In situ Generated Ruthenium Catalyst Systems Bearing Diverse N-Heterocyclic Carbene Precursors for Atom-Economic Amide Synthesis from Alcohols and Amines

Article abstract of DOI:10.1002/asia.201701734

The transition-metal-catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom-economic process. Among various catalyst systems, in situ generated N-heterocyclic carbene (NHC)-based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron-deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR-scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=?7.8 ppm in the ¹H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system.

Full text of DOI:10.1002/asia.201701734

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: In situ generated ruthenium catalytic systems bearing diverse N-
heterocyclic carbene precursors for the atom-economic amide
synthesis from alcohols and amines
Authors: Hua Cheng, Mao-Qian Xiong, Chuan-Xiang Cheng, Hua-Jing
Wang, Qiang Lu, Hong-Fu Liu, Fu-Bin Yao, Francis Verpoort,
and Cheng Chen
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Chemistry - An Asian Journal
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FULL PAPER
In situ generated ruthenium catalytic systems bearing diverse N-
heterocyclic carbene precursors for the atom-economic amide
synthesis from alcohols and amines
[b]
[a]
[b]
[c]
[b]
[b]
Hua Cheng, Mao-Qian Xiong, Chuan-Xiang Cheng, Hua-Jing Wang, Qiang Lu, Hong-Fu Liu,
[b]
[a, c, d]
and Cheng Chen*[a]
Fu-Bin Yao, Francis Verpoort*
Dedication ((optional))
Abstract: The transition-metal-catalyzed direct amide synthesis from
alcohols and amines has been demonstrated as highly
composition of biological systems.[1] Although traditional
strategies for amide synthesis are general and widely used,
stoichiometric amounts of reagents are compulsory and large
a
environmental-benign and atom-economic process. Among various
catalytic systems, in situ generated N-heterocyclic carbene (NHC)-
based ruthenium (Ru) halide catalytic systems have been testified to
be active for this attractive transformation. However, these existing
catalytic systems usually required an additional ligand to achieve
satisfactory results. In this work, through extensive screening from a
diverse variety of NHC precursors, we discovered an active in situ
catalytic system for the efficient amide synthesis without any
additional ligand. Notably, this catalytic system is insensitive to the
electronic effects of the substrates, and various electron-deficient
substrates, which were not highly reactive with our previous catalytic
systems, could be employed to efficiently afford the corresponding
amides. Furthermore, mechanistic investigations were performed to
demonstrate the rational for the high activity of the optimized catalytic
system. The NMR scale reactions indicated that the rapid formation
[
2]
amounts of by-products are produced as waste , which is
inconsistent with the concept of “green and sustainable
[
3]
chemistry”. Recently, transition-metal-catalyzed oxidative
amide synthesis directly from alcohols and amines has been
highlighted as a highly atom-economic and environmental-
friendly transformation which generates hydrogen as the sole
[
4]
byproduct. Among various transition metals, ruthenium (Ru)
has been most extensively studied for this fascinating
transformation. Inspired by the pioneer reports from the
[
5]
[6]
Murahashi and Milstein groups, numerous researchers
have developed their respective Ru-based catalytic systems
[7]
for this reaction. In particular, N-heterocyclic carbenes
(NHCs) are a class of ideal ligands as their chemical
structures could be flexibly tuned to achieve the optimal
1
[8]
of a Ru hydride intermediate (a peak at -7.8 ppm from H NMR) after
catalytic performance of their metal complexes. Hence, our
the addition of the alcohol substrate should be a pivotal factor for
manifesting the high catalytic activity. Besides, HR-MS analysis
demonstrated the possible structures of the in situ generated catalytic
system.
great attention has been poured into the development and
catalytic performance of NHC-based Ru catalytic systems.
Though several well-defined Ru-NHC halide complexes
proved to be highly active for this transformation in the
[7d, 7f, 7j, 7r, 7w]
presence of a strong base (Fig. 1a),
preparations usually require the synthesis of the
corresponding Ag-NHC complexes, followed by
their
a
Introduction
transmetallation with a commercial Ru source. Therefore, the
corresponding in situ generated NHC-based Ru catalytic
systems have attracted our growing attention since they are
easily-operating and composed of commercially-available Ru
sources. Moreover, it is not necessary to isolate and purify the
Ag-NHC as well as Ru-NHC complexes. However, with regard
to the existing in situ NHC-based Ru halide catalytic systems,
The amide bond is a fundamental functional group in organic
chemistry, and it plays a crucial role in elaboration and
[
a]
Mao-Qian Xiong, Prof. Dr. Francis Verpoort and Dr. Cheng Chen,
State Key Laboratory of Advanced Technology for Materials
Synthesis and Processing
[
7a]
[7c]
an additional ligand such as a phosphine ligand, pyridine,
or acetonitrile
[7c, 7g]
Wuhan University of Technology, Wuhan 430070, PR China
E-mails: chengchen@whut.edu.cn; francis.verpoort@ghent.ac.kr
Dr. Hua Cheng, Chuan-Xiang Cheng, Qiang Lu, Hong-Fu Liu, Fu-
Bin Yao
was usually required to achieve
satisfactory results (Fig. 1b). Herein, we envisioned that an
active in situ catalytic system without any additional ligand
could be obtained by tuning the electronic and steric
properties of NHCs (Fig. 1c). Therefore, a number of NHC
precursors bearing versatile chemical structures were
designed and synthesized. Through extensive screening, an
in situ Ru-NHC catalytic system incorporating no additional
ligand was developed for the efficient amide synthesis.
Furthermore, mechanistic investigations were performed to
demonstrate the rationale for the high activity of the newly
developed catalytic system.
[
b]
Department of Chemical Engineering and Food Science
Hubei University of Arts and Science, Xiangyang 441053, P. R.
China
[
c]
d]
Hua-Jing Wang, Prof. Dr.Francis Verpoort
School of Chemistry, Chemical Engineering and Life Sciences,
Wuhan University of Technology, Wuhan 430070, P. R. China.
Prof. Dr.Francis Verpoort
[
National Research Tomsk Polytechnic University, Lenin Avenue 30,
Tomsk 634050, Russian Federation
Supporting information for this article is given via a link at the end of
the document.
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Figure 1. The design strategy of this work
Results and Discussion
(2.5 mol%), an NHC precursor (5 mol%) and NaH (20 mol%).
