Aerobic oxidation of primary benzylic amines to amides and nitriles catalyzed by ruthenium carbonyl clusters carrying N,O-bidentate ligands

Article abstract of DOI:10.1039/d0dt00045k

Four trinuclear ruthenium carbonyl clusters, (6-BrPyCHRO)₂Ru₃(CO)₈ (R = 4-OCH₃C₆H₄, 1a; R = 4-BrC₆H₄, 1b) and (2-OC₆H₄-HCN-C₆H₄R)₂Ru₃(CO)₈ (R = 4-OCH₃, 2a; R = 4-Br, 2b), were synthesized from the reactions of Ru₃(CO)₁₂ with the corresponding N,O-bidentate ligands (two pyridyl alcohols and two Schiff bases) respectively in a ratio of 1:2. Three new complexes 1b, 2a and 2b have been fully characterized by elemental analysis, FT-IR, NMR and X-ray crystallography. The catalytic activity of these ruthenium complexes for the aerobic oxidation of primary benzylic amines to amides and nitriles in the presence of t-BuOK was investigated, of which the Schiff base complex 2a was found to exhibit the highest activity.

Full text of DOI:10.1039/d0dt00045k

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DOI: 10.1039/D0DT00045K
Journal Name
Received 00th January 20xx,
Aerobic oxidation of primary benzylic amines to amides and
nitriles catalyzed by ruthenium carbonyl clusters carrying N,O-
bidentate ligands
Xinlong Yan,a‡ Qing Dong,a‡ Ying Li,a Lizhen Meng,a Zhiqiang Hao,*a Zhangang Han,a Guo-Liang Lub
and Jin Lin*a
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Four trinuclear ruthenium carbonyl clusters (6-BrPyCHRO)2Ru3(CO)8 (R = 4-OCH3C6H4, 1a; R = 4-BrC6H4, 1b) and (2-OC6H4-
HC=N-C6H4R)2Ru3(CO)8 (R = 4-OCH3C6H4, 2a; R = 4-BrC6H4, 2b), were synthesized from the reactions of Ru3(CO)12 with the
corresponding N,O-bidentate ligands (two pyridyl alcohols and two Schiff bases) respectively in the ratio of 1:2. Three new
complexes 1b, 2a and 2b have been fully characterized by element analysis, FT-IR, NMR and X-ray crystallography. The
catalytic activity of these ruthenium complexes for the aerobic oxidation of primary benzylic amines to amides and nitriles
in the presence of t-BuOK was investigated, of which the Schiff base complex 2a was found to exhibit the highest activity.
required. Unlike heterogeneous catalysts, reports on the direct
oxidation of primary amines to amides under homogeneous systems
were relatively scarce. In 2012, Fu and co-workers reported a Cu(I)-
Introduction
Amides are an important class of nitrogen-containing compounds
catalyzed aerobic oxidative synthesis of primary amides using
DMSO-H2O as solvent in the presence of K2CO3.20 Recently,
Lahiri’s group found the homogeneous oxidation of benzylamine to
amides was highly selective (without any by-products) using
RuHCl(CO)(PPh3)3, a commercially available catalyst, and low
catalyst loading and low pressure of oxygen were needed.21 In this
regard, novel catalytic frameworks and efficient synthesis protocols
for oxidation of amines remain a hot topic.
