A highly efficient heterogeneous ruthenium-catalysed oxidative α-cyanation of tertiary amines leading to α-aminonitriles

Article abstract of DOI:10.3184/174751917X15064232103065

Oxidative α-cyanation of tertiary amines was achieved by using an MCM-41-immobilised N-alkylethylenediamine ruthenium(III) complex (MCM-41-2N-RuCl₃) as catalyst in MeOH at 60 oC in the presence of H₂O₂ as oxidant and NaCN

Full text of DOI:10.3184/174751917X15064232103065

576 RESEARCH PAPER
VOL. 41 OCTOBER, 576–580
JOURNAL OF CHEMICAL RESEARCH 2017
A highly efficient heterogeneous ruthenium-catalysed oxidative α-cyanation
of tertiary amines leading to α-aminonitriles
Xiaoming Wanga,b, Ruian Xiaob, Jingting Aia and Mingzhong Caia*
aKey Laboratory of Functional Small Organic Molecule, Ministry of Education and Department of Chemistry, Jiangxi Normal University, Nanchang 330022, P.R. China
b912 Lab Jiangxi Bureau of Geology and Mineral Exploration and Development, Yingtan 335001, P.R. China
Oxidative α-cyanation of tertiary amines was achieved by using an MCM-41-immobilised N-alkylethylenediamine ruthenium(III) complex
(MCM-41-2N-RuCl ) as catalyst in MeOH at 60 ºC in the presence of H2O2 as oxidant and NaCN in acetic acid as a cyanide source to afford
the corresponding3α-aminonitriles in good yields. The new heterogeneous ruthenium catalyst can easily be prepared by a simple two-step
procedure from commercially readily available and inexpensive reagents. It can be recovered by filtration of the reaction solution and
reused at least 7 times without significant loss of activity.
Keywords: supported ruthenium catalyst, oxidative α-cyanation, α-aminonitrile, MCM-41, heterogeneous catalysis
α-Aminonitriles are highly useful and versatile synthetic
intermediates and have been widely utilised in the construction
of biologically active nitrogen compounds such as alkaloids.1,2
The traditional methods for the synthesis of α-aminonitriles
include the Strecker reaction,3,4 the oxidative cyanation of
secondary5 or tertiary6,7 amines and anodic oxidative cyanation
of tertiary amines.8 However, most of these methods suffer
from one or more limitations, such as poor selectivity, multistep
synthesis, limited substrate scope, heavy metal oxidants
and generation of huge amount of wastes, which limit their
application. Recently, transition metal-catalysed direct oxidative
cyanation of C–H bonds in tertiary amines has provided a
simple and straightforward approach for the preparation of
these compounds. So far, a number of metal catalysts including
Ru,9–14 Fe,15–18 V,19 Mo,20 Au21,22 and Re23 in the presence of
oxidants such as H2O2, tert-butyl hydroperoxide (TBHP) and
O2 have been reported for the direct oxidative α-cyanation of
tertiary amines. However, in most cases, homogeneous metal
catalysts were used and the use of expensive metals such as
ruthenium, rhenium and gold as well as difficult recovery and
non-recyclability of the metal catalysts make these methods
of limited synthetic utility from environmental and economic
points of view. Therefore, development of an efficient, economic
and practical method for the direct synthesis of α-aminonitriles
through the oxidative α-cyanation of tertiary amines is highly
desirable.
Separation and recycling of homogeneous catalysts are
tasks of great economic and environmental importance in
the chemical and pharmaceutical industries, especially when
expensive and/or toxic heavy metal complexes are utilised.24
Immobilisation of homogeneous catalysts on various solid
supports, especially porous materials with high surface areas,
is usually the method of choice because the supported catalysts
can easily be recovered by a simple filtration of the reaction
solution. The discovery of mesoporous material MCM-41 has
provided a new possible candidate for an ideal heterogeneous
support for immobilising homogeneous catalysts.25,26 To date,
some functionalised MCM-41-immobilised palladium,27–29
rhodium,30 molybdenum,31 gold32 and copper33–35 complexes have
been successfully utilised as potentially green and sustainable
catalysts in organic reactions. In continuation of our efforts to
develop efficient, cost-effective and environmentally friendly
synthetic pathways for organic transformations,29,33–35 we wish
to report here the first synthesis of an MCM-41-immobilised
N-alkylethylenediamine Ru(III) complex (MCM-41-2N-RuCl3)
and its successful application to oxidative α-cyanation of
tertiary amines in the presence of H2O2 as oxidant and NaCN
in acetic acid as a cyanide source (Scheme 1). To the best of our
knowledge, this is the first example of using a heterogeneous
ruthenium complex for the oxidative α-cyanation of tertiary
amines with high efficiency. The new catalyst could be easily
recovered from the reaction mixture by a simple filtration of the
reaction solution and its catalytic efficiency remained unaltered
even after recycling seven times.
