N-Heterocyclic carbene catalyzed direct carbonylation of dimethylamine

Article abstract of DOI:10.1039/c1cc12047f

N-Heterocyclic carbene (NHC) catalyzed direct carbonylation of dimethylamine leading to the formation of DMF was successfully accomplished under metal-free conditions. The catalytic efficiency was investigated and the turnover numbers can reach as high as >300. The possible mechanism was also proposed.

Full text of DOI:10.1039/c1cc12047f

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COMMUNICATION
N-Heterocyclic carbene catalyzed direct carbonylation of dimethylaminew
Xiaonian Li,* Kun Liu, Xiaoliang Xu, Lei Ma, Hong Wang, Dahao Jiang, Qunfeng Zhang
and Chunshan Lu
Received 11th April 2011, Accepted 13th May 2011
DOI: 10.1039/c1cc12047f
N-Heterocyclic carbene (NHC) catalyzed direct carbonylation
of dimethylamine leading to the formation of DMF was success-
fully accomplished under metal-free conditions. The catalytic
efficiency was investigated and the turnover numbers can reach
as high as 4300. The possible mechanism was also proposed.
carbene electron pair with other kinds of semi-carbene partners,
for example CO, has not yet been fully investigated. It was
reported that transient triplet carbene, but not singlet carbene,
could react with CO to give ketenes easily maybe due to the
electronic characterization difference of two types of carbenes.15
Lyashchuk first reported that 1,3-di-1-adamantylimidazol-2-
ylidene could couple with CO to give the ketene,16 but this was
refuted by Arduengo one year later17 who demonstrated
computationally a weakly bonded ‘‘van der Waals complex’’
intermediate rather than a chemically bonded species. Later,
Bielawski18 and Betrand15b reported that cyclic alkyl amino
carbenes could react with CO to afford amino ketenes. More
recently, Frenking gave a comprehensive theoretical study of
carbonylation of CO with varied carbene structures.19 Based
on these studies and with the interest to explore the application
of NHCs, we wondered whether at increased pressure NHCs
can activate CO. If this could be acheived, then the direct
carbonylation of amines to synthesize formamide derivatives
may be accomplished.
Dimethylformamide (DMF) is an important chemical raw
material and solvent in industry and the lab, and has been
widely used for pesticides and medicinal intermediates.1 The
most common process for the formation of DMF is based on
the direct carbonylation of dimethylamine in the presence
of catalysts, such as sodium methoxide,2 KF/ZnO,3 metal
carbonyls,4 tetramethylammonium methoxide,5 CuCl6 and
so on. For commercial application, sodium methoxide is
undoubtedly a superior catalyst. Although it has many
advantages, accumulation of several kinds of inorganic sodium
salts, such as HCOONa and NaHCO3, that form in the
presence of even small amounts of CO2 and H2O, can
frequently cause the blockage of the pipeline after the reaction
cycle and consequently a considerable amount of waste water
will be produced.7 The alternative method for the production
of DMF is active hydrogenation of CO2 in the presence of
dimethylamine catalyzed by homogeneous8 or heterogenous
catalysts such as Pd(CO3)(Ph3P)2,9 Cu/ZnO,10 RANEYs
Ni,11 supported Pt, Pd etc.12 Although these methods are
effective for the synthesis of DMF, most routes involved the
use of expensive metal or metal complexes as the catalysts, and
thus result in environmental concerns. Therefore, from these
points of view, to find new metal-free and highly efficient
catalyst is highly desirable.
Initially, several imidazoline quaternary ammonium salts
IPrHCl, SIAdHCl, IMesHCl and ICyHCl (Fig. 1) were
prepared.20 We supposed that in the presence of dimethylamine
under pressure, HCl should be dissociated to form the carbene
intermediate which may catalyze the direct carbonylation
reaction. It is gratifying to find that a small amount of
DMF was detected by GC-MS or isolated after distillation.
For example, the reaction of 1 mol of dimethylamine, 2 mmol
of SIAdHCl and 3 MPa of CO, at 130 1C for 4 h in an
autoclave afforded DMF in 9% isolated yield (based on
dimethylamine) after a simple distillation procedure (Table 1).
The other carbene precusors gave slightly lower yields
compared with that of SIAdHCl. With these results, we then
NHCs have aroused considerable interest in the past two
decades due to their wide applications in organic synthesis
and organometallic chemistry.13 Since the pioneering work
reported by Breslow and Wanzlick and the first stable crystal
N-heterocyclic carbene isolated by Arduengo,14 NHCs have
been used in a variety of catalytic chemical transformations.
With respect to acting as organocatalysts, they have shown
powerful catalytic performances and distinctive features in
many organic reactions. Among several kinds of coupling
reactions catalyzed by NHCs,13 the coupling reactions of the
Institute of Industrial Catalysis, College of Chemical Engineering and
Materials Science, Zhejiang University of Technology, Hangzhou
310014, People’s Republic of China. E-mail: xnli@zjut.edu.cn;
Fax: (+86) 571 88320409; Tel: (+86) 571 88320409
Fig. 1 Imidazoline quaternary ammonium salt catalysts.
c
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Table 1 Study of imidazoline quaternary ammonium salts on catalysis
of dimethylamine to DMFa
Table 2 NHC-catalyzed direct carbonylation of aminesa
Catalyst Solvent t/h Yield (%)b TON
Entry Amine