Firstly, 1,3-dimethyl-1H-imidazol-3-ium iodide (L1) was used and
a moderate yield of 3a was obtained. Replacement of both methyl
groups in L1 with bulkier tert-butyl groups resulted in a slightly
lower yield of the desired product. Besides, sulfonated NHC
precursors L3 and L4 were also tested, but only 28% and 26%
yields were obtained, respectively. To our delight, benzimidazole-
derived precursors L5-L7 resulted in satisfactory results. Notably,
in the presence of L5, compound 3a could be yielded in a 94%
NMR yield. Unfortunately, very low yield was observed if a
perimidine-based NHC precursor (L8) was used. Except mono-
dentate precursors, numerous bi-dentate and tri-dentate
counterparts (L9-L15) were examined. However, they only
provided the product with low to moderate yields.
Considering that the electronic and steric effects of NHCs may
influence their abilities to coordinate with Ru, diverse NHC
precursors were designed and synthesized (Figure 2). L1-L8,
mono-dentate NHC precursors with different steric and electronic
properties, were firstly prepared according to the literature
procedures. In addition, various multi-dentate NHC precursors
(
L9-L15) were also afforded. With all these precursors in hand,
we anticipated that a robust catalytic system bearing an optimal
NHC precursor could be obtained via extensive screening.
Therefore,
a reaction between benzyl alcohol (1a) and
benzylamine (2a) was selected as the model reaction, and the
effect of different NHC precursors on the yield of the product (3a)
was investigated (as shown in Figure 2). Inspired by previously
2 2
reported NHC-Ru systems, we initially used [RuCl (p-cymene)]
Figure 2. Synthesis of amide 3a applying various NHC precursors
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After setting up the optimal NHC precursor, screening of other
reaction conditions was then performed (as listed in Table 1).
Different Ru sources were investigated, and [RuCl (p-cymene)]
2 2
demonstrated the best activity (entries 1-4). Besides, the amount
of NaH was found to be crucial for the reaction, and 20 mol % of
NaH showed the best productivity (entries 1, 5-10). Also, the use
of KOtBu instead of NaH exhibited only a moderate yield (entry
Besides, heterocyclic substrates 1g and 1h could be efficiently
transformed into the amides 3g and 3h. Apparently, our catalytic
system is sensitive to steric hindrance, and the modestly
congested alcohol 1i produced amide 3i in a 50% yield. Rather
disappointingly, it also showed a similar limitation on the less
basic aniline (1j), and 3j was afforded in only a 35% yield even at
an elaborated temperature. Except primary amines, secondary
amines could also be tolerated. For instance, cyclic secondary
amines (1k and 1l) and N-methyl-1-phenylmethanamine (1m)
also reacted smoothly, producing the corresponding amides (3k-
3m) with 51-68% yields. In refluxing mesitylene, a 30% yield of
the tertiary amide (3n) was obtained from the challenging dibenzyl
amine (1n). Furthermore, we studied the electronic effects on both
substrates. Excitingly, unlike our previously reported catalytic
1
1). Furthermore, reducing the catalyst loading to 2 mol% and 1
mol% resulted in lower yields of the product (75% for entry 12 and
5% for entry 13). Therefore, the optimized reaction conditions
were identified as 1 (1.00 mmol), 2 (1.10 mmol), [RuCl (p-
cymene)] (0.025 mmol), L5 (0.05 mmol), NaH (0.20 mmol),
3
2
2
o
toluene (0.6 mL), 110 C, 24 h and used for further investigations
unless otherwise noted.
With the optimized reaction conditions in hand, the substrate
scope and limitations of this strategy were investigated. A range
of amides were obtained in fair to good yields (Figure 3). High
yields were obtained for sterically nonhindered substrates (1a-1f).
In particular, a six-membered cyclic lactam (3f) was synthesized
efficiently from the amino alcohol 1f in an intramolecular manner.
systems under which electron-deficient substrates were normally
less reactive,[
7d, 7g, 7i, 7p, 7x, 7y]
this catalytic system could catalyze
both electron-rich and electron-deficient substrates (1o-1r) in
comparably high yields.
Considering the wide availability of electron-withdrawing
3
substituents such as F, Cl, and CF in numerous bioactive
molecules,[9] we further evaluated the activities of our catalytic
system in various electron-deficient substrates. Firstly, the
reactions of 2a with substituted benzyl alcohols were
Table 1. Optimization of reaction conditions.[a]
Entry
[Ru]
Base (x)
Yield[b]
1
2
3
4
5
6
7
8
9
[RuCl
[RuCl
2
(p-cymene)]
(benzene)]
2
NaH (20)
NaH (20)
NaH (20)
NaH (20)
NaH (15)
NaH (25)
NaH (30)
NaH (40)
NaH (60)
NaH (100)
KOtBu (20)
NaH (8)
94%
75%
90%
91%
85%
80%
72%
56%
53%
47%
50%
75%
35%
2
2
RuCl
3
2 3 4
RuH (PPh )
[RuCl
[RuCl
[RuCl
[RuCl
[RuCl
[RuCl
[RuCl
[RuCl
[RuCl
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
(p-cymene)]
2
2
2
2
2
2
2
2
2
1
1
1
1
0
1
2[c]
3[d]
NaH (4)
[
a] 1a (1.0 mmol), 2a (1.1 mmol), [Ru] (5 mol%), L5 (5 mol%), a base (x mol%)
and toluene (0.6 mL) were used. [b]NMR yields using 1,3,5-trimethoxybenzene
as an internal standard. [c] [RuCl (p-cymene)] (1 mol%) and L5 (2 mol%) were
used. d [RuCl
(p-cymene)] (0.5 mol%) and L5 (1 mol%) were used.
2
2
2
2
Figure 3. Amide synthesis from various alcohols and amines
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evaluated. A substituent at the para position usually afforded the
corresponding products in high yields even if longer reaction time
were required in some cases (entries 2-4). Moreover, the position
of the substituent was found to significantly affect the catalytic
performance (entries 2, 5, 6). Compared with the 4-F group, a
slightly reduced yield and a much lower yield were obtained for 3-
F and 2-F, respectively, which was probably due to the steric
effect (80% for entry 2, 72% for entry 5 and 32% for entry 6).
Secondly, compounds 3r, 3w-3z were synthesized by treatment
of 1a with electron-poor benzyl amines (entries 7-11). When an F,
1a. In contrast, for the benzimidazole-based analog L5, 1a was
almost fully consumed and 3a was obtained in a 94% NMR yield.
This result indicated that the catalytic system utilizing L5 could
catalyze the alcohol amidation much faster than the L1-containing
counterpart. Generally, it was postulated that the generation of a
Ru hydride species via an alcohol and a strong base was crucial
[
7d,
for the catalytic activities of the Ru-chloride catalytic systems.
