Selective synthesis of formamides, 1,2-bis(N-heterocyclic)ethanes and methylamines from cyclic amines and CO2/H2 catalyzed by an ionic liquid-Pd/C system

Article abstract of DOI:10.1039/c9sc03242h

The reduction of CO₂ with amines and H₂ generally produces N-formylated or N-methylated compounds over different catalysts. Herein, we report the selective synthesis of formamides, 1,2-bis(N-heterocyclic)ethanes, and methylamines, which is achieved over an ionic liquid (IL, e.g., 1-butyl-3-methylimidazolium tetrafluoroborate, [BMIm][BF₄])-Pd/C catalytic system. By simply varying the reaction temperature, formamides and methylamines can be selectively produced, respectively, in high yields. Interestingly, 1,2-bis(N-heterocyclic)ethanes can also be obtained via the McMurry reaction of the formed formamide coupled with subsequent hydrogenation. It was found that [BMIm][BF₄] can react with formamide to form a [BMIm]⁺-formamide adduct; thus combined with Pd/C it can catalyze McMurry coupling of formamide in the presence of H₂ to afford 1,2-bis(N-heterocyclic)ethane. Moreover, Pd/C-[BMIm][BF₄] can further catalyze the hydrogenolysis of 1,2-bis(N-heterocyclic)ethane to access methylamine. [BMIm][BF₄]-Pd/C was tolerant to a wide substrate scope, giving the corresponding formamides, 1,2-bis(N-heterocyclic)ethanes or methylamines in moderate to high yields. This work develops a new route to produce N-methylamine and opens the way to produce 1,2-bis(N-heterocyclic)ethane from cyclic amine as well.

Full text of DOI:10.1039/c9sc03242h

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DOI: 10.1039/C9SC03242H
ARTICLE
Selective Synthesis
of
Formamides,
1,2-Bis(N-
heterocyclic)ethanes and Methylamines from Cyclic Amines and
CO /H Catalyzed by Ionic Liquid-Pd/C system
Received 00th January 20xx,
Accepted 00th January 20xx
2
2
a,b
a,
a,b
a
a,b
a
a,b,c
DOI: 10.1039/x0xx00000x
Ruipeng Li , Yanfei Zhao *, Huan Wang , Junfeng Xiang , Yunyan Wu , Bo Yu , Buxing Han
&
a,b,c,
Zhimin Liu
*
2 2
The reduction of CO with amines and H generally produces N-formylated or N-methylated compounds over
different catalysts. Herein, we report the selective synthesis of formamides, 1,2-bis(N-heterocyclic)ethanes, and
methylamine, which is achieved over ionic liquid (IL, e.g., 1-butyl-3-methyimidazolium tetrafluoroborate,
[
4
BMIm][BF ])-Pd/C catalytic system. By simply varying the reaction temperature, formamides and methylamine
can be selectively produced, respectively, in high yields. Interestingly, 1,2-bis(N-heterocyclic)ethanes can also be
obtained via McMurry reaction of the formed formamide coupled with subsequent hydrogenation. It was found
+
that [BMIm][BF
4
] can react with formamide to form [BMIm] -formamide adduct, thus combined with Pd/C it can
catalyze McMurry coupling of formamide in the presence of H
Moreover, Pd/C-[BMIm][BF ] can further catalyze the hydrogenolysis of 1,2-bis(N-heterocyclic)ethane to access
methylamine. [BMIm][BF ]-Pd/C was tolerant to a wide substrate scope, giving the corresponding formamides or
,2-bis(N-heterocyclic)ethanes or methylamines in moderate to high yields. This work develops a new route to
2
to afford 1,2-bis(N-heterocyclic)ethane.
4
4
1
produce N-methylamine and opens the way to produce 1,2-bis(N-heterocyclic)ethane from cyclic amine as well.
Introduction
Compared to molecular solvents (e.g., water and organic
solvents), ionic liquids (ILs) that are completely composed of ions
2
Carbon dioxide (CO ) is an abundant, readily available, nontoxic and
renewable C1 building block, and its transformation into value-
added chemicals and fuels is of great significance for green and
sustainable development.
the presence of reductants such as hydrosilanes and H
widely investigated, which generally produce formamides or
have unique properties, such as wide liquid window, very low vapor
pressure, specific H-bonding between anion and cation, and so on,
2
4-28
which make them promising media for chemical processes.
1
-6
The reactions of amines with CO
2
in
Particularly, they can be designed with specific functions via
selection of suitable cations and/or anions, and have been widely
applied in catalysis, showing great potentials. For example, as both
solvent and catalyst 1-ethyl-3-methylimidazolium acetate worked
2
have been
7
-11
methylamines.
