Pd/C: an efficient, heterogeneous and reusable catalyst for carbon monoxide-free aminocarbonylation of aryl iodides

Article abstract of DOI:10.1016/j.tetlet.2008.02.049

Carbon monoxide-free aminocarbonylation is carried out efficiently via coupling of N,N-dimethylformamide (DMF) with aryl iodides using Pd/C as a heterogeneous catalyst. The catalyst exhibits remarkable activity and is reusable for up to three consecutive cycles. The reaction is applicable to a wide variety of substituted aryl iodides with different steric and electronic properties providing excellent yields of the corresponding tertiary amides.

Full text of DOI:10.1016/j.tetlet.2008.02.049

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2221–2224
Pd/C: an efficient, heterogeneous and reusable catalyst for
carbon monoxide-free aminocarbonylation of aryl iodides
Pawan J. Tambade, Yogesh P. Patil, Mayur J. Bhanushali, Bhalchandra M. Bhanage *
Department of Chemistry, Institute of Chemical Technology (Autonomous), University of Mumbai, N. Parekh Marg, Matunga, Mumbai 400 019, India
Received 12 December 2007; revised 29 January 2008; accepted 10 February 2008
Available online 13 February 2008
Abstract
Carbon monoxide-free aminocarbonylation is carried out efficiently via coupling of N,N-dimethylformamide (DMF) with aryl iodides
using Pd/C as a heterogeneous catalyst. The catalyst exhibits remarkable activity and is reusable for up to three consecutive cycles. The
reaction is applicable to a wide variety of substituted aryl iodides with different steric and electronic properties providing excellent yields
of the corresponding tertiary amides.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Carbonylation; Aryl iodides; Amides; Palladium; Heterogeneous catalyst
Catalytic reactions are generally classified as homoge-
neous and heterogeneous depending on the nature of the
catalyst employed. It is well known that homogeneous
catalysts consisting of soluble metal complexes have high
activity and selectivity compared to heterogeneous cata-
lysts.1,2 In spite of their potential utility their application
is limited due to difficulties encountered in catalyst-product
separation. Additionally the ligands (usually phosphine
ligands) which are required to stabilize the transition metal
ion are air/moisture sensitive, expensive and require special
handling techniques. To overcome these drawbacks several
modifications of these catalysts have been developed,3–5
such as anchoring of the metal complex to a polymeric or
mineral support,6 supported liquid phase catalysis,7,8
biphasic catalysis9 and transition metals on activated
carbon.10–14 As such, these catalysts can be easily recovered
from the reaction medium and reused further.
by reaction with primary or secondary amines. Tradition-
ally, carbon monoxide gas is the most commonly employed
source of the carbonyl group in these transformations.15–17
However, the use of sophisticated instruments such as high
pressure reactors, troublesome gas handling procedures
and the toxicity of carbon monoxide limits the use of
carbonylation reactions for the synthesis of compound
libraries. To overcome these difficulties, carbon mon-
oxide-free syntheses of amides using various other sources
such as formamide, metal carbonyls and DMF have been
reported.18–21 Recently, Ju et al. reported aminocarbonyl-
ation of aryl halides using Ni/phopshite as the catalytic sys-
tem.22 However, despite their potential utility, the above
methods suffer from the drawback of catalyst-product sep-
aration thereby limiting their application. Also, in many
cases, the catalysts used are homogeneous and are not
Palladium catalyzed aminocarbonylation (Heck carbon-
ylation) is a selective and useful method for the direct syn-
thesis of amides from aryl, heterocyclic and alkenyl halides
O
O
Pd/C
POCl3, 140 ºC
N
+
I
H
N
R
R
R = H, Me, OMe, Br, NO2
*
Corresponding author. Tel.: +91 22 2414 5616; fax: +91 22 2414 5614.
Scheme 1. Pd/C catalyzed aminocarbonylation of aryl iodides.
E-mail address: bhalchandra_bhanage@yahoo.com (B. M. Bhanage).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.049