7
x]
Encouraged by the above observations and the literature
reports, we planned to monitor the Ru hydride formation by two
NMR scale reactions. Initially, a mixture of [RuCl (p-cymene)]
(0.025 mmol), L1 (or L5, 0.05 mmol), NaH (0.20 mmol) and
toluene-d (0.6 mL) were added to the NMR tubes. In both cases,
2
2
3
Cl or CF group was assembled at the para position of the phenyl
ring, the corresponding amides could be transformed in good
yields (entries 7-9). Moreover, the introduction of a substituent at
either the ortho, meta or para position did not significantly affect
the yields, leading to the formation of compounds 3r, 3y and 3z in
yields ranging from 81% to 85% (entries 7, 10-11).
In order to understand the rationale for the high activity of our
catalytic system, the mechanistic investigations were performed
by making a comparison between the L1- and L5-based catalytic
systems. As shown in Figure 4, L1, an imidazole-based NHC
precursor, produced 3a in a 50% yield with 41% of the unreacted
8
no hydride peak was found at room temperature (Figure 5a and
5b, yellow lines), while two major (-11.6 and -13.2 ppm) and two
minor (-11.5 and -12.7 ppm) hydride peaks appeared after heating
at refluxing temperature for 20 min (Figure 5a and 5b, purple
lines). However, significant differences were observed for the
varied NHC precursors in the presence of the alcohol substrate
1a. For L1, no obvious change was observed after the addition of
1a at room temperature (Figure 5a, green and red lines). Upon
heating at refluxing temperature, a hydride peak at -7.8 ppm
started to appear (Figure 5a, blue line). In contrast, immediately
after the addition of 1a, the hydride peaks ranging from -10 to 15
ppm disappeared and a new peak at -7.8 ppm was formed for L5
Table 2. Synthesis of amides from electron-deficient substrates. [a]
(
1
Figure 5b, green line). Moreover, this peak persisted even after
2 h at room temperature (Figure 5b, red and blue lines). This
result implied that the faster reaction rate for L5 vs. L1 might be
attributed to the more rapid formation of the characteristic Ru
hydride species after 1a was added.
With an aim of identifying the real catalytic species, the possible
structures of the in situ generated [Ru]-L5 catalytic system were
analysed by HR-MS (as depicted in Figure 6). One major Ru
species ([Ru]-1) and two minor Ru species ([Ru]-2 and [Ru]-3)
were clearly identified in Figure 6, which represented that the Ru
species bearing one NHC and a p-cymene ligand ([Ru]-1 and
Yield[b]
Entry
Compound No.
R
H
1
R
2
1
2
3
4
5
6
7
8
9
3a
3p
3s
3t
H
H
H
H
H
H
88% (<1%[c], <1%[d]
)
[
Ru]-2) should play the major role for the catalytic activity. In
80% (4%[c], 6%[d]
addition, one p-cymene and two NHC ligands could also
coordinate to Ru spontaneously and the respective Ru species
4-F
4-Cl
4-CF
3-F
2-F
H
)
72%[e] (12%[c], 10%[d]
80%[e] (<1%[c], 7%[d]
)
(
[Ru]-3) was detected as a minor species from the HR-MS
analysis.
3
)
3u
3v
3r
72% (8%[c], 8%[d]
32% (26%[c], 8%[d]
85% (<1%[c], 3%[d]
76% (4%[c], 12%[d]
)
)
4-F
)
3w
3x
3y
3z
H
4-Cl
4-CF
3-F
)
H
3
75% (3%[c], 3%[d]
81% (8%[c], 5%[d]
)
)
1
0
1
H
1
H
2-F
85% (<1%[c], 5%)
[
a] Reaction conditions: 1 (1.00 mmol), 2 (1.10 mmol), the L5/Ru in situ catalytic
Figure 4. Comparison of the catalytic performance between L1- and L5-based
system: [RuCl (p-cymene)] (0.025 mmol), L5 (0.05 mmol), NaH (0.20 mmol),
2
2
toluene (0.6 mL), 110 oC, 24 h. [b] Isolated yields. [c] The yields of unreacted
catalytic system.
alcohols. [d] The yields of the imine byproducts. [e] 48 h.
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(a) [Ru]-L1, r.t. 0 h
(b) [Ru]-L5, r.t. 0 h
[
Ru]-L1, reflux 20 min
[Ru]-L5, reflux 20 min
[Ru]-L5 + 1a, r.t. 0 h
[Ru]-L5 + 1a, r.t. 6 h
[
Ru]-L1 + 1a, r.t. 0 h
[Ru]-L1 + 1a, r.t. 6 h
[Ru]-L5 + 1a, r.t. 12 h
[Ru]-L1 + 1a, reflux 1 h
Figure 5. NMR monitoring of (a) the [Ru]-L1 and (b) [Ru]-L5 catalytic systems. [Ru]-L1 represents the in situ generated catalytic system including [RuCl
2
(p-
cymene)] (0.025 mmol), L1 (0.05 mmol) and NaH (0.20 mmol); and [Ru]-L5 represents the in situ system including [RuCl (p-cymene)] (0.025 mmol), L5 (0.05
2
2
2
mmol) and NaH (0.20 mmol). Besides, 1a (0.15 mmol) was used for each NMR reaction.
Figure 6. The HR-MS analysis for the possible structures of the optimized in situ catalytic system.
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On the basis of the above studies and our previous
the Ru dihydride IV. We believe that the faster reaction rate for L5
is probably due to the less electron-rich nature of benzimidazole
compared to imidazole.[10] Presumably, L5 could promote the
transformation of II from I faster than L1 because the in situ
generated intermediate I from L5, which possess lower electron
density on the Ru centre than that from L1, could undergo ligand
substitution from Cl or I to the alkoxide more rapidly.
[
7d]
publication, the proposed mechanism was illustrated in Figure
. It could be concluded that the key steps were the generation of
the [Ru]H species IV from the halogen-based [Ru] intermediate I.
7
2
Apparently, the role of NaH should be to deprotonate the NHC
precursor and stimulate the generation of the Ru alkoxide species
II. Subsequent β-hydrogen elimination can generate the Ru
monohydride species III, which could be further transformed to
Figure 7. The proposed reaction mechanism for the Ru-catalyzed alcohol amidation with amines.
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methyl-1H-imidazol-3-ium) bromide (L15)[21] were prepared using
Conclusions
the procedures reported in the literature.
