Efficient and versatile catalysis of N-alkylation of heterocyclic amines with alcohols and one-pot synthesis of 2-aryl substituted benzazoles with newly designed ruthenium(ii) complexes of PNS thiosemicarbazones

Article abstract of DOI:10.1039/c4dt00006d

Ruthenium(ii) carbonyl complexes with phosphine-functionalized PNS type thiosemicarbazone ligands [RuCl(CO)(EPh₃)(L)] (1-6) (E = P or As, L = 2-(2-(diphenylphosphino)benzylidene) thiosemicarbazone (PNS-H), 2-(2-(diphenylphosphino)benzylidene)-N-methylthiosemicarbazone (PNS-Me), 2-(2-(diphenylphosphino)benzylidene)-N-phenylthiosemicarbazone (PNS-Ph)) have been synthesized and characterized by elemental analysis and spectroscopy (IR, UV-Vis, ¹H, ¹³C, ³¹P-NMR) as well as ESI mass spectrometry. The molecular structures of complexes 1, 2 and 6 were identified by means of single-crystal X-ray diffraction analysis. The analysis revealed that all the complexes possess a distorted octahedral geometry with the ligand coordinating in a uni-negative tridentate PNS fashion. All the ruthenium complexes (1-6) were tested as catalyst for N-alkylation of heteroaromatic amines with alcohols. Notably, complex 2 was found to be a very efficient and versatile catalyst towards N-alkylation of a wide range of heterocyclic amines with alcohols. Complex 2 can also catalyze the direct amination of 2-nitropyridine with benzyl alcohol to the corresponding secondary amine. Furthermore, a preliminary examination of performance for N,N-dialkylation of diamine showed promising results, giving good conversion and high selectivity. In addition, N-alkylation of ortho-substituted anilines (-NH₂, -OH and -SH) led to the one-pot synthesis of 2-aryl substituted benzimidazoles, benzoxazoles and benzothiazoles, also revealing the catalytic activity of complex 2. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4dt00006d

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PAPER
Efficient and versatile catalysis of N-alkylation of
heterocyclic amines with alcohols and one-pot
synthesis of 2-aryl substituted benzazoles with
newly designed ruthenium(II) complexes of PNS
thiosemicarbazones†
Cite this: Dalton Trans., 2014, 43,
7889
Rangasamy Ramachandran,a Govindan Prakash,a Sellappan Selvamurugan,a
Periasamy Viswanathamurthi,*a Jan Grzegorz Maleckib and
Venkatachalam Ramkumarc
Ruthenium(II) carbonyl complexes with phosphine-functionalized PNS type thiosemicarbazone ligands
[RuCl(CO)(EPh3)(L)] (1–6) (E = P or As, L = 2-(2-(diphenylphosphino)benzylidene) thiosemicarbazone
(PNS-H), 2-(2-(diphenylphosphino)benzylidene)-N-methylthiosemicarbazone (PNS-Me), 2-(2-(diphenyl-
phosphino)benzylidene)-N-phenylthiosemicarbazone (PNS-Ph)) have been synthesized and characterized
1
by elemental analysis and spectroscopy (IR, UV-Vis, H, 13C, 31P-NMR) as well as ESI mass spectrometry.
The molecular structures of complexes 1, 2 and 6 were identified by means of single-crystal X-ray diffrac-
tion analysis. The analysis revealed that all the complexes possess a distorted octahedral geometry with
the ligand coordinating in a uni-negative tridentate PNS fashion. All the ruthenium complexes (1–6) were
tested as catalyst for N-alkylation of heteroaromatic amines with alcohols. Notably, complex 2 was
found to be a very efficient and versatile catalyst towards N-alkylation of a wide range of heterocyclic
amines with alcohols. Complex 2 can also catalyze the direct amination of 2-nitropyridine with benzyl
alcohol to the corresponding secondary amine. Furthermore, a preliminary examination of performance
for N,N-dialkylation of diamine showed promising results, giving good conversion and high selectivity. In
addition, N-alkylation of ortho-substituted anilines (–NH2, –OH and –SH) led to the one-pot synthesis of
2-aryl substituted benzimidazoles, benzoxazoles and benzothiazoles, also revealing the catalytic activity
of complex 2.
Received 2nd January 2014,
Accepted 9th March 2014
DOI: 10.1039/c4dt00006d
www.rsc.org/dalton
use of multidentate thiosemicarbazone ligands having both
hard and soft donor atoms (e.g. N2S2 or XNS, X = N, O, S and
Introduction
The nature of the multidentate ligand has a profound effect on P), because of their coordination versatility2 and remarkable
the coordination chemistry of a metal complex, and so the applications in catalytic3 and biological sciences.4 Thiosemi-
design and “tailoring” of ligand properties can lead to innova- carbazones functionalized with an additional donor group
tive metal chemistry.1 Special attention has been directed to the have become important ligands due to the potential hemilabil-
ity of the new donor group, which can play a dual role in a
catalyst since they can easily enable coordination sites and, at
aDepartment of Chemistry, Periyar University, Salem-636 011, India.
the same time, protect the coordination sites by a dynamic “on
and off” chelating effect.5
E-mail: viswanathamurthi72@gmail.com; Fax: +91 427 2345124
bDepartment of Crystallography, Silsian University, Szkolna 9, 40-006 Katowice,
Several donor groups have been reported to functionalize
Poland
thiosemicarbazones, their complexes exhibit high activity
when used as a catalyst in Pd-catalyzed Suzuki–Miyaura cross
coupling,6 Heck or Buchwald–Hartwig amination reactions.7
More recently, ruthenium mediated N-alkylation and transfer
hydrogenations have also appeared in the literature.8 We have
a continuing broad interest in thiosemicarbazone ligand
systems containing diphenylphosphino pendant functional-
cDepartment of Chemistry, Indian Institute of Technology Madras, Chennai 600 036,
India
†Electronic supplementary information (ESI) available: 1H and 13C-NMR spec-
trum of ligands (PNS-H, PNS-Me, PNS-Ph) and complexes (1–6), 31P-NMR and
ESI-MS spectrum of complexes (1–6), general experimental procedures and
characterization data for N-alkylated products. CCDC 969003–969005. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c4dt00006d
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ities that can potentially form stable complexes with metal
Amines are key building blocks in industrial and medicinal
ions. Since the first synthesis, performed by Brceski and co- chemistry today.17 Traditionally, these compounds are syn-
workers,9 phosphino-thiosemicarbazone ligands have been thesized by alkylation of primary amines with good leaving
widely used in catalysis. With the simultaneous presence of groups such as alkyl halides, tosylates, mesylates and tri-
soft P, S and hard N donors, the phosphino-thiosemicarbazone flates.18 However, the procedure frequently leads to overalkyla-
ligands exhibit various coordination modes (Scheme 1): (a) tion and, considering the necessity for environmentally
neutral tridentate (P, N and S bonded to M),10 (b) monoanionic friendly processes, the high toxicity of many alkylating agents
tridentate (P, N and deprotonated S bonded to M),11 (c) neutral is a major drawback, especially in pharmaceutical, biochemi-
bidentate (P and S bonded to M)12 and (d) monoanionic brid- cal and industrial applications. Nevertheless, the use of tran-
ging ligand (P bonded to M and S bonded to M′).13 Coordi- sition metal complexes as catalysts via a borrowing-hydrogen
nation through neutral bidentate and monoanionic bridging methodology makes N-alkylation using alcohols a potentially
PNS ligands is found in some Au(I) and Ag(I) complexes.13,14 It less hazardous and more atom-economical process.19–24
has been suggested that intramolecular hydrogen bonding While both heterogeneous and homogeneous catalysts have
exists between the terminal thioamide nitrogen atoms as been known to promote the reaction,19b iridium20 and
donors and the imine nitrogen atoms as acceptors. The PNS ruthenium21–23 complexes have constituted a vast majority of
ligands, which do not form an intramolecular hydrogen bond, the homogeneous catalysts because of their high catalytic per-
tend to coordinate predominately in a neutral or monoanionic formance with high product selectivity. Several iridium and
tridentate PNS fashion. Examples of this type of coordination ruthenium catalytic systems bearing phosphine ligands have
are rare and so far only known for complexes with Cu(I) and been reported to complete the N-alkylation of amines with
Au(II).11,15 This variable mode of binding of phosphino-thio- alcohols in good yields and selectivity.24
semicarbazone has encouraged us to explore its coordination
Pyrimidine, ferrocene and sulfonamide are currently con-
chemistry further, and herein we have chosen ruthenium as sidered to be privileged scaffolds and have gained remarkable
the metal center to interact with the thiosemicarbazone. One popularity in the fields of bioorganic and medicinal chem-
reason behind the choice of this particular metal center is its istry.25 In particular, 2-(N-alkylamino)pyrimidines, 2-(N-alkyl-
ability to take up different coordination environments with amino)ferrocene and 2-(N-alkylamino)sulfonamides exhibit a
salicylaldehyde/napthaldehyde thiosemicarbazones which wide range of biological properties. Selective examples are
have been reported recently,16 which makes its coordination N-methyl-D-aspartate receptor antagonists, ferroquine and
chemistry very interesting.
