Catalytic activity of Ru/tetrahydropyrimidinium salts system for transfer hydrogenation reactions

Article abstract of DOI:10.1002/aoc.3322

New 1,3-dialkyltetrahydropyrimidinium salts as NHC precursors have been synthesized and characterized. The in situ prepared three-component 1,3-dialkyltetrahydropyrimidinium salts/[RuCl₂(p-cymene)]₂ and KOH catalyzes quantitatively t

Full text of DOI:10.1002/aoc.3322

Full Paper
Received: 29 January 2015
Revised: 16 March 2015
Accepted: 28 March 2015
Published online in Wiley Online Library: 1 May 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3322
Catalytic activity of Ru/tetrahydropyrimidinium
salts system for transfer hydrogenation reactions
Emine Özge Karacaa, Nevin Gürbüza, Hakan Arslanb, Don VanDerveerc
and İsmail Özdemira*
New 1,3-dialkyltetrahydropyrimidinium salts as NHC precursors have been synthesized and characterized. The in situ pre-
pared three-component 1,3-dialkyltetrahydropyrimidinium salts/[RuCl2(p-cymene)]2 and KOH catalyzes quantitatively the
transfer hydrogenation of ketones under mild reaction conditions in 2-propanol. Also, the molecular structure of 1,3-bis(2-
methylbenzyl)-3,4,5,6-tetrahydropyrimidinium was determined using single-crystal X-ray diffraction. Ions of the title com-
pound are linked by C–H…Cl and O–H…Cl hydrogen bonding interactions. The N–C–N bond angle (124.3(2)°) and C–N bond
lengths (1.316(3) and 1.314(3) Å) confirm the existence of strong resonance in this part of the molecule. Copyright © 2015
John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: ruthenium; tetrahydropyrimidin-2-ylidene; N-heterocyclic carbine; transfer hydrogenation; ketone
transfer hydrogenation has been described for ruthenium,[13–17]
Introduction
rhodium,[18–22] iridium,[18–20,23–26] osmium,[27] nickel[28] and
palladium[29] pre-catalysts for the reduction of carbonyl, imine
The reduction of ketones or aldehydes is an important reaction in
organic synthesis. One of the most commonly used methods is
transfer hydrogenation; it is a valuable, atom-efficient reaction,
and compared with conventional hydrogenation, using molecular
hydrogen, transfer hydrogenation offers a safer, more cost-effective
and simpler experimental procedure. Transfer hydrogenation is the
addition of hydrogen to an unsaturated molecule using a reagent
other than H2. Although the direct hydrogenation of ketones is
more widely applied, transfer hydrogenation is an attractive alter-
native. This method is often more convenient and frequently less
hazardous than direct hydrogenation with H2 gas.[1,2] Transfer
hydrogenation reactions require typically a hydrogen donor such
as 2-propanol together with a strong base and transition metal cat-
alyst, and are preferred for large-scale industrial use in the hope of
developing a greener process by reducing waste production and
energy use and lowering toxicity.[3] Catalytic transfer hydrogena-
tion represents a viable alternative to the more classical reduction
method using molecular hydrogen or metal hydrides.[4] Among
various possible hydrogen sources, alcohols,[4,5] water,[6] formic
acid[7] and alkylammonium formates[8] have found the broadest ap-
plications. So far, the transfer hydrogenation reaction has been ex-
tensively studied and continues to generate a high degree of
interest, given the need to develop environmentally friendly and
simple processes.[9]
and nitro functionalities.
The nature of the NHC ligand has a tremendous influence on the
rate of catalyzed reactions. Whilst modifications to the five-
membered ring of the ligand aryl substituent have been described,
relatively little attention has been paid to the effect of the ring size.
Due to their six-membered ring geometry, tetrahydropyrimidin-2-
ylidenes are stronger σ-donating ligands in comparison to their
five-membered relatives.[30]
We have previously reported imidazolidine, benzimidazole-2-ylidene–
ruthenium(II) complexes and an in situ formed tetrahydropyrimidine–
ruthenium(II) system which exhibit high activity.[31–33] In order to find
more efficient ruthenium catalysts we have prepared a series of new
1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts, 1a–f (Scheme 1), and
we now report the use of the in situ generated catalytic system
composed of [RuCl2(p-cymene)]2 as ruthenium source, 1a–f as carbene
precursors and KOH as a base for the transfer hydrogenation of aryl ke-
tones in 2-propanol for 1 h. All synthesized compounds were character-
ized using 1H NMR, 13C NMR and IR spectroscopy and elemental
analysis, the results of which support the proposed structures. The
molecular and crystal structure of 1,3-bis(4-methylbenzyl)-3,4,5,6-
tetrahydropyrimidinium chloride salt was determined using the single-
crystal X-ray diffraction technique.
The NHC ligand set has become well established in homoge-
neous transition metal catalysis of many transformations,[10,11] in-
cluding direct and transfer hydrogenation. Of the many reactions
that have been investigated using NHC-containing catalysts, hydro-
genation and transfer hydrogenation have featured prominently,
which is in part due to their wide-ranging use in synthetic chemistry
and continued industrial importance. The first application of an
NHC–Ru complex for the transfer hydrogenation reaction was re-
ported by Grubbs and co-workers in 2001.[12] In NHC chemistry
*
Correspondence to: İsmail Özdemir, Inönü University, Catalysis Research and
Application Center, 44280 Malatya, Turkey. E-mail: iozdemir@inonu.edu.tr
a Inönü University, Catalysis Research and Application Center, 44280 Malatya,
Turkey
b Department of Chemistry, Faculty of Arts and Science, Mersin University, 33343
Mersin, Turkey
c
Department of Chemistry, Clemson University, Clemson, SC, 29634 USA
Appl. Organometal. Chem. 2015, 29, 475–480
Copyright © 2015 John Wiley & Sons, Ltd.