In summary, based on a diverse library of NHC precursors, we
have identified an in situ generated Ru-NHC chloride catalytic
system without an additional ligand. This catalytic system is
efficient for the atom-economic alcohol amidation with amines,
and various amides were successfully yielded in moderate to high
yields. More importantly, most of the electron-poor substrates
could also be introduced to assemble the corresponding amides
in good yields. Furthermore, we attempted to reveal the reaction
mechanism by making a comparison between the imidazole- and
benzimidazole-based catalytic systems (L1 and L5, respectively).
This result indicated that the L5-containing catalytic system could
catalyze the reaction much more quickly than the L1-containing
counterpart. Further NMR scale experiments implied that
compared with L1, the faster formation of a characteristic Ru
hydride species for L5 after the alcohol addition should be an
important reason for the higher reaction rate. Finally, the possible
structures of the [Ru]-L5 catalytic system were evaluated by HR-
MS. It was indicated that the Ru species bearing a p-cymene and
one NHC ligand were probably the key species while the one with
two NHC and one p-cymene ligands were also identified as a
minor species.
General procedure for the amide synthesis.
[Ru(p-cymene)Cl2]2 (15.3 mg, 0.025 mmol), 1,3-dimethyl-1H-
benzo[d]imidazol-3-ium iodide (L5, 13.7 mg, 0.05 mmol), NaH
(
(
60 % dispersion in mineral oil, 8.0 mg, 0.2 mmol) and toluene
0.6 mL) were added to an oven-dried Schlenk tube placed inside
an argon-filled glovebox. The reaction mixture was heated to
reflux under argon for 20 min. The flask was taken out of the oil
bath before an alcohol (1.00 mmol) and an amine (1.10 mmol)
were added, and the mixture was heated to reflux in an open
condition under an argon atmosphere for 24 h. The reaction
mixture was cooled down to room temperature, and the solvent
was removed under reduced pressure. Finally, the residue was
purified by silica gel flash column chromatography to afford the
amide.
Analytical data for the amides (3a-3z).
[22]
White solid: m.p. 101.1-102.5 oC.
N-benzylbenzamide (3a).
1
Isolated yield: 88%. H NMR (500 MHz, CDCl
3
) δ 7.79 (d, J = 7.1
Hz, 2H), 7.54 – 7.47 (m, 1H), 7.43 (dd, J = 7.6, 7.4 Hz, 2H), 7.40
7.26 (m, 5H), 6.40 (s, 1H), 4.66 (d, J = 5.6 Hz, 2H). 13C NMR
126 MHz, CDCl ) δ 167.29, 138.17, 134.41, 131.53, 128.80,
28.59, 127.92, 127.64, 126.93, 44.16. IR (KBr) ν 3325, 3059,
–
(
3
Experimental Section
1
3
–
1
028, 1641, 1543, 727, 692, 665 cm . HR-MS (ESI): m/z calcd.
General considerations
+
for C14
H
14NO [M+H] : 212.1070; Found: 212.1071.
[
7i]
N-benzyl-2-phenylacetamide (3b). White solid: m.p. 118.0-
1H NMR spectra were recorded on a Bruker Avance 500
o
1
119.2 C. Isolated yield: 82%. H NMR (500 MHz, CDCl
3
) δ 7.41
spectrometer in CDCl
3
with TMS as the internal reference, and
on a Bruker Avance 500
126 MHz) spectrometer. The following abbreviations are used to
–
7.35 (m, 2H), 7.34 – 7.28 (m, 6H), 7.20 (d, J = 6.8 Hz, 2H), 5.68
1
3C NMR spectra were recorded in CDCl
3
s, 1H), 4.44 (d, J = 5.8 Hz, 2H), 3.66 (s, 2H). 13C NMR (126 MHz,
) δ 170.79, 138.13, 134.78, 129.45, 129.07, 128.66, 127.48,
27.43, 127.41, 43.89, 43.61. IR (KBr) ν 3288, 3084, 2923, 1637,
(
(
CDCl
1
1
3
designate multiplicities: s = singlet, d = doublet, t = triplet, q =
quartet, dd = doublet of doublets, m = multiplet. Melting points
were taken on a Buchi M-560 melting point apparatus and are
uncorrected. IR analysis was performed on a Bruker Vertex 80v
FT-IR spectrometer. HR-MS was done on a Thermo Fisher Q
Exactive Mass Spectrometer. All the substrates and solvents
were obtained from commercial suppliers and used as received
without further purification. The NHC precursors including 1,3-
dimethyl-1H-imidazol-3-ium iodide (L1),[11] 1,3-di-tert-butyl-1H-
imidazol-3-ium chloride (L2),[12] 3-(1-mesityl-1H-imidazol-3-ium-
–1
550, 1452, 1026, 725, 692, 601 cm . HR-MS (ESI): m/z calcd.
+
for C15
H
16NO [M+H] : 226.1226; Found: 226.1236.
[
22]
White solid: m.p. 54.5-55.6 oC.
) δ 7.52 – 7.21 (m,
N-benzylhexanamide (3c).
1
Isolated yield: 80%. H NMR (500 MHz, CDCl
3
5
H), 5.77 (s, 1H), 4.46 (d, J = 5.7 Hz, 2H), 2.23 (t, J = 7.6 Hz, 2H),
.78 – 1.60 (m, 2H), 1.46 – 1.22 (m, 4H), 0.92 (t, J = 6.8 Hz, 3H).
) δ 172.97, 138.44, 128.71, 127.84,
27.50, 43.59, 36.80, 31.50, 25.47, 22.42, 13.96. IR (KBr) ν 3293,
084, 3031, 2955, 2931, 2856, 1634, 1553, 1454, 1432, 725, 695,
1
1
3C NMR (126 MHz, CDCl
3
1
3
6
2
3
3
-yl)propane-1-sulfonate (L3),[13] 4-(1-mesityl-1H-imidazol-3-ium-
04 cm . HR-MS (ESI): m/z calcd. for C13H
20NO [M+H]+:
06.1539; Found: 206.1541.
–
1
-yl)butane-1-sulfonate
(L4),[13]
1,3-dimethyl-1H-
1,3-diisopropyl-1H-
[
14]
benzo[d]imidazol-3-ium iodide (L5),
N-hexylbenzamide (3d).[
23]
White solid: m.p. 40.5-41.6 oC.
