A green and recyclable ligand-free copper (I) catalysis system for amination of halonitrobenzenes in aqueous ammonia solution

Article abstract of DOI:10.1016/j.mcat.2019.110462

The amination of halonitrobenzenes is an important reaction to produce the corresponding nitroanilines. Direct amination of p-chloronitrobenzene (p-CNB) to p-nitroaniline (p-NAN) with aqueous NH₃ solution was investigated over various transition metal salts in the absence of ligand, inorganic base and organic solvent. It was found that CuI is the most effective catalyst with respect to p-CNB conversion, p-NAN selectivity (≈ 100%) and the post-reaction separation and recycling. A high p-NAN yield of 97% could be obtained at 200 °C in 6.5 h with molar ratios of NH₃/p-CNB and CuI/p-CNB of 21 and 0.1, respectively. A possible reaction mechanism was proposed, in which NH₃ was not only a substrate but also a ligand to coordinate with CuI and formed a water-soluble Cu complex, and then it started the catalytic cycle. The influence of reaction variables such as NH₃ concentration, CuI concentration, temperature and time on the p-CNB conversion and the p-NAN selectivity was examined. At room temperature the desired product of p-NAN is insoluble in water but the Cu complex catalyst is water-soluble and so the aqueous phase including the catalyst and NH₃ can be easily separated and reused for the subsequent reaction runs. The green and sustainable system is effective for the conversion of diverse halonitrobenzenes to nitroanilines.

Full text of DOI:10.1016/j.mcat.2019.110462

MolecularCatalysis475(2019)110462
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Molecular Catalysis
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A green and recyclable ligand-free copper (I) catalysis system for amination
of halonitrobenzenes in aqueous ammonia solution
⁎
⁎
Yan Lia,b, Ruhui Shia,c, Weiwei Lina,c, Haiyang Chenga,c, , Chao Zhanga,c, Masahiko Araia,c,
,
Fengyu Zhaoa,c
a State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
b Jilin Engineering Normal University, Changchun 130052, PR China
c Jilin Province Key Laboratory of Green Chemistry and Process, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
The amination of halonitrobenzenes is an important reaction to produce the corresponding nitroanilines. Direct
amination of p-chloronitrobenzene (p-CNB) to p-nitroaniline (p-NAN) with aqueous NH3 solution was in-
vestigated over various transition metal salts in the absence of ligand, inorganic base and organic solvent. It was
found that CuI is the most effective catalyst with respect to p-CNB conversion, p-NAN selectivity (≈ 100%) and
the post-reaction separation and recycling. A high p-NAN yield of 97% could be obtained at 200 °C in 6.5 h with
molar ratios of NH3/p-CNB and CuI/p-CNB of 21 and 0.1, respectively. A possible reaction mechanism was
proposed, in which NH3 was not only a substrate but also a ligand to coordinate with CuI and formed a water-
soluble Cu complex, and then it started the catalytic cycle. The influence of reaction variables such as NH3
concentration, CuI concentration, temperature and time on the p-CNB conversion and the p-NAN selectivity was
examined. At room temperature the desired product of p-NAN is insoluble in water but the Cu complex catalyst is
water-soluble and so the aqueous phase including the catalyst and NH3 can be easily separated and reused for the
subsequent reaction runs. The green and sustainable system is effective for the conversion of diverse haloni-
trobenzenes to nitroanilines.
Cuprous halide
Amination
Halonitrobenzene
Aqueous ammonia solution
Liquid/liquid biphasic catalysis
1. Introduction
diones [33,34], oxascorbic acid and the salts [35,36] were added in
order to promote their catalytic activity. However, some ligands are
Aromatic primary amines are important building blocks for the
preparation of large variety of organic and inorganic chemicals [1].