Results and discussion
The
new
MCM-41-supported
N-alkylethylenediamine
ruthenium(III) complex (MCM-41-2N-RuCl3) was prepared
from commercially readily available reagents according to the
procedure summarised in Scheme 2. Firstly, the mesoporous
material MCM-41 was treated with 3-(2-aminoethylamino)-
propyltrimethoxysilane in toluene at 100 °C for 24 h, followed
by silylation with Me3SiCl in toluene at room temperature for
24 h to afford 3-(2-aminoethylamino)propyl-functionalised
MCM-41 (MCM-41-2N). The latter was subsequently reacted
with RuCl3 in acetone under reflux for 72 h to give the MCM-
41-supported N-alkylethylenediamine ruthenium(III) complex
(MCM-41-2N-RuCl3) as a grey powder. The ruthenium content
of the complex was found to be 0.47 mmol g–1 according to
inductively coupled plasma atom emission spectrometry (ICP-
AES) measurements and details of XRD, EDS and XPS studies
are given in the Electronic Supplementary Information. Scheme
2 shows a reasonable proposal for the structure of the complex.
The
MCM-41-immobilised
N-alkylethylenediamine
ruthenium(III) complex (MCM-41-2N-RuCl3) was then used
as catalyst for the oxidative α-cyanation reaction of tertiary
R1
R1
MCM-41-2N-RuCl3(5 mol%)
H R3
HR3
N
N
C
N
C
C
2
R2
R2
NaCN/AcOH, MeOH, H2O2
Scheme 1
* Correspondent. E-mail: caimzhong@163.com

JOURNAL OF CHEMICAL RESEARCH 2017 577
OSiMe3
O
H
H
O
O
1. (MeO)3Si(CH2)3NH(CH2)2NH2
Toluene, 100 oC, 24 h
i
S
N
NH2
H
O
H
O
2. Me3SiCl, rt, 24 h
OMe
MCM-41-2N
MCM-41
OSiMe3
O
H
RuCl3, CH3COCH3
reflux, 72 h
i
S
N
NH2
RuCl3
O
OMe
MCM-41-2N-RuCl3
Scheme 2
Table 1 Optimisation of reaction conditions for heterogeneous Ru-
catalysed oxidative α-cyanation of N-phenylpyrrolidinea
amount was reduced to 2 mol% (Table 1, entry 13). Therefore,
the optimal catalytic system involved the use of MCM-41-2N-
RuCl3 (5 mol%) in MeOH with H2O2 as oxidant at 60 °C under
Ar for 4 h (Table 1, entry 3). The reaction also worked well
under N2 but a decreased yield was observed in air.
MCM-41-2N-RuCl3 (5 mol%)
+
N
N
NaCN/AcOH
oxidant, solvent, temp.
N
C
1a
2a
With the optimal conditions for the highly efficient and
selective oxidative cyanation of tertiary amines in hand,
we started to investigate the scope of this heterogeneous
ruthenium-catalysed reaction by using different tertiary amines
as substrates and the results are summarised in Table 2. To
our delight, all the substrates were selectively and effectively
converted into the corresponding α-aminonitriles in good
yields. Substituted N-phenylpyrrolidines 1b and 1c afforded the
desired products 2b and 2c in 81 and 78% yields respectively
(Table 2, entries 2 and 3). Other cyclic tertiary amines such as
N-arylpiperidines 1d–f and N-aryltetrahydroisoquinolines 1g–i
were also suitable substrates and could undergo the cyanation
reaction effectively to give the corresponding cyanated products
2d–i in 68–82% yields (Table 2, entries 4–9). Furthermore, the
reaction can also be applied to many acyclic tertiary amines. As
shown in Table 2, the reactions of N,N-dimethylaniline (1j) and
substituted N,N-dimethylanilines 1k–t bearing either electron-
donating or electron-withdrawing substituents proceeded
smoothly to give the corresponding cyanated products 2j–t in
64–86% yields (Table 2, entries 10–20). A variety of functional
groups such as methyl, methoxy, fluoro, chloro, bromo, cyano,
nitro, ester, alkynyl and ketone were tolerated well. The results
indicated that the electronic nature of the substituent on the
benzene ring has limited influence on this heterogeneous
ruthenium-catalysed oxidative α-cyanation reaction. It is
noteworthy that bulky N,N-dimethyl-1-naphthylamine (1u)
also afforded the expected product 2u in 76% yield (Table 2,
entry 21) and N-ethyl-N-methylaniline (1v), an unsymmetrical
aniline, underwent a regioselective oxidative cyanation at the
methyl group rather than at the methylene carbon of the ethyl
group to furnish the desired product 2v in 65% yield (Table 2,
entry 22).