2 2
For the reaction of amines with CO /H , the
production of methylamines is more difficult than the formation of
well for the transformation of alcohols to esters using O
2
as an
-philic ILs that can
via forming carbonates or carbamates have been
1
2-17
formamides,
catalysts with very high activity.
e.g., 1,2-bis(piperidine)ethane) are a kind of high value chemicals,
which requires harsh reaction conditions and the
2
9
oxidant under metal-free conditions. CO
capture CO
2
1
8-21
1,2-Bis(N-heterocyclic)ethanes
2
(
reported to be excellent media and/or catalysts for CO
2
which are generally synthesized via the reaction of cyclic amines
with ethyl halides, suffering from production of large amount of
acid waste and complicated posttreatment.
transformation into value-added chemicals.30,31 1-Butyl-3-
methylimidazolium ([BMIm]+) chloride combined with Rh
2
2,23
The synthesis of
/H
2
nanoparticles and ZnCl
2
, could realize the efficient reduction of
heteroarenes. Carbanion-functionalized IL along with Pd(OAc)
was capable of catalyzing the alkoxycarbonylation reactions of CO
1
,2-bis(N-heterocyclic)ethanes from cyclic amines and CO
2
3
2
2
provides a green and promising route, but this has not been
realized yet.
3
3
to benzoate products under ambient conditions. In these
reactions, ILs generate synergistic effects with other active species,
promoting or catalyzing the reactions.
a. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Colloid,
Interface and Thermodynamics, CAS Research, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100190, China. E-mail: liuzm@iccas.ac.cn;
lianyi302@iccas.ac.cn
University of Chinese Academy of Sciences, Beijing 100049, China.
Physical Science Laboratory, Huairou National Comprehensive Science Center.
Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [supporting figures and
tables]. See DOI: 10.1039/x0xx00000x
Herein, we report the reduction of CO with amine and H over
IL-Pd/C catalytic system, which accomplished the selective synthesis
of formamides, 1,2-bis(N-heterocyclic)ethanes and methylamines.
2
2
b.
c.
Interestingly, the combination of Pd/C with [BMIm][BF
4
] could
†
o
realize the selective production of formamides (at 120 C) or N-
o
methylamines (at 160 C) in high yields, respectively, as illustrated
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in Scheme 1. Moreover, 1,2-bis(N-heterocyclic)ethanes can also be nm. The N
obtained via McMurry reaction of the formed formamide coupled the carbon support exhibited microporous and mesoporous
2
adsorption/desorption isotherms (Fig. 1c) indicate that
View Article Online
DOI: 10.1039/C9SC03242H
2
with subsequent hydrogenation. It was found that [BMIm][BF
could react with formamide to form [BMIm] -formamide adduct, distribution curve (Fig. 1d) displayed that the pore diameters were
thus combined with Pd/C, catalyse McMurry coupling of formamide centered at 15 nm according to the BJH model, a typical feature of
4
]
structures with specific surface area of 950.6 m /g. The pore radius
+
2
in the presence of H to afford 1,2-bis(N-heterocyclic)ethane, and mesoporous materials accompanied with some micropores.
further catalyse hydrogenolysis of 1,2-bis(N-heterocyclic)ethane to
access methylamine. In addition, the detailed studies indicate that Exploration on catalytic system for reaction of piperidine with
2 2
CO /H .
the IL played multiple roles in the reactions with modifying the
electronic property of the metallic Pd particles to enhance their
catalytic activity, activating the amine and the intermediate via
Table 1. The reaction of piperidine with CO
catalytic systems.
2
/H
2
over various
a
4
strong hydrogen bonding. [BMIm][BF ]-Pd/C was tolerant to a wide
solvent
N
N
N
NH
O
N
CO2
H2
substrate scope, giving the corresponding formamides or 1,2-bis(N-
heterocyclic)ethanes or methylamines in moderate to high yields.
This work develops a new route to produce N-methylamine and
opens the way to produce 1,2-bis(N-heterocyclic)ethane from cyclic
Pd/BMC
1
a
2a
3a
4a
Yield (%)e
Entry
Solvent
2
a
3a
0
0
0
11
6
4a
0
0
2 2
amine and CO /H .
1
2
3
4
Ethanol
THF
Octane
99
99
99
6
NH
IL-Pd/C
N
0
CO2
H2
O
R
R
n
20 o
n
1
C
[BMIm][BF
[BMIm][BF
[HMIm][BF
[BMIm][Cl]
4
]
]
82
90
49
1
n=1, R=H
N
b
5
4
3
n=2, R=H, Methyl
McMurry coupling
BF4
N
6
7
8
9
1
1
4
]
17
81
46
67
99
99
16
1
22
14
hydrogenation
R
N
n
1
30-160 o
C
IL: [BMIm][BF4]
[BMIm][PF
[BMIm][NTf
6
]
2
trace 53
N
N
R
n
hydrogenolysis
R
]
13
0
0
57
77
18
0
0
26
22
n
0
1
[P4444][BF
[N4444][BF
4
]
4
]
c
Scheme 1. Selective reduction of CO
2
with amines and H
2
.
12
[BMIm][BF
[BMIm][BF
4
]+[BMIm][Cl]
]+THF
d
1
3
4
a
Results and discussion
Conditions: 1a (0.5 mmol), Pd/C (20 mg), solvent (1 mL) or IL (5 mmol), H
2
6 MPa), total pressure of 10 MPa, 160 C, 6 h. 9 h. c
pressure of 8 MPa, [BMIm][BF
MPa), total pressure of 8 MPa, [BMIm][BF
o
b
H
(5 MPa), total
(
2
Preparation and characterization of the Pd/C catalyst.
d
4
] (1.7 mmol), [BMIm][Cl] (3.3 mol), 9 h. H
2
(5
] (2.5 mmol), THF (2.5 mL), 9 h. e
4
Yield was determined by GC using trimethoxybenzene as an internal
standard.