Over the last decades, impressive progress has been made in the direct
CeN bond formation; more straightforward approach for the amination
of aryl halides with amine compounds is the copper- [2–12], palladium-
[13,14], and nickel- [15–17] catalyzed coupling reaction. While, by
comparison, the direct CeN bond formation between aryl halides and
ammonia (NH3) is an attracting method to produce aromatic primary
amines, due to the facts that NH3 is one of the most abundant, less
expensive and easy-to-handle nitrogen sources [18,19]. The reaction
can be catalyzed effectively by copper [20–23], palladium [24] and
nickel [15] catalysts, among which efforts have been given to find and
tailor active catalysts using lower-cost copper species. When copper
salts or oxides were used as catalysts, ligands such as organonitrogen
compounds [22,25–31], diones [20], N2,N2’-diisopropyloxalyldihy-
drazide [32] and oxalyldihydrazide were required to be mixed with
expensive and difficult to be separated from organic solvents under
usual conditions. Recently, some achievements have been obtained for
the amination catalyzed by Cu catalysts without ligands; for example,
CuI catalyze the amination of aryl halides (-Br and -I) with aqueous NH3
solution and CuBr, CuI and Cu(acac)2 the amination of heteroaryl
bromides with gaseous NH3 in the presence of K3PO4 in DMF [37,38].
Furthermore, CuI/Fe2O3 could catalyze the amination of aryl iodides
with NH3 in the presence of NaOH in ethanol [39], Cu2O catalyze the
amination of bromonaphthyridines with NH3 in ethylene glycol/glyme
without additional inorganic bases [40], and CuI catalyze the amination
of aryl halides (-Br and -I) with NH3 in polyethylene glycol with or
without additional inorganic bases [23,41]. As reported in the litera-
ture, the amination of aryl halides with NH3 could be catalyzed by Cu
salts or its oxides smoothly in the absence of ligands. For these reac-
tions, however, some additives and large amounts of organic solvents
were used, which are unpractical for its application (product isolation,
⁎ Corresponding authors at: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,
Changchun 130022, PR China.
E-mail addresses: hycyl@ciac.ac.cn (H. Cheng), marai@ciac.ac.cn (M. Arai).
https://doi.org/10.1016/j.mcat.2019.110462
Received 13 May 2019; Received in revised form 3 June 2019; Accepted 4 June 2019
2468-8231/©2019ElsevierB.V.Allrightsreserved.

Y. Li, et al.
MolecularCatalysis475(2019)110462
catalyst recovery). More recently, it was reported that CuO-CeO2 na-
nocomposite could catalyze the amination of aryl halides (-Br and -I)
with NH3 aqueous solution in the presence of Cs2CO3; it is a hetero-
geneous system but the stability of the CuO-CeO2 catalysts is not good
with a serious decrease in activity during recycling [21]. Thus, for the
amination reactions of aryl halides, a challenge still remains open for
the researcher to develop an efficient and clean catalytic system.
In this work, we report a new efficient and green protocol for the
amination of halonitrobenzenes with aqueous NH3 solution catalyzed
by CuI without additional ligands, inorganic bases, and organic solvent.
p-Nitroaniline (p-NAN) is one of the aromatic primary amines and an
important synthetic building block in the synthesis of antioxidants,
pharmaceuticals, gum inhibitors, poultry medicines, and corrosion in-
hibitors [1]. p-NAN can be produced via the partial hydrogenation of p-
dinitrobenzene [42] or the amination of p-halonitrobenzene
[21,23,25–28,35–37,43–45]. The partial hydrogenation of p-dini-
trobenzene to p-NAN is difficult to control because p-NAN is easily
further hydrogenated to p-phenylenediamine at the later stage of re-
action [42]. Relatively, the amination of p-halonitrobenzene to p-NAN
is easy to operate. Compared with the amination of p-bromo- and p-
iodo-nitrobenzene with NH3, the amination of p-CNB is much more
difficult. It is reported that p-bromonitrobenzene is aminated with NH3
to p-NAN in H2O/NMP over Cu2O at 80 °C, with a p-NAN yield of 86%
in 15 h, a lower p-NAN yield of 79% was obtained at 110 °C with mi-
crowave irradiation for 15 h in the amination of p-CNB [44]. Herein, the
present authors have investigated the effectiveness (activity, selectivity,
recyclability) of transition metal halides among others for the amina-
tion of p-CNB with NH3 into p-NAN in water in the absence of any
ligand, inorganic base and organic solvent. It should be noted that, with
the most effective catalyst of CuI, a high p-CNB conversion of > 97%
and a high p-NAN selectivity of > 99% were achieved at 200 °C in 6.5 h.
