Cu(0)@Al2O3/SiO2 NPs: An efficient reusable catalyst for the cross coupling reactions of aryl chlorides with amines and anilines

Article abstract of DOI:10.1039/c5ra19337k

The C-N cross coupling reaction of aryl chlorides with various alkyl/aryl amines catalyzed by copper nanoparticles impregnated on alumina/silica support (Cu(0)@Al₂O₃/SiO₂) was investigated. The prepared catalyst was characterized for its intrinsic physico-chemical and textural properties using XRD, XPS, HR-TEM, BET surface area, SEM-EDAX, H₂-TPR and ICP-AES techniques. The catalyst exhibits excellent reactivity and efficacy in the cross-coupling of a wide range of alkyl/aryl amines including challenging anilines with aryl chlorides. The catalyst offers significant advantages such as brevity, milder reaction conditions, excellent yields and high functional group tolerance for C-N cross coupling when compared with the other reported methods. Moreover, this atom-economical methodology does not require an additional ligand or co-catalyst/activator. The Cu(0)@Al₂O₃/SiO₂ catalyst was efficiently applied to a gram scale synthesis of 7-chloro-4-(4-(2-nitrophenyl)piperazin-1-yl)quinolone (2k). The robustness of the catalyst was examined by reusing it for five consecutive runs.

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Cu(0)@Al2O3/SiO2 NPs: Efficient Reusable Catalyst for the Cross
Coupling Reactions of Aryl Chlorides with Amines and Anilines
P. Linga Reddy,a R. Arundhathib and Diwan S. Rawata,*
Received 00th January 20xx,
Accepted 00th January 20xx
The C-N cross coupling reaction of aryl chlorides with various alkyl/aryl amines catalyzed by copper nanoparticles
impregnated on alumina/silica support (Cu(0)@Al2O3/SiO2) was investigated. The prepared catalyst was characterized for
its intrinsic physico-chemical and textural properties using XRD, XPS, HR-TEM, BET surface area, SEM-EDAX, H2-TPR and
ICP-AES techniques. The catalyst exhibits excellent reactivity and efficacy in the cross-coupling of a wide range of alkyl/aryl
amines including challenging anilines with aryl chlorides. The catalyst offers significant advantages such as brevity, milder
reaction conditions, excellent yields and high functional group tolerance for C-N cross coupling when compared with the
other reported methods. Moreover, this atom-economical methodology does not require an additional ligand or co-
catalyst/activator. The Cu(0)@Al2O3/SiO2 catalyst was efficiently applied to a gram scale synthesis of 7-chloro-4-(4-(2-
nitrophenyl)piperazin-1-yl)quinolone (2k). The robustness of the catalyst was examined by reusing it for five consecutive
runs.
DOI: 10.1039/x0xx00000x
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Introduction
with the limitations of poor substrate scope, requirement of
stoichiometric amounts of copper and harsh reaction
The metal catalyzed construction of Carbon–Nitrogen bond
has perhaps received more attention than any other covalent
bond formation in synthetic organic chemistry. Nitrogen
containing organic compounds not only possess diverse
biological activities,1-3 but also serve as a building block for
various macromolecules and novel materials.4 Since the
pioneering work of Ullmann and Goldberg at the beginning of
20th century wherein stoichiometric amounts of Cu salts were
used for the cross-coupling of aryl halides and amines, albeit
under harsh conditions, many methodologies have been
developed to improve the synthetic utility of the C-N cross-
coupling reactions.5 Buchwald and Hartwig developed
palladium based catalysis for the coupling of aryl chlorides and
amines.6 This methodology has some inherent advantages
over other transition metal catalyzed C-N bond forming
reactions such as high tolerance of functional groups, coupling
of challenging substrates, mild reaction conditions.7 However,
the use of precious and rare Pd metal along with an additional
ligand, besides the need of an inert atmosphere and
generation of hazardous by-products constraints the wide
usage of palladium in C-N cross-coupling. Other transition
metals (Ru, Rh Ir etc.) that have been explored for the C-N
cross-couplings also suffer from such drawbacks, which in turn,
again put the focus on the inexpensive Cu based catalysts.