histone deacetylase inhibitors.26 Bioactive molecules possessing
2-(N-alkylamino)benzothiazole core, such as R116010 (II) and
riluzole(I) can act as potent inhibitor of retinoic acid metabolism,
glutamate neurotransmitter and N-myristoyltransferase (Nmr)
inhibitor.27 In addition, benzazoles such as benzimidazoles,
benzoxazoles and benzothiazoles are important structural motifs
in pharmaceuticals,28 which involve nearly one-quarter of the top
100 selling drugs including DF203, ERB-O41 and omeprazole
(Scheme 2).29 Development of general methods for the synthesis
of these heterocyclic compounds is thus highly relevant for drug
discovery.
Scheme 1 Different coordination modes of the triphenyl phosphine-
functionalized thiosemicarbazone ligands in various metal complexes.
Scheme 2 Bioactive molecules with pyrimidine, ferrocene, sulfonamide, 2-N-(alkylaminoazole) and benzazole moieties.
7890 | Dalton Trans., 2014, 43, 7889–7902
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In view of the above and as a part of our ongoing research [RuCl(CO)(EPh3)(L)] (1–6) were synthesized by reacting PNS-H,
work,8a,16a,30 we report herein a series of ruthenium(II) carbo- PNS-Me and PNS-Ph with one equivalent of [RuHCl(CO)-
nyl complexes bearing phosphino-thiosemicarbazone ligands (EPPh3)3] in ethanol under reflux for 6–8 h (see Scheme 3 for
and investigate the role of terminal substitution of ligands and further details). These Ru complexes are air stable, were
co-ligands in determining catalytic activity for N-alkylation of obtained in good yield (73–82%), and were characterized by
amines and one-pot synthesis of 2-aryl substituted benzimid- analytical, spectroscopic methods (IR, UV-Vis, 1H, 13C, 31P-NMR
azoles, benzoxazoles and benzothiazoles. The attractive fea- and ESI-MS) (Fig. S1–S30, ESI†) and by X-ray crystallography for
tures of these reactions include the use of low toxic organic 1, 2 and 6 as described further below. The analytical data of the
materials, excellent atom economy, water as the only bypro- complexes agreed well with the proposed molecular formulae.
duct and high selectivity towards the products.
Spectroscopic studies
The IR spectra of the ligands and the corresponding
ruthenium(II) complexes provided significant information
Results and discussion
Catalyst design
about the metal–ligand bonding. A strong vibration observed
at 1546–1541 cm−1 in the ligands corresponding to νCvN was
shifted to 1592–1582 cm−1 in all the complexes indicating the
In designing Ru complexes (1–6) (Scheme 3), we were inter-
ested in probing the role of catalysis of terminal N-substitution
in phosphino-thiosemicarbazones (PNS-H, PNS-Me and
participation of azomethine nitrogen in bonding.15 A sharp
band observed at 760–758 cm−1, ascribed to νCvS in the
ligands, has completely disappeared in the spectra of all the
new Ru complexes, and the appearance of a new band at
747–738 cm−1 due to νC–S indicated the coordination of the
sulfur atom after enolisation followed by deprotonation.16a All
the complexes display a medium to strong band in the region
1962–1945 cm−1, which is attributed to the terminally co-
ordinated carbonyl group (CuO) and is observed at a slightly
higher frequency than in the precursor complexes.16b In
addition, vibrations corresponding to the presence of PPh3/
AsPh3 also appeared in the expected region. The electronic
spectra of the complexes (1–6) have been recorded in dichloro-
methane and they displayed four bands in the region around
231–435 nm. The high-energy absorption shoulder in the
region 231–258 nm has been assigned to ligand-centered (LC)
transitions,31 the lowest energy shoulder observed in the
region 343–369 nm has been attributed to the ligand to metal
charge transfer (LMCT) transitions, and the band 427–435 nm
has been assigned to a forbidden (d→d) transition.
PNS-Ph), co-ligands, and the resulting differences in the struc-
ture of the complexes (1–6). The ruthenium(II) complexes (1–6)
are closely related, only differing by H versus Me or Ph in the
terminal N-substituent and P or As in coligands. The ligand
precursors PNS-H, PNS-Me and PNS-Ph (Scheme 3) were syn-
thesized by condensation of 2-diphenylphosphinebenz-
aldehyde with thiosemicarbazide, 4-N-methylthiosemicarbazide
and 4-N-phenylthiosemicarbazide, respectively, following the
published procedure.9–15 The new Ru catalysts of the type
The 1H NMR spectra of the ligands and their complexes
(1–6) show the signals in the expected regions (Fig. S1–S9,
ESI†). The singlets that appeared for the N–NH–CvS proton of
the free ligands at 11.94–11.52 ppm are absent in the com-
plexes, supporting the enolization and coordination of the
thiolate sulfur to the Ru(II) ion. The doublet due to azomethine
proton (8.86–8.73 ppm) in the complexes are slightly downfield
compared to the free ligands (8.79–8.65 ppm), suggesting
deshielding upon coordination to the Ru(II) ion. The spectra
of the complexes showed a singlet at 8.60–8.15 ppm, which
has been assigned to NH2 or NH-R protons. Further, the
spectra of all the complexes showed a series of signals for aro-
matic protons at 7.88–6.51 ppm. In addition, a singlet
appeared around 1.22 ppm for complexes 2 and 5 corres-
ponding to the terminal –CH3 group protons.
