Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or-cobalt nanoparticles

Article abstract of DOI:10.1021/ja2080086

Considering the importance of the development of powerful green catalysts and the omnipresence of amide bonds in natural and synthetic compounds, we report here on reactions between alcohols and amines for amide bond formation in which heterogeneous gold and gold/iron, -nickel, or-cobalt nanoparticles are used as catalysts and molecular oxygen is used as terminal oxidant. Two catalysts show excellent activity and selectivity, depending on the type of alcohols used. A wide variety of alcohols and amines, including aqueous ammonia and amino acids, can be used for the amide synthesis. Furthermore, the catalysts can be recovered and reused several times without loss of activity.

Full text of DOI:10.1021/ja2080086

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pubs.acs.org/JACS
Powerful Amide Synthesis from Alcohols and Amines under Aerobic
Conditions Catalyzed by Gold or Gold/Iron, -Nickel or -Cobalt
Nanoparticles
Jean-Franc-ois Soulꢀe, Hiroyuki Miyamura, and Shu Kobayashi*
Department of Chemistry, School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S Supporting Information
b
reduced).7a,b,e Furthermore, special handling of expensive metal
ABSTRACT: Considering the importance of the develop-
ment of powerful green catalysts and the omnipresence of
amide bonds in natural and synthetic compounds, we report
here on reactions between alcohols and amines for amide
bond formation in which heterogeneous gold and gold/iron,
-nickel, or -cobalt nanoparticles are used as catalysts and
molecular oxygen is used as terminal oxidant. Two catalysts
show excellent activity and selectivity, depending on the
type of alcohols used. A wide variety of alcohols and amines,
including aqueous ammonia and amino acids, can be used
for the amide synthesis. Furthermore, the catalysts can be
recovered and reused several times without loss of activity.
complexes and ligands is required in many cases. On the other
hand, so far, relatively little work has been carried out on the
oxidative transformations. A rhodium catalyst was developed, but
a large amount of hydrogen acceptor is required.7d The oxidation
pathway (Figure 1 (3)) starting from aldehydes8 or alcohols
requires one or more equivalents of an oxidant.9 We planned to
use an alternative pathway for the amide formation from an
alcohol and an amine, namely via a tandem oxidative process
(TOP) (Figure 1 (4)).10 TOP is clearly different from the
dehydrogenative pathway (Figure 1 (2)) in that the reaction
proceeds under oxidative conditions and the only byproduct is
water. On the other hand, this oxidation process is very challeng-
ing, because there are many possible side-reaction pathways and
many byproducts, such as IX,11 X,12 XI,13 XII,14 XIII, and XI,15
might be obtained. Some groups recently studied this process;
however, yields of the desired compounds (IV) were low, and
applicable substrates were very limited.14,16 We envisioned that
the key step was the oxidation of carbinolamine VII generated
from aldehyde VI (formed in situ from alcohol V) and an amine
(Figure 1 (4)), and that this step might be catalyzed by gold
nanoparticle catalysts. Our group has recently developed gold
nanoparticle catalysts immobilized on polystyrene-based poly-
mers with cross-linked moieties, namely polymer-incarcerated
(carbon black) catalysts (PI or PICB catalysts), which show
excellent activity for the aerobic oxidation of alcohols to carbonyl
compounds13e,17 and amines to imines.15c These catalysts are
quite efficient and can be recycled many times, which makes
them one of the most important green catalysts.18 We have also
recently demonstrated a remarkable effect of bimetallic com-
plexes with gold and other noble metals like palladium or
platinum for the selective oxidation of alcohols to aldehydes,
carboxylic acids, or esters, depending on different combinations
of alloy nanoparticles.18a,19
he amide is one of the most important functional groups in
T
chemistry.1 It plays a major role in the elaboration and
composition of biological and chemical systems and polymer
compounds. While amide bond formation remains a fundamen-
tal reaction in organic chemistry,2 it is usually created by
reactions of carboxylic acids with amines using coupling reagents
or by prior conversion of carboxylic acids to derivatives such as
acid chlorides or anhydrides (Figure 1 (1)).3 Over the past few
years, chemists have made great efforts to develop suitable and
environmentally friendly processes,4 and in this context, the
development of new methodologies for amide bond formation
represents a major socioeconomic stake for chemical companies
and an important challenge for academic research groups.5
In 2007, an important discovery was made by the research
group of Milstein et al.6 They described the first coupling
between an alcohol and an amine for the amide bond formation
catalyzed by a ruthenium pincer complex, with molecular hydro-
gen being the only byproduct (Figure 1 (2)). This direct catalytic
conversion of alcohols and amines into amides and dihydrogen
(molecular hydrogen) is a particularly desirable reaction due to
its high atom efficiency, and this clean and simple reaction has
inspired several other research groups to further develop the
reactions.7 However, although several efforts have been made,
the limited availability of substrates remains a disadvantage.