Entry Oxidant
Solvent
Temp. (ºC)
Time (h)
Yield (%)b
c
1
2
H O
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
EtOAc
MeCN
MeOH
MeOH
25
40
60
70
60
60
60
60
60
60
60
60
60
24
24
4
0
48
85
81
46
24
0
79
37
35
18
84
64
H2O2
H2O2
H22O22
TBHP
O2 (1 atm)
–
3
4
3
5
24
24
24
6
6
7
8
H O
9
H2O2
H2O2
H2O2
H2O2
H22O22
24
24
24
2
10
11
12d
13e
10
aReaction conditions: N-phenylpyrrolidine (1.0 mmol), NaCN (1.2 mmol), AcOH (6.0
mmol), oxidant (2.5 mmol), MCM-41-2N-RuCl3 (5 mol%), solvent (2 mL) under Ar.
bIsolated yield.
c30% H2O2 aqueous solution.
d10 mol% Ru catalyst was used.
e2 mol% Ru catalyst was used.
amines with NaCN in acetic acid as a cyanide source. In our
initial screening experiments, the oxidative α-cyanation of
N-phenylpyrrolidine (1a) catalysed by MCM-41-2N-RuCl3 was
selected as the model reaction to optimise the reaction conditions
and the results are summarised in Table 1 (see CAUTION in
the Experimental section). At first, the temperature effect was
examined in MeOH with hydrogen peroxide as oxidant and a
significant temperature effect was observed (Table 1, entries
1–4). It is evident that the reaction did not occur at room
temperature and the reaction run at 40 ºC gave a low yield.
When the temperature was raised to 60 ºC, the desired product
2a was isolated in 85% yield. Our next studies focused on the
effect of various oxidants on the model reaction. When other
oxidants such as TBHP or molecular oxygen were used, the
reaction proceeded slowly and only low yields were obtained
(Table 1, entries 5 and 6). So hydrogen peroxide, which satisfies
environmental and sustainability demands, was found to be the
best oxidant for this transformation (Table 1, entry 3). However,
no reaction occurred in the absence of an oxidant (Table 1,
entry 7). Among the various solvents such as EtOH, MeOH,
i-PrOH, EtOAc and MeCN tested (Table 1, entries 3 and
8–11), MeOH gave the best result. Finally, the catalyst amount
was also screened and the use of 5 mol% catalyst was found
to be optimal. A lower yield was observed when the catalyst
To verify whether the observed catalysis was due to the
heterogeneous ruthenium catalyst or to a leached ruthenium
species in solution, we performed the hot filtration test.36 We
focused on the oxidative α-cyanation of N-phenylpyrrolidine
(1a). We filtered off the MCM-41-2N-RuCl3 complex after 2
h of reaction time and allowed the filtrate to react further at
60 °C. The catalyst filtration was performed at the reaction
temperature (60 °C) to avoid possible re-coordination or
precipitation of soluble ruthenium upon cooling. We found that,
after this hot filtration, no significant increase in conversion was

578 JOURNAL OF CHEMICAL RESEARCH 2017
Table 2 Heterogeneous Ru-catalysed oxidative α-cyanation of tertiary
100
80
60
40
20
0
anilinesa
R2
R2
5 mol% MCM-41-2N-RuCl3
N
HR3
N
C
C
CH2R3
+ NaCN/AcOH
N
H2O2 (2.5 equiv.), MeOH, 60 o
C
R1
R1
2
1
Entry R1–
R2– R3–
–(CH2)3–
–(CH2)3–
–(CH2)3–
–(CH2)4–
–(CH2)4–
–(CH2)4–
Product
Yield (%)b
1
2
3
4
5
6
Ph–
2a
2b
2c
2d
2e
2f
85
81
78
73
75
68
o-MeC6H4–
p-MeOC6H4–
Ph–
p-MeOC6H4–
o-NO2C6H4–
1
2
3
4
5
6
7
8
Reaction cycles
7
8
9
Ph–
2g
2h
2i
82
77
75
Fig. 1 Recycling of the MCM-41-2N-RuCl3 catalyst.
m-MeC6H4–
In summary, we have developed a novel, efficient and cost-
effective method for the preparation of α-aminonitriles through
oxidative α-cyanation of tertiary amines using an MCM-41-
immobilised N-alkylethylenediamine ruthenium(III) complex
(MCM-41-2N-RuCl3) as the catalyst in the presence of H2O2
as oxidant and NaCN in AcOH as the cyanide source. The
reactions generated a variety of α-aminonitriles in good yields
under mild conditions and were applicable to a range of cyclic or
acyclic tertiary amines. In addition, this methodology offers the
competitiveness of recyclability of the ruthenium catalyst without
significant loss of catalytic activity and the catalyst could be
easily recovered and reused at least seven times, thus making this
procedure economically and environmentally more acceptable.
