An attractive route to transamidation catalysis: Facile synthesis of new o-aryloxide-N-heterocyclic carbene ruthenium(II) complexes containing trans triphenylphosphine donors

Article abstract of DOI:10.1016/j.molcata.2015.03.015

Well-defined robust ruthenium(II) complexes 3a-d bearing o-aryloxide-N-heterocyclic carbene ligands with different wingtip substituents (3a (R = Me), 3b (R = Ph), 3c (R = ⁱPr) and 3d (R = Mes)) in the imidazole ring were synthesized in good yields by the reaction of imidazolium proligands with metal precursor [RuHCl(CO)(PPh₃)₃] by transmetallation from the corresponding silver carbene complexes. All the Ru(II)-NHC complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. The molecular structure of the complex 3a was identified by means of single-crystal X-ray diffraction analysis, which revealed that the complexes possess a distorted octahedral geometry. In order to explore the catalytic potential of the synthesized complexes, all the four [Ru-NHC] complexes [3a-d] were tested as catalysts for transamidation of carboxamides with amines. Notably, the complex 3a was found to be very efficient and versatile catalyst toward transamidation of a wide range of amides with amines.

Full text of DOI:10.1016/j.molcata.2015.03.015

Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
An attractive route to transamidation catalysis: Facile synthesis of
new o-aryloxide-N-heterocyclic carbene ruthenium(II) complexes
containing trans triphenylphosphine donors
Muthukumaran Nirmalaa, Govindan Prakasha, Periasamy Viswanathamurthia,∗
,
Jan Grzegorz Maleckib
a Department of Chemistry, Periyar University, Salem 636 011, India
b Department of Crystallography, Silesian University, Szkolna 9, 40-006 Katowice, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Well-defined robust ruthenium(II) complexes 3a–d bearing o-aryloxide-N-heterocyclic carbene ligands
with different wingtip substituents (3a (R = Me), 3b (R = Ph), 3c (R = iPr) and 3d (R = Mes)) in the imi-
dazole ring were synthesized in good yields by the reaction of imidazolium proligands with metal
precursor [RuHCl(CO)(PPh3)3] by transmetallation from the corresponding silver carbene complexes.
All the Ru(II)–NHC complexes have been characterized by elemental analyses, spectroscopic methods
as well as ESI mass spectrometry. The molecular structure of the complex 3a was identified by means
of single-crystal X-ray diffraction analysis, which revealed that the complexes possess a distorted octa-
hedral geometry. In order to explore the catalytic potential of the synthesized complexes, all the four
[Ru–NHC] complexes [3a–d] were tested as catalysts for transamidation of carboxamides with amines.
Notably, the complex 3a was found to be very efficient and versatile catalyst toward transamidation of a
wide range of amides with amines.
Received 21 January 2015
Received in revised form 2 March 2015
Accepted 22 March 2015
Available online 26 March 2015
Keywords:
Imidazolium proligands
[Ru–NHC] complexes
X-ray diffraction
Transmetallation
Transamidation
© 2015 Elsevier B.V. All rights reserved.
1. Introduction
the catalysts have the difficulties in separation from the reaction
mass and recycling, making their environmental profile unfavor-
The amide functionality is one of the most fundamental chem-
ical building blocks found in nature. It is essential to sustain
life, making up the peptide bonds in proteins such as enzymes,
and it is also one of the most prolific moieties in pharmaceu-
tical molecules, agrochemicals and natural products (Scheme 1)
[1]. The most popular and common methods for the generation of
amides involve the reaction of activated carboxylic acid derivatives,
such as chlorides, anhydrides or esters, with amines [2,3]. Alterna-
tive strategies toward the synthesis of amides are the Staudinger
reaction [4], Schmidt reaction [5], Beckmann rearrangement [6],
aminocarbonylation of haloarenes [7], alkenes [8] and alkynes [9],
oxidative amidation of aldehydes [10], hydrative amide synthe-
sis with alkynes [11] and amidation of thio acids with azides [12].
All of these methods have their own advantages, nonetheless they
suffer from certain demerits, such as stoichiometric amount of ami-
dation reagents, harsh reaction conditions, long reaction times,
low selectivities, limited substrate scopes etc. Moreover, some of
able. Therefore, there is a clear need for the synthesis of amides
with more efficient, under neutral conditions and without the gen-
eration of waste, which is a challenging goal [13].
In the search of more atom-economical and cost-effective proto-
cols for amide synthesis, metal-catalyzed organic transformations
have been emerged in the last years as attractive alternatives, offer-
ing the possibility to develop previously unavailable routes starting
from substrates other than carboxylic acids and their derivatives
[14]. Since then, a wide range of catalytic systems based on dif-
ferent transition metals have been described as catalysts for the
construction of amide bonds. Among them, ruthenium playing a
predominant role [14][14g]. For the aforementioned cases, most of
the reported catalysts bear ligands containing phosphine coordi-
nating arms usually exhibit much higher catalytic activity due to
the steric (bulkiness) and electronic effects (basicity) of the ligand
[15]. Our own research group has also succeeded in applying the
ruthenium(II) complexes as catalysts for amide synthesis [16].
Alternatively, transamidation is an attractive tool and repre-
sents one of the most convenient and straightforward methods
for the synthesis of secondary or tertiary amides through tan-
dem processes. Transamidation is a distinct biochemical activity
∗
Corresponding author. Tel.: +91 944 3775719; fax: +91 427 2345124.
E-mail address: viswanathamurthi72@gmail.com (P. Viswanathamurthi).
http://dx.doi.org/10.1016/j.molcata.2015.03.015
1381-1169/© 2015 Elsevier B.V. All rights reserved.

16
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
OH OH
Cl
H
N
O
O
HN
Cl
N2O
Chloramphenicol (1.3)
O
NH
Methylprylon (1.2)
HO
O
Paracetamol (1.1)
O
O
P
O
N
O
O
O
O
N
HO
OH
P
O
O
N
HO
OH
O
N
O
Bezipram (1.4)
N
H2N
NADH (1.5)
O
OH
O
O
O
O
O
HN
O
O
N
H
N
N
N
Bn
O
Palau'amide (1.6)
Scheme 1. Amide function in drug molecules [1.1–1[1.1–1.3], agrochemicals [1.4], biological molecules [1.5] and natural products [1.6].
[17] associated with several neurodegenerative disorders such
as Alzheimer’s and Hungtinton’s disease [18]. Recent catalysts
explored for transamidation include L-proline, cerium, hydroxy-
lamine hydrochloride, ammonium bromide, and boric acid [19].
There are many reports are available regarding the application of
transition metal complexes as catalysts for transamidation reac-
tions [20]. All of the reported catalysts have some drawbacks; they
require long reaction times and elevated temperature profile of the
reaction.
Recently, a great deal of research efforts have been devoted to
the study of transition metal complexes with anion-tethered NHC
ligands [21]. Especially, the o-hydroxyaryl-substituted NHC lig-
ands have potential applications in catalysis and hence their metal
complexes have been widely investigated by the researchers as
catalysts in various important organic transformations [22]. Their
distinctive stereo-electronic features, such as strong metal CNHC
bonding, electronic/steric tunability via the wingtips and admirable
stability of the metal–NHC complexes toward heat, air and mois-
ture are considered as the keys for the success of this versatile class
of ligands. The catalytic activity of the ruthenium complexes con-
taining various N-heterocyclic carbene ligands in amide synthesis
has been documented as well [23].
Based on the above facts, and continuation of our research on
the synthesis, characterization and catalytic applications of transi-
tion metal based N-heterocyclic carbenes [24], we here in describe
new ruthenium(II) complexes bearing o-aryloxide N-heterocyclic
carbene (NHC) ligands with different wingtip substituents in the
imidazole ring with chloride and triphenylphosphine as ancillary
ligands. It was naturally obvious that the NHC and the phosphorus
ligands have different ␴-donating or ␲-back bonding properties.
This cooperation has been tuned to increase the efficiency of the
metal center [25]. Considering the economic attractiveness and
excellent functional group tolerance of ruthenium in homoge-
nous catalysis, we became interested in developing a general
transamidation methodology of carboxamides with amines. To the
best of our knowledge, [Ru–NHC] catalyzed transamidation reac-
tion has not yet been reported. Herein, we describe our results for
the first time.
2. Results and discussion
The ruthenation was accomplished by metalation with Ag2O
to form intermediate silver carbene complexes and subsequent
transmetallation with [RuHCl(CO)(PPh3)3] indeed, as summarized
in Scheme 3
2.1. Synthetic plan
This paper is primarily focused on the carbenes derived from
five-membered heterocycles in which the carbene center is flanked
by two nitrogen atoms. Carbene center at the 2-position of the
imidazole ring would be stable due to electron-donating effects of
adjacent nitrogen atoms that provided a conceptual framework for
the development of chemistry of these species. The choice is based
on the stability and versatility of these species relative to that of the
carbenes derived from other nitrogen heterocycles. The synthetic
plan to reach the novel ruthenium complexes disclosed herein was
initially attempted by deprotonation of imidazolium salts with a
strong base (KOtBu or KHMDS) in THF followed by the addition
of metal precursor, but the products were not obtained quantita-
tively. Hence, the most widely used method of deprotonation by the
use of silver base has been used in the syntheses of N-heterocylic
carbene complexes. Among the various silver bases, Ag2O is most
commonly used as a metal base [26]. Treatment with Ag2O which
act as both base and halide scavenger, under light-free conditions
in CH2Cl2 at room temperature formed the silver carbene com-
plexes. This method is the direct path for the preparation of the
Ru-complexes involving a transmetallation step using the corre-