In our initial experiments, the reaction of piperidine (1a) with
CO /H was performed using Pd/C as the catalyst to screen the
2 2
catalytic system and reaction conditions for selective formation of
formylpiperidine (2a) or 1,2-bis(piperidine)ethane (3a) or
2 2
methylpiperidine (4a). In the absence of CO and H , no product
was detected. As shown in Table 1, the solvents significantly
affected the product selectivity. Molecular solvents including
ethanol, tetrahydrogenfuran (THF) and octane exclusively afforded
2
[
2
a (Table 1, entries 1-3), while the imidazolium-based ILs including
BMIm][BF ], [BMIm][PF ], [BMIm][NTf ] and [BMIm][Cl] could offer
a, 3a and 4a in different yields under the experimental conditions
] showed the
4
6
2
(Table 1, entries 4-9). Among these ILs, [BMIm][BF
4
2
Fig. 1 TEM (a) and HRTEM (b) images, N sorption isotherms (c) and
pore size distribution (d) of the Pd/C catalyst used in this work.
best performance for the production of 4a, achieving a yield of 90%
within 9 h (Table 1, entry 5). However, only 2a was obtained in the
4 4
ILs involving [P4444][BF ] and [N4444][BF ] (Table 1, entries 10-11).
To prepare the Pd/C catalyst with loading of 5 wt%, the porous
carbon support was first fabricated according to our previous
These results indicated that for the imidazolium-based ILs the
cations played key role in the formation of 4a, and the anions
influenced the activity of the cations. Given that 3a is an important
3
4
report , on which Pd nanoparticles were immobilized via equal
volume impregnation method followed by hydrogen reduction. In
the TEM images of the Pd/C catalyst (Fig. 1a and 1b), the dark dots
were identified as Pd nanoparticles, which were uniformly
distributed on the support with an average particle size around 1.7
chemical and it has not been accessed from 1a and CO
2 2
/H , we
optimized the reaction conditions to get 3a as the main product
(Table S1). It was indicated that combined with Pd/C the mixtures of
2
| J. Name., 2012, 00, 1-3
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[
BMIm][BF
4
] with THF or with [BMIm][Cl] could afford 3a in yields excellent yields, but difficult to access corresponding 1,2-
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bis(amino)ethane (Scheme S1).
DOI: 10.1039/C9SC03242H
higher than 50% at 160 C (Table 1, entries 12-13). Considering that
using THF as the reaction medium only 2a was obtained, it can be
deduced that [BMIm][BF
Scheme 2. Substrate scope for selective reduction of CO
2
with
4
] and Pd/C cooperated to catalyze the
amine and H
2
over the Pd/C catalyst.
formation of 3a and 4a.
R
NH
a
b
1
R
Cat.
N
N
N
N
n
O
n
R
R
n
R
n
H2, CO2
n
n=1, R=H
n=2, R=H, Methyl
2
3
4
2
b, 96%(88%);
NH
2d, 10%(5%);
4d, 74%(62%)
NH
2a, 99%(93%);
2c, 94%(90%);
NH 4c, 90%(87%)
3a, 57%(53%);
a, 90%(77%)
NH 3b, 53%(45%);
4b, 90%(75%)
4
NH 2e, 96%(90%);
2f, 64%(55%);
3f, 53%(44%);
f, 90%(73%)
NH 2g, 85%(79%);
NH
a
b
3e, 77% (70%);
e, 83%(70%)
3g, 47% (40%);
4
4
4g, 90%(78%)
c
O
2e, 96% (89%);
e,36%(30%)
d
2
e, 76%(70%);
2
h, 98%(88%);
3
e
NH
4e, 36% (32%)
Fig. 2 Effects of temperature (a) and reaction time (b) on the
conversion of 1a and the yields of 2a, 3a and 4a. (a) 9 h. (b) 160 °C.
4h, 90%(74%)
87%(81%)e
N
N
H
4e
,
H
d
N
2i, 77% (70%);
N
2a, 99%(93%);
N
c
2
f, 29% (25%);
4
i, 80%(69%)
4a, 99%(81%)
Ph
4
f, 70%(57%)
Since [BMIm][BF
methylation of 1a with CO
effects of temperature and reaction time on the reaction. As mmol), H
4
]-Pd/C showed the best performance for
For N-formylation: substrate (0.5 mmol), Pd/C (20 mg), [BMIm][BF
4
] (5
2
/H to 4a, it was applied to explore the
2
2
(3 MPa), total pressure of 5 MPa, 120 °C, 6 h, isolated yield was in
illustrated in Fig. 2a, the reaction temperature significantly the bracket. For methylation: H
influenced the product selectivity. At 120 C, 2a was the sole h, the others are same as those for N-formylation,. For accessing 1,2-bis(N-
2
(6 MPa), total pressure of 10 MPa, 160 °C, 6
o
product in an almost quantitative yield within 9 h, while both 3a
heterocyclic)ethanes: substrate (0.5 mmol), Pd/C (20 mg), [BMIm][BF
4
] (1.7
o
and 4a were detected in the temperature range of 130~160 C with
(5 MPa), total pressure of 8 MPa, 6 h. a 12
mmol), [BMIm][Cl] (3.3 mmol), H
2
o
the 4a yields increasing with temperature up to 90% at 160 C.
b
c
d
e
h. 10 h. 140 °C, 9 h. 140 °C, 12 h, 160 °C, 24 h.