The reaction mixture was examined by UV/Vis spectroscopy and a
possible reaction mechanism was proposed. Furthermore, the product is
solid and insoluble in water at room temperature and, hence, the
aqueous phase including Cu catalyst and NH3 is easily separated and
recycled. A green and recyclable Cu-based catalyst system has been
developed for the synthesis of p-NAN via the amination of p-CNB in
aqueous NH3 solution. The catalyst system can effectively catalyze the
amination of other different functionalized halonitrobenzene substrates
as well.
2.2. Catalyst recycling test
The catalyst, CuI, is soluble in aqueous NH3 solution and the sub-
strate (p-CNB) and product (p-NAN) are insoluble solids in the media at
room temperature. So, the liquid phase can be separated from the solid
materials by centrifugation and then reused for next reaction runs.
However, a small volume of aqueous phase (ca. 0.5 mL) was missed by
the separation procedures. So, required amounts of fresh 25% NH3
solution and CuI were added to the separated solution for the loss of
these species to prepare the same aqueous solution (10 mL), as used in
the first run, containing NH3 and CuI in the same concentrations; under
ordinary conditions, 0.5 mL of 25% NH3 aqueous solution and
0.032 mmol of CuI were added. Fresh p-CNB (1 g) was added into the
reactor for the next run.
2.3. Characterization
UV–vis absorption spectra of various liquid reaction mixtures were
recorded on a UV–vis spectrometer (PE Lambda 35) under ambient
conditions. In a typical measurement, a mixture of 6.35 mmol p-CNB,
0.635 mmol CuI and 10 mL aqueous NH3 solution was kept at a tem-
perature of 200 °C for a certain period of time, cooled to room tem-
perature and centrifuged. The liquid phase was separated and diluted to
500 times with water and then subjected to UV–vis measurement.
Electrospray ionization-mass spectrometer (ESI-MS, Acquity UPLC &
Quattro Premier XE) was used to examine possible Cu species in the
reaction mixture. The solid substrate and product dissolved in ethanol
phase and the aqueous ammonia phase were measured respectively.
3. Results and discussion
3.1. Catalyst screening
Transition metal salts were used as catalysts for the amination of p-
CNB with aqueous NH3 solution in the absence of ligand and inorganic
base. The obtained results are listed in Table 1. Among Cu salts ex-
amined (entries 1–9), CuI, CuCl and CuBr2 showed the best catalytic
performance in the conversion of p-CNB (> 40%) and selectivity to p-
NAN (> 98%) (entries 1, 3, 4). Cu(acac)2 was also active but the
Table 1
Amination of p-CNB to p-NAN over various catalysts.
2. Experimental
2.1. Amination reactions
Entry
Catalyst
Conversion of p-CNB (%)
Selectivity to p-NAN (%)a
In a typical experiment, p-CNB (1 g, 6.35 mmol), CuI (0.635 mmol),
commercial 25% aqueous NH3 solution (10 mL, NH3/p-CNB molar ratio
21/1) were loaded into a 50 mL stainless steel reactor and sealed. The
material of the autoclave used is AISI 316 L, for which the composition
is Cr 16–18%, Ni 10–14%, Mo 2–3%, Mn ≤ 2%, Si ≤1%, C ≤ 0.03%,
S ≤ 0.03%, P ≤ 0.045%, and the other part is Fe. After being heated to
200 °C, the reaction was conducted while stirring with a magnetic
stirrer (1200 rpm). The pressure of the vapor phase (NH3 and H2O) was
about 3 MPa at the reaction temperature. After stirring for 1 h, the re-
actor was cooled to room temperature and the reaction mixture was
separated by centrifugation. The solid substrate and product were dis-
solved in ethanol and analyzed by a gas chromatograph (Shimadzu GC-
2010) equipped with a capillary column (Rtx-5 capillary column: 30 m
×0.25 mm ×0.25 μm, carrier: N2) and a flame ionization detector
(FID) and gas chromatograph-mass spectrometer (GC-MS, Agilent 5890,
HP-5). o-Xylene was used as an internal standard for quantitative
analysis. The liquid phase was also analyzed by gas chromatograph and
no p-CNB or p-NAN were detected. The carbon balance was near 99%
and trace amount of other unidentified byproducts were observed.