The 13C NMR spectra show the expected signals in the
appropriate regions (Fig. S10–S18, ESI†). For the uncoordi-
nated ligands, the CvN and CvS signals appear in the
regions around 141.50–140.64 ppm and 178.93–175.81 ppm.
Upon coordination and formation of the new Ru complexes, a
Scheme 3 Synthesis of the ruthenium(II) complexes.
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downfield shift is observed for the signals of the CvN (around indicate the exact coordination of phosphino-thiosemicarba-
5 ppm), while the CvS carbon atom signals appeared in the zone units in them. Hence, there is a need to prove their struc-
upfield region between 176.45 and 176.03 ppm. This is consist- tures by X-ray crystallography. The crystal data and structure
ent with the P, N, S coordination and thioenolization of the refinement parameters for complexes 1, 2 and 6 are summar-
CvS of thiosemicarbazone moieties. In complexes (1–6), aro- ized in Table 1 and selected bond lengths and bond angles are
matic carbon atoms of the phenyl group observed around depicted in Table 2. The ORTEP view of complexes 1, 2 and 6
138.91–115.83 ppm are comparable to the literature values.32 along with the atomic numbering scheme are given in
The CuO carbon resonating at 206.73–206.02 ppm is compar- Fig. 1–3. The single-crystal X-ray studies revealed that com-
able with earlier observations.33 In addition, a signal appeared plexes 1 and 2 are crystallized in a monoclinic system with the
around 31.17–30.60 ppm for complexes 2 and 5 corresponding space group P21/c, whereas complex 6 crystallized in a triclinic
ˉ
to the terminal methyl group carbon.
system with the space group P1. The coordination geometry
The presence of a residual PPh3 coordinated to Ru(II) (1–3) around the Ru(II) ion is a slightly distorted octahedron, where
is confirmed by 31P NMR (Fig. S19–S24, ESI†), where two doub- the basal plane is constructed of a phosphorus atom, the
lets are observed respectively at 30.15–29.79 ppm (Jpp = 22.6 imine nitrogen and the thiolate sulfur atom of the ligand in a
Hz, PPh3) and 28.85–28.74 ppm (Jpp = 24.2 Hz, PPh2). These mononegative tridentate PNS fashion, and
a triphenyl-
values for coupling constants suggest a cis disposition between phosphine/triphenylarsine. The remaining apical coordination
the phosphorus nuclei, as already reported for other sites are filled up by a chlorine atom and a carbonyl group.
Ru(II) phosphine complexes.34 The singlet observed at The chloride and carbonyl ligands of complexes 1 and 2 are
32.73–31.38 ppm in complexes 4, 5 and 6, respectively, disordered in two orientations with the ratio 51 : 49 for 1 and
suggested the presence of the PPh2 group in the thiosemi- 55 : 45 for 2, respectively.35a,b In complexes 1, 2 and 6 the
carbazone moieties. ESI-mass spectra of the complexes (1–6) coordination sphere is the same and the general structural
generally show the molecular ion peak with the loss of a chlor- motifs differ only in the terminal substitution (R = H, Me, Ph).
ide ion (Fig. S25–S30, ESI†).
Thus the structure of one of the Ru(II) complexes 1 (Fig. 1) will
be described in detail here.
The tridentate PNS chelate ligand coordinated equatorially
to the metal ion with the formation of one six-membered ring
and another five membered ring with the bite angles of
Structural studies
Even though the analytical and spectral data gave some idea
about the molecular formulae of the complexes, they do not
Table 1 Crystal data and structure refinement parameters for complexes 1, 2 and 6
1
2
6
CCDC number
Empirical formula
Formula weight
T (K)
969003
969004
C40H34ClN3OP2RuS
803.22
969005
C45H36AsClN3OPRuS
909.24
C39H32ClN3OP2RuS·0.5(C2H8O2)
821.24
295
298
295
Wavelength ( Å)
Crystal system
Space group
0.71073
Monoclinic
P21/c
0.71073
Monoclinic
P21/c
0.71073
Triclinic
ˉ
P1
Unit cell dimensions
a (Å)
b (Å)
c (Å)
14.3822(5)
16.6752(6)
15.1543(4)
90.00
14.3388(8)
16.6137(6)
15.0818(8)
90.00
10.2991(8)
13.1254(11)
15.2952(13)
97.686(7)
α (°)
β (°)
96.312(3)
90.00
3612.4(2)
96.268(4)
90.00
3571.3(3)
94.380(7)
96.521(7)
2027.0(3)
γ (°)
Volume (Å3)
Z
4
4
2
Density (calculated) (Mg m−3
)
1.510
0.695
1680
1.494
0.699
1640
1.490
1.392
920
Absorption coefficient (mm−1
F(000)
)
Scan range for data collection (°)
Index ranges
3.42 to 25.05
−17 ≤ h ≤ 17
−19 ≤ k ≤ 18
−17 ≤ l ≤ 18
18 987/6367, 0.0353
0.997
6367/0/486
1.060
R1 = 0.035, wR2 = 0.081
R1 = 0.047, wR2 = 0.086
1.83 to 24.99
−17 ≤ h ≤ 17
−19 ≤ k ≤ 18
−17 ≤ l ≤ 17
40 742/6289, 0.1379
0.994
6289/0/382
0.994
R1 = 0.056, wR2 = 0.101
R1 = 0.093, wR2 = 0.111
3.62 to 28.70
−12 ≤ h ≤ 12
−15 ≤ k ≤ 15
−16 ≤ l ≤ 18
14 624/7165, 0.0673
0.996
7165/0/487
1.070
R1 = 0.056, wR2 = 0.114
R1 = 0.076, wR2 = 0.122
Reflections collected/unique, Rint
Completeness to thetamax
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]a
R indices (all data)
a Structures were refined on Fo2: wR2 = [∑[w(Fo2 − Fc2)2]/∑w(Fo2)2]1/2, where w−1 = [∑(Fo2) + (aP)2 + bP] and P = [max(Fo2, 0) + 2Fc2]/3.