However, the Cu-catalyzed Ullmann-type reactions suffer
conditions. The use of copper nano-catalysts can overcome
many such limitations. Copper based nanoparticles have
gained much importance in organic synthesis due to their ease
of preparation, cost-effectiveness and low toxicity while
offering better reactivity leading to various substrate scope,
low catalyst loading, high yield and short reaction time.
Recently copper based nanoparticles8 and Cu metal organic
framework (MOF) catalytic system9 were shown to catalyze
the carbon-heteroatom bond formation using -bromo or -iodo
arenes as starting materials. More recently, efforts to
incorporate metal nanoparticles on heterogeneous support
and their use for successful organic transformations have also
been reported.10 This approach is significant due to the
inherent benefits such as ease of separation/purification of the
products and recyclability of the catalyst. Use of mixed oxides
as a heterogeneous catalyst-support has many advantages like
higher surface area, stronger surface acidity/basicity and
favourable thermal stability compared to respective single
metal oxides.11 Alumina/silica mixed oxides have been
reported as a promoter/catalyst for many organic reactions.12
Amorphous alumina/silica materials are highly suitable acidic
components for the preparation of supported metal
catalysts.13 Towards this end, and in continuation of our efforts
to develop novel catalysts for the important organic
conversions,14 we synthesized copper nanoparticles
impregnated on commercially available alumina/silica
(Al2O3/SiO2, Sasol, Germany) support and successfully applied
it for the C-N cross couplings by employing inexpensive and
more challenging aryl chlorides instead of aryl bromides and
iodides with aliphatic, aromatic and N-heterocyclic amines.
a.Department of Chemistry, University of Delhi, Delhi-110007, India. Tel.: +91-40-
27193510; Fax: +91-40-27160921; e-mail: dsrawat@chemistry.du.ac.in
b.Corporate Research & Development Centre, Bharat Petroleum Corporation
Limited, Greater Noida, Uttar Pradesh-201306.
†Electronic Supplementary Information (ESI) available: 1H and 13C spectra of all
compounds. See DOI: 10.1039/x0xx00000x
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Remarkably, the catalyst prepared in this course has shown
high catalytic activity for the coupling of chlorobenzenes, a
challenging substrate for metal-catalyzed cross couplings,
showing better TON and TOF values in comparison to
previously
reported
copper
based
catalysts.8a,17-19
Furthermore, this new class of eco-friendly metal-catalyst can
be easily recovered and reused in the subsequent runs, even
for the gram scale reactions, making it amenable for industrial
use as well.
Results and discussion
Figure 1. PXRD of Cu(II)@Al2O3/SiO2 [A], CuO@Al2O3/SiO2 [B],
Cu(0)@Al2O3/SiO2 [C, fresh], and Cu(0)@Al2O3/SiO2 [D, 5th run].
Preparation of Cu(0)@Al2O3/SiO2
The copper nanoparticles on alumina/silica (Cu(0)@Al2O3/SiO2)
was impregnated in four steps.
1. 33.35 g of copper nitrate was dissolved in 500 mL of
doubly deionized water and to this solution 100 g of
alumina/silica support (Al2O3/SiO2) was added and
stirred at 60 oC for 12 h to obtain blue slurry of
Cu(II)@Al2O3/SiO2.
2. The copper impregnated support (Cu(II)@Al2O3/SiO2)
was filtered, washed thoroughly with double
deionised water and dried at 110 oC for 12 h to obtain
130 g of Cu(II)@Al2O3/SiO2 as pale blue powder.