M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
17
sponding NHC–silver(I) complex of the bidentate ligands [1a–d].
Earlier, this approach has been successfully utilized for a wide vari-
ety of transition metals and proved to be a convenient method over
other methods under certain conditions [22,26][22i,26].
complexes are in good agreement with the proposed molecular
formulae.
2.3. Spectroscopic description
Chelation of the potentially bidentate carbene ligands [1a–d]
was surmised from spectroscopic measurements in solid and
solution. Carbonyl stretching frequencies provide useful compar-
ison of the relative electron-donating abilities of the different
ligands. The new [Ru–NHC] complexes [3a–d] showed a ␯CO
stretch in the IR spectrum at ∼1939 cm−1, indicating considerable
back bonding present in this ligand. The imidazolium structures
were confirmed by the characteristic bands of 1572–1561 cm−1
2.2. Synthetic strategy
o-hydroxyaryl imidazolium pro-ligands [1a–d] were selected
as potential ligand platforms of different wingtip substituents
on imidazole ring, and were synthesized according to known
methods [27], by the reaction of 4-bromo-2,4,6-tri-tert-butyl-2,5-
cyclohexadiene-1-one with different N-substituted imidazoles in
about 40% yields (Scheme 2. The NHC–silver complex was prepared
by the reaction of 1a–d with Ag2O under light free condition at
room temperature [28]. The obtained silver complexes are highly
air and moisture stable, and soluble in CH2Cl2, CHCl3, CH3CN,
DMSO and insoluble in diethyl ether. The NHC–silver complexes
are light-sensitive to solution, but light-stable in solid form. The
disappearance of 1H NMR signal of the imidazolium ring (NCHN)
along with the appearance of a diagnostic silver–bound carbene
(NCN–Ag) peak at ∼176 ppm in the 13C NMR spectra are the
characteristic features of the silver carbene complexes [2a–d].
These values are comparable with previously reported Ag–NHC
complexes [22,22,28][22c,22h,28]. The Ag–NHC complexes reacted
with [RuHCl(CO)(PPh3)3] in CH2Cl2 under dark condition and
the reaction mixture was allowed to stir for 24 h at room tem-
perature. The ruthenium complexes [3a–d] were isolated upon
precipitation with diethyl ether as brown powder in >90% yield
and they are extremely soluble in CH2Cl2, CHCl3, THF and DMSO.
However, they are sparsely soluble in CH3CN, but hardly insol-
uble in Et2O, hexane and pentane. In fact, they were isolated
by precipitation from the reaction mixture using Et2O during
the course of their synthesis. All the complexes [3a–d] were
fully characterized by 1H, 13C & 31P NMR, mass spectra and ele-
mental analyses. The analytical data (C, H, N) of the [Ru–NHC]
(N
C
N) and 1617–1610 cm−1 (C C) stretching. The bands located
at 1459–1453 cm−1 correspond to C O stretching mode.
The 1H NMR spectra of the complexes [3a–d] showed the sig-
nals in the expected region (Figs. S1–S4, ESI†). The generation of
free carbene and subsequent formation of the [Ru–NHC] com-
plexes were unambiguously confirmed by the absence of the 1H
NMR resonances of imidazolium (NCHN) and phenolic (C OH)
protons. The imidazolium ring backbone signals appeared around
7.43–6.69 ppm. Furthermore, the spectra of all the complexes
showed a series of signals for aromatic protons at 7.87–7.18 ppm. In
addition, a singlet appeared around 3.10–2.22 ppm for complexes
3a, 3c and 3d corresponding to terminal CH3 group protons. The
spectra of the complexes showed a singlet at 1.44–0.84 ppm, which
has been assigned to tBu protons.
The 13C NMR spectra showed the expected signals in the
appropriate region (Figs. S5–S8, ESI†). The ruthenium complexes
showed their carbenic carbon resonances at ca. 184.20–180.79 ppm
(Ru–Ccarbene), characteristic of the carbenic carbon bound to ruthe-
nium. Normally, Ru–Ccarbene resonances of Ru–NHC complexes are
found in the wide range of 171–197 ppm [29]. It is worth of noting
that only one singlet was observed for the carbene carbon in the
13C NMR spectra of these complexes. The C O carbon resonating
at 206.47–200.51 ppm is comparable with earlier observations. The
Br
N
R
OH
N
tBu
OH
O
tBu
tBu
tBu
tBu
N
N R
Br2
OP(OMe3)
1
tBu
Ethylene Glycol, 135oC
tBu
R = Me (1a)
R = Ph (1b)
Br
tBu
i
R = Pr (1c)
R = Mes (1d)
Scheme 2. General preparation of o-hydroxyaryl imidazolium ligands [1a–d].
Cl
CO
Ph3P
Ru
Br
N
PPh3
R
O
OH
N
R
tBu
tBu
N
[RuHCl(CO)(PPh3)3]
DCM, 24 h, rt
Ag2O
N
Ag-NHC
DCM, 24 h, rt
1
(2a-d)
tBu
3
tBu
R = Me (1a)
R = Me (3a)
R = Ph (3b)
R = iPr (3c)
R = Mes (3d)
R = Ph (1b)
i
R = Pr (1c)
R = Mes (1d)
Scheme 3. General synthesis of [Ru–NHC] complexes [3a–d].

