Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes using acylthiourea based Ru(II)(p-cymene) complexes as precatalysts

Article abstract of DOI:10.1016/j.jorganchem.2018.08.006

A new series of Ru(II)(η⁶-p-cymene) complexes (1–5) was synthesized from pyridine based acylthiourea ligands (L₁-L₅) and [Ru(η⁶-p-cymene)Cl₂]₂. All the ligands and complexes were well characterized by UV-Visible, FT-IR, mass and ¹H & ¹³C NMR spectroscopic techniques. The molecular structures of the ligands (L₁, L₂, L₄ and L₅) and complex 1 were confirmed using single crystal X-ray diffraction study. The Ru(II)(η⁶-p-cymene) complexes (1–5) were proved to be efficient precatalysts for the transfer hydrogenation of carbonyl compounds and nitroarenes in the presence of 2-propanol as a hydrogen donor and KOH as a base. The catalytic transfer hydrogenation reactions were chemoselective towards the nitro group in presence of carbonyl group, which is a rare scenario in homogeneous catalysis. The catalyst was compatible with broad range of substrates which include furfural, quinone and many heterocycles. The catalytic reactions exhibited very high conversions (upto 100%) and excellent yields (upto 99%). Turn Over Number (TON) was found upto 990.

Full text of DOI:10.1016/j.jorganchem.2018.08.006

Accepted Manuscript
Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes using
acylthiourea based Ru(II) (p-cymene) complexes as pre-catalysts
Pushpanathan N. Sathishkumar, Neethi Raveendran, Nattamai S.P. Bhuvanesh,
Ramasamy Karvembu
PII:
S0022-328X(18)30491-1
10.1016/j.jorganchem.2018.08.006
JOM 20533
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 19 June 2018
Revised Date: 9 August 2018
Accepted Date: 10 August 2018
Please cite this article as: P.N. Sathishkumar, N. Raveendran, N.S.P. Bhuvanesh, R. Karvembu,
Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes using acylthiourea
based Ru(II) (p-cymene) complexes as pre-catalysts, Journal of Organometallic Chemistry (2018), doi:
10.1016/j.jorganchem.2018.08.006.
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ACCEPTED MANUSCRIPT
Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes
using acylthiourea based Ru(II)(p-cymene) complexes as pre-catalysts
Pushpanathan N Sathishkumar,a Neethi Raveendran,a Nattamai S. P. Bhuvaneshb and
Ramasamy Karvembu*a

ACCEPTED MANUSCRIPT
Chemoselective transfer hydrogenation of nitroarenes, ketones and aldehydes
using acylthiourea based Ru(II)(p-cymene) complexes as precatalysts
Pushpanathan N Sathishkumara, Neethi Raveendrana, Nattamai S. P. Bhuvaneshb, Ramasamy
Karvembua,*
a
Department of Chemistry, National Institute of Technology, Tiruchirappalli-620015, India
b Department of Chemistry, Texas A & M University, College Station, TX 77842, USA
Abstract
A new series of Ru(II)(η6-p-cymene) complexes (1-5) was synthesized from pyridine
based acylthiourea ligands (L1-L5) and [Ru(η6-p-cymene)Cl2]2. All the ligands and complexes
1
were well characterized by UV-Visible, FT-IR, mass and H & 13C NMR spectroscopic
techniques. The molecular structures of the ligands (L1, L2, L4, L5) and complex 1 were confirmed
using single crystal X-ray diffraction study. The Ru(II)(η6-p-cymene) complexes (1-5) were
proved to be efficient precatalysts for the transfer hydrogenation of carbonyl compounds and
nitroarenes in the presence of 2-propanol as a hydrogen donor and KOH as a base. The catalytic
transfer hydrogenation reactions were chemoselective towards the nitro group in presence of
carbonyl group, which is a rare scenario in homogeneous catalysis. The catalyst was compatible
with broad range of substrates which include conversion of furfural, quinone and many
heterocycles. The catalytic reactions exhibited very high conversions (upto 100%) and excellent
yields (upto 99%). Turn Over Number (TON) was found upto 990.
Keywords: Ruthenium; arene; acylthiourea ligands; chemoselective; transfer hydrogenation
* Corresponding author.
E-mail address: kar@nitt.edu (R. Karvembu).