3. 100 g of Cu(II)@Al2O3/SiO2 was taken in a crucible
and calcined in the presence of air at a ramping
temperature of 150 oC/1 h and 800 oC/3 h. The
calcined catalyst was then cooled to room
temperature to obtain 85
CuO@Al2O3/SiO2.
g of grey coloured
4. 5 g of CuO@Al2O3/SiO2 was then taken in SS
(stainless steel) reactor and reduced in the presence
of hydrogen flow with optimized following
parameters, temperature 250 oC, hydrogen pressure
10 bar with a flow rate of 1L/h to obtain 4.8 g black
coloured Cu(0)@Al2O3/SiO2.
Figure 2. XPS spectra of CuO@Al2O3/SiO2[A] and
Cu(0)@Al2O3/SiO2[B].
Characterization of Cu(0)@Al2O3/SiO2
The X-ray photoelectron spectroscopic analysis of freshly
prepared CuO@Al2O3/SiO2 and Cu(0)@Al2O3/SiO2 was carried
out to evaluate the oxidation state of copper nanoparticles on
alumina/silica (Cu(0)Al2O3/SiO2). As shown in Figure. 2, The
binding energies of CuO@Al2O3/SiO2 were observed at 934.48
and 954.69 eV corresponding to Cu2p3/2 and Cu2p1/2 with
satellite peaks at 942.98 and 962.63 eV which confirmed the
Cu 2p core level in +2 oxidation state. In the case of
Cu(0)@Al2O3/SiO2, the binding energies were observed at
932.48, 952.11 eV which corresponds to Cu 2p1/2, Cu 2p3/2 and
confirms the copper in metallic phase, disappearance of
satellite peaks at corresponding positions also strongly
confirms the reduction of Cu(II) to Cu(0) state.15,16
The
copper
loading
on
alumina/silica
support
(Cu(0)@Al2O3/SiO2) was found to be 2.06 wt% by SEM-EDAX
elemental analysis (ESI, Figure S4), while Al and Si were found
to be 53.78 and 0.55 wt% respectively. Figure 1 shows the
powder XRD spectrum of Cu(II)Al2O3/SiO2 [A], CuO@Al2O3/SiO2
[B], Cu(0)@Al2O3/SiO2 [C, Fresh] and Cu(0)@Al2O3/SiO2 [D,
reused]. The XRD pattern of Cu(0) nanoparticles (Figure 1)
contains peaks that are not clearly distinguishable. This could
be due to low loading and well dispersion of copper
nanoparticles.15a Further, the copper metal percentage and the
oxidation states were confirmed by SEM- EDAX (ESI Figure S4),
ICP-AES and XPS analysis.
The HR-TEM Images of Cu(0)@Al2O3/SiO2 catalyst with a Cu
loading of 2.06 wt% are shown in Figure 3. The majority of NPs
2 | J. Name., 2012, 00, 1-3
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are spherical in shape with size in range of 4 to 6 nm and well in the yield (up to 96%, table 1, entry 14). As evident from
dispersed in the mixed oxide support. The selected area Table 1, best results were obtained by using Cu(0)@Al2O3/SiO2
electron diffraction (SAED) pattern obtained from the Copper catalyst with K2CO3 as a base and DMF as solvent. Additionally,
nanoparticles depicts the characteristic Scherrer ring patterns the catalyst loading was halved (entry 15), but it was found
of the face centered cubic (fcc) Copper (figure 3D).
that 5 mol% catalyst will suffice for an efficient reaction.
Table 1. Optimization study for N-arylation of imidazole with
p-chloroacetophenone.[a]
Entry
Catalysts (mmol)
Solvents Bases Time Yield
[h]
8
8
8
8
8
8
8
8
8
8
8
4
4
3
4
[%]b
37
36
24
50
42
57
70
80
45
67
52
60
90
96
75
1
2
CuO NPs (5)
CuO/Al2O3 (5)
CuO/MgO (5)
Cu2O (5)
DMF
DMF
DMF
DMF
DMF
DMF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
3
4
5
Cu-Al HT (5)
CuO/SiO2
6
7
CuO@Al2O3/SiO2 (5) DMSO
CuO@Al2O3/SiO2 (5) DMF
8
9
CuO@Al2O3/SiO2 (5)
CuO@Al2O3/SiO2 (5)
CuO@Al2O3/SiO2 (5)
Dioxane K2CO3
Figure
3. Low to high magnified HR-TEM images of
Cu(0)@Al2O3/SiO2[A, B and C] with SAED pattern[D].
