Catalytic activity in transfer hydrogenation using ruthenium (II) carbonyl complexes containing two 1,8-naphthyridine as N-monodentate ligands

Article abstract of DOI:10.1016/j.ica.2018.10.037

A new series of novel complexes of type cis-[Ru(CO)₂Cl₂(L)₂], L = 2-phenyl-1,8-naphthyridine, 2-(4′-nitrophenyl)-1,8-naphthyridine, 2-(4′-bromophenyl)-1,8-naphthyridine, 2-(4′-methylphenyl)-1,8-naphthyridine, 2-(3′-methoxyphenyl)-1,8-naphthyridine, 2-(2′-methoxyphenyl)-1,8-naphthyridine and 2-(4′-methoxyphenyl)-1,8-naphthyridine have been successfully synthesized and characterized. We found that the complexes can be directly synthesized from [RuCl₂(CO)₂]₂ with high yield. The crystallographic structures of complex cis-[RuCl₂(CO)₂(2-(4′-methoxyphenyl)-1,8-naphthyridine-κN8)₂] and cis-[RuCl₂(CO)₂(2-(2′-methoxyphenyl)-1,8-naphthyridine-κN8)₂] have been established by X-ray single crystal diffraction studies, which indicate an octahedral geometry with two 1,8-naphthyridine ligands coordinated to the metal in a N-monodentate fashion. The ruthenium(II) complexes have been studied as catalysts in the transfer hydrogenation of acetophenone. We found that complexes show moderate activities and a 100% selectivity. The best turnover frequency (390 h^?1) is found for cis-[RuCl₂(CO)₂(2-(4′-methoxyphenyl)-1,8-naphthyridine-κN8)₂] when the substrate/catalysis ratio was 1000/1. The catalytic conditions were optimized using different substrate/catalyst and base/catalyst ratios.

Full text of DOI:10.1016/j.ica.2018.10.037

Accepted Manuscript
Research paper
Catalytic activity in transfer hydrogenation using ruthenium (II) carbonyl com-
plexes containing two 1,8-naphthyridine as N-monodentate ligands
Juana Gajardo, Juan C. Araya, Andrés Ibá ñez, Véronique Guerchais, Hubert
Le Bozec, Sergio A. Moya, Pedro Aguirre
PII:
S0020-1693(18)30762-X
https://doi.org/10.1016/j.ica.2018.10.037
ICA 18583
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
15 May 2018
18 October 2018
21 October 2018
Please cite this article as: J. Gajardo, J.C. Araya, A. Ibá ñez, V. Guerchais, H. Le Bozec, S.A. Moya, P. Aguirre,
Catalytic activity in transfer hydrogenation using ruthenium (II) carbonyl complexes containing two 1,8-
naphthyridine as N-monodentate ligands, Inorganica Chimica Acta (2018), doi: https://doi.org/10.1016/j.ica.
2018.10.037
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1
Catalytic activity in transfer hydrogenation
using ruthenium (II) carbonyl complexes containing two 1,8-naphthyridine
as N-monodentate ligands.
Juana Gajardoa, Juan C. Arayab, Andrés Ibáñezc, Véronique Guerchaisd, Hubert Le
Bozecd, Sergio A. Moya*e and Pedro Aguirre*f
aUniversidad San Sebastián, Facultad de Ciencias, Depto. de Ciencias Biológicas
y Químicas, Santiago, Chile.
bUniversidad Central, Centro de Ciencias Básicas, Facultad de Ciencias de la
Salud, Santiago, Chile.
c Universidad de Chile, Facultad de Ciencias Físicas y Matemáticas, Santiago,
Chile.
dUMR 6226 CNRS-Université de Rennes 1, Sciences Chimiques de Rennes,
Campus de Beaulieu, 35042 Rennes, France.
eUniversidad de Santiago de Chile, Facultad de Química y Biología, Avda.
Libertador Bernardo O’Higgins 3363, casilla 40, correo 33, Santiago, Chile.
sergio.moya@usach.cl
fUniversidad de Chile, Facultad de Ciencias Químicas y Farmacéuticas, Santiago,
Chile.paguirre@ciq.uchile.cl
This manuscript is dedicated to Professor Hubert Le Bozec from Rennes
University, France, who retired recently. Professor Le Bozec had a long and fruitful
collaboration with our group in Chile for 30 years. During that time many Chilean
postgraduate students made part of their theses in the University of Rennes,
supervised by Prof. Le Bozec. Throughout his collaboration with us, we have not
only an excellent co-worker but also a great friend and we are sure that our
friendship will last forever.
Abstract
A new series of novel complexes of type cis-[Ru(CO)2Cl2(L)2], L= 2-phenyl-1,8-
naphthyridine, 2-(4’-nitrophenyl)-1,8-naphthyridine,
2-(4´bromophenyl)-1,8-
naphthyridine, 2-(4´-methylphenyl)-1,8-naphthyridine, 2-(3’-methoxyphenyl)-1,8-

