Copper complex-catalysed C-N coupling reaction of aryl iodides with nitrogen-containing heterocycles

Article abstract of DOI:10.3184/174751914X13897958624063

An efficient method for the copper-catalysed arylation of nitrogen-containing heterocycles is reported using 3-(diphenylphosphino) propanoic acid as a ligand in combination of CuCl. The C-N coupling reactions afford various N-arylated products in good to excellent yields.

Full text of DOI:10.3184/174751914X13897958624063

128 RESEARCH PAPER
FEBRUARY, 128–129
JOURNAL OF CHEMICAL RESEARCH 2014
Copper complex-catalysed C–N coupling reaction of aryl iodides with
nitrogen-containing heterocycles
a
b
S. Mohammad Sajadi * and Mehdi Maham
aDepartment of Petroleum Geoscience, Faculty of Science, Soran University, PO Box 624, Soran, Kurdistan Regional Government, Iraq
bDepartment of Chemistry, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul, Iran
Anefficientmethodforthecopper-catalysedarylationofnitrogen-containingheterocyclesisreportedusing3-(diphenylphosphino)
propanoic acid as a ligand in combination of CuCl. The C–N coupling reactions afford various N-arylated products in good to
excellent yields.
Keywords: copper, arylation, heterocycles, 3-(diphenylphosphino)propanoic acid
The construction of N-arylated nitrogen compounds efficiently
Results and discussion
is currently an active area of research in the synthesis of various
Usually the ligands play an important role for a successful
copper-catalysedC–Ncouplingreaction.Inordertooptimisethe
reaction conditions, we chose the reaction of 4-methoxyphenyl
iodide with imidazole in the presence of various copper
catalysts and ligand 1 as the model reaction. The effects of the
base and solvents were examined. First, several solvents were
screened for the reaction. According to data given in Table 1,
DMSO was the most efficient solvent for this reaction (Table 1,
entry 5). After choosing DMSO as the solvent, we examined
several different Cu source and bases. As shown in Table 1,
among the various Cu sources tested in the presence of 1 as
ligand, CuCl led to a significant conversion. The reaction was
also influenced significantly by the base that was employed.
The best result was obtained in the case of NaOH (Table 1,
entry 5). The best result was obtained with 1 (20.0 mol%), CuCl
1–10
medicinal and natural products.
The classical approaches to the syntheses of compounds
11–15
bearing an arylated nitrogen moiety
are based on the
aromatic nucleophilic substitution reaction (S Ar) by nitrogen
N
nucleophiles of activated aryl halides or alternatively the
16,17
18–20
classical Ullmann coupling at higher temperature.
However, each of these methods suffer from different
drawbacks such as high reaction temperatures (often 150 °C or
as high as 200 °C), tedious work-up, the use of very expensive
palladium catalysts, or the use of stoichiometric amount of Cu
salt. These make scale-up difficult and ecologically unfriendly.
Other drawbacks are the use of toxic and air-sensitive aryl
coupling reagents that can be difficult to access, whilst excess
aryl halide starting materials are required to achieve reasonable
16–20
product yields.
Thus, it is desirable to develop a convenient
(15.0 mol%), 4-methoxyphenyl iodide (1.0 mmol), imidazole
and simple method for the copper-catalysed arylation of
nitrogen-containing heterocycles.
(1.4 mmol), NaOH (2.0 mmol) and DMSO (4 mL) which gave
the product in a good yield (94%). Increasing the amount of
ligand 1 and copper salt gave no substantial improvement in
the yield. Next, using the optimised procedure, a series of
aryl iodides possessing both electron-releasing and electron-
withdrawing groups were employed (Table 2). This newly