p-BrC6H4–
10
11
12
13
14
15
16
17
18
19
20
21
22
Ph–
Me–
Me–
Me–
Me–
Me–
Me–
Me–
H–
H–
H–
H–
H–
H–
H–
H–
H–
H–
H–
H–
H–
2j
2k
2l
86
82
80
75
71
67
78
71
64
70
73
76
65
p-MeC6H4–
m-MeC6H4–
p-BrC6H4–
m-ClC6H4–
p-CNC6H4–
p-PhC6H4–
2m
2n
2o
2p
2q
2r
2s
2t
p-(4-FC6H4)C6H4– Me–
p-MeO2CC6H4–
p-PhCCC6H4–
p-PhCOC6H4–
1-Naphthyl–
Ph–
Me–
Me–
Me–
Me–
Et–
Experimental
2u
2v
All chemicals were obtained from commercial suppliers and used as
received, unless otherwise noted. All products were characterised
by comparison of their spectra and physical data with authentic
Reaction conditions: tertiary amine (1.0 mmol), NaCN (1.2 mmol), AcOH (6.0 mmol), a
30% aqueous solution of H2O2 (2.5 mmol), MCM-41-2N-RuCl3 (5 mol%), MeOH (2 mL) at
1
samples. H NMR spectra were recorded on a Bruker Avance 400
spectrometer at 400 MHz with TMS as an internal standard in CDCl3
as solvent. 13C NMR spectra were recorded on the Bruker Avance 400
spectrometer at 100 MHz in CDCl3 as solvent. Microanalyses were
measured by using a Yanaco MT-3 CHN microelemental analyser.
HRMS spectra were recorded on a Q-Tof spectrometer with micromass
MS software using electrospray ionisation (ESI). X-ray diffraction
(XRD) measurements were carried out at room temperature using
a Philips X’pert diffractometer using Cu Ka radiation filtered by Ni.
X-ray energy dispersive spectroscopy (EDS) was performed using
a Phenom Prox scanning electron microscope. X-ray photoelectron
spectra (XPS) were recorded on an XSAM 800 instrument (Kratos).
Mesoporous material MCM-41 was prepared according to a literature
method.37
60 °C under Ar for 4 h.
b Isolated yield.
observed, demonstrating that leached ruthenium species from
the catalyst (if any) are not responsible for the observed activity.
It was confirmed by ICP-AES analysis that no ruthenium
could be detected in the hot filtered solution. The maximum
concentration which would have been undetected is 0.06 ppm.
For the practical application of an immobilised transition-
metal catalyst, its ease of separation, recoverability and
reusability are important factors. This heterogeneous ruthenium
catalyst can be easily separated and recovered by a simple
filtration of the reaction solution. We next studied recycling of
the catalyst by using the oxidative α-cyanation reaction of N,N-
dimethylaniline (1j). After carrying out the reaction, the catalyst
was recovered by a simple filtration of the reaction solution and
washed with distilled water and ethanol. After being air-dried, it
was reused directly without further purification. The recovered
ruthenium catalyst was used in the next run and almost consistent
activity was observed for eight consecutive cycles (Fig. 1). The
satisfactory reusability of the catalyst could be attributed to the
chelating action of the bidentate nitrogen ligand on ruthenium
and the mesoporous structure of the MCM-41 support. The result
is important from industrial and environmental points of view.
The high catalytic activity and excellent reusability of the MCM-
41-2N-RuCl3 complex make it a highly attractive heterogeneous
ruthenium catalyst for the parallel solution phase synthesis of
diverse libraries of compounds.
Preparation of MCM-41-2N
A solution of 3-(2-aminoethylamino)propyltrimethoxysilane (1.54 g)
in dry chloroform (18 mL) was added to a suspension of the MCM-
41 (2.2 g) in dry toluene (180 mL). The mixture was stirred for 24
h at 100 °C. The solid was then filtered off and washed with CHCl3
(2 × 20 mL) and dried under reduced pressure at 160 °C for 5 h. The
dried white solid was then soaked in a solution of Me3SiCl (3.1 g) in
dry toluene (100 mL) at room temperature under stirring for 24 h. Then
the solid was filtered off, washed with acetone (3 × 20 mL) and diethyl
ether (3 × 20 mL) and dried under reduced pressure at 120 °C for 5 h
to obtain 3.49 g of hybrid material MCM-41-2N. The nitrogen content
was found to be 1.84 mmol g–1 by elemental analysis.
Preparation of MCM-41-2N-RuCl3 complex
In a small Schlenk tube, MCM-41-2N (2.3 g) was mixed with
RuCl3·3H2O (1.3 mmol, 0.339 g) in dry acetone (50 mL). The mixture

JOURNAL OF CHEMICAL RESEARCH 2017 579
was refluxed for 72 h under an argon atmosphere. The solid product
was filtered off by suction, washed with acetone, distilled water and
acetone successively and dried at 70 °C/26.7 Pa under Ar for 5 h to
give 2.52 g of a grey ruthenium complex (MCM-41-2N-RuCl3). The
nitrogen and ruthenium contents were found to be 1.65 mmol g–1 and
0.47 mmol g–1 respectively.
2.99–2.93 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 148.4, 134.7, 129.7,
129.6, 129.4, 128.8, 127.1, 126.9, 121.9, 117.8, 117.6, 53.2, 44.2, 28.6.
