Recyclable heterogeneous iron catalyst for C-N cross-coupling under ligand-free conditions

Article abstract of DOI:10.1021/jo901095c

(Chemical Equation Presented) An efficient and ligand-free C-N cross-coupling of aryl halides with various heterocycles using Fe/C_g as a recyclable catalyst is reported. The yields are excellent to moderate. 2009 American Chemical Society.

Full text of DOI:10.1021/jo901095c

pubs.acs.org/joc
C-N cross-coupling reactions are considered to be impor-
Recyclable Heterogeneous Iron Catalyst for C-N
Cross-Coupling under Ligand-Free Conditions
tant in the synthesis of optical devices, pharmaceuticals, and
materials.1 Several metal salts such as Pd,2 Cu,3 Ni,4 Cd,5 etc.
have been reported for the catalysis of N-arylation. Of
recent, iron-catalyzed C-N bond formation developed by
Liu,6a Bolm,6b-d and Taillefer6e involving different ligands
and cocatalysts has attracted considerable attention of che-
mists due to their inexpensive, nontoxic, and environmen-
tally friendly properties. Though these results are highly
encouraging, we felt that there is still scope to further
improve these catalytic systems by making them ligand-free
with a recyclable catalyst for an efficient access to these
highly useful organic compounds.
K. Swapna, A. Vijay Kumar, V. Prakash Reddy, and
K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical
Technology, Uppal Road, Tarnaka, Hyderabad 500607, India
kakulapatirama@gmail.com
Received May 25, 2009
Herein, we report a highly efficient, reusable graphite-
supported iron(III) acetyl acetonate catalytic system for the
C-N cross-coupling of aryl halides with amines in the
absence of any external ligand. Though many metals dis-
persed on graphite, viz. M-graphite (M = K, Zn, Sn, Fe, Ti,
Pd),7 were reported, the very tedious preparation of these
systems limits their use as catalysts. We have developed a
protocol in which FeIII(acac)3 was dispersed on graphite by
simple procedure. The amount of iron8 was found to be 4.3%
on graphite by ICP-AES analysis. Initially, the reaction
between phenyl iodide (1) and 1H-pyrazole (2) in the pre-
sence of Fe/Cg catalyst was tested as a model reaction of
C-N cross-coupling (Scheme 1).
An efficient and ligand-free C-N cross-coupling of aryl
halides with various heterocycles using Fe/Cg as a recycl-
able catalyst is reported. The yields are excellent to
moderate.
SCHEME 1. Heterogeneous Fe/Cg-Catalyzed C-N Cross-
Coupling
Sustainable chemistry plays a vital role in chemical in-
dustries. As a part of this preoccupation, the search for more
economic and eco-friendly synthetic methodologies is our
primary concern. Among them, transition-metal-catalyzed
The reaction was optimized using various reaction para-
meters such as temperature, solvent, base, catalyst loading,
etc. (Table 1). No product formation could be seen in the
temperature range of 60-80 °C (Table 1, entries 1 and 2),
while lower yield was observed at 100 °C (Table 1, entry 3).
The desired C-N product formation was observed (3a) in
95% yield when the substrates were stirred for 24 h at 120 °C
in the presence of 5 wt % Fe/Cg and KOH in dry DMSO
under nitrogen atmosphere (Table 1, entry 4). Among several
solvents tested, DMF, toluene, and dioxane were less effec-
tive compared to DMSO (Table 1, entries 5-7). DMSO was
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7514 J. Org. Chem. 2009, 74, 7514–7517
Published on Web 09/01/2009
DOI: 10.1021/jo901095c
r
2009 American Chemical Society