1
CuI
42.5
37.8
43.0
40.3
25.3
41.2
31.8
25.6
23.4
22.5
43.8
24.6
30.2
18.3
19.7
31.1
17.5
99.6
99.3
99.3
98.7
99.0
82.8
99.4
99.2
99.4
97.8
99.7
93.7
96.2
98.6
99.3
99.0
98.6
2
CuBr
3
CuCl
4
CuBr2
5
CuCl2·2H2O
Cu(acac)2
CuSO4·5H2O
Cu(OAc)2·H2O
Cu(NO3)2·3H2O
MnCl2∙4H2O
FeCl3∙6H2O
FeCl2∙4H2O
CoCl2∙6H2O
NiCl2∙6H2O
ZnCl2
6
7
8
9
10
11
12
13
14
15
16b
17
CuI
–
Reaction conditions: p-CNB 1 g (6.35 mmol), 25% aqueous NH3 solution 10 mL,
NH3/p-CNB molar ratio 21/1, catalyst 0.635 mmol, 200 oC, 1 h.
a
b
Selectivity to p-NAN, others are unidentified by-products.
CuI 0.318 mmol.
2

Y. Li, et al.
MolecularCatalysis475(2019)110462
selectivity was not satisfactory (entry 6). The other Cu salts were se-
lective to the target reaction but the conversion levels were not good
(entries 2, 5, 7–9). The difference in the performance among the Cu
salts is similar as reported in the literature [37,38]. The anions in Cu
salts may affect the nucleophilic coordination of Cu salts to the active
species, which will be discussed later. Moreover, among the other
transition metal salts such as MnCl2∙4H2O, FeCl3∙6H2O, FeCl2∙4H2O,
CoCl2∙6H2O, NiCl2∙6H2O, and ZnCl2 (entries 10–15), FeCl3∙6H2O ex-
hibited the highest conversion of p-CNB (43.8%) and the highest se-
lectivity to p-NAN (99.7%) (entry 11), which were comparable to those
obtained with CuI and CuCl (entries 1, 3). The other metal salts were
less effective for the reaction and the p-CNB conversion values were
lower than 30% (entries 10, 12–15). With decreasing of CuI loading
from 10 to 5 mol.%, the conversion of p-CNB decreased from 42.5% to
31.1%, while the selectivity to p-NAN changed slightly (entries 1, 16).
The conversion of p-CNB with no catalyst was only 17.5% (entry 17),
much lower than that with CuI catalyst, and so CuI had the high cat-
alytic efficiency for the amination of p-CNB to p-NAN. In contrast to
these Cu salts, the other metal chlorides of Mn, Fe, Co, Ni, and Zn
changed from water-soluble salts to the corresponding insoluble metal
oxides during reaction; namely, they are not stable and isolated from
the solid organic product. In addition to its better catalytic performance
(entry 1), CuI and the formed Cu species were soluble in aqueous am-
monia solution during the reaction, easily separable from the organic
solid product of p-NAN, and reusable for the recycling runs. Hence, CuI
was chosen as a catalyst for the subsequent work to examine the effects
of reaction conditions and the reusability of aqueous phase in which Cu
catalyst and NH3 were soluble. Note a conversion of 17.5% was ob-
tained in the absence of catalyst (entry 17), as above-mentioned, and
the same conversion was also observed in a Teflon-lined reactor, in-
dicating no reactor wall effect on the reaction.
Fig. 1. Influence of reaction time on the amination of p-CNB. Reaction condi-
tions: p-CNB 1 g (6.35 mmol), 25% aqueous NH3 10 mL, NH3/p-CNB molar ratio
21/1, CuI 0.635 mmol, 200 °C.
3.2. Influence of reaction conditions
Fig. 2. Plot of ln[1/(1-xt)] against reaction time for the data in Fig. 1. xt is
conversion at a reaction time t. The four data can be correlated by a straight line
going through the origin, y = 0.5600x – 0.0024 with a correlation coefficient,
R = 0.99996.