2-(3-Methylphenyl)-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile
1
(2h):38 Yellow oil; H NMR (400 MHz, CDCl3): δ 7.31–7.18 (m, 5H),
6.89–6.85 (m, 2H), 6.82 (d, J = 7.2 Hz, 1H), 5.49 (s, 1H), 3.80–3.69 (m,
1H), 3.48–3.39 (m, 1H), 3.13–3.07 (m, 1H), 2.97–2.89 (m, 1H), 2.35 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 148.5, 139.4, 134.7, 129.8, 129.4,
128.7, 127.1, 126.8, 122.8, 118.4, 117.8, 114.7, 53.3, 44.2, 28.6, 21.7.
2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile
(2i): Yellow solid; m.p. 155–156 ºC (lit.38 153–154 °C); 1H NMR
(400 MHz, CDCl3): δ 7.47–7.41 (m, 2H), 7.34–7.19 (m, 4H), 6.94 (d,
J = 8.8 Hz, 2H), 5.45 (s, 1H), 3.75–3.64 (m, 1H), 3.52–3.41 (m, 1H),
3.19–3.11 (m, 1H), 3.02–2.89 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
147.4, 134.4, 132.5, 129.4, 129.3, 128.9, 127.1, 127.0, 119.1, 117.5, 114.4,
52.9, 44.3, 28.4.
Heterogeneous Ru-catalysed oxidative α-cyanation of tertiary
amines; general procedure
CAUTION: Special precautions should be taken in all procedures
involving cyanides due to toxicity. Care should also be taken when
heating H2O2 or TPHB with organic materials depending on the
amounts involved (possible explosion?).
A 25 mL round-bottomed flask equipped with a magnetic stirring
bar and a balloon filled with Ar was charged with tertiary amine (1.0
mmol), NaCN (1.2 mmol), acetic acid (6 mmol), MCM-41-2N-RuCl3
(0.05 mmol) and MeOH (2 mL). A 30% H2O2 aqueous solution (2.5
mmol) at 60 ºC was added dropwise to the mixture over a period of
1.5 h and the mixture was stirred at 60 ºC for an additional 2.5 h. After
completion of the reaction, the mixture was diluted with ethyl acetate
(20 mL) and filtered. The catalyst was washed with distilled water
(5 mL) and EtOH (2 × 5 mL) and reused in the next run. The filtrate
was washed with aqueous NaHCO3 and brine and dried over MgSO4.
After removal of the solvent under reduced pressure, the residue was
purified by flash column chromatography on silica gel using a mixture
of petroleum ether (boiling range 30–60 °C) and EtOAc as eluent.
2-[Methyl(phenyl)amino]acetonitrile (2j):10 Colourless oil;1H NMR
(400 MHz, CDCl3): δ 7.32 (t, J = 7.6 Hz, 2H), 6.92 (t, J = 7.4 Hz, 1H),
6.87 (d, J = 8.4 Hz, 2H), 4.17 (s, 2H), 3.01 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 147.4, 129.1, 119.6, 115.4, 114.3, 41.6, 38.7.
2-[Methyl(p-tolyl)amino]acetonitrile (2k):10 Colourless oil;
1H NMR (400 MHz, CDCl3): δ 7.12 (d, J = 8.0 Hz, 2H), 6.80 (d,
J = 8.4 Hz, 2H), 4.13 (s, 2H), 2.96 (s, 3H), 2.29 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 145.3, 129.5, 129.4, 127.5, 115.0, 42.4, 39.0, 19.9.
2-[Methyl(m-tolyl)amino]acetonitrile (2l):11 Colourless oil;
1H NMR (400 MHz, CDCl3): δ 7.27–7.11 (m, 1H), 6.74 (d, J = 7.6 Hz,
1H), 6.70–6.66 (m, 2H), 4.14 (s, 2H), 2.98 (s, 3H), 2.34 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 147.4, 138.8, 128.8, 124.4, 120.6, 115.2,
111.6, 41.8, 38.8, 21.3.
1
1-Phenylpyrrolidine-2-carbonitrile (2a):21 Colourless oil; H NMR
2-[(4-Bromophenyl)methylamino]acetonitrile (2m):10 Colourless
oil; 1H NMR (400 MHz, CDCl3): δ 7.39 (dd, J = 7.2, 2.0 Hz, 2H), 6.73
(dd, J = 8.8, 2.0 Hz, 2H), 4.14 (s, 2H), 2.99 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 146.3, 131.8, 115.9, 114.7, 112.0, 41.7, 38.9.
(400 MHz, CDCl3): δ 7.30 (t, J = 8.0 Hz, 2H), 6.83 (t, J = 7.2 Hz,
1H), 6.69 (d, J = 8.4 Hz, 2H), 4.43 (dd, J = 7.6, 3.6 Hz, 1H), 3.49–3.41
(m, 1H), 3.39–3.33 (m, 1H), 2.44–2.37 (m, 1H), 2.34–2.14 (m, 3H);
13C NMR (100 MHz, CDCl3): δ 145.3, 129.5, 119.3, 118.3, 112.7, 49.1,
47.5, 31.6, 24.0.
