Methanol Promoted Palladium-Catalyzed Amine Formylation with CO2 and H2 by the Formation of HCOOCH3

Article abstract of DOI:10.1002/cctc.201801404

The N-formylation reaction of amines is one of the most effective measures to make the best use of CO₂, since the formamides have widespread applications in industry. Herein, we performed the N-formylation reaction over Mg?Al layered double hydroxide (Mg?Al LDH) supported Pd catalyst (Pd/LDH) for the first time and studied the relation between the solvent and the mechanism. In this reaction, the methanol can greatly improve the yield of the desired product by forming the HCOOCH₃. The catalytic system is effective for various amines including cyclic and alkyl secondary amines. Under the optimized reaction condition, we gained 88.5 %–97.4 % yields of the formamides for various substrates.

Full text of DOI:10.1002/cctc.201801404

Accepted Article
Title: Methanol Promoted Palladium-catalyzed Amine Formylation with
CO2 and H2 by the Formation of HCOOCH3
Authors: Yanyan Wang, Bingfeng Chen, Shulin Liu, Xiaojun Shen,
Shaopeng Li, Youdi Yang, Huizhen Liu, and Buxing Han
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the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201801404
Link to VoR: http://dx.doi.org/10.1002/cctc.201801404
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10.1002/cctc.201801404
ChemCatChem
COMMUNICATION
Methanol Promoted Palladium-catalyzed Amine Formylation with
CO2 and H2 by the Formation of HCOOCH3
Yanyan Wang,[a,b] Bingfeng Chen,[a] Shulin Liu,[a,b] Xiaojun Shen, [a,b] Shaopeng Li, [a,b] Youdi Yang, [a,b]
Huizhen Liu,*[a,b] and Buxing Han*[a,b]
Dedication ((optional))
Abstract: The N-formylation reaction of amines is one of the most
effective measures to make the best use of CO2, since the
formamides have widespread applications in industry. Herein, we
performed the N-formylation reaction over Mg-Al layered double
hydroxide (Mg-Al LDH) supported Pd catalyst (Pd/LDH) for the first
time and studied the relation between the solvent and the
mechanism. In this reaction, the methanol can greatly improve the
yield of the desired product by forming the HCOOCH3. The catalytic
system is effective for various amines including cyclic and alkyl
secondary amines. Under the optimized reaction condition, we
checked the effect of solvent and found that the best solvent
was methanol for the N-formylation reaction over pyridine-
functionalized organic porous polymers supported Ru catalyst.[9]
According to the results reported in the literature, we found that
the different solvent was used over different catalytic system.
The reaction path is also important for the N-formylation
reaction. In our previous work, we proposed the mechanism of
the Cu-catalyzed formylation reaction in THF, where the salt
(alkyl ammonium alkyl carbamate) served as the intermediate.[10]
Except for this reaction pathway, the route to N-formylation
gained 88.5%-97.4% yields of the formamides for various substrates. reaction with CO2 and H2 through formic acid was also reported,
where HCOOH is formed from the hydrogenation of CO2.[8] In
spite of the good performance with different catalysts in various
Nowadays, carbon dioxide chemistry has attracted
solvents, the reports about the effect of the solvent on the
extensive interest in both academic and industrial community[1]
performance of the reaction and the relation between the solvent
since the greenhouse effect becomes more and more serious,
and the mechanism is little up to now.
where CO2 contributes a lot. Catalytic chemical reduction of CO2
Layered double hydroxides (LDHs) are a class of synthetic
to valuable compounds is one of the most effective measures to
make waste profitable.[2] On the one hand, CO2 can be
anionic clay. Generally, the layered double hydroxide is
3+
represented by the formula [M2+
M
x(OH)2]x+(An-)x/n∙mH2O,
1-x
converted to high value-added chemical fuels through
hydrogenation,[3] such as alcohols, hydrocarbons and so on; on
the other hand, via the carbonylation or methylation reaction, we
can gain a series of carbonyl containing chemicals including
formamides, methylamines, esters, ureas, etc.[4] Among these
products, the formamide has widespread applications in industry.