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Table 2 Selected geometrical parameters for complexes 1, 2 and 6
1
2
6
Interatomic distances (Å)
Ru(1)–C(1A)a
Ru(1)–C(1B)a
Ru(1)–N(1)
Ru(1)–P(1)
Ru(1)–S(1)
1.88(2)
Ru(1)–C(41)a
Ru(1)–C(41A)a
Ru(1)–N(1)
Ru(1)–P(1)
1.8183
1.8384
2.128(4)
2.3429
2.3882
2.3929
2.4181
2.4478
Ru(1)–C(1)
—
1.89(3)
—
1.809(18)
2.125(3)
2.344(8)
2.386(8)
2.398(8)
2.441(4)
2.397(5)
Ru(1)–N(1)
Ru(1)–P(1)
Ru(1)–S(1)
Ru(1)–As(1)
Ru(1)–Cl(1)
—
2.02(2)
2.333(8)
2.393(8)
2.469(4)
2.425(9)
—
Ru(1)–S(1)
Ru(1)–P(2)
Ru(1)–P(2)
Ru(1)–Cl(1)a
Ru(1)–Cl(2)a
Ru(1)–Cl(1)a
Ru(1)–Cl(1A)a
Bond angles (°)
C(1B)–Ru(1)–N(1)
C(1B)–Ru(1)–P(1)
C(1B)–Ru(1)–S(1)
C(1B)–Ru(1)–P(2)
C(1B)–Ru(1)–Cl(1)a
C(1B)–Ru(1)–Cl(2)a
N(1)–Ru(1)–P(1)
N(1)–Ru(1)–S(1)
N(1)–Ru(1)–P(2)
N(1)–Ru(1)–Cl(1)
P(1)–Ru(1)–S(1)
P(1)–Ru(1)–P(2)
P(1)–Ru(1)–Cl(1)
S(1)–Ru(1)–P(2)
S(1)–Ru(1)–Cl(1)
P(2)–Ru(1)–Cl(1)
87.4(6)
91.1(6)
90.2(6)
90.2(6)
C(41)–Ru(1)–P(1)
C(41)–Ru(1)–S(1)
C(41)–Ru(1)–P(2)
C(41)–Ru(1)–Cl(1A)a
N(1)–Ru(1)–C(41)
C(41A)–Ru(1)–Cl(1)a
N(1)–Ru(1)–P(1)
N(1)–Ru(1)–S(1)
N(1)–Ru(1)–P(2)
N(1)–Ru(1)–Cl(1)
P(1)–Ru(1)–S(1)
P(1)–Ru(1)–P(2)
P(1)–Ru(1)–Cl(1)
S(1)–Ru(1)–P(2)
S(1)–Ru(1)–Cl(1)
P(2)–Ru(1)–Cl(1)
91.3
89.3
90.3
168.9
87.01(11)
169.6
91.04(11)
81.15(11)
168.74(11)
85.08(11)
172.1
C(1)–Ru(1)–N(1)
C(1)–Ru(1)–P(1)
C(1)–Ru(1)–S(1)
C(1)–Ru(1)–Cl(1)
C(1)–Ru(1)–As(1)
—
N(1)–Ru(1)–P(1)
N(1)–Ru(1)–S(1)
N(1)–Ru(1)–Cl(1)
N(1)–Ru(1)–As(1)
P(1)–Ru(1)–S(1)
P(1)–Ru(1)–Cl(1)
P(1)–Ru(1)–As(1)
S(1)–Ru(1)–Cl(1)
S(1)–Ru(1)–As(1)
Cl(1)–Ru(1)–As(1)
89.6(10)
92.4(8)
91.3(8)
174.5(8)
88.5(8)
—
92.0(6)
79.0(6)
85.0(7)
166.3(6)
170.2(3)
86.9(3)
101.7(2)
88.6(3)
87.5(2)
97.0(2)
166.6(6)
173.7(5)
90.63(7)
81.21(7)
169.37(7)
79.29(16)
171.67(3)
99.78(3)
87.63(8)
88.45(3)
89.22(8)
103.15(14)
100.0
91.8
87.9
88.6
92.1
a The molecular structures 1 and 2 show a disorder in which the Cl ligand and CO ligand have two orientations in the ratio of about 51 : 49 and
55 : 45 for 1 and 2, respectively.
Fig. 1 ORTEP plot of complex [RuCl(CO)(PPh3)(PNS-H)] (1). Thermal
Fig. 2 ORTEP plot of [RuCl(CO)(PPh3)(PNS-Me)] (2). Thermal ellipsoids
ellipsoids have been drawn at the 50% probability level. Hydrogen atoms
and the solvent are omitted for clarity. Carbonyl and chloride ligands are
omitted for clarity. Carbonyl and chloride ligands are located in two
located in two positions, owing to disorder.
have been drawn at the 50% probability level and hydrogen atoms are
positions, owing to disorder.
90.63(7) [N(1)–Ru(1)–P(1)] and 81.21(7) [N(1)–Ru(1)–S(1)]. This
results in significant distortion of the {RuP2NS(CO)Cl} core
from the ideal octahedral geometry, which is reflected in the
twelve cis and three trans angles. As expected, the PPh3 ligand
occupies mutually cis position to the PPh2 head in the thio-
semicarbazone chain for better π interaction.35b The large devi-
ation of the [P(1)–Ru(1)–P(2)] angle [99.78(3)] from 90 may be
ascribed to the steric repulsion between the two adjacent
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Table 3 Optimization of N-alkylation reaction conditionsa
Entry
Base
Alcohol–amine–base
Yieldb (%)
Aminec (%)
1
2
3
4
5
6
7
8
—
1 : 1
0
0
0
—
—
—
—
86
90
94
94
62
67
74
75
78
—
K2CO3
K2CO3
K2CO3
KOH
KOH
KOH
1 : 1 : 1
1 : 1 : 2
1 : 1 : 3
1 : 1 : 1
1 : 1 : 1.5
1 : 1 : 2
1 : 1 : 3
1 : 1 : 1
1 : 1 : 1.5
1 : 1 : 2
1 : 1 : 3
1 : 1 : 2
1 : 1 : 2
0
90
92
94
94
88
93
96
95
95
0
KOH
9
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
NaOH
NaHCO3
10
11
12
13
14
Fig. 3 ORTEP plot of complex [RuCl(CO)(AsPh3)(PNS-Ph)] (6). Thermal
ellipsoids have been drawn at the 50% probability level and hydrogen
atoms are omitted for clarity.
a Reaction conditions: 2.00 mmol of benzyl alcohol, 2.00 mmol of
2-aminopyridine, base (4 mmol), catalyst 1 (0.5 mol%) in 5 mL of
toluene at 100 °C. b Based on GC-MS of a crude reaction mixture.
c Conversions determined by GC-MS. Formation of the corresponding
imine as a byproduct accounts for the difference in conversion.
bulky phosphine molecules. The equatorial bond lengths are
2.127(11) [Ru(1)–N(1)] Å, 2.125(3) Å [Ru(1)–P(2)], 2.3859(8)
[Ru(1)–S(1)] Å and Ru(1)–P(2) = 2.3982(8) Å. For complexes
bearing P, N-iminophosphine ligands, the higher trans influ-
ence of the phosphorus atom in comparison to that of the
imine donor functionality leads to longer distances for bonds
trans to the phosphorus.36 On the other hand, in the presence
of tridentate P,N,S ligands (with N being an iminic nitrogen)
the reverse situation is usually observed;15 the related bond
distances in [RuCl(CO)(PPh3)(PNS-H)] (namely, Ru(1)–N(1) =
2.125(3) Å, Ru(1)–P(2) = 2.3982(8)) follow this rule. The other
two axial sites are occupied by a carbonyl group and one chlor-
ine ligand with Ru(1)–C(1A) and Ru(1)–Cl(1) distances of
1.88(2) Å and 2.441(4) Å. The CO group occupies the site trans
to the Cl (N(1)–Ru1–P(2) = 169.37(7)). This may be a conse-
quence of strong RuII→CO back donation as indicated by the
short Ru–C [1.88(2) Å] bond and the low CO stretching fre-
quency (1949 cm−1), which prefers σ or π weak donor groups
occupying the site opposite to CO to favor the d–π back
donation.