that have served as the precursors for a wide range of value-added
chemicals and materials such as peptides, pharmaceuticals,
1-3
pigments, polymers etc
Common methods forthe synthesis of
amides include the reaction of amines with activated carboxylic acid
derivatives and the Beckmann rearrangement of ketoximes or
aldoximes4-8. However, these classic methods involve multiple steps
or generate large amounts of chemical wastes.4-8 Therefore, more
efficient and environment friendly methods are in demand to access
various amides particularly primary amides and many efforts have
been made to obtained such transformations.9-12 For examples, the
oxidation of alcohols has been studied in the presence of aqueous
ammonia as nitrogen source using different oxidative reagents such
as MnO2/graphene oxide,13 manganese-based octahedral molecular
sieves (OMS-2)14 and the metal-free I2/TBHP/K2CO3 system.15
(Scheme 1a). A one-pot synthesis of primary amides was achieved
via the conversion of alcohols (or aldehydes) to oximes followed by
rearrangement in situ (Scheme 1b).16,17 7Amides were also been
made from primary amines through the direct aerobic oxidation of
the α-methylene group in primary amines (Scheme 1c). For instance,
Mizuno et al. reported that a heterogeneous catalyst Ru(OH)3/Al2O3
displayed high activity in the aerobic oxidation of primary amines.18
Recently, Xiao’s group developed a manganese oxide nanorods (N-
MnOx)-catalyzed aerobic oxidation of amines to amides.19 These
heterogeneous catalytic systems are highly efficient but the defect is
that high pressure (5-15 atm) and high temperature (120-160°C) are
Nitrile-containing compounds are another class of compounds
widely used for pharmaceuticals and are key building blocks for the
synthesis of various organic molecules.22,23 Conventional routes for
the preparation of nitrile compounds include the Sandmeyer
reaction,24 Rosenmund-von Braun reaction25 and transition-metal-
catalyzed cyanation.26 Besides, Nitriles can also be generated
27,28
through dehydrogenation of amines
or dehydration of primary
amides.29 Considering that primary amides and nitriles can be
converted into each other by hydrolysis or dehydration, if the two
compounds can be selectively synthesized by one reaction without
changing reaction conditions and adding any dehydrating agents, it
will be an effective methodology from an atom-economic point of
view. Recently, others and we reported some organic ligand-based
Ru clusters which exhibited good catalytic activities in several
homogenous organic transformation reactions.30-34 Out of our
interests in metal clusters and the aforementioned hypothesis, we
demonstrate here a mild and efficient method for the selective
oxygenation of primary amines to amides and nitriles with N,O-
aHebei Key Laboratory of Organic Functional Molecules, The College of Chemistry bidentate ligands supported Ru3 clusters (Scheme 1d).
and Material Science, Hebei Normal University, Shijiazhuang 050024, People’s
Republic of China. E-mail: haozhiqiang1001@163.com; linjin64@126.com
bAuckland Cancer Society Research Centre, Faculty of Medical and Health Sciences,
The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
†Electronic Supplementary Information (ESI) available. NMR spectra of all the
synthetic substrates, crystallographic data and refinements for complexes 1b and
2a-2b in CIF format or other electronic format see DOI:10.1039/x0xx00000x
‡ Both authors contributed equally to this work.
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a) Ammoxidation of alcohols to amides
previous work:
Scheme 2 Synthesis of ruthenium carbonyl complexes 1a
View Article Online
DOI: 10.1039/D0DT00045K
and 1b.
O
MnO2/GO/O2 (Hou's work)
I2/TBHP/K2CO3( Xie' work)
Thermal treatment of Ru3(CO)12 with Schiff bases L3H and
L4H in refluxing toluene for 9 h afforded the corresponding
ruthenium complexes (2-OC6H4-HC=N-C6H4R)2Ru3(CO)8 (R = 4-
OCH3C6H4, 2a; R = 4-BrC6H4, 2b) as orange powders (Scheme 3).
Both two complexes are air and moisture stable that have been
characterized by IR, NMR and single crystal X-ray diffraction. IR
spectra of them showed five peaks in the range of 1931-2049 cm-1,
+
NH3(aq.)
OH
R
NH2
NH2
O
R
b) Conversion of alcohols or aldehydes to amides via oximes
OH
O
R
R
O
[Ir(Cp*)Cl2]2 (Williams' work)
or
+ NH2OH.HCl
R
phenol based Ru (Bharathi' work)
1
which can be attributed to the C = O stretching vibrations. In their
c) Direct activation of C-H Bond of benzyl amine to amides
Ru(OH)X/Al2O3 or OMS-2 (Mizuno's works)
H NMR spectra, the singlets of HC=N at 7.76 ppm (for 2a) and 7.77
ppm (for 2b) were observed and the signals of -OH for the free
ligands (L3H and L4H) disappeared. 13C NMR spectra of 2a and 2b
confirmed that only terminal carbonyls exist in the complexes.
NR-MnOx/H2O (Xiao' work)
NH2
R
+ O2
NH2
R
RuHClCO(PPh3)3/base (Maiti' work)
CuBr/K2CO3/DMSO-H2O (Fu's work)
O
H
O
O
toluene
reflux, 9 h
N
N
Ru
N
R
+
3(CO)12
R
Ru
(CO)2
Ru
(CO)2
R
Ru
L3
L4
H
(CO)4
H -
This work: d) highly selective a-oxygenation of primary amines to nitriles or amides
O
2a
2b
)
R = OCH3
(
); R= Br (
Ru clusters/ base/ air
NH2
N
R
Scheme 3 Synthesis of ruthenium carbonyl complexes 2a and
2b.