Notably, the yield of 3a was maintained around 20% in this
temperature range, while at 160 C it decreased significantly and 4a
became the main product. From the dependence of the 2a and 3a
yields on the reaction time at 160 C (Fig. 2b), it was deduced that
The roles of the IL.
To explore the roles of the IL in the reactions, the interactions of
the IL with Pd/C and with 1a, 2a, and 3a were investigated.
Thermogravimetric analysis on the Pd/C catalysts after absorbing IL
at 120 C and 160 C (Fig. S1) indicates that the amounts of the IL
adsorbed on Pd/C reached 1.28 and 0.69 wt%, respectively, and its
decomposed temperature (500 C) was much higher than that of
the free IL (380 C). These results indicate that the IL had strong
interaction with Pd/C.
2
a and 3a finally converted into 4a under the experimental
conditions.
Generality of the [BMIm][BF
To explore the generality of the [BMIm][BF
4
]-Pd/C catalytic system.
]-Pd/C catalytic system,
it was applied in the reactions of various cyclic amines with CO /H
As shown in Scheme 2, this catalytic system was effective for
catalyzing the reactions of the tested substrates with CO /H , and
4
2
2
.
2
2
formylated and methylated products were selectively obtained at
o
1
20 and 160
C, respectively. Pyrrolidine, piperidine,
hexamethyleneimine, and morpholine exhibited good reactivity,
affording corresponding formylated and methylated products in 90-
9
9% yields under the optimized conditions. By using substituted
piperidines like 3-methylpiperidine, 4-methylpiperidine, 2-
methylpiperidine,
tetrahydroisoquinoline
3,5-dimethylpiperidine,
and
1,2,3,4-
1,2,3,4-tetrahydroquinoline as
substrates, the reaction also proceeded smoothly and selectively
furnished the desired products in moderate to high yields. Whereas, Fig. 3 Pd 3d XPS spectra of (a) Pd/C and (b) IL-Pd/C
2
-methylpiperidine was converted into corresponding formamide
o
(2d) only in 10% yield at 120 C, and 1,2,3,4-tetrahydroquinoline led
The Pd/C adsorbing 1.28 wt% [BMIm][BF
was examined by XPS. In the XPS spectrum of IL-Pd/C, the peaks at
40.8 (Pd 3d3/2) and 335.5 eV (Pd 3d5/2) attributing to Pd in Pd/C-IL
exhibited a downshift of 0.3 eV compared with those of Pd/C (Fig.
), indicating a possible electron transfer from IL to the metallic Pd
4
] (denoted as IL-Pd/C)
to corresponding methylamine in low yield.
After detailed screening of reaction conditions, 1,2-bis(N-
heterocyclic)ethanes could be achieved in moderate yields in most
cases. The highest yield of 1,2-bis(N-heterocyclic)ethane (e.g., 3e)
reached up to 77%. Interestingly, using pyridine, 4-methylpyridine,
0
3
3
particles. This was also verified by the upshift of N 1s peak of IL-
Pd/C as compared to that of IL-C (Fig. S2, IL-C refers to the IL-
adsorbed on carbon support). The IR analysis (Fig. S3) indicates that
the adsorbed IL on Pd/C showed red-shifted C-N stretching band of
4
-phenylpyridine as the substrates, they were first hydrogenated,
and corresponding formamides and methylamines were obtained in
high yields. However, in these cases corresponding 1,2-bis(N-
heterocyclic)ethanes were detected in small amounts, and the
-1
IL cation from 1580 to 1575 cm , which is consistent with electron
reason is unclear. In addition, [BMIm][BF
for chain secondary amine (e.g., 1,2-diaminopropane) reacting with
CO /H , selectively producing formamide or methylamine in
4
]-Pd/C was also effective
+
donation from N atom in [BMIm] to the Pd particles. FT-EXAFS
spectra also gave the evidence that the IL complexed with Pd (Fig.
S4). It is reasonable that the lone electron pair of N can affect the
2
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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1
electronic state of the Pd particles attached to them because one N IL and 2a together with K CO was examined. Based on the H NMR
2
3
View Article Online
+
2
atom in [BMIm] cation is essentially in the sp hybridization state.
1
1
DOI: 10.1039/C9SC03242H
and H- H correlation spectroscopy (COSY) analysis (Fig. 4c and Fig.
S10), an intermediate from [BMIm][BF ] and 2a (denoted as [BMIm-
4
OH-2a][BF
the detection of {[BMIm-OH-2a][BF
4
]) was detected (Fig. 4c)，which was also confirmed by
+
4
][BMIm](2a)} (m/z=591.4) in
the electrospray-ionization mass spectrometry (ESI-MS) (Fig. S11).
