One-pot synthesis of N,N-dimethylanilines from nitroarenes with skeletal Cu as chemoselective catalyst

Article abstract of DOI:10.1016/j.catcom.2013.07.023

A range of N,N-dimethylanilines were synthesized with excellent yields in one-pot by the hydrogenation and alkylation of nitroarenes with H₂ and HCHO over quenched skeletal Cu catalyst, which provides a facile, economical, and environmentally benign alternative methodology for C-N bonds formation.

Full text of DOI:10.1016/j.catcom.2013.07.023

Catalysis Communications 41 (2013) 115–118
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
One-pot synthesis of N,N-dimethylanilines from nitroarenes with
skeletal Cu as chemoselective catalyst
⁎
Zeming Rong , Wenjun Zhang, Peng Zhang, Zhuohua Sun, Jinkun lv, Wenqiang Du, Yue Wang
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 May 2013
Received in revised form 9 July 2013
Accepted 10 July 2013
Available online 19 July 2013
A range of N,N-dimethylanilines were synthesized with excellent yields in one-pot by the hydrogenation and alkyl-
ation of nitroarenes with H2 and HCHO over quenched skeletal Cu catalyst, which provides a facile, economical, and
environmentally benign alternative methodology for C-N bonds formation.
© 2013 Elsevier B.V. All rights reserved.
Keywords:
N,N-dimethylanilines
One-pot
Alkylation
Nitroarenes
Skeletal Cu
1. Introduction
In this study, we have developed a simple one-pot synthesis of NNDA
through the hydrogenation of nitroarenes and subsequent dimethylation
N,N-dimethylanilines (NNDA) are valuable compounds in pharma-
ceutical, agrochemicals and fine chemical industries [1–5]. Currently,
NNDA are mostly produced from a two-step process involving the
reduction of nitroarenes into anilines and the subsequent alkylation
(Scheme 1) [6–10]. In contrast, one-pot reactions are of much interest
since they are more favorable process avoiding intermediate separation
and purifications steps, and therefore minimizing energy during reac-
tion [11,12]. However, it remains challenging to perform the reduction
and alkylation simultaneously in the same reaction vessel due to the
distinct optimal reaction conditions for each step such as catalyst
functionality and hydrogen donor source uniformity. So there are few
reports on one-pot synthesis of NNDA during last decades [13].
Recently, several research groups reported the synthesis of N-
alkylated anilines from nitroarenes using alcohols as the alkyl-source
in the presence of (P ~ N)Ru(CO)2Cl2 [14], [Ru(p-cymene)Cl2]2 [15]
and Ag/Al2O3 [16]. However, the secondary amines instead of the tertia-
ry amines were obtained by the N-monoalkylation due to the bulkiness
of alkylating agents. Li utilized methanol acting as an alkylating reagent,
hydrogen source and solvent, simultaneously [17]. N,N-dimethylaniline
was obtained from in-situ hydrogenation of nitrobenzene with
hydrogen generated from methanol over Raney-Ni catalyst followed
by alkylation. However, the major drawbacks were low efficiency
with a large quantity of catalysts (370–440 mol% Raney Ni with respect
to nitrobenzene), harsh reaction conditions and long reaction time [16].
with HCHO as the alkyl source. Skeletal Cu prepared by the quenching
techniques plays dual roles in this hydro-dialkylation process, which
has never been reported to the best of our knowledge.
2. Experimental section
The catalytic hydrogenation reaction was conducted in a stainless-
steel autoclave reactor (70 mL capacity) heated in oil bath. Substrate
(6 mmol), solvent (20 mL) and catalyst (0.5 g) were directly added
into the reactor. The autoclave was purged with N2 and H2 three
times before the reaction started. The reaction process was monitored
by gas chromatography (GC) (Agilent 6890) with a flame ionization
detector (FID) system.
The catalyst's preparation and characterization were detailedly
described in the supporting information.
3. Results and discussion
Similar to the preparation of skeletal Ni catalyst [18], the skeletal Cu
catalyst was obtained by leaching Al with 20 wt.% NaOH solution from
Cu–Al alloy. Fig. 1 shows some representative SEM images of Cu–Al
alloy and the skeletal Cu catalyst. It was clearly found that the alloy pos-
sessed uniform structure (Fig. 1a,b). The rich dislocation array in alloy
provided high active centre for skeletal Cu catalyst (Fig. 1c). The possible
active site for hydrogenation and alkylation was composed by the
terraces, corners (Fig. 1d) and holes (Fig. 1e,f).
To better understand the structure–activity relationship, the skeletal
Cu catalyst was also analyzed by XPS and results were presented in
⁎
Corresponding author. Tel.: +86 411 84986242.
E-mail address: zeming@dlut.edu.cn (Z. Rong).
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.07.023

