Preparation of the Ru3(CO)8-pyridine-alcohol cluster and its use for the selective catalytic transformation of primary to secondary amines

Article abstract of DOI:10.1039/c8dt02972e

The synthesis of pyridine alcohol based ruthenium carbonyl clusters Ru₃(hep)₂(CO)₈ (1), Ru₃(hpp)₂(CO)₈ (2), and Ru₃(bhmp-H)₂(CO)₈ (3) {hep-H = 2-(2-hydroxyethyl)pyridine, hpp-H = 2-(3-hydroxypropyl)pyridine and bhmp-H₂ = 2,6-bis(hydroxymethyl)pyridine} has been carried out by the reaction of the corresponding pyridine-alcohol ligands with Ru₃(CO)₁₂. Clusters 1-3 have been characterized using elemental analysis, NMR, FT-IR, mass spectrometry and single-crystal X-ray structures. The clusters were explored for the selective catalytic transformation of primary amines into secondary amines using alcohols as the mono-alkylating agents via hydrogen transfer reactions. All three display efficient catalytic activity with 1 being the most effective.

Full text of DOI:10.1039/c8dt02972e

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Preparation of Ru3(CO)8ꢀpyridineꢀalcohol cluster and its use for
selective catalytic transformation of primary to secondary amines†
Ajeet Singh,a Shaikh M. Mobin*,a,b,c and Pradeep Mathur*,a
aDiscipline of Chemistry, bDiscipline for Biosciences and BioꢀMedical Engineering, and c Discipline
of Metallurgy Engineering and Materials Science, Indian Institute of Technology Indore, Simrol,
Khandwa Road, Indore 453552, India
Email address: Shaikh M. Mobin (xray@iiti.ac.in) and Pradeep Mathur (director@iiti.ac.in)
1

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Abstract
The synthesis of pyridine alcohol based ruthenium carbonyl clusters Ru3(hep)2(CO)8 (1),
Ru3(hpp)2(CO)8 (2), and Ru3(bhmpꢀH)2(CO)8 (3) {hepꢀH = 2ꢀ(2ꢀhydroxyethyl)pyridine, hppꢀH = 2ꢀ
(3ꢀhydroxypropyl)pyridine and bhmpꢀH2 = 2,6ꢀbis(hydroxymethyl)pyridine} has been carried out
by the reaction of corresponding pyridineꢀalcohol ligands with Ru3(CO)12. Clusters 1–3 have been
characterized by elemental analysis, NMR, FTꢀIR, TGA, mass spectrometry and singleꢀcrystal Xꢀray
structures. The clusters were explored for selective catalytic transformation of primary amines into
secondary amines using alcohols as the mono alkylating agents via hydrogen transfer reactions. All
three display efficient catalytic activity with 1 being the most effective.
2

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Introduction
Pyridines based ruthenium complexes and clusters have attracted much attention over the last
few decades as innovative catalysts for selective transformations and functionalization of specific
substrates.1ꢀ8 Park and Ko et al. have reported the influence of the size of the alkyl formate chain in a
2ꢀalkylformate ligand with Ru3(CO)12 as the catalyst for the hydroesterification reactions of alkenes
without decarbonylation incase of 2ꢀpyridyl methylformate.9, 10 Ko et al. also introduced chelating Nꢀ
(pyridinꢀ2ꢀyl)formamide with Ru3(CO)12 as an efficient catalyst for hydroamidation reaction of
alkenes.11
Chart A. Secondary amine derivatives present in various psychoactive drugs
Preparation of secondary amines as scaffolds present in various psychoactive drugs12ꢀ14 poses a
challenge (Chart A), as alkylation of primary amine, in general, yields a mixture of secondary and
tertiary amines.15ꢀ19 Therefore, we undertook to study the selective Nꢀalkylation of primary amines.