E. Ö. Karaca et al.
concerning data collection and refinement are given in Table 1. Mo-
lecular graphics were prepared with SHELXTL software.[36]
General Preparation of
1,3-Dialkyl-3,4,5,6-tetrahydropyrimidinium Salts (1)
Aromatic aldehyde (20 mmol) and 1,3-propanediamine (10 mmol)
were stirred overnight in methanol. The diimine was collected as
a white solid, filtered and recrystallized from an alcohol–ether mix-
ture. The diimine (10mmol) was subsequently reduced using
NaBH4 (30 mmol) in CH3OH (30 ml). The solution was then treated
with 1 N HCl, and the organic phase was extracted with CH2Cl2
(3× 30 ml). After drying over MgSO4 and evaporating, the diamine
was isolated as a solid. The diamine was then treated in a large
excess of triethyl orthoformate (50 ml) in the presence of 10 mmol
of NH4Cl or NH4BF4 at 110°C in a distillation apparatus until the
removal of ethanol ceased. Upon cooling to room temperature, a
colorless solid precipitated, which was collected by filtration and
dried under vacuum. The crude product was recrystallized from
absolute ethanol to give colorless needles and the solid was
washed with diethyl ether (2× 10 ml) and dried under vacuum.
Scheme 1. Preparation 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts.
Experimental
Materials
All reactions for the preparation of 1 were carried out under argon
in flame-dried glassware using standard Schlenk-type flasks.
Chemicals and solvents were purchased from Sigma Aldrich Co.
(Dorset, UK). The solvents used were purified by distillation over
drying agents (Et2O over Na/K alloy; C2H5OH over Mg) and were
transferred under argon. Elemental analyses were performed by
the İnönu University Scientific and Technology Center.
1,3-Bis(2-methylbenzyl)-3,4,5,6-tetrahydropirimidinium
Chloride (1a)
1
Yield 5.17 g (90%); m.p. 107–108°C. IR, ν(CN): 1670 cmꢀ1. H NMR
Melting Point Determination
(399.9 MHz, CDCl3, δ, ppm): 2.02 (quin, J = 6 Hz, 2H, NCH2CH2CH2N),
2.38 (s, 6H, CH2C6H4(CH3)-2), 3.24 (t, J = 6 Hz, 4H, NCH2CH2CH2N),
4.98 (s, 4H, CH2C6H4(CH3)-2), 7.18–7.30 (m, 8H, CH2C6H4(CH3)-2),
10.08 (s, 1H, NCHN). 13C{H}NMR (100.5 MHz, CDCl3, δ, ppm): 18.9
(NCH2CH2CH2N), 19.5 (CH2C6H2(CH3)-2), 41.9 (NCH2CH2CH2N), 56.6
(CH2C6H4(CH3)-4), 126.6, 129.1, 129.7, 131.0, 131.2, 137.2 (CH2C6H4
Melting points were measured in open capillary tubes with an Elec-
trothermal 9200 melting point apparatus and are uncorrected.
IR Spectroscopy
IR spectra were recorded as KBr pellets in the range 400–4000 cmꢀ1
Table 1. Crystal data, data collection and refinement values for 1,3-bis
(2-methylbenzyl)-3,4,5,6-tetrahydropyrimidinium chloride monohydrate
using an ATI UNICAM 1000 spectrometer.
Crystal data
NMR Spectroscopy
1H NMR and 13C NMR spectra were recorded using a Varian As 400
Merkur spectrometer operating at 400MHz (1H) or 100 MHz (13C) in
CDCl3 with tetramethylsilane as an internal reference. The NMR
studies were carried out using high-quality 5 mm NMR tubes.
Signals are quoted in parts per million downfield from
tetramethylsilane (0.00 ppm). Coupling constants (J values) are
given in hertz. NMR multiplicities are abbreviated as follows: s, sin-
glet; d, doublet; t, triplet; m, multiplet.
C
20H25N2 · H2O · Cl
V = 1883.4(6) Å3
Z = 4
Mr = 346.89
Monoclinic, P21/n
a = 11.631(2) Å
b = 7.6612(15) Å
c = 21.136(4) Å
β = 90.22(3)°
Mo Kα radiation, λ = 0.71073 Å
μ = 0.21 mmꢀ1
T = 272 K
0.48 × 0.48 × 0.14 mm
Data collection
Rigaku AFC8S Mercury CCD
diffractometer
3374 independent reflections
2921 reflections with I > 2σ(I)
Rint = 0.025
Gas Chromatography
Absorption correction:
multi-scan Jacobson, R. (1998)
All reactions were monitored using an Agilent 6890 N GC system
with flame ionization detection with an HP-5 column of 30 m
length, 0.32 mm diameter and 0.25 μm film thickness.