18
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
shows that the C/O-functionalized NHC ligand 1a coordinates to the
ruthenium center through the carbenoid-C and the aryloxygen-O
donors with Ru(1) C(2) and Ru(1) O(2) bond lengths measur-
ing 2.012(4) and 2.095(3) Å, respectively, to form a six-membered
chelate ring with a bite angle of 85.03(14)◦. The coordination geom-
etry around the Ru(II) ion is slightly distorted octahedron where
the basal plane is constructed of a carbene and oxygen atom of the
ligand in a uni-negative bidentate CO fashion and one molecule
of CO and one molecule of chloride. A pair of triphenylphosphine
ligands completes the apical coordination. Though the PPh3 lig-
ands usually prefer to occupy mutually cis positions for better
␲-interaction, in this complex the presence of CO, a stronger ␲-
acidic ligand, might have forced the bulky PPh3 ligands to take
up mutually trans positions for steric reasons. The bond distances
are 1.820(5) (Ru(1) C(1)), 2.4549(11) (Ru(1) Cl(1)), 2.3966(12)
(Ru(1) P(1)) and 2.4045(13) Å (Ru(1) P(2)) within the expected
range. The chlorido ligand was trans to the carbene ligand and
the Ru Cl bond lengths being essentially identical to the six-
coordinate cases (∼2.452 Å). The CO group occupies the site trans to
the aryloxygen (C(2) Ru(1) P(2) = 94.38(12)). This may be a conse-
quence of strong RuII → CO back donation as indicated by the short
Ru(1) C(1) [1.820(5) Å] bond and the low CO stretching frequency
(∼1939 cm−1), which prefers ␴ or ␲ weak donor groups occupying
the site opposite to CO to favor the d → ␲ back donation. The bond-
ing parameters around the ruthenium center confirm a slightly
distorted octahedral geometry and are in a comparable range to
those of the closely related ruthenium complexes in the literature
[30]. The results confirmed that the C/O functionalized NHC lig-
and, Cl and CO as well as the phosphine ligand remain intact at the
ruthenium center in 3a. The tert-butyl group on the o-aryloxy NHC
ligand is slightly distorted away from the metal center as a result
of steric repulsion. We tried to grow single crystals in different
solvents such as acetonitrile, chloroform, methanol, dimethyl sul-
foxide, and dimethylformamide of complexes 3b–d, unfortunately
we have not yet obtained high-quality crystals suitable for X-ray
single-crystal diffraction, suggesting that subtle structural factors
are critical to stabilizing this species. But the similarity in their spec-
troscopic characteristics suggests that 3a is a good structural model
for all other three complexes.
Fig. 1. ORTEP representation of the X-ray crystal structure of 3a (R = Me). The solvent
molecule of crystallization and hydrogen atoms has been omitted for clarity. Ther-
mal ellipsoids are shown at 30% probability. Selected bond lengths (Å) and angles
(deg) with standard uncertainties given in parentheses: Ru(1) C(1) = 1.820(5),
Ru(1) C(2) = 2.012(4),
Ru(1) O(2) = 2.095(3),
Ru(1) P(1) = 2.3966(12),
Ru(1) P(2) = 2.4045(13), Ru(1) Cl(1) = 2.4549(11), C(1) Ru(1) C(2) = 94.11(18),
C(1) Ru(1) O(2) = 174.96(15),
C(1) Ru(1) P(1) = 87.15(13),
O(2) Ru(1) P(1) = 97.83(8),
C(2) Ru(1) P(2) = 94.38(12),
P(1) Ru(1) P(2) = 174.29(13),
C(2) Ru(1) Cl(1) = 169.70(12),
C(2) Ru(1) O(2) = 85.03(14),
C(2) Ru(1) P(1) = 91.33(12),
C(1) Ru(1) P(2) = 92.14(14),
O(2) Ru(1) P(2) = 82.98(8),
C(1) Ru(1) Cl(1) = 95.60(14),
O(2) Ru(1) Cl(1) = 85.59(8),
P(1) Ru(1) Cl(1) = 85.75(5), P(2) Ru(1) Cl(1) = 88.68(5).
presence of peak in the region ∼158.21 ppm has been assigned to
aryloxy carbon. The signal observed at 143.77–104.29 ppm in the
spectra of complexes is due to aromatic carbons. The presence of
chemical shifts in the range of 39.34–27.42 ppm belonged to the
methyl protons.
To the best of our knowledge, the scaffold of Ru–NHC containing
salicylaldimine framework is still meager. Accounting this fact, we
present the synthesis of complexes containing both NHC and phos-
phine moieties and their applications in transamidation catalysis
in this article.
31P NMR spectra of the complexes were recorded to confirm
the presence of triphenylphosphine groups coordinated to ruthe-
nium center and to determine the geometry of the complexes (Figs.
S9–S12, ESI†). All the complexes [3a–d] exhibited only one signal
at 29.13–24.35 ppm, consistent with the presence of two triph-
enylphosphine ligands, which were trans to each other. ESI-mass
spectra of the complexes [3a–d] generally showed the molecular
ion peak with the loss of a chloride ion [M–Cl]+(Figs. S13–S15, ESI†).
3. Catalytic studies
3.1. Catalytic transamidation of carboxamides with amines
2.4. X-ray crystal structure description of complex 3a
There are numerous reports have demonstrated that ruthenium
complexes are good catalysts for the synthesis of amides [31]. It
has also been established that the introduction of NHC ligand to
the metal center would enhance the catalytic activity. Thus, with
the new carbene complexes in hand, their abilities to catalyze
transamidation of carboxamides with amines were studied. In prin-
ciple, the transamidation of primary amides should be synthetically
useful because it can provide a route to higher amides through
expulsion of a molecule of ammonia. Thanks to its low boiling point,
this can readily be removed from the reaction, providing secondary
or tertiary amides efficiently.
Even though the analytical and spectral data gave some idea
about the molecular formulae of the complexes, they do not indi-
cate the exact coordination of carbene–aryloxygen units in them.
To gain additional insight into the coordination chemistry and the
structural parameters of the complexes, single crystals of one of
the complexes [3a] were grown by slow evaporation of the con-
centrated dichloromethane solution of the respective complex into
Et2O and characterized by X-ray diffraction analysis. The crystal-
lographic and refinement data for the complex 3a are collated in
Table S1 (provided as Supporting information (ESI†)). ORTEP dia-
gram of the complex 3a is displayed in Fig. 1 along with selected
bond angles and inter atomic distances. Packing arrangement of
the molecules in the unit cell is shown in supporting information
(Fig. S16, ESI†). The complex crystallizes in the monoclinic space
group P2/c with four units residing at the unit cell. Crystal structure
3.2. Evaluation of conditions for transamidation reaction
At the outset of our investigations, a screen was performed for a
model reaction between acetamide and aniline and the results are

M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
19
Table 1
Evaluation of conditions for the model reaction using complex 3aa.
NH2
O
O
NH3
+
+
NH2
N
H
Entry Catalyst (mol%) Solvent
Temp. (◦C) Time (h) Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
–
–
–
110
110
110
110
110
110
rt
110
110
110
110
24
24
24
12
6
Nil
Nil
45
56
74
94
Nil
54
<5
19
69
27
Nil
57
36
23
94
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Acetonitrile
DMF
DMSO
p-Xylene
Chlorobenzene 110
n-C5H11OH
iPrOH
0.15
0.25
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
Fig. 2. Effect of solvent on transamidation of carboxamide with amine.
8
24
24
24
24
24
24
24
24
24
24
24
100
94%
78%
80
60
40
20
0
76%
72%
110
100
100
100
110
EtOH
H2O
Toluene
a
Reaction conditions: acetamide (5 mmol), aniline (5 mmol).
Yields were calculated after isolation of the amide product through column
b
chromatography using silica gel (200–400 mesh).
solvents such as toluene and p-xylene (Table 1, entries 6, 11) were
found to be better reaction media than polar aprotic (DMF, DMSO;
Table 1, entries 9, 10) or protic solvents (Table 1, entries 14–16),
whereas n-C5H11OH proved completely futile (Table 1, entry 13).
Pleasingly, toluene was found to be the solvent of choice, giving
94% yield in 8 h, whereas acetonitrile were inferior (Table 1, entries
6, 8).
1
3a
2
3
4
3d
3c
3b
[Ru-NHC] complex in 0.5 mol %
Fig. 3. Influence of wingtip substituents and catalyst loading on the catalytic activity
of [Ru–NHC] complexes.
depicted in Table 1. To ensure its catalytic role, the control experi-
ment was performed in the absence of [Ru–NHC] and as expected,
no further gain in the conversion was obtained after a prolonged
reaction time up to 24 h (Table 1, entries 1, 2). Addition of [Ru–NHC]
complex 3a (0.5 mol%) to the reaction mixture resulted in the
desired transformation, but these conditions were not very active.
An increase in the mol% of catalyst did not improve the yield further
(Table 1, entry 17). Conversely, a decrease in the catalyst (mol%) led
to diminish the yield of the product considerably (Table 1, entries
3, 4). It is well known that the solvent can have profound effect
on the transamidation reaction. We are interested in exploring the
solvent-dependent differences in the activities of catalysts on car-
rying out the model reaction in the most frequently used solvents
such as, toluene, xylene, chlorobenzene, acetonitrile, DMF, DMSO,
n-C5H11OH, iPrOH, EtOH and H2O (Fig. 2). Aromatic hydrocarbon
3.3. Influence of wingtip substituents and catalyst loading
We continued the transamidation reaction optimization pro-
cess to study the influence of the wingtip substituents and catalyst
loadings on the catalytic activity (Fig. 3). The results are sum-
marized in Table 2. It indicates that the lower catalyst loadings
lead to moderate yields and longer reaction times are required to
achieve maximum conversion. Further, the [Ru–NHC] complex con-
taining Methyl (Table 2, entry 1) as a wingtip substituent lead to
higher yields than those containing phenyl, isopropyl or mesityl at
0.5 mol% of catalyst was used. This behavior indicates that steric
effects may be played an important role in the catalytic activity. In
addition, significantly shorter reaction times are needed to com-
plete all the transamidation process.
The optimization process led us toward the determination of the
best reaction conditions to analyze the substrate scope. Catalyst 3a
was proved to be the most efficient complex for the transamidation
of carboxamides with amines in terms of yield and selectivity.
Table 2
Influence of wingtip substituents and catalyst loading on the catalytic activity of
[Ru–NHC] complexesa.
NH2
3.4. Transamidation of acetamide with various amines
O
O
NH3
+
+
NH2
N
H
After we established suitable reaction conditions, a number of
structurally diverse amides and amines were coupled to evaluate
the reliability of the reaction and the results are summarized in
Tables 3–5. We were pleased to see that all the reactions proceeded
smoothly and afforded the desired products in reasonable to excel-
lent yields upon isolation. The transamidation of acetamide with
various amines demonstrate (Table 3) that the catalytic process
is able to tolerate a variety of functional groups and substituents
including CH3, OCH3, NO2 and Cl. Various amines having both elec-
tron donating and electron withdrawing groups underwent the
reaction smoothly and gave rise to good to excellent product yields
Entry Catalyst Amount of catalyst (mol%) Wingtip (R) Time (h) Yield (%)b
1
2
3
4
5
3a
3b
3c
3d
–
0.5
0.5
0.5
0.5
–
Me
Ph
iPr
Mes
–
8
8
8
8
24
94
72
78
76
–
a
Reaction conditions: acetamide (5 mmol), aniline (5 mmol).
Yields were calculated after isolation of the amide product through column
chromatography using silica gel (200–400 mesh).
b