2
naphthyridine, 2-(2’-methoxyphenyl)-1,8-naphthyridine and 2-(4’-methoxyphenyl)-
1,8-naphthyridine have been successfully synthesized and characterized. We
found that the complexes can be directly synthesized from [RuCl2(CO)2]2 with high
yield.
The crystallographic structures of complex cis-[RuCl2(CO)2(2-(4'-
and cis-[RuCl2(CO)2(2-(2'-
methoxyphenyl)-1,8-naphthyridine-κN8)2]
methoxyphenyl)-1,8-naphthyridine-κN8)2] have been established by X-Ray single
crystal diffraction studies, which indicate an octahedral geometry with two 1,8-
naphthyridine ligands coordinated to the metal in a N-monodentate fashion. The
ruthenium(II) complexes have been studied as catalysts in the transfer
hydrogenation of acetophenone. We found that complexes show moderate
activities and a 100 % selectivity. The best turnover frequency (390 h-1) is found for
cis-[RuCl2(CO)2(2-(4'-methoxyphenyl)-1,8-naphthyridine-κN8)2]
when
the
substrate/catalysis ratio was 1000/1. The catalytic conditions were optimized using
different substrate/catalyst and base/catalyst ratios.
Keywords: Ruthenium (II), 1,8-naphthyridine complexes, transfer hydrogenation,
acetophenone, homogeneous catalysis.
Introduction
The naphthyridines (NAPs) are a group of diazanaphthalenes that contain a single
nitrogen atom in each ring but no nitrogen atom at either of the bridgehead
positions [1]. Several structural isomers exist, where the 1,8-NAPs are key
components of a number of antibacterial agents [2]. The synthetic procedure are
prepared via the Friedländer condensation of 2-aminonicotinaldehyde with the
corresponding acyl derivatives[3-6]. In this system, the precursor 2-
aminonicotinaldehyde must be freshly prepared and used immediately after
isolation to avoid self-condensation side reactions. Indeed, a facile synthesis of 2-
aminonicotinaldehyde was reported by Caluwe and co-workers in 1974 [5], with
modifications being introduced later by Dunbar et all.,Rivera et al. [7, 8]. In
addition, the preparation of various alkylsubstituted (i.e., 2- and/or 3-position) NAP
ligands has also been reported [9-14]. During the formation of mononuclear

3
ruthenium complexes, 1,8-NAP (1) tends to act as either a monodentate or a
bidentate ligand. However, chelation is generally disfavored due to the small bite
angle of the four-membered chelate ring.
Ruthenium complexes derived from 1,8-NAP have also been applied in
homogeneous catalytic reactions as substitutes for 2,2-bipyridine or 1,10-
phenanthroline (phen). For example, the catalytic potential of ruthenium complexes
containing monodentate 1,8-NAPs, was investigated in the hydroformylation of
styrene in dimethylformamide [15].
Ruthenium arene complexes, [(η6-p-cymene)2Ru2(L)Cl2](PF6)2 L = 7-bis(di-2-
pyridinyl)-1,8- naphthyridine] was synthesized and characterized by spectroscopic
and analytical techniques. The use of these ruthenium complexes as pre-catalysts
for oxidative coupling of 1,2-diols/1,2-aminoalcohol with o-phenylenediamines
leading to quinoxalines was investigated. [16]. Other ruthenium complexes
containing 1,8 NAP derivate have been succefully prepared and used as anticarcer
compunds[ 17]
Other authors found that ruthenium-hydride complexes containing 1,8 NaPs
ligands are effective catalysts in the transformation of primary alcohols, including
amino alcohols, into the corresponding carboxylic acid in the presence of alkaline
water [18]. This work proposed that the 1,8-NAP unit enhances the nucleophilicity
of a water molecule through hydrogen bonding, and that the noncoordinated
nitrogen atom in the 1,8-NAP unit promotes solvated hydroxide attack through
hydrogen bonding with a water molecule of the solvent cage. Alternatively,
uncoordinated nitrogen atom may facilitate hydroxide attack by coordination with
Na+.

