Rapid microwave induced palladium catalyzed amination of aryl bromides

Article abstract of DOI:10.1007/s007060200011

The palladium-catalyzed coupling reaction of aryl bromides with various amines under microwave irradiation was studied using PdCl₂ [P(o-tolyl)₃]₂ which gave various aryl amines in good yields. The reactions were carried out under normal atmospheric conditions.

Full text of DOI:10.1007/s007060200011

Monatshefte fuÈr Chemie 133, 329±332 ꢀ2002)
Rapid Microwave Induced Palladium
Catalyzed Amination of Aryl Bromides
Ali Shari®1;Ã, Rahman Hosseinzadeh2;Ã, and Mojtaba Mirzaei1
1
Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
2
Department of Chemistry, Mazandaran University, Babolsar, Iran
Summary. The palladium-catalyzed coupling reaction of aryl bromides with various amines under
microwave irradiation was studied using PdCl2 [Pꢀo-tolyl)3]2 which gave various aryl amines in good
yields. The reactions were carried out under normal atmospheric conditions.
Keywords. Amination; Palladium; Microwave; Coupling reaction; Arylamines.
Introduction
Owing to the many important applications of aniline derivatives, a considerable
amount of effort has been recently devoted to the development of new and more
general methods for their preparation [1]. Procedures for the synthesis of aniline
derivatives involve nitration, reduction, or substitution. Some of these procedures are
incompatible with many functional groups and often involve protection and de-
protection steps [2]. Palladium- and nickel-catalyzed amination of aromatic halides
and tri¯ates, pioneered by Buchwald [1a, 1c] and Hartwig [1b, 3], provide an
ef®cient, safer, and mild route for the synthesis of substituted anilines. This impor-
tant discovery opens up a new route for the preparation of many interesting organic
molecules that are otherwise dif®cult to prepare [4].
Microwave irradiation is known to accelerate some organic reactions in polar
solvents [5], and microwave assisted palladium-catalyzed reactions have been
recently reported [6]. We here present the microwave assisted facile amination of aryl
bromides with secondary or tertiary amines using PdCl2 [Pꢀo-tolyl)3]2 in toluene
under normal atmosphere.
Results and Discussion
The results of the amination reactions are summarized in Table 1. The data indicate
that coupling between a variety of aryl bromides and secondary or primary amines
readily occurs under microwave irradiation.
The cross-coupling of 2-bromonaphthalene with dibenzylamine was selected for
optimization of the reaction conditions. No reaction occurred in the absence of
Ã
Corresponding author. E-mail: rahman@umcc.ac.ir

330
A. Shari® et al.
Table 1. Palladium-catalyzed amination of aryl bromides under microwave irradiation
Entry Ar±Br
Catalysta
Product
t=min Yield=%b
1
PdCl2=2PPh3
15
trace
2
3
4
5
1a
1a
1a
1a
PdCl2ꢀPhCN)2
PdꢀPPh3)4
3a
3a
3a
15
15
15
4
trace
25
PdCl2ꢀPPh3)2
45
PdCl2 [Pꢀo-tolyl)3] 3a
86
c
6
1a
7
70
c
c
c
7
8
9
6
7
6
85
50
48
1b
1b
c
10
11
1b
6
5
32
c
83
ꢀcontinued )

Amination of Aryl Bromides
331
Table 1 ꢀcontinued )
Entry Ar±Br
Catalysta
Product
t=min Yield=%b
c
12
6
6
51
42
c
13
1d
a
Condition: 1 equiv. arylbromide, 1.5 equiv. amine, 1.5 equiv. sodium tert-butoxide, 0.02 equiv. Pd
catalyst. PdCl2=2PPh3 and PdCl2ꢀPhCN)2 also did not serve as an effective
palladium source for the above reaction ꢀTable 1, entries 1±2). However, a 45% yield
of amination product was obtained when the reaction was performed in the presence
of PdꢀPPh3)4 ꢀentry 4). With PdCl2 [Pꢀo-tolyl)3]2 the yield was improved to 86%
ꢀentry 5). We also examined the same amination reaction with other aryl bromides.
Bromobenzene ꢀ1b, entry 7) or 4-methylbromobenzene ꢀ1c, entry 11) gave very
good yields. However, when 4-methoxybromobenzene ꢀ1d) was treated with di-
benzylamine under the same conditions, aryl amine 3h was obtained with a lower
yield ꢀentry 12). The results indicate that an electron donating group on the aromatic
ring leads to moderate yields ꢀca. 40±50%). Table 1 also shows the cross-coupling
results obtained with bromobenzene and a diverse selection of amines ꢀentries 7±
10). The coupling of diethylamine with aryl bromides gives low yields of the cor-
responding aniline derivatives, obviously due to the volatility of the amine ꢀentry 10).
In summary, a reliable, rapid, and practical procedure for the synthesis of
arylamines via a palladium-catalyzed coupling reaction under microwave irradiation
was developed. A particularly noteworthy feature of this method is the dramatically
shortened reaction time ꢀfrom hours to a few minutes) without the need to employ
inert conditions.
Experimental
All reactions were carried out in a domestic microwave oven ꢀMoulinex Microchef, 900 W) at
2450 MHz. All reported yields refer to isolated products.
General procedure for the palladium catalyzed amination of aryl bromides
under microwave irradiation
A mixture of aryl bromide ꢀ1 mmol), amine ꢀ1.5 mmol), sodium tert-butoxide ꢀ1.5 mmol), and
palladium catalyst ꢀ0.02 mmol) in toluene ꢀ3 cm3) in a 25 cm3 beaker was irradiated in a microwave
oven for 4±15 min. After cooling to room temperature, the reaction mixture was washed with water,
dried over sodium sulfate, and the solvent was evaporated using a rotavapor. The residue was puri®ed

332
A. Shari® et al.: Amination of Aryl Bromides
with a short silica gel column ꢀeluent: light petroleum ether:ethyl acetate ˆ 20:1). The structures of
the products were ascertained by comparison of their physical and spectroscopic data with those
given in the literature.
Acknowledgements
We thank the Chemistry and Chemical Engineering Research Center of Iran and the University of
Mazandaran for ®nancial support.
References
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Received September 3, 2001. Accepted October 10, 2001