Although the catalysts showed excellent activity with sterically
unhindered alcohols and amines, limited activity was observed
with sterically hindered alcohols and amines, less basic amines,
and secondary amines. Moreover, since the reactions were
conducted under reductive conditions (hydrogen is formed),
unsaturated bonds such as CdC were not tolerated (they were
Here, we report the first selective and general amidation using
TOP starting from an alcohol and an amine, in a one-to-one
equivalent, in the presence of PICB-Au or a new generation of
bimetallic nanoparticle catalysts consisting of gold and inexpen-
sive metals, such as iron, nickel, or cobalt, under mild conditions
with water being the only byproduct.
First, we investigated the amidation of 3-phenylpropan-1-ol
(for an aliphatic case) and 4-methylbenzyl alcohol (for a benzylic
alcohol case) in the presence of one equivalent of benzylamine
with O2 and PICB catalysts (Table 1).20 We found that such
Received: August 24, 2011
Published: October 21, 2011
r
2011 American Chemical Society
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Table 1. Optimization of Reaction Conditionsf
Figure 1. Different pathways for the amide bond formation.
reactions proceeded when one equivalent of NaOH in a mixed
solvent, THF/water in a 19:1 ratio, was used.21 We initially
investigated PICB-Au catalysts prepared by a procedure pub-
lished previously.17b However, we found that the catalysts were
not very active for the amidation of an aliphatic alcohol and not
selective for a benzylic alcohol (Table 1, entries 1 and 10). For
the aliphatic case, a low conversion (53%) but high selectivity of
the amide product 3aa was obtained. The first oxidation of an
alcohol 1a to an aldehyde 4a was found to be more difficult in the
presence of one equivalent of an amine than in the absence of an
amine (Table 1, entries 1,2). To improve the activity, we raised
the temperature from room temperature to 40 °C, and good
conversion and good selectivity were observed (Table 1, entry 6).
For the benzylic alcohol, good conversion but low selectivity was
obtained with PICB-Au at room temperature. The yield of amide
3ba was only 45%, and imine 6ba was the major byproduct.
To improve the amide yield and the selectivity, we searched
for other catalysts. We found that PICB-Au/Pt and PICB-Au/Pd
did not exhibit good activity for this reaction (Table 1, entries
11,12). However, we established that a new association between
gold and inexpensive metals of period 4 (nickel, iron, or cobalt)
has a positive effect on the amide selectivity (Table 1, entries
13À15). In these new catalysts, the association of gold and cobalt
is the best combination, and the desired amide 3ba was obtained
in 94% isolated yield. To the best of our knowledge, this is the
first example of a positive effect of gold nanoparticles doped with
cobalt, nickel, or iron.
a Determined by gas chromatography (GC) analysis using dodecane as
an internal standard. Number in parentheses is isolated yield. b Deter-
mined by 1H NMR. c The reaction was performed without amine.
d Reaction was performed under an atmosphere of air for 24 h. e 4-
Methylbenzyl 4-methylbenzoate was used instead of 1b. (n.d. = not
detected, n.r. = no reaction).
f
benzylamine 2a under the same conditions (Table 1, entry 22)
led to formation of the corresponding imine as major product.