) δ 7.79 (d, J = 7.3
benzo[d]imidazol-3-ium bromide (L6),[14] 1,3,5,6-tetramethyl-1H-
benzo[d]imidazol-3-ium iodide (L7),[14] 1,3-dimethyl-1H-perimidin-
1
Isolated yield: 83%. H NMR (500 MHz, CDCl
3
-ium chloride (L8),[15]
Hz, 2H), 7.45 (dd, J = 7.6, 7.4 Hz, 1H), 7.37 (dd, J = 7.6, 7.4 Hz,
2H), 6.77 (s, 1H), 3.40 (q, J = 6.8 Hz, 2H), 1.67 – 1.49 (m, 2H),
3
1,3-di(pyridin-2-yl)-1H-imidazol-3-ium
chloride (L9),[16] 2-(3-(pyridin-2-ylmethyl)-1H-imidazol-3-ium-1-
1.39 – 1.18 (m, 6H), 0.88 (t, J = 6.7 Hz, 3H). 1
CDCl ) δ 167.63, 134.86, 131.17, 128.40, 126.95, 40.15, 31.53,
29.62, 26.70, 22.57, 14.02. IR (KBr) ν 3318, 2929, 2858, 1642,
3C NMR (126 MHz,
(L10),[17]
yl)acetate
1-(2-ethoxy-2-oxoethyl)-3-(pyridin-2-
ylmethyl)-1H-imidazol-3-ium chloride (L11),[17] 3,3'-(pyridazine-
3
,6-diyl)bis(1-methyl-1H-imidazol-3-ium) chloride (L12),[18] 1,1'-
3
–
1
1
578, 1541, 1491, 1310, 695 cm . HR-MS (ESI): m/z calcd. for
(
(
pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)
bromide
+
L13),[
19]
C H NO [M+H] : 206.1539; Found: 206.1538.
1,1'-(1,3-phenylene)bis(3-methyl-1H-imidazol-3-ium)
13 20
iodide
(L14),[20]
1,1'-(pyridine-2,6-diylbis(methylene))bis(3-
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Chemistry - An Asian Journal
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N-phenethylbenzamide (3e).[ White solid: m.p. 118.8-120.2
24]
4H), 1.55 (s, 2H). 13C NMR (126 MHz, CDCl
) δ 170.31, 136.58,
3
129.31, 128.38, 126.79, 48.81, 43.11, 26.65, 25.65, 24.62. IR
o
1
C. Isolated yield: 85%. H NMR (500 MHz, CDCl
3
) δ 7.71 (d, J =
6
7
3
.9 Hz, 2H), 7.54 – 7.47 (m, 1H), 7.43 (dd, J = 8.5, 6.9 Hz, 2H),
.36 (dd, J = 7.6, 7.5 Hz, 2H), 7.37-7.26 (m, 3H), 6.14 (s, 1H),
.76 (q, J = 6.6 Hz, 2H), 2.97 (t, J = 7.0 Hz, 2H). 13C NMR (126
(KBr) ν 3058, 2998, 2936, 2854, 1632, 1578, 1444, 1430, 1276,
1259, 1238, 1112, 1029, 1003, 852, 788, 731, 708, 631 cm . HR-
–
1
+
MS (ESI): m/z calcd. for C12
190.1242.
H
16NO [M+H] : 190.1226; Found:
MHz, CDCl
3
) δ 167.42, 138.90, 134.70, 131.38, 128.81, 128.72,
28.55, 126.78, 126.60, 41.11, 35.72. IR (KBr) ν 3342, 3059,
026, 2931, 2861, 1640, 1544, 1313, 1295, 1194, 1156, 799, 750,
[
23]
1
3
6
Morpholino(phenyl)methanone (3l). White solid: m.p. 73.5-
74.9 C. Isolated yield: 55%. H NMR (500 MHz, CDCl
7.33 (m, 5H), 4.05 – 3.15 (m, 8H). 13C NMR (126 MHz, CDCl
3
o
1
3
) δ 7.62 –
–
1
95, 667, 502, 422 cm . HR-MS (ESI): m/z calcd. for C15
H16NO
) δ
+
[
M+H] : 226.1226; Found: 226.1229.
170.41, 135.34, 129.83, 128.53, 127.06, 66.88, 48.24, 42.57. IR
Piperidin-2-one (3f).[7d] Pale yellow oil. Isolated yield: 75%. H
1
(KBr) ν 3059, 2971, 2917, 2900, 2857, 1849, 1708, 1629, 1430,
–1
NMR (500 MHz, CDCl
3
) δ 7.17 (s, 1H), 3.41 – 3.13 (m, 2H), 2.29
1273, 1257, 1155, 1111, 1017, 842, 790, 735, 711, 544 cm . HR-
t, J = 6.5 Hz, 2H), 1.83 – 1.60 (m, 4H). 13C NMR (126 MHz,
MS (ESI): m/z calcd. for C11
192.1034.
H
14NO
[M+H] : 192.1019; Found:
+
(
2
3
CDCl ) δ 172.72, 42.10, 31.43, 22.21, 20.81. IR (KBr) ν 3219,
[27]
2
9
1
944, 2868, 1666, 1497, 1409, 1352, 1328, 1307, 1180, 1113,
37, 660 cm . HR-MS (ESI): m/z calcd. for C
00.0757; Found: 100.0761.
N-benzyl-N-methylbenzamide (3m). White solid: m.p. 163.5-
–
1
10NO [M+H]+:
o
1
5
H
164.9 C. Isolated yield: 68%. H NMR (500 MHz, CDCl
– 7.46 (m, 2H), 7.47 – 7.30 (m, 7H), 7.20 (s, 1H), 4.98 – 4.31 (m,
2H), 3.26 – 2.68 (m, 3H). 13C NMR (126 MHz, CDCl
) δ 172.29,
3
) δ 7.52
[
22]
N-benzylfuran-2-carboxamide (3g). White solid: m.p. 109.8-
3
o
1
111.3 C. Isolated yield: 70%. H NMR (500 MHz, CDCl
3
) δ 7.44
171.60, 137.06, 136.67, 136.30, 129.59, 128.77, 128.43, 128.19,
(
s, 1H), 7.38 (d, J = 4.3 Hz, 4H), 7.32 (q, J = 4.5 Hz, 1H), 7.17 (d,
J = 3.5 Hz, 1H), 6.65 (s, 1H), 6.53 (s, 1H), 4.65 (d, J = 5.9 Hz, 2H).
13C NMR (126 MHz, CDCl
) δ 158.23, 147.92, 143.84, 138.00,
28.74, 127.88, 127.61, 114.37, 112.15, 43.17. IR (KBr) ν 3285,
125, 3061, 3028, 1639, 1574, 1543, 1475, 1319, 750, 737, 700,
127.55, 126.95, 126.86, 55.19, 50.84, 37.00, 33.17. IR (KBr) ν
3061, 3028, 2922, 1634, 1498, 1447, 1399, 1264, 1069, 1026,
–1
3
790, 718, 699 cm . HR-MS (ESI): m/z calcd. for C15
H
16NO
+
1
3
6
2
[M+H] : 226.1226; Found: 226.1232.