The above results indicate that the IL can activate 2a to form
+
[
BMIm] -formamide adduct, which may be favorable to the
formation of 3a and 4a. In addition, 3a can also be activated by the
IL, supported by the NMR analysis with the obvious changes of
chemical shifts as it mixed with the IL in the presence of 2a (Fig.
S12), which can explain why the IL promotes the hydrogenolysis of
3
a.
Possible Reaction pathway.
To gain deep insight into the reaction pathway to form 3a and 4a,
control experiments were performed. Previous reports revealed
that 2a could catalytically convert to 4a via hydrogenation under
3
6
appropriate conditions. However, in this work taking 2a as the
substrate to react with CO /H or only with H over Pd/C in
BMIm][BF ], no 4a was detectable (Scheme S2A and S2B). This
indicates that Pd/C could not catalyze the direct hydrogenation of
a to 4a in [BMIm][BF ], which excludes the pathway of 2a
, and implies that 2a undergoes 3a to form 4a.
2
2
2
[
4
2
4
reduction with H
2
2
mol% Pd/C
a
N
N
1
N
O
N
5mmol [BMIm][BF4]
H2, 6 MPa, 160 oC, 8 h
N
Fig. 4 H NMR (a), FT-IR spectra (b) of [Bmim][BF
4
], 2a and their
1
mixture, and H NMR (c) of the mixture of IL and 2a together with
2
a, 1 mmol
4a, 0.5 mmol
3a, 0.31 mmol
4a, 0.86 mmol
2
K CO3.
b
N
N
3
h
N
Furthermore, the interactions of [BMIm][BF
and 3a were investigated via NMR analysis. No new signals or
4
] with CO
2
, 1a, 2a
H
2
mol% Pd/C
N
N
O
5mmol [BMIm][BF4]
H2, 6 MPa, 160 o
1a, 0.5 mmol
3a, 0.19 mmol
4a, 0.5 mmol
1
13
19
11
C
obvious chemical shifts were observed in the H, C, F and
NMR spectra of the mixture of [BMIm][BF ] and CO (Fig. S5),
indicating that this IL cannot activate CO noticeably. Given that 1a
is easily converted to white solid, dihydropyridine-monocarboxylic
B
12 h
N
2
a, 1 mmol
4a, 0.99 mmol
4
2
2
c
McMurry Reaction
Pd/C, H2, IL
N
Pd/C, H2
IL
N
N
O
N
N
acid, once exposing to CO
2
, it is supposed that CO
2
is activated by
1
1
a via forming adduct. The H, 15N, 11B NMR (Fig. S6, S7A and S7B)
2a
3a
4
and FTIR (Fig. S8) analysis on the [BMIm][BF ]-1a mixture indicate
that 1a was activated by the IL via hydrogen bonding and
d
2 mol% Pd/C
5mmol [BMIm][BF4]
N
1
N
electrostatic interaction. In the H NMR spectrum of [BMIm][BF
4
]-2a
N
t-BuOK 0.5 mmol
H2, 6 MPa, 160 oC, 8 h
1
mixture (Fig. 4a), the H signal to the formyl group in 2a and those
to the H atoms in [BMIm] shifted greatly, suggesting the strong C–
H···O interaction between the acidic H(2) of [BMIm] and the O
atom of formyl group in 2a. Specifically, the C NMR signals to
formyl group also shifted accordingly (Fig. S9), further revealing the
activation of formyl group by the IL. In the FTIR spectrum, the
absorption band at 1669 cm attributing to stretching vibration of
C=O of 1a shifted to 1664 cm-1 upon 1a interacting with
3a
4a
+
Scheme 3. Control experiments. Reaction of 2a to 3a in the
presence of 4a (a). Reaction of 2a to 3a and/or 4a in the presence
of 1a at different reaction time (b). The possible reaction pathway
from 2a to 3a (c). Reaction of 3a to 4a in the presence of t-BuOK (d).