20
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
Table 3
Transamidation of acetamide with various aminesa.
O
O
H
N
+
NH2
[Ru-NHC] 3a (0.5 mol%)
R1
CH3
N
H
CH3
+
NH3
Toluene, 110oC, 8 h
R1
O
H
4*
O
H
CH3
N
N
H
CH3
N
H
CH3
O
CH3
4b; 94%
4a; 98 %
4c; 95%
O
O
O
Cl
N
H
CH3
N
H
CH3
N
CH3
H
OCH3
Cl
4f; 65%
4e; 87%
4d; 90%
O
Cl
O
H
CH3
N
F
N
CH3
N
CH3
H
H
O
CH3
4i; 74%
4g; 97%
4h; 80%
H
O
CH3
N
H
N
CH3
N
H
CH3
O
O
Cl
4k; 94%
4l; 91%
4j; 49%
H
N
O
CH3
CH3
O
N
N
CH3
O
O
H
4n; 67%
4m; 90%
4o; 85%
H
N
CH3
CH3
N
O
O
O2N
4p; 76%
4q; 52%
*Yields were calculated after isolation of the amide product through column chromatography using silica gel (200–400 mesh).
a
Reaction conditions: amide (5 mmol), amine (5 mmol), [Ru–NHC] 3a (0.5 mol%), toluene (5 mL), reflux.
regardless of the substituted positions (Table 3, entry 4a, 4c–h).
The less nucleophilic aniline, methyl aniline and 3-chloroaniline,
provide good to moderate yields (Table 3, entry 4b, 4i, 4j). We
assume this may be due to the delocalization of the nitrogen lone
pair of electrons on the aromatic ring, which is apparent accord-
ing to the literature [19][19c]. But in the case of p-nitro aniline, as
expected due to its decreased nucleophilicity, the reaction was very
slow and gave a yield of 76% in 8 h (Table 3, entry 4p). Acetamide
could be transamidate with aromatic amines like phenethylamine,
3-phenyl propylamine and 3-phenyl butylamine to gave the cor-
responding amides in high yield (Table 3, entries 4k–m), but in
the case of morpholine, the reaction was very slow and gave 67%
yield in 8 h (Table 3, entry 4n). Similarly, acetamide was suc-
cessfully transamidate with cyclohexylamine, gave 85% yield in
8 h (Table 3, entry 4o). As for as the steric effects are concerned,
we have also examined the effectiveness of the current catalytic
system for the amidation of hindered secondary amine such as
N,N-diphenylamine. The desired amide product was obtained as
moderate yield (Table 3, entry 4q). Notably, alkyl aromatic, aliphatic
and secondary amides were also successfully accomplished
under our investigated conditions, albeit at a somewhat higher
temperature.
3.5. Expanded substrate scope
In order to check the versatility of our catalysts, we decided to
study the expanded substrate scope of the catalyst 3a with a vari-
ety of benzylic, aromatic, aliphatic, propargylic, heteroaromatic and
secondary amines with other amides. The results showed in Table 4
summarize the effect of the substrates on the yield and selectiv-
ity of the catalytic reaction using a 0.5 mol% loading of catalyst
in toluene at 110 ◦C. Benzamide containing electron-donating or
electron-with drawing functionalities underwent facile reactions
with various amines, including aniline, benzylamine and phenethy-
lamine giving the corresponding amides in good to moderate yields
(Table 4, entry 5a–h, 5j). The reaction of aliphatic amines with vari-
ety of aromatic amides led to reduction in yield due to losses in
product isolation (Table 4, entry 5i, 5k, 5l, 5o). Similarly, the reac-
tion was also found to be slow between p-nitrobenzamide, carrying
an electron withdrawing group and benzylamine, gave yield of 79%

M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
21
Table 4
Expanded substrate scope of transamidation methoda.
O
O
H
N
[Ru-NHC] 3a (0.5 mol%)
R3
H
+
R1
N
R2
+
NH3
Toluene, 110oC, 8 h
N
H
R1
R2
R3
5*
O
O
O
N
H
N
H
N
H
Cl
F
5a; 98%
5c; 90%
5b; 78%
O
O
H
N
N
H
N
H
O
OCH3
Cl
5e; 72%
5f; 87%
5d; 69%
O
O
Ph
O
N
N
H
N
H
O
5i; 59%
5h; 75%
5g; 94%
O
O
O
NH
H3C
N
H
N
H
O
CH3
5k; 48%
5l; 36%
5j; 81%
O
O
N
H
N
H
N
H
O
O2N
5o; 54%
5m; 89%
5n; 79%
O
O
N
N
N
N
H
O
O
5p; 91%
5q; 89%
5r; 48 %
*Yields were calculated after isolation of the amide product through column chromatography using silica gel (200–400 mesh).
a
Reaction conditions: amide (5 mmol), amine (5 mmol), [Ru–NHC] 3a (0.5 mol%), toluene (5 mL), reflux.
in 8 h (Table 4, entry 5n). Furthermore, it was found that 2-furamide
an acid labile heterocyclic amide, which is difficult to transamidate
under homogeneous catalysis, reacted smoothly with benzylamine
and gave very good yield (Table 4, entry 5m). Phenyl acetamides
were transamidate using nicotinamide and morpholine, in these
cases, the reaction was smooth and gave the corresponding amides
in good yields (Table 4, entry 5p, 5q). A sterically hindered sec-
ondary amine such as N,N-diphenylamine gave the corresponding
amide product in lower yield (Table 4, entry 5r).
using hazardous, toxic, and unstable reagents (mixed formic/acetic
anhydride, cyanomethyl formate, pentafluorophenyl formate, and
formyl fluoride). This led us to carry out a more comprehensive
study of scope and limitation of formylation using the present
methodology (Table 5). The formylation of amines is a useful
synthetic procedure for the preparation of N-formyl protected
amides and therefore the N-formylation of formamide with various
aliphatic, aromatic, alicyclic, benzylic, and hetero-aromatic amines
were studied in detail (Table 5, entries 6a–m). With regards to the
reactivities of the amines (Table 5, entry 6h), the aliphatic amines
performed better, where as both the furylamine and morpholine
worked well in these transamidation reaction (Table 5, entries 6f,
6i). We have explored an effective transamidation of formamide
with different amine partners containing electron withdrawing
substituents afford diverse carboxamides in reasonably good to
excellent yields (Table 5, entries 6d, 6e, 6j, 6k). The reaction with
benzylamine proceeded smoothly at temperature of 110 ◦C to fur-
nish excellent yields (Table 5, entry 6g). Concerning the reactivity of
aromatic primary amines, those having electron-donating groups
performed better in these transamidation reactions, afforded the
clean conversion without formation of side products (Table 5, entry
3.6. N-formylation of amines
Encouraged by these promising results, we turned our atten-
tion to the N-formylation of amines through transamidation using
formamide. The N-formylation of amines is one of the most impor-
tant reactions in organic and industrial chemical synthesis. We
were particularly intrigued by the high reactivity of unsubsti-
tuted formamide toward different amines under [Ru–NHC] 3a
catalyzed conditions. As expected, the results were good, with
a series of different amines coupled with formamide and gave
good yields. Typically, the N-formylation of amine is carried out

22
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
Table 5
a
[Ru–NHC]-catalyzed amine formylation using HCONH2
.
O
O
H
N
[Ru-NHC] 3a (0.5 mol %)
Toluene, 110oC, 8 h
R2
+
H
N
R1
NH3
+
H
NH2
R1
R2
6*
H
H
N
H
N
H
H
N
H
O
O
O
CH3
OCH3
6a; 95%
6b; 98%
6c; 91%
H
H
N
H
N
H
H
N
H
O
O
O
O
O
NO2
Cl
6f; 82%
6d; 99%
6e; 85%
O
H
N
O
H
O
N
N
H
H
O
H
6i; 82%
6h; 79%
6g; 97%
Cl
O
O
H
N
H
N
H
H
N
H
H
OCH3
Cl
6j; 97%
6l; 81%
6k; 98%
O
H
N
O
N
H
H
6m; 79%
6n; 42%
*Yields were calculated after isolation of the amide product through column chromatography using silica gel (200–400 mesh).
a
Reaction conditions: amide (5 mmol), amine (5 mmol), [Ru–NHC] 3a (0.5 mol %), toluene (5 mL), reflux.
6b, 6c, 6l). For the reaction of N,N-diphenylamine with formamide
to gave the corresponding amide product in lower yield under opti-
mized condition (Table 5, entry 6n). It is worth mentioning that
the complex 3a can also catalyze the transamidation of formamide
with different amines, which is more sustainable for the synthesis
of amides.
Based on previous literature report [20][20k], the reaction of
15N-labeled benzamide with unlabeled benzylamine led to the
exclusive formation of unlabeled secondary amide product, and it
is proposed that, the [Ru–NHC] catalyzed transamidation reaction
was also take place by the addition of amine–amide.
to ascertain the specific role of catalyst and exact nature of the
catalytic intermediate for these novel transamidation reactions.
Efforts are underway to elucidate the mechanistic details of these
NH bond forming reactions.
To our knowledge, these results provide the first demonstration
of [Ru–NHC] catalyzed transamidation under moderate conditions.
The data provide several insights regarding the identity of success-
ful catalysts. Gratifyingly, all the reactions proceeded efficiently and
furnished all types of substituted amides in good to excellent yields.
4. Summary and outlook
3.7. Mechanistic study
Our study has furnished the following results. The combination
of phosphine and NHC in one unique metal complex has led to
important discoveries in organometallic chemistry, providing cat-
alytic improvements. In this paper, we designed and synthesized
new o-aryloxide-N-heterocyclic carbene ruthenium(II) complexes
[3a–d] containing trans triphenylphosphine donors in two consec-
utive steps. The ruthenation was accomplished by metalation with
Ag2O to form intermediate silver carbene complexes and subse-
quent transmetallation with [RuHCl(CO)(PPh3)3]. The yields were
promising. The [Ru–NHC] complexes [3a–d] displayed excellent
stability toward air and moisture which are the additional advan-
tages for a better catalyst.
On the basis of previous investigations, a possible mechanism
was proposed for [Ru–NHC] catalyzed transamidation, which has
been schematically represented (Scheme 4). Catalyst forms a ruthe-
nium amide complex (Ru–NHRꢀ) by the ligand exchange reaction
of amine with catalyst. We consider that this amide complex
enhance the addition of amide with the catalyst. This is evident
from the second order kinetics of the reaction with amine. The
obtained intermediate undergone inter ligand reaction as shown
in Scheme 4. Addition of new amine restores the (Ru–NHRꢀ) com-
plex with the liberation of N-substituted amide and ammonia.
Although the complete elucidation of the mechanism has not
been undertaken, we have conducted some control experiments
In addition, transamidation catalysis was explored for the one-
pot synthesis of amides from carboxamides with amines. This