Using the most active copper catalyst (CuI), some variables were
studied. Table 2 shows the influence of temperature over conversion
and selectivity values (entries 1–4). Under the conditions used, the
conversion increased from 13.3% at 180 °C to 87.6% at 230 °C and the
high p-NAN selectivity of > 99% remained unchanged at these tem-
peratures. The amount of NH3 was observed to affect the amination of
p-CNB (Table 2). When NH3/p-CNB molar ratio was raised from 10.5 to
26.25 (entries 2, 5–7), the p-CNB conversion increased from 9.2% to
58.1% and the p-NAN selectivity reached to 99.6% at a NH3/p-CNB
molar ratio of 21. The present amination reaction took place in a liquid
- liquid biphasic mixture including aqueous (NH3, CuI) and organic (p-
CNB) phases, in which the catalytic reactions should occur at interfacial
layer, as detailed later. With increasing of bulk NH3 concentration, the
NH3 concentration at the interfacial layer may increase and promote
the rate of amination.
investigated at 200 °C. The results obtained are shown in Figs. 1 and 2.
The p-CNB conversion increased smoothly with time, the p-NAN se-
lectivity was close to 100% at the initial stage of reaction and the high
selectivity remained unchanged at higher conversion levels (Fig. 1).
Fig. 2 shows that the amination of p-CNB follows a pseudo first order
reaction kinetics with respect to the concentration of p-CNB. The phase
behavior of reaction mixture is illustrated in Scheme 1. The CuI catalyst
can be soluble in aqueous NH3 solution but the solid substrate of p-CNB
is insoluble at room temperature. At reaction temperature of 200 °C, p-
CNB melts but it is insoluble in aqueous NH3 solution; so, the reaction
occurs at the aqueous - organic p-CNB two-phase interface. The pressure
of the vapor phase (NH3, H2O) was initially ca. 3 MPa and the pressure
slightly changed during reaction. The desired product of p-NAN is
The influence of reaction time on the amination of p-CNB with
aqueous NH3 solution at a NH3/p-CNB molar ratio of 21/1 was
Table 2
Influence of temperature and NH3/p-CNB molar ratio on the amination of p-CNB to p-NAN.
Entry
T (ºC)
Volume of aqueous
Total volume of
NH3/p-CNB molar
Conv. (%)
Sel. (%)
NH3 solution (mL)
aqueous phase (mL)
ratio
1
2
3
4
5
6
7
180
200
220
230
200
200
200
10
10
10
10
5
10
21
13.3
42.5
75.5
87.6
9.2
100
10
21
99.6
99.7
99.4
98.4
99.0
99.5
10
21
10
21
10
10.5
15.75
26.25
7.5
12.5
10
27.0
58.1
12.5
Reaction conditions: p-CNB 1 g (6.35 mmol), CuI 0.635 mmol, 1 h.
3

Y. Li, et al.
MolecularCatalysis475(2019)110462
Scheme 1. Reaction, separation, and recycling processes for the amination of p-CNB with aqueous NH3 solution catalyzed by CuI. Condition: p-CNB 1 g (6.35 mmol),
25% aqueous NH3 10 mL, NH3/p-CNB molar ratio 21/1, CuI 0.635 mmol. R.T.: room temperature.
Table 3
Comparison of the catalytic performance for the amination of p-CNB among the present catalytic system with other ones.
Catalyst
Solvent
Base/Ligand
NH3/p-CNB molar ratio
T (°C)
Time (h)
Yield (%)
Ref.
Cu2O
CuO
H2O/NMP
–/–
10
110a
120
100
100
120
200
15
24
8
79
46
69
74
< 5
97
[44]
H2O/TBAB
K3PO4/L1
K2CO3/L2
–/L3
13
[33]
CuSO4·5H2O
CuI
H2O/DMSO/glycerol
29.6
21.45
28.6
21
[36]
H2O
H2O
H2O
36
24
6.5
[35]
CuI
–/L4
[27]
CuI
–/–
This work
L1: oxalyldihydrazide and hexane-2,5-dione, L2: L-ascorbic acid sodium salt, L3: ascorbic acid, L4: 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl) piperazine.
a
Microwave irradiation (110 °C, 150 W).
completely soluble in aqueous NH3 solution at 200 °C, but, after reac-
tion and cooling, it becomes insoluble and precipitates as a needle-like
solid. The Cu active species is soluble in aqueous NH3 solution. Thus,
the reaction occurs at the interfacial layer of the aqueous - organic p-
CNB liquid-liquid two phases, the volume of organic phase decreases
with the conversion (the consumption of p-CNB), resulting in the de-
crease of area of the interfacial layer and thus in the rate of amination,
which apparently obeys the first order kinetics (Fig. 2). The present
amination is not a homogeneous reaction and so detailed reaction ki-
netics analysis should be made by considering several variables fea-
turing multiphase reactions.
