Alkylation of 2-methylquinoline with alcohols under additive-free conditions by Al2O3-supported Pt catalyst

Article abstract of DOI:10.1016/j.tetlet.2013.09.077

Supported metal nanoparticle catalysts are studied for alkylation of 2-methylquinoline with benzyl alcohol under additive-free conditions in N ₂ atmosphere. Among various metal-loaded Al₂O₃ catalysts and supported Pt catal

Full text of DOI:10.1016/j.tetlet.2013.09.077

Tetrahedron Letters 54 (2013) 6490–6493
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Tetrahedron Letters
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Alkylation of 2-methylquinoline with alcohols under additive-free
conditions by Al2O3-supported Pt catalyst
Chandan Chaudhari a, S. M. A. Hakim Siddiki b, Ken-ichi Shimizu a,b,
⇑
a Catalysis Research Center, Hokkaido University, N-21, W-10, Sapporo 001-0021, Japan
b Elements Strategy Initiative for Catalysts and Batteries, Kyoto University, Katsura, Kyoto 615-8520, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Supported metal nanoparticle catalysts are studied for alkylation of 2-methylquinoline with benzyl alco-
hol under additive-free conditions in N2 atmosphere. Among various metal-loaded Al2O3 catalysts and
supported Pt catalysts, Pt metal nanocluster loaded-Al2O3 pre-reduced in H2 at 500 °C shows highest
yield (82%) of the product (2-phenethyl-quinoline). The catalyst is reusable, shows higher turnover num-
ber than a previous homogeneous catalyst, and shows good to moderate yield for alkylation of 2-meth-
ylquinoline with various alcohols. The reaction is driven by the borrowing-hydrogen pathway, in which
aldehyde formed by dehydrogenation of alcohol undergoes aldol condensation with 2-methylquinoline
to give the alkene intermediate which is finally hydrogenated by Pt-H species.
Received 22 August 2013
Revised 6 September 2013
Accepted 17 September 2013
Available online 25 September 2013
Keywords:
Alkylation
Alcohols
Methylquinoline
Platinum
Ó 2013 Elsevier Ltd. All rights reserved.
Introduction
combined with a phosphine ligand and a base.19 The reaction pro-
vides a simple and atom-economical direct route to alkylquino-
Quinolines and their derivatives have great importance in phar-
maceutical and agriculture industries.1,2 Among various methods
for synthesizing quinolines,3 the introduction of alkyl-chain moie-
ties into benzoquinones using methylquinolines as a starting mate-
rial is of particular importance,4,5 because methylquinolines are
easily accessible. The classical synthetic method of alkylquinolines
is the reaction of a 2-methylquinoline with n-BuLi, followed by
reaction with an alkyl halide. However, the main drawback of this
method is the formation of stoichiometric amount of waste salts
and use of hazardous reagent. In recent years, much attention
has focused on the alkylation reactions using alcohols as alkylating
agent driven by the borrowing-hydrogen6 (or hydrogen-autotrans-
fer7) mechanism. It provides excellent protocols for selective C–C
lines, as the exclusive products, in high yields. However, this
method suffers from drawbacks such as low turnover number
(TON), necessity of substoichiometric amount (50 mol %) of base,
and difficulties in catalyst-product separation and catalyst reuse.
As a part of our continuing interest in the heterogeneous catalysis
for hydrogen-transfer reactions,17,20,21 we report herein the first
heterogeneous catalytic system for selective alkylation of methyl-
quinolines by alcohols using Pt nanocluster-loaded
c-Al2O3
catalyst. This method has advantages over the previous homoge-
neous system in terms of higher TON, catalyst reusability, and
greener (additive-free) conditions.
Results and discussion
bond formations9–19 such as -alkylation of ketones,8 b-alkylation
a
of secondary alcohols,9–12 and Guerbet-type dimerizations of alco-
hols.13–16 In these protocols, alcohol is initially dehydrogenated,
then undergoes a functionalization reaction, and finally, re-hydro-
genated by in situ formed hydride species. Recently, this method-
ology has been used for alkylation of more challenging substrates.
