Ruthenium(II)-NHC-catalyzed (NHC = perhydrobenzimidazol-2-ylidene) alkylation of amines using the hydrogen borrowing methodology under solvent-free conditions

Article abstract of DOI:10.1007/s11243-019-00313-7

New ruthenium(II) complexes with N-heterocyclic carbene ligand were synthesized by transmetalation reactions between silver(I) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂. The complexes were characterized by physicochemical and spectroscopic methods. These ruthenium complexes were applied to the N-monoalkylation of aromatic amines with a wide range of primary alcohols under solvent-free conditions using the hydrogen borrowing strategy. The catalytic reactions using all ruthenium complexes resulted in N-monoalkylated products with high selectivities using furfuryl alcohol as the alkylating agent.

Full text of DOI:10.1007/s11243-019-00313-7

Transition Metal Chemistry
https://doi.org/10.1007/s11243-019-00313-7
Ruthenium(II)‑NHC‑catalyzed(NHC = perhydrobenzimidazol‑2‑ylidene)
alkylation of amines using the hydrogen borrowing methodology
under solvent‑free conditions
Murat Yiğit1 · Emine Özge Karaca2 · Beyhan Yiğit1 · Nevin Gürbüz2,3 · İsmail Özdemir2,3
Received: 16 January 2019 / Accepted: 26 February 2019
© Springer Nature Switzerland AG 2019
Abstract
New ruthenium(II) complexes with N-heterocyclic carbene ligand were synthesized by transmetalation reactions between
silver(I) N-heterocyclic carbene complexes and [RuCl2(p-cymene)]2. The complexes were characterized by physicochemical
and spectroscopic methods. These ruthenium complexes were applied to the N-monoalkylation of aromatic amines with a
wide range of primary alcohols under solvent-free conditions using the hydrogen borrowing strategy. The catalytic reactions
using all ruthenium complexes resulted in N-monoalkylated products with high selectivities using furfuryl alcohol as the
alkylating agent.
Introduction
borrowing methodology also called hydrogen auto-transfer
constitutes one of the most important synthetic methods for
the preparation of alkylated amines, which involves a sim-
ple operation process and mild conditions [8]. This process
involves three steps but carried out in one pot. In the initial
step, hydrogen is temporarily removed from alcohol with
a transition metal catalyst to form a carbonyl compound,
and then, the carbonyl compound reacts with a nucleophile
to form an unsaturated intermediate. In the last step, the
unsaturated molecule is reduced by the metal hydride com-
plex to obtain the fnal product (Scheme 1). Particularly, the
use of alcohols instead of alkyl halides as alkylating agents
in the alkylation of amines is highly attractive, because they
are readily available, relatively cheap and less toxic than the
corresponding alkyl halide, and water is the only by-product
in the overall process [9]. Besides alcohols, amines can also
be used as alkylating agents in this process, but the use of
amines for the alkylation of amines is much more limited
[10].
Alkylation of amines has received much attention by syn-
thetic chemists, as alkylated amines are important com-
pounds widely found in natural products, pharmaceuti-
cals, bulk and fne chemicals [1]. Traditional methods for
alkylation of amines involve substitution reactions with
alkyl halides [2] or reductive aminations using stoichio-
metric reducing agents [3]. However, these reactions have
signifcant drawbacks, such as toxicity of alkylating and
reducing agents, the formation of large amounts of waste,
acidic reaction conditions and undesired side products.
Due to the importance of arylated and alkylated amines
in the chemical industry, during the last decades, several
catalytic methods have been developed for the arylation
and alkylation of amines, including Buchwald–Hartwig
amination [4], hydroamination [5], hydroaminomethyla-
tion [6] and hydrogen borrowing methodology [7]. Among
the carbon–nitrogen bond-forming reactions, the hydrogen
The hydrogen borrowing methodology has been success-
fully applied for the formation of new carbon–heteroatom
and carbon–carbon bonds under catalytic conditions [11].
The frst N-alkylation of amines with alcohols was described
independently by Grigg [12] and Watanabe [13] using rho-
dium- and ruthenium-phosphine complexes as catalysts,
respectively, in 1981. Since then, a number of homogene-
ous and heterogeneous catalytic systems based on ruthe-
nium [14], iridium [15], palladium [16], silver [17], cobalt
[18], copper [19] and rhodium [20] have been developed
* Murat Yiğit
myigit@adiyaman.edu.tr
1
Department of Chemistry, Faculty of Science and Art,
Adıyaman University, 02040 Adıyaman, Turkey
2
Catalysis Research and Application Center, Inönü University,
44280 Malatya, Turkey
3
Department of Chemistry, Faculty of Science and Art, Inönü
University, 44280 Malatya, Turkey
Vol.:(0123456789)
1 3

Transition Metal Chemistry
dichloromethane. The catalytic activity of these complexes
was evaluated in N-alkylation reactions of aniline with aryl-
methyl alcohols.