Fig. 1 shows that the conversion of p-CNB reaches 97.2% in 6.5 h,
the selectivity to p-NAN was > 99.5% at any conversion level, and the
yield of p-NAN reaches 97%. These results are comparable to the best
results in the partial hydrogenation of p-dinitrobenzene [42] and the
amination of p-bromo- and p-iodo-nitrobenzene substrates
[21,23,25–28,35,37,43], but it is much better than the results in the
amination of p-CNB in literature (Table 3) [35,36,44,45]. For example,
in the amination of p-CNB with aqueous NH3 solution, a yield of 79% of
p-NAN was obtained over Cu2O in H2O/NMP at 110 °C in 15 h under
microwave irradiation [44], and a p-NAN yield of 69% was observed
with CuSO4·5H2O catalyst in the presence of L-ascorbic acid sodium salt
and K2CO3 in a mixed solvent of DMSO and glycerol at 100 °C in 8 h
[36],Therefore, the present catalytic system is efficient and green for
the amination of p-CNB, in which water was used as solvent and any
other additives were not required.
Fig. 3. The recycling of CuI in the amination of p-CNB. Reaction conditions: p-
CNB 1 g, 25% aqueous NH3 10 ml, NH3/p-CNB molar ratio 21/1, catalyst
10 mol%, 200 °C, 4 h.
3.3. Catalyst system recycling test
The desired product of p-NAN is completely soluble in aqueous NH3
solution at a reaction temperature but, after reaction and cooling, it
becomes insoluble and precipitates as a needle-like solid (Scheme 1).
The Cu active species is soluble in aqueous NH3 solution. Thus, the
aqueous solution including soluble Cu catalyst and NH3 can be easily
separated from solid p-NAN via simple centrifugation. Since some
4

Y. Li, et al.
MolecularCatalysis475(2019)110462
Fig. 4. UV–vis spectra of various liquid mixtures. Conditions: (a) 0.635 mmol
CuI and 10 mL H2O was mixed at room temperature (RT) for 0.5 h and the
solution was centrifuged. (b) 10 mL NH3 solution (c, d) 6.35 mmol p-CNB or p-
NAN and 10 mL NH3 solution were mixed at RT for 0.5 h, followed by cen-
trifugation. (e) 0.635 mmol CuI and 10 mL NH3 solution was mixed at RT for
0.5 h, (f1) 6.35 mmol, p-CNB, 0.635 mmol CuI and 10 mL NH3 solution were
mixed at RT for 0.5 h and the solution was centrifuged, (f2-5) 6.35 mmol p-CNB,
0.635 mmol CuI and 10 mL NH3 solution was kept at 200 °C for 0.5, 2, 4, 6.5 h,
respectively, and, after cooling to RT, the solution was centrifuged. All these
liquid samples were diluted to 1/500 with H2O before UV/Vis measurements.
Scheme 2. A possible catalytic cycle for Cu-catalyzed amination of p-CNB with
NH3 in water.
volume (ca. 0.5 mL) of the aqueous solution was missed by the se-
paration, certain amounts of aqueous NH3 solution and CuI were added
to the separated aqueous phase to prepare a 10 mL aqueous solution
including the same contents of NH3 and CuI as used in the first run and
this solution was used for next reaction run. The results of so repeated
reactions are given in Fig. 3, showing no obvious changes in the con-
version of p-CNB and in the selectivity to p-NAN for 5 runs. Namely, the
present aqueous catalyst system is recyclable. Moreover, the addition of
25.4 mmol NH4Cl (the quadruple of the amount of p-CNB) into the
system had no effect on the conversion of p-CNB (86.6%) and the se-
lectivity to p-NAN (99.7%), and the conversion of p-CNB and the se-
lectivity to p-NAN did not change on the generation and accumulation
of NH4Cl in the recycling experiment, indicating no significant effect of
the accumulation of NH4Cl on the present amination reaction.