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1. Introduction
Hydrogenation reactions play a vital role in modern organic synthesis. Transition metal
catalyzed transfer hydrogenation (TH) is trending as it is an environment benign pathway. It
doesn’t need pressurized H2 gas or expensive experimental setup. Recently, TH is directed
towards the chemoselectivity and compatibility for a broad range of substrates with low catalyst
loading, mild reaction conditions. Chemoselectivity and compatibility for a wide range of
substrates are very important in pharmaceuticals since many drug molecules possess multi-
functional moieties. The hydrogen source used should be readily available, cheaper and easy to
handle. The hydrogenated products like alcohols, amines, etc have been used for the production
of pharmaceuticals, dyes, fertilizers, fragrances, flavors, fuels, precursors for many fine
chemicals etc [1,2].
Many phosphine based organoruthenium catalysts were reported for TH reactions. Since
phosphine based ligands are expensive and less stable in air, an alternative ligand system is
needed. The mechanism of catalytic TH reactions is influenced by both ligand and metal center.
Noyori and coworkers discovered that the ligand containing N−H moiety enhances the activity of
catalyst through bifunctional mechanism [3-5]. Acylthiourea ligands which are “phosphine free”,
contain N−H moiety, so the complexes of acylthiourea ligands are expected to follow
bifunctional mechanistic pathway for the catalytic TH reactions. There is a possibility for
introducing various substituents in acylthiourea derivatives, which can help in tuning the
catalytic behaviour of their complexes [6]. Due to these significances, acylthiourea derivatives
were used widely in both organocatalysis [7,8] and metal-based catalysis [9,10]. Ru(II)-arene
based catalysts are well known for the transfer hydrogenation reactions [11]. Acylthiourea based
Ru(II)-arene complexes have a wide range of applications in the field of bioinorganic chemistry
[12,13] and catalysis. Sheeba et. al. reported the chiral acylthiourea based Ru(II)(p-cymene)
complexes as pre-catalysts for asymmetric TH (ATH) of ketones with excellent conversions and
enantiomeric excesses [14]. But the chemoselectivity of the reactions was not studied.
In general, nitro reduction was done by direct hydrogenation, catalytic TH, hydride
transfer reductions, metal dissolving reductions or metal free reduction methodologies [15,16].

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Mostly, the chemoselective TH of nitroarenes readily proceeded by catalytic TH through the
heterogeneous pathway [17-23]. Many homogeneous TH reports are available for the
chemoselective reduction of aldehydes, ketones, alkenes etc. But only a very few reports are
available on the chemoselective TH of nitroarenes in homogeneous pathway [24-31]. As an
interesting case, Jia et. al. reported the homogeneous reduction of nitroarenes using a series of
Ru(II)(p-cymene) complexes containing Schiff base ligands as pre-catalysts and sodium
tetrahydroborate as reducing agent in water. This system was not chemoselective since it reduced
both ketone/aldehyde and nitro groups [32]. Recently, the same group reported half-sandwich
Ru(II) phenolate−oxazoline complexes as catalysts for TH of nitroarenes. The catalysts have no
chemoselectivity in the case of 4-nitrobenzaldehyde since it reduced both aldehyde and nitro
groups [33]. Rohini et. al. reported the Ru(II)(benzene) complexes of dibenzosuberenyl
appended acylthiourea as pre-catalysts for TH reactions in which nitro was chemoselectively
reduced to amine. But the scope of the reaction was very limited as only one nitroarene was
tested [34]. Herein we report the chemoselective TH of nitroarenes into amines and also TH of
carbonyl compounds into their corresponding alcohols catalyzed by homogenous Ru(II)(η6-p-
cymene) pre-catalysts containing acylthiourea ligands under aerobic condition using 2-propanol
as a hydrogen source and KOH as a base. We have extended the scope to broad range of
substrates with excellent compatibility. Our catalytic system exhibited higher TON number than
previously reported acylthiourea based Ru(II)-arene catalysts for TH/ATH reactions [14, 34-37].
Moreover, the ligands and catalysts were prepared from readily available precursors under mild
conditions.
2. Experimental section
2.1 Materials and methods
All the chemicals were obtained from commercial sources and used as received. The
solvents were purified and dried by the standard procedures. [RuCl2(η
6-p-cymene)]2 was
synthesized by following a literature procedure [38]. Melting points were recorded with Sigma
melting point apparatus. FT-IR spectra were recorded as KBr pellets with a Thermo Scientific
Nicolet iS5 FT-IR spectrometer in the range of 4000-550 cm-1. UV-Vis spectra were recorded in
a Shimadzu UV-2600 instrument. 1H and 13C NMR spectra were recorded on a Bruker 500 MHz
and 126 MHz spectrometer respectively. CDCl3 / DMSO-d6 were used as solvents and