Kempe and co-workers reported the catalytic alkylation of methyl-
N-heteroaromatics by alcohols in the presence of homogeneous
catalyst [IrCl(cod)]2 with Py2NP(i-Pr)2 ligand under basic condi-
tion.18 Recently, Obora et al. developed a selective alkylation of
methylquinolines by alcohols using the [Ir(OH)(cod)]2 complex
The structure of Pt species in the standard catalyst, Pt/Al2O3
(Pt = 1 wt %) prepared by an impregnation method followed by
H2-reduction at 500 °C, was examined by Pt L3-edge X-ray absorp-
tion near-edge structure (XANES) in Figure 1A and X-ray absorp-
tion fine structure (EXAFS) in Figure 1B. XANES features of Pt/
Al2O3 are close to those of Pt foil. The EXAFS curve-fitting analysis
(Table 1) showed that the EXAFS of Pt/Al2O3 mainly consists of a
Pt–Pt bond at 2.70 Å with coordination number of 6.4. The Pt–Pt
distance shorter than that of bulk Pt (2.76 Å) and Pt–Pt coordina-
tion number lower than that of bulk Pt (12) are characteristic fea-
tures of small Pt metal clusters.22 These features are consistent
with the average diameter of Pt metal estimated by CO adsorption
experiment (2.3 nm). From these results, it is revealed that
⇑
Corresponding author. Tel.: +81 11 706 9240; fax: +81 11 706 9163.
E-mail address: kshimizu@cat.hokudai.ac.jp (K. Shimizu).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.077

C. Chaudhari et al. / Tetrahedron Letters 54 (2013) 6490–6493
6491
alkylated product. Table 3 shows the effect of support on the activ-
ity of Pt-loaded catalysts. Among various support materials, Al2O3
was found to be the best support. From these results, Pt/Al2O3 was
found to be the most effective catalyst for the alkylation of 2-meth-
ylquinoline with benzyl alcohol.
A
B
Pt foil
2.0
Pt/Al2O3-air
Pt/Al2O3
CHO
Pt foil
Pt/Al2O3 (2 mol%)
x 0.4
N
N
mesitylene (1 g))
170°C 36h
,
1.1 mmol
1 mmol
70% yield
Pt/Al2O3-air
Pt/Al2O3
ð1Þ
OH Pt/Al2O3 (2 mol%)
mesitylene (1 g)
N
N
170°C, 36h
11540
11560
11580
0
1
2
3
4
5
6
0.70 mmol
60% yield
0.77 mmol
X-ray energy/eV
R / Å
ð2Þ
Figure 1. (A) XANES spectra and (B) EXAFS Fourier transforms at Pt L3-edge for Pt
Next we studied the scope of substrates for alkylation of 2-
methylquinoline (1 mmol) with various alcohols (1.1 mmol) by
Pt/Al2O3 (Table 4). The substituted benzyl alcohols with electron
donating groups (entries 2 and 3) and that with electron with-
drawing group (entry 4) gave good yields (70–75%). 4-Fluoro ben-
zyl alcohol (entry 5) resulted in a moderate yield (50%). Aliphatic
alcohols such as octanol and hexanol (entries 6 and 7) also resulted
in moderate yields (60–63%). Note that, unlike the homogeneous Ir
catalyst reported by Obora,19 our system does not require additives
and excess molar amount of 2-methylquinoline.
We studied leaching test and reusability study for the Pt/Al2O3-
catalyzed alkylation of 2-methylquinoline with benzyl alcohol. The
reaction was completely terminated by removal of the catalyst
from the reaction mixture after 4 h; further heating of the filtrate
for 36 h under the reflux condition did not increase the yield.