R'
R'
R
R
N
H
R
R
OH
[M]
Experimental
[MH2]
All reactions for the preparation of the ruthenium(II)-NHC
complexes were carried out under argon in fame-dried
glassware using standard Schlenk techniques. The sol-
vents were purifed by distillation over the drying agents
indicated and were transferred under Ar: THF, Et2O (Na/K
alloy), CH2Cl2 (P4O10), hexane, toluene (Na). All reagents
were purchased from Sigma-Aldrich, Merck and Fluka.
1H-NMR and 13C-NMR spectra were recorded with a Var-
ian AS 400 Merkur spectrometer operating at 400 MHz
(1H), 100 MHz (13C) in CDCl3 with tetramethylsilane as an
internal reference. Coupling constants (J values) are given
in Hertz. NMR multiplicities are abbreviated as follows:
s = singlet, d = doublet, t = triplet, q = quartet, sept = sep-
tet and m = multiplet signal. FTIR spectra were recorded
on ATR unit in the range 400–4000 cm−1 on PerkinElmer
Spectrum 100. GC was measured by GC-FID on an Agilent
6890 N gas chromatograph equipped with an HP-5 column
of 30 m length, 0.32 mm diameter and 0.25 μm flm thick-
ness. Melting points were measured in open capillary tubes
with an Electrothermal-9200 melting point apparatus and
uncorrected. Elemental analyses were performed at Inönü
University research center.
N
O
H2O
R'-NH2
Scheme 1 Hydrogen borrowing strategy for the alkylation of amines
with alcohols using a metal complex
by Williams and other groups for alkylation of amines with
alcohols. The most important results for the preparation
of the secondary amines have largely been achieved using
ruthenium and iridium complexes. Recently, important pro-
gress in hydrogen borrowing reactions was achieved with Au
and Zr as the catalysts with excellent results [21]. In addi-
tion, alkylation of amines with alcohols has been performed
using biocatalysts for the preparation of enantiopure amines
via biocatalytic hydrogen methodology [22].
N-Heterocyclic carbenes (NHC) are an important class
of widely used and investigated ligands in organometallic
chemistry and catalysis because of their readily tunable
steric and electronic properties, and their ease of synthe-
sis [23]. Generally, NHCs have good σ-donor and weak
π-acceptor properties and are very strong nucleophiles. The
strong electron-donating property of N-heterocyclic car-
bene ligands leads to the formation of stable metal–NHC
complexes with strong covalent bonds [24]. This strong
metal–carbon bond avoids the decomposition of NHC com-
plexes during the course of catalytic reactions. A variety
of NHC complexes have been successfully synthesized and
used as antimicrobial, antitumor and anticancer agents [25],
photoluminescent materials [26] and catalysts for various
transformations [27]. In recent years, NHC complexes have
been widely used as catalysts in hydrogen borrowing reac-
tions [28–31]. In particular, NHC complexes of iridium and
ruthenium have demonstrated good activity for these trans-
formations [32–35]. However, the use of ruthenium(II)-NHC
complexes in the alkylation of amines with alcohols is rare
[36, 37]. To the best of our knowledge, ruthenium(II) com-
plexes bearing a perhydrobenzimidazol-2-ylidene ligand for
N-alkylation reactions have not been reported to date.
In this study, the new [RuCl2(NHC)(p-cymene)]
(NHC=perhydrobenzimidazol-2-ylidene) complexes were
readily synthesized by treating the [RuCl2(p-cymene)]2
dimer directly with the corresponding Ag(I)-NHC com-
plexes, which was prepared in situ by reaction of Ag2O with
symmetrical 1,3-dialkylperhydrobenzimidazolium salts in
Synthesis of perhydrobenzimidazolium salts 1
A mixture of N,N′-dialkyl-1,2-diaminocyclohexane
(4.0 mmol), NH4Cl (4.0 mmol) and triethyl orthoformate
(10 mL) was heated for 12 h at 110 °C. Upon cooling to
room temperature, colorless crystals were obtained. These
were fltered of, washed with diethyl ether (3×15 mL) and
dried under vacuum. The crude product was recrystallized
from EtOH/Et2O.
1,3‑Bis(4‑diethylaminobenzyl)perhydrobenzimidazo‑
lium chloride 1c Yield: 1.79 g, 93%, m.p. 172–174 °C.