4
Scheme 1. Hydrogen transfer reaction of ketones (HTR).
Transfer hydrogenation of ketones by propan-2-ol is convenient in large-scale
synthesis since there is no need to employ a high hydrogen pressure or to use
hazardous reducing agents (scheme 1). Transition metal complexes containing a
coordinative unsaturated metal center and a Brønsted basic π-donor ligand have
been reported in homogeneous transfer hydrogenation. Ligands with different
transition metals such as amido [19-22], thiolate [23-28], phosphido [29], imido [30-
40], oxo [41-46], and sulfido [47] have been investigated for this reaction. The most
active and selective catalysts for the transfer hydrogenation reactions are
ruthenium [48], iridium [49] and rhodium [50] complexes containing nitrogen,
oxygen and N,O-donor ligands [51- 58]. We have investigated the synthesis of
ruthenium complexes containing polypyridine ligands and their application as
potential homogeneous catalysts. We found that the compounds are active in the
transfer hydrogenation where the active species is a ruthenium hydride complex
containing 2,2-bipyridine, phenanthroline and 1,8-naphthyridine ligands.
Herein, we report the synthesis and the catalytic behavior of ruthenium complexes
of the type cis-[Ru(CO)2Cl2(L)2] with L = 2-phenyl-1,8-naphthyridine; L1, 2-(4’-
nitrophenyl)-1,8-naphthyridine; , L2, 2(4'-bromophenyl)-1,8-naphthyridine; , L3, 2-
(4'-methylphenyl)1,8-naphthyridine; , L4, 2-(4'-methoxyphenyl)-1,8-naphthyridine; ,
L5, 2-(3'-methoxyphenyl)-1,8-naphthyridine;; , L6 and 2-(2'-methoxyphenyl)-1,8-
naphthyridine, L7, in hydrogenation reaction of ketones. The X-Ray structures of
complexes show that two naphthyridines ligands coordinate in an N-monodentate
fashion to the metal. We will describe detailed studies on their catalytic activities for
the hydrogen transfer reaction of ketones (HTR).
Experimental part.
Materials and general methods
All the reagents used were chemically pure and analytical grade.
Acetophenone was used as supplied from Sigma-Aldrich. [RuCl2(CO)2]2 [59] was
prepared by refluxing commercial RuCl3•3H2O in a mixture of 37 % hydrochloric
acid and 88 % formic acid (1:1) during 24 hours under nitrogen. The ligands were

5
prepared from 2-aminonicotinaldehyde and substituted acetophenone. The
substrates were obtained from Sigma-Aldrich.
The catalytic conversions were determinated by gas chromatography using an
Agilent 6890 Series GC System equipped with a flame ionization detector and a
(30 m•0.25 mm• 0.25 µm) HP-INNOWAX column.
Crystal structure analysis of complexes. The data were collected at a
temperature of 293 ± 2o K on an Oxford Diffraction X calibur Saphir 3 diffractometer
equipped with graphite monochromated MoKα radiation (= 0.71069 Å). The
structure was solved with SIR-97, which reveals the non-hydrogen atoms of the
molecules. The structure was solved in the space group P21/c by Patterson or
direct method and refined by the full-matrix least-squares fitting on F2 using
SHELXTL-97 with initial isotropic parameters.
General procedure
Synthesis of ligands
A suspension of 2-aminonicotinaldehyde (500 mg; 4.09 mmol), substituted
acetophenone (4.09 mmol), and NaOH (200 mg; 5 mmol) in EtOH (40 mL) was
refluxed under argon for 4 hours. The solvent was removed under vacuum. The
residue was extracted from a mixture of CH2Cl2 /water and the organic layer was
dried over magnesium sulfate; the product was purified by column chromatography
on silica gel eluting with CH2Cl2:EtOAc (6:1). After the solvent was removed, the
desired product was obtained as a white solid. (more information about ligands
characterization see supplemental material) .
Synthesis of complexes
The ligands L (1.316 mmol) and [RuCl2(CO)2]2 (0.658 mmol) were mixed in
ethanol/H2O (9/1) (50 mL) The mixture was refluxed for 24 hours under nitrogen
atmosphere. The precipitate was separated by filtration and the solid was washed
with, ethanol, acetone, chloroform and ether ethylic.
Cis-[RuCl2(CO)2(2-phenyl-1,8-naphthyridine-κN8)2](Ru-1).
1H-NMR (200 MHz, CDCl3) 10.44 (dd, H7,J = 5.4 Hz, J = 2.0 Hz,1H), 8.98 (dd, H7’,
J = 5.3 Hz, 1.9 Hz,1H), 8.83 (dd, H5, J = 8.0 Hz, J = 2.0 Hz, 1H), 8.75 (m, o-Ph, m-
Ph, 2H), 8.65 (d, H4, J = 8.4 Hz,1H), 8.45 (d, H4’, J = 8.8 Hz,1H ), 8.43 (d, H3’, J =
8.8 Hz, 1H), 8.29 (dd, H5’, J = 8.0 Hz, J = 1.9 Hz, 1H), 8.10 (d, H3, J = 8.4 Hz, 1H),
8.01 (dd, H6, J = 8.0 Hz, J = 5.4 Hz, 1H), 7.78 (m, m-Ph, 1H), 7.70 (m, p-Ph, 1H),
7.37 (m, m-Ph, 1H), 7.35 (m, o-Ph, 1H), 7.24 (m, o-Ph, 1H), 7.09 (dd, H6’, J = 8.0
Hz, J = 5.3 Hz, 1H), 6.95 (m, o-Ph, 1H). Yield 65%. MP 340 °C (d). IR (KBr, cm-1)