NH2
R
Ru clusters/ base/ air
The molecular geometries of 1b, 2a and 2b fromX-ray
R
4 Å molecular sieve
diffraction analysis are depicted in Figs. 1-3. Their structural
parameters are listed in Table S2 (see ESI†). Complex 1b
crystallizes in monoclinic system with space group C2/c. In the solid
state, complex 1b features a trinuclear unit in the crystal lattice. The
distance between Ru(1) and Ru(1i) is 3.0496(8) Å, which is in
agreement with that of 1a (3.0406(6) Å)31 and the values found in
other pyridyl ethanol-based Ru clusters (3.030 Å–3.045 Å).34 The
two Ru-N bond lengths are 2.264(4) Å, slightly longer than that of
Scheme 1 Different routes for amides formation.
Results and discussion
Syntheses and characterization of ligands and complexes
Reactions of pyridyl alcohol ligands L1H and L2H with Ru3(CO)12
in refluxing xylene gave the Ru3 clusters (6-BrpyCHRO)2Ru3(CO)8
(R = 4-OCH3C6H4, 1a; R = 4-BrC6H4, 1b), respectively (Scheme 2).
Complex 1a has been reported previously to catalyze the oxidation
of alcohols30 Complex 1b was characterized by IR and NMR
spectroscopy. The IR spectrum of complex 1b is similar to that of
1a. Both of them have four strong peaks around 1913-2082 cm-1
assigned to the terminal C≡O bonds. In the 1 H NMR spectrum of
complex 1b, a sharp singlet at 5.52 ppm corresponds to their
methanetriyl proton (-CH-) and the resonance peaks of pyridyl and
phenyl protons appear in the region of 7.64-6.61 ppm. The 13C NMR
spectrum of 1b shows four signals (205.7-189.7 ppm) of the terminal
carbonyls.
2.164(3)
(C5H4N)(C9H5)}Ru3(CO)9.35 The distance of Ru(1i)-O(1i) is
2.080(3) , slightly shorter than the Ru(1)-O(1i) bond distance
Å
observed in trinuclear complex {μ2-η5:η1-
Å
(2.129(3)Å) and also shorter than the Ru-O bond distance (2.161(2)
Å-2.143 Å) found in the reported complex [Ru3(CO)8(µ,η5-
C63NO2(Py)(Ph)2)].36 Complexes 2a and 2b crystallize in the triclinic
system with space group P-1, which display an open triangular
cluster of Ru atoms coordinated by two deprotonated Schiff base
ligands, respectively. In each molecule, all the four ruthenium
carbonyl complexes are identified to have the same coordination
mode. The Ru-Nimino distances (2.218(3) Å and 2.196(4) Å for 2a,
2.189(3) Å and 2.171(3) Å for 2b, respectively) are comparable to
the Ru-Npy distances in 1a (2.258(4) Å and 2.240(4) Å) and 1b
(2.264(4) Å). The other structural features of 2a and 2b are similar.
1R2 R2
1
R
R
R1
xylene
reflux, 9 h
R2
N
N
Ru
+
3(CO)12
O
O
Br
N
Br
Br
Ru
Ru(CO)2
(CO)2
O
H
L1
L2
H
H -
Ru
(CO)
4
R1 = H, R2 = 4-OCH3C6H4
(
)
1a
R1 = H, R2 = 4-BrC6H4
(
1b
)
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DOI: 10.1039/D0DT00045K
Fig. 1 Perspective view of 1b (CCDC: 1559100) with thermal Fig. 3 Perspective view of 2b (CCDC: 1504156) with thermal
ellipsoids drawn at 30% probability level. Hydrogens have been ellipsoids drawn at 30% probability level. Hydrogens have been
omitted for clarity. The selected bond lengths (Å) and angles (°): omitted for clarity. The selected bond lengths (Å) and angles (°):
Ru(1)-O(1) 2.080(3), Ru(1)-O(1i) 2.129(3), Ru(1)-N(1) N(1)-Ru(1) 2.189(3), N(2)-Ru(2) 2.171(3), O(9)-Ru(1) 2.159(2),
2.264(4), Ru(1)-Ru(2) 2.7562(6), Ru(1)-Ru(1i) 3.0496(8), Ru(2)- O(9)-Ru(2) 2.106(2), O(10)-Ru(1) 2.111(2), Ru(1)-Ru(3)
Ru(1i) 2.7562(6), Ru(1)-O(1)-Ru(1i) 92.87(12), N(1)-Ru(1)- 2.7806(4), O(10)-Ru(1)-O(9) 75.70(9), C(33)-Ru(1)-N(1)
Ru(2) 156.35(10).