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tetramethylsilane (TMS) was used as an internal standard. HRMS was recorded on Thermo
Exactive Orbitrap instrument. GC and GCMS analyses were performed using Shimadzu GC
2010 and Shimadzu GCMS-QP2010 Ultra respectively.
2.2 Synthesis of the ligands (L)
A solution of acyl chloride (5 mmol) in ethyl acetate (10 mL) was added to a solution of
potassium thiocyanate (5 mmol) in ethyl acetate (10 mL). The mixture was refluxed for about 1
h. Then, the reaction mixture was cooled to room temperature and a solution of 2-
(aminomethyl)pyridine (5 mmol) in ethyl acetate (10 mL) was added drop wise and then the
reaction was continued for another 3 h at room temperature. The resulting solution was filtered.
The filtrate was washed with water, dried in sodium sulphate and kept for crystallization.
[N-((pyridin-2-ylmethyl)carbamothioyl)thiophene-2-carboxamide] (L1)
Yield: 73 %. Mp.: 169 °C. 1H NMR (500 MHz, DMSO-d6): δ, ppm 11.54 (s, 2H), 8.58 (d, J = 4.5
Hz, 1H), 8.41–8.32 (m, 1H), 8.07–7.98 (m, 1H), 7.81 (td, J = 7.7, 1.7 Hz, 1H), 7.43 (d, J = 7.8
Hz, 1H), 7.33 (dd, J = 7.1, 5.2 Hz, 1H), 7.24 (dd, J = 4.7, 4.1 Hz, 1H), 4.94 (d, J = 4.8 Hz, 2H).
13C NMR (126 MHz, CDCl3): δ, ppm 179.28, 160.81, 154.59, 149.48, 136.81, 136.31, 133.91,
130.56, 128.39, 122.65, 121.83, 50.88. FT-IR (KBr, cm−1): 3143 (m; ν(amide N−H)), 3104 (m;
ν(thiourea N−H)), 1657 (s; ν(C=O)), 1280 (s; ν(C=S)). UV-vis (Methanol): λ (nm) 202, 231,
262, 288. ESI-MS (m/z): Found 278.04200 [M + 1]+ (Calcd. 278.04218).
[N-((pyridin-2-ylmethyl)carbamothioyl)furan-2-carboxamide] (L2)
1
Yield: 80 %. Mp.: 175°C. H NMR (500 MHz, DMSO-d6): δ, ppm 11.44 (t, J = 4.6 Hz, 1H),
11.18 (s, 1H), 8.57 (d, J = 4.4 Hz, 1H), 8.05 (d, J = 1.0 Hz, 1H), 7.84–7.79 (m, 2H), 7.42 (d, J =
7.8 Hz, 1H), 7.33 (dd, J = 7.0, 5.2 Hz, 1H), 6.75 (dd, J = 3.6, 1.7 Hz, 1H), 4.94 (d, J = 4.9 Hz,
2H). 13C NMR (126 MHz, CDCl3): δ, ppm 179.19, 156.50, 154.61, 149.43, 146.15, 145.24,
136.80, 122.63, 121.83, 118.57, 113.28, 50.80. FT-IR (KBr, cm−1): 3306 (m; ν(amide N−H)),
3222 (m; ν(thiourea N−H)), 1670 (s; ν(C=O)), 1271 (s; ν(C=S)). UV-vis (Methanol): λ (nm)
203, 223, 270. ESI-MS (m/z): Found 262.06434 [M+1]+ (Calcd. 262.06502).

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[N-((pyridin-2-ylmethyl)carbamothioyl)benzamide] (L3) [39,40]
Yield: 79 %. Mp.: 147°C. 1H NMR (500 MHz, CDCl3): δ, ppm 11.67 (s, 1H), 9.14 (s, 1H), 8.66
(d, J = 4.5 Hz, 1H), 7.94–7.85 (m, 2H), 7.70 (td, J = 7.7, 1.7 Hz, 1H), 7.63 (t, J = 7.4 Hz, 1H),
7.52 (t, J = 7.8 Hz, 2H), 7.34 (d, J = 7.8 Hz, 1H), 7.29–7.21 (m, 1H), 5.03 (d, J = 4.6 Hz, 2H).
13C NMR (126 MHz, CDCl3): δ, ppm 179.63, 166.62, 154.66, 149.50, 136.83, 133.50, 131.92,
129.13, 127.53, 122.66, 121.88, 50.86. FT-IR (KBr, cm−1): 3187 (b; ν(amide N−H)) and
ν(thiourea N−H)), 1667 (s; ν(C=O)), 1247 (s; ν(C=S)). UV-vis (Methanol): λ (nm) 202, 225,
270. ESI-MS (m/z): Found 272.08561 [M+1]+ (Calcd. 272.08576).
[2, 4-dichloro-N-((pyridin-2-ylmethyl)carbamothioyl)benzamide] (L4)
1
Yield: 81 %. Mp.: 182°C. H NMR (500 MHz, DMSO-d6): δ, ppm 11.90 (s, 1H), 11.37 (t, J =
4.6 Hz, 1H), 8.58 (d, J = 4.4 Hz, 1H), 7.83 (td, J = 7.7, 1.6 Hz, 1H), 7.76 (d, J = 1.9 Hz, 1H),
7.65 (d, J = 8.3 Hz, 1H), 7.54 (dd, J = 8.3, 1.9 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.34 (dd, J =
7.0, 5.3 Hz, 1H), 4.94 (d, J = 4.8 Hz, 2H). 13C NMR (126 MHz, CDCl3): δ, ppm 178.83, 164.64,
154.38, 149.46, 138.91, 136.86, 132.04, 131.68, 130.77, 130.71, 127.98, 122.72, 121.92, 50.82.
FT-IR (KBr, cm−1): 3230 (b; ν(amide N−H)), 3149 ν(thiourea N−H)), 1684 (s; ν(C=O)), 1278 (s;
ν(C=S)). UV-vis (Methanol): λ (nm) 204, 229, 262, 281. ESI-MS (m/z): Found 340.00709
[M+1]+ (Calcd. 340.00781).
[N-((pyridin-2-ylmethyl)carbamothioyl)cyclohexanecarboxamide ] (L5)
Yield: 69 %. Mp.: 186°C. 1H NMR (500 MHz, CDCl3): δ, ppm 11.49 (s, 1H), 8.84 (s, 1H), 8.65–
8.59 (m, 1H), 7.68 (td, J = 7.7, 1.7 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.22 (dd, J = 7.0, 5.4 Hz,
1H), 4.96 (d, J = 4.6 Hz, 2H), 2.23 (tt, J = 11.7, 3.5 Hz, 1H), 1.92 (dd, J = 13.7, 1.6 Hz, 2H),
1.86–1.80 (m, 2H), 1.72–1.67 (m, 1H), 1.49 (qd, J = 12.4, 2.9 Hz, 2H), 1.35–1.27 (m, 2H), 1.24–
1.17 (m, 1H). 13C NMR (126 MHz, CDCl3): δ, ppm 179.77, 176.59, 154.67, 149.48, 136.78,
122.60, 121.84, 77.30, 77.04, 76.79, 50.72, 45.94, 29.00, 25.44, 25.32. FT-IR (KBr, cm−1): 3212
(b; ν(amide N−H)), 3181 ν(thiourea N−H)), 1689 (s; ν(C=O)), 1190 (s; ν(C=S)). UV-vis
(Methanol): λ (nm) 204, 221, 268. ESI-MS (m/z): Found 278.13254 [M+1]+ (Calcd. 278.13271).

