Cadmium(II)-catalyzed C-N cross-coupling of amines with aryl iodides

Article abstract of DOI:10.1002/adsc.200700480

Cadmium diacetate dihydrate [Cd(OAc)₂·2H₂O] in combination with ethylene glycol catalyzes efficiently the C-N cross-coupling of amines with aryl iodides by a benzyne mechanism. Alkyl, aryl and heterocyclic amines are compatible with this system affording the aminated products in high to excellent yield.

Full text of DOI:10.1002/adsc.200700480

COMMUNICATIONS
DOI: 10.1002/adsc.200700480
À
Cadmium(II)-Catalyzed C N Cross-Coupling of Amines with
Aryl Iodides
Laxmidhar Rout,a Prasenjit Saha,a Suribabu Jammi,a
and Tharmalingam Punniyamurthya,*
a
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Fax : (+91)-0361-269-0762; e-mail: tpunni@iitg.ernet.in
Received: September 30, 2007; Published online: February 5, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Cadmium diacetate dihydrate [Cd-
(OAc)2·2H2O] in combination with ethylene glycol
catalyzes efficiently the C N cross-coupling of
amines with aryl iodides by a benzyne mechanism.
Alkyl, aryl and heterocyclic amines are compatible
with this system affording the aminated products in
high to excellent yield.
First, we studied the reaction of aniline with iodo-
benzene as model substrates (Table 1). The reaction
occurred to provide the desired C N cross-coupled
diphenylamine in 92% yield when the substrates were
stirred for 2 h at 1108C in the presence of 0.5 mol%
ACHTREUNG
À
À
Cd(OAc)2·2H2O, 1 mol% ethylene glycol and 1 equiv.
G
KOH in dimethyl sulfoxide (DMSO). CdCl2,
CdCl2·2H2O and CdI2 were also investigated as the
catalysts, but they were less effective in comparison to
Keywords: amination; aryl halides; benzyne mecha-
À
nism; cadmium; C N cross-coupling
Cd(OAc)2·2H2O. Among the solvents studied,
A
DMSO, toluene, dioxane and DMF, the former pro-
vided the best results. The reaction with KOH was su-
perior to that using K2CO3, Cs2CO3, NEt3 and pyri-
dine. Among the aryl halides, iodobenzene was more
The amination of aryl halides represents a powerful reactive compared to bromo- and chlorobenzene.
means for the preparation of numerous compounds in
Next, to study the scope of the procedure, the reac-
biological, pharmaceutical and material sciences.[1] tion of other amines with iodobenzene was studied
The traditional methods available for this purpose, (Table 2, Table 3, and Table 4). 4-Bromo-, 4-chloro-,
however, often require stoichiometric amounts of 2-methyl-, 2-methoxy-, 4-methoxy-, 4-nitro- and 2,4-
metal reagents, which, on scale-up, leads to a problem dimethylaniline underwent the reaction to provide
of waste disposal.[2] To overcome these drawbacks, the corresponding C N cross-coupled products in 70–
À
considerable attention has been recently focused to 98% yield (Table 2). Anilines having electron-donat-
develop catalytic systems for this purpose by cross- ing groups were more reactive in comparison to those
coupling reactions.[3] In 1983 Migita and co-workers with electron-withdrawing groups. Similar result was
first reported the cross-coupling of tributyltin amide observed with alkylamines, benzylamine, furfuryla-
with aryl bromide catalyzed by PdCl2{P(o- mine, n-butylamine, cyclohexylamine, pyrrolidine, pi-
N
C6H4Me)3}2.[4] Since then palladium complexes bear- peridine and morpholine, affording the C N cross-
ing sterically hindered phosphine ligands[5] and copper coupled products in 82–98% yield (Table 3). N-Heter-
complexes having electron-rich ligands such as ocyclic compounds such as pyrrole, indole, imidazole,
amines,[6] ethylene glycol,[7a] N,N-diethylsalicylami- 2-methylimidazole and benzimidazole underwent the
de,[7b] 1,10-phenanthroline,[8] N-oximes,[9] thiophencar- reaction to give the aminated products in 96–98%
boxylates,[10] amino acids[11] and 1,3-dicarbonyl com- yield (Table 4). The imidazole derivatives were less
pound[12] have been studied for the coupling of reactive in comparison to alkyl- and arylamines.
À
À
amines with aryl halides. In this contribution, we
Finally, we studied the C N cross-coupling of pyr-
report that Cd(OAc)2·2H2O in combination with eth- rolidine with the substituted iodobenzenes, 2-me-
G
À
ylene glycol catalyzes efficiently the C N cross-cou- thoxy-, 4-methoxy-, 4-nitro- and 2,4-dimethyliodoben-
pling of amines with aryl iodides in excellent yield. zene (Table 5). The reactions occurred to afford a
The procedure is compatible with alkyl, aryl and N- mixture of regioisomers in high yield. The reactivity
heterocyclic amines and takes place at moderate tem- of an aryl iodide with an electron-withdrawing group
peratures in air.
was greater in comparison to that having an electron-
Adv. Synth. Catal. 2008, 350, 395 – 398
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
395