101.77(14), O(9)-Ru(1)-N(1) 88.72(10), O(10)-Ru(1)-Ru(3)
82.36(7), N(1)-Ru(1)-Ru(3) 167.12(8), Ru(3)-Ru(1)-Ru(2)
56.450(9).
Catalytic oxidation of primary amines to amides and nitriles
The direct α-oxygenation of amines is a useful method for producing
amides. Thus, the potential utility of these ruthenium culters
sevrving as catalysts for oxidation of amines were examined. We
commenced our study by treating benzylamine (3a) (1.0 mmol) in
various solvents (4.0 mL) and bases (1.0 equiv) at reflux in the
presence of 1b (3.0 mol%) under air to determine the most effective
solvent and base (see ESI†, Table S1). Among the different
combinations, t-BuOH/t-BuOK was found to be the best pair,
leading to a good yield of benzamide (4a) with a small amount of
benzonitrile (Run 7, Table S1). Notably, almost no imines or other
undesired compounds were detected by GC analysis. Then the
loading of catalyst and base was screened, and the results were
presented in Table 1. Varying the catalyst loading from 3.0 mol% to
0.5 mol%, the conversion and benzamide yield decreased slightly
first and then dropped dramatically (Table 1, runs 1-4). Since there
was no obvious difference in the yields of the desired product
between the reactions using 3.0 mol% and 2.0 mol% of 1b (Run 1 vs
Run 2, Table 1), 2.0 mol% was selected as the optimized loading.
When the amount of base was increased doubly, the yield of 4a
decreased slightly and more 5a formed (Run 5 vs Run 2, Table
1). Moreover, the yield dropped considerably (from 89% to
54%) when the amount of base was reduced to half equivalent
(Run 2 vs Run 6, Table 1). Thus, 1.0 equivalent of base was
selected for the following experiments. It is worth noting that the
base loading not only influenced the catalyst activity, but also had a
pronounced effect on the product selectivity. When the reaction
proceeded in the absence of either 1b or t-BuOK, a significantly
lower conversion and trace amount of benzamides was obtained
(Runs 7 and 8, Table 1), suggesting both the catalyst and base
play a crucial role in the reaction. Lowering the temperature to
70°C or 60 °C resulted in dropping the yield of 4a to 74% and
Fig. 2 Perspective view of 2a (CCDC: 1558722) with thermal
ellipsoids drawn at 30% probability level. Hydrogens have been
omitted for clarity. The selected bond lengths (Å) and angles (°):
Ru(1)-O(1) 2.144(3), Ru(2)-O(1) 2.194(3), Ru(1)-N(1) 2.218(3),
Ru(1)-Ru(3) 2.8350(5), Ru(2)-O(3) 2.144(3), Ru(2)-N(2)
2.196(4), Ru(2)-Ru(3) 2.8308(5), C(29)-Ru(1)-O(1) 98.55(17),
C(30)-Ru(1)-N(1)
85.55(12),O(1)-Ru(1)-O(3)
88.99(12).
101.31(17),
O(1)-Ru(1)-N(1)
N(1)-Ru(1)-O(3)
75.25(11),
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62%, respectively (Runs 9 and 10, Table 1). Finally, 10% of
5a and no 4a formed under N2 atmosphere, indicating O2 is
indispensable for the oxidation. (Run 11, Table 1).
View Article Online
DOI: 10.1039/D0DT00045K
O
NH2
N
NH2
cat., t-BuOK
+
Table 1 Optimizing conditions for the oxidation of
benzylamine catalyzed by 1ba
t-BuOH, air, reflux
3a
4a
5a
Yieldb (%)
O
Run
Catalyst
Base
Conv.b (%)
4a
87
77
92
84
5a
8
11
7
NH2
N
NH2
1b
cat. , t-BuOK
1
2
3
4
1a
1b
2a
2b
t-BuOK
t-BuOK
t-BuOK
t-BuOK
95
88
99
89
+
t-BuOH, air, refulx
3a
4a
5a
5
a Reaction conditions: benzylamine (1.0 mmol), cat. (2.0 mol%), t-
BuOK (1.0 mmol), t-BuOH (4.0 mL), t = 12 h. b Determined by GC.
Yieldb (%)
Catalyst
(mol%)
Base
(mmol)
Conv.b
(%)
Run
4a
5a
1
2
3
2
1
1
90
77
13
89
78
54
91
78
11
19
84
76
14
78
61
40
75
58
7
11
17
14
16
20
—
15
10
14
10
The impact of the reaction time on the oxidation rate was also
investigated (Fig. 4). Under the newly optimized condition, complex
2a/t-BuOH/t-BuOK system drove the conversion to completion in 8
h to give benzamide and benzonitrile. It should be noted that
benzonitrile was formed as the main product in the early stage of the
reaction (t = 3 h). With the extension of reaction time, the yield of
benzonitrile decreased sharply, whereas the yield of benzamide was
gradually increased up to 92% on the contrary. Further extending
reaction time hardly increased the yield of benzamide after 10 h.
