Acceptorless dehydrogenative synthesis of 2-substituted quinazolines from 2-aminobenzylamine with primary alcohols or aldehydes by heterogeneous Pt catalysts

Article abstract of DOI:10.1039/c4ra09205h

CeO₂-supported Pt nanoparticle catalysts enabled the acceptorless dehydrogenative synthesis of 2-substituted quinazolines from 2-aminobenzylamine with aliphatic and benzyl primary alcohols or aldehydes with low catalyst loading, wide substrate

Full text of DOI:10.1039/c4ra09205h

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Acceptorless dehydrogenative synthesis of
2-substituted quinazolines from
Cite this: RSC Adv., 2014, 4, 53374
2-aminobenzylamine with primary alcohols or
aldehydes by heterogeneous Pt catalysts†
Received 25th August 2014
Accepted 9th October 2014
Chandan Chaudhari,a S. M. A. Hakim Siddiki,b Masazumi Tamurac
DOI: 10.1039/c4ra09205h
ab
*
and Ken-ichi Shimizu
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CeO2-supported Pt nanoparticle catalysts enabled the acceptorless aldehydes, use of primary alcohols instead of aldehydes is also
dehydrogenative synthesis of 2-substituted quinazolines from 2- an important alternative, but acceptorless methods are not
aminobenzylamine with aliphatic and benzyl primary alcohols or reported. The only one example using the Ir-catalyst12 with the
aldehydes with low catalyst loading, wide substrate scope and good acceptor was applicable only to an activated alcohol, benzy-
catalyst reusability, demonstrating the first acceptor-free and lalcohol. As a part of our continuing interest in heterogeneous
additive-free catalytic system for this reaction.
Pt catalysts for the acceptorless dehydrogenation of alcohols14
and acceptorless dehydrogenative coupling reactions,15,16 we
report herein the rst acceptorless method for the synthesis of
2-substituted quinazolines from 2-aminomethyl-phenyl amine
and alcohols or aldehydes using a CeO2-supported Pt catalyst
(Pt/CeO2).
Quinazolines are important compounds in organic synthesis
and the industrial production of pharmaceutical compounds
which show various biological activities1–6 such as antibacte-
rial,1 antiviral,2 antitubercular3 and anticancer4,6 activities.
Various methods have been reported for the synthesis of 2-
substituted quinazolines. One of the representative methods is
the oxidative condensation of 2-aminobenzylamines with alde-
hydes via aminal intermediates using stoichiometric amounts
of toxic oxidants such as DDQ,7 MnO2 (ref. 8) and NaClO.9 Yu
et al.10 reported more atom-efficient synthesis of 2-substituted
quinazolines: an aerobic oxidative process by 5 mol% CuCl/
DABCO/TEMPO catalyst. Kobayashi et al. reported that Pt/Ir
bimetallic nanoclusters cooperated with dimeric catechol
derivative effectively catalyzed the aerobic oxidative synthesis of
quinazolines from 2-aminobenzylamines and aldehydes at 35
ꢀC under basic conditions.11 Recently, Fang et al.12 showed an
anaerobic method using [Cp*IrCl2] complex in presence of
excess amount (4 equiv.) of acceptor (styrene) under basic
conditions. The most attractive methodology is an anaerobic
method in the absence of any oxidant (acceptor), so called
dehydrogenative acceptorless coupling reactions.13 Considering
that alcohols are more stable and readily available than
First, we studied the acceptorless dehydrogenative synthesis
of 2-substituted quinazolines from 2-aminobenzylamine 1a and
primary alcohols, which was unprecedented in the literature.
We carried out catalyst screening tests adopting the model
reaction of 1a (1 mmol) with 1-octanol (1.2 mmol) under the
same conditions: reux in mesitylene under N2 for 48 h using
1 mol% of metal catalysts. Table 1 lists the yields of 2-
substituted quinazoline 3a (the main product) and an inter-
mediate, 2-heptyl-1,2,3,4-tetrahydro-quinazoline 2a (a byprod-
uct). Among various transition metal nanoparticles loaded on
CeO2 (entries 1–8), Pt/CeO2 (entry 1) showed the highest yield
(90%) of 3a without forming the byproduct 2a. CeO2 itself was
inert (entry 9). The effect of support materials of Pt catalysts
(entries 1, 11–17) showed that CeO2 was the most effective
support of Pt. Other supports such as TiO2, MgO and Nb2O5
gave moderate yields. Consequently, Pt/CeO2 was found to be
the most effective catalyst for the dehydrogenative synthesis of
3a from 1a and 1-octanol.