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2.3 Synthesis of the complexes
A mixture of [RuCl2(η6-p-cymene)]2 (0.15 mmol) and L (0.3 mmol) was stirred in toluene
(20 mL) at room temperature for about 4-5 h. Hexane was added to precipitate the product which
was filtered, washed and dried in vacuum. The solid product was then crystallized in
dichloromethane.
[RuCl2(η6-p-cymene)L1] (1)
1
Yield: 83 %. Mp.: 220°C. H NMR (500 MHz, CDCl3): δ, ppm 11.94 (s, 1H), 11.00 (s, 1H),
8.65 (d, J = 4.6 Hz, 1H), 8.50–8.46 (m, 1H), 7.72 (td, J = 7.7, 1.6 Hz, 1H), 7.60 (dd, J = 4.9, 0.6
Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.26 (dd, J = 9.6, 4.5 Hz, 1H), 7.12 (dd, J = 4.7, 4.2 Hz, 1H),
5.48 (d, J = 5.9 Hz, 2H), 5.31 (d, J = 5.9 Hz, 2H), 5.01 (d, J = 4.6 Hz, 2H), 3.09–2.98 (m, 1H),
2.30 (s, 3H), 1.34 (d, J = 6.9 Hz, 6H). 13C NMR (126 MHz, CDCl3): δ, ppm 178.46, 162.81,
153.45, 149.47, 137.09, 136.30, 135.18, 134.19, 128.86, 122.90, 121.56, 103.44, 100.03, 84.30,
82.72, 77.31, 77.06, 76.80, 50.13, 30.48, 22.26, 18.39. FT-IR (KBr, cm−1): 3228 (m; ν(amide
N−H)), 3219 (m; ν(thiourea N−H)), 1688 (s; ν(C=O)), 1271 (s; ν(C=S)). UV-vis (Methanol): λ
(nm) 203, 260, 289, 445. ESI-MS (m/z): Found 512.04094 [M-2H-2Cl+H]+ (Calcd. 512.04043).
[RuCl2(η6-p-cymene)L2] (2)
1
Yield: 89 %. Mp.: 210°C. H NMR (500 MHz, CDCl3): δ, ppm 11.91 (s, 1H), 10.90 (s, 1H),
8.63 (d, J = 4.5 Hz, 1H), 7.93 (d, J = 3.6 Hz, 1H), 7.72 (td, J = 7.7, 1.1 Hz, 1H), 7.62 (s, 1H),
7.31 (d, J = 7.8 Hz, 1H), 7.28–7.25 (m, 2H), 6.51 (dd, J = 3.4, 1.3 Hz, 1H), 5.48 (d, J = 5.8 Hz,
2H), 5.30 (d, J = 5.8 Hz, 2H), 5.01 (d, J = 4.5 Hz, 2H), 3.08–2.98 (m, 1H), 2.30 (s, 3H), 1.34 (d,
13
J = 6.9 Hz, 6H). C NMR (126 MHz, CDCl3): δ, ppm 178.70, 158.35, 153.31, 149.18, 147.67,
144.81, 137.31, 122.98, 121.61, 121.22, 112.63, 103.49, 100.03, 84.27, 82.65, 49.93, 30.49,
22.26, 18.39. FT-IR (KBr, cm−1): 3148 (m; ν(amide N−H)), 3128 (m; ν(thiourea N−H)), 1684 (s;
ν(C=O)), 1253 (s; ν(C=S)). UV-vis (Methanol): λ (nm) 206, 270, 451. ESI-MS (m/z): Found
496.06242 [M-2H-2Cl+H]+ (Calcd. 496.06327).
[RuCl2(η
6-p-cymene)L3] (3)
Yield: 93 %. Mp.: 178°C. 1H NMR (500 MHz, CDCl3): δ, ppm 12.23 (s, 1H), 11.23 (s, 1H), 8.67
(d, J = 4.4 Hz, 1H), 8.27 (d, J = 7.6 Hz, 2H), 7.78–7.73 (m, 1H), 7.53 (t, J = 7.3 Hz, 1H), 7.46 (t,
J = 7.7 Hz, 2H), 7.35 (d, J = 7.8 Hz, 1H), 7.32–7.27 (m, 1H), 5.47 (d, J = 5.9 Hz, 2H), 5.30 (d, J

