aniline (1a) with benzyl alcohol (2a)a
Entry Cat. (mol %)
Base
Solvent
T (ꢀC) Yield/%b
1
2
3
4
5
6
7
8
Ph3PAuCl (5%)
t-BuOK
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 60
1,4-Dioxane 80
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
1,4-Dioxane 100
25
26
48
14
n.d.
9
37
59
78
81
82
16
25
6
Ph3PAuCl (5%)þCs2CO3 (5%) t-BuOK
Ph3PAuCl (5%)/AgOTf (5%)
AgOTf (5%)
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
Ph3PAuCl (5%)/AgOTf (5%)
Ph3PAuCl (5%)/AgOTf (5%)
Ph3PAuCl (3%)/AgOTf (3%)
Ph3PAuCl (8%)/AgOTf (8%)
Ph3PAuCl (10%)/AgOTf (10%) t-BuOK
Ph3PAuCl (12%)/AgOTf (12%) t-BuOK
Ph3PAuCl (15%)/AgOTf (15%) t-BuOK
Ph3PAuCl (10%)/AgOTf (10%) NaOH
Ph3PAuCl (10%)/AgOTf (10%) KOH
Ph3PAuCl (10%)/AgOTf (10%) K2CO3
2.3. N-alkylation of anilines with various primary alcohols
9
10
11
12
13
14
15
16
17
18
19
Reactions of different primary alcohols with aniline (1a) were
examined to extend the scope of this catalytic system. Benzyl al-
cohol bearing electron-donating groups of eCH3, eOMe, and
naphthalene methanol were successfully alkylated with aniline in
moderate to good yield (Table 3, entries 1e3). The electron-
withdrawing group of eCl substituted benzyl alcohol were toler-
ated in the reaction while a small amount of 3aa as a dehalogena-
tion byproduct was formed (Table 3, entry 4), which could be
ascribed to the catalytic reduction of the desired product 3ae with
the intermediate AueH species. However, no desired product was
obtained in the reaction using benzyl alcohol bearing the strong
Ph3PAuCl (10%)/AgOTf (10%) K3PO4$3H2O 1,4-Dioxane 100
8
18
Ph3PAuCl (10%)/AgOTf (10%) t-BuOK
Ph3PAuCl (10%)/AgOTf (10%) t-BuOK
Ph3PAuCl (10%)/AgOTf (10%) t-BuOK
Ph3PAuCl (10%)/AgOTf (10%) t-BuOK
PhCH3
THF
MeCN
100
Reflux 0
Reflux 8
ClCH2CH2Cl Reflux 5
a
The reaction was carried out with aniline (1.0 mmol), benzyl alcohol (1.2 mmol),
catalyst (10 mol %), and base (1.0 equiv) in 2 mL solvent for 48 h.
b
Isolated yield.

H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
8831
Table 2
N-alkylation of primary amines with benzyl alcohol (2a) affording secondary aminesa
Entry
1
Amine
Product
Yield/%b
90
87
2
3
4
92
72
5
6
7
76
12
78
14
73
15
8
0
63
87
81
9
10
11
a
Reaction conditions: 1 (1.0 mmol), 2a (1.2 mmol), Ph3PAuCl (0.1 mmol), AgOTf (0.1 mmol) in 1,4-dioxane (2 mL), t-BuOK (1.0 equiv), 100 ꢀC.
Isolated yield.
b

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H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
Table 3
N-alkylation of anilines (1a) with various primary alcohols affording secondary aminesa
Entry
1
Alcohol
Product
Yield/%b
80
2
3
78
75
4
64
13
5
0
63
60
6c
7c
8c
64
58
0
9c
10d
a
Reaction conditions: 1a (1.0 mmol), 2 (1.2 mmol), Ph3PAuCl (0.1 mmol), AgOTf (0.1 mmol) in 1,4-dioxane (2 mL), t-BuOK (1.0 equiv), 100 ꢀC.
Isolated yield.
The reaction times were 3 d.
The reaction time was 4 d.
b
c
d
electron-withdrawing group of eNO2 at the para-position (Table 3,
2.4. Mechanistic consideration of the N-alkylation of amines
with alcohols catalyzed by gold(I) complex
entry 5). Non-activated aliphatic alcohols proceeded smoothly to
produce the corresponding secondary amines in moderate yields
(Table 3, entries 6e9). Cyclic secondary alcohols were not appli-
cable in this catalytic system, which attribute to the difficulty of
being oxidized to ketone by this Au(I) catalyst system due to their
steric effect (Table 3, entry 10).
