N-heterocyclic carbene - Palladium complexes as efficient catalysts for the oxidative carbonylation of amines to ureas

Article abstract of DOI:10.1002/hlca.200790152

A highly efficient oxidative carbonylation reaction of amines to ureas was developed making use of carbene-palladium complexes in the absence of any promoter. Both aliphatic amines and aromatic amines were transformed in good to excellent yields to the expected ureas.

Full text of DOI:10.1002/hlca.200790152

Helvetica Chimica Acta – Vol. 90 (2007)
1471
N-Heterocyclic Carbene – Palladium Complexes as Efficient Catalysts for the
Oxidative Carbonylation of Amines to Ureas
by Shuzhan Zhenga)b), Xingao Penga)b), Jianming Liua)b), Wei Suna), and Chungu Xia*a)
a) State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical
Physics, Chinese Academy of Sciences, Lanzhou, 730000, P. R. China
(fax: þ 869318277088; e-mail: cgxia@lzb.ac.cn)
b) Graduate School of the Chinese Academy of Sciences, Beijing, 100039, P. R. China
A highly efficient oxidative carbonylation reaction of amines to ureas was developed making use of
carbene – palladium complexes in the absence of any promoter. Both aliphatic amines and aromatic
amines were transformed in good to excellent yields to the expected ureas.
Introduction. – Since the discovery of a stable, crystalline N-heterocyclic carbene
(NHC) by Arduengo and co-workers [1], the use of NHCs as ligands in organometallic
chemistry and homogeneous catalysis has become increasingly popular in the last few
years [2]. A series of highly active catalytic systems with NHC ligands for divers
transformations have been developed, such as ruthenium-mediated olefin metathesis
[3], iridium-catalyzed hydrogenation [4], nickel-catalyzed aerobic alcohol oxidations
[5], and palladium-mediated cross-coupling reactions [6]. Recently, NHC complexes
have also been used in carbonylation reactions: Crudden and co-workers, Weberskirch
and co-workers, Fernandez and Peris and co-workers, and Nuyken and Buchmeiser and
co-workers reported carbene – rhodium-complex-catalyzed hydroformylations of ole-
fins [7], and Nacci and co-workers used a [Pd(benzothiazolylidene)] complex as
catalyst for the carbonylation of aryl halides [8]. These studies showed that NHC –
palladium complexes also could be efficient catalysts in carbonylation reactions.
Ureas are important chemicals widely used as agrochemicals, dyes, antioxidants,
resin precursors, synthetic intermediates (also for the production of carbamates and
isocyanates), and HIV inhibitors [9]. The conventional methods for the preparation of
ureas utilize highly toxic phosgene as the carbonyl source, which may cause serious
environmental pollution and equipment corrosion [10]. In recent years, many non-
phosgene routes, including those involving reductive [11] and oxidative carbonylation
[12] have been extensively studied. The latter reaction is particularly attractive from
the standpoint of atom economy and environmental concern; it employs an amine,
carbon monoxide, and oxygen as starting materials and produces only H2O as by-
product (Eqn. 1). The corresponding catalytic turnover frequencies (TOF), however,
are still not high enough for industrial applications, and the development of more
efficient catalysts is necessary. The NHC complexes are stable toward high temper-
ature, air, and moisture and tolerant towards oxidation conditions [13]. These
properties make NHC complexes ideal candidates for oxidative carbonylation
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