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= 5.9 Hz, 2H), 5.05 (d, J = 4.5 Hz, 2H), 3.08–2.98 (m, 1H), 2.28 (s, 3H), 1.33 (d, J = 6.9 Hz,
6H). 13C NMR (126 MHz, CDCl3): δ, ppm 179.19, 168.87, 153.48, 149.27, 137.34, 133.41,
131.24, 129.72, 128.48, 122.98, 121.73, 103.39, 99.99, 84.30, 82.76, 77.32, 77.06, 76.81, 50.04,
30.48, 22.26, 18.38. FT-IR (KBr, cm−1): 3250 (m; ν(amide N−H)), 3231 (m; ν(thiourea N−H)),
1681 (s; ν(C=O)), 1192 (s; ν(C=S)). UV-vis (Methanol): λ (nm) 202, 243,444. ESI-MS (m/z):
Found 506.08401 [M-2H-2Cl+H]+ (Calcd. 506.08401).
[RuCl2(η6-p-cymene)L4] (4)
Yield: 84%. Mp.: 185°C. 1H NMR (500 MHz, CDCl3): δ, ppm 11.85 (s, 1H), 11.47 (s, 1H), 8.65
(d, J = 4.5 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.40 (d, J = 1.2 Hz, 1H),
7.34 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 6.4 Hz, 1H), 5.43 (d, J = 5.8 Hz, 2H), 5.26 (d, J = 5.8 Hz,
13
2H), 5.03 (d, J = 4.4 Hz, 2H), 2.99 (m, 1H), 2.25 (s, 3H), 1.32 (d, J = 6.9 Hz, 6H). C NMR
(126 MHz, CDCl3): δ, ppm 179.42, 166.80, 153.08, 149.32, 138.33, 137.34, 133.64, 132.31,
130.52, 130.00, 127.28, 123.07, 121.70, 103.45, 99.87, 84.05, 82.74, 50.06, 30.48, 22.22, 18.38.
FT-IR (KBr, cm−1): 3141 (m; ν(amide N−H)), 3049 (m; ν(thiourea N−H)), 1686 (s; ν(C=O)),
1246 (s; ν(C=S)). UV-vis (Methanol): λ (nm) 203, 260, 290, 448. ESI-MS (m/z): Found
574.00343 [M-2H-2Cl+H]+ (Calcd. 574.00606).
[RuCl2(η6-p-cymene)L5] (5)
Yield: 81 %. Mp.: 190°C. 1H NMR (500 MHz, CDCl3): δ, ppm 11.70 (s, 1H), 10.80 (s, 1H), 8.62
(d, J = 4.4 Hz, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.24 (d, J = 7.1 Hz, 1H),
5.44 (d, J = 5.8 Hz, 2H), 5.28 (d, J = 5.8 Hz, 2H), 4.93 (d, J = 4.5 Hz, 2H), 3.02 (dt, J = 13.8, 6.9
Hz, 1H), 2.39 (dt, J = 11.5, 3.3 Hz, 1H), 2.29 (s, 3H), 1.99–1.94 (m, 2H), 1.72 (dd, J = 9.9, 2.8
Hz, 4H), 1.62 (d, J = 12.8 Hz, 2H), 1.33 (d, J = 6.9 Hz, 6H), 1.28–1.23 (m, 2H). 13C NMR (126
MHz, CDCl3): δ, ppm 178.81, 178.62, 153.49, 149.49, 137.05, 122.87, 121.58, 103.25, 99.90,
84.06, 82.67, 49.91, 45.59, 30.47, 28.22, 25.59, 25.11, 22.26, 18.46. FT-IR (KBr, cm−1): 3197
(m; ν(amide N−H)), 3134 (m; ν(thiourea N−H)), 1700 (s; ν(C=O)), 1191 (s; ν(C=S)). UV-vis
(Methanol): λ (nm) 204, 258, 437. ESI-MS (m/z): Found 512.13098 [M-2H-2Cl+H]+ (Calcd.
512.13096).

