Multifunctional catalysis of a ruthenium-grafted hydrotalcite: One-pot synthesis of quinolines from 2-aminobenzyl alcohol and various carbonyl compounds via aerobic oxidation and aldol reaction

Article abstract of DOI:10.1016/j.tetlet.2004.06.023

The Ru-grafted hydrotalcite was found to be an excellent multifunctional catalyst for one-pot synthesis of quinolines from 2-aminobenzyl alcohol and various carbonyl compounds. These quinolines were obtained through aerobic oxidation by the Ru species, followed by aldol reaction on base sites of the hydrotalcite.

Full text of DOI:10.1016/j.tetlet.2004.06.023

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6029–6032
Multifunctional catalysis of a ruthenium-grafted hydrotalcite:
one-pot synthesis of quinolines from 2-aminobenzyl
alcohol and various carbonyl compounds via aerobic
oxidation and aldol reaction
Ken Motokura, Tomoo Mizugaki, Kohki Ebitani and Kiyotomi Kaneda*
Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University,
1
-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
Received 21 April 2004; revised 3 June 2004; accepted 4 June 2004
Available online 24 June 2004
Abstract—The Ru-grafted hydrotalcite was found to be an excellent multifunctional catalyst for one-pot synthesis of quinolines
from 2-aminobenzyl alcohol and various carbonyl compounds. These quinolines were obtained through aerobic oxidation by the Ru
species, followed by aldol reaction on base sites of the hydrotalcite.
ꢀ
2004 Elsevier Ltd. All rights reserved.
9
One-pot syntheses that involve economically and envi-
ronmental friendly chemical processes, have received
attention as a next strategy for ‘green’ organic synthe-
catalyst system with a stoichiometric amount of KOH.
This one-pot method is superior to traditional Friedla-
ender quinoline synthesis
10
because 2-aminobenzyl
1
;2
ses. Solid catalysts that accommodate various active
sites on their surface show promise for promoting
alcohol is less expensive and more stable than is 2-
aminobenzaldehyde. Herein, we report a more envi-
ronmentally benign one-pot quinoline synthesis from 2-
aminobenzyl alcohol and various carbonyl compounds
using the heterogeneous Ru/HT catalyst without
homogeneous bases (Eq. 1). The present catalytic system
described here has significant advantages over catalysts
3
multiple reactions in a single pot. Hydrotalcites (HTs)
are useful solid catalysts for nano-scale design of active
sites because of their unique properties such as alter-
nating cationic and anionic layers, surface tunable bas-
4–6
icity, and adsorption capacity. Recently, we succeeded
in preparing a Ru-grafted hydrotalcite (Ru/HT), a
multifunctional heterogeneous catalyst, for direct
a-alkylation of nitriles via several sequential reactions
9
previously reported, including: (i) high catalytic activity
and wide applicability to various carbonyl compounds;
(ii) no need for homogeneous bases; and (iii) the use of
molecular oxygen as a green oxidant. This is the first
reported one-pot quinoline synthesis using heterogeneous
catalysts.
7
through cooperative action of Ru species and base sites.
The quinoline nucleus plays an important role as an
intermediate in the design of pharmacologically active
8
compounds, and many synthetic routes of quinolines
R2
have been developed. Shim and co-workers proposed
the direct formation of quinolines from 2-aminobenzyl
alcohol and ketones via hydrogen transfer reaction and
cyclization mediated by a homogeneous Ru complex
OH
NH2
O
R1
Ru/HT
O (1 atm)
R2
+
R1
2
N
ð1Þ
Preparation of the Ru/HT in the presence of triethyl-
ꢀ
3
amine (Ru/HT-N) is as follows. A 3.33 · 10 M aque-
ous solution of RuCl ÆnH O (60 mL) was slowly added
to the mixture of
Mg Al (OH) CO (2.0 g), and triethylamine (10 mmol)
Keywords: Quinoline synthesis; 2-Aminobenzyl alcohol; Hetero-
geneous catalyst; Hydrotalcite; Ruthenium; Molecular oxygen.
3
2
11
a
hydrotalcite (HT),
*
Corresponding author. Tel./fax: +81-6-6850-6260; e-mail: kaneda@
cheng.es.osaka-u.ac.jp
6
2
16
3
in water (140 mL) with vigorous stirring. Then, the
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.023