p-CNB into the sample e, the peaks of absorption bands at 225 and
273 nm increased a little for sample f1, suggesting the ligand exchange
of p-CNB with complex 1 to form complex 2. When the sample f1 was
kept at 200 °C for 0.5 h (sample f2), the absorbance band at 225 nm
decreased a little; that at 273 nm decreased and shifted to 269 nm, and
a new absorption band appeared at 392 nm. The decrease of the ab-
sorbance peaks at 225 and 269 nm may be due to the decrease of
amount of p-CNB by the amination reaction. The new absorption band
located at 392 nm may be assignable to the complex 3 and/or 4. With
extending reaction time to 4 h (samples f2 - f4), the intensity of the
three peaks increased, but decreased with the further extending reac-
tion time to 6.5 h (sample f5), The absorption bands at 225, 269, and
392 nm may also be assigned to the complex 3 and/or 4; when the
reaction time was extended to 6.5 h, almost all p-CNB was transformed
to p-NAN, the amount of complex 3 and/or 4 decreased (the intensity of
the absorption bands at 225, 269, and 392 nm decreased). Complexes 3
and 4 were confirmed to exist during the reaction as their derivatives
dissociated a Cl ion were detected from EMI-MS measurement (Fig. 5).
3.4. Possible catalytic mechanisms
On the basis of Cu-catalyzed coupling mechanisms as proposed in
previous studies [46,47], a possible catalytic cycle for the CuI - cata-
lyzed amination of p-CNB with aqueous NH3 solution without ligand,
inorganic base, and organic solvent is proposed in Scheme 2. Initially,
CuI is complexed with NH3·H2O to form a [Cu(NH3)2]OH (complex 1),
in which NH3 can act as a ligand. The neutral [Cu(NH3)2]OH complex
should be the active Cu species rather than the CuI salt according to the
previous results [47,48]. Then, the ligand exchange, oxidative addition,
deprotonation, and reductive elimination occurred and the final pro-
duct of p-NAN was formed. At the end of a catalytic cycle, CuCl is
formed and used for the next catalytic cycle. The deprotonation via H2O
is more kinetically likely to occur than that via HCl and so no strong
inorganic base is needed for the amination reaction [47]. The differ-
ences in the catalytic performance among the Cu salts observed
(Table 1) are similar as reported in the literature [37,38], and the dif-
ferent anions in the Cu salts may affect the nucleophilic coordination of
Cu salts to the active species (Scheme 2).
3.5. Amination of various halonitrobenzenes
The applicability of the most effective catalyst, CuI, and aqueous
NH3 solution was further examined with various halonitrobenzene
substrates. Table 4 summarizes the results of their amination reaction
obtained. Similar to p-CNB (entry 1), excellent conversion and se-
lectivity were observed for o-CNB (entry 2) but the results were not so
good for m-CNB (entry 3), showing the steric hindrance of the sub-
stituent position, and the same phenomenon was also reported in the
literature [35]. The catalyst system was also effective for p-bromo- and
p-iodo-nitrobenzenes, and the activities of both substrates were higher
than that of p-CNB (entries 3, 4). It has been reported that the reactivity
follows the order of iodo- > bromo- > chloro-nitrobenzene in the
amination of halonitrobenzenes [21,36,37,44], which may be due to
the difference in the atomic radius I > Br > Cl and the easier elim-
ination of C-X (X: I, Br, or Cl) with the bigger atomic radius of X. For p-
CNB compounds bearing -NH2, -COOH and -CN groups at o-position to
-Cl, satisfactory results were obtained (entries 6–8). However, the total
conversion and the selectivity to the desired corresponding amine
compounds were low for p-CNB with -CH3 (entry 9) and -OCH3 (entry
10), respectively. The amination reactivity of C-Cl could be increased
by the electron-withdrawing groups but decreased by the electron-
To obtain more information about the present amination reaction,
UV/Vis spectroscopy was used to examine various liquid mixtures
(Fig. 4). CuI was insoluble in H2O and the substrate of p-CNB was in-
soluble in aqueous NH3 solution, so no obvious absorbance peaks were
seen for samples a–c. The product of p-NAN was slightly soluble in
aqueous NH3 (solubility < 0.1%) at room temperature, the absorbance
band was apparent at 381 nm for sample d. When aqueous NH3 solution
was added to CuI, it became momentarily soluble and the solution was
blue and transparent; the absorbance bands appeared at 225 and
273 nm for sample e, indicating NH3 acted as a ligand and complexed
with CuI easily to form complex 1 (Scheme 2). With the introduction of
5