It can not only serve as solvent but also raw material for the
synthesis of many significant chemicals.
Among various synthetic routes to formamides, the N-
formylation of amines using CO2 and H2 seems to be an ideal
route because the only byproduct is water. Various catalysts
have been reported for the N-formylation of amines with CO2
and H2 in different solvents.[5] Ding et al. reported the
homogeneous ruthenium catalyzed N-formylation reaction with
THF as the solvent.[6] Shi et al. found that the heterogeneous
catalyst palladium was also active for this kind of reactions with
octane as the solvent.[7] Mitsudome and his co-authors reported
the selective N-formylation of functionalized amines in
dimethylacetamide with carbon dioxide and hydrogen.[8] Liu et al.
where An- represents the intercalated anion between the positive
divalent and trivalent cationic layers. Because of the high
adsorption capacity and composition diversity, LDHs can serve
as effective supports in the immobilization of catalytically active
species on the surface.[11] It has been reported that LDH
supported heterogeneous catalysts exhibit good performance in
various reaction systems.[12]
In this work, we performed the N-formylation reaction over
Mg-Al layered double hydroxide (Mg-Al LDH) supported Pd
catalyst (Pd/LDH) for the first time and found that the reaction
intermediates were different in different solvents. The methanol
can greatly improve the yield of the desired product by forming
the HCOOCH3. As far as we know, this is the first work to report
the solvent effect and connect the solvent with the reaction
mechanism for the N-formylation reaction of various amines.
The Mg-Al LDH was prepared by the co-precipitation
method which was similar to that reported previously.[13] The
supported Pd catalyst was prepared by impregnation method
with NaBH4 as the reducing agent (the details are shown in the
supporting information).
Figure 1a shows the transmission electron microscopy
(TEM) image of the prepared Pd/LDH, in which the
nanoparticles with an average diameter of about 2.8 nm (Figure
1b) are immobilized uniformly on the support. The crystalline
structure of the catalyst was characterized by the X-ray
diffraction (XRD) and the result is shown in Figure 1c. It is
noteworthy that no obvious diffraction peaks of metallic Pd were
observed, which is due to very small size and well dispersion of
the Pd particles. The crystal planes of (003), (006), (012), (015),
(018), (110) and (113) were obviously observed, which is
corresponding to a typical layered double hydroxide material.[14]
The XPS measurement was used to study the surface electronic
[a] Dr. Y. Wang, Dr. B. Chen, Dr. S. Liu, Dr. X. Shen, Dr. S. Li, Dr. Y. Yang. Prof. Dr. H. Liu,
Prof. Dr. B. Han, Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory
of Colloid and Interface and Thermodynamics Institute of Chemistry, Chinese Academy of
Sciences Beijing 100190 (P.R. China) E-mail:liuhz@iccas.ac.cn, hanbx@iccas.ac.cn
[b] Dr. Y. Wang, Dr. S. Liu, Dr. X. Shen, Dr. S. Li, Dr. Y. Yang. Prof. Dr. H. Liu, Prof. Dr. B.
Han, School of Chemistry and Chemical Engineering, University of Chinese Academy of
Sciences, Beijing 100049, P. R. China
Supporting information for this article is given via a link at the end of the document. ((Please
delete this text if not appropriate))
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10.1002/cctc.201801404
ChemCatChem
COMMUNICATION
state of the palladium catalyst. The peak at 335.54 eV is
assigned to the Pd0 3d5/2 and the peak at 337.08 eV is assigned
to the Pd2+ 3d5/2. The other spin-orbit component, 3d3/2, appears
at 340.62 eV and 342.41 eV for Pd0 and Pd2+, respectively.[15] It
is demonstrated that 86.5% of the palladium species have been
reduced to Pd0 in spite of a small quantity of Pd2+ after reduction.