Swapna et al.
JOCNote
TABLE 1. Optimization of Reaction Conditions for the C-N Cross-
TABLE 2. Efficiency of Different Iron Sources in the C-N Cross-
Coupling of 1 and 2 Using Fe/Cg Catalysta
Couplinga
entry catalyst (%) temp (°C)
solvent
base
yield (%)
entry
X
Fe source
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18c
a
5
5
5
5
5
5
5
5
5
5
5
5
3
2.5
1
5
5
5
60
80
DMSO
DMSO
DMSO
DMSO
DMF
KOH
KOH
KOH
KOH
KOH
KOH
1
2
I
I
I
Br
I
I
I
I
Br
I
none
Fe2O3
Fe2O3
Fe2O3
Fe2O3
Fe2O3
Fe3O4
Fe3O4
Fe3O4
Fe(acac)3
Fe/Cg
graphite
75
20
30
15
20
70
25
35
100
120
120
120
120
120
120
120
120
120
120
120
120
120
rt
30
95
30
20
25
15
10
55
trace
trace
85
60
40
3b
4
5c
6d
7
Toluene
Dioxane KOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
K2CO3
Cs2CO3
NaOH
NaOtBu
KOtBu
KOH
KOH
KOH
KOH
KOH
KOH
8b
9
10
11
12
a
20
95
I
I
trace10
Reaction conditions: PhX (1.0 mmol), 2 (1.0 mmol), Fe/Cg
(116 mg, 5 wt %), KOH (2.5 equiv), dry DMSO (1.5 mL), N2, 120 °C.
bDMF as solvent. cReaction carried out under standard conditions by
using L-proline as a ligand. dUsing DMEDA as a ligand.
65
120
Reaction conditions:
1
(1.0 mmol), 2 (1.0 mmol), Fe/Cg
(5 wt %), N2. bReaction stopped at 10 h. cReaction conducted in
air under the same reaction conditions.
substituent on the aromatic ring (e.g., p-nitro-iodobenzene),
no formation of the product could be seen. To study the
scope of the procedure, the reaction with other N-nucleo-
philes was next studied. Indole, benzamide, morpholine,
imidazole, benzimidazole, thiobenzamide, and aromatic
and aliphatic amines were found to be effective N-nucleo-
philes which underwent reaction to give good to moderate
yields (Table 4).
Next, we studied the reusability of the heterogeneous
Fe/Cg in the C-N cross-coupling reaction of 1 with 2
(Figure 1). After completion of the reaction, the catalyst
was recovered by centrifugation and washed with ethyl
acetate followed by acetone then dried in a hot air oven
at 80 °C.
The recovered catalyst was employed in the next run, and
no substantial loss of activity was observed up to five
cycles.11 It is also observed from the following spectral
studies that there is no change in the nature of the catalyst
even after the fifth cycle.The binding energy values [(C 1s
(283 eV), O 1s (530 eV) and Fe 2p3/2 (710.6 eV), 2p1/2 (724.0
eV)] from the X-ray photoelectron spectroscopy (XPS) of the
native and the catalyst after the fifth cycle confirmed the þ3
oxidation state of iron.14 The absorption at 1575 cm-1 in
IR14 attributed to the formation of anionic acetylacetone
complex12 that was present both in the native and the reused
catalyst. Fe-O stretching band13 at 580 cm-1 in IR is absent
in all of the cases. This observation strongly confirms that
Fe(acac)3 on graphite is intact even after the fifth cycle.
Next, the leaching of iron from the heterogeneous
support was checked. After the reaction, the supernatant
the solvent of choice in terms of higher yield. It is noteworthy
to observe that the choice of KOH as a base with DMSO as
the solvent was crucial for our N-arylation of nucleophiles.
The reaction with KOH was superior to K2CO3, Cs2CO3,
and NaOH, whereas only trace amount of product forma-
tion takes place with NaOtBu and KOtBu (Table 1, entries
8-12). A decrease in catalyst loading from 5 to 3 to 1 wt %
afforded the product in decreased yields (Table 1, entries
13-15). Five wt % of the catalyst was found to be optimal.
When the reaction was stopped at 10 h, the desired C-N
product was obtained in 65% yield (Table 1, entry 16). No
product formation was observed at rt (Table 1, entry 17) as
well as at 120 °C in air (Table 1, entry 18).9 We have also
performed a comparative study of the catalytic activities with
other Fe heterogeneous systems viz. Fe/Cg, Fe2O3, and
Fe3O4 and tested with PhBr and PhI for the formation of
the coupling partners (Table 2). However, it is observed from
these studies that the catalytic activities of other catalysts
were lower than Fe/Cg. Fe/Cg turned out to be the best
catalyst for the coupling reaction.
This catalysis for the C-N cross-coupling reaction was
carried out with a diverse range of aryl halides (iodo, bromo)
against pyrazole under the optimized conditions (Table 3). In
general, aryl iodides were more reactive than aryl bromides,
giving the corresponding N-arylated products in high yields
(up to 95%). The electronic effects were studied with various
aryl halides containing electron-rich and withdrawing
groups (Table 3, entries 1-12). The ortho substitution
hampered the reaction and led to the formation of the
product in lower yields (Table 3, entry 2). With nitro
(10) This catalysis may be due to the presence of iron and oxygen
impurities. Nagai, M.; Yoda, T.; Omi, S.; Kodomari, M. J. Catal. 2001,
201, 105–112.
(11) The catalyst, when taken for reaction directly after centrifugation
and washing without drying in the oven, did not yield any product.
(12) Sohn, J. R.; Lee, S. II. J. Ind. Eng. Chem. 1997, 3, 198–202.
(13) Maity, D.; Kale, S. N.; Ghanekar, R. K.; Xue, J. M.; Ding, J. J.
Magn. Magn. Mater. 2009, 321, 3093–3098.
(9) Dimsyl ion produced from DMSO in the presence of KOH acts as a
base. However, this dimsyl ion is air-sensitive and reacts rapidly in the
presence of water and oxygen. (a) Price, G. G.; Whiting, M. C. Chem. Ind.
1963, 775–776. (b) Ledwith, A.; Mcfarlance, N. Proc. Chem. Soc. 1964, 108–
109. (c) Hiller, L. K. Jr. Anal. Chem. 1964, 42, 30–36.
(14) See Supporting Information.
J. Org. Chem. Vol. 74, No. 19, 2009 7515