The imine did not react under these conditions (Table 1, entry
24). These results suggest that a low concentration of aldehyde
during the reaction is required to obtain a high selective reaction.
On the other hand, when the reaction was conducted with
4-methylbenzoic acid 5b or 4-methylbenzyl-4-methylbenzoate
instead, no reactions were observed (Table 1, entries 23 and 25).
These results suggest that benzoic acid and ester are not
intermediate in this reaction and the reaction proceeds by a
carbinolamine. At this stage, we thought that cobalt might
stabilize the carbinolamine and inhibit the dehydration process
and that, if cobalt and gold particles were in close proximity, the
reaction would then proceed with a better selectivity.
To confirm this observation, we conducted several control
experiments. First, the activity of Co2+ ions in the presence of
PICB-Au (Table 1, entry 21) was examined, and different
selectivity in favor of amide 3ba was observed. Results indicated
that the active species was not the Co2+ ions. Second, we carried
out this reaction using two catalysts prepared independently
(Table 1, entry 20). In this case, lower selectivity compared with
that obtained when using PICB-Au/Co, but better selectivity
compared with that obtained when using PICB-Au only was
observed. The reaction between 4-methylbenzaldehyde 4b and
The catalyst was recovered by simple filtration and reused
without significant loss of activity.22 The recovered catalyst could
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Table 2. Scope of the Reaction
Figure 2. STEM and EDS analyses of PICB-Au/Co catalysts. (1)
Typical STEM image and size distribution. (2) EDS line analysis of a
cluster (green: Au; red: Co). (3) EDS line analysis of several clusters
(green: Au; red: Co).
be washed with water, THF, or CH2Cl2 and then heated at
170 °C for 5 h to facilitate its reuse.21 Finally, we examined the
TOP using air (under balloon pressure) as the terminal oxidant
and found that the reaction proceeded smoothly under our
optimized reaction conditions (Table 1, entries 7 and 16).
Next, we conducted scanning transmission electron micro-
scopy (STEM) and energy dispersive spectroscopy (EDS)
analyses to characterize the newly prepared bifunctional compo-
site catalyst PICB-Au/Co (Figure 2). EDS line analysis revealed
the following: a single Gaussian distribution of X-rays of Au
across the nanoparticle (5 nm) and independent multiple
Gaussian distributions of X-rays of Au and Co. This observation
indicated the random arrangement of Au and Co atoms without
formation of Au/Co alloys as previously reported in the case of
PICB-Au/Pt or PICB-Au/Pd.19b,c Moreover, these results sug-
gested that Co does not exist inside the Au nanoparticles but is
dispersed throughout the polymer/CB composite material, and
Au and Co lie in close proximity. Additional proof of this
proximity between Au and Co is provided by EDS mapping
analysis.21 At this stage, we think that Co has two effects: (a) with
an electronic interaction between Au and Co (Table 1, substrate
= 1a, entries 1 and 4) the reactivity of Au is decreased, and (b) Co
can stabilize the carbinolamine during the oxidation step
(Table 1, substrate = 1b, entries 10 and 15. See also Figure 1).
To demonstrate the general applicability of the PICB-Au/X
system, various alcohols were tested in amidation reactions with
benzylamine 2a. In general, the catalytic experiments were
conducted under a dioxygen atmosphere in the presence of
1 mol % PICB-Au/Co catalyst at 25 °C (conditions A) for benzylic
alcohols, and 1.5 mol % PICB-Au at 40 °C (conditions B) for
nonbenzylic alcohols. It was found that both electron-poor and -
rich benzylic alcohols (Table 2, entries 2À4) were successfully
converted to the corresponding amides 3baÀda in good to
excellent yields. We also determined that the reactions of alcohols
bearing heterocycles and naphthalene proceeded very well to afford
the corresponding amides in good yields (Table 2, entries 5À7).
a Yield of coresponding imines. b 2 equiv of alcohol was used. c 6 equiv of
aqueous ammonia was used. d 2 mol% of catalyst was used, and the
reaction was performed in THF/water (9:1) in the presence of 2 equiv
of base.