N,N-dibenzylbenzamide (3n).[ White solid: m.p. 112.3-113.6
C. Isolated yield: 30%. H NMR (500 MHz, CDCl
28]
–
1
[M+H]+:
o
1
19 cm . HR-MS (ESI): m/z calcd. for C12
02.0863; Found: 202.0872.
H
12NO
2
3
) δ 7.57 – 7.48
(m, 2H), 7.46 – 7.28 (m, 11H), 7.17 (s, 2H), 4.74 (s, 2H), 4.44 (s,
2H).13C NMR (126 MHz, CDCl
) δ 172.25, 137.01, 136.49, 136.23,
[
25]
N-(furan-2-ylmethyl)benzamide (3h). White solid: m.p. 99.8-
3
o
1
1
01.1 C. Isolated yield: 60%. H NMR (500 MHz, CDCl
3
) δ 7.81
129.63, 128.78, 128.75, 128.54, 128.44, 127.59, 127.56, 127.07,
(
dd, J = 7.1, 1.4 Hz, 2H), 7.56 – 7.49 (m, 1H), 7.49 – 7.42 (m, 2H),
126.73, 51.58, 46.93. IR (KBr) ν 3062, 3027, 2956, 2916, 2852,
1638, 1495, 1448, 1419, 1254, 997, 792, 745, 727, 698 cm . HR-
–
1
7
4
1
3
1
.40 (d, J = 2.0 Hz, 1H), 6.53 – 6.40 (m, 1H), 6.40 – 6.29 (m, 2H),
.67 (d, J = 5.5 Hz, 2H). 13C NMR (126 MHz, CDCl
) δ 167.16,
MS (ESI): m/z calcd. for C21
302.1534.
H
20NO [M+H] : 302.1539; Found:
+
3
51.19, 142.32, 134.22, 131.60, 128.58, 126.98, 110.52, 107.69,
[
7p]
7.04. IR (KBr) ν 3299, 2922, 2852, 1641, 1549, 1424, 1347, 1311,
N-benzyl-4-methylbenzamide (3o). White solid: m.p. 134.3-
–
1
o
1
249, 1013, 988, 806, 748, 692 cm . HR-MS (ESI): m/z calcd. for
3
135.6 C. Isolated yield: 88%. H NMR (500 MHz, CDCl ) δ 7.75
+
C
12
H
12NO
2
[M+H] : 202.0863; Found: 202.0843.
– 7.70 (m, 2H), 7.38 (d, J = 4.4 Hz, 4H), 7.35 – 7.30 (m, 1H), 7.25
(d, J = 7.9 Hz, 2H), 6.37 (s, 1H), 4.67 (d, J = 5.7 Hz, 2H), 2.42 (s,
[26]
N-benzyl-2-phenylpropanamide (3i). White solid: m.p. 76.6-
8.0 C. Isolated yield: 50%. H NMR (500 MHz, CDCl
o
1
3H).13C NMR (126 MHz, CDCl
7
3
) δ 7.43 –
3
) δ 167.26, 141.96, 138.33, 131.57,
7
(
.25 (m, 8H), 7.17 (d, J = 7.3 Hz, 2H), 5.77 (s, 1H), 4.51 – 4.30
129.24, 128.77, 127.92, 127.58, 126.94, 44.11, 21.42. IR (KBr) ν
m, 2H), 3.63 (q, J = 7.2 Hz, 1H), 1.59 (d, J = 7.2 Hz, 3H). 13C
3310, 3057, 3026, 2918, 1640, 1547, 843, 721, 673 cm . HR-MS
–1
+
NMR (126 MHz, CDCl
3
) δ 173.99, 141.28, 138.30, 128.87, 128.55, (ESI): m/z calcd. for C15
226.1235.
N-benzyl-4-fluorobenzamide (3p).
H
16NO [M+H] : 226.1226; Found:
127.60, 127.39, 127.28, 127.24, 47.11, 43.51, 18.50. IR (KBr) ν
[
7p]
3305, 3064, 3030, 2918, 1649, 1544, 1452, 1072, 1016, 727, 696
White solid: m.p. 134.3-
135.6 C. Isolated yield: 80%. H NMR (500 MHz, CDCl ) δ 7.83
–1
17NONa [M+Na]+:
o
1
cm . HR-MS (ESI): m/z calcd. for
62.1202; Found: 262.1203.
C
16
H
3
2
(dd, J = 8.4, 5.2 Hz, 2H), 7.46 – 7.31 (m, 5H), 7.13 (dd, J = 8.5,
8.4 Hz, 2H), 6.39 (s, 1H), 4.66 (d, J = 5.6 Hz, 2H). 13C NMR (126
N-phenylbenzamide (3j).[ White solid: m.p. 165.6-167.0 C.
22]
o
1
Isolated yield: 35%. H NMR (500 MHz, CDCl
3
) δ 7.95 – 7.78 (m,
3
MHz, CDCl ) δ 166.26, 164.77 (d, J = 252.0 Hz), 138.05, 130.58
3
(
H), 7.67 (d, J = 7.9 Hz, 2H), 7.58 (dd, J = 7.4, 7.2 Hz, 1H), 7.51
dd, J = 7.6, 7.4 Hz, 2H), 7.40 (dd, J = 8.0, 7.8 Hz, 2H), 7.18 (dd,
J = 7.6, 7.4 Hz, 1H). 13C NMR (126 MHz, CDCl
) δ 165.68, 137.92,
35.04, 131.85, 129.12, 128.82, 127.00, 124.59, 120.17. IR (KBr)
ν 3343, 3051, 2962, 1655, 1599, 1531, 1437, 1322, 1261, 802,
(d, J = 3.3 Hz), 129.27 (d, J = 9.0 Hz), 128.83, 127.94, 127.71,
115.63 (d, J = 21.9 Hz), 44.25. IR (KBr) ν 3321, 3068, 3031, 1641,
–1
3
1552, 1502, 1325, 1229, 1161, 856, 723, 667 cm . HR-MS (ESI):
+
1
m/z calcd. for C14
H
13FNO [M+H] : 230.0976; Found: 230.0970.
[
29]
N-(4-methylbenzyl)benzamide (3q). White solid: m.p. 137.3-
–
1
o
1
750, 715, 690, 647, 582, 508 cm . HR-MS (ESI): m/z calcd. for
3
138.6 C. Isolated yield: 83%. H NMR (500 MHz, CDCl ) δ 7.85
+
C
13
H
12NO [M+H] : 198.0913; Found: 198.0912.