6
M-CO 2044.7; 1983.2. Anal. Calcd. (%) for: C30H20Cl2N4O2Ru C, 56.26; H, 3.15; N,
8.75. Found (%): C, 55.95; H, 2.95; N, 8.76.
Cis-[RuCl2(CO)2(2-(4’-nitrophenyl)-1,8-naphthyridine-κN8)2] (Ru-2).
1H-NMR (200 MHz, CDCl3) 10.93 (dd, H7, J = 5.3 Hz, J = 1.8 Hz, 1H), 8.98 (m, H7’,
Ph´ 3H), 8.91 (dd, H5, J = 8.1, J = 1.8, 1H), 8.71 (m, 2H, Ph), 8.69 (d, H4, J = 8.4
Hz, 1H), 8.56 (d, H4’, J = 8.6 Hz, 1H), 8.49 (d, H3’,J = 8.6, 1H), 8.32 (dd, H5’, J = 8.0
Hz , J = 1.6 Hz, 1H), 8.15 (d, H3, J = 8.4 Hz, 1H), 8.1 (dd, H6, J = 8.1, J = 5.3, 1H),
7.82 (m. Ph’, 2H), 7.57 (m, Ph, 2H), 7.09 (dd, H6´, J = 8.0 Hz, J = 5.2 Hz, 1H). Yield
57%. MP 328 °C (d). IR (KBr, cm-1): M-CO 2051.6; 1987.6. Anal. Calcd. (%) for
C30H18Cl2N6O6Ru: C, 49.33; H, 2.48; N, 11.50. Found (%): C, 48.96; H, 2.32; N,
11.26.
Cis-[RuCl2(CO)2(2-(4’-bromophenyl)-1,8-naphthyridine-κN8)2] (Ru-3).
1H-NMR (200 MHz, CDCl3) 10.05 (dd, H7, J = 5.4 Hz, J = 1.8 Hz, 1H), 9.76(dd, H7’,
J = 5.4 Hz , J = 1.8 Hz, 1H), 8.52 (dd, H5, J = 8.1 Hz, J = 1.8 Hz, 1H), 8.47(d, H3, J
= 8.6 Hz, 1H), 8.36 (dd, H5’, J = 8.1 Hz, 1.8 Hz, 1H), 8.35 (d, H4, J = 8.9 Hz, 1H),
8.17(d, H3’, J = 8.6 Hz, 1H), 8.09 (d, H3, J = 8.9 Hz, 1H), 8.05 ( m, Ph, Ph´, 3H),
7.82 (dd, H6, J = 8.1 Hz, J = 5.4 Hz), 7.79 (d, Ph´, J = 8.7 Hz), 2H), 7.64 (dd. H6´, J
= 8.1 Hz, J = 5.4 Hz). Yield 67%. MP 368 °C (d). IR (KBr, cm-1) M-CO 2050.2;
1985.6. Calcd. (%) for C30H18Br2N4O2Ru: C, 45.14; H, 2.27; N, 7.02. Found (%): C,
44.96; H, 2.37; N, 6.79.
Cis-[RuCl2(CO)2(2-(4’-methylphenyl)-1,8-naphthyridine-κN8)2] (Ru-4).
1H-NMR (200 MHz, CDCl3) 10.47 (dd, H7, J = 5.5 Hz, J = 1.9 Hz, 1H), 8.85 (dd, H7’,
J = 5.4 Hz, J = 1.0 Hz), 8.46 (d, Ph,1H), 8.38 (dd, H5, J = 7.8 Hz , J = 1.9 Hz, 1H),
8.20 (d, H4, H4’, J = 8.4 Hz, 2H), 8.05 ( d, H3, J = 8.5 Hz, 1H), 7.78 (m,H5’,H6, 2H,),
7.70 (d, Ph, J = 7.50 Hz, 1H), 7.69 (d, H3’, J = 8.4 Hz, 1H), 7.50 (m, Ph, 2H), 7.07
(d, Ph´, 1H), 6.72 (dd, H6’, J = 7.8 Hz, J = 5.4 Hz, 1H), 6.66 (d, Ph´, J = 8.0 Hz, 1H
), 6.60 (d, Ph´, J = 8.0 Hz), 2.52 (s, Me), 2,25 (s, Me). Yield 69%. MP 341 °C (d).
IR (KBr, cm-1) M-CO 2055.0, 1988.9. Anal.Calcd. (%) for C32H24Cl2N4O2Ru: C,
57.49; H, 3.62; N, 8.38. Found (%): C, 57.20; H, 4.00; N, 8.28.
Cis-[RuCl2(CO)2(2-(4’-metoxyphenyl)-1,8-naphthyridine-κN8)2] (Ru-5).
1H-NMR (200 MHz, CDCl3) 10.54 (dd, H7, J = 5.5 Hz, J = 2.2 Hz,1H), 9.03 (dd, H7’,
J = 5.7 Hz, J = 1.8 Hz, 1H), 8.93 (m,H5, Ph, 2H), 8.71 (d, H4, J = 8.8 Hz, 1H), 8.68
(d, H4’, J = 8.6 Hz, 1H), 8.59 (d,H3’, J = 8.6 Hz, 1H), 8.42 (dd, H5´, J = 8.1 Hz, J =
1.8 Hz, 1H), 8.21 (d, H3, J = 8.8 Hz), 8.1 (dd, H6, J = 8.2 Hz, J = 5.5 Hz, 1H), 7.50
(m, Ph´,2H), 7.21 (dd, H6’, J = 8.1 Hz, J = 5.7 Hz, 1H), 6.58 (m, Ph´,2H), 4.14
(OMe), 3.91 (OMe). Yield 68%. MP 337 °C (d). IR (KBr, cm-1) M-CO 2050.0,
1988.2. Anal. Calcd. (%) for C32H24Cl2N4O4Ru: C, 54.86; H, 3.45; N, 8.00. Found
(%): C, 54.09; H, 3.95; N, 7.98.