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Chart B. Homogeneous catalysts (i–iv) used so far for Nꢀalkylation of primary amine
Grigg20 and Watanabe21 have reported Nꢀalkylation using homogeneous catalysts RhH(PPh3)4
and RuCl2(PPh3)3,respectively. Yamaguchi22 and Kempe23, 24 used [Cp*IrCl2]2, and [IrCl(PN)COD],
respectively to perform Nꢀmono and N,Nꢀdi alkylation reactions. Hollmann et al. utilized Shvo’s
ruthenium catalyst (Chart B, i) for alkylation of indoles25 whereas Williams employed a rutheniumꢀ
dimer catalyst (Chart B, ii) for Nꢀalkylation of primary amines.26 Milstein and coꢀworkers
contributed to Nꢀalkylation or the primary amine preparation from ammonia and primary alcohol
using PNP pincer ruthenium complex (Chart B, iii) at high temperature (130–180 °C).27 Matute and
coꢀworkers also reported Nꢀalkylation of primary amines using RuꢀCNN pincer complex (Chart B,
iv)28 whereas Ramachandran et al. made use of mononuclear phosphineꢀruthenium complex for Nꢀ
alkylation of primary amines.29, 30
4

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The earlier reported ruthenium catalysts for the Nꢀalkylation of primary amine involve
rutheniumꢀhydride, phosphine, or pincer ruthenium catalyst. Either the synthesis of those catalysts
requires sophisticated conditions or the catalyst loading for the Nꢀalkylation reaction is relatively
high. In contrast, we report a facile preparation of ruthenium carbonyl clusters involving chelation of
simple pyridine alcohol as ligands, with the catalyst loading as low as 0.5mol % which is much
lower than previously reported other catalyst loading. Additionally, the cluster catalyst is found to be
active for a variety of aromatic and aliphatic amines.
Kim et al. had shown that in situ addition of various pyridine alcohols viz. 2ꢀhydroxypyridine, 2ꢀ
(2ꢀhydroxyethyl)pyridine, 2ꢀ(3ꢀhydroxypropyl)pyridine and 2,6ꢀbis(hydroxymethyl)pyridine along
with Ru3(CO)12 and sodium formate catalyzed the hydroesterification reaction of alkenes at 170 °C,
in which the 2ꢀ(hydroxymethyl)pyridine ligand offers better catalyst activity than other pyridine
alcohols.4 This proved that the chelating functional pyridine alcohols have a positive influence on
Ru3(CO)12 to promote as a catalytic hydroesterification reaction of alkenes.
The chelation effect observations of pyridineꢀalcohol ligands motivated us to explore the
structural modifications of the triruthenium unit by varying the nature and length of the side chain of
the functional pyridineꢀalcohol ligands. Thus, the coordination of 2ꢀ(2ꢀhydroxyethyl)pyridine (hepꢀ
H), 2ꢀ(3ꢀhydroxypropyl)pyridine (hppꢀH) and 2,6ꢀbis(hydroxymethyl)pyridine (bhmpꢀH2) with the
Ru3(CO)12 precursor have been studied. We report that two of these ligands can be incorporated into
the trinuclear structure to afford the ruthenium cluster complexes Ru3(hep)2(CO)8 (1),
Ru3(hpp)2(CO)8 (2), and Ru3(bhmpꢀH)2(CO)8 (3). The compound 1 and its analogues have been
reported by Doorn et al.,31 Herein, we report for the first time the crystal structures of 1–3 which
have the similar mode of ligand binding as reported by them.
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We also report that the clusters 1–3 catalyze the mono Nꢀalkylation of primary amines with
alcohols via a hydrogen transfer reaction resulting in the selective production of secondary amines
and show the influence of the nature of the chelating ligand in the Ru3 clusters as catalysts.
6

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Experimental
All reactions were done under an inert gas atmosphere. Ruthenium carbonyl, pyridine
alcohols, and other alcohols along with amine derivatives were purchased from Aldrich and TCI
chemicals. Reagents used for purification and crystallization were purchased either from Rankem or
Merck and distilled before use. NMR spectra were recorded in deuterated acetone (CD3COCD3) on a
Bruker Avance (III) spectrometer (400 MHz). Single crystal xꢀray diffraction studies of complexes
1–3 were carried out using an Agilent Technologies Supernova CCD system. The mass
chromatograms were recorded on a BrukerꢀDaltonicsꢀmicroTOFꢀQII mass spectrometer. Elemental
analysis was performed by using a Thermo Scientific FLASH 200 instrument. GC Samples were
analyzed in Shimadzu QP2010 Ultra. The parameters used in the column oven program were as
follows: 40 °C (hold 5 min.) →20 °C/min.→ 280 °C (hold 13 min.) along with injection temperature
280 °C, the interface temperature was 300 °C, and the ion source temperature was 220 °C.