M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
23
PPh3
CO
gel (200–400 mesh). Melting points were checked in open capillary
tubes on a Technico micro heating table and are uncorrected.
O
C
Ru
5.2. Materials
Cl
PPh3
1-Substituted imidazoles [32], 4-bromo-2,4,6-tri-tert-butyl-
2,5-cyclohexadien-1-one [33], o-hydroxyaryl-substituted imida-
zolium salts [1a–d] [22][22a] and [RuHCl(CO)(PPh3)3] [34] were
prepared according to the previously published procedures.
H
N
R'
H
R
PPh3
CO
O
NH3
5.3. Spectroscopy
R
NHR'
O
O
Ru
NH2
R'
Infrared spectra of the ligands and the metal complexes were
recorded as KBr discs in the range of 4000–400 cm−1 using a Nico-
let Avatar model FT-IR spectrophotometer. 1H (300.13 MHz), 13C
(75.47 MHz) and 31P NMR (162 MHz) spectra were taken in DMSO-
d6 or CDCl3 at room temperature with a Bruker AV400 instrument
with chemical shifts relative to tetramethylsilane (1H, 13C) and o-
phosphoric acid (31P). Electrospray ionization mass spectra were
recorded by liquid chromatography mass spectrometry quadrupole
time-of-flight Micro Analyzer (Shimadzu) at SAIF, Panjab Univer-
sity, Chandigarh.
N
C
H
PPh3
PPh3
CO
PPh3
CO
O
C
NHR'
O
C
O
Ru
R
R
O
H
Ru
NH2
H
H
N
NH2
N
PPh3
R'
PPh3
R'
5.4. Elemental analyses
PPh3
CO
Microanalyses of carbon, hydrogen and nitrogen were carried
out using a Vario EL III elemental analyzer at SAIF, Cochin, India.
H
O
C
R
N
R'
O
Ru
H
NH2
5.5. Representative syntheses
N
H
PPh3
R'
The milder conditions of the “transmetalation” pathway make
it an attractive choice for the synthesis of ruthenium complexes.
o-hydroxyaryl-substituted imidazolium ligands (R = Me [1a], Ph
[1b], iPr [1c], Mes [1d], 2 mmol) was dissolved in 25 mL of
dichloromethane and transferred into a Schlenk vessel. Silver(I)
oxide (0.231 g, 1 mmol) was added, and the mixture was stirred for
24 h at room temperature under argon atmosphere. The unreacted
Ag2O was filtered through a plug of Celite, and in most cases the
solution was directly applied for further synthetic steps. The prod-
uct can be isolated by removing the solvent under reduced pressure
to give a solid, stable to oxygen and water. [RuHCl(CO)(PPh3)3]
(0.9524 g, 1 mmol) was taken up in 5 mL of dichloromethane and
added to a solution of Ag complex in 10 mL of CH2Cl2. A white pre-
cipitate (AgBr) formed, and the mixture was stirred overnight at
room temperature. After filtration in air, the solvent was removed
in vacuum to give a brown waxy substance. The waxy substance
was triturated with diethyl ether. The final compound is stable
in air. The crude product was purified by column chromatogra-
phy (SiO2, 10:1CH2Cl2/Acetone). Single crystal of the compound 3a
was obtained by slow diffusion of diethyl ether onto a concentrated
solution of the yellow powder isolated via column chromatography
in dichloromethane.
Scheme 4. Possible mechanism for [Ru–NHC] catalyzed transamidation.
method has a great potential for the preparation of amides, because
it tolerates a wide range of substrates with excellent yield. To
our knowledge, these results provide the first demonstration of
[Ru–NHC] catalyzed transamidation under moderate conditions
with lower catalyst loadings. We were delighted to find that
the catalytic activities observed are unprecedented and repre-
sented a substantial step toward a long-range goal of conducting
transamidation reactions with carboxamides under mild reaction
conditions. In the catalysis reaction the complex 3a has proven
to be a versatile and efficient catalyst under mild reaction condi-
tion in comparison with other three ruthenium complexes [3a–d].
The steric effect of wingtip substituents at the NHCs slightly influ-
enced the catalytic activities. Efforts are currently underway in our
research group to expand the scope of this method to a library of
different functionalized substrates and elucidation of mechanistic
principles underlying these novel transamidation reactions with
even greater activity.
5. Experimental
5.5.1. Compound 3a (R = Me)
The synthetic procedure of this compound was the same as that
of above representative procedure, using 1-methyl imidazole to
give a yellow solid 3a. Yield: 92%, Rf (CH2Cl2/acetone, 10/1). M. pt:
210–213 ◦C. Anal. Calcd for C55H55N2O2ClP2Ru: C, 67.79; H, 5.69;
N, 2.87%. Found: C, 67.54; H, 5.42; N, 2.61%. IR (KBr disks, cm−1);
5.1. General comments
All reactions involving the syntheses of metal complexes were
carried out in oven- or flame dried glassware with magnetic stirrer
under argon atmosphere with anhydrous solvents, using stan-
dard Schlenk techniques. Silver reactions were conducted in the
absence of light. All commercial chemicals were used as purchased.
Thin-layer chromatography (TLC) was performed on Merck 1.0555
aluminum sheets precoated with silica gel 60 F254, and the spots
were visualized with UV light at 254 nm or under iodine. Column
chromatography purifications were performed using Merck silica
1937 (C O), 1610 (C C), 1572 (N
C N), 1458 (C C), 1416 (C O).
1H NMR (300.13 MHz, CDCl3): ı = 7.49–7.44 (m, 5H, aryl-H), 7.43
(m, 8H, aryl-H), 7.25 (m, 7H, aryl-H), 7.21 (m, 8H, aryl-H), 7.18 (s,
2H, aryl-H), 7.09 (d, 1H, J = 2.2 Hz, imi-H), 6.69 (d, 1H, J = 2.8 Hz, imi-
H), 3.09 (s, 3H, CH3), 1.25 (s, 9H, C(CH3)3), 0.84 (s, 9H, C(CH3)3).
13C NMR (75.47 MHz, CDCl3): ı = 206.5 (C O), 180.8 (Ru–Ccarbene),
162.1 (C O), 143.8 (Cquat, aryl), 136.2 (Cquat, aryl), 135.3 (Cquat
,