The ICP-AES suggests that the palladium content is 2.9%.
for solubility were shown in supporting information. The results
showed that 2.6% and 53.4% of alkyl ammonium alkyl
carbamate produced from 1 mmol morpholine and 3 MPa CO2
can be dissolved in 2 mL hexane and in 2 mL THF, respectively.
We didn’t observe the solid products in 2 mL methanol, ethanol
and the mixed solvent of THF and methanol (1:1 in volume). It is
obvious that the solubility of the alkyl ammonium alkyl
carbamate in various solvents is related to the carbon balance
value. The poorer the solubility of the alkyl ammonium alkyl
carbamate in the solvent, the lower the carbon balance value.
The carbon balance value in hexane and THF is far less than
100% because the insoluble salts can’t be detected by gas
phase chromatography.
Table 1. N-formylation of morpholine with CO2 and H2 in various solvents
Conversion
(%)
Carbon
balance
Entry
Solvent
Yield (%)
9.0%
87.6%
99.8%
99.3%
98.7%
1
2
3
4
5
hexane
THF
94.6
47.2
56.0
55.3
92.7
3.6
34.8
55.8
54.6
91.4
CH3CH2OH
THF+CH3OH
CH3OH
Figure 1. (a) TEM image of the Pd/LDH. (b) the corresponding size
analysis of the Pd nanoparticles. (c) XRD patterns of the Pd/LDH. (d)
XPS spectra of the Pd/LDH.
Reaction conditions: morpholine (1 mmol), Pd/LDH (1 mol% of the substrate),
solvent (2 mL), PH2 (3 MPa), PCO2 (3 MPa), temperature (140 oC), reaction time
(16 h).
Initially, we optimized the reaction conditions in methanol
using the N–formylation of morpholine as the model reaction and
the results are shown in Table S1. The optimized reaction
Entry 4, THF: CH3OH = 1:1 in volume
o
temperature is 140 C and the optimized catalyst dosage was 1
mol% of the substrate. 3.0 MPa CO2 and 3.0 MPa H2 was the
optimized pressure, and 16 h was enough to realize the high
yield of the product.
The effect of different solvents were checked under the
optimized reaction conditions for the N–formylation reaction of
morpholine and the carbon balance values were calculated from
morpholine, N-formylmorpholine (Table 1). In hexane, the
conversion of morpholine reached up to 94.6% while the yield of
the N-formylmorpholine was 3.6% with only 9.0% carbon
balance value (Table 1, Entry 1). In THF, the conversion of the
Generally, CO2 can be reduced to HCOOH or HCOOCH3
depending upon the catalytic system used and reaction
conditions operated. In this work, we also investigated HCOOH
or HCOOCH3 as the C1 source to find out their performances in
N-formylation reaction of morpholine, and the results are given
in Table 2. With the increase of HCOOH or HCOOCH3, the yield
increased gradually. Interestingly, at the same concentration of
C1 source, HCOOCH3 gave higher yield of N-formylmorpholine.