Tmin = 0.905, Tmax = 0.971
14 246 measured reflections
Refinement
X-ray Diffraction
R[F2 > 2σ(F2)] = 0.055
wR(F2) = 0.154
3 restraints
H atoms treated by a mixture of
independent and constrained
refinement
Δρmax = 0.84 e Åꢀ3
Δρmin = ꢀ0.32 e Åꢀ3
Single-crystal X-ray diffraction data were collected with a Rigaku
AFC8S Mercury CCD diffractometer[34] using monochromated Mo
Kα radiation. The structure was solved using direct and conven-
tional Fourier methods.[35] Full-matrix least-squares refinement[35]
was based on F2. Apart from hydrogen, all atoms were refined
anisotropically; hydrogen atom coordinates were calculated at ide-
alized positions and refined using a riding model. Further details
S = 1.05
3374 reflections
225 parameters
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 475–480

In situ prepared catalyst system for transfer hydrogenation
(CH3)-2), 154.7 (NCHN). Anal. Calcd for C20H25N2Cl (%): C, 73.04; H,
7.16; N, 8.52. Found (%): C, 72.93; H, 7.16; N, 8.58.
1,3-Bis(3,4-dimethoxybenzyl)-3,4,5,6-tetrahydropyrimidinium
Chloride (1f)
Yield 4.99 g (79%); m.p. 213–214°C. IR, ν(CN): 1684 cmꢀ1 1H
.
NMR (399.9 MHz, CDCl3, δ, ppm): 1.93 (quin, J = 6 Hz, 2H,
NCH2CH2CH2N), 3.20 (t, J = 5.7 Hz, 4H, NCH2CH2CH2N), 3.83
(s, 6H, CH2C6H4(OCH3)2-3), 3.90 (s, 6H, CH2C6H4(OCH3)2-4),
4.81 (s, 4H, CH2C6H3(OCH3)2-3,4), 6.78 (d, 1H, J = 5.4 Hz), 6.89
(d, 1H, J = 5.4 Hz), 7.18 (s, 1H, CH2C6H3(OCH3)2-3,4), 10.52
(s, 1H, NCHN). 13C{H}NMR (100.5 MHz, CDCl3, δ, ppm): 19.0
(NCH2CH2CH2N), 42.2 (NCH2CH2CH2N), 55.9 (CH2C6H2(OCH3)2-3),
56.5 (CH2C6H2(OCH3)2-4), 58.4 (CH2C6H4(OCH3)2-3,4), 111.0, 112.3,
121.5, 125.6, 149.5, 149.6 (CH2C6H4(OCH3)2-3,4), 154.2 (NCHN). Anal.
Calcd for C22H29N2ClO4 (%): C,62.77; H, 6.94; N, 6.6. Found (%): C,
62.81; H, 6.97; N, 6.64.
1,3-Bis(4-methylbenzyl)-3,4,5,6-tetrahydropyrimidinium
Chloride (1b)
1
Yield 5.11 g (89%); m.p. 214–215°C. IR, ν(CN): 1684 cmꢀ1. H NMR
(399.9 MHz, CDCl3, δ, ppm): 1.91 (quin, J = 6 Hz, 2H, NCH2CH2CH2N),
2.31 (s, 6H, CH2C6H4(CH3)-4), 3.18 (t, J = 6 Hz, 4H, NCH2CH2CH2N),
4.83 (s, 4H, CH2C6H4(CH3)-4), 7.13 and 7.28 (d, J = 7.8 Hz, 8H,
CH2C6H4(CH3)-4), 10.47 (s, 1H, NCHN). 13C{H}NMR (100.5MHz, CDCl3,
δ, ppm): 18.9 (NCH2CH2CH2N), 21.2 (CH2C6H2(CH3)-4), 41.7
(NCH2CH2CH2N), 58.1 (CH2C6H4(CH3)-4), 128.8, 129.8, 130.1, 138.8
(CH2C6H4(CH3)-4), 154.2 (NCHN). Anal. Calcd for C20H25N2Cl (%):
C, 73.04; H, 7.16; N, 8.52. Found (%): C, 72.98; H, 7.18; N, 8.49.
Typical Procedure for Catalytic Transfer Hydrogenation of
Ketones
1,3-Bis(4-ethylbenzyl)-3,4,5,6-tetrahydropyrimidinium Chlo-
ride (1c)
Under an inert atmosphere, [RuCl2(p-cymene)]2 (0.01mmol),
tetrahydropyrimidinium salts 1a–1f (0.02 mmol), KOH (2 mmol)
and 10 ml of i-PrOH were added to a small Schlenk tube and the
mixture was stirred at room temperature for 0.5 h. Then ketone
(1mmol) was added to mixture and was heated at 80°C for 1 h. At
the conclusion of the reaction, the mixture was cooled, and the sol-
vent was removed under reduced pressure and extracted with
ethyl acetate–hexane (1:5), filtered through a pad of silica gel with
copious washing, concentrated and purified by flash chromatogra-
phy on silica gel. The product distribution was determined using 1H
NMR spectroscopy and GC. The yield calculations were based on
the relative areas of signal peaks of chromatograms.
