A Titanium Dioxide Supported Gold Nanoparticle Catalyst for the Selective N-Formylation of Functionalized Amines with Carbon Dioxide and Hydrogen

Article abstract of DOI:10.1002/cctc.201700726

A TiO₂-supported, gold nanoparticle catalyst was found to allow the N-formylation of various amines, including normally unreactive anilines, by using CO₂ as the carbonyl source under a H₂ atmosphere. A series of reducible functional groups, such as olefins, halogens, carbonyls, carbamates, and cyano moieties, were completely retained during the formylation, which proved the highly selective nature of the formylation reaction. The catalyst was also found to be reusable without any loss of activity or selectivity.

Full text of DOI:10.1002/cctc.201700726

Accepted Article
Title: A Titanium Dioxide-supported Gold Nanoparticle Catalyst for the
Selective N-Formylation of Functionalized Amines with CO2 and
H2
Authors: Kiyotomi Kaneda, Takato Mitsudome, Teppei Urayama, Shu
Fujita, Zen Maeno, Tomoo Mizugaki, and Koichiro Jitsukawa
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To be cited as: ChemCatChem 10.1002/cctc.201700726
Link to VoR: http://dx.doi.org/10.1002/cctc.201700726
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10.1002/cctc.201700726
ChemCatChem
A Titanium Dioxide-supported Gold Nanoparticle Catalyst for the
Selective N-Formylation of Functionalized Amines with CO2 and H2
Takato Mitsudome, Teppei Urayama, Shu Fujita, Zen Maeno, Tomoo Mizugaki,
Koichiro Jitsukawa, Kiyotomi Kaneda*
[*]Dr. T. Mitsudome, Dr. T. Urayama, S. Fujita, Dr. Z. Maeno, Dr. T. Mizugaki,
Prof. Dr. K. Jitsukawa, Prof. Dr. K. Kaneda
Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka
University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan
Fax: (+81) 6-6850-6260, E-mail: kaneda@cheng.es.osaka-u.ac.jp
K. Kaneda
Research Center for Solar Energy Chemistry, Osaka University,
1-3, Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)
[**]This work was supported by JSPS KAKENHI Grant Nos. 26289303, 26630410,
26105003 and 24246129. This work was also supported by the Program for Creating
Future Wisdom, Osaka University, as selected in 2014. The TEM experiments were
carried out at the Institute for NanoScience Design Center, Osaka University.
Keywords: amine, formylation, gold, heterogeneous catalyst, titanium dioxide
Abstract: A TiO2-supported gold nanoparticle catalyst was found to allow the N-formylation of
various amines, including normally unreactive anilines, using CO2 as the carbonyl source under a H2
atmosphere. A series of reducible functional groups, such as olefins, halogens, carbonyls, carbamates
and cyano moieties, were completely retained during the formylation, demonstrating the highly
selective formylation of functional amines. The catalyst was also found to be reusable without any
loss of activity or selectivity.
1
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Main text: The chemical utilization of carbon dioxide (CO2) has attracted considerable attention
owing to the potential for reducing this greenhouse gas in the atmosphere and because of the
abundance of readily available carbon.[1] In this context, the replacement of harmful C1 building
blocks, such as phosgene and carbon monoxide, that are currently used in the chemical industry with
low-cost, non-toxic CO2 could allow the sustainable production of valuable chemicals. To date, CO2
has been used as a carbonyl source for the catalytic synthesis of a number of compounds, including
formamides,[2] formic acid,[3] carbonates,[4] urea[5] and carbamates.[6] Among these, formamides are
important intermediates for the production of pharmaceuticals, insecticidal agents and fine
chemicals.[7] Formamides are currently synthesized by low-atom-efficient reactions using
hydrosilanes as reducing reagents.[8] Therefore, the catalytic N-formylation of amines using CO2
together with hydrogen (H2) represents a desirable, atom-economical route because it generates only
water as a byproduct. Recently, the formylation of amines using CO2 with H2 has been studied
employing both homogeneous and heterogeneous catalysts.[2] However, these catalysts are only
applicable to simple amines, and the N-formylation of functionalized amines has been rarely
examined.[9] The selective N-formylation of functionalized amines bearing reducible groups, such as
olefins, halogens, ketones and carbamates, is challenging because the N-formylation of amines
generally requires the application of high H2 pressures and elevated temperatures, which can
deteriorate these reducible groups. Therefore, there is a strong incentive to develop selective catalysts
for the N-formylation of functionalized amines.