After a careful search of the literature concerning ruthe-
nium complexes derived from thiosemicarbazone ligands, we
have found several examples of ruthenium complexes with the
XNS (O, N, C) thiosemicarbazone ligand type.8b,16,37 Neverthe-
less, complexes containing Ru PNS thiosemicarbazone are still
scarce. Taking this fact into account, we must stress the
novelty of the ruthenium(II) complexes (1–6) reported in this
article, because it is the first example of phosphine-functiona-
lized thiosemicarbazone ruthenium(II) complexes.
bases such as K2CO3 and NaHCO3 were ineffective (entries 1–2
and 14). The reaction was considerably accelerated by the
addition of a strong base (entries 5–13). When the reaction
was carried out in the presence of KOH, N-benzylaminopyri-
dine was formed in an excellent yield (up to 99%), which we
considered to be the choice for the base (entries 5–8). Other
strong bases such as KOtBu and NaOH were also found
effective (entries 9–12 and 13). In addition, to obtain almost
quantitative yields and avoid the presence of the imine as a
secondary product, from a lack of hydrogenation of the con-
densation product, at least 2 equivalents of the base with
respect to the substrate are needed.
The ability to use small amounts of a catalyst and still
achieve high conversions is of great importance in N-alkylation
reactions due to the high cost of the metals and ligands used.
We continued the N-alkylation reaction optimization process
after finding the need for a strong base to activate the ruthe-
nium complex 1. The following step was to study the influence
of the terminal substituents, coligands and catalyst loadings
on the catalytic activity. The results are summarized in
Table 4. The blank experiment was carried out without a cata-
lyst, and no product formation is observed under these con-
ditions, which excluded the contribution of base itself as a
catalyst (entry 1). The results indicate that lower catalyst load-
ings lead to moderate yields, and longer reaction times are
required to achieve maximum conversion (entries 2–13). Also,
as expected, higher catalyst loadings led to higher yields and
higher amine content in the product distribution (entries
14–19). Furthermore, considering the results when 0.5 mol%
of the catalyst was used, it is clear that ruthenium complexes
containing the methyl group (entry 15) as a terminal substitu-
ent lead to higher yields than those containing hydrogen or
Catalytic studies
Optimization for N-alkylation reaction conditions. To investi-
gate a promising catalytic system, a screen was performed for a
model reaction between 2-aminopyridine and benzyl alcohol.
Representative results are shown in Table 3. In the absence of
a base, N-alkylation of amine was not observed (entry 1). Weak
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Table 4 Influence of terminal substituents, coligands and catalyst loading on the catalytic activity of ruthenium(II) complexesa
Terminal substituents
(R)/coligands
Amount [Ru]
(mol%)
Entry
[Ru]
Time (h)
Yieldb (%)
Aminec (%)
1
2
3
4
5
6
7
8
—
1
2
3
4
5
6
1
2
3
4
5
6
1
2
3
4
5
6
—
H/PPh3
—
24
24
24
24
24
24
24
18
18
18
18
18
18
12
12
12
12
12
12
—
71
64
59
68
67
56
89
84
75
87
83
74
83
>99
92
81
97
90
—
52
61
59
45
59
54
62
82
76
59
78
74
82
>99
91
78
97
89
0.1
0.1
0.1
0.1
0.1
0.1
0.3
0.3
0.3
0.3
0.3
0.3
0.5
0.5
0.5
0.5
0.5
0.5
Me/PPh3
Ph/PPh3
H/AsPh3
Me/AsPh3
Ph/AsPh3
H/PPh3
Me/PPh3
Ph/PPh3
H/AsPh3
Me/AsPh3
Ph/AsPh3
H/PPh3
Me/PPh3
Ph/PPh3
H/AsPh3
Me/AsPh3
Ph/AsPh3
9
10
11
12
13
14
15
16
17
18
19
a N-alkylation reaction conditions: 2.00 mmol of benzyl alcohol, 2.00 mmol of 2-amino pyridine, KOH (4 mmol), catalyst (0.1–0.5 mol%) in 5 mL
of toluene at 100 °C. b Based on GC-MS of a crude reaction mixture. c Conversions determined by GC-MS. Formation of the corresponding imine
as a byproduct accounts for the difference in conversion.
phenyl (entries 14 and 16) and significantly shorter reaction the effect of the substrates on the yield and selectivity of the
times are needed to complete the N-alkylation process. This catalytic reaction, using a 0.5 mol% loading of the catalyst in
behavior indicates that steric effects may also play an impor- toluene at 100 °C. The reactions of 2-aminopyridine with
tant role in terms of catalyst efficiency or in terms of the gene- benzyl alcohols bearing electron-donating and -withdrawing
ration of the catalytically active species. In addition, complexes substituents at the aromatic ring proceeded smoothly to give
1, 3, and 6 showed good activity at lower catalyst loadings, but the corresponding N-benzylaminopyridine in good to high
when the catalyst concentration was increased, it was not poss- yields (1a–1e). Benzyl alcohols with p-MeO, p-Cl and p-Br were
ible to obtain yields as high as those with their analogues. tolerant (1c–1e). The reaction of sterically demanding
However, it is important to note that, among complexes with 2-methylbenzyl alcohol also proceeded to give the corres-
methyl substituents in the terminal positions, those contain- ponding amine in good yield (1b). Similar to the case of
ing PPh3 and AsPh3 coligands (2 and 5) showed the best 2-aminopyridine, the N-alkylation of 2-aminopyrimidine with
selectivity toward the synthesis of the amine (entries 15 and benzyl alcohol and para-methyl, -methoxy substituted benzyl
18). Thus, electronic properties may also account for the cata- alcohols gave the corresponding products 2a–2c with 97, 86 and
lytic activity, although not as much as steric effects.
83% yields, respectively. The N-alkylation with benzyl alcohols
We believe that the catalytic amine alkylation with bearing a halogen atom (Cl or Br) proceeded to give the corres-
ruthenium(II) complexes follows the ‘borrowed hydrogen’ ponding products 2d and 2e with excellent yields as well. 2-Amino-
pathway, extensively studied by Williams, Fujita, Yamaguchi benzothiazole also reacted with benzylic alcohols to afford the
and others.19–27 The alcohol is catalytically dehydrogenated to desired products in 92, 81, 79, 97 and 94% yields, respectively
the corresponding aldehyde (in situ oxidation) in the first step. (3a–3e). Interestingly, the reaction of p-toluenesulfonamide with
Then, the aldehyde condenses with the amine to give an inter- benzylic alcohols afforded the corresponding alkylated sulfona-
mediate imine, which is subsequently hydrogenated mide in good to excellent yields (76–99%; 4a–4e). The present
(reduction) by the catalyst. Thus, there is no net H2 consump- protocol also performed for N-alkylation of amines such as ami-
tion in this process; however, the reaction benefits from being nobenzene, 2-aminopyridine, 4-methyl, 4-chloro and 4-bromoa-
run in a closed system preventing irreversible H2 loss.
niline with ferrocenemethanol in high yield (5a–5e).