Preparation of cluster Ru3(hep)2(CO)8 (1).
Pyridinꢀ2ꢀylꢀethanol (113 ꢁL, 1 mmol) and KOH (42 mg, 1.05 mmol), were placed into a round
bottom flask using water (1 mL) as a solvent, and the reaction mixture was stirred for 1 hour at room
temperature. After 1 hour, water was evaporated and residual water was removed using high vacuum
pump. Ru3(CO)12 (0.320 g, 0.5 mmol) was added along with 25 mL of dry toluene into the same
flask and refluxed at 110 °C for 3 hours, the yellow colored solution was cooled and evaporated by
rotavapor, and the resulting precipitate was washed with hexane five times and once with a small
quantity of diethyl ether. Later, the precipitate was dissolved in acetoneꢀdichloromethane mixture;
filtered using celite and the filtered solvent was evaporated. The residue was recrystallized in toluene
solvent. The yellow coloured crystalline solid was obtained. The identity of the complex was
determined by using 1H and 13C NMR, mass spectrometry, CHN elemental analysis and a singleꢀ
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crystal XRD study. Yield: 62% (0.240 g), 1H NMR (400 MHz, acetoneꢀd6, 25 °C , ppm): δ 8.97 (d,
1H), 7.94 (t, 1H), 7.50 (t, 1H), 7.41 (d, 1H), 4.08 (tt, 1H), 3.04 (m, 2H), 2.68 (t, 1H); 13C NMR (100
MHz, acetoneꢀd6, 25 °C, ppm): δ 205.4, 205.2, 203.9, 196.1, 162.7, 155.2, 139.8, 127.1, 124.6, 65.5,
43.6; Elem. Anal. Calcd: C, 34.25; H, 2.09; N, 3.63; Found: C, 34.29; H, 1.95; N, 3.64; Selected IR
on (KBr, cm−1): 2950(w), 2915(w), 2847(s), 2060(s), 1985(s), 1914(s), 1603(w), 1079(s); ESIꢀMS
(m/z) 687.55.
Preparation of cluster Ru3(hpp)2(CO)8 (2)
Using same conditions as those for Ru3(hep)2(CO)8 (1) preparation, the Ru3(hpp)2(CO)8 (2)
complex was prepared by using the 2ꢀpyridinꢀ2ꢀylꢀpropanol (129 ꢁL, 1 mmol) with KOH (41 mg,
1.03 mmol) and Ru3(CO)12 (0.320 g, 0.5 mmol) into 25 mL of toluene as the solvent. After
recrystallization, red coloured complex 2 was obtained. Yield: 54%, 1H NMR (400 MHz, acetoneꢀd6,
25 °C , ppm): δ 8.78 (d, 1H), 7.79 (t, 1H), 7.32 (dd, 2H), 4.28 (t, 1H), 3.90 (d, 1H), 3.36 (t, 1H), 3.12
(dd, 1H), 1.95 (t, 1H), 1.55 (q, 1H); 13C NMR (100 MHz, acetoneꢀd6, 25 °C, ppm): δ 206.2, 205.8,
203.4, 195.7, 166.8, 154.0, 139.8, 127.9, 123.8, 74.8, 38.1, 35.9; Elem. Anal. Calcd: C, 36.05; H,
2.52; N, 3.50; Found: C, 36.99; H, 2.43; N, 3.61; Selected IR on (KBr, cm−1): 2943(w), 2912(w),
2840(s), 2066(s), 1987(s), 1914(s), 1602(w), 1085(s); ESIꢀMS (m/z) 542.61
Preparation of cluster Ru3(bhmpꢀH)2(CO)8 (3)
Using same conditions as those for Ru3(hep)2(CO)8 (1) preparation, the Ru3(bhmpꢀH)2(CO)8 (3)
complex was prepared by using the (6ꢀhydroxymethylꢀpyridinꢀ2ꢀyl)ꢀmethanol (0.139 g, 1 mmol)
with KOH (40 mg, 1 mmol) and Ru3(CO)12 (0.320 g, 0.5 mmol) with 25 mL of toluene as the
1
solvent. After recrystallization, yellow crystalline solid was obtained. Yield: 58%, H NMR (400
MHz, acetoneꢀd6, 25 °C , ppm): δ 7.76 (d, 2H), 6.73 (t, 1H), 5.16 (m, 2H), 5.01 (m, 2H), 4.27 (d,
13