+
1
3
-1
As known, McMurry coupling is a reductive reaction, in which
two ketone or aldehyde groups are coupled to form an alkene using
titanium chloride compound (e.g., titanium (IV) chloride) and a
reducing agent (e.g, Zinc) in the presence of a base. In the process
2 2
of 1a reacting with CO /H , the reaction system always kept basic
environment due to the presence of the amine feedstock or the
formed methylamine, which might facilitate McMurry reaction of
the formed formamide to occur. To verify this, we treated 2a in the
presence of 1a or 4a over Pd/C in [BMIm][BF
Scheme 3a, 3b), and 3a was excitingly obtained in appreciate yields
-1
[
BMIm][BF
4
], and the peaks at 3162 and 3122 cm belonging to the
+
stretching vibration of C-H from imidazole ring of [BMIm] shifted
accordingly. The FTIR analysis gave the evidence of interaction
between 1a and the IL, also supporting the NMR results (Fig. 4b). As
reported, reactive carbenes can be generated at the C(2) position of
37
+
35
[
BMIm] under mild basic conditions. In this work, the basic
reaction environment provided by 1a or 4a may be favorable to the
4
], respectively
+
formation of carbenes from [BMIm] , which may further react with
(
2
4
a to form intermediate. To confirm this hypothesis, the mixture of
| J. Name., 2012, 00, 1-3
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in both cases, different from the results as shown in Scheme S2A
Based on the experimental results, a possibleViewpaAtrthicwleaOynlinies
and S2B. This suggests that McMurry reaction of 2a may occur to proposed, as shown in Scheme 4. Initially, 1DaOIi:s1a0c.1t0iv3a9t/eCd9SbCy03th24e2IHL
produce 1,2-bis(piperidine)ethylene although it was not detected in via hydrogen bond and electrostatic interaction, and undergoes
the reaction process, because it can be rapidly hydrogenated to 3a formylation with CO
catalyzed by Pd/C (Scheme 3c). Notably, prolonging reaction time to intermediate [BMIm-OH-2a][BF
2
/H
2
to yield 2a over Pd/C. Subsequently, an
+
4
] is formed from 2a and [BMIm] in
1
2 h, both 2a and 3a disappeared, and 4a became the sole product the presence of 1a, and McMurry reaction proceeds through
Scheme 3b). This indicates that 3a further converted into 4a via coupling of [BMIm-OH-2a][BF with 2a to produce N-(N-
hydrogenolysis under the experimental conditions, which was piperidinoglycolyl)piperidine, followed by hydrogenation to form
confirmed by the reaction of 3a with H over Pd/C in [BMIm][BF 3a. Finally, hydrogenolysis of 3a results in the formation of 4a.
containing t-BuOK to produce 4a (Scheme 3d). Generally, C-N bond Notably, it is for the first time to realize McMurry reaction of
(
4
]
2
4
]
breaks more easily than C-C bond. However, in this work the C-C formamide over Pd/C using H
bond rather than C-N bond in 3a was broken. To give the the traditional routes.
reasonable explanation on this, Gaussian calculation was
2
as a reductant, very different from
performed, which showed that the acidic hydrogen atom H(2) of
+
Conclusions
[
BMIm] could interact with N atom of 3a, inducing the length of C-
C bond in 3a to become longer (Fig. S13). This may be responsible
for the cleavage of C-C bond in 3a to give 4a. [BMIm][BF ] played
In summary, selective reduction of CO
was realized over the [BMIm][BF ]-Pd/C catalytic system, and 1,2-
bis(N-heterocyclic)ethanes were obtained via McMurry reaction of
formamide coupled with subsequent hydrogenation. [BMIm][BF
displayed multiple functions with improving the catalytic activity of
Pd particles, and activating the amine substrate and the formed
2 2
with cyclic amines and H
4
4
the crucial role in the hydrogenolysis of 3a to 4a, deduced from the
fact that without the IL the hydrogenolysis of 3a did not occur even
in the presence of base t-BuOK (Scheme S2C).
IL, 1a
4
]
HO
4
formamide intermediate. [BMIm][BF ]-Pd/C was tolerant to a wide
N
2
N
substrate scope, giving the corresponding formamides or 1,2-bis(N-
heterocyclic)ethanes or methylamines in moderate to high yields.
We believe that these findings provide insights into achieving
cooperativity between IL and metal catalysts.
H
,
2
O
N
2
a
BF4
CO
N
Pd/C
C H
4
9
[
BMIm-OH-2a][BF4]
N
H
IL,
Pd/C
2a
Experimental
C H
General procedures for the reaction of N-containing
compounds with CO /H All reactions were performed in a
4
9
N
N
BF4
2
2.
stainless steel autoclave equipped with a Teflon tube (16 mL
inner volume) and a magnetic stirrer. In a typical experiment,
piperidine (0.5 mmol), [BMIm][BF ] (5 mmol) and Pd/C (20 mg)
4
N
N
Pd/C
O
were successively loaded into the autoclave under an N2
N
OH
N
H
C H
N
N
4
9
C H
atmosphere, and then the autoclave was sealed. H
2
(6 MPa)
1
a
4
9
N
and CO were charged successively into the reactor until the
2
BF4
BF4
total pressure reached to 10 MPa at room temperature. The
autoclave was moved to a heating furnace of 433 K. After
desired reaction time, the reactor was cooled down in ice
water and the gas inside was vented slowly.
Trimethoxybenzene (internal standard) and diethyl ether were
added to the reaction solution, stirred vigorously and
centrifuged. The upper liquid was extracted to analyse.
N
IL,
Pd/C
H2
Pd/C
IL,
H2
N
N
Scheme 4. Plausible pathways for formation of 2a, 3a and 4a.