Here, the optimum reaction time was determined to be 10 h.
3
1
1
4
0.5
2
1
5
2
6
2
0.5
1
7
—
2
8
—
1
trace
74
62
—
9c
10d
11e
2
2
1
2
1
a Reaction conditions: benzylamine (1.0 mmol), t-BuOH (4.0 mL),
b
c
T = 83 °C, t = 12 h. Determined by GC. T = 70 °C., d T =
60 °C.e N2 atmosphere.
Next, catalytic activities of the four Ru3 clusters were tested
under the optimized conditions, i.e. using 2.0 mol% of catalyst and
1.0 equivalent of t-BuOK in t-BuOH under air. The results are
summarized in Table 2. As shown, all the four Ru3 clusters could
promote the oxidation of benzylamine to benzamide in good to
excellent yield, among which 2a exhibited the highest catalytic
activity (92% yield of 4a. Run 3, Table 2). This may attribute to the
intrinsic higher electron density of salicylaldimine ligands compared
to pyridyl alcohol ligands (Runs 1-2 vs Runs 3-4, Table 2). The
Fig. 4 Time-dependent reaction profile of the catalytic oxidation of
benzylamine with catalyst 2a. Reaction condition: benzylamine (1.0
mmol), complex 2a (2.0 mol%), t-BuOK (1.0 mmol) and t-BuOH
complex bearing electron-donating -OMe group (2a) displays higher (4.0 mL), at 83 °C and under ambient air. Conversion and selectivity
catalytic activity than the complex containing -Br substituent (2b),
which suggests electronic properties of the para group also plays a
were determined by GC analysis.
role in the reaction.
Table 3 Oxidation of primary amines to the corresponding
Table 2 Comparison of the catalytic activities of various
ruthenium clusters for oxidation of benzylaminea
amides by complex 2aa
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O
NH2
DOI: O10.1039/D0DT00045K
2a
cat. , t-BuOK
Ar
NH2
t-BuOH, air, reflux
Ar
NH2
8
9
91
F
NH2
3a-3o
4a-4o
3i
4i
F
Yieldb
(%)
Run
Substrate
Product
O
NH2
NH2
83
O
3j
NH2
4j
F
NH2
H3C
F
1
94
91
3b
4b
H3C
O
NH2
NH2
O
10
11
78
F
NH2
3c
F
3k
NH2
4c
4k
2
CH3
O
CH3
NH2
NH2
O
84
NH2
4l
O
O
NH2
CH3
3l
NH2
CH3
3
4
5
83
95
93
O
3d
4d
N
12
13c
14
88
<5
9
NH2
N
O
4m
NH2
3m
NH2
MeO
O
H3CO
4e
3e
NH2
3
NH2
NH2
3
4n
3n
O
NH2
NH2
O
N
H
4f
3f
3o
3a
4a
O
NH2
O
NH2
NH2
6
7
90
86
Cl
15d
83
NH2
Cl
3g
4g
4a
O
NH2
a
Reaction conditions: substrate (1.0 mmol), 2a (2.0 mol%), t-
NH2
F3C
BuOK (1.0 mmol), t-BuOH (4.0 mL), t = 10 h. b Isolated yield.
c
Determined by GC. d Benzylamine (1.0 g, 9.33 mmol)
F3C
3h
4h
Based on these findings above, we subsequently examined the
substrate scope and generality for α-oxygenation using complex 2a
as catalyst. As shown in Table 3, various aromatic primary amines
containing electron-donating or electron-withdrawing substitutes at
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different positions can be oxygenated efficiently to produce
corresponding amides in high to excellent yields (78%-95%, Runs 1-
12). The benzylamines carrying an ortho-substituent (Runs 3 and 10)
showed relatively lower activities than those meta- or para-
substituted analogues (Runs 1, 2, 8 and 9) possibly due to the higher
steric hindrance of ortho-substituents. Benzylamines substituted with
electron-donating group (e.g. Me and OMe) showed a slightly higher
yields than benzylamines bearing electron-withdrawing group (e.g.