1H); C NMR (100 MHz, acetoneꢀd6, 25 °C, ppm): δ 207.7, 204.5, 203.6, 193.9, 167.4, 162.9,
8

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138.7, 121.0, 117.3, 78.5, 68.0; Elem. Anal. Calcd: C, 32.88; H, 2.01; N, 3.49. Found: C, 33.29; H,
2.06; N, 3.45; Selected IR on (KBr, cm−1): 3408(br), 2925(w), 2855(w), 2076(s), 1993(s), 1910(s),
1604(w), 1078(s); ESIꢀMS (m/z) 750.20
Mercury Poisoning Study
Mercury Poisoning experiment for the monoꢀalkylation of primary amine was performed in a 25ꢀ
mL tube capped with a glass stopper. In a sealed tube, an 8 x 4 mm ovalꢀshaped stirring bar, 4 Å
mol. sieves, 1mmol of picolylamine, 1mmol of benzyl alcohol, mercury (1mmol), and catalyst (4
mg) along with the KOtBu (1mmol) along with 1mL of toluene was added and flushed with N2. The
reaction was carried out at 110°C for 24h. As the reaction was completed, the unꢀreacted drops of
mercury were present in the reaction mixture. Then after washing out the reaction mixture, mercury
was quenched. Furthermore, the yield was calculated.
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Results and Discussion
Synthesis of Ru3 clusters 1–3
The reaction of Ru3(CO)12 with pyridineꢀalcohol, { 2ꢀ(2ꢀhydroxyethyl)pyridine (hepꢀH) (for
cluster 1) and 2ꢀ(3ꢀhydroxypropyl)pyridine (hppꢀH) (for cluster 2) has been carried out in 1:2 molar
ratio in toluene (25 mL) at 110 °C for 4h using 2 equivalent of KOH (Scheme 1).
Scheme 1. Synthesis of pyridine alcohol containing ruthenium carbonyl complexes 1–3
On varying the ratio, 1:4 and 1:6 of Ru3(CO)12: ligand the same products, 1 and 2 were obtained in
good yield. We investigated whether 2,6ꢀbis(hydroxymethyl)pyridine (bhmpꢀH2) would change the
nature of the resulting cluster by maintaining the above synthetic conditions. Surprisingly, we
obtained cluster 3, similar to 1 and 2, but with two pendant CH2OH arms. Fine crystals of 1–3 were
10

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obtained from toluene, (Fig. S1†), and the new clusters have been characterized by infrared and 1H,
and 13C NMR spectroscopy, mass spectrometry, and CHN analysis. Their molecular structures were
established by single crystal Xꢀray diffraction studies. Infrared and 13C NMR spectra of 1–3
confirmed the presence of only terminal carbonyls. Mass spectra of all three compounds showed the
respective molecular ion peaks and additional ones corresponding to successive loss of carbonyl
groups (Fig. S2–S13†).
The molecular structures of 1–3 are shown in Fig. 1, and their structural parameters are presented
in Table 1. The distance between two neighbouring unbonded Ru1 and Ru2 atoms in 1–3 are in the
range of 3.030 Å – 3.045 Å which is larger than the bonded RuꢀRu distances (2.775 Å – 2.815 Å).32
In 3, the two free ꢀOH groups are oriented away from the Ru3 unit, other structural features are
unexceptional (Fig. S14–S27†). Along with 1–3, the other toluene solvated form of cluster 1 is also
analyzed and named as Cluster 1a (Fig. S14†, Table S5).