1
IR, υ: 1521 cm−1 (NCN). H NMR (CDCI3) δ: 1.15
(t, 12H, J = 6.9 Hz, N(CH2CH3)2), 1.17–1.36 (m, 4H,
NCHCH2CH2CH2CH2CHN), 1.80–2.25 (m, 4H, NCHCH-
2CH2CH2CH2CHN), 3.10–3.12 (m, 2H, NCHCH2CH2CH-
2CH2CHN), 3.36 (d, 8H, J = 7.2 Hz, N(CH2CH3)2), 4.45
and 5.05 (d, 4H, J=14.4 Hz, NCH2Ar), 6.61 and 7.22 (d,
8H, J = 8.7 Hz, CH2C6H4N(CH2CH3)2-4), 10.75 (s, 1H,
NCHN). 13C NMR (CDCI3) δ: 12.5 (N(CH2CH3)2), 23.6,
27.3 and 50.3 (NCH(CH2)4CHN), 44.2 (N(CH2CH3)2),
66.0 (NCH2Ar), 111.7, 118.8, 129.9 and 147.9
1 3

Transition Metal Chemistry
(CH2C6H4N(CH2CH3)2-4), 161.5 (NCHN); Anal. Calcd. for
C29H43N4CI: C, 72.12; H, 8.91; N, 11.60. Found C, 72.16;
H, 8.87; N, 11.62%.
(CDCI3) δ: 18.6 (p-CH3C6H4CH(CH3)2), 21.8 (p-CH3C6H
4CH(CH3)2), 30.6 (p-CH3C6H4CH(CH3)2), 23.2, 24.2, 29.6,
53.7 and 55.4 (NCH(CH2)4CHN), 67.8 and 69.7 (NCH2Ar),
70.0 (OCH2Ar), 82.9, 84.2, 85.8, 86.3, 97.5 and 108.4 (p-CH
3C6H4CH(CH3)2), 114.4, 114.8, 127.5, 127.8, 128.0, 128.5,
129.1, 131.0, 136.9 and 158.0 (CH2C6H4OCH2C6H5-4),
214.5 (Ru-Ccarb). Anal. Calc. for C45H50N2O2RuCl2: C,
65.69; H, 6.08; N, 3.41. Found: C, 65.66; H, 6.05; N, 3.43%.
Synthesis of ruthenium(II)‑NHC complexes 2
Ag2O (0.54 mmol) was added to a solution of the appropriate
perhydrobenzimidazolium chloride (1.08 mmol) in dichlo-
romethane (25 mL). The mixture was stirred for 24 h at room
temperature in the dark conditions, covered with aluminum
foil under argon and then fltered through Celite to remove
the AgCl formed. [RuCl2(p-cymene)]2 (0.43 mmol) was
added to the colorless solution, and the reaction mixture was
stirred for 24 h at room temperature. The resulting mixture
was fltered through Celite, and the solvent was removed
under vacuum to aford the product. The crude product was
recrystallized from dichloromethane/diethyl ether (1:2) at
room temperature. The orange-brown crystals were fltered
of, washed with diethyl ether (3×10 mL) and dried under
vacuum.
Dichloro‑[1,3‑bis(4‑diethylaminobenzyl)perhydrobenzimi‑
dazol‑2‑ylidene](p‑cymene)ruthenium(II) 2c Yield: 0.12 g,
75%, m.p=223–224 °C. IR, υ: 1519 cm−1 (NCN). 1H NMR
(CDCI3) δ: 0.95–1.06 (m, 4H, NCHCH2CH2CH2CH2CHN),
1.16–1.18 (m, 12H, N(CH2CH3)2), 1.19 and 1.22 (d, 6H,
J=8 Hz, p-CH3C6H4CH(CH3)2), 1.55–1.77 (m, 4H, NCH-
CH2CH2CH2CH2CHN), 2.06 (s, 3H, p-CH3C6H4CH(CH3)2),
2.80 (sept, 1H, J=8 Hz, p-CH3C6H4CH(CH3)2), 3.13–3.25
(m, 2H, NCHCH2CH2CH2CH2CHN), 3.33–3.35 (m, 8H,
N(CH2CH3)2), 4.52, 4.81, 5.40 and 5.64 (d, 4H, J=16 Hz,
p-CH3C6H4CH(CH3)2), 5.10, 5.20, 5.31 and 5.44 (d, 4H,
J = 8 Hz, NCH2Ar), 6.65, 6.70 and 7.19 (d, 8H, J = 8 Hz,
CH2C6H4N(CH2CH3)2-4). 13C NMR (CDCI3) δ: 12.6
(N(CH2CH3)2), 18.4 (p-CH3C6H4CH(CH3)2), 21.9 (p-C
H3C6H4CH(CH3)2), 30.5 (p-CH3C6H4CH(CH3)2), 23.2,
24.2, 29.2, 29.8, 53.7 and 54.8 (NCH(CH2)4CHN), 44.2
(N(CH2CH3)2), 68.2 and 68.5 (NCH2Ar), 83.4, 84.9, 85.5,
85.6, 96.7 and 107.4 (p-CH3C6H4CH(CH3)2), 111.9 124.7,
126.0, 127.3, 128.8 and 147.0 (CH2C6H4N(CH2CH3)2-4),
213.7 (Ru-Ccarb). Anal. Calc. for C39H56N4RuCI2: C, 62.23;
H, 7.45; N, 7.45. Found: C, 62.20; H, 7.43; N, 7.49%.