It is established that the O1s binding energy of metal oxides
decreases with increase in the electron density of oxygen in the
metal oxide, or in other words, basicity of the metal oxide
surface.17–19 In our previous report,19 we measured the binding
energy of the O1s electron in the support oxide by XPS analysis.
XPS spectra of Nb2O5, TiO2 and MgO were added to the previous
results as shown in Fig. 3. The O1s binding energy of the peak
maxima decreased in the order of SiO2Al2O3 > SiO2 > g-Al2O3 >
Nb2O5 > ZrO2 > TiO2 > MgO > CeO2. Fig. 4 shows the yield of 3a
aCatalysis Research Center, Hokkaido University, N-21, W-10, Sapporo 001-0021,
Japan. E-mail: kshimizu@cat.hokudai.ac.jp; Fax: +81-11-706-9163
bElements Strategy Initiative for Catalysts and Batteries, Kyoto University, Katsura,
Kyoto 615-8520, Japan
cDepartment of Applied Chemistry, School of Engineering, Tohoku University, 6-6-07,
Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra09205h
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Table 1 Synthesis of 3a from 1a and 1-octanol by 1 wt% metal-loaded catalysts
Entry
Catalysts
2a yield (%)
3a yielda (%)
1
2
3
4
5
6
7
8
Pt/CeO2
Pd/CeO2
Ir/CeO2
Re/CeO2
Rh/CeO2
Ru/CeO2
Cu/CeO2
Ni/CeO2
PtOx/CeO2
CeO2
0
0
20
10
18
0
0
0
0
0
0
0
30
20
0
0
0
0
0
90
17
16
12
10
7
0
0
0
0
65
45
43
26
24
18
10
10
10
9b
10c
11
12
13
14
15
16
17
18
19
Pt/TiO2
Pt/MgO
Pt/Nb2O5
Pt/Al2O3
Pt/ZrO2
Pt/SiO2Al2O3
Pt/SiO2
Pt/HBEA
Pt/La2O3
a
Yield based on 1a determined by GC. b Tested without pre-reduction. c Catalyst amount was 197 mg.
Fig. 1 Time course of the reaction of 1a with 1-octanol by Pt/CeO2.
Conditions are shown in Table 1.
Fig. 3 XPS spectra of the O(1s) core level region of the support
materials.
Fig. 4 Yield of 3a for the reaction of 1a with n-octanal by Pt-loaded
metal oxides as a function of O1s binding energy of support oxides.
Fig. 2 Time course of the reaction of 1a with n-octanal by Pt/CeO2.
Conditions are shown in Table 3.
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from 1a and 1-octanol (Table 1) as a function of the O1s binding
With the optimized catalyst in hand, we examined the
energy of the support oxides. There is a general tendency that substrate scope of the dehydrogenative quinazolines syntheses.
the support with higher O1s binding energy gives higher yield, Table 2 shows the isolated yields of the 2-substituted quinazo-
which indicates that the activity increase with basicity of the lines from the reaction of 1a with different primary alcohols
support.
using 1 mol% of Pt/CeO2. Linear and branched aliphatic
a
Table 2 Synthesis of 2-substituted quinazolines from 1a and alcohols by Pt/CeO2
Entry
Alcohol
Product
Isolated yielda (%)
1
2
3
89
75
89
4b
5
76
52
6
51
a
Yield based on 1a determined by weight of the isolated products. b 1.5 mmol alcohol.