To identify possible intermediate in the reaction process, the Product analysis. Liquid sample was analysed by gas
reaction solution was analyzed by means of electrospray ionization chromatography (Agilent 4890D) equipped with an ultra-inert
mass spectrometry (ESI-MS.) As shown in the Fig. S14, capillary column (19091S-433UI HP-5ms). NMR spectra were
+
+
+
+
6
{
(
(
(
{
(
H[BMIm][BF
m/z=423.3),
m/z=464.4),
4
](1a)]}
(m/z=312.2),
{H[BMIm][BF
4
](3a)]}
collected in a coaxial insert NMR tube with d -DMSO in the
1
{[BMIm][N-(N-piperidinoglycolyl)piperidine](4a)}
{[BMIm-[N-(N-piperidinoglycolyl)piperidine](2a)}
internal tube as a reference, recorded by Bruker 400 HD ( H
NMR, B NMR and C NMR spectra) and Bruker 600
11
13
+
15
19
1
1
m/z=476.4), {[BMIm-OH-2a][BF
([BMIm][BF ]) [BF
4
][BMIm](2a)} (m/z=591.4) and instruments ( N NMR, F NMR spectra and H- H correlation
][N-(N-piperidinoglycolyl)piperidine]}-
1
1
11
19
4
2
4
spectrum ( H- H COSY)). B NMR and F NMR spectra were
1
m/z=765.4) were detected, suggesting that under the experimental operated in the same equipment in succession. H NMR data
6
conditions,
[BMIm-OH-2a][BF
4
],
and
N-(N- recorded in d -DMSO was listed as the residual of DMSO as
1
3
1
piperidinoglycolyl)piperidine were the key intermediates and 2.50 ppm, while C NMR as 39.51 ppm, H NMR data in d-
1
3
[
BMIm][BF
4
] played a vital role in activating and stabilizing them.
3 3
CDCl was listed as the residual of CHCl as 7.26 ppm, while C
NMR as 77.17 ppm. FT-IR spectra were recorded by Bruker
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-1
Tensor-27 instrument, scanning from 400 to 4000 cm . The 12 O. Jacquet, C. Das Neves Gomes, M. Ephritikhine VaienwdATrt.icCleaOnntlainte,
J. Am. Chem. Soc., 2012, 134, 2934.
3 H. Lv, Q. Xing, C. T. Yue, Z. Q. Lei and F. W. Li, Chem. Commun.,
016, 52, 6545.
4 M. A. Affan and P. G. Jessop, Inorg. Chem., 2017, 56, 7301-
305.
5 Y. J. Zhang, H. L. Wang, H. K. Yuan and F. Shi, ACS Sustainable
Chem. Eng., 2017, 5, 5758.
DOI: 10.1039/C9SC03242H
transmission electron microscopy (TEM) images were obtained
by JEOL-2100F. X-ray photoelectron spectroscopy (XPS) were
collected on an ESCALab220i-XL electron spectrometer from
VG Scientific at a pressure of 3× 10 mbar using 300 W Al-Kα
radiation. The binding energies (BEs) were referenced to the C
1
1
1
1
2
-9
7
1
s line at 284.8 eV from adventitious carbon. The X-ray
absorption data at the Pd K-edge of the samples were
recorded at room temperature in fluorescence mode with
6 U. Jayarathne, N. Hazari and W. H. Bernskoetter, ACS Catal.,
2
018, 8, 1338.
silicon drift fluorescence detector at beam line BL14W1 of the 17 X. J. Cui, X. C. Dai, Y. Zhang, Y. Q. Deng and F, Shi. Chem. Sci.,
Shanghai Synchrotron Radiation Facility (SSRF), China. The
2014, 5, 649.
electron storage ring was operated at 3.5 GeV. Data processing 18 K. Beydoun, G. Ghattas, K. Thenert, J. Klankermayer and W.
Leitner, Angew. Chem. Int. Ed., 2014, 53, 11010.
9 K. Kon, S. M. A. H. Siddiki, W. Onodera and K.-i. Shimizu, Chem.
was performed using the program ATHENA. The electrospray
ionization mass spectrometry (ESI-MS) data (in both the
negative and positive modes) was collected by Bruker 9.4T
Solarix instrument model.
1
2
2
2
-
Eur. J., 2014, 20, 6264.
0 I. Sorribes, J. R. Cabrero-Antonino, C. Vicent, K. Junge and M.
Beller, J. Am. Chem. Soc., 2015, 137, 13580.
1 C. Fang, C. L. Lu, M. H. Liu, Y. L. Zhu, Y. Fu and B. L. Lin, ACS
Catal., 2016, 6, 7876.
Conflicts of interest
2 H. Yang and F. C. Thyrion, Int. J. Chem. Kinet., 1994, 26, 309.
There are no conflicts to declare.
23 S. A. Gamzaeva, P. S. Mamedova, K. M. Allakhverdieva, G. K.
Velieva, M. A. Akhundova and M. A. Allakhverdiev, Russ. J. Appl.
Chem., 2009, 82, 1577.
2
4 K. H. Chen, G. L. Shi, W. D. Zhang, H. R. Li and C. M. Wang, J.
Am. Chem. Soc., 2016, 138, 14198.
5 Z. R. Zhang, J. L. Song and B. X. Han, Chem. Rev., 2017, 117,
Acknowledge
This work was financially supported by National Key Research
and Development Program of China (2017YFA0403102,
2
6
834.
2
017YFA0403003), Natural Science Foundation of China 26 A. Weilhard, M. I. Qadir, V. Sans and J. Dupont, ACS Catal.,
(
21890761, 21533011, 21773266), Chinese Academy of
2018, 8, 1628.