1
Yield 4.70 g (88%); m.p. 195–196°C. IR, ν(CN): 1692 cmꢀ1. H NMR
(399.9 MHz, CDCl3, δ, ppm): 1.74 (t, J = 7.5Hz, 6H, CH2C6H4
(CH2CH3)-4), 2.49 (quin, J = 6 Hz, 2H, NCH2CH2CH2N), 3.15
(q, J = 7.5 Hz, 4H, CH2C6H4(CH2CH3)-4), 3.74 (t, J = 6 Hz, 4H,
NCH2CH2CH2N), 4.19 (s, 4H, CH2C6H4(CH2CH3)-4), 7.71 and 7.78
(d, J= 8.1 Hz, 8H, CH2C6H4(CH2CH3)-4), 9.06 (s, 1H, NCHN). 13C{H}
NMR (100.5 MHz, CDCl3, δ, ppm): 15.4 (CH2C6H2(CH2CH3)-4), 18.8
(NCH2CH2CH2N), 28.3 (CH2C6H2(CH2CH3)-4), 41.9 (NCH2CH2CH2N),
58.9 (CH2C6H4(CH2CH3)-4), 128.7, 128.8, 130.0, 145.2 (CH2C6H4
(CH2CH3)-4), 153.0 (NCHN). Anal. Calcd for C22H29N2Cl (%):
C, 74.03; H, 8.19; N, 7.85. Found (%): C, 74.09; H, 8.22; N, 7.81.
1,3-Bis(4-isopropylbenzyl)-3,4,5,6-tetrahydropyrimidinium
Chloride (1d)
Results and Discussion
1
Yield 4.68 g (81%); m.p. 207–208°C. IR, ν(CN): 1692 cmꢀ1. H NMR
Synthesis of Tetrahydropyrimidinium Salts
(399.9 MHz, CDCl3, δ, ppm): 1.20 (d, J = 6.9 Hz, 12H, CH2C6H4(CH
(CH3)2)-4), 1.95 (quin, J = 6.3 Hz, 2H, NCH2CH2CH2N), 2.87 (sep,
J =6.9 Hz, 2H, CH2C6H4(CH(CH3)2)-4), 3.21 (t, J =6.3 Hz, 4H,
NCH2CH2CH2N), 4.97 (s, 4H, CH2C6H4(CH(CH3)2)-4), 7.19 and 7.29
(d, J = 7.8Hz, 8H, CH2C6H4(CH(CH3)2)-4), 10.29 (s, 1H, NCHN). 13C{H}
NMR (100.5 MHz, CDCl3, δ, ppm): 19.9 (NCH2CH2CH2N), 23.9
(CH2C6H2(CH(CH3)2)-4), 33.8 (CH2C6H2(CH(CH3)2)-4), 41.3 (NCH2
CH2CH2N), 56.3 (CH2C6H4(CH(CH3)2)-4), 127.2, 128.8, 130.5, 149.7
(CH2C6H4(CH3)-4), 154.2 (NCHN). Anal. Calcd for C24H33N2Cl (%): C,
74.87; H, 8.64; N, 7.28. Found (%): C, 74.79; H, 8.71; N, 7.33.
The symmetric NHC precursors were prepared according to the
general reaction pathway depicted in Scheme 1. The syntheses of
the 1,3-diaryl-3,4,5,6-tetrahydropyrimidinium salts (1) were
achieved according to Saba et al.[37] by reaction of N,N-
dialkylpropane with triethyl orthoformate. Treatment of 1,3-
propylenediamine with 2 equivalents of aromatic aldehyde in
methanol at room temperature leads to the formation of the
corresponding diimines. Their reduction with sodium borohy-
dride in methanol, followed by treatment with triethyl
orthoformate in the presence of ammonium chloride or ammo-
nium tetrafluoroborate with continuous elimination of ethanol
leads to the formation of the expected tetrahydropyrimidinium
salts in excellent yields.
1,3-Bis(4-diethylaminobenzyl)-3,4,5,6-tetrahydropyrimidinium
Tetrafluoroborate (1e)
The tetrahydropyrimidinium salts were isolated as colorless
1
1
Yield 6.29 g (81%); m.p. 157–158°C. IR, ν(CN): 1691 cmꢀ1. H NMR
solids in very good yields and fully characterized using H NMR,
(399.9 MHz, CDCl3, δ, ppm): 1.15 (t, J = 6.9Hz, 12H, CH2C6H4N
(CH2CH3)-4)2, 1.94 (quin, J =6 Hz, 2H, NCH2CH2CH2N), 3.22
(t, J = 6 Hz, 4H, NCH2CH2CH2N), 3.22 (q, J = 6.9Hz, 8H, CH2C6H4N
(CH2CH3)2-4), 4.53 (s, 4H, CH2C6H4N(CH2CH3)2-4), 6.62 and 7.17
(d, J = 8.7Hz, 8H, CH2C6H4N(CH2CH3)2-4), 8.35 (s, 1H, NCHN). 13C{H}
NMR (100.5 MHz, CDCl3, δ, ppm): 12.5 (CH2C6H2N(CH2CH3)2-4),
18.8 (NCH2CH2CH2N), 41.8 (NCH2CH2CH2N), 44.3 (CH2C6H2N
(CH2CH3)2-4), 58.7 (CH2C6H4N(CH2CH3)2-4), 111.7, 118.6, 130.3,
148.1 (CH2C6H4N(CH2CH3)2-4), 151.8 (NCHN). Anal. Calcd for
C26H39N4BF4 (%): C, 63.16; H, 7.95; N, 11.33. Found (%): C, 63.05;
H, 7.80; N, 11.39.