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Z. Rong et al. / Catalysis Communications 41 (2013) 115–118
One Pot
We initiated the hydrogenation and dimethylation of nitroarenes by
screening 8 different catalysts using p-chloronitrobenzene (p-CNB) as
substrate and 37 wt% HCHO as the alkylating agent under the same re-
action conditions (373 K and 15 bar H2, Table 1). Among the noble
metal catalysts Pd/C, Pt/C, Ru/C and Rh/C, Rh/C provided 87% conversion
to p-chloro-N,N-dimethylaniline (p-CDMA), but the selectivity to p-
CDMA was only 56.6%. Besides, the condensation by-products due to
high activity of noble metal catalysts were also detected by GC analysis.
In addition, skeletal Ni, Fe, Co and Cu were investigated in this model
reaction. Up to 100% p-CNB conversion was achieved when S-Ni, S-Co,
and S-Cu were used. Obviously, S-Cu showed best performance in the
control experiment and the selectivity was up to 99.4% (entry 8).
Employing S-Cu catalyst, effect of temperature, pressure, solvent, the
amounts of formaldehyde and catalyst were investigated (Table S2–6,
see the supporting information). The optimal reaction conditions were
373 K, 13 bar H2, which were much milder comparing with the reported
results [17] and the catalyst's dosage was significantly reduced, simulta-
neously. Furthermore, the relationships of components concentration
versus reaction time were investigated and shown in Fig. 3. The hydroge-
nation and methylation of p-CNB should be practically more complicated,
p-chloroaniline (p-CAN, 2-b in Scheme 2), p-chloro-N-methyleneaniline
(Schiff's base, 2-c), p-chloro-N-methylaniline (imine, 2-d) and 4-
chloride-N,N-bis(methoxymethyl)-benzenamine (2-e) may exist
as the main intermediates in the reaction system.
Based on the above results and parallel experiments (Table S-8), a
mechanism is proposed shown in Scheme 2. Firstly, 2-a was hydroge-
nated to 2-b over S-Cu catalyst (Entry 1) and 2-c was obtained through
next addition-elimination of 2-b and HCHO [13] (Entry 2 and 3). Judged
by the main intermediates, 2-c was probably converted into the
p-CDMA (2-f) through two routes in this reaction system. 2-c was hy-
drogenated into 2-d [15,16], and then converted into 2-f through
Route 1 [17,21]. Alternatively, 2-c was presumably converted into 2-e
and further 2-f with multiple steps of addition and elimination through
Route 2, which have never been reported to the best of our knowledge.
2-e is unstable when concentrating solvent or purification with gel
chromatography. Therefore it could not be separated from the reaction
system and presumably identified by GC-MS and HPLC-MS (see the
supporting information). Comparing with Entry 4 and 5, 2-e disappeared
NO2
NH2
N
3
Reduction
Alkylation
R
R
R
1
2
Scheme 1. The hydro-dimethylation of nitroarenes.
Fig. 2. Detailed description in high-resolution XPS spectra clearly indi-
cates that surface active sites are mainly consisted of metallic Cu,
which provides three response spectra for binding energy. The Cu 2p
spectrum exhibits two contributions, 2p3/2 and 2p1/2 (resulting from
the spin-orbit splitting), located at respectively 932.6 eV and 952.5 eV
(Fig. 2b). The 122.6 eV was assigned to the Cu 3 s orbit (Fig. 2c). The
75 eV and 77 eV were assigned to Cu 3p orbit (Fig. 2d). The O 1 s
spectrum (Fig. 2e) allows identifying Cu-O that was obtained by the
oxidation of skeletal Cu in the preparation of detected sample. The
skeletal Cu was unstable in air due to its porous structure filled
with hydrogen, which was formed in Al leaching process. Finally, the
binding energy scale was calibrated using the C 1 s at 284.6 eV (Fig. 2f).
The crystallite morphology of Cu–Al alloy and skeletal Cu catalyst
were characterized by XRD (seeing the supporting information). It
could be concluded that the alloy was mainly composed of CuAl2
phase (Fig. S-1). In addition, typical Cu (111), Cu (200) and Cu (220)
peaks were detected in the skeletal Cu sample (Fig. S-2). Using
Scherrer's equation, the average crystalline size of skeletal Cu was esti-
mated to be about 14 nm. The surface area and pore distribution for
skeletal Cu were also measured by nitrogen adsorption isotherms at
77 K using BET method (Fig. S-3 and S-4). Type IV adsorption isotherms
(IUPAC classification) [19,20] indicates that the skeletal Cu catalyst was
mainly composed of the mesoporous structure. The BET surface area for
skeletal Cu was 29.9 m2/g and the pore diameter was 6.7 nm by using
BJH method calculation.
Fig. 1. Scanning electron microscope (SEM) images for the Cu–Al alloy (a,b,c) and the skeletal Cu catalyst (d,e,f).