6030
K. Motokura et al. / Tetrahedron Letters 45 (2004) 6029–6032
a
Table 1. One-pot quinoline synthesis using various catalysts
powder (Ru content: 1.0 wt %). The absence of nitrogen
in the Ru/HT-N was confirmed by XPS analysis.
O
OH
NH2
catalyst
+
N
Reaction of 2-aminobenzyl alcohol (1) with acetophe-
none using various kinds of Ru supported catalysts was
carried out in the presence of molecular oxygen as
O (1 atm)
2
1
2
12
b
b
shown in Table 1. Interestingly, the Ru/HT-N exhib-
ited the highest catalytic activity to give 2-phenylquin-
Entry
Catalyst
Convn of 1 (%)
Yield of 2 (%)
1
2
3
4
5
6
7
Ru/HT-N
Ru/HT
>99
>99
87
61
13
oline in 87% yield (entry 1). The reactions hardly
occurred using the parent HT (entry 7). Other hetero-
c
Ru/Al
2
O
3
>99
3
geneous Ru catalysts, such as Ru/Al
Mg(OH) , and Ru/Al(OH) were inactive for this
2 3
O , Ru/MgO, Ru/
Ru/MgO
Ru/Al(OH)
37
33
Trace
Trace
Trace
Trace
3
2
3
Ru/Mg(OH)
HT
2
54
Trace
quinoline synthesis (entries 3–6). Compared with the
conventional synthesis method using hydrogen transfer
9
a
to ketones from 1, only 1.2 equiv of ketones were
required in this catalyst system.
1
(1.0 mmol), acetophenone (1.2 mmol), catalyst (0.3 g, Ru:
3
.0 mol %), toluene (5 mL), 100 ꢁC, 20 h, under O atmosphere.
2
b
c
Determined by GC.
Oligomeric products were formed from 1.
Quinoline syntheses using various ketones in the pres-
ence of the Ru/HT-N catalyst are summarized in Table
2
. A wide variety of ketones reacted smoothly with 1, to
heterogeneous mixture was stirred at 25 ꢁC for 1 h. The
solid product was separated by centrifugation, washed
thoroughly with deionized water, and dried in vacuo at
room temperature, affording the Ru/HT-N as a gray
give the corresponding quinolines in high yields. The
electronic variable substituents on the aromatic ring of
acetophenone did not strongly affect the yield of quin-
0
olines except for 2 -methylacetophenone (entries 1–9).
a
Table 2. Quinoline synthesis from various ketones
R2
N
R1
Ru/HT-N
OH
NH2
O
+
R2
R1
O (1 atm)
2
b
Entry
Ketone
Product
Yield of quinoline (%)
O
N
R
R
c
1
2
3
4
5
6
7
8
9
R ¼ H
R ¼ H
84
83
c
R ¼ 4-Cl
R ¼ 4-F
R ¼ 3-CF
R ¼ 4-Cl
R ¼ 4-F
c
90
c
3
R ¼ 3-CF
3
78
35
R ¼ 2-Me
R ¼ 3-Me
R ¼ 4-Me
R ¼ 4-OMe
R ¼ 2-Me
R ¼ 3-Me
R ¼ 4-Me
R ¼ 4-OMe
c
94
83
c
c
79
R ¼ 4-NO
2
R ¼ 4-NO
2
83
O
d
c
10
89
N
O
d
c
1
1
1
2
74
N
e
O
N
c
74
N
N
O
d
d
d
1
1
1
3
4
5
N
S
O
88
77
80
O
O
S
N
N
O