10
11
12
13
14
15
NMP
K2CO3
K2CO3
K3PO4
K2CO3
K2CO3
K2CO3
Xylene
The temperature programmed reduction (H2-TPR) analysis was
performed for Cu(0)@Al2O3/SiO2 (fresh) and reused
Cu(0)@Al2O3/SiO2 (recovered after 5th run) catalysts to confirm
the zero oxidation state of copper. The results revealed that no
oxidation of copper nanoparticles (Cu(0)@Al2O3/SiO2) was
observed even after five successive runs, whereas
Cu(II)@Al2O3/SiO2 and CuO@Al2O3/SiO2 showed reduction of
Cu(II) to Cu(0) (ESI, Figure S2). Further the surface area of
Alumina/Silica (Al2O3/SiO2) and Cu(0)Al2O3/SiO2 were
determined by BET analysis. The increase in surface area of
Al2O3/SiO2 to Cu(0)@Al2O3/SiO2 was found to be 220 and 240
m2/g.
Cu(0)@Al2O3/SiO2(5) NMP
Cu(0)@Al2O3/SiO2 5) DMSO
Cu(0)@Al2O3/SiO2(5) DMF
Cu(0)@Al2O3/SiO2
(2.5)
DMF
[a]Reaction conditions: p-chloroacetophenone (1.0 mmol), imidazole
(1.1mmol), catalyst (0.05 mmol), K2CO3 (1.5 mmol) and DMF (2 mL)
were stirred under N2 at 150 oC for appropriate time. [b]Isolated
yield
A variety of substituted halo benzenes were coupled with
imidazole, benzimidazole and triazoles in the presence of
Cu(0)@Al2O3/SiO2 catalyst leading to corresponding N-arylated
As shown in table 1, for the C-N cross coupling between p-
chloroacetophenone and imidazole, various catalysts were
screened to find an effective catalytic system for a successful
conversion. Initially copper oxide nanoparticles impregnated
on various supports like Al2O3, SiO2, MgO, Al2O3/SiO2 and
hydrotalcite were prepared and screened for their catalytic
ability. CuO NPs, CuO/Al2O3 and CuO/MgO (Table 1, entry 1-3)
gave low yields. In case of Cu2O and Cu-Al/HT and CuO/SiO2
(Table 1, entry 4-6) the yields were moderate but increase in
yields up to 80% was observed with CuO on Al2O3/SiO2 (Table
1, entry 8). Recently, Cu(0) NPs have been reported for
successful C-C cross-coupling reactions.16 So, in order to check
the veracity of Cu(0) in the present C-N cross-coupling
reaction, Cu(0) NPs impregnated on Al2O3/SiO2 were prepared.
Amusingly, screening of Cu(0)@Al2O3/SiO2 gave sharp increase
products in good to excellent yields (Table 2, entries 1a
expected, electron-withdrawing groups containing
chloroarenes such as –COCH3, -CN and –NO2 gave excellent
yields in shorter reaction times (Table 2, entries 1a 1f) in
-1s). As
-
comparison to halobenzenes having electron-donating groups
(Table 2, 1g-1h and 1j-1k). Also, it was noticed that electron
withdrawing groups such as –NO2 or –CN present at ortho-
position to the halide (leaving group) increased the yield of
corresponding N-arylated products compared to the meta- and
para- substituents (Table 2, entries 1a-1e). Coupling of
chlorobenzenes with benzimidazole and triazole was also
performed and gave good results but 1H-benzimidazole was
relatively difficult to react with, when compared to imidazole
(Table 2, entries 1a and 1r). The expediency of this method
was also checked with electron-deficient heteroaryl chlorides
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(Table 2, entries 1m-1o). To our delight, the cross-coupling of substituted groups decreases (Table 3, entries 2a-2j).
