Tetrahedron Letters
Copper powder-catalyzed N-arylation of imidazoles in water using
2-(hydrazinecarbonyl)pyridine N-oxides as the new ligands
⇑
Feng-Tian Wu, Nan-Nan Yan, Ping Liu, Jian-Wei Xie , Yan Liu, Bin Dai
School of Chemistry and Chemical Engineering/The Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, North 4th Road,
Shihezi 832003, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 January 2014
Revised 2 April 2014
Accepted 10 April 2014
Available online 23 April 2014
2-(2-Hydrazinecarbonyl)pyridine N-oxides, which were derived from pyrrole-2-carbohydrazides and
pyridine N-oxides, were synthesized and utilized as the ligands for copper powder-catalyzed N-arylation
of imidazoles with aryl halides in water. Imidazoles could be arylated smoothly with various aryl halides
to provide the title products in preferable yields without the need of an inert atmosphere.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Copper powder
N,O-Ligand
N-arylation
Cross-coupling
Water-chemistry
N-Arylimidazoles are common and useful motifs in medicinal,
biological, and material sciences.1 The traditional method for the
preparation of these moieties is via SNAr substitution of imidazoles
with activated aryl halides or the classic Ullmann-type coupling
reaction.2 However, the drawbacks of these methods are the use
of stoichiometric amounts of copper reagents and high reaction
temperatures. Fortunately, some N- and O-based ligands were
found to facilitate the copper-catalyzed C–N coupling reactions
by Buchwald et al.3 and Taillefer et al.,4 respectively. Thereafter,
a series of practical ligands, including monodentate and bidentate
ones, have been developed to expedite the Ullmann-type C–N
formation.5
we reasonably assume that 2-(hydrazinecarbonyl)-pyridine
N-oxides, which replaced pyrrole ring with pyridine N-oxide, might
be a novel series of ligand and should possess higher efficiency for
Cu-based C–N coupling reactions due to the more stable structure
and excellent solubility in water (Scheme 1). Herein, we wish to
report 2-(hydrazinecarbonyl)pyridine N-oxide and its analogue as
efficient N,O-bidentate ligands for the formation of copper-
catalyzed C–N bonds in water.
In our initial experiment, 4-iodoanisole and imidazole were
chosen as the model substrates to optimize reaction conditions
including copper sources, ligands, bases, reaction temperature,
and time, and the results are shown in Table 1.
Recently, water has emerged as a highly desirable solvent for
organic transformations in terms of cost, safety, availability, and
environmental concerns,6 of which the copper-based amination of
aryl halides in water have also attracted much attention.7 Among
them, Wan and co-workers reported a typical copper-catalyzed
C–N coupling in water with utilization of pyrrole-2-carbohydra-
zides as ligands.7c However, probably because of the poor water-
soluble and unstable nature of the ligand, the relatively high molar
ratio (5:1) of ligand and copper was needed. At the same time, Zhou
and co-workers7a reported pyridine N-oxide could efficiently pro-
mote Cu-catalyzed N-arylation of imidazoles in water, and superior
solubility of the ligand maybe played an essential role. Therefore,
L
25 mol%
5 mol% CuI
NHR2R3
Het-NH
Het-NH
NHNHPh
O L
X
NR2R3
N-Het
N-Het
N
H
R1
R
TBAB, KOH, MW
H2O,130 °C, 5 min
R1
Ref. 7c
20 mol% L
10 mol% CuSO4
X
N
O
N
O
Cs2CO3, H2O
120 °C, 24 h
Y
R
Y
Y
Ref. 7a
L
[Cu], L
X
NHNHR
N
O
R
R
base, TBAB, H2O
O
This work
L
⇑
Corresponding author. Tel.: +86 09932057213; fax: +86 13899508309.
Scheme 1. Previous works and our work.
0040-4039/Ó 2013 Elsevier Ltd. All rights reserved.