ICP-AES analysis of the filtrate confirmed that the content of Pt
in the solution was below the detection limit. These results confirm
that the reaction is attributed to the heterogeneous catalysis of Pt/
Al2O3. Figure 2 shows the results of catalyst reuse. After the reac-
tion of cycle 1 (Table 4, entry 1), we separated catalyst from reac-
tion mixture by centrifugation. The separated catalyst was dried at
90 °C at 12 h and then reduced in H2 at 500 °C for 0.5 h. The recov-
ered catalyst was reused at least four times without marked indi-
cation of catalyst deactivation. The total TON for the five cycles
was 195. This value is an order of magnitude higher than that of
the homogeneous Ir (TON = 18.4 for the same reaction).19
catalysts and a reference compound (Pt foil).
Table 1
Curve-fitting analysis of Pt L3-edge EXAFS
Sample
Shell
Na
Rb (Å)
rc (Å)
Rfd (%)
Pt/Al2O
Pt/Al2O3–air
Pt
O
Pt
Pt
6.4
1.6
3.9
(12)
2.70
2.03
2.68
(2.76)
0.080
0.071
0.094
—
1.6
2.1
Pt foil
—
a
b
c
Coordination numbers.
Bond distance.
Debye–Waller factor.
Residual factor.
d
dominant Pt species in Pt/Al2O3 is the metallic Pt nanocluster. The
catalyst named Pt/Al2O3–air was prepared by exposing the as-re-
duced Pt/Al2O3 catalyst to the ambient conditions for 0.5 h. The EX-
AFS result of Pt/Al2O3–air (Table 1) showed that air-exposure of Pt/
Al2O3 resulted in an appearance of the Pt-O shell with coordination
number of 1.6 and a decrease in the Pt–Pt coordination number
from 6.4 to 3.9. The XANES result showed that air-exposure of
Pt/Al2O3 resulted in an increase in the white line intensity. These
results indicate that the metallic Pt species are partially re-oxi-
dized in air.
Using various supported metal nanoparticle catalysts, we car-
ried out catalysts screening study. We adopted the alkylation of
2-methylquinoline (1 mmol) with benzyl alcohol (1.1 mmol) in
mesitylene (1 g) under reflux conditions in the presence of
2 mol % of the metal catalyst as a model reaction. Table 2 shows
the effect of metal species on the activity of various metal-loaded
Al2O3. Among various transition metals (Pt, Ir, Re, Rh, Pd, Ag, Ni,
Co, and Cu), the Pt catalyst showed the highest yield (82%) of the
In analogy to the proposed mechanism for the C-3 alkylation of
indole with alcohols,19 the present reaction may proceed through
the hydrogen-borrowing pathway (Fig. 3). The time course of the
reaction (Fig. 4) shows a profile characteristic to a consecutive
reaction mechanism via the unreduced intermediate, phenylethe-
nylquinoline, detected by GC–MS analysis; the intermediate
formed at an initial induction period is consumed to give the
Table 2
Table 3
a
Alkylation of 2-methylquinoline with benzyl alcohol with 1 wt % metal-loaded Al2O3
Alkylation of 2-methylquinoline with benzyl alcohol with 1 wt % Pt-loaded catalystsa
Entry
Catalysts
Conv. (%)
Yield (%)
Entry
Catalysts
Conv. (%)
Yield (%)
1
2
3
4
5
6
7
8
9
Pt/Al2O3
Ir/Al2O3
83
79
47
39
29
15
7
82
53
6
31
32
5
4
0
0
1
2
3
4
5
6
7
8
9
Pt/Al2O3
Pt/Nb2O5
Pt/C
Pt/BEA
Pt/ZrO2
Pt/CeO2
Pt/MgO
PtOx/Al2O3
Pt/Al2O3-air
83
50
12
5
15
10
8
82
20
7
1
1
0
0
40
5
Re/Al2O3
Rh/Al2O3
Pd/Al2O3
Ag/Al2O3
Ni/Al2O3
Co/Al2O3
Cu/Al2O3
0
0
45
18
a
a
Conditions: 2-methylquinoline (1 mmol), benzyl alcohol (1.1 mmol), metal
(0.02 mmol), mesitylene (1 g), 170 °C, 36 h.