reaction with electron-deficient heteroaryl chlorides such as Presence of the electron-withdrawing groups at ortho-position
pyridine and quinoline has also shown excellent to good yields of the aryl chlorides gave higher yields with shorter reaction-
times compared to the corresponding para-substituted aryl
chlorides (Table 3, entries 2b 2c and 2e 2f). It was also
(87-99%)
-
-
observed that the formyl substituent was oxidized to a
carboxylic group during the reaction (Table 3, entry 2d). which
offers a method for the preparation of N-substituted amino-
benzoic acids in a single step. The coupling of different
chloroarenes with cycloalkylamines (cyclopentylamine and
cyloheptylamine) and secondary cyclic amines (morpholine
and N-substituted piperazines) was performed and reactions
with the latter occurred at a relatively lower reaction time
compared to reported methods and the results are
Table
2
.
Cu(0)@Al2O3/SiO2 catalyzed N-arylation of
heterocyclic amines with aryl chlorides[a]
summarized in Table 3 (Table 3, entries 2e-2m).
Table
3: Cu(0)@Al2O3/SiO2 catalysed amination of aryl
chlorides with primary and secondary amines[a]
Cu(0)@Al2O3/SiO2
( 0.05 mmol)
Cl
NR1R2
+ HNR1R2
R
R
K2CO3, DMF, N2, 150 o
C
H
N
H
N
H
N
7
7
7
NC
O2N
CN
2b, (3h, 95%)
2c, (2h, 97%)
2a, (3h, 98%)
H
H
N
H
N
N
7
CHO
O2N
2e, (3h, 98%)
NO2
2d,* (3h, 96%)
2f, (2h, 98%)
O
O
H
N
N
N
O2N
NC
CN
2g, (3h, 97%)
2h, (3h, 92%)
Cl
2i, (3h, 94%)
O
O2N
N
N
N
N
MeO
Cl
2j, (4h, 92%)
2k, (6h, 90%b)
N
NO2
N
NH
N
N
N
NO2
Cl
N
2l, (8h, 82%)
2m, (6h, 92%)
[a]Reaction conditions: halo benzene (1 mmol), amine (1.1 mmol),
Cu(0)@Al2O3/SiO2 (0.05 mmol), K2CO3 (1.5 mmol), DMF (2 mL) were
stirred under N2 at 150 oC for appropriate time, [b]scaled up by gram
scale and isolated yield, *carbonyl group gets oxidised to carboxylic
acid.
[a]Reaction conditions: halo benzene (1 mmol), amine (1.1 mmol),
Cu(0)@Al2O3/SiO2 (0.05 mmol), K2CO3 (1.5 mmol) and DMF (2 mL)
were stirred under N2 at 150 oC for appropriate time; [b] Yield after fifth
cycle; [c] Scaled up by factor 10 and isolated yield.
Further, in view of biological importance of anilines as
intermediates for the synthesis of various active drug
ingredients, the present methodology was explored for the
synthesis of antimalarial aminoquinoline intermediates (Table
In order to study the versatility of the prepared catalyst,
various aryl chlorides were successfully coupled with a variety
of aliphatic primary and secondary amines under the
optimized set of conditions. As observed before, the reactivity
of aryl chlorides decreases as the electron-withdrawing nature
3, entries 2k
-2m). The gram scale reaction of 7-chloro-4-
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(piperazin-1-yl)quinoline (1 g, 2.7 mmol) with 1-chloro-2-
nitrobenzene (0.45 g 2.9 mmol) offered desired 7-chloro-4-(4-
quinoline analogues (1d and 2k), proves the superiority of
Cu(0)@Al2O3/SiO2 over other copper based heterogeneous
systems for C-N cross couplings.