24
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
aryl), 134.3 (Cquat, aryl), 132.9 (Cquat, aryl), 131.2 (Cquat, aryl), 124.9
(Cquat, aryl), 122.0 (Cquat, aryl), 59.2 (NCH2), 45.2 (Cquat, tBu), 44.9
(Cquat, tBu), 36.6 (CH3, tBu), 35.6 (CH3, tBu), 35.1 (CH3, tBu), 30.3
(N-CH3). 31P NMR (162 MHz, CDCl3): ı = 24.35 (s). ESI: m/z calcd.
For C55H55N2O2ClP2Ru [M–Cl]+, 939.057; Found, [M–Cl]+, 939.12.
tBu), 31.8 (CH3, tBu), 29.9 (CH3, tBu), 28.8 (CH3), 28.3 (CH3), 27.4
(CH3). 31P NMR (162 MHz, CDCl3): ı = 29.13 (s). ESI: m/z calcd. For
C
63H63N2O2ClP2Ru [M–Cl]+, 1043.207; Found, [M–Cl]+, 1043.31.
5.6. Representative procedure for transamidation reaction
5.5.2. Compound 3b (R = Ph)
A mixture of amide (5 mmol), amine (5 mmol), [Ru–NHC] com-
plex (0.5 mol%) and toluene (5 mL) was stirred in a sealed tube
under nitrogen atmosphere at 110 ◦C for 8 h. After cooling down to
room temperature, the reaction solvent was removed under vac-
uum. After removal of the solvent, the crude reaction mixture was
dissolved in CH2Cl2 and purified by column chromatography on sil-
ica gel (200–400 mesh) eluting with heptane:ethanol [25:1] to give
corresponding amides as a white solid. The yields are mentioned
in Tables 3–5. The product was confirmed by NMR spectroscopy.
Reported isolated yields are an average of two runs.
The synthetic procedure of this compound was the same as that
of above representative procedure, using 1-phenyl imidazole to
give a yellow solid 3b. Yield: 90%, Rf (CH2Cl2/acetone, 10/1). M.
pt: 224–226 ◦C. Anal. Calcd for C60H57N2O2ClP2Ru: C, 69.52; H,
5.54; N, 2.70%. Found: C, 69.81; H, 5.21; N, 2.42%. IR (KBr disks,
cm−1); 1939 (C O), 1614 (C C), 1569 (N
C N), 1453 (C C), 1412
(C O). 1H NMR (300.13 MHz, CDCl3): ı = 7.77 (d, 1H, J = 7.5 Hz, aryl-
H), 7.74 (m, 5H, aryl-H), 7.71 (m, 2H, aryl-H), 7.65 (m, 8H, aryl-H),
7.58 (m, 8H, aryl-H), 7.55 (m, 8H, aryl-H), 7.47 (m, 3H, aryl-H), 7.46
(s, 1H, aryl-H), 7.44 (d, 1H, J = 1.8 Hz, imi-H), 7.29 (d, 1H, J = 1.8 Hz,
imi-H), 7.22–7.19 (m, 3H, aryl-H), 1.28 (s, 9H, C(CH3)3), 1.45 (s,
9H, C(CH3)3). 13C NMR (75.47 MHz, CDCl3): ı = 202.1 (C O), 184.2
(Ru–Ccarbene), 153.3 (C O), 141.3 (Cquat, aryl), 139.9 (Cquat, aryl),
5.7. Crystal structure determination
Crystals of complex 3a were mounted on glass fibers used
for data collection. Crystal data were collected at 295 K using
a Gemini A Ultra Oxford Diffraction automatic diffractometer.
Graphite monochromated Mo-K␣ radiation (ꢀ = 0.71073 Å) was
used throughout. The absorption corrections were performed by
the multi-scan method. Corrections were made for Lorentz and
polarization effects. The structure was solved by direct methods
using the program SHELXS [35]. Refinement and all further cal-
culations were carried out using SHELXL [35]. The H atoms were
included in calculated positions and treated as riding atoms using
the SHELXL default parameters. The non-hydrogen atoms were
refined anisotropically using weighted full-matrix least squares on
F2. Atomic scattering factors were incorporated into the computer
programs.
138.3 (Cquat, aryl), 137.4 (Cquat, aryl), 136.2 (Cquat, aryl), 131.1 (Cquat
,
aryl), 127.2 (Cquat, aryl), 121.3 (Cquat, aryl), 109.1 (Cquat, aryl), 101.8
(Cquat, aryl), 104.3 (Cquat, aryl), 55.1 (NCH2), 41.3 (Cquat, tBu), 40.0
(Cquat, tBu), 39.3 (CH3, tBu), 36.4 (CH3, tBu), 35.4 (CH3, tBu). 31P
NMR (162 MHz, CDCl3): ı = 25.61 (s).
5.5.3. Compound 3c (R = iPr)
The synthetic procedure of this compound was the same as that
of above representative procedure, using 1-isopropyl imidazole to
give a yellow solid 3c. Yield: 94%, Rf (CH2Cl2/Acetone, 10/1). M. pt:
219–222 ◦C. Anal. Calcd for C57H59N2O2ClP2Ru: C, 68.29; H, 5.93;
N, 2.79%. Found: C, 69.59; H, 5.62; N, 2.57%. IR (KBr disks, cm−1);
1938 (C O), 1617 (C C), 1564 (N
C N), 1457 (C C), 1417 (C O).
1H NMR (300.13 MHz, CDCl3): ı = 7.85 (m, 6H, aryl-H), 7.81 (m, 8H,
aryl-H), 7.74 (m, 4H, aryl-H), 7.54 (m, 5H, aryl-H), 7.51 (m, 6H,
aryl-H), 7.43 (d, 1H, J = 1.8 Hz, imi-H), 7.34 (d, 1H, J = 2.1 Hz, imi-
H), 7.31 (d, 1H, J = 2.2 Hz, aryl-H), 7.24 (d, 1H, J = 2.1 Hz, aryl-H),
2.82 (m, 1H, CH(CH3)3), 2.17 (d, 3H, J = 6.7 Hz, CH CH3), 1.91 (d,
3H, J = 6.7 Hz, CH CH3), 1.44 (s, 9H, C(CH3)3), 1.01 (s, 9H, C(CH3)3).
13C NMR (75.47 MHz, CDCl3): ı = 201.3 (C O), 183.8 (Ru–Ccarbene),
Supporting information
CCDC reference number 985755 contains the supplementary
crystallographic data for 3a. The data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, U.K.; fax: +44 1223 336 033; or email: Repre-
sentative NMR 1H, 13C, 31P and ESI MS spectra of complexes, the
unit cell packing diagram for the complex 3a, detailed experimental
procedure and spectral data for amide products.
149.9 (C O), 142.9 (Cquat, aryl), 139.9 (Cquat, aryl), 138.5 (Cquat
,
aryl), 136.3 (Cquat, aryl), 133.6 (Cquat, aryl), 131.1 (Cquat, aryl), 128.5
(Cquat, aryl), 128.2 (Cquat, aryl), 127.7 (Cquat, aryl), 127.4 (Cquat, aryl),
126.0 (Cquat, aryl), 125.7 (Cquat, aryl), 107.7 (Cquat, aryl), 51.9 (NCH2),
39.5 (Cquat, tBu), 38.2 (Cquat, tBu), 34.9 (CHCH3), 34.1 (CHCH3), 32.7
(CH3, tBu), 30.9 (CH3, tBu), 31.2 (CH3, tBu). 31P NMR (162 MHz,
CDCl3): ı = 26.01 (s). ESI: m/z calcd. For C57H59N2O2ClP2Ru [M–Cl]+,
967.107; Found, [M–Cl]+, 967.15.
Acknowledgments
The authors express their sincere thanks to Department of Sci-
ence and Technology, New Delhi, India for financial support for this
work under the DST FAST TRACK Scheme (No. SR/FT/CS-66/2011).
One of the authors (MN) thanks DST-SERB for the award of fellow-
ship.
5.5.4. Compound 3d (R = Mes)
The synthetic procedure of this compound was the same as that
of above representative procedure, using 1-mesityl imidazole to
give a yellow solid 3d. Yield: 89%, Rf (CH2Cl2/acetone, 10/1). M.
pt: 226–228 ◦C. Anal. Calcd for C63H63N2O2ClP2Ru: C, 70.15; H,
5.89; N, 2.60%. Found: C, 69.89; H, 5.64; N, 2.49%. IR (KBr disks,
Appendix A. Supplementary data
cm−1); 1937 (C O), 1615 (C C), 1561 (N
C N), 1459 (C C), 1421
(C O). 1H NMR (300.13 MHz, CDCl3): ı = 7.87 (d, 1H, J = 2.4 Hz, aryl-
H), 7.58 (m, 6H, aryl-H), 7.49 (m, 7H, aryl-H), 7.46 (d, 1H, aryl-H),
7.40 (m, 9H, aryl-H), 7.38 (m, 9H, aryl-H), 7. 35 (d, 1H, J = 2.5 Hz,
imi-H), 7.21 (d, 1H, J = 2.1 Hz, imi-H), 2.48 (s, 3H, CH3), 2.25 (s, 3H,
CH3), 1.91 (s, 3H, CH3), 1.44 (s, 9H, C(CH3)3), 1.07 (s, 9H, C(CH3)3).
13C NMR (75.47 MHz, CDCl3): ı = 200.5 (C O), 182.4 (Ru–Ccarbene),
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2015.03.015.
References
[1] (a) N. Sewald, H.-D. Jakubke, Peptides: Chemistry and Biology, Wiley, New
York, 2009.
[2] (a) The Amide Linkage: Structural Significance in Chemistry, Biochemistry
and Materials Science, in: A. Greenberg, C.M. Breneman, J.F. Liebman (Eds.),
John Wiley & Sons, New York, 2000;
158.2 (C O), 147.4 (Cquat, aryl), 137.5 (Cquat, aryl), 135.6 (Cquat
aryl), 133.9 (Cquat, aryl), 129.1 (Cquat, aryl), 128.7 (Cquat, aryl), 128.3
(Cquat, aryl), 126.3 (Cquat, aryl), 123.7 (Cquat, aryl), 120.1 (Cquat
aryl), 49.6 (NCH2), 38.7 (Cquat, tBu), 37.4 (Cquat, tBu), 35.8 (CH3,
,
,

