10.1002/cctc.201800609
ChemCatChem
COMMUNICATION
or DMA respectively. The advantages of the present protocol are
moderate to excellent yields, no requirement of inert
atmosphere, easy workup, and purification procedures. In
addition, this study presents the conditions of temperature and
use of suitable substrates to prevent N-formylation and N-
acylation impurities in the C-N cross coupling of amines with aryl
halides when DMF and DMA are used as solvents.
Table 3. Screening of Aromatic, Aliphatic, and Heterocyclic Amines for C-N
Cross Coupling Reactiona
CuI (5 mol%)
ligand (L1) (10 mol%)
K2CO3 (3 equiv)
R1
R1
N
R2
I
H
O
H
N
N
R2
R1
R2
DMF, 120 °C, 24 h
1
6
7
2
R1 = H, aliphatic, aromatic
R2 = H, aliphatic, aromatic, heterocyclic
desired product N-formyl product
Experimental Section
sr.
no.
amine
(1)
desired product
N-formyl product
(2) yieldb (%)
(7) yieldb (%)
See supporting information.
H
H
N
NH2
N
H
1
2
3
O
O
1a
1b
7a, 71%
2a, 15%
Acknowledgements
H
N
H
N
NH2
H
Authors thank Baburaoji Gholap Research Center for its support.
7b, 75%
2b, 17%
H
N
H
N
NH2
H
Keywords: 1,2,4-triazole • C-N cross coupling reaction • Cu-(II)
catalyzed • N-acylation • N-formylation
O
1d
7c, 76%
2d, 15%
H
N
H
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H
N
NH2
4
5
1v
O
2v, 72%
7d, 0%
O
[2]
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NH2
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H
H
1w
7e, 0%
2w, 76%
H
O
NH
N
N
[3]
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6
7f, 0%
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H
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7
8
1z
7g, 0%
2z, 70%
H
O
[5]
O
O
N
O
N
1aa
7h, 0%
2aa, 75%
H
N
H
N
NH2
9c
O
3a, 10%d
7a, 68%
1a
aAll reactions were carried out on approximately a 0.5 g scale using amine (1)
(1 equiv), iodobenzene (6) (1.5 equiv), catalyst CuI (5 mol%), ligand (L1) (10
mol%), K2CO3 (3 equiv), DMF (2.5 mL, 5 volume), temperature 120 °C for 24
h. All reagent and substrate addition was done at room temperature (25 °C).
bIsolated yields. cDMA (2.5 mL, 5 volume). dN-acyl product (3a).
[6]
This study reflects that, the aliphatic and heterocyclic
amines are more reactive towards N-formyl products than
aromatic amines and inhibits the coupling reaction. This may be
attributed because of the nucleophilicity of aliphatic and
heterocyclic amines which is known to be more than the
anilines, that results in nucleophilic attack of amines on activated
DMF or DMA for the formation of a tetrahedral intermediate-A
(scheme 6) and act as base as well as N-formyl carrier. These
facts were also reflected during optimization of N-formylation
and N-acylation (Table 1, entries 5-7) and thus supports the
observations.
Hence, it can be concluded that, at higher temperature (i.e.
above 100 °C) DMF and DMA is not a suitable solvent for C-N
cross coupling of amines (typically for aliphatic and heterocyclic)
as undesired N-formyl and N-acyl products formation takes
place and decrease the yield of C-N cross coupled product or
inhibit the coupling reaction.
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In summary, a highly efficient, simple, and novel protocol
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using Cu-(II) catalyst [CuCl2.2H2O]
and ligand 8-
hydroxyquinoline or [Cu(quin)2] has been developed with 1,2,4-
triazole as homogeneous medium for N-formylation and N-
acylation of aliphatic, aromatic, and heterocyclic amines in DMF
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