7
Cis-[RuCl2(CO)2(2-(3’-methoxyphenyl)-1,8-naphthyridine-κN8)2](Ru-6).
1H-NMR (200 MHz, CDCl3) 10.47 (dd, H7, J = 5.4 Hz, J = 1.8 Hz, 1H), 8.80 (dd,
H7’, J = 5.3 Hz, J = 1,8 Hz, 1H), 8.41 (dd,H5, J = 7.9 Hz, J = 1.8 Hz, 1H), 8.23 (m ,
Ph, 2H), 7.98 (m, H4’, H4, 2H), 7.79 (m, H3’,H5’, H3, 3H), 7.58 (m, H6, Ph, 2H), 7.18
(m, Ph, 1H), 6.91 (m, Ph´,1H), 6.68 (m ,H6, Ph´, Ph, 4H), 4.05 (s, m-OMe), 3.35 (s,
m-OMe). Yield 62%. MP 358 °C (d). IR (KBr, cm-1) M-CO 2055.5, 1986. Anal.
Calcd. (%) for C32H24Cl2N4O4Ru: C, 54.86; H, 3.45; N, 8.00. Found (%): C, 54.06;
H, 3.53; N, 8.10.
Cis-[RuCl2(CO)2(2-(2’-methoxiphenyl)-1,8-naphthyridine-κN8)2] (Ru-7).
1H-NMR (200 MHz, CDCl3) 10.54 (dd, H7, J = 5.5 Hz, J = 2.0 Hz, 1H), 9.03 (dd,
H7’, J = 5.7 Hz, J = 1,8 Hz,1H), 8.93 (m,H5, Ph, 3H), 8.68 (d, H4’, J = 8.6 Hz, 1H),
8.71 (d, H4, J = 8.8 Hz, 1H), 8.59 (d, H3´, J = 8.6 Hz, 1H), 8.42 (dd, H5´, J = 8.1 Hz,
J = 1.8 Hz, 1H), 8.21 (d, H3, J = 8.8 Hz, 1H), 8.10 ( dd, H6, J = 8.2 Hz, J = 5.5 Hz,
1H), 7.50 (m, Ph, Ph´, 4H), 7.21 (d ,H6’, 1H, J = 8.1 Hz, J = 5.7 1Hz, 1H), 6.58 (m,
Ph´. 2H), 4.14 (s, o-OMe), 3.91 (s, o-OMe). Yield 50%. MP 287 °C (d). IR (KBr,
cm-1) M-CO; 2056.0, 1989.0. Anal. Calcd. (%) for C32H24Cl2N4O4Ru: C, 54.86; H,
3.45; N, 8.00. Found (%): C, 54.04; H, 3.91; N, 7.89.
Catalytic procedure.
In a glass reactor fitted with a condenser, NaOH (0.475 mmol) was added to
propan-2-ol (5 mL) and stirred for 1 hour at 80 °C under nitrogen. Next, the
ruthenium complex (0.0125 mmol), propan-2-ol (4 mL) and a solution (1 mL) of p-
cymene as internal standard(1.92 mmol) were added to the corresponding
substrate (2.56 mmol) dissolved in propan-2-ol completing a total volume of 10 mL.
Identities of reaction components were determined by comparison with commercial
samples by gas chromatography.
Results and discussion.
A series of ruthenium (II) complexes with different substituted naphthyridine
ligands have been prepared and characterized. The ligands L1-L7 were
synthesized from 2-aminonicotinaldehyde and the corresponding substituted
acetophenone (Scheme 2).