CF3 and F). These results indicated that the present catalytic system
showed good functional-group compatibility but was sensitive to
steric hindrance to some extent. Heteroatom-containing amines also
reacted smoothly to afford the corresponding amides in high yields
(84-88%, Runs 11 and 12). However, primary aliphatic amine 3n
and secondary amine 3o were found to be unsuitable substrates and
were hardly oxidized to their corresponding amides under standard
conditions (Runs 13 and 14). Strikingly, the typical reaction (Run 1)
was scaled up and worked well (83% yield, Run 15), highlighting
the synthetic utility and practicality of the present catalytic system.
View Article Online
CN
NH2
DOI: 10.1039/D0DT00045K
6
87
3e
5e
NH2
CN
Cl
F
7
8
79
Cl
F
3f
5f
CN
NH2
77
3g
5g
CN
NH2
9
72
5h
3h
Table 4 Transformation of primary amines to nitriles
catalyzed by complex 2a a
F
F
CN
NH2
NH2
10
75
O
2a
cat. , t-BuOK,t-BuOH
O
Ar
NH2
3a-3j
Ar
N
3i
5i
air, reflux, 4Å MS
5a-5j
CN
Yieldb
(%)
Run
Substrate
Product
N
11
N
77
CN
NH2
NH2
3j
5j
1c
78
90
a
Reaction conditions: substrate (1.0 mmol), 2a (2.0 mol%), t-
BuOK (1.0 mmol), t-BuOH (4.0 mL), 4 Å mol. sieves, t = 8 h.
b
3a
5a
Isolated yield. c T = 10 h.
CN
Lastly, the optimized reaction was applied to the preparation of
nitriles (Table 4). Benzonitrile (5a) was obtained in good yield from
benzylamine (3a) in the presence of 4Å molecular sieves after 10 h
(78%, Run 1, Table 4). In the absence of molecular sieves, under the
similar reaction condition, (Run1 in Table 4vs Run 2 in Table 1).
The observation supports the role of MS is to absorb water and
prevent further hydrolysis of nitriles. Given that long reaction time
was preferred to transform nitriles to amides based on kinetic study
(Fig. 4), the reaction for 8 h was attempted for the oxidation of 3a
and 90% yield of 5a was observed (Run 2, Table 4), which is more
efficient than the reactions catalyzed by Ru and Fe carbonyl
complexes reported in the lateratures.32,37-38 To explore the scope
further, various substituted benzylamines and heteroarylamines were
studied, resulting in the corresponding nitrile derivatives in good
isolated yields (Runs 3-11, Table 4).
2
3a
5a
CN
NH2
H3C
3
4
5
85
84
80
H3C
3b
5b
CN
NH2
3c
5c
CH3
CH3
CN
NH2
MeO
MeO
3d
5d
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O
Conclusion
View Article Online
N
In summary, a series of Ru clusters ligaDteOdI: 1w0i.1th039N/D,O0-DbTid00en0t4a5tKe
ligands have been synthesized and well characterized. All the
ruthenium complexes have served as highly active homogeneous
catalysts for the synthesis of nitriles and amides by oxygenation of
primary amines with environmentally friendly oxygen (air) as
oxidant. The present protocol endows the catalytic system with great
flexibility in the selective synthesis of amide or nitrile from the same
reactants by adding 4Å molecular sieves or not, which can avoid the
utilization of dehydrating agents that, in many cases, generates large
amounts of harmful by-products. We believe the method developed
herein is attractive for the preparation of a diverse range of nitrile
and amide derivatives using readily available staring materials under
mild conditions.
NH2
calalyst-free, t-BuOK (1.0 equiv.)
H O
a
b
t-BuOH,
(2.5 equiv.), reflux, air, 10 h
2
94% yield
O
1.0 mmol
2a
cat. (2.0 mol%), t-BuOK(1.0 equiv.)
NH2
NH2
TEMPO
t-BuOH,
(0.4 equiv.),reflux, air,10 h
1.0 mmol
85% yield
Scheme 4 Control experiments for the mechanism study
Proposed Mechanism
It was demonstrated that benzonitrile is formed as an intermediate at
the beginning of the reaction (Fig.4). The 4 Å MS plays a key role in
the product selectivity (Table 4), which indicates that water is
formed during the reaction and then hydrolyzes benzonitrile to give
benzamide in the presence of base. The catalyst-free experiment
(Scheme 4a) provided evidence for the formation of nitrile as an
intermediate. Another control experiment(Scheme 4b) showed that
when the reaction was carried out in the presence of TEMPO, the
yield of benzamide was almost not affected by the radical trapping
agent. This observation proved no radical species is formed during
the catalytic pathway. Based on the above experimental results and
literature reports, a plausible reaction mechanism is proposed in
Scheme 5. Ruthenium complex (I) reacts with O2 (air) to form a oxo-
ruthenium (Ru=O) species (II), which is then reduced by t-BuOH to
give a ruthenium-hydroxyl complex (III). The reaction of amine
substrate with III occurs to furnish ruthenium-amido complex IV,
which undergoes β-hydride elimination to give Ru-H species V and
imine intermediate. Subsequently, the Ru-H species V is oxidized by
oxygen to produce an oxo-ruthenium hydride VI, which further
regenates III in the presence of t-BuOK to finish the catalytic cycle.