N-alkylation of heterocyclic amines and amides. In order to
It is worth mentioning that complex 2 can also catalyze the
check the versatility of our catalysts, we decided to study the direct amination of 2-nitropyridine with benzyl alcohol, which
substrate scope of catalyst 2 with other amine/amide and is more sustainable for the synthesis of amines.38 Typically, a
alcohol derivatives. The results shown in Table 5 summarize mixture of 2-nitropyridine, potassium hydroxide, catalyst 2 and
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Table 5 N-alkylation of (hetero)aromatic amine/amide with alcohols
catalyzed by 2a,b
Scheme 5 Selective N,N’-dialkylation of diamine with alcohols cata-
lyzed by 2, and the isolated yields in %. Reaction conditions: 4 mmol of
alcohol, 2.00 mmol of diamine, base (4 mmol), catalyst 2 (1 mol%) in
5 mL of toluene at 120 °C.
tron-withdrawing substituents in the para position are well-tol-
erated, these reactions affording the dialkylated products in
yields ranging from 62 to 93% (4a–4e). Also, the reaction with
ferrocenemethanol did not distress the yield of the corres-
ponding dialkylated product (6f).
a Reaction conditions: 2.00 mmol of alcohol, 2.00 mmol of amine/
amide, base (4 mmol), catalyst 2 (0.5 mol%) in 5 mL of toluene at
100 °C. b Isolated yields.
N-alkylation of ortho-substituted anilines: synthesis of benz-
imidazoles, benzothiazoles and benzoxazoles. The most com-
monly used methods for the synthesis of benzazoles include
the condensation of ortho-substituted (–NH2 or –SH or –OH)
anilines with aldehydes,41 nitriles,42 carboxylic acids,43 or acyl
chlorides.44 Most of these methods are associated with limit-
ations such as poor selectivity, side reactions, tedious work-up
procedures and requirement of a special oxidation process.
Alternatively, few reports are also available on the synthesis of
benzazoles directly from alcohols.45 Recently, Ru/Xanthphos,46
Ru,47 and IBX48 have been applied for the synthesis of benz-
imidazoles. Deng et al. reported dppf [1,1′-bis(diphenyl-
phosphino)ferrocene] catalyzed synthesis of 2-arylbenzoxazoles
directly from o-nitrophenols and benzyl alcohols.49
Although the reaction conditions were similar to those of
the N-alkylation, the reaction took a longer time for com-
pletion at slightly higher temperatures. Various experiments
were carried out to optimize the N-alkylation of ortho-substi-
tuted anilines (Table 6). In order to explore the scope of the
present method, the reactions of o-substituted (–NH2 or –OH
or –SH) anilines were successfully performed with a variety of
alcohols (Table 7). The reaction of o-phenylenediamine was
carried out with benzyl alcohol to obtain 2-phenylbenzimid-
azole (7a) in 93% yield. Functionalized alcohols, such as
4-methoxybenzyl alcohol and 4-chlorobenzyl alcohol, were uti-
lized to afford the corresponding products 7b and 7c in 81 and
98% yields, respectively. Heterocyclic alcohol, 2-pyridylmetha-
nol, gave the corresponding product (7d) in high yield.
However, a low yield was obtained with an aliphatic alcohol,
isoamyl alcohol (7e). The reaction of 2-aminophenol with
benzyl alcohol and benzyl alcohols bearing an electron-donat-
ing group and an electron-withdrawing group afforded the
benzyl alcohol was heated at 100 °C for 12 h, and N-benzylpyri-
dine was obtained in 96% yield (Scheme 4). Apparently, the
reduction of a nitro group can be achieved by a hydrogen
transfer reduction with 2.
N-alkylation of heteroaromatic diamine. One of the out-
standing properties of the present catalyst is its high selectivity
for monoalkylation of heteroaromatic amines. Hence, it was of
interest to determine whether this selectivity for the monoalky-
lation of primary aromatic functions could be used for the
N,N-dialkylation of diamines. Only very few synthetic pro-
cedures for the preparation of such compounds can be found
in the literature.39 In most cases, these transformations are
either not selective or have to be performed in several steps
and thus lack in general applicability towards a broad range of
substrates.40 As evident from the results in Scheme 5, it is
possible to selectively monoalkylate both amino functions of
the diamine, affording the corresponding product (6a–6f) in
excellent yields. First, 2,6-diaminopyridine was reacted with
benzyl alcohol, which afforded N,N′-dibenzylpyridine-2,6-
diamine (87%; 6a). Next, several substituted benzyl alcohols
were employed and, as determined before for the alkylation of
heterocyclic amines (Table 5), both electron-donating and elec-
Scheme 4 Direct amination of nitropyridine with benzyl alcohol.
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Table 6 Optimization of reaction conditions for the synthesis of 2-aryl-
benzazoles catalyzed by ruthenium(II) complexesa
Terminal substituents
(R)/coligands
Time
(h)
Yieldb
(%)
Entry
[Ru]
Base
1
2
3
4
5
6
7
8
—
1
1
2
2
2
3
4
5
6
2
2
2
2
—
—
H/PPh3
H/PPh3
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOt-Bu
NaOH
K2CO3
NaHCO3
KOH
24
12
24
12
24
36
24
24
24
24
24
24
24
24
24
5
78
81
90
93
93
88
75
90
82
53
66
7
CH3/PPh3
CH3/PPh3
CH3/PPh3
C6H5/PPh3
H/AsPh3
CH3/AsPh3
C6H5/AsPh3
CH3/PPh3
CH3/PPh3
CH3/PPh3
CH3/PPh3
—
Scheme 6 Plausible mechanism of ruthenium catalyzed N-alkylation
of o-heterosubstituted anilines.
lent yields. In the case of benzyl alcohol (93%, 7k), 4-methoxy-
benzyl alcohol (81%, 7l) and 4-chlorobenzyl alcohol (96%,
7m), good to excellent yields were observed. The reaction was
also applied to 2-pyridylmethanol, but the desired products
were obtained in low yield.
9
10
11
12
13
13
14
11
82c
A possible mechanism to rationalize this transformation is
illustrated in Scheme 6. Starting from alcohol, catalytic hydro-
gen transfer to an appropriate H2 acceptor (Ru catalyst) via
“Oxidation 1” would lead to the formation of aldehyde A. Con-
densation of A with ortho-substituted anilines generate an
intermediate imine B, which can be in equilibrium with
dihydrobenzazole C. A second hydrogen-transfer process from
C then provides a route to benzazole D via “Oxidation 2” with
the ruthenium(II) catalyst. To confirm this, controlled experi-
ments were carried out with and without the ruthenium cata-
lyst (entries 1 and 5 respectively, Table 6). The yield of the
desired product decreased drastically without the ruthenium
catalyst. On the other hand reaction of o-phenylenediamine
with benzaldehyde instead of alcohol in the absence of a cata-
lyst gave 85% of 2-phenylbenzimidazole (entry 14, Table 6).
This confirmed that the ruthenium catalyst is mainly involved
in the oxidation of alcohols to aldehydes. Further experiments
are ongoing to explain these results.
a Reaction conditions: 3.00 mmol of benzyl alcohol, 2.00 mmol of,
o-phenylenediamine, base (4 mmol), catalyst (0.5 mol%) in 5 mL of
toluene at 120 °C. b GC-MS yield. Reaction with benzaldehyde
(2 mmol). c Reaction with benzaldehyde (2 mmol).