Although the exact mechanism for the present reaction is not
clear yet, a possible mechanism is shown in Scheme 2. The re-
action mechanism involves three elementary steps (Scheme 2). At
the first step, a hydrido-gold species would be formed from the

H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
8833
secondary amines as product). Besides, compared with the
known catalytic system of ruthenium or rhodium, the present
catalytic system can be carried out under moderate temperature
of 100 ꢀC.
4. Experimental section
4.1. General consideration
Most of the chemical reagents were purchased from Aldrich
and used without further purification in most cases. Solvents are
commercially available and used without further purification. 1H
NMR and 13C spectra were recorded on 500 MHz Brucker in-
strument. Chemical shifts are in parts per million from tetrame-
thylsilane (TMS). Melting points were determined on an
electrothermal apparatus and uncorrected. All the major products
were isolated by flash column chromatography on silica gel, with
eluents of mixed solvents (ethyl acetate and petroleum ether). TLC
was performed on a Merck Kieselgel F254, 0.2 mm thick.
Scheme 2. The plausible mechanism for N-alkylation of primary amines with alcohols
catalyzed by Au(I).
4.2. General procedure for the N-mono-alkylation of amines
with alcohols catalyzed by gold(I) complex
alcohol to [Au]. Initially, Ph3PAuOTf, which generated from
Ph3PAuCl and AgOTf, provides the cationic Au(I), then reacts with
alcohol to afford alkoxo-gold species A in the presence of t-BuOK.
After a mixture of Ph3PAuCl (13 mg, 0.02 mmol) and AgOTf
(7 mg, 0.02 mmol) was stirred in 1,4-dioxane (2 mL) for 10 min in
a Schlenk tube, amine derivatives (1, 1.0 mmol), alcohol derivatives
(2, 1.2 mmol), and t-BuOK (112 mg, 1.0 equiv) were added to the
mixture. The reaction mixture was heated to 100 ꢀC. After 48 h, the
reaction mixture was filtered out and the filtrate was evaporated
under reduced pressure. Then the crude product was purified by
column chromatography on silica gel (petroleum ether/ethyl ace-
tate) to give the corresponding product 3.
[Au]eH would be generated by b-hydrogen elimination of alkoxo
moiety with the formation of the corresponding aldehyde B. The
second step involves the formation of imine C intermediates by
the dehydration condensation reaction between aldehyde and
primary amine. At the last step, [Au] catalyst would be regen-
erated from [Au]eH to imine C intermediates. The amido gold
species D would be formed by the addition of the [Au]eH to the
C]N of imine C. Then the secondary amine 3 was released from
imine D and t-BuOH accompanying with regeneration of the
catalytically active Au(I).
4.3. Selected physical and spectroscopic data
4.3.1. N-Benzylaniline (3aa).16 The crude product was purified by
column chromatography on silica gel (40:1; petroleum ether/
EtOAc). Yellow oil was obtained (142.7 mg, 78%). 1H NMR (500 MHz,
In order to support the above mechanism of the hydrogen
autotransfer reaction, we carried out the following reactions. Ani-
line and benzaldehyde were stirred to generate N-benzylidenea-
CDCl3)
d
7.44e7.34 (m, 4H), 7.31 (t, J¼7.0 Hz, 1H), 7.24e7.16 (m, 2H),
6.75 (t, J¼7.3 Hz, 1H), 6.71e6.63 (m, 2H), 4.36 (s, 2H). 13C NMR
niline (C1) in 92% yield for
4 h without catalyst at room
temperature. Then benzyl alcohol as the hydrogen donor and the
Ph3PAuCl/AgOTf as catalyst were added to the solution of C1 under
the optimized condition. The expected product (3aa) and benzal-
dehyde were obtained in 77% and 81% yields, respectively
(Scheme 3). It shows that the key imine intermediate in the third
reduction mechanism step could afford the product 3aa with the
gold hydride species.
(126 MHz, CDCl3)
d 147.23, 138.53, 128.36, 127.72, 126.59, 126.31,
119.98, 116.64, 111.93, 47.37.
4.3.2. N-Benzyl-4-methylbenzenamine (3ba).17 The crude product
was purified by column chromatography on silica gel (50:1; pe-
troleum ether/EtOAc). Yellow oil was obtained (177.3 mg, 90%). 1H
NMR (500 MHz, CDCl3)
d
7.56e7.46 (m, 4H), 7.43 (t, J¼6.8 Hz, 1H),
Scheme 3. Reaction of the key imine intermediate with benzyl alcohol to support the proposed mechanism.