Dichloro‑[1,3‑bis(4‑phenylbenzyl)perhydrobenzimida‑
zol‑2‑ylidene](p‑cymene)ruthenium(II) 2a Yield: 0.13 g,
81%, m.p=257–258 °C. IR, υ: 1516 cm−1 (NCN). 1H NMR
(CDCI3) δ: 0.95–1.20 (m, 4H, NCHCH2CH2CH2CH2CHN),
1.22 and 1.29 (d, 6H, J=4 Hz, p-CH3C6H4CH(CH3)2), 1.57–
1.79 (m, 4H, NCHCH2CH2CH2CH2CHN), 2.14 (s, 3H, p-C
H3C6H4CH(CH3)2), 2.88 (sept, 1H, J=8 Hz, p-CH3C6H4C
H(CH3)2), 3.20–3.35 (m, 2H, NCHCH2CH2CH2CH2CHN),
4.64, 4.90, 5.79 and 6.00 (d, 4H, J = 16 Hz, p-CH3C6H4
CH(CH3)2), 5.10, 5.18, 5.34 and 5.49 (d, 4H, J = 8 Hz,
NCH2Ar), 7.26–7.61 (m, 18H, CH2C6H4C6H5-4). 13C NMR
(CDCI3) δ: 18.7 (p-CH3C6H4CH(CH3)2), 21.8 (p-CH3C6H
4CH(CH3)2), 30.6 (p-CH3C6H4CH(CH3)2), 23.4, 24.1, 29.7,
54.1 and 55.7 (NCH(CH2)4CHN), 68.0 and 69.8 (NCH2Ar),
83.0, 84.4, 85.9, 86.3, 97.6 and 108.4 (p-CH3C6H4CH
(CH3)2), 126.7, 126.9, 127.1, 127.3, 128.3, 128.7, 128.8,
137.5, 138.0, 140.0, 140.5 and 140.8 (CH2C6H4C6H5-4),
215.2 (Ru-Ccarb). Anal. Calc. for C43H46N2RuCl2: C, 67.71;
H, 6.04; N, 3.67. Found: C, 67.74; H, 6.06; N, 3.66%.
Dichloro‑[1,3‑bis(2,4,6‑trimethoxybenzyl)perhydrobenzimi‑
dazol‑2‑ylidene](p‑cymene)ruthenium(II) 2d Yield: 0.14 g,
83%, m.p=200–2001 °C. IR, υ: 1591 cm−1 (NCN). 1H NMR
(CDCI3) δ: 0.67–1.05 (m, 4H, NCHCH2CH2CH2CH2CHN),
1.24 and 1.28 (d, 6H, J=8 Hz, p-CH3C6H4CH(CH3)2), 1.39–
1.56 (m, 4H, NCHCH2CH2CH2CH2CHN), 2.08 (s, 3H, p-C
H3C6H4CH(CH3)2), 2.62–2.68 (m, 1H, J=8 Hz, p-CH3C6H4
CH(CH3)2), 2.78–3.09 (m, 2H, NCHCH2CH2CH2CH2CHN),
3.83 and 3.85 (s, 18H, CH2C6H2(OCH3)2-2,4,6), 4.98–5.05
(m, 4H, p-CH3C6H4CH(CH3)2), 5.65 and 5.69 (d, 4H,
J=4 Hz, NCH2Ar), 6.13 (s, 4H, CH2C6H2(OCH3)2-2,4,6).