2222
P. J. Tambade et al. / Tetrahedron Letters 49 (2008) 2221–2224
recyclable. The loss of a palladium catalyst, even at ppm
level, is not desirable due to its high cost. Therefore, the
search for a heterogeneous and reusable catalyst which
could efficiently catalyze the aminocarbonylation reaction
is the subject of the present work.
We herein report an efficient carbon monoxide-free
aminocarbonylation of aryl iodides using Pd/C as a hetero-
geneous and reusable catalyst in the presence of DMF and
phosphoryl chloride (Scheme 1). The catalyst showed
remarkable activity and the system tolerates a wide variety
of functional groups such as NO2, Br, CH3 and OCH3 on
the aryl halide. The catalyst was also found to be reusable
for up to three consecutive cycles without any significant
loss in activity.
yields of the desired product. The use of PdCl2/4PPh3
was found to be ineffective. Since the reusability of the
catalyst was the primary aim of this study 5% and 10%
Pd supported on activated carbon (Pd/C) were employed
as the catalyst. However, 5% Pd/C afforded only a 16%
yield whereas 10% Pd/C gave 76% yield of the desired ter-
tiary amide. In an effort to determine the optimum concen-
tration of the catalyst, various catalyst loadings were
studied as shown in Table 1 (entries 11–14). The yield
increased on increasing the catalyst concentration. Opti-
mum results with respect to yield (76%) were obtained
when 10 mol % of Pd/C was used. Hence, the optimum
reaction parameters were: temperature 140 °C, 10% Pd/C,
10 mol % catalyst loading and a time of 24 h.
To optimize the reaction conditions, the coupling of
N,N-dimethylformamide with iodobenzene in the presence
of POCl3 was chosen as a model system. The influence of
various parameters such as temperature, catalyst and cata-
lyst loading (Table 1) was examined on the model reaction.
The reaction was carried out at five different tempera-
tures (80, 100, 120, 140 and 160 °C). It was observed that
at 80 °C the yield of the desired product was too low. On
increasing the temperature to 140 °C, a 76% yield was
obtained within 24 h. Although a similar result was
obtained when the reaction was carried out at 120 °C, at
140 °C thermal redeposition of the catalyst was more effec-
tive as discussed later. With further increase of the temper-
ature to 160 °C, the yield of the desired product decreased
to 68%. Hence, 140 °C was the optimum temperature for
this reaction. The effect of various catalysts on the reaction
was investigated (Table 1, entries 6–10). Several homo-
geneous palladium salts with and without ligands were
tested. Both Pd(OAc)2 and PdCl2 provided 59% and 73%
The scope of Pd/C as the aminocarbonylation catalyst
was further demonstrated in the reaction of various substi-
tuted aryl halides with DMF in the presence of POCl3. The
desired products were obtained in good to moderate yields
(Table 2, entries 1–7).23
The reaction of iodobenzene with DMF proceeded
smoothly providing a 76% yield of N,N-dimethylbenz-
amide. Various electron-donating and electron-withdraw-
ing groups on the aryl halide such as Me, OMe and Br were
well tolerated to give the desired tertiary amides in good
yields. 4-Iodonitrobenzene which is a deactivated substrate
Table 2
Pd/C catalyzed aminocarbonylation of aryl iodidesa
Entry
1
Aryl iodide
Product
Yieldb (%)
76
O
I
N
O
Me
I
2
3
4
5
6
N
73
68
70
66
63
67
Table 1
Me
Effect of reaction parameters on the aminocarbonylation of PhIa
Me
O
Entry
Catalyst
Temp (°C)
Catalyst loading
(mol %)
Yieldb (%)
I
N
Me
Influence of temperature
1
2
3
4
5
Pd/C (10%)
Pd/C (10%)
Pd/C (10%)
Pd/C (10%)
Pd/C (10%)
80
10
10
10
10
10
43
64
76
76
68
O
100
120
140
160
MeO
O2N
I
N
MeO
O2N
O
Influence of catalyst
N
I
6
7
8
9
10
Pd(OAc)2
PdCl2
Pd/C (10%)
Pd/C (5%)
PdCl2/4PPh3
140
140
140
140
140
10
10
10
10
10
59
73
76
16
O
Br
I
N
No reaction
Br
Influence of catalyst loading
11
12
13
14
a
Pd/C (10%)
Pd/C (10%)
Pd/C (10%)
Pd/C (10%)
140
140
140
140
2.5
5
10
15
35
58
76
78
I
O
N
7
a
Reaction conditions: Iodobenzene (1 mmol), POCl3 (2 mmol), DMF
Reaction condition: aryl iodide (1 mmol), Pd/C (0.1 mmol), POCl3
(10 ml), time = 24 h.
(2 mmol), DMF (10 ml) at 140 °C, time = 24 h.
b
b
Yields based on GC analysis.
Isolated yields.