Conditions: 2-methylquinoline (1 mmol), benzyl alcohol (1.1 mmol), Pt
(0.02 mmol), mesitylene (1 g), 170 °C, 36 h.

6492
C. Chaudhari et al. / Tetrahedron Letters 54 (2013) 6490–6493
Table 4
R
OH
a
Alkylation of 2-methylquinoline with alcohols with Pt/Al2O3
N
N
R
R
Pt
Pt/Al2O3 (2 mol%)
+
R
OH
N
mesitylene (1 g)
170 oC, 36 h
N
R
1.1 mmol
1 mmol
Pt-H
R
O
Entry
Product
Yield (%)
1
2
82 (75)
72 (65)
N
N
N
N
Figure 3. Presumable catalytic cycle for Pt/Al2O3-catalyzed alkylation of 2-meth-
ylquinoline with alcohols.
100
N
N
80
60
3
70 (60)
40
4
5
75 (70)
50 (42)
N
N
Cl
F
20
0
N
10
20
30
0
t / h
6b
7b
63 (55)
60 (50)
Figure 4. Time-yield profile for the alkylation of 2-methylquinoline (1 mmol) with
benzyl alcohol (1.1 mmol) in mesitylene (1 g) under reflux conditions in the
N
N
presence of 1 mol % of Pt/Al2O3: yields of unreacted 2-methylquinoline ( ), 2-
r
phenethyl-quinoline (s), and phenylethenylquinoline (d).
a
Conditions: 2-methylquinoline (1 mmol), alcohol (1.1 mmol) , Pt (0.02 mmol),
condensation of aldehyde and 2-methylquinoline gives alkenyl-
quinoline, which is hydrogenated by the Pt-H species to give alkyl-
ated quinoline.
mesitylene (1 g), 170 °C, 36 h. Isolated yields are in parentheses.
b
Undecane (1 g) as solvent, 200 °C, 36 h.
In summary we have shown that
c-Al2O3 supported Pt metal
nanoclusters catalyze the alkylation reaction of 2-methylquinoline
with various alcohols under additive free conditions. Considering
the fact that the previous system using a homogeneous Ir catalyst
with 50 mol % t-BuOK and 20 mol % Ph3P is the only successful cat-
alytic method of the title reaction, our method provides the most
environmentally benign catalytic system for this reaction because
of the following advantages: (1) high TON, (2) easy catalyst/prod-
uct separation, (3) catalyst reuse, (4) no need of additives, and ex-
cess molar amount of 2-methylquinoline.
100
80
60
40
20
Acknowledgment
0
1
2
3
4
5
Cycle number
This work was supported by a MEXT program ‘Elements Strat-
egy Initiative to Form Core Research Center’ (since 2012), Japan.
Figure 2. Recycle study for alkylation of 2-methylquinoline with alcohols with Pt/
Al2O3.
Supplementary data
hydrogenated product. As shown in Eq. 1, the reaction of benzalde-
hyde and 2-methylquinoline with Pt/Al2O3 under N2 resulted in the
formation of the unreduced intermediate, phenylethenylquinoline,
in 70% yield. As shown in Eq. 2, the transfer hydrogenation of phe-
nylethenylquinoline by benzyl alcohol with Pt/Al2O3 gave the
hydrogenated product in 60% yield. From these considerations,
we propose a possible catalytic cycle shown in Figure 3. First,
hydrogen transfer from alcohol to a Pt° site on a Pt metal cluster,
gives aldehyde and Pt-H species. Then, Al2O3-catalyzed aldol
Supplementary data (general method, characterization data)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2013.09.077.
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