Z. Rong et al. / Catalysis Communications 41 (2013) 115–118
117
Fig. 2. (a) Survey and high-resolution XPS spectra of (b) Cu 2p (c) Cu 3 s (d) Cu 3p (e) O1s (f) C1s region for skeletal Cu sample.
when THF was used as solvent instead of CH3OH and the reaction time
was prolonged from 60 min to 105 min (Table S-6). So we have reasons
to believe that the CH3OH solvent participates in this reaction, which was
confirmed when replacing CH3OH (Fig. S-10, 2-e m/z = 215) with
CD3OD (Fig. S-11, 2-e m/z = 221). Moreover, we noticed 2-b was easily
converted to 2-f even without any catalyst under H2, N2 or air (Entries
5–7), which might speed up the reaction rates by transforming the
reaction path.
In entry 9, the hydro-dialkylation of p-acetylnitrobenzene was in-
vestigated at 373 K for 68 min but the selectivity was only 88.2%,
which was caused by excessive hydrogenation of the carbonyl
group in products. We also studied the hydro-dialkylation of p-
nitroaniline and p-dinitrobenzene with double-N atoms under the
optimized reaction conditions. Results showed that N1,N1,N4,N4-
tetramethyl-1,4-benzenediamine as main product could be obtained
with high selectivity in one-pot (Table 2, entries 10–11).
Inspired by these results, we investigated a series of nitroarenes with
different substituents on NNDA under optimized reaction conditions and
the results are summarized in Table 2. The corresponding NNDA were all
obtained with high selectivity (entries 1–11, 83–99%). As expected, the
substituent types and relative positions of nitroarenes have important
impact on the corresponding products' selectivity. For instance, the
selectivity for hydro-dimethylation of o-chloronitrobenzene was
only 82.9% at 373 K for 250 min, indicating the reaction rate and
selectivity are lower compared with p-chloronitrobenzene and m-
chloronitrobenzene (Table 2, entries 2–4). The main by-product is
o-chloro-N-methylaniline via hydrogenation and N-monoalkylation
of o-chloronitrobenzene, which might be attributed to the steric
hindrance. The selectivity to NNDA is about 96% under optimal con-
ditions when the para-positions in nitrobenzene were replaced by
the –OH, CH3 and OCH3 groups, respectively (Table 2, entries 5–7).
4. Conclusion
In conclusion, we have demonstrated a simple and efficient protocol
for the synthesis of NNDA in one-pot with skeletal Cu catalyst, which
was prepared by the quenching technique and played bifunctional
roles in the hydrogenation and alkylation process. The reaction conditions
are very mild with less catalyst's dosage. Mechanism studies indicate that
nitroarene converts to NNDA through two pathways. Methanol solvent
participated in this process through Route 2 and obviously accelerated
the reaction rate comparing with THF solvent. Furthermore, a wide
Table 1
Effect of the different catalysts on the hydro-dimethylation of p-CNB.a
Entry
Cat.
Catalysis (g)
t(min)
Conversion (%)
Selectivityb(%)
1
2
3
4
5
6
7
8
Pd/C
Pt/C
Rh/C
Ru/C
S-Ni
S-Fe
S-Co
S-Cu
0.04
0.07
0.04
0.05
0.5
0.5
0.5
0.5
120
120
120
120
30
120
120
60
14
14.5
87
32.8
100
43
100
100
30.5
10.7
56.6
0.8
91.3
4.8
16.8
99.4
a
Reaction conditions: 373 K, 15 bar H2, p-CNB = 1.0 g, CH3OH = 20 mL, HCHO
Fig. 3. The concentration–time plots for the hydro-dimethylation of p-CNB (reaction
conditions: 373 K, 13 bar H2, p-CNB = 6 mmol, CH3OH = 20 mL, HCHO (37 wt.%) =
1.35 mL, S-Cu(wet) = 0.5 g).
(37 wt.%) = 1.35 mL.
b
Conversion and selectivity were determined by GC.

118
Z. Rong et al. / Catalysis Communications 41 (2013) 115–118
NO2
NH2
H2
Route 1
Cl
a
Cl
b
N
OH
N
NH
H2
HCHO
-H2O
Cl
1
Cl
Cl
CH2
H 2
f
N
d
Route 2
Cl
c
H
O
N
O
N
HO
N
O
O
CH3OH
-H2O
HCHO
Cl
e
Cl
2
Cl
3
Scheme 2. The possible pathway for hydro-dimethylation of p-CNB.
Table 2
Acknowledgments
Hydro-dimethylation of different nitroarenes to NNDA over skeletal Cu catalyst.a
Substrate
T(K) t(min) Product
Conversion (%) Selectivityb(%)
This work was financially supported by the National Natural Science
Foundation of China (21206015), Specialized Research Fund for the
Doctoral Program of Higher Education (20120041120022), the Funda-
mental Research Funds for the Central Universities (DUT13LK29) and
the Scientific Research Project for Institute of Higher Education of Edu-
cation Bureau, Liaoning (LT2010021).
353
85
100
90.5
373
60
100
99.4
373
127
100
82.9
Appendix A. Supplementary data
373
373
343
75
57
80
100
100
100
99.6
96.0
96.4
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.catcom.2013.07.023.
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b
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