Table 7 N-alkylation of o-heterosubstituted aniline with alcohols cata-
lyzed by 2a,b
Conclusions
We have reported the synthesis and characterization of novel
air-stable complexes [RuCl(CO)(EPh3)(L)] (1–6), in which the
substituents on the terminal position of the ligands and coli-
gands have been modified. The crystal structures of three of
the complexes prepared, 1, 2, and 6, have been described. The
catalytic study of [RuCl(CO)(EPh3)(L)] complexes 1–6 toward
amine N-alkylation and one-pot synthesis of benzoxazoles was
completed, showing that all catalysts are active toward catalytic
transformations. The results also showed that steric effects in
the ligands play a more important role than electronic effects
in the catalytic activity of the new complexes. In the N-alkyl-
ation process, complex 2 has been proven to be a versatile and
efficient catalyst under mild conditions in comparison to its
analogues and other ruthenium and iridium complexes.50
Also, complex 2 has shown high tolerance to functional groups
a Reaction conditions:
3
mmol of alcohol, 2.00 mmol of
o-heterosubstituted aniline, base (4 mmol), catalyst 2 (0.5 mol %) in
5 mL of toluene at 120 °C. b Isolated yields.
corresponding products 7f–7i with 84–99% yields respectively.
In addition, heteroaromatic alcohol gave the corresponding
benzothioazole product in high yield. Reaction of aminothio-
phenol with benzyl alcohol and 4-substituted benzyl alcohols
afforded the desired 2-aryl substituted benzoxazoles in excel-
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in the amine and alcohol moieties. The present process is appli- with PNS-H (0.038 g, 0.105 mmol) and the mixture was gently
cable for the direct amination of 2-nitropyridine with benzyl refluxed for 6 h. During this time, the color changed to orange.
alcohol leading to the secondary amine with 2 as the catalyst. After it was cooled to room temperature, the suspension was
Furthermore, complex 2 has been proven to selectively catalyze filtered and the orange solid was thoroughly washed with cold
the synthesis of N,N-dialkylated amine when diamines are used ethanol and diethyl ether. Yield 78% (0.10 g), mp: 256–258 °C.
as substrates. On the other hand, complex 2 has been proven to Anal. Calcd for C39H32ClN3OP2RuS: C, 59.35; H, 4.09; N, 5.32;
be a very efficient and versatile catalyst for the synthesis of S, 4.06. Found: C, 59.49; H, 4.12; N, 5.14; S, 4.26. IR (KBr disks,
2-substituted benzimidazoles, benzoxazoles and benzothiazoles.
cm−1): 3434 (ms, νNH); 3064 (m, νNH); 1949 (s, νCuO); 1582 +
1474 (s, νCvN + νC–N); 742 (s, νC–S); 1434, 1089, 693 (s, for
1
PPh3). UV-Vis (CH2Cl2), λmax (nm): 234, 258, 343, 427. H NMR
(400 MHz, DMSO-d6): δ (ppm) = 8.73 (d, 1H, J = 8.8 Hz,
CHvN), 8.50 (s, –NH2), 7.71–7.53 (m, 4H, Ar H), 7.49–7.19 (m,
14H, Ar H), 7.13–7.09 (m, 4H, Ar H), 6.67 (t, 7H, J = 8.0 Hz, Ar
H), 6.55–6.51 (m, 4H, Ar H). 13C NMR (100 MHz, DMSO-d6): δ
(ppm) = 206.73 (CuO), 176.12 (C–S), 154.60 (–CHvN), 138.82
(Ar C), 137.43 (Ar C), 137.24 (Ar C), 136.05 (Ar C), 135.70 (Ar C),
135.60 (Ar C), 133.50 (Ar C), 133.36 (Ar C), 132.94 (Ar C),
129.87 (Ar C), 129.12 (Ar C), 129.01 (Ar C), 128.85 (Ar C),
128.78 (Ar C), 128.01 (Ar C), 127.44 (Ar C), 125.55 (Ar C),
125.26 (Ar C). 31P NMR (162 MHz, DMSO-d6): δ (ppm) = 30.05
(d, J = 22.6 Hz, PPh3), 28.74 (d, J = 22.6 Hz, PPh2). MS (ESI,
m/z): 753.6 [M − Cl]+. Single crystals suitable for an X-ray deter-
mination were grown by slow evaporation of dichloromethane–
methanol solution of 1 at room temperature.
[RuCl(CO)(PPh3)(PNS-Me)] (2). It was prepared as described
for 1 by the suspension of [RuHCl(CO)(PPh3)3] (0.100 g,
0.105 mmol) with PNS-Me (0.039 g, 0.105 mmol). Yield 73%
(0.10 g), mp: 254–256 °C. Anal. Calcd for C40H34ClN3OP2RuS:
C, 59.81; H, 4.27; N, 5.23; S, 3.99. Found: C, 59.49; H, 4.09; N,
5.14; S, 4.26. IR (KBr disks, cm−1): 3420 (ms, νNH); 1945 (s,
νCuO); 1584 + 1471 (s, νCvN + νC–N); 747 (s, νC–S); 1432, 1091,
695 (s, PPh3). UV-Vis (CH2Cl2), λmax (nm): 233, 245, 355, 430.
1H NMR (400 MHz, DMSO): δ (ppm) = 8.75 (d, 1H, J = 8.0 Hz
–CHvN); 8.57 (s, 1H, –NH), 7.62–7.58 (m, 1H, Ar H), 7.56–7.13
(m, 24H, Ar H), 6.89 (t, 2H, J = 10.8 Hz, Ar H), 6.78 (t, 1H, J =
11.2 Hz, Ar H), 6.72 (t, 2H, J = 11.6 Hz, Ar H), 1.22 (s, 3H,
–CH3). 13C NMR (100 MHz, DMSO-d6): δ (ppm) = 206.48
(CuO), 176.45 (C–S), 155.53 (–CHvN), 136.48 (Ar C), 135.27
(Ar C), 133.84 (Ar C), 132.17 (Ar C), 131.95 (Ar C), 130.71 (Ar C),
130.61 (Ar C), 130.55 (Ar C), 130.38 (Ar C), 130.27, (Ar C),
129.65 (Ar C), 127.91 (Ar C), 127.86 (Ar C), 127.79 (Ar C),
127.65 (Ar C), 127.53 (Ar C), 127.30 (Ar C), 126.51 (Ar C),
126.33 (Ar C), 125.45 (Ar C), 123.81 (Ar C), 123.53 (Ar C), 31.17
(–CH3). 31P NMR (162 MHz, DMSO-d6): δ (ppm) = 30.15 (d, J =
22.6 Hz, PPh3), 28.85 (d, J = 25.9 Hz, PPh2). MS (ESI, m/z):
794.1 [M − Cl]+. Orange colored crystals obtained in the
reaction mixture itself were found to be suitable for X-ray
diffraction.