P. J. Tambade et al. / Tetrahedron Letters 49 (2008) 2221–2224
2223
Cl
for coupling reactions (since it is easily dehalogenated to
Cl
Cl
+
+
N Me
H
the corresponding arene) afforded a satisfactory yield of
the desired product (entry 5). ortho-Substituents on the aryl
halide were also viable partners for the coupling reaction.
Encouraged by these results, the catalyst was then utilized
for the aminocarbonylation of sterically hindered 1-iodo-
naphthalene to afford a 67% yield of N,N-dimethyl-
naphthamide. Thus the protocol is effective for the
coupling of aryl iodides having different steric and
electronic properties.
2
N Me
+
2
H
Ar
N Me
2
Ar
2
PdX
3
O
O
Ar-Pd-X
H-Pd-X
Ar
NMe
2
NMe
H
2
1
Pd (0)
Ar-X
H-X
Scheme 2. Mechanism of the reaction.
The methodology was further extended to the coupling
of formamide and its derivatives with aryl iodides. How-
ever, no coupling product was observed. Similarly, the
reaction of bromobenzene with DMF was also attempted,
but no product formation was detected. Thus, only aryl
iodides and DMF are viable partners for these coupling
reactions.
The probable mechanism for the aminocarbonylation of
the aryl iodide is shown in Scheme 2. Initially, oxidative
insertion of Pd(0) into the C–X bond produces an aryl pall-
adium halide 1 under the present reaction conditions.25
Then nucleophilic addition of the aryl palladium halide
to the imminium salt 2 (generated from the reaction of
POCl3 and DMF, also known as the Vilsmeier reagent)
occurs to form 3, which undergoes b-hydride elimination
followed by hydrolysis to give the desired product. As
earlier reported by Hosoi et al.,21 the formation of the
Vilsmeier reagent in this case is essential for the reaction
to occur and no base is employed to regenerate Pd(0) from
hydro palladium halide species (H–Pd–X).
In conclusion, we have reported an efficient, hetero-
geneous and reusable catalyst system for the carbon mono-
xide-free synthesis of various substituted tertiary amides.
The reaction was optimized with respect to various param-
eters and could be used for the coupling of electron-rich,
electron deficient and sterically hindered aryl iodides.
Catalyst reusability and Pd leaching were also examined
and effective redeposition of Pd metal on the support was
carried out using thermal deposition.
The reusability of the catalyst was also examined in the
standard reaction of iodobenzene with DMF. It is well
known that the supported palladium leaches out into the
solvent and the reaction is catalyzed mainly by these dis-
solved palladium species. To reuse the catalyst, redeposi-
tion of palladium was attempted using methods such as
(a) chemical redeposition in which a reducing agent like
sodium formate is added to the solution, (b) chemical rede-
position using ultrasound,13 and (c) thermal redeposition
which can occur in situ at higher temperature.10 Redeposi-
tion of the catalyst was monitored using ICP-AES analysis.
When chemical redeposition using sodium formate in the
presence of ultrasound was performed, ICP-AES analysis
of the reaction mixture revealed the palladium content to
be 43.65 ppm. We then attempted thermal redeposition.
At 120 °C thermal redeposition was not effective and the
Pd content of the reaction mixture was found to be
37.79 ppm, whereas at 140 °C efficient redeposition of Pd
took place and the Pd content was found to be 4.45 ppm
which is also in agreement with literature reports for
similar catalyst systems used for the Heck reaction.10
The redeposited catalyst was then given prior treatment
and used for the next cycle.24 The catalyst required activa-
tion at 200 °C for 12 h prior to the next recycle and gave a
74% yield of the desired product. Thus the catalyst was suc-
cessfully recycled and the reusability procedure was tested
up to three times and consistent results were obtained
(Fig. 1).
Acknowledgement
Financial assistance from the Technical Education
Quality Improvement Programme (TEQIP), Government
of India is kindly acknowledged.
References and notes
1. Applied Homogeneous Catalysis with Organometallic Compounds;
Cornils, B., Herrmann, W. A., Eds.; Wiley: Weinheim, 2000.
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211–218.
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2000, 6, 1773–1780.
7. Fujita, S.; Yoshida, Y.; Bhanage, B. M.; Shirai, M.; Arai, M. J. Mol.
Catal. A. 2002, 180, 277–284.
8. Bhanage, B. M.; Shirai, M.; Arai, M. J. Mol. Catal. A. 1999, 145, 69–
74.
100
76
74
73
72
80
60
40
20
0
1
2
3
4
9. (a) Chaudhari, R. V.; Bhanage, B. M.; Deshpande, R. M.; Delmas, H.
Nature 1995, 373, 501–503; (b) Bhanage, B. M.; Ikushima, Y.; Shirai,
M.; Arai, M. Tetrahedron Lett. 1999, 40, 6427–6430.
Cycle
Fig. 1. Catalyst reusability.