13C NMR and IR spectroscopies and elemental analyses, and their
melting points were determined (see Experimental section). The
1H NMR spectra of the tetrahydropyrimidinium salts further sup-
port the assigned structures; the resonances for acidic C(2)–H
are observed as a sharp singlet at 10.08, 10.47, 9.06, 10.29, 8.35
and 10.52 ppm, respectively, for 1a–f. The position of the
diethylamino groups on the phenyl rings also has a strong influ-
ence on the acidity of the proton as a chemical shift of
8.35 ppm is observed in the case of the 4-substitution in 1e,
whereas the 4-substituted dimethoxy pattern in 1f leads to a
signal at 10.52 ppm. 13C NMR chemical shifts are consistent with
Appl. Organometal. Chem. 2015, 29, 475–480
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

E. Ö. Karaca et al.
the proposed structures; the imino carbon appears as a typical
singlet in the 1H-decoupled mode at 154.7, 154.2, 153.0, 154.2,
151.8 and 154.2 ppm, respectively, for 1a–f. The IR data for 1a–f
clearly indicate the presence of the –C¼N– group with ν(C¼N)
vibrations at 1670, 1684, 1692, 1692, 1691 and 1684 cmꢀ1, respec-
tively, for 1a–f. The NMR values are similar to those reported for
other tetrahydropyrimidinium salts.[38,39] The salts are air- and
moisture-stable both in the solid state and in solution.
(a)
Structural Characterization
The structure of 1,3-bis(2-methylbenzyl)-3,4,5,6-tetrahydropyri-
midinium chloride monohydrate was confirmed using
crystallographic analyses. The molecular structure of 1,3-bis(2-
methylbenzyl)-3,4,5,6-tetrahydropyrimidinium chloride monohy-
drate is depicted in Fig. 1, with selected bond lengths and angles
provided in Table 2.
The structure consists of
a
1,3-bis(2-methylbenzyl)-3,4,5,6-
tetrahydropyrimidinium cation, a Clꢀ anion and 1 mol water molecule
(Fig. 1). In the 1,3-bis(2-methylbenzyl)-3,4,5,6-tetrahydropyrimidinium
cation (Fig. 1), the pyrimidine ring (C1/N6/C5/C4/C3/N2) is not planar,
having total puckering amplitude QT = 0.456(2) Å. The pyrimidine ring
has an envelope conformation (ϕ = 238.7(4)° and θ = 49.7(3)°) with atom
C4 on the flap.[40,41] The deviation of atom C4 from the mean plane of
the remaining five atoms C1/N6/C5/C3/N2 is 0.634(3) Å.
Atoms N1 and N6 are sp2-hybridized, as evidenced by the sum of
the valence angles around them, 359.68(18)° and 359.53(18)°, re-
spectively. In addition, the C1–N2 and C1–N6 bonds are almost
equivalent and both are shorter than the normal C–N single bond
(1.48Å). These results can be explained by the existence of reso-
nance in this part of the molecule. All the other bond lengths are
in normal ranges.[36]
(b)
The crystal structure is stabilized by C–H…Cl and O–H…Cl hydro-
gen bonding interactions (Fig. 1). In addition, intermolecular hydro-
gen bonds link the molecules, generating R24(8) (Fig. 1) ring motif,[42]
to form a three-dimensional network.
Figure 1. (a) Molecular structure of 1,3-bis(2-methylbenzyl)-3,4,5,6-
tetrahydropyrimidinium chloride monohydrate including atom labels.
Symmetry code: Cl1A = ꢀx, 1 ꢀ y, 1 ꢀ z. The anisotropic displacement
parameters are displayed at a 50% probability level. Selected bond lengths
(Å) and angles (°): C1–N2 = 1.316(3), C1–N6 = 1.314(3), N2–C3 = 1.469(3),
C5–N6 = 1.469(3), C3–C5 = 1.520(3), C4–C5 = 1.517(3), N6–C1–N2 = 124.3(2),
C1–N2–C3 = 121.06(18), C1–N2–C7 = 120.10(18), C1–N5–C5 = 121.21(18),
C1–N6–C15 = 120.11(18), C5–C4–C3 = 110.57(18). (b) Packing diagram (unit
cell shown) and hydrogen bonding of 1,3-bis(2-methylbenzyl)-3,4,5,6-
tetrahydropyrimidinium chloride monohydrate including atom labels.
Hydrogen bonds are indicated as dashed lines. Symmetry codes: A = 0.5
+ x, 1.5 ꢀ y, ꢀ0.5 + z; B = 1 ꢀ x, 1 ꢀ y, 1 ꢀ z; D = 0.5 ꢀ x, ꢀ0.5 + y, 1.5 ꢀ z.
Catalytic Transfer Hydrogenation of Ketones
Catalytic reduction is preferred to stoichiometric reduction for
large-scale industrial uses of ketones and hydrogenation is well
known.[43] Hydrogen gas presents considerable safety hazards es-
pecially for large-scale reactions. The use of a solvent that can do-
nate hydrogen overcomes these difficulties. 2-Propanol is a
popular reactive solvent for transfer hydrogenation since it is easy
to handle (b.p. 82°C), relatively non-toxic, environmentally benign
and inexpensive. The volatile acetone product can also be easily re-
moved to shift an unfavorable equilibrium.[1] Owing to their effi-
ciency in the transfer hydrogenation of acetophenone derivatives,
in situ generated ruthenium complexes were further investigated
for the transfer hydrogenation of various methyl aryl ketones.