8
Scheme 2. Synthesis of 1,8-naphthyridine ligands (1,8 NAPs).
Then, the Ru(II) complexes Ru-1-Ru-7 were readily prepared by reaction of the
carbonyl precursor [RuCl2(CO)2]2 and the naphthyridine derivatives L by the
procedures reported in the literature [56-60].
Scheme 3. Synthesis of ruthenium complexes containing naphthyridine ligands.
All the complexes RuCl2(CO)2(L)2 were isolated in good yield. Two 1,8-
naphthyridine ligands L coordinate to the metal center in a N-monodentate fashion.
Whatever the reaction conditions, we do not observe the formation complexes

9
containing N,N-bidentate L ligands. Examples of N,N-bidentate coordination of
naphthyridines have been reported in the case of the phosphine complex
Ru(L)(PPh3)2Cl2 [57].
The chemical structure of the complexes, Ru-5, and Ru-7 were confirmed by X-
Ray crystallographic studies (Figures 1 and 2). Table 1 presents selected bond
lengths and Table 2 selected bond angles. The two complexes have an octahedral
geometry, in which the two naphthyridine ligands are cis to each other, one is trans
to a chloride and the second one is trans to a carbonyl. The high sterical hindrance
of phenyl substituted naphthyridine ligands does not preclude a cis configuration.
The bond distances and bond angles are similar to those found in related
complexes reported by us [53].

10
Figure 1. Molecular view of the complex cis-[RuCl2(CO)2(2-(4'-methoxyphenyl)-
1,8-naphthyridine-κN8)2], Ru-5 showing the labeling scheme.

11
Figure 2. Molecular view of the complex cis-[RuCl2(CO)2(2-(2'-methoxyphenyl)-
1,8-naphthyridine-κN8)2], (Ru-7) showing the labeling scheme.

12
Catalytic results.
Table 3 summarizes the catalytic activity in the transfer hydrogenation of
acetophenone shown by the ruthenium (II) complexes Ru-1 to Ru-5 in the
presence of NaOH. In all cases, only one product, 1-phenyl ethanol, is obtained
with 100% selectivity. Entry 6 shows that the best activity (66% and 70% of
conversion) after 1 hour of reaction is observed for Ru-4 and Ru-5 respectively.
The lesser is found for Ru-2 (R1=NO2). In the hydrogen transfer reaction, the first
ten minutes of reaction is very important since the reaction of the precatalyst with
propan-2-ol allows the formation of the actives species of the reaction, during this
time the metal hydride is formed. The proposed mechanism of the hydrogen
transfer reaction suggests that the ruthenium hydride is the active species in this
reaction (Figure 3).
The results reported here (table 3) show that the formation of the active species
(the dihydride complex) (see (Figure 3) could depend on the nature of the ligand L.
The presence of the electron-withdrawing group into the ligand (L3) (NO2 and Br)
could be disfavor the dihydride complex formation showing a lower conversion
during the first thirty minutes of reaction. When the ruthenium hydride active
species is formed the conversion for all catalysts become similar (Entry 8), where
all catalysts converge to a maximum conversion between 80 to 95%. With the aim
of optimizing the catalyst activity of Ru-4 that showed the larger activity, we did
comparative studies using two types of base: NaOH and t-BuOK. The role of the
base is essential as it activates the coordinated isopropanoxy leading to the
formation of the hydride species (Figure 3). The results are summarized in Table 4.
During the course of the reaction, the TOF fluctuates, due to the decrease in
substrate concentration during the catalytic reaction, affecting the conversion rate.