1-(o-Tolyl)pyrrolidine-2-carbonitrile (2b):22 Brown oil; 1H NMR
(400 MHz, CDCl3): δ 7.20–7.12 (m, 3H), 7.03 (t, J = 7.2 Hz, 1H),
4.38 (dd, J = 7.6, 3.6 Hz, 1H), 3.49–3.42 (m, 1H), 3.17–3.12 (m, 1H),
2.42–2.35 (m, 1H), 2.31 (s, 3H), 2.29–1.97 (m, 3H); 13C NMR (100
MHz, CDCl3): δ 144.9, 132.2, 131.5, 126.8, 124.2, 119.8, 119.1, 52.0,
50.0, 30.7, 22.8, 18.8.
2-[(3-Chlorophenyl)methylamino]acetonitrile (2n):22 Yellow oil;
1H NMR (400 MHz, CDCl3): δ = 7.18–7.12 (m, 1H), 6.80 (dd, J = 8.0,
2.0 Hz, 1H), 6.74 (t, J = 2.2 Hz, 1H), 6.64 (dd, J = 8.4, 2.8 Hz, 1H), 4.08
(s, 2H), 2.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 147.8, 134.3,
129.4, 118.9, 114.2, 113.7, 111.6, 40.9, 38.1.
4-[(Cyanomethyl)methylamino]benzonitrile (2o): Yellow solid; m.p.
1
105–106 ºC (lit.14 106–107 °C); H NMR (400 MHz, CDCl3): δ 7.58
(d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 4.26 (s, 2H), 3.13 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 149.8, 144.4, 133.3, 117.7, 114.0, 112.9,
40.5, 38.5.
1-(4-Methoxyphenyl)pyrrolidine-2-carbonitrile (2c): White solid;
1
m.p. 58–59 ºC (lit.10 60–61 °C); H NMR (400 MHz, CDCl3): δ 6.89
(d, J = 9.2 Hz, 2H), 6.66 (d, J = 9.2 Hz, 2H), 4.37 (dd, J = 7.6, 3.6 Hz,
1H), 3.77 (s, 3H), 3.46–3.40 (m, 1H), 3.15–3.10 (m, 1H), 2.40–2.33 (m,
1H), 2.27–1.96 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 152.8, 139.9,
119.8, 115.2, 114.1, 55.6, 49.9, 47.8, 31.5, 23.9.
2-[Biphenyl-4-yl(methyl)amino]acetonitrile (2p): White solid; m.p.
103–104 ºC; H NMR (400 MHz, CDCl3): δ 7.57–7.52 (m, 4H), 7.41
(t, J = 7.8 Hz, 2H), 7.32–7.28 (m, 1H), 6.92 (d, J = 8.8 Hz, 2H), 4.18 (s,
2H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 147.1, 140.6, 133.0,
128.8, 128.1, 126.7, 126.6, 115.5, 115.1, 42.2, 39.3; HRMS (ESI) m/z
calcd for C15H14N2+ [M+]: 222.1157; found: 222.1164.
1
1-Phenylpiperidine-2-carbonitrile (2d):10 Colourless oil; 1H NMR
(400 MHz, CDCl3): δ 7.31 (t, J = 7.2 Hz, 2H), 7.02–6.97 (m, 3H),
4.64–4.61 (m, 1H), 3.47–3.41 (m, 1H), 3.07–2.97 (m, 1H), 2.04–1.99
(m, 2H), 1.86–1.82 (m, 2H), 1.71–1.66 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 149.8, 129.5, 122.3, 118.5, 117.2, 52.1, 46.6, 29.3, 25.2, 20.2.
1-(4-Methoxyphenyl)piperidine-2-carbonitrile (2e): White solid;
m.p. 93–94 ºC (lit.10 91–93 °C); 1H NMR (400 MHz, CDCl3): δ = 6.97
(d, J = 9.2 Hz, 2H), 6.84 (d, J = 9.2 Hz, 2H), 4.47–4.41 (m, 1H), 3.78
(s, 3H), 3.26–3.20 (m, 1H), 3.05–2.99 (m, 1H), 2.03–1.98 (m, 2H),
1.84–1.79 (m, 2H), 1.68–1.63 (m, 2H); 13C NMR (100 MHz, CDCl3): δ
= 155.6, 143.9, 120.8, 117.3, 114.6, 55.6, 53.8, 47.9, 29.1, 25.3, 20.2.
1-(2-Nitrophenyl)piperidine-2-carbonitrile (2f): Yellow solid; m.p.
2-[(4’-Fluorobiphenyl-4-yl)(methyl)amino]acetonitrile (2q): White
solid; m.p. 121–123 ºC; 1H NMR (400 MHz, CDCl3): δ 7.51–7.46 (m,
4H), 7.12–7.06 (m, 2H), 6.91 (d, J = 8.8 Hz, 2H), 4.19 (s, 2H), 3.03 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 162.1 (d, 1JC–F = 244.1 Hz), 147.0,
4
136.7 (d, JC–F = 3.2 Hz), 132.1, 128.1 (d, 3JC–F = 7.9 Hz), 128.0, 115.6
(d, 2JC–F = 21.2 Hz), 115.4, 115.1, 42.2, 39.3; HRMS (ESI) m/z calcd for
C15H13FN2+ [M+]: 240.1063; found: 240.1051.