3. Conclusions
7.16 (d, J¼8.2 Hz, 2H), 6.71 (d, J¼8.2 Hz, 2H), 4.44 (s, 2H), 2.42 (s,
3H). 13C NMR (126 MHz, CDCl3)
145.12, 138.89, 128.95, 127.78,
d
We have developed a new and highly efficient homogeneous
gold(I) catalytic system for N-alkylation of primary amines with
alcohols through a hydrogen autotransfer process. It should be
noted that the reaction has excellent selectivity for the forma-
tion of secondary amines with this catalyst system (only
126.68, 126.32, 125.82, 112.20, 47.75, 19.63.
4.3.3. N-Benzyl-2-methylbenzenamine (3ca).17 The crude product
was purified by column chromatography on silica gel (50:1; pe-
troleum ether/EtOAc). Yellow oil was obtained (171.0 mg, 87%). 1H

8834
H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
NMR (500 MHz, acetone-d6)
d
7.42 (d, J¼7.6 Hz, 2H), 7.33 (t,
petroleum ether/EtOAc). Brown solid was obtained (188.5 mg, 81%).
J¼7.6 Hz, 2H), 7.24 (t, J¼7.3 Hz, 1H), 7.10e6.92 (m, 2H), 6.63e6.48
Mp 71e73 ꢀC. 1H NMR (500 MHz, CDCl3)
d
7.68 (dd, J¼11.5, 4.6 Hz,
(m, 2H), 4.44 (d, J¼5.4 Hz, 2H), 2.22 (s, 3H). 13C NMR (126 MHz,
2H), 7.46e6.96 (m, 9H), 6.50 (d, J¼7.2 Hz, 1H), 4.34 (s, 2H). 13C
acetone-d6)
d
145.43, 139.51, 128.86, 127.38, 126.13, 125.80, 125.72,
NMR (126 MHz, CDCl3) d 142.23, 138.15, 133.40, 127.82, 126.85,
120.90, 115.43, 108.96, 46.31, 16.08.
126.51, 125.72, 124.86, 123.87, 122.73, 122.50, 119.04, 116.81, 103.98,
47.72.
4.3.4. N-Benzyl-4-methoxybenzenamine (3da).18 The crude product
was purified by column chromatography on silica gel (45:1; pe-
troleum ether/EtOAc). Yellow oil was obtained (196.1 mg, 92%). 1H
4.3.12. N-(4-Methylbenzyl)benzenamine (3ab).1a The crude product
was purified by column chromatography on silica gel (30:1; pe-
troleum ether/EtOAc). Yellow oil was obtained (157.3 mg, 80%). 1H
NMR (500 MHz, CDCl3)
1H), 6.87e6.80 (m, 2H), 6.70e6.63 (m, 2H), 4.33 (s, 2H), 3.79 (s, 3H).
13C NMR (126 MHz, CDCl3)
151.25, 141.54, 138.78, 127.65, 126.60,
d
7.41 (dt, J¼7.7, 6.6 Hz, 4H), 7.33 (t, J¼7.0 Hz,
NMR (500 MHz, CDCl3)
6.86e6.80 (m, 1H), 6.75e6.70 (m, 2H), 4.37 (s, 2H), 4.05 (s, 1H), 2.46
(s, 3H). 13C NMR (126 MHz, CDCl3)
147.36, 135.96, 135.52, 128.43,
d
7.37 (d, J¼8.0 Hz, 2H), 7.31e7.24 (m, 4H),
d
126.22, 113.98, 113.18, 54.85, 48.28.
d
128.38, 126.64, 116.60, 111.97, 47.17, 20.24.
4.3.5. N-Benzyl-4-(trifluoromethoxy)benzenamine
crude product was purified by column chromatography on silica gel
(3ea).19 The
4.3.13. N-(4-Methoxybenzyl)benzenamine (3ac).4d The crude prod-
uct was purified by column chromatography on silica gel (50:1;
petroleum ether/EtOAc). Pale yellow solid was obtained (166.1 mg,
(40:1; petroleum ether/EtOAc). Dark yellow oil was obtained
(192.1 mg, 72%). 1H NMR (500 MHz, CDCl3)
d
7.46e7.37 (m, 4H),
7.37e7.31 (m, 1H), 7.10 (d, J¼8.4 Hz, 2H), 6.73 (d, J¼8.8 Hz, 2H), 4.36
(s, 2H). 13C NMR (126 MHz, CDCl3)
144.18, 140.71, 136.74, 127.81,
78%). Mp 59e61 ꢀC. 1H NMR (500 MHz, CDCl3)
d
7.38 (d, J¼8.4 Hz,
d
2H), 7.28 (t, J¼7.7 Hz, 2H), 6.98 (d, J¼8.4 Hz, 2H), 6.83 (t, J¼7.3 Hz,
126.94e126.76 (d, J¼22.68 Hz), 122.80e116.70 (q, J¼768.6 Hz),
1H), 6.73 (d, J¼8.0 Hz, 2H), 4.33 (s, 2H), 3.88 (s, 3H). 13C NMR
121.43, 113.71, 48.45.