– 7.73 (m, 2H), 7.53 – 7.47 (m, 1H), 7.46 – 7.39 (m, 2H), 7.25 (s,
2H), 7.17 (d, J = 7.8 Hz, 2H), 6.31 (s, 1H), 4.61 (d, J = 5.6 Hz, 2H),
[
22]
Phenyl(piperidin-1-yl)methanone (3k).
White solid: m.p.
6.8-47.9 C. Isolated yield: 51%. H NMR (500 MHz, CDCl ) δ
.41 (s, 5H), 3.73 (s, 2H), 3.36 (s, 2H), 1.81 – 1.66 (d, J = 5.7 Hz,
o
1
2.35 (s, 3H).13C NMR (126 MHz, CDCl
4
7
3
3
) δ 167.25, 137.27, 135.16,
134.47, 131.41, 129.39, 128.50, 127.88, 126.92, 43.88, 21.05. IR
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Chemistry - An Asian Journal
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(
8
C
KBr) ν 3306, 3024, 2918, 1633, 1543, 1488, 1443, 1316, 1295,
04, 703, 667, 567, 476 cm . HR-MS (ESI): m/z calcd. for
Hz, 2H), 7.36 – 7.30 (m, 4H), 6.53 (s, 1H), 4.63 (d, J = 6.1 Hz, 2H).
–
1
13C NMR (126 MHz, CDCl
3
) δ 167.39, 136.81, 134.20, 133.42,
+
15
H
16NO [M+H] : 226.1226; Found: 226.1211.
131.68, 129.21, 128.89, 128.64, 126.95, 43.39. IR (KBr) ν 3342,
3310, 3062, 3028, 2927, 1640, 1546, 1491, 1420, 1315, 1296,
[30]
N-(4-fluorobenzyl)benzamide (3r). White solid: m.p. 115.3-
16.6 C. Isolated yield: 85%. H NMR (500 MHz, CDCl
o
1
–1
1
(
3
) δ 7.81
801, 791, 694, 653 cm . HR-MS (ESI): m/z calcd. for C14
H13ClNO
+
dd, J = 8.4, 1.4 Hz, 2H), 7.60 – 7.50 (m, 1H), 7.50 – 7.41 (m, 2H),
[M+H] : 246.0680; Found: 246.0667.
N-(4-trifluoromethylbenzyl)benzamide (3x). White solid: m.p.
[
31]
7
4
1
1
4
1
.40 – 7.31 (m, 2H), 7.06 (dd, J = 8.8, 8.6 Hz, 2H), 6.39 (s, 1H),
.65 (d, J = 5.7 Hz, 2H). 13C NMR (126 MHz, CDCl
) δ 167.30,
o
1
3
3
143.8-145.1 C. Isolated yield: 75%. H NMR (500 MHz, CDCl ) δ
62.28 (d, J = 246.0 Hz), 134.28, 134.03 (d, J = 3.4 Hz), 131.64,
29.60 (d, J = 8.1 Hz), 128.64, 126.92, 115.64 (d, J = 21.5 Hz),
7.83 (d, J = 7.7 Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.58 – 7.40 (m,
5H), 6.60 (s, 1H), 4.73 (d, J = 6.0 Hz, 2H). 13C NMR (126 MHz,
3
3.42. IR (KBr) ν 3299, 3070, 2926, 1636, 1549, 1509, 1421, 1316, CDCl ) δ 167.50, 142.39, 134.04, 131.80, 129.88 (q, J = 32.7 Hz),
–
1
220, 1160, 845, 802, 692, 672, 495 cm . HR-MS (ESI): m/z
128.69, 127.98, 126.96, 125.71, 124.06 (q, J = 272.1 Hz), 43.55.
δ. IR (KBr) ν 3291, 3066, 2918, 1642, 1547, 1420, 1413, 1334,
+
calcd. for C14
H
13FNO [M+H] : 230.0976; Found: 230.0960.
[
7g]
–1
N-benzyl-4-chlorobenzamide (3s). White solid: m.p. 115.3-
1267, 1174, 1099, 1064, 850, 801, 697, 674 cm . HR-MS (ESI):
o
1
+
1
(
6
16.6 C. Isolated yield: 72%. H NMR (500 MHz, CDCl
d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H), 7.40 – 7.29 (m, 5H),
.51 (s, 1H), 4.64 (d, J = 5.6 Hz, 2H). 13C NMR (126 MHz, CDCl
δ 166.30, 137.96, 137.80, 132.75, 128.84, 128.42, 127.93, 127.73, J = 7.6 Hz, 2H), 7.51 (dd, J = 7.0, 6.8 Hz, 1H), 7.42 (dd, J = 7.6,
3
) δ 7.75
m/z calcd. for C15
H
13
F
3
NO [M+H] : 280.0944; Found: 280.0938.
[
32]
N-(3-fluorobenzyl)benzamide (3y).
87.8 C. Isolated yield: 81%. H NMR (500 MHz, CDCl ) δ 7.81 (d,
White solid: m.p. 86.8-
o
1
3
)
3
4
4.24. IR (KBr) ν 3314, 3085, 2963, 2924, 1639, 1595, 1553, 1487, 7.5 Hz, 2H), 7.34 – 7.23 (m, 1H), 7.10 (d, J = 7.5 Hz, 1H), 7.03 (d,
–
1
J = 9.4 Hz, 1H), 7.01 – 6.68 (m, 2H), 4.60 (d, J = 6.0 Hz, 2H). 13
1421, 1318, 1259, 849, 799, 736, 712, 670, 524, 472, 455 cm .
C
+
HR-MS (ESI): m/z calcd. for C14
Found: 246.0659.
H
13ClNO [M+H] : 246.0680;
NMR (126 MHz, CDCl ) δ 167.58, 163.01 (d, J = 246.5 Hz),
3
140.96 (d, J = 6.1 Hz), 134.16, 131.66, 130.22 (d, J = 8.1 Hz),
128.60, 127.03, 123.24, 114.56 (d, J = 21.7 Hz), 114.36 (d, J =
21.1 Hz), 43.46. IR (KBr) ν 3289, 3083, 2925, 1640, 1616, 1553,
[
7p]
N-benzyl-4-trifluoromethylbenzamide (3t). White solid: m.p.
o
1
1
7
5
3
62.0-163.5 C. Isolated yield: 80%. H NMR (500 MHz, CDCl ) δ
.92 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.46 – 7.30 (m,
H), 6.54 (s, 1H), 4.68 (d, J = 5.7 Hz, 2H). 13C NMR (126 MHz,
1491, 1448, 1416, 1317, 1252, 1129, 995, 914, 779, 746, 698,
–1
H
13FNO [M+H]+:
686 cm . HR-MS (ESI): m/z calcd. for C14
CDCl
3
) δ 166.05, 137.74, 137.67, 133.32 (q, J = 32.5 Hz), 128.88,
27.94, 127.83, 127.45, 125.65 (q, J = 3.7 Hz). 123.64 (q, J =
72.8 Hz), 44.34. IR (KBr) ν 3329, 2928, 1641, 1551, 1331, 1167,
230.0976; Found: 230.0968.