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Fig. 1 Perspective view of 1, 2 and 3
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Table 1 Crystal data and structure refinement33,34 for 1, 2 and 3
Identification code
Empirical formula
Formula weight
Temperature/K
Crystal system
1
2
3
C22H16N2O10Ru3
C24H20N2O10Ru3
799.63
293(2)
C22H16N2O12Ru3
803.58
293(2)
monoclinic
P21/n
771.58
293
monoclinic
P21/n
Triclinic
Space group
P
ī
10.5526(2)
14.8131(3)
16.8846(2)
90
93.161(2)
90
2635.33(10)
4
1.945
9.9410(6)
9.9539(8)
14.4372(10)
89.273(6)
76.892(6)
81.270(6)
1374.89(17)
2
10.5934(7)
13.4587(9)
18.7560(11)
90
97.916(7)
90
2648.6(3)
4
2.015
a/Å
b/Å
c/Å
α/°
β/°
γ/°
Volume/Å3
Z
ρcalc Mg/m3
ꢁ/mmꢀ1
F(000)
1.932
1.683
780
1.753
1496.0
1.754
1560.0
Crystal size/mm3
Radiation
0.34× 0.32 × 0.28 0.34 × 0.32 × 0.3
0.32 × 0.30 × 0.28
Mo Kα
MoKα
MoKα
(λ = 0.71073)
3.004 to 29.007
ꢀ13 ≤ h ≤ 14,
ꢀ19 ≤ k ≤ 20,
ꢀ22 ≤ l ≤ 22
30798
(λ = 0.71073)
3.182 to 32.247
ꢀ14 ≤ h ≤ 14,
ꢀ12 ≤ k ≤ 14,
ꢀ21 ≤ l ≤ 17
16236
(λ = 0.71073)
3.027 to 32.156
ꢀ15 ≤ h ≤ 15,
ꢀ18 ≤ k ≤ 20,
ꢀ28 ≤ l ≤ 27
35820
2θ range for data collection/°
Index ranges
Reflections collected
Refinement method
Fullꢀmatrix leastꢀ Fullꢀmatrix
leastꢀ Fullꢀmatrix leastꢀsquares
squares on F2
6385
squares on F2
8893
on F2
8800
Independent reflections
[Rint = 0.0365,
Rsigma = 0.0236]
6385/0/334
[Rint = 0.0271,
Rsigma = 0.0380]
8893/40/439
[Rint = 0.1548,
Rsigma = 0.1626]
8800/0/354
Data/restraints/parameters
Goodnessꢀofꢀfit on F2
1.059
1.147
1.002
R1 = 0.0264,
wR2 = 0.658
R1 = 0.0314,
wR2 = 0.0696
R1 = 0.0379,
wR2 = 0.0838
R1 = 0.0504,
wR2 = 0.0932
R1 = 0.0650,
wR2 = 0.1071
R1 = 0.1830,
wR2 = 0.1519
1.068/ꢀ1.188
1541897
Final R indexes [I>=2σ (I)]
Final R indexes [all data]
Largest diff. peak/hole / e Åꢀ3
CCDC No.
0.561/ꢀ0.698
1852237
1.185/ꢀ1.019
1539166
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Ru3 clusters catalyzed monoꢀalkylation of primary amines with alcohol
A search of the literature reveals the presence of several hydride/pincer complexes of rhodium,
iridium, and ruthenium along with their phosphine complexes for catalysis of monoꢀalkylation of
amines with alcohols (Table 2). Grigg et al. used Rh catalyst (5 mol %) to achieve the Nꢀ
methylation of pyrrolidine. Aminoarenes were converted to secondary and tertiary amines by the
reaction around 180 °C with primary alcohols in the presence of dichlorotris(tripheny1phosphine)ꢀ
ruthenium (1 mol %). Fujita et al. utilized [Cp∗IrCl2]2 (1.0 mol % Ir catalyst) for Nꢀalkylation
reaction. Blank and Yamaguchi also utilized the Ir catalysts for the Nꢀalkylation of amines using
primary alcohols. Hollman et al. used 1 mol % ruthenium catalyst and performed the Nꢀalkylation
reaction at 150 °C. Hamid et al. utilized ruthenium catalyst (0.5–2.5 mol %) for excellent Nꢀ
alkylation of amines in reflux toluene. Gunanathan and Milstein performed the outstanding direct
primary amine synthesis utilizing ruthenium PNP catalyst using only 0.1 mol % of the catalyst.