We examined the catalytic activity of in situ prepared
tetrahydropyrimidinium salt/[RuCl2(p-cymene)]2 catalyst system in
the transfer hydrogenation of aryl ketones with isopropanol to
the corresponding alcohol. Isopropanol is the hydrogen source
and KOH presumably enhances catalysis by promoting the forma-
tion of intermediates and deprotonation of salts. The reduction of
acetophenone to 1-phenylethanol was initially used as a model
reaction with in situ prepared Ru(II) systems with 1a–f as catalysts
in the transfer hydrogenation. In order to ensure complete
formation of the active catalyst, a 2-propanol solution of 1 mol%
[RuCl2(p-cymene)]2 and 2 mol% 1a is stirred in the presence of
Table 2. Hydrogen bond geometry
D–H · · · A
D–H (Å)
H · · · A (Å)
D · · · A (Å) D–H · · · A (°)
O1–H1A · · · Cl1a
O1–H1B · · · Cl1b
C1–H(1) · · · Cl(1)c
0.85(2)
0.85(2)
0.96
2.32(2)
2.37(2)
2.53
3.162(2)
3.213(2)
3.453(2)
170(3)
172(3)
162
aSymmetry codes: x + 1, y, z + 1.
bSymmetry codes: ꢀx + 1, ꢀy, ꢀz + 1.
cSymmetry codes: ꢀx, 1 ꢀ y, 1 ꢀ z.
2 mmol of KOH at room temperature for 0.5h. According to the lit-
erature during the formation of Ru–carbene complexes with [RuCl2
(p-cymene)]2, one carbene molecule bonds to the Ru center.[17,31,32]
Then acetophenone (1.00 mmol) is added and the reaction
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 475–480

In situ prepared catalyst system for transfer hydrogenation
performed at 80°C for 1 h. When a lower catalyst molar ratio is used,
conversion decreases (Table 3, entries 10 and 11). The reactions are
conducted at a substrate/catalyst/base molar ratio of 1:0.01:2. When
[RuCl2(p-cymene)]2 is used as catalyst, phenylethanol is obtained in
55% yield.
Table 4. Transfer hydrogenation of ketones with catalyst system [RuCl2
(p-cymene)]2/(1a–f)a
Since the base facilitates the formation of a ruthenium alkoxide
by abstracting a proton from isopropanol, various bases were used
as promoters in the transfer hydrogenation of ketones.
Acetophenone was kept as a test substrate and was allowed to re-
act in isopropanol with [RuCl2(p-cymene)]2/1a in the presence of
various bases, namely NEt3, Cs2CO3, K2CO3, NaOH, KOH, t-BuOK
and NaOAc. With the organic base NEt3 we observe only poor yields
(Table 3, entry 1). Using inorganic bases the conversion shows a de-
pendency upon the base strength. It is observed that NaOH and
KOH show good conversions when compared to Cs2CO3, K2CO3,
t-BuOK and NaOAc in the hydrogenation reactions. As in previous
studies, the best results are obtained with KOH.[31–33] In the absence
of a base no transfer hydrogenation of ketones is observed. Also,
when the catalytic system is used in transfer hydrogenation of
acetophenone at room temperature, formation of phenylethanol
is not appreciable. When this catalytic system is used at 50°C,
phenylethanol is observed in 10% yield (Table 3, entry 9). We tried
this reaction for a duration of 30 min. However the yields are lower
than those obtained for 1 h; for example, the reduction of
acetophenone with 1a is completed within 30 min with a yield of
69% (Table 3, entry 8).
Entry
Precursor
R
Yield (%)
1
1a
H
85
84
90
83
69
66
98
93
98
90
62
86
96
90
94
75
50
80
93
89
90
71
60
78
90
85
93
67
50
70
98
95
95
91
40
82
2
p-OMe
p-F
3
4
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
H
5
6
7
1b
1c
1d
1e
1f
8
p-OMe
p-F
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
H
p-OMe
p-F
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
H
p-OMe
p-F
Under the reaction conditions, the [RuCl2(p-cymene)]2/1b system
proves to be the most effective catalyst relative to 1a, 1c, 1d, 1e
and 1 f. The reduction of acetophenone with [RuCl2(p-cymene)]2/
1b is completed within 1 h with a yield of 98% (Table 4, entry 7).
We next extended our investigations to include transfer
hydrogenation of substituted acetophenone derivatives. A variety
of ketones are transformed to the corresponding secondary
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
H
p-OMe
p-F
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
H
Table 3. Screening of transfer hydrogenation reaction conditionsa
p-OMe
p-F
Entry
Catalyst
Catalyst amount Base Yield
TOF
b
3,4,5-OMe
2,4,6-Me
p-C(O)Ph
(%)
(%)
(hꢀ1
)
1
2
3
4
5
6
7
8
9
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
[RuCl2(p-cymene)]2/1a
1
NEt3
Cs2CO3
K2CO3
NaOH
KOH
9
9
1
65
51
82
85
74
39
69c
10d
65
65
51
82
85
74
39
aReaction conditions: [RuCl2(p-cymene)]2 (0.01 mmol), tetrahydropy
rimidinium halide 1a–1e (0.02 mmol), KOH (2 mmol), PrOH (10 ml),
substrate (1.0 mmol), 80°C, 1 h. Purity of compounds checked using
GC and yields are based on ketones.