Methyl 4-[(cyanomethyl)methylamino]benzoate (2r): White solid;
1
m.p. 80–81 ºC (lit.22 81–82 °C); H NMR (400 MHz, CDCl3): δ 7.98
(dd, J = 7.2, 2.0 Hz, 2H), 6.80 (dd, J = 7.2, 2.0 Hz, 2H), 4.25 (s, 2H),
3.88 (s, 3H), 3.10 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 166.9, 150.9,
131.5, 120.8, 115.2, 112.8, 51.8, 41.2, 39.0.
1
55–56 ºC (lit.22 56–57 °C); H NMR (400 MHz, CDCl3): δ 7.80 (d,
J = 7.2 Hz, 1H), 7.60 (t, J = 7.0 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.29
(t, J = 7.4 Hz, 1H), 4.52–4.49 (m, 1H), 3.38–3.31 (m, 1H), 3.01–2.95
(m, 1H), 2.13–2.07 (m, 1H), 1.99–1.94 (m, 1H), 1.86–1.68 (m, 4H);
13C NMR (100 MHz, CDCl3): δ 146.5, 144.1, 133.7, 125.6, 125.2, 124.4,
117.1, 54.3, 48.7, 28.9, 25.3, 19.9.
2-{Methyl[4-(phenylethynyl)phenyl]amino}acetonitrile (2s): Yellow
1
solid; m.p. 107–109 ºC; H NMR (400 MHz, CDCl3): δ 7.53–7.44 (m,
4H), 7.36–7.28 (m, 3H), 6.78 (dd, J = 7.2, 2.0 Hz, 2H), 4.15 (s, 2H), 3.01
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 147.4, 133.0, 131.5, 128.4, 128.0,
123.7, 115.3, 114.2, 114.1, 89.5, 88.4, 41.7, 39.1. HRMS (ESI) m/z calcd
for C17H14N2+ [M+]: 246.1157; found: 246.1162.
2-Phenyl-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile
(2g):10
Colourless oil; 1H NMR (400 MHz, CDCl3): δ 7.36 (t, J = 7.6 Hz, 2H),
7.30–7.21 (m, 4H), 7.08 (d, J = 7.6 Hz, 2H), 7.01 (t, J = 7.0 Hz, 1H),
5.51 (s, 1H), 3.78–3.72 (m, 1H), 3.51–3.43 (m, 1H), 3.21–3.13 (m, 1H),
2-[(4-Benzoylphenyl)methylamino]acetonitrile (2t): Yellow solid;
1
m.p. 94–95 ºC (lit.39 92–93 °C); H NMR (400 MHz, CDCl3): δ 7.84

580 JOURNAL OF CHEMICAL RESEARCH 2017
6
C.-K. Chen, A.G. Hortmann and M.R. Marzabadi, J. Am. Chem. Soc.,
1988, 110, 4829.
A. Wagner and A.R. Ofial, J. Org. Chem., 2015, 80, 2848.
V.H. Vu, F. Louafi, N. Girard, R. Marion, T. Roisnel, V. Dorcet and J.-P.
Hurvois, J. Org. Chem., 2014, 79, 3358.
(d, J = 8.8 Hz, 2H), 7.77–7.72 (m, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.47
(t, J = 7.4 Hz, 2H), 6.84 (d, J = 9.2 Hz, 2H), 4.29 (s, 2H), 3.14 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 195.3, 150.8, 138.4, 132.7, 132.6, 129.7,
128.3, 128.2, 115.1, 112.6, 41.2, 39.1.
7
8
2-[Methyl(naphthalen-1-yl)amino]acetonitrile (2u): Yellow solid;
m.p. 91–93 ºC (lit.39 91–92 °C); 1H NMR (400 MHz, CDCl3): δ 8.10
(d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H),
7.55–7.47 (m, 2H), 7.44 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H),
4.10 (s, 2H), 3.04 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 146.6, 128.2,
127.5, 125.7, 125.5, 125.2, 124.9, 124.6, 122.2, 117.0, 116.7, 45.6, 40.9.
9
S.I. Murahashi, N. Komiya, H. Terai and T. Nakae, J. Am. Chem. Soc.,
2003, 125, 15312.
10 S.I. Murahashi, N. Komiya and H. Terai, Angew. Chem., Int. Ed., 2005,
44, 6931.
11 S.I. Murahashi, T. Nakae, H. Terai and N. Komiya, J. Am. Chem. Soc.,
2008, 130, 11005.
12 P. Kumar, S. Varma and S.L. Jain, J. Mater. Chem. A, 2014, 2, 4514.
13 S. Varma, S.L. Jain and B. Sain, ChemCatChem, 2011, 3, 1329.
14 K.H.V. Reddy, G. Satish, V.P. Reddy, B.S.P.A. Kumar and Y.V.D. Nageswar,
RSC Adv., 2012, 2, 11084.