Among various methods for the transition copper-catalysed
arylation of nitrogen-containing heterocycles with aryl halides,
amino acids, diamines, Schiff-bases, [1,10]-phenanthroline,
quinoline, amino-arenethiol, and oxime-phosphine oxide have
21–24
been investigated as effective ligands.
In spite of these
methods, there are no reports on the synthesis of N-arylated
nitrogen compounds via arylation of nitrogen-containing
heterocycles using 3-(diphenylphosphino)propanoic acid as an
efficient ligand.
Table 1 Copper-catalysed arylation of imidazole with 4-methoxyphenyl
iodidea
Cu source
mol%
Ligand
/mol %
Base
/mol %
Yield
/%b
Entry
Solvent
/
As part of our ongoing interest in the chemistry of nitrogen-
2
5,26
1
2
3
4
5
6
7
8
9
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
CuCl (15)
Cu(OAc) .H O (15)
20
20
20
20
20
20
20
20
20
20
20
20
10
25
Toluene NaOH
Dioxane NaOH
0
0
0
containing compounds and the synthesis of heterocyclics,
we now report the copper-catalysed arylation of nitrogen-
containing heterocycles with aryl iodides in the presence of
MeOH
DMF
NaOH
NaOH
NaOH
Trace
94
10
20
18
16
75
65
79
78
95
3
-(diphenylphosphino)propanoic acid as a new ligand (1) under
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
thermal conditions (Scheme 1).
Et N
3
K CO3
2
CuCl, Ligand 1, NaOH
ArI + Het-NH
Het-NAr
o
Na CO3
14 h
2
DMF, 120 C,
K3PO4
NaOH
NaOH
NaOH
NaOH
NaOH
10
2
2
O
1
1
CuI (15)
1
2
Cu O (15)
2
P
OH
1
3
CuCl (10)
CuCl (15)
14
1
aGeneral reaction conditions: imidazole (1.4 mmol), 4-methoxyphenyl
iodide (1.0 mmol), Cu source (15 mol%), Ligand 1 (20.0 mol%), base
(
2.0 mmol), DMSO (4 mL), 120 °C, 14 h, pressure tube, N atm.
2
b
Scheme 1
Yields are after work-up.
*
Correspondent. E-mail: phytochem2006@gmail.com; mohammad.s@soranu.com
JCR1302287_FINAL.indd 128
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JOURNAL OF CHEMICAL RESEARCH 2014 129
Table 2 Formation of N-arylated nitrogen compounds via Cu-catalysed
vigorously stirred at 120 °C for 14 h under a dry nitrogen atmosphere.
a
arylation of nitrogen-containing heterocycles
After completion of the reaction (as monitored by TLC), H O was
2
Yield
M.p.
/°C
Lit. m.p.
added and the organic layer was extracted with EtOAc, washed with
Entry Substrate
Het-NH
b
Ref.
/
%
/°C
brine and dried over MgSO . The solution was filtered and the solvent
4
1
2
3
4
5
6
7
8
9
0
C H I
1H-Imidazole
77
Oil
Oil27
was evaporated under reduced pressure. The residue was purified by
column chromatography. The purity of the compounds was checked
6
5
2
8
p-MeOC H I 1H-Imidazole
o-MeC H I 1H-Imidazole
p-MeC H I 1H-Imidazole
p-NH C H I 1H-Imidazole
p-BrC H I
p-CHOC H I 1H-Imidazole
94 122–124 121–122
81
95
75 138–140 138–139
92 118–120 118–1202
93 153–155 153–15530
88 124–129 124–12930
80 198–203 198–20330
6
4
1
2
8
by H NMR and yields are based on aryl iodide. All the products are
Oil
Oil
Oil
Oil
6
4
2
9
known and the spectroscopic data (FT-IR and NMR) and melting
6
4
2
7–31
2
8
points were consistent with those reported in the literature.
2
6
4
7
1H-Imidazole
6
4
We gratefully acknowledge Soran University for support of this
work.
6
4
p-FC H I
1H-Imidazole
6
4
p-NO C H I 1H-Imidazole
2
6
4
Received 15 November 2013; accepted 7 January 2014
Paper 1302287 doi: 10.3184/174751914X13897958624063
Published online: 5 February 2014
1
p-CF C H I 1H-Imidazole
92
84 171–173 170–17331
p-MeC H I 1H-Benzo[d]imidazole 88 Oil
Oil31
71–73
7130
3
6
4
12
p-NO C H I 1H-1,2,4-Triazole
2 6 4
13
6
4
aGeneral reaction conditions: nitrogen-containing heterocycle (1.4 mmol),
aryl iodide (1.0 mmol), Cu source (15 mol%), Ligand 1 (20.0 mol%), NaOH
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