(2-nitrophenyl)piperazin-1-yl)quinolone
(Scheme 1).
(2k) in 90% yield
Table
5. Comparison of Cu(0)@Al2O3/SiO2 with reported
catalysts for the synthesis of 1b
S.no Catalyst
Time Yield
TON TOF
[h-1]
Ref.
[h]
[%]
100
86
1
2
3
4
5
CuFAP
3
13.6 4.56 17
Nano-CuO
4
8.6
9.2
8.1
2.15 18
0.46 19
0.47 8(a)
CuI, Indion-770
CuNPs/Mag-Si
Cu(0)@Al2O3/SiO2
20
18
2
92
Scheme
1
.
Gram
scale
synthesis
of
7-chloro-4-(4-(2-
87
nitrophenyl)piperazin-1-yl)quinoline (2k).
99
19.8 9.9
Pre-
sent
Next, we extended the scope of the catalyst by coupling
different substituted anilines with 1-chloro-2-nitrobenzene.
The electron-rich p-phenylenediamine gave excellent yield
(98%, Table 4, entry 3f). While the reaction with anilines
containing electron-donating substituents (-methoxy, -methyl
and -isopropyl) was satisfactory with 87-94% yields (Table 4,
Recyclability study of Cu(0)@Al2O3/SiO2
To check the robustness and re-usability of the catalyst after
completion of the reaction, catalyst was separated by
centrifugation and washed several times with ethyl acetate to
remove organic impurities and re-used it for subsequent runs.
Further, we examined the heterogeneity of catalyst by hot
filtration method. The reaction was stopped and filtered at
50% conversion of starting materials and allowed to stir for
further reaction time, no change in progress of the reaction
indicating active catalyst was not leaching from the support.
ICP-AES analysis of re-used catalyst also shown no leaching of
Cu(0) from Al2O3/SiO2.
entries 3a-3c), with 3,5-dimethoxyaniline, the yield was lower
which can be attributed to the cumulative effect of the two
methoxy groups present meta- to the aniline-group (Table 4,
entry 3d).
Table 4. Cu(0)@Al2O3/SiO2 catalysed N-arylation of aryl
chlorides with aniline[a]
Table 6. Recyclable yields of 1b up to five successive runs[a]
.
Yields of isolated product (%)
Run 1
99
Run 2
99
Run 3
98
Run 4
96
Run 5
97
Run 6
96
[a]Reaction conditions: o-chloro nitrobenzene (1 mmol), imidazole
(1.1 mmol), Cu(0)@Al2O3/SiO2 (150 mg, 0.05 mmol), K2CO3 (1.5
mmol) and DMF (2 mL) were stirred under N2 at 150 oC for
appropriate time.
[a]
Reaction conditions: halo benzene (1 mmol), aniline (1.1 mmol),
Cu(0)@Al2O3/SiO2 (0.05 mmol), K2CO3 (1.5 mmol) and DMF (2mL) were
stirred under N2 at 150 oC for appropriate time, [b] Isolated yield.
The catalyst prepared during the course of study showed good
catalytic activity for the C-N cross coupling reactions with a
wide range of amines, anilines and heteroaromatic amines.
Compared with other recent copper-based heterogeneous
catalysts, the turnover number (TON) and turnover frequency
(TOF) of the present catalyst exhibited higher values (19.8 and
9.9, Table 5). This, along with the amenability of the present
catalyst towards gram scale synthesis of imidazole and
Figure 3. Recyclability of catalyst for synthesis of 1b up to five
successive runs.
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Experimental section
Anal. Calcd. For C15H17N2O2: 257.1285 (MH)+; Found: 257.1281
(MH)+.
An oven dried 10 mL round bottom flask was charged with Dry
DMF (2 mL), K2CO3 (1.5 mmol) and the catalyst (150 mg, 5
mol% of Cu(0)) and stirred for about 0.5 h under nitrogen, to
this amine (1.1 mmol) and aryl chloride were added (1 mmol)
and stirred further for about 0.5h under nitrogen atmosphere.