13C NMR (CDCI3) δ: 18.8 (p-CH3C6H4CH(CH3)2), 22.3 (p-
CH3C6H4CH(CH3)2), 30.4 (p-CH3C6H4CH(CH3)2), 23.2,
24.5, 29.2, 30.2, 44.7 and 45.5 (NCH(CH2)4CHN), 55.3, 55.8
(CH2C6H2(OCH3)2-2,4,6), 65.8 and 66.3 (NCH2Ar), 83.5,
84.1, 87.9, 90.6, 92.9 and 104.8 (p-CH3C6H4CH(CH3)2),
159.8, 160.0, 160.7 and 160.8 (CH2C6H2(OCH3)2-2,4,6),
213.9 (Ru-Ccarb). Anal. Calc. for C37H50N2O6RuCl2: C,
56.20; H, 6.33; N, 3.54. Found: C, 56.24; H, 6.30; N, 3.56%.
Dichloro‑[1,3‑bis(4‑benzyloxybenzyl)perhydrobenzimida‑
zol‑2‑ylidene](p‑cymene)ruthenium(II) 2b Yield: 0.14 g,
79%, m.p=214–216 °C. IR, υ: 1511 cm−1 (NCN). 1H NMR
(CDCI3) δ: 0.90–1.19 (m, 4H, NCHCH2CH2CH2CH2CHN),
1.21 and 1.27 (d, 6H, J=8 Hz, p-CH3C6H4CH(CH3)2), 1.57–
1.75 (m, 4H, NCHCH2CH2CH2CH2CHN), 2.10 (s, 3H, p-C
H3C6H4CH(CH3)2), 2.85 (sept, 1H, J=8 Hz, p-CH3C6H4C
H(CH3)2), 3.10–3.27 (m, 2H, NCHCH2CH2CH2CH2CHN),
4.49, 4.83, 5.57 and 5.88 (d, 4H, J = 16 Hz, p-CH3C6H4
CH(CH3)2), 5.04, 5.12, 5.30 and 5.44 (d, 4H, J = 8 Hz,
NCH2Ar), 5.05 and 5.06 (s, 4H, OCH2Ar), 6.90–6.99 and
7.26–7.43 (m, 18H, CH2C6H4OCH2C6H5-4). 13C NMR
1 3

Transition Metal Chemistry
chloroform and toluene and insoluble in non-polar solvents.
Single crystals of these complexes suitable for X-ray dif-
fraction studies could not be obtained. Therefore, all of the
General procedure for the N‑alkylation of amines
with alcohols
1
Under an inert atmosphere, KOBut (1 mmol), aromatic
amine (1 mmol), alcohol derivative (1.5 mmol) and Ru-NHC
complex (2.5 mol%) were added to Schlenk tube. The sealed
Schlenk tube was stirred at 120 °C for 24 h. At the end of
the reaction, the reaction mixture was cooled to room tem-
perature, and CH2Cl2 (2 ml) was added and fltered through
a short pad of SiO2. The fltrate was analyzed by GC–MS
with the calibrations based on dodecane.
Ru(II)-NHC complexes were characterized by H NMR,
13C NMR, IR spectroscopy and elemental analysis, which
all supported the proposed structures. They exhibit char-
acteristic υ(C=N) band typically at 1516, 1511, 1519 and
1591 cm−1, respectively, for 2a–d. In the NMR spectrum
of ruthenium complexes 2a–d, the characteristic downfeld
NCHN proton and NCHN carbon resonances of perhyd-
robenzimidazolium salts 1a–d were disappeared upon com-
plexation with ruthenium. The 13C chemical shifts provide
a useful diagnostic tool for this type of metal–carbene com-
plexes and show that Ccarbene is substantially deshielded. The
chemical shifts for the carbene carbon atom of 2a–d com-
plexes were observed at 215.2, 214.5, 213.7 and 213.9 ppm,
respectively, for 2a–d, and these values were similar to
those found for other (p-cymene)-ruthenium(II)-NHC com-
plexes. These new complexes show typical spectroscopic
signatures which are in line with those recently reported for
other [RuCl2(NHC)(p-cymene)] complexes [42]. The results
obtained from the elemental analysis of complexes 2a–d
are in agreement with the theoretical requirements of their
structures.
Results and discussion
Synthesis of perhydrobenzimidazolium salts
The symmetrical 1,3-dialkylperhydrobenzimidazolium
salts 1 as NHC precursors were synthesized from the N,N′-
dialkylcyclohexan-1,2-diamines, triethyl orthoformate and
ammonium chloride. Perhydrobenzimidazolium salts are
colorless solids and were obtained in good yields. The salts
were characterized by 1H and 13C NMR spectroscopy, FTIR
and elemental analysis. The spectral properties of 1c are
similar to those of other reported perhydrobenzimidazolium
salts. In the 1H NMR spectra of 1c, NCHN proton appeared
as a singlet at 10.75 ppm and benzylic protons appeared
as two doublets at 4.45 and 5.05 ppm. The NCHN carbon
resonance of 1c was observed at 161.5 ppm in the 13C NMR
spectra. The appearances of these downfeld signals indicate
the formation of 1c. The other perhydrobenzimidazolium
salts used in this study (1a, 1b and 1d) were previously
reported by our group [38–40].