i
1
1
1
1
t-BuOK
NaOAc
KOH
1
1
138
10
alcohols. Typical results are shown in Table 4. Under those condi-
tions p-methoxyacetophenone, p-fluoroacetophenone and 3,4,5-
trimethoxyacetophenone react very cleanly and in good yields with
2-propanol (Table 4, entries 8, 9, 10 and 15). The presence of an
electron-withdrawing (F) or electron-donating (OCH3) substituent
on acetophenone (Table 4, entries 8 and 15) has a significant effect
on the reduction of ketones to their corresponding alcohols. The
maximum conversion of 4-fluoroacetophenone to corresponding
alcohol is achieved over a period of 1 h (Table 4, entry 9). The
conversion of ketones with a bulky substituent on the aromatic ring
is not observed or is slightly decreased. For example, when 2,4,6-
trimethylbenzylmethyl ketone is used conversion decreases
1
KOH
10 [RuCl2(p-cymene)]2/1a
11 [RuCl2(p-cymene)]2/1a
0.5
0.25
1
KOH
130
168
55
KOH
42
55
9
12
13
[RuCl2(p-cymene)]2
KOH
—
—
KOH
9
i
aReaction conditions: KOH (2 mmol), PrOH (10 ml), substrate (1.0
mmol), 80°C, 1 h. Purity of compounds checked using GC and yields
are based on ketones.
bTOF = (mol product/mol catalyst) × hꢀ1
.
cReaction time is 30 min.
d50°C, 1 h.
Appl. Organometal. Chem. 2015, 29, 475–480
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

E. Ö. Karaca et al.
[11] S. Diez-Gonzalez, N. Marion, S. P. Nolan, Chem. Rev. 2009, 109, 3612.
[12] J. Louie, C. W. Bielawski, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123,
11312.
[13] İ. Özdemir, S. Yaşar, B. Çetinkaya, Transition Met. Chem. 2005, 30, 831.
[14] F. L. Zeng, Z. K. Yu, Organometallics 2008, 27, 6025.
[15] D. Gnanamgari, E. L. O. Sauer, N. D. Schley, C. Butler, C. D. Incarvito,
R. H. Crabtree, Organometallics 2009, 28, 321.
[16] J. Witt, A. Pöthig, F. E. Kühn, W. Baratta, Organometallics 2013, 32, 4042.
[17] S. Yaşar, S. Çekirdek, İ. Özdemir, J. Coord. Chem. 2014, 67, 1236.
[18] E. Mas-Marza, J. A. Mata, E. Peris, Angew. Chem. Int. Ed. 2007, 46, 3729.
[19] H. Türkmen, T. Pape, F. E. Hahn, B. Çetinkaya, Eur. J. Inorg. Chem. 2008,
36, 5418.
[20] S. Yaşar, K. J. Cavell, B. D. Ward, B. Kariuki, Appl. Organometal. Chem.
2011, 25, 374.
[21] N. B. Jokić, M. Zhang-Presse, S. L. M. Goh, C. S. Straubinger, B. Bechlars,
W. A. Herrmann, F. E. Kühn, J. Organometal. Chem. 2011, 696, 3900.
[22] V. Gierz, A. Urbanaite, A. Seyboldt, D. Kunz, Organometallics 2012, 31,
7532.
(Table 4, entries 25–30). The in situ catalytic system also catalyzes
the transfer hydrogenation of benzophenone very effectively
(Table 4, entries 6, 12, 18, 24, 30, 36).
Under the reaction conditions, salts 1f and 1b prove to be the
most effective catalysts relative to the other salts. The reduction
of acetophenone with tetrahydropyrimidinium salts is completed
within 1 h in high yields. It is evident that the NHC precursors that
contain electron-donating methoxy substituent (1f) and methyl
substituent (1b) are the most effective of the salts examined.
Catalytic transfer hydrogenation by the use of inorganic salts
is well established. It is noted that these reactions rely on long
reaction times.[44,45] Beller and co-workers reported the applica-
tion of in situ generated ruthenium carbene complexes in the
reduction of various ketones. Acetophenone derivatives were
reduced at 100°C for 12 h.[46] Bala and co-workers reported the
use of ferrocenylimidazolium salts as catalysts for the transfer
hydrogenation of ketones in propanol at 82°C for 24 h.[47] Com-
pared with these results, the in situ prepared three-component
1,3-dialkyltetrahydropyrimidinium salts/[RuCl2(p-cymene)]2 and
KOH are active in the reduction of ketones under mild
conditions with almost quantitative conversions and short reac-
tion times.
[23] A. Azua, J. A. Mata, E. Peris, F. Lamaty, J. Martinez, E. Colacino,
Organometallics 2012, 31, 3911.
[24] M. Blanco, P. Álvarez, C. Blanco, M. V. Jiménez, J. Fernández-Tornos,
J. J. Pérez-Torrente, L. A. Oro, R. Menéndez, ACS Catal. 2013, 3, 1307.
[25] S. Gülcemal, A. G. Gökçe, B. Çetinkaya, Inorg. Chem. 2013, 52, 10601.
[26] U. Hintermair, J. Campos, T. P. Brewster, L. M. Pratt, N. D. Schley,
R. H. Crabtree, ACS Catal. 2014, 4, 99.
[27] R. Castarlenas, M. A. Esteruelas, E. Onate, Organometallics 2008, 27,
3240.