Y. Li, et al.
MolecularCatalysis475(2019)110462
Fig. 5. ESI-MS of the aqueous NH3 phase of the mixture of amination of p-CNB. Reaction conditions: p-CNB 1 g (6.35 mmol), 25% aqueous NH3 solution 10 mL, NH3/
p-CNB molar ratio 21/1, catalyst 0.635 mmol, 200 °C, 2 h.
inorganic base and organic solvent. The most effective catalyst, CuI,
gave a p-CNB conversion of 97.2% and a p-NAN selectivity of 99.6% at
200 °C in 6.5 h under conditions that NH3/p-CNB and CuI/p-CNB molar
ratios were 21 and 0.1, respectively. For the amination of p-CNB, the
yield to p-NAN (97%) with this catalytic system is much better than
those with state-of-the-art catalytic systems (Cu2O-H2O/NMP, yield:
79%; CuI-H2O-ascorbic acid, yield: 74%). In the present reaction, NH3
is not only a substrate but also a ligand to coordinate with CuI and
forms a water-soluble Cu complex that starts the catalytic cycle from p-
CNB to p-NAN. At room temperature the Cu catalyst is soluble in water
but the desired product of p-NAN obtained is insoluble; therefore, the
aqueous phase including Cu catalyst and NH3 can be easily separated
from the solid product and then recyclable for the subsequent reaction
runs. This efficient, green and recyclable catalytic reaction system can
effectively catalyze the amination of other different functionalized ha-
lonitrobenzenes to the corresponding nitroanilines as well, and will
attract much attention of researchers in the fields of industrial catalysis
and chemical engineering.
Table 4
Amination of halonitrobenzenes to corresponding amines over CuI.
Entry
Substrate
Product
Conv. (%)
Sel. (%)
99.6
1
97.2
2
3
53.0
100
86.0
96.9
4
100
100
100
100
100
24.1
100
100
100
96.7
99.6
95.3
92.1
83.8
86.7
67.8
87.2
72.3
5
6
7
8
9
10
11a
12
Acknowledgements
This work was supported by the National Basic Research Program of
China (2016YFA0602900), Youth Innovation Promotion Association
CAS (2016206), and Chinese Academy of Sciences President’s
International Fellowship Initiative (2018VCA0012).
Reaction conditions: Substrate, 6.35 mmol, 25% aqueous NH3 10 mL, NH3/
substrate molar ratio 21/1, CuI 0.635 mmol, 200 oC, 6.5 h. 3 h.
a
Appendix A. Supplementary data
donating groups. It has been reported that the electron-withdrawing
groups such as ketone, cyano, nitro, carboxylic ester, acetamino and
hydroxy increase the amination activity of iodobenzene [25], but the
electron-donating groups of -CH3 and -OCH3 has an opposite, negative
effect in the amination of iodo- and bromo-benzenes [25,35]. For some
reactant, the selectivity to the target amination product was not so high
due to the formation of condensation products (entries 2, 8–10). For the
amination of a dichoronitro-compound of 3,4-dichoronitrobenzene, p-
Cl was first aminated, in which the selectivity to 2-choro-4-nitroaniline
was 87.2%. Then, m-Cl was further aminated or dechlorinated with the
extending reaction time, decreasing the selectivity of 2-choro-4-ni-
troaniline to 72.3% (entries 11, 12). The amination reactivity of 3,4-
dichoronitrobenzene was much higher than that of p-CNB due to the
electro-withdrawing effect of m-Cl group (entries 1, 11). It is noted that
the present catalytic system is also effective for the amination of other
halogenated benzenes such as chlorobenzene, 1-bromo-4-ethylbenzene,
and iodobenzene (Table S1).
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2019.110462.
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