Ramachandran et al. used mononuclear phosphineꢀruthenium complex for the Nꢀalkylation reaction,
but they used 1.0 mol % or KOH in their reaction. Our catalyst is comparable to many catalysts
reported so far (Table 2) as, the catalytic reaction used a smaller amount of catalyst (0.5 mol %), the
catalyzed reaction is performed at a relatively low temperature (110 °C). The synthetic procedure for
cluster 1–3, is relatively uncomplicated and requires shorter time and to the best of our knowledge,
this is the first example of use of ruthenium carbonyl clusters 1–3 for catalysis of monoꢀalkylation
of amines with primary alcohols.
Table 2. Comparison of cluster 1 with previous homogeneous catalysts for alkylation reaction of
primary amines with primary alcohols
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Substrates
Entry
No.
Reaction
parameters
Yield
(%)
Catalyst or preꢀcatalyst
Reference
R1OH and
R2NH2
pyrrolidine +
MeOH
Reflux, 4 h,
70 °C
20
21
1
2
98%
Aniline
+ EtOH
180 °C, 5 h.
74%
75%
94%
NH4BF4 +
RCH2OH
NaHCO3,
140 °C, 17h
22 35
3
4
5
,
Aniline +
benzyl
alcohol
oꢀamino
pyridine +
benzyl
NaHCO3, 110
°C, 17h
KOtBu, 70 °C,
17h (2 mol %
catalyst)
24
25
97%
98%
alcohol
2ꢀmethylꢀ
Hexyl amine, butanꢀol, 150
aryl amine
°C (1 mol %
catalyst)
5 mol % dppf,
toluene,
110 °C, 24h
(2.5 mol %
catalyst)
tBuNH2,
benzyl
alcohol
26
6
7
94%
83%
toluene,
110 °C, 24h
(0.1 mol %
catalyst)
Benzyl
alcohol, NH3
27
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KOtBu,
toluene,
110 °C, 24h (1
mol %
Benzyl
alcohol, NH3
28
8
92%
catalyst)
2ꢀamino
benzothiazole,
benzyl
KOH, toluene,
110 °C, 12h
(0.5 mol %
catalyst)
29
9
96%
alcohol
KOtBu,
toluene,
110 °C, 24h
(0.5 mol %
catalyst)
2ꢀamino
pyridine,
benzyl
10
96%
this work
alcohol
Catalytic application of clusters 1–3 for amine monoꢀalkylation with primary alcohols
Clusters 1–3 and Ru3(CO)12 were evaluated as catalysts for the transformation of primary amine
2ꢀpicolylamine to a secondary amine in the model reaction (Table 3). Typically, the reaction was
performed using 1.0 mmol of benzyl alcohol and 2ꢀpicolylamine as reactants, low loading (0.5 mol
%) of catalyst 1–3 and 1.0 mmol potassium tertꢀbutoxide as a base, 4 Å mol. sieve, and stirred in
600 µL of toluene.
In the absence of ruthenium catalyst and base, the amine alkylation was not observed (Table 3,
entries 1, 2). The optimization of reaction conditions was performed at room temperature, 55 °C, 75
°C and 110 °C. The reaction was not observed below 110 °C. The effect of time on the reaction was
observed, and within 24 h at 110 °C, the reaction was completed with catalyst 1 (entries 3–6).