The formed imines undergoes oxidation to give nitriles and two
molecules of water. Finally, the hydration of these nitriles occurs to
Experimental section
General considerations
The syntheses of metal complexes were performed under a nitrogen
atmosphere using standard vacuum lines and Schlenk techniques.
Chemicals obtained from commercial suppliers were of reagent
grade and used without further purification. All solvents such as
toluene, xylene, THF, dioxane, tert-butanol, dichloromethane and n-
hexane were dried by the general methods. FT-IR spectra were
recorded as potassium bromide pellets using a Thermo Fisher iS50
spectrometer in the range 4000 to 400 cm-1, and elemental analyses
were performed using a Vario EL III analyzer. NMR spectra were
recorded in CDCl3 and DMSO-d6 at room temperature on Bruker
Avance 500 and 400 MHz NMR spectrometers. NMR chemical
shifts in ppm indicate downfield shift relative to tetra-methylsilane
(δ 0.00 ppm) and were referenced relative to the signal of the solvent
(1 H: CDCl3 7.26 ppm, DMSO-d6 2.50 ppm; 13 C: CDCl3 77.16 ppm,
DMSO-d6 39.52 ppm). Ru3(CO)12 was synthesized by the reaction of
RuCl3·xH2O with CO according to the literature.39 Ligands L1H-L4H
have been reported in literatures.40-41
deliver the amides under basic condition.
Synthesis of Complex 1b
In a 50 mL Schlenk flask were placed L2H (0.202 g, 0.938
mmol), Ru3(CO)12 (0.300 g, 0.469 mmol) and xylene (20 mL). The
mixture was heated at reflux for 9 h under an N2 atmosphere. After
the mixture was cooled to room temperature, the solvent was
removed in vacuo. The residue was chromatographed on an Al2O3
column (eluent ethyl acetate/petroleum ether: 1:3, v/v), and then
recrystallized from CH2Cl2/hexane to give 1b (0.305 g, 68%) as
orange crystals. Anal. Calc. for C32H16Br4N2O10Ru3: C, 31.73; H,
O
O
O
O
I
N
N
Ar
N
N
Ar
Ar
Ru(CO)2
Ar
(CO)2Ru
O2
Ru(CO)2
(CO)2Ru
Ru
(CO)4
II
Ru(CO)4
O
O
t-BuOH
t-BuO
NH2
2
O
R
O
N
N
Ar
Ar
tBuOH
Ru(CO)2
(CO)2 Ru
O
2 H2
Ru
(CO)4
HO
OH
1
tBuO
1.33; N, 2.31. Found (%): C, 31.85; H, 1.47; N, 2.45. H NMR
III
(CDCl3, 500 MHz, 298 K): δ 7.64 (d, J = 7.7 Hz, 2H, Py-H), 7.43 (d,
J = 8.4 Hz, 4H, Ar-H), 7.32 (t, J = 7.7 Hz, 2H, Py-H), 7.02 (d, J =
8.4 Hz, 4H, Ar-H), 6.61 (d, J = 7.6 Hz, 2H, Py-H), 5.52 (s, 2H, CH)
ppm. 13C NMR (CDCl3, 125 MHz, 298 K): δ 205.7, 202.8, 200.9,
189.7, 170.0, 144.9, 142.3, 138.3, 132.0, 129.6, 128.7, 122.4, 119.9,
90.9 ppm. IR (υCO, KBr, cm-1): 2082(s), 2013(s), 1968(s), 1913(s).
Synthesis of Complex 2a
O
O
N
N
O
O
Ar
Ar
N
N
(CO)
Ru(CO)2
2 Ru
Ar
Ar
(CO)2 Ru
Ru(CO)2
Ru
(CO)4
NH
HN
R
H
R
Ru
(CO)4
O
H
O
H
H
H
H
VI
IV
-H elimination
2 RCH=NH
O
t-BuO
H2O
Ru /O2/t-BuOK
2 RC
N
R
NH2
O
O
O2
N
N
Ar
Ar
H2O
Ru(CO)2
(CO)2 Ru
In a fashion similar to that for the synthesis of 1b, complex 2a
was synthesized by the reaction of L3H (0.213 g, 0.938 mmol) with
Ru3(CO)12 (0.300 g, 0.469 mmol) in 20 mL of toluene. Complex 2a
was obtained as orange crystals (0.213 g, 45%). Anal. Calc. for
Ru
H
H
(CO)4
V
Scheme 5 Possible mechanism for the formation of nitriles and
amides.