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reactions. However, there are few reports on oxidative carbonylations in the presence
of NHC – palladium-complex catalysts. Nevertheless, it is worthy to note that Sugiyama
and co-workers have reported on the [Pd(NHC)]-catalyzed oxidative carbonylation of
phenol to diphenyl carbonate [14]. Here, we report the successful synthesis of ureas
from amines by oxidative carbonylation in the presence of [Pd(NHC)] complexes.
2 RNH2 þ CO þ 1/2 O2 ! (RNH)2CO þ H2O
(1)
Results and Discussion. – The initial investigation of oxidative carbonylation with
CO/O2 was carried out with aniline as substrate and [PdI2(NHC)(PPh3)] complex 1
[15] as catalyst to optimize the reaction conditions (Table 1). Interestingly, 1 was found
to be effective even at a loading as low as 0.02 mol-%. HPLC and GC/MS Analysis of
the reaction mixture revealed a 93% conversion of aniline and a high selectivity (99%).
It should be noted that in most of the oxidative carbonylation reactions an excess of
promoter is required [11]. In contrast, carbene – metal catalyst 1 gave good results in
the absence of any promoter and within much shorter times. The catalytic system was
sensitive to the reaction temperature; optimal results were obtained at 1508 (Table 1,
Entry 2), decreasing or increasing the temperature both resulted in a dramatic loss of
catalytic activity. Additionally, the solvent played a key role. High catalytic activities
were obtained in the polar solvent DMF. In less polar solvents, such as 1,4-dioxane or
THF, poor conversions were achieved (Table 1, Entries 6 and 7). When using 1,2-
dimethoxyethane (MeOCH2CH2OMe) as solvent, the conversion was good but the
selectivity unsatisfactory (Table 1, Entry 5).
It is known that the performance of homogeneous catalysts is highly dependent on
the ancillary ligand coordinated to the metal center [16], non-NHC ligands have a
remarkable influence on the properties of [Pd(NHC)] complexes [15]. Thus,
complexes 2 – 4 were synthesized and investigated in the oxidative carbonylation
reactions, complex 2 [17] having two NHC ligands, complex 3 an NHC and a pyridine
ligand, and complex 4 an NHC and an aniline ligand, as compared to the NHC and PPh3
ligand of 1. The activity of 2 (70% conversion) was lower than that of 1 (93%
conversion), 3 (86% conversion), and 4 (99% conversion) under the same conditions
(Table 1). This may be due to the fact that NHC is a tightly bound ligand hard to
dissociate during catalysis to generate the active species [18]. On the other hand, PPh3
and aniline were more labile ligands as compared to NHC, i.e., their dissociation were
more easy; thus 1 and 4 showed higher activities. Remarkably, although the activities
were different, all the [Pd(NHC)] complexes 1 – 4 showed high selectivities. Especially,
4 exhibited excellent activity and selectivity. Complex 4 is a new type of Pd-complex

Helvetica Chimica Acta – Vol. 90 (2007)
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Table 1. Synthesis of N,N’-Diphenylurea by Oxidative Carbonylation of Aniline in the Presence of
Catalysts 1 – 4a)
Entry Catalyst T [8] Solvent
Conversionb) [%] Selectivityb) [%] TOF [hÀ1]c)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
2
3
4
140
150
160
170
150
150
150
150
150
150
DMF
DMF
DMF
DMF
86
9399
91
98
4600
4200
99
99
76
99
99
99
99
99
4500
4200
3400
440
3700
3400
4200
4900
86
MeOCH2CH2OMe 92
dioxane
THF
DMF
DMF
DMF
9
75
70
86
99
10
a) Reaction conditions: catalyst (0.0044 mmol), aniline (22 mmol), solvent (6 ml); P(CO, O2) ¼ 3.2,
0.8 MPa; time 1 h. b) Determined by HPLC. c) Mol of amine converted per mol of catalyst per hour.
containing both an NHC and an aniline as ligands. The structure of 4 was confirmed by
a single-crystal X-ray diffraction analysis (Fig.). The ORTEP diagram reveals an
unusual coordination mode in the carbene – palladium complex 4, in which an aniline
and an NHC are both bound to one Pd-atom, which is a rare case. According to the
above results, more labile non-NHC ligands have a remarkable influence on the
catalytic activity of [Pd(NHC)] complexes in this reaction.
Figure. ORTEP Diagram of 4. Arbitrary atom numbering. Selected distances [Š] and angles [8]:
Pd(1)ÀI(1) 2.6052(6), Pd(1)ÀI(2) 2.6169(6), Pd(1)ÀC(7) 1.958(5), and Pd(1)ÀN(1) 2.147(3);
Pd(1)ÀN(1)ÀC(1)
110.2(2),
N(1)ÀPd(1)ÀC(7)
174.6(2),
I(1)ÀPd(1)ÀI(2)
175.051(18),
C(7)ÀPd(1)ÀI(1) 88.18(16), and C(7)ÀPd(1)ÀI(2) 88.56(16).
After the systematic optimization of the reaction conditions, we successfully applied
the highly efficient oxidative carbonylation with CO/O2 in the presence of only a
[Pd(NHC)] catalyst without any promoter to other primary amines (Table 2). And to
the best of our knowledge, this is the first time that an NHC is used in the oxidative