Among all the rutheniumꢀbased clusters, 1–3, similar catalytic activity was obtained, but the most
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active catalyst was cluster 1, likely due to the sixꢀmembered ring formed by the coordination of 2ꢀ(2ꢀ
hydroxyethyl)pyridine ligand to Ru3(CO)8 (entries 6–8). The precursor Ru3(CO)12 in the absence of
pyridineꢀalcohol shows a much lower conversion (entry 9) thus, demonstrating the importance of the
chelating ligand (N
O).
Table 3. Optimization of the catalytic reaction conditions for Nꢀalkylation of 2ꢀpicolylamine
using benzyl alcohol and Ru3 cluster catalysts.
Entry
Catalyst
NA
Base
tBuOK
NA
Time (h)
Conv.
0
Yield
0
1
2
3
4
5
6
7
8
9
24
24
6
Cat.1
0
0
Cat. 1
Cat. 1
Cat. 1
Cat. 1
Cat. 2
Cat. 3
Ru3(CO)12
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
79
74
80
88
96
85
90
54
12
18
24
24
24
24
85
92
100
90
95
70
Under the optimized conditions (entry 6) {cat.1 (0.5 mol %), benzyl alcohol (1.0 mmol), 2ꢀ
picolylamine (1.0 mmol), and 1.0 mmol potassium tertꢀbutoxide in toluene (500 µL) charged with 4
Å, mol. sieves, were heated in a closed tube}; the desired secondary amine was obtained in high
yield (96%).
Encouraged by this catalytic transformation, the monoꢀalkylation of various primary amines
bearing electron donating or electron withdrawing substituents were explored (Table 4). Higher
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yields were observed with para electron donating substituents on the aniline ring whereas the ortho-
substituted aniline was less reactive likely due to the steric hindrance (Table 4, entries 3, 4 and 7).
With halogen substituents on pyridine ring, the conversion was observed, but the desired product
yields were low. The catalyst was active even with aliphatic amines (entries 2, 6 and 8) but for
heterocycles containing the imidazole and furan rings (entries 9–10), the monoꢀalkylation was not
observed. 4ꢀaminopyridine and piperonylamine also gave excellent yields for the monoꢀalkylation of
primary amines (entries 11–12). In case of haloꢀaniline, the paraꢀfluoro aniline gave the highest yield
followed by chloro, bromo and iodo aniline (entries 13–16). Aniline, (2ꢀchlorophenyl)methanamine,
and pꢀtolylmethanamine, also gave the desired product in good yield, and at last reactant with
maximum substitution like trimethoxyaniline monoꢀalkylation also produced the secondary amine
product in better yield (entries 17–20).
Table 4. Direct formation of secondary amines from benzyl alcohol and various primary amines
with cluster 1 as catalyst
.
RNH2
Conv.
100%
C6H5 CH2HNR
Yield
96%
Entry
1
2
3
52%
64%
51%
56%
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4
5
44%
65%
41%
19%
6
7
72%
48%
55%
46%
8
9
22%
ꢀꢀ
20%
ꢀꢀ
ꢀNRꢀ
ꢀNRꢀ
10
ꢀꢀ
11
12
73%
70%
62%
>90%
13
14
79%
64%
72%
62%
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15
55%
50%
16
17
52%
72%
38%
68%
18
19
58%
70%
50%
47%
20
74%
60%
aComplex 1 (0.5 mol %), benzyl alcohol (1.0 mmol), primary amine (1.0 mmol), and toluene
(500 µL) charged with 4 Å, mol. sieves, were heated in a closed tube. bConversion of alcohol and
yield of products were determined by GCꢀMS. cIsolated yields (1, 4, 7, 11, 20) were analyzed by 1H
and 13C NMR along with GCꢀMS.
Catalyst 1 showed significant results even when pyridine alcohols, pyridinꢀ2ꢀylmethanol,
pyridinꢀ2ꢀylethanol, and pyridinꢀ2ꢀylpropanol were screened (Table 5, entries 1–3). The three
synthesized dipyridyl secondary amines are the precursors of significant NNNꢀpincer ligands.
Presence of functional groups on benzyl alcohol substrates did not prevent the catalytic secondary
amine formation (Table 5, entries 5, 6). Haloꢀbenzyl alcohol also gave the expected product, but the
less stable bromo derivative gave lower yield in the reaction (Table 5, entries 7, 8).