M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
25
(b) I. Johansson, Kirk-Othmer Encyclopedia of Chemical Technology, John
Wiley & Sons, New York, 2004.
[3] (a) P.D. Bailey, T.J. Mills, R. Pettecrew, R.A. Price, Comprehensive Organic
Functional Group Transformations II, in: A.R. Katritzky, R.J.K. Taylor (Eds.),
Elsevier, Oxford, 2005;
(b) C.A.G.N. Montalbetti, V. Falque, Tetrahedron 61 (2005) 10827–10852;
(c) E. Valeur, M. Bradley, Chem. Soc. Rev. 38 (2009) 606–631.
[4] (a) E. Saxon, C.R. Bertozzi, Science 287 (2000) 2007–2010;
(b) F. Damkaci, P. DeShong, J. Am. Chem. Soc. 125 (2003) 4408–4409.
[5] (a) T. Ribelin, C.E. Katz, D.G. English, S. Smith, A.K. Manukyan, V.W. Day, B.
Neuenswander, J.L. Poutsma, J. Aub, Angew. Chem. Int. Ed. 120 (2008)
6329–6332;
(b) S. Lang, J.A. Murphy, Chem. Soc. Rev. 35 (2006) 146–156.
[6] (a) N.A. Owston, A.J. Parker, J.M.J. Williams, Org. Lett. 9 (2007) 3599–3601;
(b) M. Hashimoto, Y. Obora, S. Sakaguchi, Y. Ishii, J. Org. Chem. 73 (2008)
2894–2897.
(m) R. Vanjari, B.K. Allam, K.N. Singh, RSC Adv. 3 (2013) 1691–1694;
(n) M.A. Ali, S.M.A.H. Siddiki, K. Kon, K.-I. Shimizu, Tetrahedron Lett. 55 (2014)
1316–1319;
(o) L.B. Figueroa, A.O. Porras, D.G. Sanchez, J. Org. Chem. 79 (2014) 4544–4552.
[21] (a) S.T. Liddle, I.S. Edworthy, P.L. Arnold, Chem. Soc. Rev. 36 (2007) 1732–1744.
[22] (a) For o-aryloxide NHCs, see: Y. Kong, H. Ren, S. Xu, H. Song, B. Liu, B. Wang,
Organometallics 28 (2009) 5934–5940;
(b) A.W. Waltman, R.H. Grubbs, Organometallics 23 (2004) 3105–3107;
(c) Y. Kong, S. Xu, H. Song, B. Wang, Organometallics 31 (2012) 5527–5532;
(d) A. Meyer, Y. Unger, A. Poethig, T. Strassner, Organometallics 30 (2011)
2980–2985;
(e) D.R. Weinberg, N. Hazari, J.A. Labinger, J.E. Bercaw, Organometallics 29
(2010) 89–100;
(f) A.A.J. Boydston, J.D. Rice, M.D. Sanderson, O.L. Dykhno, C.W. Bielawski,
Organometallics 25 (2006) 6087–6098;
(g) N. Ledoux, B. Allaert, F. Verpoort, Eur. J. Inorg. Chem. (2007) 5578–5583;
(h) Y. Kong, Y. Tang, Z. Wang, S. Xu, H. Song, B. Wang, Macromol. Chem. Phys.
214 (2013) 492–498;
[7] (a) J.R. Martinelli, T.P. Clark, D.A. Watson, R.H. Munday, S.L. Buchwald, Angew.
Chem. 119 (2007) 8612–8615;
(b) P. Nanayakkara, H. Alper, Chem. Commun. (2003) 2384–2385.
[8] M. Beller, B. Cornils, C.D. Frohning, J. Mol. Catal. A: Chem. 104 (1995) 17–85.
[9] (a) B.E. Ali, J. Tijani, Appl. Organomet. Chem. 17 (2003) 921–931;
(b) D.J. Knapton, T.Y. Meyer, Org. Lett. 6 (2004) 687–689;
(c) Y. Uenoyama, T. Fukuyama, O. Nobuta, H. Matsubara, I. Ryu, Angew. Chem.
Int. Ed. 117 (2005) 1099–1102.
(i) H. Ren, P. Yao, S. Xu, H. Song, B. Wang, J. Organomet. Chem. 692 (2007)
2092–2098;
(j) Y. Kong, L. Wen, H. Song, S. Xu, M. Yang, B. Liu, B. Wang, Organometallics
30 (2011) 153–159;
(k) Y. Kong, M. Cheng, H. Ren, S. Xu, H. Song, M. Yang, B. Liu, B. Wang,
Organometallics 30 (2011) 1677–1681;
[10] (a) J.W.W. Chang, P.W.H. Chan, Angew. Chem. 120 (2008) 1154–1156;
(b) W.J. Yoo, C.J. Li, J. Am. Chem. Soc. 128 (2006) 13064–13065.
[11] S. Cho, E. Yoo, I. Bae, S. Chang, J. Am. Chem. Soc. 127 (2005) 16046–16047.
[12] (a) R.V. Kolakowski, N. Shangguan, R.R. Sauers, L.J. Williams, J. Am. Chem. Soc.
128 (2006) 5695–5702;
(l) L. Dang, J. Guo, H. Song, B. Liub, B. Wang, Dalton Trans. 17 (2014)
1677–17183, 43;
(m) L. Dang, H. Song, B. Wang, Organometallics 33 (2014) 6812–6818.
[23] (a) L.U. Nordstrøm, H. Vogt, R. Madsen, J. Am. Chem. Soc. 130 (2008)
17672–17673;
(b) X. Zhang, F. Li, C.F. Liu, Bioconjugate Chem. 20 (2009) 197–200.
[13] (a) P. Anastas, N. Eghbali, Chem. Soc. Rev. 39 (2010) 301–312;
(b) D.J.C. Constable, P.J. Dunn, J.D. Hayler, G.R. Humphrey, J.J.L. Leazer, R.J.
Linderman, K. Lorenz, J. Manley, B.A. Pearlman, A. Wells, A. Zaks, T.Y. Zhang,
Green Chem. 9 (2007) 411–420.
[14] (a) For review articles covering innovative amide bond forming reactions, see:
C.L. Allen, J.M.J. Williams, Chem. Soc. Rev. 40 (2011) 3405–3415;
(b) V.R. Pattabiraman, J.W. Bode, Nature 480 (2011) 471–479;
(c) S. Roy, S. Roy, G.W. Gribble, Tetrahedron 68 (2012) 9867–9923;
(d) P. Xie, C. Xia, H. Huang, Org. Lett. 15 (2013) 3370–3373;
(e) R. García-Álvarez, P. Crochet, V. Cadierno, Green Chem. 15 (2013) 46–66;
(f) J.W. Bode, Top. Organomet. Chem. 44 (2013) 13–33;
(g) P. Crochet, V. Cadierno, Top. Organomet. Chem. 48 (2014) 81–118.
[15] (a) P. Kumar, A.K. Singh, R. Pandey, D.S. Pandey, J. Organomet. Chem. 696
(2011) 3454–3464;
(b) J.H. Dam, G. Osztrovszky, L.U. Nordstrøm, R. Madsen, Eur. J. Chem. 16
(2010) 6820–6827;
(c) I.S. Makarov, P. Fristrup, R. Madsen, Eur. J. Chem. 18 (2012) 15683–15692;
(d) A. Maggi, R. Madsen, Organometallics 31 (2012) 451–455;
(e) A. Sølvhøj, R. Madsen, Organometallics 30 (2011) 6044–6048;
(f) S.C. Ghosh, S. Muthaiah, Y. Zhang, X. Xu, S.H. Hong, Adv. Synth. Catal. 351
(2009) 2643–2649;
(g) S.C. Ghosh, S.H. Hong, Eur. J. Org. Chem. (2010) 4266–4270;
(h) S. Muthaiah, S.C. Ghosh, J.-E. Jee, C. Chen, J. Zhang, S.H. Hong, J. Org. Chem.
75 (2010) 3002–3006;
(i) Y. Zhang, C. Chen, S.C. Ghosh, Y. Li, S.H. Hong, Organometallics 29 (2010)
1374–1378;
(j) C. Chen, S.H. Hong, Org. Biomol. Chem. 9 (2011) 20–26;
(k) Z. Fu, J. Lee, B. Kang, S.H. Hong, Org. Lett. 14 (2012) 6028–6031.
[24] M. Nirmala, G. Prakash, R. Ramachandran, P. Viswanathamurthi, J.G. Malecki,
W.G. Linert, J. Mol. Catal. A: Chem. 397 (2015) 56–67.
[25] (a) C. Samojlowicz, M. Bieniek, K. Grela, For an example of the influence of a
phosphorus-based ligand in metathesis: Chem. Rev. 109 (2009) 3708–3742;
(b) X. Bantreil, T.E. Schmid, R.A.M. Randall, A.M.Z. Slawin, C.S.J. Cazin, For an
example of NHC ligand influence in metathesis, see: Chem. Commun. 46
(2010) 7115–7117;
(b) R.N. Prabhu, R. Ramesh, RSC Adv. 2 (2012) 4515–4524;
(c) N. Raja, M.U. Raja, R. Ramesh, Inorg. Chem. Commun. 19 (2012) 51–54.
[16] (a) R. Manikandan, G. Prakash, R. Kathirvel, P. Viswanathamurthi,
Spectrochim. Acta A 116 (2013) 501–508;
(b) M. Nirmala, R. Manikandan, G. Prakash, P. Viswanathamurthi, Appl.
Organomet. Chem. 28 (2014) 18–26;
(c) G. Prakash, P. Viswanathamurthi, Spectrochim. Acta A 129 (2014) 352–358.
[17] (a) J.H. Jeon, S.Y. Cho, C.W. Kim, D.M. Shin, J.C. Kweon, K.H. Choi, S.M.C. Park,
I.G. Kim, Biochem. Biophys. Res. Commun. 294 (2002) 818–822;
(b) F. Rossin, D. D’Eletto, M.G. Macdonald, M. Farrace, R.P. Piacentini, Amino
Acids 42 (2012) 1793–1802.
(c) M. Scholl, S. Ding, C.W. Lee, R.H. Grubbs, Org. Lett. 1 (1999) 953–956.
[26] (a) X. Hu, I. Castro-Rodriguez, K. Olsen, K. Meyer, Organometallics 23 (2004)
755–764;
(b) H.M.J. Wang, I.J.B. Lin, Organometallics 17 (1998) 972–975;
(c) A.A.D. Tulloch, A.A. Danopoulos, S. Winston, S. Kleinhenz, G. Eastham, J.
Chem. Soc. Dalton Trans. (2000) 4499–4506;
(d) W.A. Herrmann, S.K. Schneider, K. Ofele, M. Sakamoto, E. Herdtweck, J.
Organomet. Chem. 689 (2004) 2441–2449;
[18] (a) Anderson, P. Degano, A.J. Godkin, D.P. Jewell, A.V. Hill, Nat. Med. 6 (2000)
337–342;
(b) H. Green, Cell 74 (1993) 955–956;
(c) L. Lorand, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 14310–14313.
[19] (a) S.N. Rao, D.C. Mohan, S. Adimurthy, Org. Lett. 15 (2013) 1496–1499;
(b) M. Tamura, T. Tonomura, K. Shimizu, A. Satsuma, Green Chem. 14 (2012)
717–724;
(e) M.K. Mayr, K.H. Wurst, M.R. Ongania, V. Buchmeiser, Eur. J. Chem. 10
(2004) 1256–1266;
(f) V. Cesar, S. Bellemin-Laponnaz, L.H. Gade, Organometallics 21 (2002)
5204–5208;
(c) C.L. Allen, B.N. Atkinson, J.M.J. Williams, Angew. Chem. Int. Ed. 51 (2012)
1383–1386;
(g) K.M. Lee, H.M.J. Wang, I.J.B. Lin, J. Chem. Soc. Dalton Trans. (2002)
2852–2856.
(d) T.B. Nguyen, J. Sorres, M.Q. Tran, L. Ermolenko, A. Al-Mourabst, Org. Lett.
14 (2012) 3202–3205.
[20] (a) For representative examples of metal catalyzed transamidation, see: E.
Bon, D.C.H. Bigg, G. Bertrand, J. Org. Chem. 59 (1994) 4035–4036;
(b) S.E. Eldred, D.A. Stone, S.H. Gellman, S.S. Stahl, J. Am. Chem. Soc. 125
(2003) 3422–3423;
[27] (a) P. Csabai, F. Joo, Organometallics 23 (2004) 5640–5643;
(b) J. Lemke, N. Metzler-Nolte, Eur. J. Inorg. Chem. 21 (2008) 3359–3366;
(c) T.K. Maishal, J.M. Basset, M. Boualleg, C. Coperet, L. Veyre, C. Thieuleux,
Dalton Trans. 35 (2009) 6956–6959.
[28] (a) C.D. Pozo, M. Iglesias, F. Sanchez, Organometallics 30 (2011) 2180–2188.
[29] (a) M. Poyatos, J.A. Mata, E. Falomir, R.H. Crabtree, E. Peris, Organometallics 22
(2003) 1110–1114;
(b) X. Cheng, Y. Lu, H.J. Xu, Y.Z. Li, X.T. Chen, Z.L. Xue, Inorg. Chim. Acta 363
(2010) 430–437;
(c) F.L. Zeng, Z.K. Yu, Organometallics 27 (2008) 6025–6028.
[30] (a) S.B. Garber, J.S. Kingsbury, B.L. Gray, A.H. Hoveyda, J. Am. Chem. Soc. 122
(2000) 8168–8179;
(c) M. Shi, S. Cui, Synth. Commun. 35 (2005) 2847–2858;
(d) S. Calimsiz, M.A. Lipton, J. Org. Chem. 70 (2005) 6218–6221;
(e) D.A. Kissounko, I.A. Guzei, S.H. Gellman, S.S. Stahl, Organometallics 24
(2005) 5208–5210;
(f) J.M. Hoerter, K.M. Otte, S.H. Gellman, S.S. Stahl, J. Am. Chem. Soc. 128
(2006) 5177–5183;
(g) S.S. Stahl, S.H. Gellman, S.E. Eldred, US Patent, 2006, 7154004;
(h) D.A. Kissounko, J.M. Hoerter, I.A. Guzei, Q. Cui, S.H. Gellman, S.S. Stahl, J.
Am. Chem. Soc. 129 (2007) 1776–1783;
(b) L. Delaude, A. Demonceau, A.F. Noels, Chem. Commun. (2001) 986–987;
(c) L. Delaude, M. Szypa, A. Demonceau, A.F. Noels, Adv. Synth. Catal. 344
(2002) 749–756;
(i) J.M. Hoerter, K.M. Otte, S.H. Gellman, Q. Cui, S.S. Stahl, J. Am. Chem. Soc.
130 (2008) 647–654;
(d) A.A. Danopoulos, S. Winston, W.B. Motherwell, Chem. Commun. (2002)
1376–1377;
(j) M. Zhang, S. Imm, S. Bahn, L. Neubert, H. Neumann, M. Beller, Angew.
Chem. Int. Ed. 51 (2012) 3905–3909;
(e) M. Poyatos, E. Mas-Marza, M. Sanau, E. Peris, Inorg. Chem. 43 (2004)
1793–1798;
(k) B.N. Atkinson, A.R. Chhatwal, H.V. Lomax, J.W. Walton, J.M. Williams,
Chem. Commun. 11 (2012) 626–11628;
(f) M.R. Buchmeiser, D. Wang, Y. Zhang, S. Naumov, K. Wurst, Eur. J. Inorg.
Chem. (2007) 3988–4000;
(l) S.P. Pathare, A.K.H. Jain, K.G. Akamanchi, RSC Adv. 3 (2013) 7697–7703;
(g) M. Baya, B. Eguillor, M.A. Esteruelas, M. Olivan, E. Onate, Organometallics