13
Table 3. Catalytic activities in the hydrogen transfer reaction of acetophenone with
ruthenium complexes containing naphthyridine ligands.
Conversion (%) Complexes
Run Time(min)
Ru-1
32
Ru-2
23
Ru-3
28
Ru-4
36
Ru-5
39
1
2
3
4
5
6
7
8
5
10
35
23
29
38
41
15
35
29
33
40
45
30
42
31
36
56
53
45
53
35
45
63
67
60
57
35
53
66
70
185
300
78
74
79
84
79
87
85
88
91
95
Reaction conditions: acetophenone (2.56 mmol), catalyst (0.0125 mmol), NaOH (0.475 mmol), p-cymene (1.92 mmol),
propan-2-ol (10 mL), 80 °C, N2. Substrate/catalyst ratio = 205/1. cis-[RuCl2CO)2(2-phenyl-1,8-naphthyridine-κN8)2] (Ru-1),
cis-[RuCl2(CO)2(2-(4'-nitrophenyl)-1,8-naphthyridine-κN8)2] (Ru-2), cis-[RuCl2(CO)2(2-(4'-bromophenyl)-1,8- naphthyridine-
κN8)2] (Ru-3),), cis-[RuCl2(CO)2(2-(4'-methylphenyl)-1,8-naphthyridine-κN8)2] (Ru-4), cis-[RuCl2(CO)2(2-(4'-methoxyphenyl)-
1,8-naphthyridine-κN8)2] (Ru-5).
Using the inorganic base (NaOH) as a co-catalyst and after 1 hour of
reaction, the activity of catalyst Ru-4 is 66% and the turnover frequency (TOF) is
135 h-1, this activity is similar for catalyst Ru-5. This latter value is greater that
than obtained by employing of t-BuOK. Our group have been studied the hydrogen
transfer using different ruthenium complexes containing polypyridine ligands which
showed that the complex containing polypiridine ligands are active catalysts in this
reaction [53, 55]. The catalyst loading was also studied with the goal of optimizing
the maximum substrate concentration at which the catalyst shows good
performance.

14
Table 4. Effect of the base in the transfer hydrogenation of acetophenone using
the complex cis-[RuCl2(CO)2(2-(4'-methylphenyl)-1,8-naphthyridine-κN8)2], (Ru-4)
as precatalyst.
Base NaOH
Conversion
Base t-BuOK
Conversion
Time (min)
TOF (h-1)
TOF(h-1)
(%)
%
5
36
886
467
328
230
172
135
44
1082
542
361
180
137
103
10
15
30
45
60
38
40
56
63
66
44
44
44
50
50
Reaction conditions: acetophenone (2.56 mmol), catalyst (0.0125 mmol), base (0.475 mmol), p-
cymene (1.92 mmol), propan-2-ol (10 mL), 80 oC, N2. Substrate/catalyst ratio = 205/1.
Table 5 shows the conversion and the turnover frequencies obtained using
different substrate/catalyst ratio for 1 hour of reaction. If the substrate/catalyst ratio
is larger, the TOF value increases. Thus, in the case of a ratio of 1000/1, the TOF
value is 390 h-1. We consider that this ratio is optimal, although the conversion,
down to 39%, is only 3% lesser than that obtained when the substrate catalyst ratio
is 700/1. Although the conversion diminishes as the concentration of catalyst
increases, the turnover frequency is higher. By contrast, when the reaction is
performed between 3-5 hours, the conversions were close to 95% whatever the
substrate/catalyst ratio used. The mechanism of hydrogen transfer reaction has
been reported by several authors. Van Leeuwen [61, 62] reported a detailed
mechanism for this reaction. In a first stage, the dichloro precursor is converted
into the metal dihydride complex (b) following the reported mechanism.

15
Table 5. Effect of the substrate/catalyst ratio in the transfer hydrogenation of
acetophenone with the complex cis-[RuCl2(CO)2(2-(4’-methylphenyl)-1,8-
naphthyridine-κN8)2], (Ru-4).
Substrate/catalyst
Conversion
TOF(h-1)
%
66
47
42
39
205/1
500/1
700/1
1000/1
135
235
294
390
Reaction conditions: substrate acetophenone, catalyst (0.0125 mmol), NaOH (0.475 mmol), p-
cymene (1.92 mmol), propan-2-ol (10 mL), 80 oC, N2. Reaction time:1 hour.
Then addition of the ketone gives rises to the formation of the [Ru]-
OC(CH3)(H)(Ph) (c) species. The species (c) undergoes reductive elimination to
form a tetracoordinate metal complex (d) together with a molecule of the
hydrogenated product which leaves the cycle. Then this tetracoordinate
intermediate reacts with propanol-2-ol to generate the metal hydride complex (e).
Finally, species (e) through a ẞ-elimination produces acetone regenerating the
dihydride hexacoordinate complex (b), thus closing the catalytic cycle.

16
L
L
Cl
Cl
Ru
CO
CO
a
Base /2-propanol
L
CH3
Ph
L
H
Ru
CH3
CH3
O
CO
H
O
CO
Beta hydride
elimination
b
H
Ph
CH3
H
CH3
L
L
CH3
L
O
L
O
Ru
H
Ru
CH3
CO
H
CO
H
CH3
CO
OH
CO
c
e
Reductive elimination
Ph
L
L
Ru
CH3
CO
CO
OH
d
L= 1,8-Napthyridine ligands
Figure 3. Proposed mechanism for the hydrogen transfer reaction of
acetophenone.