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Table 5. Direct formation of secondary amines from primary amines and varying alcohols using
1 as catalyst
Entry
R2CH2OH
Conv.
52%
C5H4NCH2NHCH2R2
Yield
41%
1
2
82%
75%
3
4
90%
75%
54%
64%
5
90%
78%
6
7
67%
80%
50%
8%
8
73%
55%
aComplex 1 (0.5 mol %), primary alcohol (1.0 mmol), pyridinꢀ2ꢀylmethanamine (1.0 mmol), and
b
toluene (500 µL) charged with 4 Å, mol. sieves, were heated in a closed tube. Conversion of
alcohols and yield of products were analyzed by GCꢀMS. cIsolated yields (1, 5) were analyzed by 1H
and 13C NMR along with GCꢀMS. NMR and GCꢀMS data can be found in Fig. S28–S73†.
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Mercury Poisoning Study
We have also investigated the influence of mercury(0)36 on the monoꢀalkylation of primary
amines using alcohol in the presence of 1. The yield of the monoꢀalkylation does not reduce
significantly when mercury(0) is introduced in the reaction mixture (from 96% to 84%). The failure
of Hg(0) to halt the reaction suggests that the reaction involves the homogenous ruthenium pyridine
alcohol cluster catalyst. Fig. 2 displays condition 1 as the optimized reaction condition (Fig. S31†)
and condition 2 as the reaction condition in the presence of Hg(0) (Fig. S74†) with the respective
yields.
Fig. 2 Mercury poisoning study of Ru3(hep)2(CO)8 cluster catalyst for monoꢀalkylation of amine
with alcohol
Conclusion
The above results show that pyridine alcohols react with Ru3(CO)12 to form clusters
Ru3(hep)2(CO)8 (1), Ru3(hpp)2(CO)8 (2), and Ru3(bhmpꢀH)2(CO)8 (3). They all contain a trans pyꢀ
RuꢀRuꢀpy arrangement, and the chelating ligands offer 2 oxygen atom bridging the nonꢀbonded
Ru(1) and Ru(2) sites. The catalytic transformation highlights the high efficiency and versatility of
the clusters Ru3(N
O)2(CO)8 catalyst (L= hep, hpp, bhmpꢀH). Cluster 1 was the most efficient
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catalyst for the Nꢀalkylation reactions of primary amines. The catalytic transformations are entirely
selective leading to excellent yields of secondary amine. This work has created simple Ru3 catalysts,
with pyridine alcohol chelating ligands, which do not contain pincer or hydride ligands, and
excellent catalytic activity for monoꢀalkylation for primary amines is achieved successfully. Other
catalytic transformations like hydrogen production from renewable alcohols, oxidation of alcohols
into carboxylates, usually performed by pincer metal catalysts, can be explored by employing these
Ru3 1–3 clusters.
Conflicts of interest
There are no conflicts of interest to declare
Associated Content:
Electronic Supplementary Information
The electronic supplementary information includes all spectral data and explanations of
interaction present in crystals 1–3. CCDC Number 1852237, 1539166, and 1541897 contain the
supplementary crystallographic data for 1, 2 and 3, respectively. The data is available free of
charge at http://www.ccdc.cam.ac.uk/conts/retrieving.html, or the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223ꢀ336ꢀ033; or eꢀmail:
deposit@ccdc.cam.ac.uk.
Author Information
Corresponding Author: *Eꢀmail: xray@iiti.ac.in and director@iiti.ac.in
Acknowledgements
Financial support from the SERBꢀDST (Project No. EMR/2016/001113), New Delhi, and IIT
Indore is gratefully acknowledged by S.M.M. We thank Sophisticated Instrumentation Centre (SIC),
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IIT Indore, for providing all of the characterization facilities. A. S. thanks, UGC, New Delhi for
providing a fellowship. P. M. gratefully acknowledges the J. C. Bose National Fellowship.
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This report has created simple Ru3 pyridine alcohol cluster catalysts which are excellent catalyst
for mono-alkylation for primary amines.