26
M. Nirmala et al. / Journal of Molecular Catalysis A: Chemical 403 (2015) 15–26
26 (2007) 6556–6563;
(h) M. Poyatos, W. McNamara, C. Incarvito, E. Clot, E. Peris, R.H. Crabtree,
Organometallics 27 (2008) 2128–2136;
[32] (a) A.A. Gridnev, I.M. Mihaltseva, Synth. Commun. 24 (1994) 1547–1555;
(b) J. Liu, J. Chen, J. Zhao, Y. Zhao, L. Li, H. Zhang, Synthesis 17 (2003)
2661–2666;
(i) W. Ghattas, H. Muller-Bunz, M. Albrecht, Organometallics 29 (2010)
6782–6789.
[31] (a) C. Gunanathan, Y.B. David, D. Milstein, Science 317 (2007) 790–792;
(b) M.H.G. Prechtl, K. Wobser, N. Theyssen, Y.B. David, D. Milstein, W. Leitner,
Catal. Sci. Technol. 2 (2012) 2039–2042;
(c) B. Sreedhar, K.B. Shiva, P. Kumar Srinivas, V. Balasubrahmanyam, G.T.
Venkanna, J. Mol. Catal. A: Chem. 265 (2007) 183–185.
[33] D.E. Pearson, S.D. Venkataramu, W.E. Childers, Synth. Commun. 9 (1979) 5–10.
[34] N. Ahmed, S.J. Levison, S.D. Robinson, M.F. Uttley, Inorg. Synth. 15 (1974)
48–64.
(c) R.M. Lanigan, T.D. Sheppard, Eur. J. Org. Chem. 33 (2013) 7453–7465.
[35] G.M. Sheldrick, Acta Crystallogr. Sect. A 64 (2008) 112–122.