Heterogeneous metal nanoparticle (NP) catalysts have been recently demonstrated to be quite
effective for the chemoselective hydrogenation of various functional groups in the presence of other
reducible moieties.[10] This chemoselectivity for specific functional groups is obtained by precisely
controlling the size and shape of the NPs as well as by selecting the appropriate supports and tuning
the NP composition. Especially, small Au NPs on the appropriate supports have exhibited high activity
2
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and selectivity compared to other supported metal NPs.[11] As an example, atomically precise
Au25(SR)18 NPs catalyze the selective hydrogenation of unsaturated carbonyl compounds to allylic
alcohols.[10c] In addition, Au/TiO2 has been shown to selectively hydrogenate substituted
nitroaromatics to the corresponding anilines.[10a] Our own group has also reported that Au NPs
supported on hydrotalcite (Au/HT) and CeO2-encapsulated Au NPs (Au@CeO2) promote the highly
chemoselective hydrogenation of epoxides and alkynes to the corresponding alkenes.[11d, g, h]
Herein, we report a TiO2-supported Au NP catalyst that enables the selective N-formylation of a
diverse range of functionalized amines using CO2 as a carbonyl source under a H2 atmosphere. A
number of reducible functional groups, such as olefins, halogens, ketones, carbamates, aryl, and cyano
moieties were completely retained during these formylation reactions, thus achieving highly selective
synthesis of functionalized formamides. In addition to this high selectivity, the TiO2-supported Au NP
catalyst showed high reusability without any loss of catalytic performance.
Initially, we assessed the catalytic activity of various metal NPs on TiO2 in the formylation of 5-
hexen-1-amine (1) as a model functionalized amine under 20 atm of CO2 and 30 atm of H2 at 100 °C
for 2 h. It was found that Au NPs with a mean diameter of 4.2 nm on TiO2 (Au/TiO2) gave the highest
activity and afforded the desired product (2), while leaving the olefinic moiety of 1 intact (Table 1,
entry 1). Upon prolonging the reaction time to 10 h, 2 was obtained as the sole product in >99% yield
(Table 1, entry 2) without hydrogenation or migration of the olefinic moiety. In sharp contrast, all the
other metal NPs tested, including Pd, Ru, Pt, Rh, Ag and Cu, did not afford 2 at all and, resulted in
hydrogenation of the olefinic moiety of 1 (Table 1, entries 3-8). These data demonstrated the highly
unique catalytic properties of Au NPs for the selective production of 2. Subsequently, the effect of the
support used in conjunction with the Au NPs was investigated in the N-formylation of 1 (Table 1,
entries 1 and 9-15). Interestingly, the catalytic activity of the Au NPs varied significantly with the type
of support. TiO2 was found to be especially effective, giving 2 in high yield (Table 1, entry 1), while
3
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the other supports showed minimal activity for the N-formylation of 1 (Table 1, entries 9-15). It is
evident from the above results that a combination of Au NPs and TiO2 is able to efficiently promote
the selective formylation of 1 to 2.
With Au/TiO2 in hand, the N-formylation of the functionalized amines shown in Table 2 with a
combination of CO2 and H2 was investigated. These amines contained a wide range of reducible
functional groups, including olefin (Table 2, entries 1, 5 and 6), carbonyl (Table 2, entry 8), amide
(Table 2, entry 9), carbamate (Table 2, entry 10), halogen (Table 2, entries 11 and 12), aryl (Table 2,
entries 4,8,11,12,14-16), and cyano (Table 2, entry 13) moieties. All were found to remain intact
during the formylation, thereby achieving the highly selective synthesis of functionalized formamides
4
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in over 99% yields without any formation of by-products. To the best of our knowledge, this is the
first example of the highly selective N-formylation of amines with reducible functional groups being
retained completely intact. The Au/TiO2 catalyst was also found to be active for normally unreactive
aniline derivatives, giving the corresponding anilides in quantitative yields (Table 2, entries 14 and
15). To our knowledge, there has been only one report of a homogeneous Ru catalyst achieving aniline
formylation using H2, and this reaction requires the use of the strong base DBU.[2e] In contrast, the
present Au/TiO2 allowed aniline formylation without any additives. Moreover, Au/TiO2 was also
found to be applicable to the formylation of o-phenylenediamine. The intermediate formanilide
evidently underwent a subsequent intramolecular cyclization to afford benzimidazole, which is a key
compound in various functional materials, pesticides, and pharmaceuticals (Table 2, entry 16).