Swapna et al.
JOCNote
TABLE 3. Fe/Cg Catalyzed C-N Cross-Coupling of Pyrazole (2) with
TABLE 4. Fe/Cg Catalyzed C-N Cross-Coupling of Aryl Iodides with
Aryl Halidesa
Various Aminesa
a
Reaction conditions: aryl halide (1.0 mmol), 2 (1.0 mmol), Fe/Cg
(5 wt %), N2.
a
was collected by filtration of the catalyst, and the filtrate was
tested for iron by ICP-AES technique. It was found that
0.001% iron leached into the solution. This study clearly
demonstrated that iron was intact to a considerable extent
with the heterogeneous support, and there is no significant
amount of leaching.
Reaction conditions: aryl iodide (1.0 mmol), nucleophile (1.0 mmol),
Fe/Cg (5 wt %), N2, 120 °C, 24 h.
In conclusion, we have developed a robust recyclable
heterogeneous iron catalytic system for the N-arylation of
nucleophiles under ligand-free conditions, contributing to
the progress of sustainable chemistry in the field of iron-
catalyzed reactions.
Experimental Section
Preparation of Graphite-Supported Iron Catalyst. Graphite
(10 g) was charged in a round-bottom flask containing
THF solution (250 mL) of Fe(acac)3 (1 g) and stirred
under nitrogen atmosphere for 24 h. The resultant catalyst
was filtered off and washed two (or three) times with
THF. The residue was dried in a hot air oven for 24 h to afford
the catalyst (i.e., heterogeneous Fe/Cg catalyst). The loading of
iron was determined to be 4.3% as analyzed by ICP-AES
technique.
FIGURE 1. Reusability study of heterogeneous Fe/Cg in the cross-
coupling of 1 and 2.
7516 J. Org. Chem. Vol. 74, No. 19, 2009

Swapna et al.
JOCNote
General Procedure for the Iron-Catalyzed C-N Cross-
Coupling. 1H-Pyrazole (2; 68 mg, 1.0 mmol), Fe/Cg (116 mg,
5 wt %), KOH (2.5 equiv), and iodobenzene (1; 0.1 mL,
1.0 mmol) were charged in a 25 mL round-bottom flask with a
condenser under nitrogen atmosphere, followed by dry DMSO
(1.5 mL). The round-bottom flask was flushed and sealed under
nitrogen atmosphere, and the mixture was heated in an oil bath
at 120 °C and stirred at this temperature for 24 h. After
completion of the reaction as monitored by TLC, the hetero-
geneous mixture was then cooled to room temperature and
treated with water (2 mL). The aqueous layer was separated
and extracted with ethyl acetate (3 ꢀ 5 mL). The combined
organic layers were dried with anhydrous Na2SO4 and concen-
trated under reduced pressure to yield the product, which was
purified by silica gel column chromatography (with ethyl acetate
and hexane as eluent) to get 3a (134 mg, 95%) as a pale yellow
oil: 1H NMR (300 MHz, CDCl3) δ = 7.89-7.88 (m, 1H),
7.69-7.65 (m, 3H), 7.45-7.39 (m, 2H), 7.27-7.20 (m, 1H),
6.42 (t, 1H, J = 2.26 Hz); 13C NMR (75 MHz, CDCl3) δ =
140.9, 140.1, 129.4, 126.8, 126.5, 119.2, 107.5. All of the products
were characterized by 1H and 13C NMR and MS and compared
with the literature values.14
Acknowledgment. We are grateful to UGC, New Delhi,
for the research fellowships to K.S. and A.V.K., and CSIR,
New Delhi, for V.P.R.
Supporting Information Available: Synthetic procedures,
1
characterization data, and copies of H NMR and 13C NMR.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 19, 2009 7517