CopperII phthalocyanine as an efficient and reusable catalyst for the N-arylation of nitrogen containing heterocycles

Article abstract of DOI:10.1016/j.tetlet.2017.06.067

Copper phthalocyanine (Cu^IIPc) was found to be an efficient catalyst for the catalyzed N-arylation of N–H heterocycles with aryl iodides and bromides under mild reaction conditions. A variety of hindered and functionalized N–H heterocycles and aryl halides were successfully used as the substrates for the given catalytic reaction and were transformed in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2017.06.067

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Accepted Manuscript
CopperII phthalocyanine as an efficient and reusable catalyst for the N-arylation
of nitrogen containing heterocycles
Kumar Karitkey Yadav, Uma Narang, Soumee Bhattacharya, Shive M.S.
Chauhan
PII:
S0040-4039(17)30805-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.06.067
TETL 49059
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 May 2017
20 June 2017
22 June 2017
Please cite this article as: Yadav, K.K., Narang, U., Bhattacharya, S., Chauhan, S.M.S., CopperII phthalocyanine as
an efficient and reusable catalyst for the N-arylation of nitrogen containing heterocycles, Tetrahedron Letters (2017),
doi: http://dx.doi.org/10.1016/j.tetlet.2017.06.067
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CopperII phthalocyanine as an efficient and reusable
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Kumar Karitkey Yadav, Uma Narang, Soumee Bhattacharya and Shive M.S. Chauhan
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Tetrahedron Letters
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CopperII phthalocyanine as an efficient and reusable catalyst for the N-arylation
of nitrogen containing heterocycles
Kumar Karitkey Yadav,a Uma Narang,a Soumee Bhattacharyaa and Shive M.S. Chauhana*
a Bio-Organic Research Laboratory, Department of Chemistry, University of Delhi, Delhi-110007, India; Email: smschauhan@chemistry.du.ac.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Copper phthalocyanine (CuIIPc) was found to be an efficient catalyst for the catalyzed N-
arylation of N-H heterocycles with aryl iodides and bromides under mild reaction conditions. A
variety of hindered and functionalized N-H heterocycles and aryl halides were successfully used
as the substrates for the given catalytic reaction and were transformed in good to excellent
yields.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Copper phthalocyanine
N-Arylation
Indole
Benzimidazole
N-Arylazoles
are
important
building
blocks
in
commercially available and are difficult to synthesize in lab.
Hence, the development of an efficient, mild and versatile
method for the C-N coupling reaction of N-H heterocycles and
aryl halides for the synthesis of N-aryl heterocycles is an active
ongoing research area and there is scope for further improvement
toward milder reaction conditions and avoid of expensive
ligands.
pharmaceutical,1 agrochemical,2 material sciences3 and in organic
synthesis.4 Nitrogen containing heterocycles are of interest as
antipsychotic,5 antiallergic,6 COX-2 inhibitors,7 herbicidal
agents,8 and melatonin receptor MT1 agonists.9 These
heterocycles are also used as biological intermediates in the
synthesis of many biologically active compounds.10 The copper-
catalyzed Ullmann-Goldberg coupling11 is a traditional method
for the synthesis of N-arylated heterocycles with the reaction of
aromatic halides. However, the harsh reaction conditions such as
the necessity of a stoichiometric amount of copper catalyst,12-14
high reaction temperatures (125-250°C),15 and the low to
moderate yields of the products15 have undoubtedly prevented
these reactions from being employed to their full potential.
Phthalocyanine metal complexes (MPcs) are purely synthetic
molecules and are structurally analogous to porphyrin
complexes.27 Due to the structural similarity with porphyrin
metal complexes, it shows bioinspired chemistry associated with
porphyrin complexes.28 Recently phthalocyanines have been
successfully utilized as catalysts for different synthetic
reactions.29-32 The catalytic properties of metallophthalocyanines
depend on the metal atom and structure of the phthalocyanine
moiety. Different metals are inserted in the core of the
phthalocyanine ring to utilize them in specific reactions.
Recently different Pd based catalytic systems along with
different sterically hindered phosphine ligands have been
developed for the cross coupling of N-H heterocycles and aryl
halides.16 After the discovery of Ullmann type coupling reaction
of copper catalyzed N-arylation of heterocycles in the presence of
ligands, the economic significance of copper led to a renaissance
of interest. The efficient ligands which were utilized along with
copper salts, were from the groups of amino acids,12 diimines,13
diamines, phosphines ligands,14 pyridine functionalized 1,3-
In connection with our ongoing research for the development
of
simple,
economic
and
efficient
methods
for
metallophthalocyanine catalyzed organic reactions,29, 31-32 herein
we report the first example the N-arylation of N-H heterocycles
with aryl halides directly catalyzed by copperII phthalocyanines
without any ligands under mild reaction conditions in DMSO
with satisfactory results. The current catalytic system possess
several advantages over reported procedures as no additional
ligand is used, low reaction temperature, low catalyst loading,
substrate selectivity, simple work up procedure with excellent
yields and reusability of the catalyst.
diketones,17
natural
alkaloids,18
4,7-dimethoxy-1,10-
phenanthroline,19 diazabutadiene,20 benzotriazole,21 etc. In recent
years several other transition metals based catalytic systems such
as Fe,22 Fe/Cu,23 Ni,24 Ru25 and Cd26 in combination with various
ligands has been reported for C-N coupling reactions.
Unsatisfactory product yields, long reaction times, higher
temperature and use of relatively expensive reagents are the
drawbacks associated with these methods. Particularly, some of
the ligands applied in these reported reactions are not
The metallophthalocyanines were synthesized by the
tetramerization of phthalonitriles and metal salts by following the
procedure reported by us.33 Metallophthalocyanine was purified,

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2
Tetrahedron
characterized and used as the catalysts for the N-arylation
reactions of N-H heterocycles and aryl halides in the presence of
base.
Figure 1. Structure of the CopperII phthalocyanine (4).
Table 1. Screening of the catalytic system for the reaction of
indole and 4-methoxyiodobenzene
To optimize the catalytic reaction conditions, indole (1a) and
4-methoxyiodobenzene (2c) was selected as the model substrate.
The catalytic activity of metallophthalocyanines for the N-
arylation of indole (1 mmol) with 4-methoxyiodobenzene (1
mmol) was evaluated in the presence of NaOH at 120°C for 12h
in DMSO and results are presented in table 1. In the absence of
catalyst, the reaction did not proceed and the starting materials
were recovered as such from the reaction (Table 1, entry1).
When CuIIPc (0.01 mmol) was used as catalyst, indole reacted
with 4-methoxyiodobenzene to give the 1-(4-methoxyphenyl)-
1H-indole (3c) as a product. When CuIIPc was replaced with
ZnIIPc, NiIIPc and CoIIPc and used as catalysts for the current
reaction, products were obtained in low yields (Table 1, entry 2-
5). When solvent was changed from DMSO to DMF, ethanol,
toluene and water, product yield was constantly decreased and in
water reactant and catalyst were recovered as such from the
reaction medium. Thus DMSO was observed as the best solvent
for the current reaction. Further the effect of change of base was
screened and NaOEt, K2CO3 and NaOH were used as the base for
the current catalytic reaction; out of which NaOH gave the best
results. The decrease of temperature from 120oC to 100oC did not
affect the yield of the reaction but further decrease to 80oC
lowered the yield of the reaction (Table 1, entry 12-13). On
decreasing the amount of catalyst from 1 mol% to 0.5 mol%,
yield of product was decreased.
Table 2. Reaction of N-H heterocycles with aryl halides
catalyzed by CuIIPc and NaOH in DMSO