This heterogeneous Au/TiO2 catalyst also has the significant advantages of separation and reuse
compared to homogeneous catalysts. Following its use in a reaction, the Au/TiO2 was easily removed
from the reaction mixture by filtration and could then be reused for a subsequent reaction without any
pre-treatment. The Au/TiO2 retained its high catalytic activity and selectivity for the formylation of 1
even after the fifth recycling (Table 2, entry 2). Inductively coupled plasma atomic emission
spectrometry (ICP-AES) analysis of the resulting filtrate revealed the absence of Au species (at a
detection limit of 0.1 ppm), demonstrating no leaching of Au species during the reaction. The
transmission electron microscopy (TEM) images of the reused Au/TiO2 catalyst (Fig. S1) showed that
the average diameter of the Au NPs was 4.2 nm, similar to that of the fresh catalyst, thus confirming
the high durability of the Au/TiO2.
5
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To elucidate the origin of the high selectivity of Au/TiO2 during the N-formylation of functionalized
amines, several control experiments were carried out. The N-formylation of 1 using Au/TiO2 was
found not to proceed under a CO atmosphere (Scheme 1a). In addition, the product 2 was not
consumed when employed as the starting material under the same reaction conditions as in Table 1
(Scheme 1b). The N-formylation of n-hexylamine using Au/TiO2 in the presence of 1-hexene gave n-
hexylformamide in 99% yield, while 1-hexene was not hydrogenated and was quantitatively recovered
(Scheme 1c). These results show that Au/TiO2 is effective for the hydrogenation of CO2, but
completely inactive for the hydrogenation of the olefinic moiety. In situ Fourier transform infrared
(FTIR) analysis of the Au/TiO2 after treatment with a mixture of H2 (120 mmHg) and CO2 (30 mmHg)
found new peaks attributed to the formation of formic acid (Figure S3). Moreover, subjecting formic
acid to a dimethylacetamide (DMA) solution of 1 in the presence of TiO2 under an Ar atmosphere at
room temperature selectively generated 2 (Scheme 1d). From these results, it is evident that the Au
NPs hydrogenate CO2 to formic acid while not attacking various functional groups on the amine.[12]
Subsequently, the formic acid generated in situ is activated by the Lewis acid sites of the TiO2[13] and
the nucleophilic attack of the adsorbed amine on the formic acid gives the corresponding formamide
(Scheme 2).[14] This cooperative bifunctional catalysis, in which the Au NPs hydrogenate CO2 to
formic acid and the TiO2 promotes the N-formylation of the amine with formic acid, enables the
selective N-formylation of functionalized amines.
7
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Scheme 1. Control experiments for N-formylation using Au/TiO2 or TiO2.
Scheme 2. Proposed reaction path for the Au/TiO2-catalized N-formylation of amines with CO2 and
H2.
In conclusion, the highly selective N-formylation of functionalized amines using CO2 with H2 was
achieved with a Au/TiO2 catalyst. The Au/TiO2 efficiently promoted the selective N-formylation of a
number of different amines to formamides in excellent yields without hydrogenation of reducible
functional groups. This catalytic system allows simple work-up procedures and exhibits excellent
reusability while demonstrating a broad substrate range. The cooperative bifunctional catalysis of the
Au NPs, which provide CO2 hydrogenation, and the TiO2, which promotes amine formylation with
8
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formic acid, plays a crucial role in the selective N-formylation.
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[12] A control experiment involving the N-formylation of 1 with formic acid using various metal
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12
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COMMUNICATION
Takato Mitsudome, Teppei Urayama,
Shu Fujita, Zen Maeno, Tomoo
Mizugaki, Koichiro Jitsukawa, Kiyotomi
Kaneda*
For the first time, TiO2-supported Au NPs have been shown to promote the
selective N-formylation of various amines to formamides in excellent yields without
hydrogenation of reducible functional groups. This catalytic system has the
significant advantages of simple work-up procedures, high reusability, and
applicability to a wide range of substrates.
Page No. – Page No.
A Titania-supported Gold Nanoparticle
Catalyst for
the Selective N-
Formylation of Functionalized Amines
with CO2 and H2
13
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