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2.4 Transfer hydrogenation of carbonyl/nitro compounds
Catalyst (0.1 mol %) and KOH (1 mmol) were dissolved in 2-propanol (4 mL). To this
solution, substrate (1 mmol) was added and the mixture was refluxed (82 °C). The progress of
the reaction was monitored by GC at regular intervals. After the completion of the reaction, the
reaction mixture was cooled to room temperature and filtered through silica gel or alumina bed,
and eluted using 50% ethyl acetate-hexane mixture. The eluted solution was reduced and
analyzed by GC and/or GCMS.
3. Results and discussion
The acylthiourea ligands were synthesized from acyl chloride, potassium thiocyanate and
2-(aminomethyl)pyridine in ethyl acetate. The reaction between [RuCl2(η6-p-cymene)]2 and
ligand (L) in toluene led to the formation of complexes of the type [RuCl2(η6-p-cymene)L]
(Scheme 1).
H2N
O
S
O
N
KSCN
O
S
X
N
N
C
Cl
X
Ethyl acetate
55-60 oC, 1 h
Ethyl acetate
27-30 oC, 3 h
X
X
N
H
H
N
L1-L5
O
S
Toluene
N
H
N
Cl
Ru
Cl
Ru
H
Cl
O
N
27-30 oC
4-5 h
Ru
Cl
S
Cl
L1-L5
Cl
X
N
N
H
H
N
1-5
X
Ligand
L1
1
L2
2
L3
3
L4
4
L5
Complex
5

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Scheme 1 Synthesis of the ligands (L1-L5) and their Ru(II)(p-cymene) complexes (1-5)
3.1 Characterization
FT-IR spectra of the free ligands showed N−H, C=O and C=S stretching frequencies
around 3104-3306, 1657-1689 and 1190-1280 cm-1 respectively. On complexation, C=S
stretching frequency was decreased, which indicated the formation of the complexes through
coordination of S in the acylthiourea ligands. Electronic spectra of the ligands and their
complexes showed strong absorption bands in the range 202-231 and 243-290 nm which were
attributed to π→π and n→π transitions respectively. A less intense band at 437-451 nm in the
spectra of the complexes indicated d→d transition.
1
In the H NMR spectra of the ligands and their complexes, the amidic and thioamidic N−H
protons were observed as singlet around 11.44-12.23 and 8.84-11.54 ppm respectively. The
signals due to N−H were slightly deshielded in the spectra of the complexes. The aromatic
protons of the ligands and their complexes were observed in the range 6.51-8.67 ppm. A doublet
due to methylene protons was detected at 4.93-5.05 ppm. The new signals observed around 5.26-
5.48 (d), 2.98-3.09 (m), 2.25-2.30 (s) and 1.32-1.34 (d) ppm in the spectra of the complexes
indicated the presence of p-cymene. In the 13C NMR spectra of the ligands and their complexes,
signals were found around 178.5-179.8 and 156.5-178.6 ppm, which corresponded to the
thiocarbonyl and carbonyl carbons respectively. The signal due to shielded methylene carbon
appeared around 49.9-50.9 ppm. In the spectra of the complexes, new signals were observed in
the range 82.6-103.5 and 18.3-30.5 ppm, which corresponded to the carbons of p-cymene. The
cyclohexyl carbons of L5 and 5 were observed around 22.2-45.6 ppm. The calculated [M+H]+
mass of the ligands were exactly matching with the found mass. But in the case of the
complexes, the two chloride ligands were labile; hence, the found mass of the complexes were
matching with the calculated [M-2H-2Cl+H]+ mass.12 From the spectroscopic data, the formation
of the ligands and their Ru(II)(p-cymene) complexes was confirmed.

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3.2 Molecular structures
The molecular structure of ligands L1, L2, L4 and L5, and complex 1 was confirmed by
single crystal X-ray crystallography. The ligands (L1, L2, L4 and L5) and complex 1 were
crystallized by slow evaporation technique. L1 crystallized in orthorhombic crystal system
with space group P212121 and seems to be a chiral molecule (Fig 1). It was a twinned
inversion crystal and its flack parameter was 0.4(11), close to 0.5. Hence, it was achiral
which was further confirmed by polarimeter as no significant optical rotation value was
observed. The ligands L2, L4 and L5 crystallized in triclinic crystal system with P-1 space
group.
Fig. 1 Molecular structure of L1 [Important bond lengths (Å) and angles (°): S(2)−C(6) 1.676(3),
N(1)−C(6) 1.395(4), N(1)−H(1) 0.88, N(1)−C(5) 1.374(4), O(1)−C(5) 1.228(4), N(2)−C(6)
1.326(4), N(1)−H(2) 0.88, O(1) H(2) 1.91, N(3) H(1) 2.11, 1.98N(2)−C(6)−S(2) 125.3(2),
N(1)−C(6)−S(2) 118.8(2), N(2)−C(6)−N(1) 115.9(3)].
Complex 1 crystallized in orthorhombic crystal system with Pbca space group. The inter-
and intra-molecular hydrogen bonding interactions in the ligands and complex 1 were revealed.
The intramolecular hydrogen bonding between H O was strong since its bond length was less
than 2 Å. The other hydrogen bonding interactions were weak since their bond lengths were