17
Correlation between Hammet parameters for the substrate substituent and
conversion, is shown in Table 6, when the catalyst Ru-4 was studied in the
hydrogen transfer reaction. When a chloride is incorporated in the para-position of
the phenyl group, the conversion improves by 20% with respect to the
unsubstituted substrate. By contarst, when an electron-donating group, a p-methyl
or p-methoxy is introduced into the substrate, the activity decreases considerably.
Based on the mechanism proposed for this reaction, the presence of an electron-
withdrawing on the substrate favors hydride attack (step (c)  (d), (Figure 3). The
hydrogen transfer to the substrate is favored by the presence of the chloride
substituent on the phenyl ring, as illustrated by Figure 4 which shows good
correlation between Hammet parameters and TOF values. This suggests that the
step (c)  (d), is the determining step in the transfer hydrogenation reaction of
acetophenone by ruthenium(II) complexes incorporating naphthyridine ligands.
Additionally, the study of the activity vs. time (Table 3) confirms that the formation
of a metal hydride (b) depends on the nature of the naphthyridine ligand.
Table 6. Effect of the substrate in hydrogen transfer reaction of acetophenone
using the cis-[RuCl2(2-(4’-methylphenyl)-1,8-naphthyridine-κN8)2(CO)2] complex,
Ru-5.
Substrate
Conversion
Hammett parameter
%
77
57
35
23
p-ClC6H4-C(O)-CH3
C6H4C(O)-CH3
0,23
0,0
p-CH3-C6H4-C(O)-CH3
p-CH3O-C6H4-C(O)-CH3
-0,17
-0,27
Reaction conditions: substrate (2.56 mmol), pre-catalyst (0.0125 mmol), NaOH (4.75 mmol), p-
cymene (1.92 mmol), propanol-2-ol (10 mL), 80 °C, N2. Substrate / catalyst ratio = 205/1

18
500
450
400
350
300
250
200
Cl
H
Me
r2 = 0.984
r = 0.992
OMe
-0.3
-0.2
-0.1
0.0
0.1
0.2
0.3
p
Figure 4. Correlation between Hammett parameter and the turnover frequency for
different substrates in hydrogen transfer reaction of Ru-5.
.
Conclusions
A series of ruthenium(II) complexes of the general molecular formula Ru
(CO)Cl2(L)2 (where L = substituted naphthyridine ligands) were successfully
synthesized and characterized. The characterization of the complexes was
accomplished by standard analytical and spectral methods. Single crystal X-ray
diffraction analysis confirms the coordination of two naphthyridine ligands to the
metal, showing that they are bonded to the metal through a monodentate N-
coordination mode, generating a distorted octahedral structure.
We have demonstrated that all complexes exhibit a moderate catalytic activity in
the transfer hydrogenation of acetophenone in the presence of a base. It is
noteworthy that these complexes exhibit 100% selectivity, the corresponding

19
alcohol being formed and a low load of the base (NaOH) is required in order to
achieve the observed activities.
The catalyst (Ru-5) shown turnover frequency value between 135-390 h-1 ,
depending the substrate/catalyst ratio. In addition, the catalyst is active for various
acetophenone derivatives. The reaction is sensitive to the nature of the substituent
on the phenyl ring. The best activity is obtained when the ring was substituted by
Cl in para position, indicating that the rate-determining step is the reductive
elimination.
Acknowledgments
This work has been supported by ECOS-CONICYT (Action C14E02) and Fondecyt
1160505. J. C. Araya and J. Gajardo gratefully acknowledge CONICYT-Chile for
their doctoral fellowships. S.A.M acknowledges the financial support provided by
DICYT-USACH-Chile. This research has been performed as part of the Chilean-
French “Joint Laboratory for Inorganic Functional Materials” (LIA MIF).

20
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24
Abstract
O
R
Catalysts
N
CO
N
N
Ru
Cl
N
OC
Cl
HO
R
R1= -NO2, -Br,-H , -CH3, -OCH3,

25
Highlights
1. - Ruthenium complexes containing polypyridine ligands are active catalysts
in hydrogen transfer reactions.
2. - The hydrogen transfer reaction is catalyzed by ruthenium 1,8-
naphthyridine derivate complexes.
3. - Ruthenium complexes containing 1,8-naphthyridine ligands show high
conversions in ketones hydrogenation.
4. - Ruthenium complexes containing polypyridine ligands are alternative
catalysts in hydrogenation reactions.
5. - 1,8-Naphthyridine ligands coordinate in a monodentate fashion into the
ruthenium monometallic complexes.
6. - The donor properties of the 1,8-naphthyridine ligand stabilize the
ruthenium complexes favoring the hydrogenation process.