Catalytic studies
The catalytic activities of new ruthenium complexes 2a–d
for the N-alkylation of aromatic amines with arylmethyl
alcohols were evaluated. Initially, the reaction of aniline with
benzyl alcohol was selected as a model reaction to determine
the optimal catalytic conditions with 2c as a catalyst. The
efect of the base, reaction time, solvent and catalyst loading
was examined. The results are summarized in Table 1. The
bases were crucial to the efciency of this reaction. Cs2CO3,
K2CO3, KOH and KOBut were tested as the base. Among the
tested bases, KOBut displayed the highest reactivity (entry
3). KOH was less efective (entry 2), while alkali metal car-
bonates Cs2CO3 and K2CO3 stopped the reaction completely
at the dehydrogenation step. It is noteworthy that, in the
absence of base and ruthenium complex, no reaction was
observed (entry 11). Toluene and dioxane often used these
reactions and gave excellent or poor conversions (entries 2
and 5). However, in the absence of a solvent, an excellent
conversion was also observed. Reducing the catalyst loading
to 1 mol% decreased the conversion (entry 9). Excellent con-
version and selectivity were obtained by the use of 2.5 mol%
of 2c (entry 10). Lower temperature (100 °C) or shorter time
(15 h) reduced the conversion (entries 2 and 1), whereas
full conversion was observed at 120 °C for 24 h (entry 7).
The catalytic experiments were carried out using 1 mmol
aromatic amine, 1.5 mmol arylmethyl alcohol, 0.01 mmol
KOBut and 0.025 mmol 2a–d at 120 °C for 24 h under argon
Synthesis of Ru(II)‑NHC complexes
There are several methods in the literature that describe the
synthesis of Ru(II)-NHC complexes. One of these is the gen-
eration of silver(I)-NHC complex, followed by transfer of
the carbene unit to ruthenium metal. The new [RuCl2(NHC)
(p-cymene)] complexes were prepared by transmetalation
from the corresponding silver N-heterocyclic carbene com-
plexes in two steps (Scheme 2). In the frst step, the Ag(I)-
NHC complexes were synthesized according to the general
method described by Wang and Lin [41] by reaction of Ag2O
with 2 equiv. of 1,3-dialkylperhydrobenzimidazolium salts
in dichloromethane at ambient temperature in the dark. In
the second step, in situ prepared Ag(I)-NHC complexes were
converted into the orange-brown monocarbene Ru(II)-NHC
complexes at ambient temperature. Ruthenium(II)-NHC
complexes were purifed by crystallization. The air- and
moisture-stable ruthenium–carbene complexes in the solid
state were soluble in solvents such as dichloromethane,
1 3

Transition Metal Chemistry
Scheme 2 The synthesis of (p-cymene)-ruthenium(II)-NHC complexes
without any solvent or additive. Under these reaction con-
ditions, the ruthenium-catalyzed N-alkylation of aromatic
amines (aniline, 2,4-dimethylaniline and 2-aminopyridine)
with arylmethyl alcohols (benzyl alcohol, 4-methylbenzyl
alcohol, 4-methoxybenzyl alcohol and furfuryl alcohol)
was examined. In all cases, only monoalkylated amines and
imines were formed, and no bis-alkylated products were
detected. The reaction products were characterized by NMR.
The conversions and selectivity were screened by GC and
GC–MS analysis.
using complexes 2a–d as catalysts gave also corresponding
monoalkylated amines in conversions between 95–100% and
85–91%, respectively, under these conditions. 4-Methoxy-
benzyl alcohol aforded the corresponding monoalkylated
product N-(4-methoxybenzyl)aniline with excellent selec-
tivities for all complexes 2a–d (Table 2, entry 3). Complete
selectivity was achieved with catalysts 2b–d (Table 2, entry
2). High yields were obtained with complexes 2c and 2d
(Table 2, entry 1–4). These results show that the electron-
donating substituent (4-methyl and 4-methoxy) on benzyl
alcohol gave higher selectivity when compared to benzyl
alcohol itself. When using furfuryl alcohol as the alkylating
agent, N-(furan-2-ylmethyl)aniline with 100% selectivity
was obtained for all complexes 2a–d, but conversions of
reactions were slightly lower than others (Table 2, entry 4).