The reaction flask is then transferred to a pre heated 150 oC oil
bath and continued stirring for an appropriate reaction time.
After completion of the reaction (progress was monitored by
TLC at different time intervals) the reaction mixture was
cooled to room temperature and the catalyst was recovered
by centrifugation. The solid catalyst is washed several times
with ethyl acetate to make the catalyst free of all the organic
matter, the organic layers were dried over on Na2SO4 and then
subjected to column chromatography (silica gel 100-200 mesh)
using ethyl acetate and hexane as eluents to afford the desired
N-alkylated/arylated product in excellent yields. The
spectroscopic characterization of the product(s) is in
conformation with the literature precedents.
3,5-dimethoxy-N-(2-nitrophenyl)aniline (Table 4, Entry 3d):
1
Brown solid, mp 85-87; H NMR (400 MHz, CDCl3) : δ = 9.41
(brs, 1H, NH), 8.19 (d, J = 8.39 Hz, 1H), 7.42-7.30 (m, 2H), 6.78
(t, J = 7.63 Hz, 1H), 6.43 (d, J = 2.29 Hz, 2H), 6.33 (t, J = 2.29 Hz,
1H), 3.79 (s, 6H); 13C NMR (100 MHz, CDCl3): δ = 161.6, 142.5,
140.4, 135.6, 133.3, 126.5, 117.6, 116.6, 102.1, 97.5, 54.4; IR
(cm-1, Film): 3355, 3018, 2927, 2852, 1600, 1504, 1469, 1270,
1213, 1157, 751; ESI-HRMS (m/z) Anal. Calcd. For C14H15N2O4:
275.1026 (MH)+; Found: 275.1056 (MH)+.
N1-(2-nitrophenyl)benzene-1,4-diamine (Table 4, Entry 3f):
1
Brown solid mp 111-113; H NMR (400 MHz, CDCl3): δ = 9.37
(brs, 1H, NH), 8.21-8.15 (m, 1H), 7.33-7.27 (m, 1H), 7.05 (d, J =
8.39 Hz, 1H), 6.97 (d, J = 8.39 Hz, 1H), 6.73 (d, J = 8.39 Hz, 2H),
6.71-6.65 (m, 1H), 3.74 (brs, 2H, NH2); 13C NMR (100 MHz,
CDCl3): δ = 144.9, 135.6, 132.1, 129.0, 127.3,126.5, 116.3,
115.9, 115.8, 102.3; IR (cm-1, Film): 3358, 3021, 1619, 1507,
1412, 1351, 1260, 1215, 745; ESI-HRMS (m/z) Anal. Calcd. For
C12H12N3O2: 230.0924 (MH)+; Found: 230.0924 (MH)+.
Spectral data of selected compounds
7-chloro-4-(4-(2-nitrophenyl)piperazin-1-yl)quinoline
(2k):
Yellow solid, mp 177-179 oC; 1H NMR (400 MHz, CDCl3): δ =
8.76 (d, J = 5.04 Hz, 1H), 8.07 (d, J = 2.29 Hz, 1H), 7.99 (d, J =
8.70 Hz,1H), 7.82 (dd, J = 8.24 Hz, J = 1.83 Hz, 1H), 7.59-7.53
(m, 1H), 7.45 (dd, J = 8.70 Hz, J = 1.83 Hz, 1H), 7.30-7.27 (m,
1H), 7.18-7.11 (m, 1H), 6.91 (d, J = 5.04 Hz, 1H), 3.42-3.33 (m,
8H); 13C NMR (100 MHz, CDCl3): δ = 156.6, 152.0, 150.1, 145.6,
144.0, 134.9, 133.5, 128.9, 126.3, 125.8, 124.9, 122.7, 121.8,
121.4, 109.3, 52.2, 51.8; IR (cm-1, Film): 2924, 2850, 1595,
1498, 1320, 1237, 1115, 754; ESI-HRMS (m/z) Anal. Calcd. for
C19H18ClN4O2: 369.1113 (MH)+; Found: 369.1119 (MH)+.