1
2
1
N-(2-fluorobenzyl)benzamide (3z).[33] m.p. 86.6-87.9 oC.
1
Isolated yield: 85%. H NMR (500 MHz, CDCl
3
) δ 7.80 (d, J = 7.6
–
1
124, 1070, 862, 727, 696, 669 cm . HR-MS (ESI): m/z calcd. for
Hz, 2H), 7.51 (dd, J = 7.6, 7.5 Hz, 1H), 7.48 – 7.39 (m, 3H), 7.29
(d, J = 6.4 Hz, 1H), 7.13 (dd, J = 7.6, 7.5 Hz, 1H), 7.08 (dd, J =
9.3, 9.2 Hz, 1H), 6.68 (s, 1H), 4.71 (d, J = 5.9 Hz, 2H). 13C NMR
+
C
15
H
13
F
3
NO [M+H] : 280.0944; Found: 280.0958.
[
7p]
N-benzyl-3-fluorobenzamide (3u).
White solid: m.p. 90.5-
1.8 C. Isolated yield: 72%. H NMR (500 MHz, CDCl ) δ 7.60 –
.50 (m, 2H), 7.45 – 7.30 (m, 6H), 7.26 – 7.16 (m, 1H), 6.59 (s,
H), 4.64 (d, J = 5.2 Hz, 2H). 13C NMR (126 MHz, CDCl
) δ 166.12, 126.99, 125.22 (d, J = 14.7 Hz), 124.37 (d, J = 3.6 Hz), 115.41 (d,
62.76 (d, J = 247.8 Hz), 137.91, 136.68 (d, J = 6.7 Hz), 130.23
o
1
9
7
1
1
3
(126 MHz, CDCl
3
) δ 167.41, 161.11 (d, J = 246.0 Hz), 134.29,
131.56, 130.38 (d, J = 4.2 Hz), 129.36 (d, J = 8.2 Hz), 128.57,
3
J = 21.3 Hz), 38.09 (d, J = 3.7 Hz). IR (KBr) ν 3291, 3066, 2918,
(
d, J = 7.5 Hz), 128.82, 127.91, 127.72, 122.42, 118.53 (d, J =
1.3, 2.3 Hz), 114.45 (d, J = 22.7 Hz), 44.24. IR (KBr) ν 3329,
1641, 1547, 1490, 1421, 1413, 1334, 1267, 1174, 1098, 1066,
–
1
2
3
8
1018, 990, 850, 801, 696, 674 cm . HR-MS (ESI): m/z calcd. for
+
078, 3060, 3033, 1643, 1585, 1546, 1483, 1419, 1324, 1227,
C
14
H
13FNO [M+H] : 230.0976; Found: 230.0988.
–
1
95, 885, 808, 758, 722, 690 cm . HR-MS (ESI): m/z calcd. for
+
C
14
H
13FNO [M+H] : 230.0976; Found: 230.0949.
[
7p]
N-benzyl-2-fluorobenzamide (3v).
White solid: m.p. 48.9-
9.9 C. Isolated yield: 32%. H NMR (500 MHz, CDCl ) δ 8.15
dd, J = 8.1, 8.0 Hz, 1H), 7.48 (d, J = 7.1 Hz, 1H), 7.38 (d, J = 4.9
Hz, 4H), 7.34 – 7.26 (m, 2H), 7.17 – 7.01 (m, 2H), 4.71 (d, J = 5.5
Hz, 2H). 13C NMR (126 MHz, CDCl
) δ 163.29 (d, J = 3.2 Hz),
60.64 (d, J = 247.2 Hz), 138.05, 133.32 (d, J = 9.2 Hz), 132.14
d, J = 2.2 Hz), 128.76, 127.73, 127.55, 124.83 (d, J = 3.2 Hz),
21.04 (d, J = 11.6 Hz), 116.00 (d, J = 24.8 Hz), 44.08. IR (KBr)
ν 3357, 3062, 3034, 2936, 1646, 1613, 1482, 1451, 1425, 1305,
Acknowledgements
o
1
4
(
3
This research was supported by the National Natural Science
Foundation of China (No. 21502062), Hubei Provincial
Department of Education (No. Q20102606), Xiangyang Science
and Technology Bureau (No. 2010GG1B33), and an open project
of electromechanical-automobile discipline of Hubei province (No.
XKQ2017027). F.V. acknowledges the support from the Tomsk
Polytechnic University Competitiveness Enhancement Program
grant (VIU-316/2017).
3
1
(
1
–
1
1
(
223, 1097, 835, 783, 755, 742, 699, 649, 602 cm . HR-MS
+
ESI): m/z calcd. for C14
H
13FNO [M+H] : 230.0976; Found:
2
30.0957.
Keywords: In situ • ruthenium • N-heterocyclic carbene(s) • atom-
economic • amide synthesis
[
22]
N-(4-chlorobenzyl)benzamide (3w). White solid: m.p. 139.6-
o
1
3
141.0 C. Isolated yield: 76%. H NMR (500 MHz, CDCl ) δ 7.81
(
d, J = 7.7 Hz, 2H), 7.53 (d, J = 7.5 Hz, 1H), 7.45 (dd, J = 7.6, 7.4
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An in situ generated N-heterocyclic
carbene (NHC)-based Ru catalytic
system, which is efficient for the atom-
economic amide synthesis from
alcohols and amines, has been
discovered and reported in this paper.
Notably, this catalytic system does not
require any additional ligand and is
effective for most electron-deficient
Hua Cheng,[b] Mao-Qian Xiong,[a] Chuan-
Xiang Cheng,[ Hua-Jing Wang, Qiang
b]
[c]
Lu,[b] Hong-Fu Liu,[b] Fu-Bin Yao,[b]
Francis Verpoort*[a,
Chen*[a]
c, d]
and Cheng
Page No. – Page No.
In situ generated ruthenium catalytic
systems bearing diverse N-
heterocyclic carbene precursors for
the atom-economic amide synthesis
from alcohols and amines
substrates.
mechanistic
Moreover,
further
investigations
demonstrated the rationale for the high
potency of the catalytic system.
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