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more than 2 Å. The centroid distance between p-cymene ring and Ru(II) was 1.664 Å. The
monodentate neutral coordination mode of the ligand through S atom was confirmed from the
crystal structure of 1. Due to the coordination of S to Ru, the C=S bond length was increased
from 1.676 to 1.708 Å. From the bond angles around Ru(II), the pseudo-octahedral geometry of
1 was confirmed (Fig 2).
Fig. 2 Molecular structure of 1 [Important bond lengths (Å) and angles (°): Ru(1)−S(1)
2.4147(6), Ru(1)−Cl(1) 2.4278(6), Ru(1)−Cl(2) 2.4290(6), Ru(1)−C(13) 2.188(2), S(1)−C(1)
1.708(2), N(1)−C(1) 1.369(3), N(1)−H(1) 0.88, N(1)−C(2) 1.387(3), N(2)−H(2) 0.88, N(2)−C(1)
1.326(3), O(1)−C(2) 1.221(3), O(1) H(2) 1.97,
Cl(2) H(1) 2.44, Cl(1) H(1) 2.62,
Cl(1)−Ru(1)−Cl(2) 87.66(2), S(1)−Ru(1)−Cl(1) 92.18(2), S(1)−Ru(1)−Cl(2) 90.68(2),
C(13)−Ru(1)−Cl(1) 87.42(6), N(2)−C(1)−S(1) 120.28(18), N(1)−C(1)−S(1) 120.88(17),
N(1)−C(1)−N(2) 118.8(2)].
3.3 Catalytic activity
The newly synthesized complexes were observed to be excellent precatalysts for the TH
of carbonyl and nitro compounds using 2-propanol as a hydrogen source and KOH as a base. The
reaction conditions were optimized using acetophenone as a model substrate (Table S3-S7).
There was no significant conversion in the absence of a base. In the absence of the catalyst, the

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maximum conversion obtained was 34%. The effect of temperature was optimized and there was
no significant conversion below 80 °C. The optimized molar ratio of the substrate : base :
catalyst was 1:1:0.001. Though all the complexes showed good catalytic activity towards TH of
acetophenone (99%), complex 1 was chosen for scope extension. The scope of the present
system was extended to various substituted ketones, aldehydes and nitroarenes. All the substrates
were reduced in good to excellent yields which were analyzed by GCMS. Some of the products
were isolated and further confirmed by 1H NMR study.
Analogous Ru(II) catalyst containing chiral acylthiourea ligand took 24 h for the
conversion of acetophenone to 1-phenylethanol, but catalyst 1 containing pyridine based
acylthiourea took only 14 h for the same conversion.14 The electronic effect of the substituents
present in the substrates played a predominant role. The substrates with electron withdrawing
group were more reactive than those with electron donating group due to the increase of electron
deficiency in the nitro/carbonyl group (Table 1 and 2). Thus, benzophenone took only 12 h for
the complete conversion (Table 1, entry 2) whereas acetophenone took 14 h (Table 1, entry 1).
Similarly, the substrates with electron releasing group required more than 14 h and even then, the
conversion was incomplete (Table 1, entries 9-12; Table 2, entry 2). The alicyclic substrates
were readily reduced with excellent TON and TOF values (Table 1, entries 13-14, 20-21, 34).
Notably, the reduction of quinone was explored due to its biological and industrial significance.
Only few reports were available for the metal based reduction of quinones [41]. Interestingly,
entry 21 showed that the quinone was readily reduced to hydroquinone with high TON (990) and
TOF (110). The bromo and fluoro substituted substrates showed moderate yield of corresponding
alcohol due to the formation of hydrodehalogenated alcohol as side product (Table 1, entries 5, 6,
8, 27, 28). This was due to the labile nature of Br− and F−. But this was not the case with respect
to chloro substituted substrates. The substrates with para substituent gave the corresponding
alcohol readily than those with the ortho substituent due to the steric effect (Table 1, entries 3-4,
9-10, 24-26). In the case of entries 27 and 28, the conversion was 100 %, but the ortho
substituted aldehyde yielded higher amount of product compared to the para substituted
analogue. This was due to the easy formation of hydrodehalogenated alcohol as side product in
the case of para substituted aldehyde. The TH of heterocyclic compounds is always a
challenging one since there is a possibility of coordination of hetero atom to metal and poison the
catalyst. It was observed in the present case that the catalyst readily reduced the heterocyclic

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carbonyl compounds to their corresponding alcohols with excellent yields of up to 99% (Table 1,
entries 15-20, 31-33). These heterocyclic alcohols have a wide range of applications in synthetic
chemistry and pharmaceuticals. Interestingly, furfural was reduced to furfuryl alcohol which was
a platform chemical in the biomass conversion. The conversion of furfural to furfuryl
alcohol/furfuryl acetate/levulinic acid/γ-valerolactone has a significant value in biofuel research
[42,43]. The TH of alkene was not successful, which led to the chemoselective reduction of
unsaturated carbonyl compounds and nitroarenes. For instance, 3-cyclohexene-1-carboxaldehyde
was selectively reduced to 3-cyclohexene-1-methanol with significant TON (890) (Table 1, entry
34).
Interestingly, we have observed the chemoselective reduction of the nitro group in 3-
nitroacetophenone with 99% yield. So, we have extended the scope to more nitroarenes and
found that the nitroarenes with electron withdrawing substituent were readily reduced to their
corresponding amines (Table 2, entries 5-10). But in the case of nitroarenes with electron
donating substituent, the reaction was incomplete (Table 2, entry 2). The conversion was 100%
during the reduction of nitrobenzene but the yield of aniline was only 46% (Table 2, entry 1).
The lower yield was due to the formation of intermediate azobenzene. This clearly confirmed
that the reduction of nitroarenes proceeded via azoxybenzene and azobenzene intermediates
[44,45]. The importance of present catalytic system lies in chemoselectivity and wide substrate
scope. Nitro group was selectively reduced to amine without the ketone/aldehyde was being
reduced (Table 2, entries 8-10) with high TON. The chemoselective nitro reduction is of
tremendous importance in organic synthesis particularly when multiple reducible functional
groups are present. Thus, multistep reactions can be reduced to one step. In general, nitro
reduction was done by classical Pd/C or other heterogeneous catalysts which require harsh
experimental conditions [46-49]. The present catalytic system can replace the conventional
catalysts.