Table 3 Synthesis of 3a from 1a and n-octanal with 1 wt% metal loaded catalysts
Entry
Catalysts
2a yield (%)
3a yielda (%)
1
2
3
4
5
6
7
8
Pt/CeO2
Pd/CeO2
Rh/CeO2
Re/CeO2
Ni/CeO2
Ir/CeO2
Ru/CeO2
Cu/CeO2
CeO2
Pt/TiO2
Pt/MgO
Pt/Nb2O5
Pt/Al2O3
Pt/ZrO2
Pt/HBEA
Pt/La2O3
0
0
17
7
22
75
60
40
20
0
29
0
0
0
0
98
60
55
42
18
12
12
10
0
99
56
90
89
70
69
95
9b
10
11
12
13
14
15
16
0
a
Yield based on 1a determined by GC. b Catalyst amount was 197 mg.
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(1)
(2)
Table 4 Synthesis of 2-substituted quinazolines from 1a and aldehydes by Pt/CeO2
Entry
Aldehyde
Product
Isolated yielda (%)
1
93 (95), (90),c (90)d
2
70
92
84
3
4b
5b
6
88
50
7
8
9
72
85
77
10
90
57
11
a
b
Yield based on 1a determined by weight of the isolated products. GC yields are in the parentheses. 1.5 mmol aldehyde. c Reuse 1. d Reuse 2.
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alcohols (entries 1–3) were converted to the corresponding preliminary studies on the aldehyde scope for this reaction, we
2-substituted quinazolines in good yields (75–89%). Benzy- selected Pt/CeO2 as the standard catalyst. The reaction with
lalcohol and 4-uoro benzylalcohol resulted in moderate yields CeO2 gave 20% yield of the non-dehydrogenated intermediate
(52, 51%). This is the rst example of the acceptorless dehy- 2a but no yield of the dehydrogenated product 3a (entry 9).
drogenative synthesis of 2-substituted quinazolines from 1a
Table 4 shows the general applicability of the dehydrogen-
and various primary alcohols.
ative synthesis of 2-substituted quinazolines from 1a and
Next, we studied the dehydrogenative synthesis of 2- aldehydes using 1 mol% of Pt/CeO2. Various aliphatic aldehydes
substituted quinazolines from 1a and aldehydes. Table 3 including linear, branched and cyclic aldehydes (entries 1–7)
summarizes the result of catalyst screening for the model were converted to the 2-substituted quinazolines in moderate to
reaction of 1a and n-octanal. Among various metal-loaded CeO2 high isolated yields (50–93%). The reactions of 1a and benzal-
(entries 1–8) and Pt-loaded metal oxides (entries 10–16), Pt/ dehydes with electron-donating and electron-withdrawing
CeO2, Pt/TiO2 and Pt/La2O3 were found to be effective exhibiting substituents proceeded to give moderate to high isolated yield
high yields (95–99%) of 1a. On the basis of the results of (entries 8–11). For the reactions with n-octanal (eqn (1)) and
(3)
(4)
(5)
(6)
Scheme 1 A possible pathway of Pt/CeO2-catalyzed dehydrogenative synthesis of quinazolines 3 from 1a with alcohols or aldehydes.
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benzaldehyde (eqn (2)), we carried out synthesis of 2-substituted aminobenzylamine and alcohols or aldehydes using Pt/CeO2 as
quinazolines using small amount (0.2 mol%) of the Pt/CeO2 a reusable heterogeneous catalyst.
catalyst for 52 h, and the results showed 95 and 90% yield,
corresponding to the turnover number (TON) of 470 and 450.
The TON of 450 for the reaction of 1a and benzaldehyde was
Acknowledgements
higher than those of the previous catalytic systems in the This work was supported by Grant-in-Aids for Scientic
presence of oxidants: TONs of 19 (CuCl/TEMPO/DABCO),10 26 Research B (26289299) from MEXT (Japan), a MEXT program
([IrCp*Cl2]2/KOH)12 and 190 (PI/CB-Pt/Ir/TTSBI/K2CO3.11
“Elements Strategy Initiative to Form Core Research Center”
We studied leaching test and reusability of Pt/CeO2 for the and a Grant-in-Aid for Scientic Research on Innovative Areas
synthesis of 3a from 1a and n-octanal. The reaction was “Nano Informatics” (25106010) from JSPS.
completely terminated by removal of the catalyst from the
reaction mixture aer 1 h (29% yield of 3a); further heating of
the ltrate for 48 h under the reux conditions did not
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