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carbonylation of amines to prepare symmetrically N,N’-disubstituted ureas. Good to
excellent yields of isolated ureas were obtained. As expected, the presence of an
electron-releasing or an electron-withdrawing substituent at the para-position of
aniline strongly affected the reactivity of the substrate, electron-attracting substituents
slightly retarding the reaction (87% and 60% conversion for p-Cl- and p-Ac-
substituted aniline (Entries 2 and 5), resp.). Sterically more crowded substrates such as
2,6-dimethylaniline also gave good yields (Entry 4, 72%). Aliphatic amines were less
reactive than aromatic ones when the reactions were performed at 1508 and in DMF as
solvent (Entry 6). This was due to the formation of formamide and oxamide as by-
products. Satisfactory results were obtained for the aliphatic amines by using
MeOCH2CH2OMe as solvent at a lower temperature, i.e., at 1008 (Entries 7 and 8).
Benzylamine gave also good yields (Entry 9).
Table 2. Synthesis of Ureas by Oxidative Carbonylation of Primary Amines in the Presence of Catalyst 4a)
Entry
Substrate RNH2
Product (RNH)2CO
Yieldb)
1
2
3
4
5
6
7c)
8c)
9c)
4-MeÀC6H4ÀNH2
4-ClÀC6H4ÀNH2
2,4-Me2C6H3ÀNH2
2,6-Me2C6H3ÀNH2
4-AcÀC6H4ÀNH2
BuNH2
BuNH2
tBuNH2
PhCH2NH2
(4-MeÀC6H4ÀNH)2CO
(4-ClÀC6H4ÀNH)2CO
(2,4-Me2C6H3ÀNH)2CO
(2,6-Me2C6H3ÀNH)2CO
(4-AcÀC6H4ÀNH)2CO
(BuNH)2CO
(BuNH)2CO
(tBuNH)2CO
(PhCH2NH)2CO
99
87
85
72
60
46
75
70
75
a) Reaction conditions: Catalyst 4 (0.0044 mmol), substrate (22 mmol), DMF (6 ml); P(CO, O2) ¼ 3.2,
0.8 MPa; time 1 h, temp. 1508. b) Yields of isolated material. c) Temp. 1008, time 10 h, solvent
MeOCH2CH2OMe.
Conclusions. – In summary, a by-product-free catalytic method for the synthesis of
symmetrically N,N’-substituted ureas from amines, CO, and O2 was developed. Therein,
the carbene – palladium complexes were highly efficient catalysts at a low loading and
in the absence of any promoter. Both aliphatic and aromatic amines gave good to
excellent yields of ureas. Efforts are underway to elucidate the mechanistic details of
this oxidative carbonylation reaction catalyzed by [Pd(NHC)] complexes.
We gratefully acknowledge financial support from the National Science Foundation of China
(20533080, 20625308). We thank Dr. Jun Zhang for assistance in performing the X-ray crystal-structure
analysis.
Experimental Part
General. THF was purified by distillation from sodium/benzophenone immediately before use as
solvent. Unless otherwise noted, all chemicals were purchased from commercial suppliers and used
without further purification. Flash chromatography (FC): silica gel 200 – 300 mesh. GC Analyses: HP
6890/5973-GC-MS and HP 5890-GC apparatus. IR Spectra: n in cmÀ1. NMR Spectra: Varian 400-MHz-
~
FT-NMR spectrometer; d in ppm, J in Hz.