2
2
7 Y. F. Zhao, Z. Z. Yang, B. Yu, H. Y. Zhang, H. J. Xu, L. D. Hao, B. X.
Han and Z. M. Liu, Chem. Sci., 2015, 6, 2297.
8 X. X. Sang, J. L. Zhang, J. F. Xiang, J. Cui, L. R. Zheng, J. Zhang, Z.
H. Wu, Z. H. Li, G. Mo, Y. Xu, J. L. Song, C. C. Liu, X. N. Tan, T.
Luo, B. X. Zhang and B. X. Han, Nat. Commun., 2017, 8, 175.
9 M. Y. Liu, Z. R. Zhang, H. Z. Liu, Z. B. Xie, Q. Q. Mei and B. X.
Han, Sci. Adv., 2018, 4, eaas9319.
Sciences (QYZDY-SSW-SLH013-2), and Beijing Municipal
Science & Technology Commission (Z181100004218004).
Notes and references
2
1
2
3
4
5
M. Y. He, Y. H. Sun and B. X. Han, Angew. Chem. Int. Ed., 2013, 30 Y. F. Zhao, B. Yu, Z. Z. Yang, H. Y. Zhang, L. D. Hao, X. Gao and Z.
2, 9620.
M. Liu, Angew. Chem. Int. Ed., 2014, 53, 5922.
D. X. Yang, Q. G. Zhu, C. J. Chen, H. Z. Liu, Z. M. Liu, Z. J. Zhao, X. 31 Y. F. Zhao, Y. Y. Wu, G. F. Yuan, L. D. Hao, X. Gao, Z. Z. Yang, B.
Y. Zhang, S. J. Liu and B. X. Han, Nat. Commun., 2019, 10, 677.
Yu, H. Y. Zhang and Z. M. Liu, Chem. - Asian J., 2016, 11, 2735.
Z. Lian, D. U. Nielsen, A. T. Lindhardt, K. Daasbjerg and T. 32 A. Karakulina, A. Gopakumar, İ. Akçok, B. L. Roulier, T.
5
Skrydstrup, Nat. Commun., 2016, 7, 13782.
Y. M. Ni, Z. Y. Chen, Y. Fu, Y. Liu, W. L. Zhu and Z. M. Liu, Nat.
Commun., 2018, 9, 3457.
LaGrange, S. A. Katsyuba, S. Das and P. J. Dyson, Angew. Chem.
Int. Ed., 2015, 55, 292.
33 D. J. Tao, F. F. Chen, Z. Q. Tian, K. Huang, S. M. Mahurin, D. E.
Jiang and S. Dai, Angew. Chem. Int. Ed., 2017, 56, 6843.
C. X. Qian, W. Sun, D. L. H. Hung, C. Y. Qiu, M. Makaremi, S. G.
Hari Kumar, L. Wan, M. Ghoussoub, T. E. Wood, M. K. Xia, A. A. 34 Z. S. Ma, H. Y. Zhang, Z. Z. Yang, Y. F. Zhao, B. Yu and Z. M. Liu, J.
Tountas, Y. F. Li, L. Wang, Y. C. Dong, I. Gourevich, C. V. Singh
and G. A. Ozin, Nat. Catal., 2019, 2, 46.
C. S. Yang, R. T. Mu, G. S. Wang, J. M. Song, H. Tian, Z. J. Zhao
and J. L. Gong, Chem. Sci., 2019, 10, 3161.
Mater. Chem. A, 2014, 2, 19324.
35 V. K. Aggarwal, I. Emme, and A. Mereu, Chem. Commun.,
2
002, 1612.
6
7
8
9
1
1
3
3
6 X. L. Du, G. Tang, H. L. Bao, Z. Jiang, X. H. Zhong, D. S. Su and J.
Q. Wang, ChemSusChem, 2015, 8, 3489.
7 X. F. Duan, J. Zeng, J. W. Lü and Z. B. Zhang, J. Org. Chem., 2006,
A. Tlili, E. Blondiaux, X. Frogneux and T. Cantat, Green Chem.,
2
015, 17, 157-168.
Y. H. Li, X. J. Cui, K. W. Dong, K. Junge and M. Beller, ACS Catal.,
017, 7, 1077.
7
1, 9873.
2
R. H. Lam, C. M. A. McQueen, I. Pernik, R. T. McBurney, A. F.
Hilland B. A. Messerle. Green Chem., 2019, 21, 538.
0 X.-D. Li, S.-M. Xia, K.-H. Chen, X.-F. Liu, H.-R. Liand L.-N. He.
Green Chem., 2018, 20, 4853.
1 R. L. Nicholls, J. A. McManus, C. M. Rayner, J. A. Morales-Serna,
A. J. P. Whiteand B. N. Nguyen. ACS Catal., 2018, 8, 3678.
6
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View Article Online
DOI: 10.1039/C9SC03242H
Selective Synthesis of Formamides, 1,2-Bis(N-heterocyclic)ethanes and Methylamines from Cyclic Amines
and CO2/H2 Catalyzed by Ionic Liquid-Pd/C system
8
0x40mm (300 x 300 DPI)