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C36H24N2O12Ru3: C, 44.13; H, 2.47; N, 2.86. Found (%): C, 44.36; H,
2.61; N, 2.67. H NMR (500 MHz, CDCl3, 298K): δ 7.76 (s, 2H, Conflicts of interest
View Article Online
DOI: 10.1039/D0DT00045K
1
N=(CH)), 7.09–7.13 (m, 4H, Ar-H), 6.82 (t, J = 7.4 Hz, 2H, Ar-H), There are no conflicts of interest to declare.
6.70–6.73 (m, 6H, Ar-H), 6.42 (d, J = 8.7 Hz, 4H, Ar-H), 3.83 (s, 6H,
OCH3) ppm. 13C NMR (125 MHz, CDCl3, 298K): δ 205.4, 204.2, Acknowledgements
202.9, 192.9, 165.1, 162.7, 158.3, 149.8, 136.1, 135.7, 123.6, 123.3, The authors gratefully acknowledge the financial supports from the
122.4, 119.0, 113.7, 55.7 ppm. IR (υCO, KBr, cm-1): 2076 (m), 2026 Hebei Natural Science Foundation of China (Nos. B2017205006 and
(s), 1997 (s), 1942 (m), 1915 (m).
Synthesis of Complex 2b
B2019205087), the Education Department Foundation of Hebei
Province (Nos. ZD2018005 and QN2019036), and the Science
In a fashion similar to that for the synthesis of 1b, complex 2b Foundation of Hebei Normal University (Nos. L2017Z02 and
was synthesized by the reaction of L4H (0.258 g, 0.938 mmol) with L2018B08).
Ru3(CO)12 (0.300 g, 0.469 mmol) in 20 mL of toluene. Complex 2b
was obtained as orange crystals (0.310 g, 60%). Anal. Calc. for
Notes and references
C34H18Br2N2O10Ru3: C, 37.90; H, 1.68; N, 2.60. Found (%): C, 37.71;
H, 1.80; N, 2.78. 1H NMR (500 MHz, CDCl3, 298K): δ 7.77 (s, 2H,
1
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amides
In a 10 mL of round-bottom flask, a mixture of an amine substrate
(1.0 mmol), ruthenium catalyst (0.02 mmol) and t-BuOK (1.0 mmol)
in t-BuOH (4.0 mL) was refluxed for 10 h under air. The reaction
was monitored by GC. After the reaction was completed, the mixture
was cooled to room temperature and condensed under reduced
pressure. The residue was subject to purification by silica gel flash
column chromatography using ethyl acetate/petroleum ether (v:v =
1:1) to afford the corresponding amide, which was then identified by
NMR analyses.
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nitriles
In a 10 mL of round-bottom flask, a mixture of an amine
substrate (1.0 mmol), ruthenium catalyst (0.02 mmol), t-BuOK
(1.0 mmol), t-BuOH (4.0 mL) and 4Å molecular sieves (2.0 g)
was refluxed with stirring for 8 h under air. After the reaction
was completed, the mixture was cooled down to room
temperature and condensed under reduced pressure. The residue
was purified by column chromatography using ethyl
acetate/petroleum ether (v:v
= 1:5~10) to afford the
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Crystal structure determination
Good-quality crystals of the ruthenium complexes 1b, 2a and 2b
suitable for single-crystal X-ray diffraction analysis were obtained
from the slow evaporation of a hexane/CH2Cl2 solution. X-ray
crystallographic data were collected on a Bruker AXS SMART 1000
CCD diffractometer, using graphite monochromated Mo Kα
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DOI: 10.1039/D0DT00045K
Table of content
An efficient method for direct oxygenation of primary arylamine to nitriles and
amides with switchable selectivity was developed using N,O-bidentate Ru3 clusters as
catalysts.
t-BuOH/t-BuOK/air
O
NH2
R
NH2
NH2
Ar
air- and moisture-stable
good to excellent yields
selective synthesis
O
O
or
N
N
Ar
Ru(CO)2
(CO)
Ar
(CO)2Ru
(Het)Ar
Ru
N
4
R
t-BuOH/t-BuOK/air/4Å MS