K. Motokura et al. / Tetrahedron Letters 45 (2004) 6029–6032
6031
Table 2 (continued)
b
Entry
Ketone
Product
Yield of quinoline (%)
O
f
c
1
1
1
6
7
8
N
82
O
f
f
c
O
O
O
O
76
N
N
O
MeO
MeO
OMe
OMe
84
a
b
c
d
e
f
2
2
-Aminobenzylalcohol (1 mmol), ketone (1.2 mmol), Ru/HT-N (0.3 g, Ru: 3.0 mol %), toluene (5 mL), 20 h, 100 ꢁC, O (1 atm).
Yield was determined by HPLC and GC using an internal standard based on 2-aminobenzyl alcohol.
Isolated yield.
1
5
50 ꢁC, in a stainless autoclave.
mmol of acetone was used in autoclave.
HT (0.15 g) was used, 40 h.
OH
NH2
1. Ru/HT-N, O2 (1 atm)
2. 1-octanal
(a)
N
(
81 %)
OH
NH2
1. Ru/HT-N, O (1 atm)
2
(b)
CN
2
.
N
NH2
(
90 %)
Scheme 1. Reagents and conditions: (a) (1) 1 (1 mmol), Ru/HT-N (0.3 g; Ru: 3.0 mol %), toluene (5 mL), 100 ꢁC, 10 h, O
2
. (2) 1-Octanal (2 mmol) was
. (2) Phenylacetonitrile
slowly added in flask during 12 h at 100 ꢁC; (b) (1) 1 (1 mmol), Ru/HT-N (0.3 g; Ru: 3.0 mol %), toluene (5 mL), 100 ꢁC, 7 h, O
1.5 mmol), 160 ꢁC, 7 h.
2
(
Reactions using 2-acetonaphthone and a-tetralone also
yielded 2-naphthylquinoline and 5,6-dihydrobenzo[c]-
acridine, respectively, in high yields (entries 10 and 11).
This catalyst system was applicable to the heteroaro-
matic compounds 2-acetylthiophene, 2-acetylpyridine,
and 2-acetylfuran (entries 13–15). A large-scale reaction
of 1 with acetophenone afforded the quinoline in 89%
amylquinoline and 2-amino-3-phenylquinoline in 81%
and 90% yields, respectively (Scheme 1).To the best of
our knowledge, this is the first example of a one-pot
quinoline synthesis from 2-aminobenzyl alcohol with
unsaturated ketones, aldehydes, and nitrile compounds.
In summary, the Ru/HT-N acted as an efficient hetero-
geneous bifunctional catalyst for the one-pot synthesis
of substituted quinolines from 2-aminobenzyl alcohols
and various carbonyl compounds under atmospheric
oxygen.
14
isolated yield. It should be noted that the Ru/HT-N
catalyst could be reused with retention of a high product
yield; a recycling experiment resulted in 81% yield of 2-
15
phenylquinoline. The mechanism of a one-pot quino-
line synthesis using the Ru/HT is proposed as follows:
the surface Ru species oxidizes 2-aminobenzyl alcohol to
16
2
lowed by aldol reaction with ketones catalyzed by the
-aminobenzaldehyde under an O
2
atmosphere, fol-
Acknowledgements
7;17
base sites of the HT to yield the quinolines.
This work is financially supported by the center of
excellence (21COE) program ‘Creation of Integrated
EcoChemistry’ of Osaka University. We are also grate-
ful to the Department of Materials Engineering Science,
Graduate School of Engineering Science, Osaka Uni-
versity, for scientific support with the gas–hydrate ana-
lyzing system (GHAS) and lend-lease laboratory system.
The applicability of the Ru/HT-catalyzed one-pot syn-
thesis is highlighted by the reaction of a,b-unsaturated
ketones with carbon–carbon double bonds that are
18
easily reduced by metal–hydride species. The reactions
of benzalacetone derivatives with 1 afforded styryl
quinolines, precursors of naturally occurring tetra-
hydroquinoline alkaloids and inhibitors of viral prolif-
19
eration, in good yields (Table 2, entries 16–18).
Reduction of C–C double bonds did not occur because
of the smooth oxidation of the Ru–H species by
molecular oxygen. Furthermore, 1-octanal and phenyl-
acetonitrile were also reacted as donors to afford 3-
References and notes
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4
5
15. Recycling experiment of the Ru/HT-N is as follows. The
reaction of 2-aminobenzyl alcohol (1.0 mmol) and ace-
tophenone (1.2 mmol) in toluene (8 mL) with Ru/HT-N
(0.30 g, Ru: 0.03 mmol) and MS4A (0.3 g) was carried out
under reflux. After 20 h, the Ru/HT-N was removed by
filtration and GC analysis of the filtrate showed an 84%
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washed with toluene, acetone, and water successively, and
then dried in vacuo before reuse. The recycling reaction
using the spent Ru/HT-N catalyst afforded the quinoline
in 81% GC yield under same reaction conditions.
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1
1
1
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1. Hydrotalcite was available from TOMITA Pharmaceuti-
cal Co., Ltd.
2. The preparation of the Ru/HT and other Ru catalysts: see
Ref. 7.