Laxmidhar Rout et al.
COMMUNICATIONS
Table 1. Reaction of aniline with aryl halides.
Catalyst
X
Solvent
Base
Temp. [oC]
Time [h]
Yield [%][a,b]
CdCl2
CdI2
CdCl2·2H2O
I
I
I
I
I
I
I
I
I
I
I
I
Br
Cl
DMSO
DMSO
DMSO
DMSO
toluene
DMF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
K2CO3
Cs2CO3
NEt3
110
110
110
110
110
110
90
6
6
6
2
12
12
12
12
10
10
8
86
86
90
92
40
15
30
trace
20
50
0
Cd
A
Cd
Cd
Cd
Cd
Cd
C
25
110
110
110
110
110
110
Cd
Cd
Cd
C
pyridine
KOH
KOH
8
9
12
5
85
65
Cd
Cd
U
[a]
Catalyst (0.5 mol%), ethylene glycol (1 mol%), aryl halide (1 mmol), aniline (1.2 mmol), KOH (1 mmol) and solvent
(1 mL) were stirred in air.
Isolated yield.
[b]
Table 2. Reaction of arylamines with iodobenzene.
Table 3. Reaction of alkylamines with iodobenzene.
[a]
Cd(OAc)2·2H2O (0.5 mol%), ethylene glycol (1 mol%),
A
iodobenzene (1 mmol), amine (1.2 mmol) and KOH
(1 mmol) were stirred at 1108C in DMSO (1 mL) in air.
Isolated yield.
[b]
[a]
Cd(OAc)2·2H2O (0.5 mol%), ethylene glycol (1 mol%),
A
iodobenzene (1 mmol), amine (1.2 mmol) and KOH
(1 mmol) were stirred at appropriate temperature in
DMSO (1 mL) under air.
[b]
donating group. These results suggest that reaction
takes place by a benzyne mechanism (Scheme 1). The
Isolated yield.
reaction of aryl iodide with Cd(OAc)2·2H2O can give
an intermediate a which can react with base to pro- with the intermediate b can lead to the C N cross-
vide the benzyne intermediate b. Addition of amine coupled products as a mixture of regioisomers.
A
À
396
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Adv. Synth. Catal. 2008, 350, 395 – 398

À
Cadmium(II)-Catalyzed C N Cross-Coupling of Amines with Aryl Iodides
COMMUNICATIONS
Table 4. Reaction of N-heterocyclic compounds with iodo-
benzene.
Scheme 1.
Experimental Section
General Procedure
To a stirred solution of amine (1.2 mmol), aryl iodide
(1 mmol) and KOH (1 mmol) in DMSO (1 mL), a homoge-
[a]
Cd(OAc)2·2H2O (0.5 mol%), ethylene glycol (1 mol%),
amine (1.2 mmol), iodobenzene (1 mmol) and KOH
N
neous stock solution prepared from Cd(OAc)2·2H2O (0.5
A
mol%) and ethylene glycol (1 mol%) in (DMSO) (50 mL)
was added. The solution was heated at 80–1108C for the ap-
propriate time under air (Table 1–Table 5). The progress of
the reaction was monitored by TLC using ethyl acetate and
hexane as eluent. The reaction mixture was then cooled to
room temperature and treated with ethyl acetate (5 mL)
and water (2 mL). The aqueous layer was separated and ex-
tracted with ethyl acetate (3”5 mL). The combined organic
solution, after successively being washed with brine (3”
5 mL) and water (1”5 mL), was dried (Na2SO4) and passed
through celite. Evaporation of the solvent usually provided
analytically pure aminated products which do not require
further purification. Wherever the reaction was incomplete,
the product was purified on silica gel column chromatogra-
phy using ethyl acetate and hexane as eluent.
(1 mmol) were stirred at 1108C in DMSO (1 mL) under
air.
Isolated yield.
Catalyst (1 mol%) used.
[b]
[c]
Table 5. Reaction of substituted iodobenzenes with pyrroli-
dine.[a]
Acknowledgements
Entry R1
R2
Time [h] A [Yield%][b] B [Yield,%][b]
This work was supported by Department of Science and
Technology, New Delhi and Council of Scientific and Indus-
trial Research, New Delhi.
1
2
3
4
OMe H
12
22
26
77
37
35
42
18
55
H
OMe 8
H
NO2 2.5
Me
Me
15
[a]
Catalyst (0.5 mol%), ethylene glycol (1 mol%), aryl
iodide (1 mmol), pyrrolidine (1.2 mmol) and KOH
(1 mmol) were stirred in DMSO (1 mL) under air.
Isolated yield.
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with aryl iodides by the combined use of Cd-
(OAc)2·2H2O and ethylene glycol has been found to
take place in high yield. The reaction is simple, effi-
cient and functions in air by a benzyne mechanism.
Further optimization of this reaction with other aryl
halides is currently being studied.
Adv. Synth. Catal. 2008, 350, 395 – 398
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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