[28] S. Kuhl, R. Schneider, Y. Fort, Organometallics 2003, 22, 4184.
[29] D. S. Tromp, P. Hauwert, C. J. Elsevier, Appl. Organometal. Chem. 2012,
26, 335.
[30] W. A. Herrmann, K. Öfele, D. Preysing, E. Herdtweck, J. Organometal.
Chem. 2003, 684, 235.
Conclusions
We have synthesized new 3,4,5,6-tetrahydropyrimidinium salts as
precursors of N-heterocyclic carbenes. All the compounds were
characterized using 1H NMR, 13C NMR and IR spectroscopies and el-
emental analysis. One ligand was structurally characterized using
single-crystal X-ray diffraction. They were associated with [RuCl2
(p-cymene)]2 to generate catalytic species. This concept for making
catalysts in situ opens the way for the discovery of many new
catalysts via the interaction of metal complexes and suitable
ligands. The catalytic effects of this in situ prepared catalyst system
have been investigated in the reduction of acetophenone and its
derivatives using 2-propanol and KOH under mild reaction condi-
tions. Also, the procedure is simple and efficient towards various
aryl ketones. Detailed investigations focusing on new metal–NHC
complexes and other applications are ongoing.
[31] N. Gürbüz, S. Yaşar, E. Ö. Özcan, İ. Özdemir, B. Çetinkaya, Eur. J. Inorg.
Chem. 2010, 3051.
[32] N. Gürbüz, E. Ö. Özcan, İ. Özdemir, B. Çetinkaya, O. Şahin,
O. Büyükgüngör, Dalton Trans. 2012, 41, 2330.
[33] E. Ö. Özcan, D. Mercan, N. Gürbüz, E. Çetinkaya, B. Çetinkaya, İ. Özdemir,
Turk. J. Chem. 2011, 35, 699.
[34] CrystalClear, Molecular Structure Corporation, The Woodlands, TX/
Rigaku Corporation, Tokyo, 2006.
[35] G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112.
[36] F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, R. Taylor,
J. Chem. Soc. Perkin Trans. 2 1987, S1.
[37] S. Saba, A.-M. Brescia, M. K. Kaloustin, Tetrahedron Lett. 1991, 32, 5031.
[38] İ. Özdemir, S. Demir, B. Çetinkaya, Tetrahedron 2005, 61, 9791.
[39] S. Yaşar, E. Ö. Özcan, N. Gürbüz, B. Çetinkaya, İ. Özdemir, Molecules
2010, 15, 649.
[40] M. Nardelli, Acta Crystallogr. 1983, C39, 1141.
[41] D. Cremer, J. A. Pople, J. Am. Chem. Soc. 1975, 97, 1354.
[42] J. Bernstein, R. E. Davis, L. Shimoni, N. L. Chang, Angew. Chem. Int. Ed.
Engl. 1995, 34, 1555.
Acknowledgements
[43] J.-P. Genet, Acc. Chem. Res. 2003, 36, 908.
This work was financially supported by the Technological and
Scientific Research Council of Turkey TUBİTAK (TBAG (107 T098))
and İnönü University Research Fund (İÜBAP: 2013/51).
[44] A. Ouali, J.-P. Majoral, A.-M. Caminade, M. Taillefer, ChemCatChem 2009,
1, 504.
[45] V. Polshettiwar, R. S. Varma, Green Chem. 2009, 11, 1313.
[46] S. Enthaler, R. Jackstell, B. Hagemann, K. Junge, G. Erre, M. Beller,
J. Organometal. Chem. 2006, 691, 4652.
[47] M. I. Ikhile, M. D. Bala, V. O. Nyamori, J. C. Ngila, Appl. Organometal.
Chem. 2013, 27, 98.
References
[1] R. Noyori, S. Hashiguchi, Acc. Chem. Res. 1997, 30, 97.
[2] H. U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer, Adv.
Synth. Catal. 2003, 345, 103.
[3] S. Gladiali, E. Alberico, Chem. Soc. Rev. 2006, 35, 226.
[4] J. S. M. Samec, J.-E. Bäckvall, P. G. Andersson, P. Brandt, Chem. Soc. Rev.
2006, 35, 237.
[5] J. R. Miecznikowski, R. H. Crabtree, Polyhedron 2004, 23, 2857.
[6] A. G. Campaña, R. E. Estévez, N. Fuentes, R. Robles, J. M. Cuerva,
E. Buñuel, D. Cárdenas, J. E. Oltra, Org. Lett. 2007, 9, 2195.
[7] T. Koike, T. Ikariya, Adv. Synth. Catal. 2004, 346, 37.
[8] P. Hauwert, R. Boerleider, S. Warsink, J. J. Weigand, C. Elsevier, J. Am.
Chem. Soc. 2010, 132, 16900.
[9] a) R. Malacea, R. Poli, E. Manoury, Coord. Chem. Rev. 2010, 254, 729; b)
T. Ikariya, A. J. Blacker, Acc. Chem. Res. 2007, 40, 1300.
[10] J. A. Mata, M. Poyatos, E. Peris, Coord. Chem. Rev. 2007, 251, 841.
Supporting Information
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web-site.
Crystallographic data for the structure reported in this paper has
been deposited with the Cambridge Crystallographic Data Center:
CCDC-1019867 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
the Cambridge Crystallographic Data Centre, www.ccdc.cam.ac.
uk/data request/cif.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 475–480