We next examined the reactions of 2,4-dimethylaniline
with benzyl alcohol, 4-methylbenzyl alcohol, 4-methoxy-
benzyl alcohol and furfuryl alcohol in the presence of com-
plexes 2a–d as catalysts under the same reaction conditions
(Table 2, entries 5–8). Thus, 2,4-dimethylaniline was treated
With the determined optimal conditions in hand, we frst
investigated complexes 2a–d as catalysts the N-alkylation of
aniline with benzyl alcohol, 4-methylbenzyl alcohol, 4-meth-
oxybenzyl alcohol and furfuryl alcohol. In all reactions,
alkylation of aniline with high selectivity was achieved. The
reaction of aniline with benzyl alcohol gave the N-benzylani-
line in 96–99% conversions (Table 2, entry 1). The forma-
tion of N-benzylamine with high selectivity was obtained
with complex 2c (Table 2, entry 1). The treatment of aniline
with 4-methylbenzyl alcohol and 4-methoxybenzyl alcohol
1 3

Transition Metal Chemistry
Table 1 Determination of reaction conditions for alkylation of aniline with benzyl alcohola–d
NH2
+
NH
N
+
OH
A
B
Entry
2c (mol%)
Base
Time (h)
Temp. (°C)
Conversion (%)
A/B (%)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
2.5
2.5
1
2.5
–
KOH
KOH
KOBut
KOH
KOH
KOBut
KOBut
KOBut
KOBut
KOBut
–
15
24
24
24
24
24
24
24
24
24
24
100
100
100
150
100
120
120
120
120
120
120
52
71
82
86
12
91
100
97
37/63
43/57
57/43
48/52
13/87b
78/22
89/11
52/48c
60/40d
88/12d
–/–
9
10
11
84
100
No reaction
aReaction Conditions: Aniline (1 mmol), benzylalcohol (1 mmol), base (0.5 mmol), toluene (3 mL)
bDioxane
cBase (0.025 mmol)
dSolvent free
Yields are determined by GC and GC–MS
with benzyl alcohol for all complexes 2a–d under optimized
reaction conditions to obtain the corresponding N-benzyl-
2,4-dimethylaniline in 70–84% conversions with 74–87%
selectivity (Table 2, entry 5). The reaction of 2,4-dimethy-
laniline with 4-methylbenzyl alcohol and 4-methoxybenzyl
alcohol also aforded corresponding monoalkylated amines
in conversions between 75–92% and 70–87% with 80–100%
and 55–77% selectivity, respectively. The above results show
that the electron-donating substituents such as Me and OMe
on both benzyl alcohol and aniline slightly increased the
selectivity of monoalkylated amine products under the same
conditions (Table 2, entries 1–3, and Table 2, entries 5–7).
Similar trends have been observed for the other Ru(II) sys-
tems bearing NHC ligands [36]. When the furfuryl alcohol
was used as an alkylating agent, only the corresponding
monoalkylated amine was obtained with 100% selectivity
for all complexes 2a–d (Table 2, entry 8). No imine or bis-
alkylated products were detected.
catalysts. Moreover, the heteroaromatic moiety in 2-ami-
nopyridine was also well tolerated under this catalytic sys-
tem. In all reactions, only the nitrogen atom of the amino
group of 2-aminopyridine was alkylated; the products with
N-alkylpyridine were not detected. 2-Aminopyridine was
efciently arylated with benzyl alcohol and furfuryl alco-
hol for all complexes 2a–d with 100% selectivity (Table 3,
entries 1 and 4). The reaction of 2-aminopyridine with
4-methylbenzyl alcohol and 4-methoxybenzyl alcohol
also gave corresponding products in conversions between
98–100% and 98–99% with 71–100% and 96–98% selectiv-
ity, respectively. As shown in Tables 2 and 3, ruthenium
complexes (2c, 2 d) bearing NHC ligands with diethyl-
amino or methoxy substituents on benzyl group exhibited
better catalytic activity in some cases than the others for the
N-alkylation of aromatic amines with arylmethyl alcohols.