When 0.5 mmol HCOOH was used as the C1 source in
methanol, the yield of N-formylmorpholine was only 1.8% (Table
2, Entry 1). However, the yield could reach up to 54.3% by using
0.5 mmol HCOOCH3 as the C1 source (Table 2, Entry 4). 1.0
mmol HCOOCH3 was enough to realize the high yield of
morpholine (Table 2, Entry 5). However, with the same amount
HCOOH, the yield was only 16.3% (Table 2, Entry 2). When we
increased the amount of HCOOH to 2.5 mmol, we also gained
high yield of the product (Table 2, Entry 3), which is consistent
with the HCOOH-mediated formylation reaction report.[8] Besides,
we compared the reaction rate using the same amount of
HCOOH and HCOOCH3 as C1 source in other solvents and
other catalytic systems for the N-formylation reaction. In THF,
there was no product detected with HCOOH as the carbon
source (Table 2, Entry 7), while the yield of N-formylmorpholine
can reach up to 91.7% by using HCOOCH3 under the same
conditions (Table 2, Entry 8). With commercial 5% Pd/C as the
catalyst, the yield of the product was 84.8% by using HCOOCH3
(Table 2, Entry10), while there was little product detected by
using HCOOH (Table 2, Entry 9). In commercial 1% Pd/Al2O3
catalytic system, the yields of the product by using HCOOH and
morpholine was 47.2% with
a 34.8% yield of the N-
formylmorpholine and the carbon balance value was 87.6%
(Table 1, Entry 2). The carbon balance values far from 100% in
THF and hexane mean that there are other products besides N-
formylmorpholine in these solvents. That is to say, the yield of
the by-products in hexane is more than that in THF. The carbon
balance values in the other solvents are near 100% (Table 1,
Entries 3-5), which illustrates that N-formylmorpholine is the only
product in these solvents. Under optimal reaction conditions,
methanol exhibits the best performance for the N-formylation
reaction of morpholine with 92.7% conversion and 91.4% yield
(Table 1, Entry 5).
It has been reported that the amine can quickly react with
CO2 to form the corresponding alkyl ammonium alkyl
carbamate.[16] The existence of alkyl ammonium alkyl carbamate
was also proved by the white solid product from reacting 1 mmol
morpholine with 3 MPa CO2 at room temperature for 10 min in
our experiment. The solubility of alkyl ammonium alkyl
carbamate was checked in different solvents. The test methods
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HCOOCH3 were 52.3% and 90.2%, respectively (Table 2,
Entries 11-12). These results illustrate that the HCOOCH3-
mediated reaction pathway is superior to the HCOOH-mediated
pathway for the N-formylation reaction. More importantly, the
superiority of the HCOOCH3-mediated reaction pathway is
universal but not limited to our catalytic system.
corresponding products in the HCOOCH3-mediated reaction
pathway.
When the N-formylation reaction of morpholine with CO2
and H2 was performed in methanol, we detected a small amount
of methyl formate. It means that the HCOOCH3 is the reaction
intermediate in CH3OH. When the reaction was performed in
THF or in ethanol, the reaction went only through the salt or
HCOOH-mediated pathway since HCOOCH3 can’t be produced
in these reaction systems. The absence of HCOOCH3
intermediate in THF and ethanol greatly slowed down the
reaction rate and resulted in the lower yields than that in
methanol.
Scheme 1. The possible reaction paths involved in HCOOH (a) and
HCOOCH3 (b).
To test the versatility of the Pd/LDH catalytic system, we
explored the formylation of various substrates with CO2 and H2
(Table 3). By using 1-methylpiperizine as the substrate, we
gained the desired product with 88.5% yield (Table 3, Entry 1).
Besides, the N-formylation reactions of other cyclic secondary
amines, such as tetrahydropyrrole and 4-methylpiperidine, also
proceeded smoothly and the yield of the desired product was
96.4% and 95.0%, respectively (Table 3, Entries 2 and 3). The
catalytic system exhibited excellent performance not only for the
cyclic secondary amines, but also for the secondary alkyl
amines. Both the yields of the desired product were higher than
90.0% when we used N-methylpropylamine and N-
methylbutylamine as the substrates (Table 3, Entries 4 and 5).
Excitingly, the reaction also went smoothly by employing the
primary amine as the substrate. The yield of the butylformamide
can reach up to 97.4% (Table 3, Entry 6).