Conclusion
We have developed a simple, efficient, environmentally-
benign and cost-effective heterogeneous copper catalytic
system for the efficient C-N cross coupling of different
chlorobenzenes with
a variety of amines, anilines and
heterocyclic amines under ligand-free conditions at relatively
mild conditions. The present work provides an improved
protocol that obviates the need of high stoichiometric
amounts of Cu-catalyst for C-N bond formation reactions.
Moreover, this recyclable heterogeneous catalyst viz.
Cu(0)@Al2O3/SiO2 offers several advantages including
simplicity in handling, easy purification, and high yields in
relatively shorter reaction times. Furthermore the use of
Al2O3/SiO2 as support for impregnation of copper paves a way
for the industrial use of copper in the synthesis of amines with
challenging aryl chlorides, the catalyst was recyclable which
makes this approach efficacious and atom-economical To the
best of our knowledge Al2O3/SiO2 support is used fist time for
the amines synthesis.
7-chloro-N-(2-(4-(2-nitrophenyl)piperazin-1-yl)ethyl)quinolin-
1
4-amine (2m): Yellow solid, mp 103-105; H NMR (400 MHz,
CDCl3) : δ = 8.41 (s, 1H), 8.05 (s, 1H), 7.92 (d, J = 8.70 Hz, 1H),
7.79-7.75 (m, 1H), 7.53-7.47 (m, 1H), 7.38 (d, J = 8.70 Hz, 1H),
7.17 (d, J = 8.24 Hz, 1H), 7.07 (t, J = 7.79 Hz, 1H), 6.43 (d, J =
4.58 Hz, 1H), 3.73 (brs, 1H, NH), 3.51-3.44 (m, 2H), 3.18-3.10
(m, 4H), 2.90 (t, J = 5.50 Hz, 2H), 2.78-2.71(m, 4H); 13C NMR
(100 MHz, DMSO): δ = 151.9, 149.9, 149.0, 134.1, 133.3, 131.5,
128.7, 127.5, 125.6, 124.8, 124.1, 123.9, 117.3, 98.7, 56.5,
54.3, 45.6; IR (cm-1, Film): 3360, 3011, 2923, 2852, 1668, 1607,
1578, 1520, 1484, 1217, 744; ESI-HRMS (m/z) Anal. Calcd. for
C21H23ClN5O2: 412.1535 (MH)+; Found: 412.1549 (MH)+.
Acknowledgements
DSR thanks DU-DST PURSE grant and R & D grant, University of
Delhi for the financial support. PLR and RA thanks UGC and
BPCL for their fellowship and encouragement. Thanks to USIC-
CIF, University of Delhi for analytical data. We also like to
thank Dr. B. Sreedhar, CSIR-IICT for XPS analysis.
N-(4-isopropylphenyl)-2nitroaniline (Table 4, Entry 3c): Thick
oil; 1H NMR (400 MHz, CDCl3) : δ = 9.48 (brs, 1H, NH), 8.19 (dd,
J = 8.70 Hz, J = 1.83 Hz, 1H), 7.37-7.32 (m, 1H), 7.30-7.25 (m,
2H), 7.22-7.16 (m, 3H), 6.77-6.71 (m, 1H), 3.00-2.88 (m, 1H),
1.32-1.24 (d, J = 6.87 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ =
146.6, 143.6, 136.1, 135.6, 132.7,127.6, 126.5, 124.7, 117.0,
115.9, 33.6, 23.9; IR (cm-1, Film): 3355, 3022, 2961, 2964, 2858,
1611, 1574, 1503, 1406, 1348, 1261, 747; ESI-HRMS (m/z)
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