2224
P. J. Tambade et al. / Tetrahedron Letters 49 (2008) 2221–2224
10. Zhao, F.; Bhanage, B. M.; Shirai, M.; Arai, M. Chem. Eur. J. 2000, 6,
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under nitrogen. After completion, the reaction mixture was cooled to
room temperature and filtered using a sintered funnel. The filtrate was
poured into a saturated solution of NaHCO3. The aqueous layer was
then extracted with ethyl acetate. The combined organic layers were
dried over Na2SO4 and the solvents were removed in vacuo to afford
the crude product which was purified by column chromatography
using chloroform/methanol as eluent. Spectral data for selected
products:
1
Table 2, entry 1: H NMR (300 MHz, CDCl3, 25 °C, TMS): d 3.1 (s,
6H), 7.4 (s, 5H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d
35.4, 127.1, 128.4, 129.6, 136.4, 171.8 ppm. MS (70 eV, EI): m/z (%):
149 (27) (M+), 148 (59), 105 (100), 77 (62).
1
Table 2, entry 4: H NMR (300 MHz, CDCl3, 25 °C, TMS); d 2.9 (s,
17. Beller, M.; Cornils, B.; Frohning, C. D.; Kohlpaintner, C. W. J. Mol.
Catal. A: Chem. 1995, 104, 17–85.
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5588.
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4615–4618.
23. General procedure for the aminocarbonylation of aryl halides:
A mixture of aryl iodide (1 mmol) and Pd/C (10 mol %) in DMF
(10 ml) was taken in a 25 ml two-necked round-bottom flask and
stirred for 10 min at room temperature. Then POCl3 (2 mmol) was
added to the reaction mixture with stirring over a period of 15 min.
The reaction mixture was magnetically stirred at 140 °C for 24 h
6H), 3.8 (s, 3H), 6.9 (d, J = 2.1 Hz, 6.6 Hz, 2H), 7.41 (dd, J = 2.1 Hz,
6.6 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C, TMS): d 35.3,
55.1, 113.3, 128.1, 128.9, 162.4, 171.3 ppm. MS (70 eV, EI): m/z (%):
179 (19) (M+), 178 (25), 135 (100), 77 (24).
1
Table 2, entry 5: H NMR (300 MHz, CDCl3, 25 °C, TMS): d 2.9 (s,
6H), 7.7 (dd, J = 2.1 Hz, 6.9 Hz, 2H), 8.3 (dd, J = 2.1 Hz, 6.9 Hz,
2H), ppm. 13C NMR (75 MHz, CDCl3, 25 °C, TMS): d 35.3, 123.7,
128.0, 142.5, 148.2, 169.2 ppm. MS (70 eV, EI): m/z (%): 194 (35)
(M+), 193 (100), 150 (82), 104 (55).
24. Procedure for catalyst recycling: The catalyst obtained after filtration
was washed with saturated NaHCO3 solution (5 ml  3) to remove
any acidic impurities if present and then with water (5 ml  3) and
finally with dichloromethane (5 ml  3) to remove any organic
impurities. The resulting catalyst was dried in oven at 200 °C for
12 h and used for the next cycle.
25. Heck, R. F. In Palladium Reagents in Organic Synthesis; Academic
Press: London, 1985; p 352.