Table 2. N-formylation of morpholine with different carbon source of various
amounts
Entry
1
Carbon source
HCOOH
Amount (mmol)
Yield (%)
1.8
0.5
1.0
2.5
0.5
1.0
2.5
1.0
1.0
1.0
1.0
1.0
1.0
2
HCOOH
16.3
92.1
54.3
88.6
92.7
0
3
HCOOH
4
HCOOCH3
HCOOCH3
HCOOCH3
HCOOH
5
6
Table 3. N-formylation of other substrates with CO2 and H2
7[a]
8[a]
9[b]
10[b]
11[c]
12[c]
HCOOCH3
HCOOH
91.7
1.2
Entry
1
Substrate
Product
Yield (%)
88.5
HCOOCH3
HCOOH
84.8
52.3
90.2
2
3
4
5
6
96.4
95.0
93.0
94.8
97.4
HCOOCH3
Reaction conditions: morpholine (1 mmol), Pd/LDH (1 mol% of the
substrate), solvent (2 mL CH3OH), temperature (140 oC), reaction time (16
h)
[a] solvent (2 mL THF), reaction time (12 h)
[b] commercial 5% Pd/C (1 mol% of the substrate), solvent (2 mL THF),
reaction time (12 h)
[c] commercial 1% Pd/Al2O3 (0.33 mol% of the substrate), solvent (2 mL
THF), reaction time (12 h)
The possible reason for the superiority of the HCOOCH3-
mediated reaction pathway to the HCOOH-mediated reaction
pathway is also discussed. The possible reaction paths involved
in HCOOH and HCOOCH3 are shown in Scheme 1. Formamides
are obtained through the nucleophilic attack of the amines to
HCOOH or HCOOCH3. Amine could form corresponding
quaternary ammonium salt in the presence of HCOOH, which
will lower the ability for nucleophilic attack of the amine in the
reaction system. However, the amines with lone electron pairs
can directly attack the HCOOCH3 intermediate to obtain the
Reaction conditions: morpholine (1 mmol), Pd/LDH (1 mol% of the
substrate), solvent (2 mL CH3OH), PH2 (3 MPa), PCO2 (3 MPa), temperature
(140 oC), reaction time (16 h).
In conclusion, with the Pd/LDH catalytic system, the
formylation reaction of amines with CO2 and H2 in methanol
exhibited unique superiority compared to that in other solvents.
Methanol plays a significant role in accelerating the formylation
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[16] C. Wu, H. Cheng, R. Liu, Q. Wang, Y. Hao, Y. Yu, F. Zhao, Green
Chem. 2010, 12, 1811-1816.
reaction rates since it provides another reaction pathway where
HCOOCH3 behaves as the intermediate. Under the optimized
reaction condition, 88.5%-97.4% yields of the formamides were
obtained for various substrates in methanol. This work provides
a guideline for the choice of the solvent for the N-formylation
reaction, also a direction for the research on the relation
between the reaction mechanism and the solvent employed in
the reaction system.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21603235), National Key Research and
Development
Program
of
China
(2017YFA0403003),
Recruitment Program of Global Youth Experts of China and
Chinese Academy of Sciences (QYZDY-SSW-SLH013)
Keywords: formamide •supported Pd catalyst • solvent effect
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Layout 1:
COMMUNICATION
We performed the N-formylation
reaction of amines with CO2 and H2
over Mg-Al layered double hydroxide
(Mg-Al LDH) supported Pd catalyst
(Pd/LDH) in various solvents. Among
the solvents we checked, methanol
exhibits unique performance since it
provides a new HCOOCH3-mediated
reaction pathway, which can greatly
accelerate the reaction rate. This
catalytic system is also effective for
various amines including cyclic and
alkyl secondary amines.
Yanyan Wang,[a,b] Bingfeng Chen,[a]
Shulin Liu,[a,b] Xiaojun Shen, [a,b]
Shaopeng Li, [a,b] Youdi Yang, [a,b]
Huizhen Liu,*[a,b] and Buxing Han*[a,b]
Page No. – Page No.
Methanol promoted palladium-
catalyzed amine formylation with CO2
and H2 by the formation of HCOOCH3
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