Next, allylic alcohols were also tried. Using cinnamyl alcohol,
conditions A furnished a moderate yield; however, a poor yield
(39%) was observed under conditions B (Table 2, entries 8À9).
Allylic alcohol was also tried, and a 60% yield of amide 3ia was
obtained.23 It was noted that the CdC double bond moieties were
tolerant in the present amide formation, whereas the reduction of
double bond moieties occurred in alternative processes using
ruthenium catalysts. When aliphatic alcohols 1a and 1jÀl were
used as coupling partners, conditions B were used, and the desired
amides 3aa and 3kaÀla were obtained in good yields (Table 2,
entries 1 and 10À12).
We also investigated the amines. Excellent yields were ob-
tained with benzylic amine 2a or aliphatic amines (Table 2,
entries 14À19). Steric effects of the amine may play a key role.
A bulky group, such as cC5H11 2g, afforded amide 3mg in moderate
yield (Table 2, entry 19), but no product was obtained when
using a bulkier amine (Table 2, entry 21). The reaction with a
primary aromatic amine (Table 2, entry 22) proceeded smoothly
to afford the amide 3mj in good yield. When using an aqueous
solution of ammonia, this TOP can directly provide the primary
amide 3mk in good yield. To the best of our knowledge, this free
amidation reaction, using aqueous ammonia and starting from an
alcohol, is the first reported. With a secondary amine, only a trace
of amide 3bl was observed when PICB-Au/Co was used. We
then decided to optimize the reaction conditions. When condi-
tions B were used, amide 3bl was isolated in 70% yield. Cyclic
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secondary amines such as piperidine and morpholine (Table 2,
entries 26 and 25, respectively) offered better yields than the
simple secondary amines (Table 2, entries 24 and 27). Interest-
ingly, when the oxidative amidation reaction was applied to an
optically active amino acid and its derivates, the reaction pro-
ceeded smoothly with yields of 73% and 69% (Table 2, entries 28
and 30). No racemization occurred in this reaction, and a free
amino acid could be used directly.
Currently available data do not allow one to explain clearly the
several remarkable effects of the bimetallic Au/Co complex for
the selective formation of amide products and the difference in
activities for PICB-Au and PICB-Au/Co, but there are several
possibilities. The cobalt center may stabilize the carbinolamine
form and decrease the activity of gold nanoparticles in the first
oxidation step. Although the mechanistic issues are yet to be
resolved, the results of this work have demonstrated that,
depending on the catalyst system, the amide bond formation
from alcohols and amines when using molecular oxygen as a
terminal oxidant can be conducted with high selectivity and in
high yields when using heterogeneous catalysts. These catalysts
can be reused several times. The method has been generalized
and a wide variety of substrates has been tested (benzylic, allylic,
and aliphatic alcohols; primary and secondary amines; aniline;
aqueous ammonia; and amino acids), and these have shown good
activity in this coupling. Our results indicate that this is one of the
greenest and most general methods for amide bond formation
from alcohols and amines.
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’ ASSOCIATED CONTENT
S
Supporting Information. Reaction procedure and spec-
b
tra. This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
shu_kobayashi@chem.s.u-tokyo.ac.jp
’ ACKNOWLEDGMENT
This work was partially supported by a Grant-in-Aid for
Science Research from the Japan Society for the Promotion of
Science (JSPS), Global COE Program, The University of Tokyo,
MEXT, Japan, and NEDO. We also thank Mr. Noriaki Kuramitsu
(The University of Tokyo) for STEM and EDS analysis.
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