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Table 1 Transfer hydrogenation of carbonyl compounds
Time
(h)
Yieldb
(%)
Entry
Substrate
Product
TONc
TOFd
1
14
12
99
98
990
70.7
2
3
980
950
81.7
67.9
14
14
14
14
14
95
87
60
68
93
4
5
6
7
870
600
680
930
62.14
42.9
48.6
66.4

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8
14
55
550
39.3
9
18
18
14
94
65
55
940
650
550
52.2
36.1
39.3
10e
11e
12e
18
70
700
38.9
13
14
12
12
98
99
980
990
81.6
82.5
15e
16
16
14
86
97
860
970
53.8
69.3
17
18
19
14
14
14
96
96
98
960
960
980
68.6
68.6
70.0

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20e
21
12
9
89
99
890
990
74.2
110.0
22f
23
24
14
12
12
99
95
99
990
956
990
70.7
79.2
82.5
25
12
99
990
82.5
26
27
28
29
30
12
12
12
14
14
88
79
87
91
97
880
790
870
910
970
73.3
65.8
72.5
65.0
69.3

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31
32
33
34
14
14
12
14
85
80
99
89
850
800
990
890
60.7
57.1
82.5
63.6
b Yield (%) was analyzed by GCMS
c Turn over number (TON) = No. of moles of product / No. of moles of catalyst
d Turn over frequency (TOF) = TON / Time in hours
e Conversion was not 100%
f Mercury drop test

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Table 2 Transfer hydrogenation of nitroarenes
Time Yield
Product
Entry
Substrate
TON TOF
(h)
(%)
1
16
46
460
700
720
960
28.9
29.2
45.0
68.6
2e
3
24
16
14
70
72
96
4
5
6
14
14
99
99
990
990
70.7
70.7
7
8
14
12
99
99
990
990
70.7
82.5

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9
12
12
99
99
990
990
82.5
82.5
10
b Yield (%) was analyzed by GCMS
The reaction mechanism was similar to Noyori’s outer sphere mechanism. The labile Cl−
was easily replaced by 2-propanol in the presence of KOH and led to the formation of active
RuH species through intramolecular hydrogen transfer. Six-membered transition state was
formed with the substrate through the bifunctional mechanism and desired product was
eliminated. The common side product observed was corresponding acetates which was formed
by the esterification of alcohol product with acetic acid formed from 2-propanol. The true
catalyst (Ru−H species) was isolated and characterized by FT-IR spectrum in which peak at 2189
cm-1 corresponding to Ru−H stretching was observed. The homogeneity of the reaction was
tested using mercury drop test which showed no formation of Ru amalgam as the conversion of
acetophenone to 1-phenylethanol was 100% in presence of mercury under identical reaction
conditions (Table 1, entry 22). This confirmed the absence of Ru particles in the reaction mixture
and homogeneous pathway [50].
4. Conclusion
Ru(II)(η
6-p-cymene) complexes (1-5) containing pyridyl based acylthiourea ligands (L1-
L5) was synthesized and characterized. The molecular structure of ligands L1, L2, L4 and L5, and
complex 1 was confirmed by single crystal XRD study. All the complexes were found to be good
pre-catalysts for the TH of ketones, aldehydes and nitroarenes. But alkene was unreactive with
these catalysts and paved the way for the selective TH of unsaturated carbonyl compounds and
nitroarenes. Remarkably, the nitro group was selectively reduced in the presence of carbonyl
with these catalysts, which is unusual in homogeneous catalysis. The catalyst was compatible
towards wide range of substrates including heterocycles.

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Highlights
V Ru(II)(η6-p-cymene) complexes containing 2-(aminomethyl)pyridine based acylthiourea
ligands were synthesized and characterized
V The molecular structure of ligands and one of the complexes was confirmed by single
crystal XRD study
V All the complexes were found to be good pre-catalysts for the TH of ketones, aldehydes
and nitroarenes
V Alkene was unreactive with these catalysts and paved the way for the selective TH of
unsaturated carbonyl compounds and nitroarenes
V The catalysts were compatible with broad range of substrates which include furfural,
quinone and heterocycles