To the best of our knowledge, studies of Ru-NHC
complexes for the alkylation of amines with alcohols are
rare in the literature. Recently, our group has investigated
ruthenium–carbene complexes in the alkylation of amines
with alcohols [37]. In this work, we described the synthe-
sis and characterization of benzimidazole–ruthenium(II)
complexes of the general formula [RuCl2(NHC)(η6-p-
cymene)]. These complexes were tested as catalysts for
the N-alkylation of aniline with arylmethyl alcohols. In
Finally, we also investigated the N-alkylation of 2-ami-
nopyridine with the same alcohols (benzyl alcohol, 4-meth-
ylbenzyl alcohol, 4-methoxybenzyl alcohol and furfuryl
alcohol) by using ruthenium(II)-NHC 2a–d catalysts in
order to obtain N-alkylated amines under the same reac-
tion conditions. 2-(N-alkylamino)pyridines were obtained in
good-to-excellent selectivities in the presence of 2.5 mol%
1 3

Transition Metal Chemistry
Table 2 N-alkylation of anilines with benzyl alcohols
Entry
Amine
Alcohol
[Ru]
Conversion (Yield A:B%)
2a
2b
2c
2d
1
2
3
4
98 (79/21) 96 (63/37) 100 (81/19) 98 (66/34)
95 (76/24) 98 (71/29) 100 (77/33) 98 (100/0)
84 (98/2)
89 (100/0) 79 (100/0)
87 (100/0)
87 (100/0)
70 (74/26)
78 (80/20)
87 (77/23)
83 (100/0)
85 (100/0) 97 (100/0) 79 (100/0)
79 (87/13) 81 (85/15) 84 (75/25)
5
6
7
8
92 (86/14) 83 (100/0)
75 (97/3)
79 (72/28) 70 (77/23) 81 (55/45)
87 (100/0)
78 (100/0) 82 (100/0)
Reaction conditions: Complexes 2a–d (0.025 mmol, 2.5 mol%), arylmethyl alcohol (1.5 mmol), heterocyclic amine (1 mmol), KOBut (1 mmol),
120 °C, 24 h. The conversions and the selectivity determined by GC and GC–MS analysis with the calibrations were based on dodecane
this work we described the synthesis and characteriza-
tion of perhydrobenzimidazole-ruthenium(II) complexes
of the general formula [RuCl2(NHC)(η6-p-cymene)].
By comparison, reported for related Ru catalysts such
as N-heterocyclic carbene ruthenium(II) complexes,
similar results were obtained. The present catalytic sys-
tem using NHC–ruthenium(II) complexes is particu-
larly efective and selective for amines formation (A)
despite low-temperature and solvent-free condition [37].
For example in the case of furfuryl alcohol, the amine
product (A) was obtained in 84–93% when benzimida-
zole–ruthenium(II) complexes were employed, whereas
the perhydrobenzimidazole–ruthenium(II) complexes
(2a–d) aforded full conversion and the amine product (A)
was favored (Table 2, entry 4).
Conclusion
In summary, ruthenium(II)-NHC complexes 2a–d have been
easily prepared by the reaction of silver(I)-NHC complexes
as a carbene transfer reagent with [RuCl2(p-cymene)]2 in
dichloromethane at room temperature in good yields. The
catalytic activity of these complexes was investigated in
1 3

Transition Metal Chemistry
Table 3 N-alkylation of
2-pyridyl amine with arylmethyl
alcohols
[Ru]
Conversion (Yield A:B%)
2b 2c
Entry
Alcohol
2a
2d
1
2
3
4
96 (100/0) 97 (100/0) 100 (100/0) 98 (100/0)
98 (76/24) 98 (71/29) 100 (100/0) 100 (100/0)
99 (97/3)
98 (96/4)
99 (98/2)
99 (98/2)
98 (100/0) 99 (100/0)
96 (100/0) 97 (100/0)
Reaction conditions: aniline (1 mmol), alcohol (1.5 mmol), Ru-NHC (0.025 mmol), KOBut (1 mmol),
120 °C, 24 h. The conversions and the selectivity determined by GC and GC–MS analysis with the cali-
brations were based on dodecane
3. Storer RI, Carrera DE, Ni Y, MacMillan DWC (2006) J Am Chem
Soc 128:84
N-alkylation reactions of aniline, 2,4-dimethylaniline and
2-aminopyridine with arylmethyl alcohols including benzyl
alcohol, 4-methyl benzyl alcohol, 4-methoxybenzyl alcohol
and furfuryl alcohol. The N-alkylation of amines was per-
formed in solvent-free conditions for 24 h at 120 °C using
2.5 mol% of complexes 2a–d. All of these complexes were
found to be suitable for N-alkylation of aromatic amines
with arylmethyl alcohols via hydrogen borrowing reactions.
In this study, high selectivity was obtained. In all cases only
monoalkylated amines were formed and no bis-alkylated
products were detected.
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Compliance with ethical standards
14. Hamid MHSA, Allen CL, Lamb GW, Maxwell AC, Maytum HC,
Watson AJA, Williams JMJ (2009) J Am Chem Soc 131:1766
15. Saidi O, Blacker AJ, Farah MM, Marsden SP, Williams JMJ
(2010) Chem Commun 46:1541
Conflict of interest The authors declare that they have no confict of
interest.
16. Llabres-Campaner PJ, Ballesteros-Carrido R, Ballesteros R,
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