(126 MHz, CDCl3) d 157.95, 147.32, 130.53, 128.35, 127.90, 116.58,
113.12, 111.95, 54.37, 46.85.
4.3.6. N-Benzyl-3-chlorobenzenamine (3fa).20 The crude product
was purified by column chromatography on silica gel (45:1; pe-
troleum ether/EtOAc). Dark yellow oil was obtained (165.0 mg,
4.3.14. N-(Naphthalen-1-ylmethyl)benzenamine (3ad).23 The crude
product was purified by column chromatography on silica gel
(40:1; petroleum ether/EtOAc). Dark yellow solid was obtained
(174.5 mg, 75%). Mp 67e69 ꢀC. 1H NMR (500 MHz, CDCl3)
76%). 1H NMR (500 MHz, CDCl3)
d
7.40e7.35 (m, 4H), 7.35e7.30 (m,
1H), 7.09 (t, J¼8.0 Hz, 1H), 6.73e6.68 (m, 1H), 6.64 (t, J¼2.1 Hz, 1H),
6.54e6.49 (m, 1H), 4.33 (s, 2H). 13C NMR (126 MHz, CDCl3)
148.28,
d
d
8.13e7.96 (m, 1H), 7.93e7.83 (m, 1H), 7.79 (d, J¼8.2 Hz, 1H),
137.80, 134.06, 129.26, 127.78, 126.50, 116.44, 111.54, 110.17, 47.12.
7.55e7.45 (m, 3H), 7.45e7.36 (m, 1H), 7.27e7.16 (m, 2H), 6.76 (t,
J¼7.3 Hz, 1H), 6.68e6.60 (m, 2H), 4.66 (s, 2H). 13C NMR (126 MHz,
4.3.7. N-Benzyl-4-chlorobenzenamine (3ga).18 The crude product
was purified by column chromatography on silica gel (50:1; pe-
troleum ether/EtOAc). Dark yellow oil was obtained (169.4 mg,
CDCl3) d 147.40, 133.52, 133.04, 130.71, 128.50, 127.95, 127.31,
125.49, 125.15, 125.01, 124.73, 122.76, 116.72, 111.91, 45.50.
78%). 1H NMR (500 MHz, acetone-d6)
d
7.42 (d, J¼7.6 Hz, 2H), 7.33 (t,
4.3.15. N-Octylbenzenamine (3ag).24 The crude product was puri-
fied by column chromatography on silica gel (60:1; petroleum
ether/EtOAc). Yellow oil was obtained (129.1 mg, 63%). 1H NMR
J¼7.6 Hz, 2H), 7.24 (t, J¼7.3 Hz, 1H), 7.10e6.85 (m, 2H), 6.65e6.43
(m, 2H), 4.92 (s, 1H), 4.44 (d, J¼5.4 Hz, 2H). 13C NMR (126 MHz,
acetone-d6)
d
146.72, 138.85, 127.69, 127.42, 126.26, 125.87, 119.40,
(500 MHz, CDCl3)
d
7.11 (t, J¼7.9 Hz, 2H), 6.62 (t, J¼7.3 Hz, 1H), 6.54
112.88, 46.31.
(d, J¼7.8 Hz, 2H), 3.04 (t, J¼7.1 Hz, 2H), 1.67e1.48 (m, 2H), 1.30e1.07
(m, 12H), 0.83 (t, J¼6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3)
d 147.55,
4.3.8. N-Benzyl-4-bromobenzenamine (3ha).1b The crude product
was purified by column chromatography on silica gel (40:1; pe-
troleum ether/EtOAc). Dark yellow oil was obtained (191.1 mg, 73%).
128.23, 116.10, 111.72, 43.04, 30.85, 28.60, 28.44, 28.29, 26.21, 21.68,
13.11.