Entry
Catalyst
Yield (%)
1
2
3
(CH3)2NH
IPr
IMes
IPr
IPr
IPr
IPr
IPr
MeOH
MeOH
4
4
19.3
6.4
97
32
1
2
3
4
SIAdHCl
IPrHCl
IMesHCl
ICyHCl
9
7
5.8
7
(CH3)2NH
(CH3)2NH
(CH3)2NH
(CH3)2NH
(CH3)2NH
(CH3)2NH
MeOH 36 47.6
MeOH 36 62.5
MeOH 36 93.4
MeOH 36 38.5
MeOH 36 32.2
MeOH 36 12.1
238
309
187
192
161
60
4c
5d
6e
7f
8
a
Dimethylamine (1 mol), catalyst (2 mmol), methanol (200 mL), CO
(3 MPa), 130 1C, 4 h; the reaction was carried in autoclave.
(C2H5)2NH IPr
9
PhNH2
IPr
IPr
IPr
PPh3
—
MeOH 36
—
36 61
—
10
11
12g
13
CH3NH2
(CH3)2NH
(CH3)2NH
(CH3)2NH
H2O
H2O
305
208
17
used the stable carbene directly to catalyze this reaction with
the anticipation to improve the yield.
36 41.6
MeOH 24 14
MeOH 24
Based on the above results, two stable NHCs IPr and IMes
were examined for this direct carbonylation reaction (Fig. 2).
We were pleased to find that the catalytic effect of carbene was
better than that of the corresponding precursors under the
same reaction conditions (Table 2). With IPr as the catalyst,
the isolated yield of DMF could be increased to 19.3% (entry 1).
Compared with that of IPr, the catalytic activity of IMes was
lower (entry 2). When the reaction time was prolonged to 36 h
with IPr as the catalyst, the desired DMF can be obtained in
47.6% yield (entry 3). When the molar ratio of dimethylamine
and catalyst was 500 : 1, increasing the CO pressure resulted in
higher yield of DMF. Thus, 62.5% yield of DMF was
obtained when 6 MPa of CO was applied (entry 4). Excellent
yield (93.4%) was obtained when the molar ratio of dimethyl-
amine and IPr catalyst was changed from 500 : 1 to 200 : 1
(entry 5). The recovered catalyst can be used repeatedly with
reasonable activities (entries 6–7). Diethylamine as a substrate
gave the carbonylation product in only 12.1% yield under the
optimized conditions (entry 8). When dimethylamine was
replaced by 33% aqueous methylamine solution, the desired
N-methylformamide was obtained in 61% yield (entry 10).
However, the use of the poorly nucleophilic aniline as a
substrate did not give any desired product (entry 9). It is
interesting to find that the use of water as a solvent can give
DMF in 41.6% yield (entry 11), although toluene, ethanol,
THF, DMF as the solvents did not afford any DMF. In the
absence of any catalyst, DMF was only obtained in about 3%
yield under 3 MPa of CO, 1 mol of dimethylamine at 130 1C
for 24 h (entry 13). It is interesting to observe 14% yield of
DMF when 4 mmol of PPh3 was used as a catalyst (entry 12).
In order to elucidate the reaction mechanism, several
experiments were performed. Under 3 MPa of CO, 130 1C
for 24 h, 1 mmol of IPr as a catalyst, 200 mL of methanol as a
solvent in stainless steel batch reactor, the mixture was
checked by GC-MS and silver mirror reaction after cooling.
According to the result of GC-MS and Tollens reagent, methyl
formate can not be detected so that the ketene intermediate
may be not formed, which is in accordance with the results of
3
—
a
Standard conditions: amine (1 mol), carbon monoxide (3 MPa),
catalyst (2 mmol), methanol (200 mL), 130 1C until otherwise noted.
The reaction was carried in autoclave. Isolated yield based on
b
c
dialkylamine. 6 MPa. 5 mmol IPr. Recovered catalyst from entry
f
5 was used. Recovered catalyst from entry 6 was used. 4 mmol PPh3.
d
e
g
Fig. 3 Proposed catalytic mechanism.
Arduengo.17 Combined with the literature findings15–19 and
aforementioned experimental results, a postulated mechanism
is proposed in Fig. 3. First, carbon monoxide, dimethylamine
and IPr are coupled to form the intermediate A, which releases
one molecule of DMF and liberates IPr to complete this
reaction. The driving force for the formation of A may be a
weakly bonded ‘‘van der Waals complex’’.
In conclusion, an efficient NHC-catalyzed carbonylation
of dimethylamine with carbon monoxide was successfully
established notably with metal-free catalyst, which provided
a new method for the synthesis of DMF. Further investigation
including the mechanism, scope, and synthetic application of
this system are in progress.
The authors are grateful to the National Natural Science
Foundation of China (NSFC-20976164) and National Basic
Research Program of China (973 Program) (No. 2011CB710800).
Notes and references
w Reaction: The direct carbonylation of dimethylamine was carried
out in a stainless steel batch reactor of 500 mL. 1 mol of dimethyl-
amine gas was introduced into 150 mL of methanol at 0 1C. Then this
solution was pressed into a batch reactor which contained the
combined mixture of a known amount of catalyst and 50 mL of
methanol. The reactor was heated to 130 1C with stirring speed about
900 rpm. Then CO was charged into the reactor until an indicated
pressure was reached. After a certain time, the reactor was placed in
ice–water and the gas was released. The reaction mixture was trans-
ferred into a three-necked flask. Methanol was evaporated and the
mixture was distilled to give the purified product DMF. The quanti-
tative and qualitative analysis of the reaction mixture was conducted
using an Agilent GC-6890, MS-5973 instrument. Recovery process for
catalyst: After distillation of DMF, black and semi-solid material was
left over in the distillation flask. Water was added and the mixture was
extracted by ethyl acetate three times. The combined organic phase
Fig. 2 N-Heterocyclic carbene catalysts.
c
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