Helvetica Chimica Acta – Vol. 90 (2007)
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(1-Butyl-1,3-dihydro-3-methyl-2H-imidazol-2-ylidene)diiodopyridinepalladium (3). To a soln. of
bis(1-butyl-1,3-dihydro-3-methyl-2H-imidazol-2-ylidene)di-m-iododiiododipalladium (150 mg) [17] in
THF (2 ml), pyridine (25 ml) was added and the mixture was stirred for 10 min at r.t. (red ! yellow).
Then, hexane (10 ml) was added and the yellow precipitate filtered, washed with hexane (3ꢀ), and dried
1
in vacuo: 3 (166 mg, 96%). H-NMR (400 MHz, CDCl3): 9.02 (q, J ¼ 4.8, 2 H, Py); 7.71 (t, J ¼ 7.6, 1 H,
Py); 7.30 (t, J ¼ 6.8, 2 H, Py); 6.91 (d, J ¼ 2.0, 2 CHN); 4.37 (t, J ¼ 7.6, CH2N); 3.95 (s, MeN); 2.01 (m,
1 CH2), 1.45 (m, 1 CH2), 1.01 (t, J ¼ 7.6, Me). 13C-NMR (100 MHz, CDCl3): 153.8 (CN2); 139.7 (Py);
124.4 (Py); 123.1 (Py); 121.5 (CHN); 109.8 (CHN); 51.3 (CH2N); 39.2 (MeN); 31.4 (CH2); 19.9 (CH2);
13.7 (Me). Anal. calc. for C13H19I2N3Pd: C 27.04, H 3.32, N 7.27; found: C 26.96, H 3.50, N 7.44.
(Benzenamine)(1-butyl-1,3-dihydro-3-methyl-2H-imidazol-2-ylidene)diiodopalladium (4). As de-
scribed for 3, with bis(1-butyl-1,3-dihydro-3-methyl-2H-imidazol-2-ylidene)di-m-iododiiododipalladium
[17], THF (2 ml), and aniline (30 ml): 4 (170 mg, 98%). Crystals of 4 suitable for X-ray crystallographic
analysis were obtained from a sat. soln. in THF by slow evaporation of the solvent at r.t. IR (KBr): 3272,
3221, 1599, 1581, 1491, 1469, 1068, 755, 690. 1H-NMR (400 MHz, CDCl3): 7.44 (d, J ¼ 8.4, 2 H, Ph); 7.29 (t,
J ¼ 7.6, 2 H, Ph); 7.11 (t, J ¼ 7.2, 1 H, Ph); 6.91 (d, J ¼ 2.0, 1 CHN); 6.85 (d, J ¼ 2.0, 1 CHN); 4.45 (s, NH2);
4.16 (t, J ¼ 8.0, CH2N); 3.79 (s, MeN); 1.88 (m, 1 CH2); 1.31 (m, 1 CH2); 0.89 (t, J ¼ 7.2, CH3). 13C-NMR
(100 MHz, CDCl3): 144.8 (N2C); 139.7 (Ph); 128.9 (Ph); 124.8 (Ph); 123.0 (Ph); 121.7 (CHN); 121.6
(CHN); 51.3(CH 2N); 39.1 (MeN); 31.4 (CH2); 19.8 (CH2); 13.6 (Me). Anal. calc. for C14H21I2N3Pd: C
28.42, H 3.57, N 7.10; found: C 29.10, H 3.69, N 6.94.
CCDC-624386 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.
Catalytic Oxidative Carbonylation: General Procedure. A 75-ml autoclave equipped with a magnetic
stirring bar and automatic temp. control was charged with the mentioned amounts of an amine, catalyst,
and solvent (6 ml) and then pressurized with CO (3.2 MPa) and O2 (0.8 MPa) to a total pressure of
4.0 MPa. The reactor was heated at the specified temp. for 1 h. After cooling, the autoclave was degassed
and the mixture analyzed by HPLC and GC/MS. Then, H2O was poured into the mixture to precipitate
the crude product, which was purified by washing with acetone: pure product as white solid. The filtrate
was concentrated and the residue washed with acetone to afford another crop of the product.
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Received January 29, 2007