15 W. Han and A.R. Ofial, Chem. Commun., 2009, 5024.
16 S. Singhal, S.L. Jain and B. Sain, Adv. Synth. Catal., 2010, 352, 1338.
17 V. Panwar, P. Kumar, A. Bansal, S.S. Ray and S.L. Jain, Appl. Catal., A,
2015, 498, 25.
18 P. Liu, Y. Liu, E.L. Wong, S. Xiang and C.-M. Che, Chem. Sci., 2011, 2, 2187.
19 S. Singhal, S.L. Jain and B. Sain, Chem. Commun., 2009, 2371.
20 K. Alagiri and K.R. Prabhu, Org. Biomol. Chem., 2012, 10, 835.
21 Y. Zhang, H. Peng, M. Zhang, Y. Cheng and C. Zhu, Chem. Commun., 2011,
47, 2354.
22 W. Yang, L. Wei, F. Yi and M. Cai, Tetrahedron, 2016, 72, 4059.
23 A. Lin, H. Peng, A. Abdukader and C. Zhu, Eur. J. Org. Chem., 2013, 7286.
24 D.J. Cole-Hamilton, Science, 2003, 299, 1702.
1
2-[Ethyl(phenyl)amino]acetonitrile (2v):17 Colourless oil; H NMR
(400 MHz, CDCl3): δ 7.31 (t, J = 8.0 Hz, 2H), 6.92 (t, J = 7.2 Hz, 1H),
6.86 (d, J = 8.0 Hz, 2H), 4.14 (s, 2H), 3.44 (q, J = 7.2 Hz, 2H), 1.24 (t,
J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 146.4, 129.1, 119.3,
115.9, 114.5, 45.8, 39.0, 11.8.
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 21464021) and Key Laboratory of Functional Small
Organic Molecule, Ministry of Education (No. KLFS-
KF-201409) for financial support.
Electronic Supplementary Information
25 C.T. Kresge, M.E. Leonowicz, W.J. Roth, J.C. Vartuli and J.S. Beck, Nature,
1992, 359, 710.
26 R.M. Martin-Aranda and J. Cejka, Top. Catal., 2010, 53, 141.
27 P.C. Mehnert, D.W. Weaver and J.Y. Ying, J. Am. Chem. Soc., 1998, 120,
12289.
The ESI (details of XRD, EDS and XPS characterisation data
for the MCM-41-2N-RuCl3 complex) is available through
ht t p : / / i ngent acon ne ct.com / cont ent / st l /jc r / 2017/
00000041/00000010
28 K. Mukhopadhyay, B.R. Sarkar and R.V. Chaudhari, J. Am. Chem. Soc.,
2002, 124, 9692.
Received 10 July 2017; accepted 31 August 2017
Paper 1704874
https://doi.org/10.3184/174751917X15064232103065
Published online: 4 October 2017
29 M. Cai, J. Peng, W. Hao and G. Ding, Green Chem., 2011, 13, 190.
30 S.-G. Shyu, S.-W. Cheng and D.-L. Tzou, Chem. Commun., 1999, 2337.
31 M. Jia, A. Seifert and W.R. Thiel, Chem. Mater., 2003, 15, 2174.
32 G. Villaverde, A. Corma, M. Iglesias and F. Sanchez, ACS Catal., 2012, 2,
399.
33 H. Zhao, W. He, R. Yao and M. Cai, Adv. Synth. Catal., 2014, 356, 3092.
34 M. Cai, R. Yao, L. Chen and H. Zhao, J. Mol. Catal. A: Chem., 2014, 395,
349.
35 H. Zhao, W. He, L. Wei and M. Cai, Catal. Sci. Technol., 2016, 6, 1488.
36 H.E.B. Lempers and R.A. Sheldon, J. Catal., 1998, 175, 62.
37 M.H. Lim and A. Stein, Chem. Mater., 1999, 11, 3285.
38 G. Zhang, Y. Ma, G. Cheng, D. Liu and R. Wang, Org. Lett., 2014, 16, 656.
39 A. Wagner, W. Han, P. Mayer and A.R. Ofial, Adv. Synth. Catal., 2013,
355, 3058.
References
1
2
3
V. Ritleng, C. Sirlin and M. Pfeffer, Chem. Rev., 2002, 102, 1731.
D. En, G.-F. Zou, Y. Guo and W.-W. Liao, J. Org. Chem., 2014, 79, 4456.
M. North, Comprehensive organic functional group transformations, eds
A.R. Katritzky, O. Meth-Cohn, C.W. Rees and G. Pattenden. Pergamon,
Oxford, 1995, Vol. 3, pp. 611–617.
4
5
K. Surendra, N.S. Krishnaveni, A. Mahesh and K.R. Rao, J. Org. Chem.,
2006, 71, 2532.
D.H.R. Barton, A. Billion and J. Boivin, Tetrahedron Lett., 1985, 26, 1229.