1H NMR (500 MHz, CDCl3)
d
7.40e7.34 (m, 4H), 7.31 (dd, J¼8.7,
4.3.16. N-Hexylbenzenamine (3ah).25 The crude product was puri-
fied by column chromatography on silica gel (60:1; petroleum
ether/EtOAc). Pale yellow oil was obtained (106.1 mg, 60%). 1H NMR
4.4 Hz, 1H), 7.28e7.24 (m, 2H), 6.52 (d, J¼8.7 Hz, 2H), 4.32 (s, 2H).
13C NMR (126 MHz, CDCl3)
113.45, 108.15, 47.26.
d 146.06, 137.87, 130.96, 127.74, 126.42,
(500 MHz, CDCl3)
d
7.18 (dd, J¼8.5, 7.4 Hz, 2H), 6.70 (t, J¼7.3 Hz, 1H),
6.65e6.56 (m, 2H), 3.12 (t, J¼7.1 Hz, 2H),1.63 (dt, J¼14.8, 7.2 Hz, 2H),
4.3.9. N-Benzylpyridin-2-amine (3ka).17 The crude product was
purified by column chromatography on silica gel (25:1; petroleum
ether/EtOAc). Pale yellow solid was obtained (159.8 mg, 87%). Mp
1.34 (ddd, J¼10.9, 7.5, 3.8 Hz, 7H), 0.91 (dd, J¼11.5, 4.5 Hz, 3H). 13
C
NMR (126 MHz, CDCl3) d 147.57, 128.23, 116.08, 111.71, 43.03, 30.68,
28.73, 28.58, 25.88, 21.65, 13.06.
97e99 ꢀC.1H NMR (500 MHz, CDCl3)
d
7.91 (d, J¼4.8 Hz,1H), 7.24e7.15
(m, 5H), 7.10 (3, J¼6.8 Hz, 1H), 6.43e6.40 (m, 2H), 6.19 (d, J¼8.4 Hz,
2H), 4.94 (s, 1H), 4.33 (s, 2H). 13C NMR (126 MHz, CDCl3)
157.71,
4.3.17. N-Pentylbenzenamine (3ai).26 The crude product was puri-
fied by column chromatography on silica gel (55:1; petroleum
ether/EtOAc). Yellow oil was obtained (104.1 mg, 64%). 1H NMR
d
147.17, 138.21, 136.57, 127.67, 126.43, 126.26, 112.14, 105.80, 45.35.
(500 MHz, CDCl3)
d
7.20 (t, J¼7.9 Hz, 2H), 6.72 (t, J¼7.3 Hz, 1H), 6.65
4.3.10. N-(4-Chlorobenzyl)benzenamine (3ae).21 The crude product
was purified by column chromatography on silica gel (35:1; pe-
troleum ether/EtOAc). Dark yellow oil was obtained (139.2 mg,
(d, J¼7.8 Hz, 2H), 3.13 (t, J¼7.2 Hz, 2H), 1.70e1.58 (m, 2H), 1.44e1.35
(m, 5H), 0.93 (dd, J¼12.0, 4.9 Hz, 4H). 13C NMR (126 MHz, CDCl3)
d
147.26, 128.25, 116.38, 111.96, 43.22, 28.35, 28.21, 21.52, 13.05.
64%). 1H NMR (500 MHz, CDCl3)
d
7.42e7.29 (m, 4H), 7.24 (dd, J¼8.4,
7.4 Hz, 2H), 6.80 (t, J¼7.3 Hz, 1H), 6.67 (d, J¼7.7 Hz, 2H), 4.35 (s, 2H),
4.09 (s, 1H). 13C NMR (126 MHz, CDCl3)
146.92, 137.12, 131.90,
130.00, 128.39, 127.79, 116.86, 111.97, 46.64.
4.3.18. N-Butylbenzenamine (3aj).27 The crude product was puri-
fied by column chromatography on silica gel (55:1; petroleum
ether/EtOAc). Yellow oil was obtained (86.2 mg, 58%). 1H NMR
d
(500 MHz, CDCl3)
d
7.19 (dd, J¼8.4, 7.4 Hz, 2H), 6.70 (t, J¼7.3 Hz, 1H),
4.3.11. N-Benzylnaphthalen-1-amine (3la).22 The crude product
was purified by column chromatography on silica gel (35:1;
6.62 (d, J¼7.7 Hz, 2H), 3.13 (t, J¼7.1 Hz, 2H), 1.63 (dt, J¼14.7, 7.3 Hz,
2H), 1.45 (dd, J¼15.0, 7.5 Hz, 2H), 1.01e0.94 (m, 3H). 13C NMR

H. Yang et al. / Tetrahedron 70 (2014) 8829e8835
8835
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Acknowledgements
This work was supported by the National Natural Science
Foundation of Jiangsu Province (BK2011696) and the National
Natural Science Foundation of China (No. 21376121).
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.10.007.
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