Experimental section
General
Unless otherwise noted, all reactions were performed under an
atmosphere of air. Thin-layer chromatography (TLC) was per-
formed on Merck 1.05554 aluminum sheets precoated with
silica gel 60 F254, and the spots were visualized with UV light
at 254 nm or under iodine. Column chromatography purifi-
cations were performed by using Merck silica gel 60
(0.063–0.200 mm). Elemental analyses (C, H, N, S) were per-
formed on a Vario EL III Elemental analyzer. Infrared spectra
of the ligands and the metal complexes were recorded as KBr
discs in the range of 4000–400 cm−1 using a Nicolet Avatar
model FT-IR spectrophotometer. The electronic spectra of the
complexes were recorded with a Shimadzu UV-1650 PC
spectrophotometer using dichloromethane as the solvent. 1H
(300 and 400 MHz), 13C (100 MHz) and 31P NMR (162 MHz)
spectra were taken in DMSO or CDCl3 at room temperature
with a Bruker AV400 instrument with chemical shifts relative
to tetramethylsilane (1H, 13C) and o-phosphoric acid (31P).
Mass spectra were recorded on a LC-MS Q-ToF Micro Analyzer
(Shimadzu), using the electrospray ionization (ESI) mode. GC-
mass spectrometry was performed using a JEOL GCMATE II
GC-MS system. The melting points were recorded with a Lab
India melting point apparatus.
Commercially available RuCl3·3H2O was used as supplied
from Loba Chemie Pvt. Ltd. All the reagents used in this study
were of Analar grade, and the solvents were purified and dried
according to standard procedures. Triphenylphosphine/triphenyl-
arsine, 2-(diphenylphosphino)-benzaldehyde and thiosemicar-
bazone derivatives were purchased from Aldrich and were used
as received. The ruthenium metallic precursors [RuHCl(CO)-
(PPh3)3] and [RuHCl(CO)(AsPh3)3] were prepared according to
literature methods.51
Synthesis of the ligands
The ligands 2-(2-(diphenylphosphino)benzylidene) thiosemi-
carbazone (PNS-H) and 2-(2-(diphenylphosphino)benzylidene)-
N-methylthiosemicarbazone (PNS-Me) 2-(2-(diphenylphos-
phino)benzylidene)-N-phenylthiosemicarbazone (PNS-Ph) were
prepared following the procedure reported previously.9–15
[RuCl(CO)(PPh3)(PNS-Ph)] (3). It was prepared as described
for 1 by the suspension of [RuHCl(CO)(PPh3)3] (0.100 g,
0.105 mmol) with PNS-Ph (0.039 g, 0.105 mmol). Yield 78%
(0.10 g), mp: 254–256 °C. Anal. Calcd for C45H36ClN3OP2RuS:
C, 62.46; H, 4.19; N, 4.86; S, 3.71. Found: C, 62.61; H, 4.21; N,
4.94; S, 3.91. IR (KBr disks, cm−1): 3390 (ms, νNH); 1962 (s,
Synthesis of the complexes
[RuCl(CO)(PPh3)(PNS-H)] (1). A suspension of [RuHCl(CO)- νCuO); 1591 + 1482 (s, νCvN + νC–N); 738 (s, νC–S); 1433, 1092,
(PPh3)3] (0.100 g, 0.105 mmol) in ethanol (15 mL) was treated 694 (s, PPh3). UV-Vis (CH2Cl2), λmax (nm): 236, 256, 369, 428.
7898 | Dalton Trans., 2014, 43, 7889–7902
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1H NMR (400 MHz, DMSO-d6): δ (ppm) = 8.75 (d, 1H, J = (Ar C), 133.54 (Ar C), 133.12 (Ar C), 132.91 (Ar C), 132.80 (Ar C),
8.7 Hz, –CHvN), 8.60 (s, 1H, –NH), 7.68 (d, 2H, J = 8.4 Hz, 131.79 (Ar C), 131.68 (Ar C), 131.38 (Ar C), 131.29 (Ar C),
Ar H), 7.63 (s, 2H, Ar H), 7.57–7.46 (m, 9H, Ar H), 7.33 (t, 6H, 131.03 (Ar C), 130.48 (Ar C), 130.32 (Ar C), 129.89 (Ar C),
J = 6.3 Hz, Ar H), 7.25–7.16 (m, 9H, Ar H), 7.06 (t, 2H, J = 7.2 129.06 (Ar C), 128.64 (Ar C), 128.41 (Ar C), 128.10 (Ar C),
Hz, Ar H), 6.90 (t, 1H, J = 6.9 Hz, Ar H), 6.78 (t, 1H, J = 8.4 Hz, 128.00 (Ar C), 30.60 (–CH3). 31P NMR (162 MHz, DMSO-d6): δ
Ar H), 6.59 (t, 2H, J = 8.7 Hz, Ar H). 13C NMR (100 MHz, (ppm) = 32.73 (s, PPh2). MS (ESI, m/z): 811.8 [M − Cl]+.
DMSO-d6): δ (ppm) = 206.40 (CuO), 170.42 (C–S), 156.56
[RuCl(CO)(AsPh3)(PNS-Ph)] (6). It was prepared as described
(–CHvN), 136.93 (Ar C), 136.76 (Ar C), 136.13 (Ar C), 136.05 for
4
by suspension of [RuHCl(CO)(AsPh3)3] (0.100 g,
(Ar C), 134.39 (Ar C), 133.81 (Ar C), 133.73 (Ar C), 133.50 (Ar C), 0.092 mmol) with PNS-Ph (0.039 g, 0.092 mmol). Yield 76%
133.40 (Ar C), 133.30 (Ar C), 133.27 (Ar C), 133.08 (Ar C), (0.105 g), mp: 132–134 °C. Anal. Calcd for C45H36AsClN3O-
132.00 (Ar C), 131.90 (Ar C), 131.68 (Ar C), 131.30 (Ar C), PRuS: C, 59.44; H, 3.99; N, 4.62; S, 3.53. Found: C, 59.28; H,
131.15 (Ar C), 130.58 (Ar C), 130.24 (Ar C), 129.96 (Ar C), 3.89; N, 4.81; S, 3.26. IR (KBr disks, cm−1): 3390 (ms, νNH);
128.90 (Ar C), 128.91 (Ar C), 128.73 (Ar C), 128.66 (Ar C), 1962 (s, νCuO); 1591 + 1482 (s, νCvN + νC–N); 738 (s, νC–S); 1433,
128.57 (Ar C), 128.48 (Ar C), 128.30 (Ar C), 128.05 (Ar C), 1092, 694 (s, for AsPh3). UV-Vis (CH2Cl2), λmax (nm): 235, 258,
127.95 (Ar C), 127.75 (Ar C), 127.66 (Ar C), 126.66 (Ar C), 367, 429. 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 8.74 (d, 1H,
126.24 (Ar C), 121.16 (Ar C), 119.07 (Ar C). 31P NMR (162 MHz, J = 7.6 Hz, –CHvN), 8.52 (s, 1H, –NH), 7.88–7.85 (m, 1H, Ar
DMSO-d6): δ (ppm) = 29.79 (d, J = 22.6 Hz, PPh3), 28.85 (d, J = H), 7.74 (d, 2H, J = 7.6 Hz, Ar H), 7.63–7.10 (m, 27H, Ar H),
22.6 Hz, PPh2). MS (ESI, m/z): 830.2 [M − Cl]+.
6.89 (t, 1H, J = 7.2 Hz, Ar H), 6.72–6.60 (m, 1H, Ar H), 6.57 (t,
[RuCl(CO)(AsPh3)(PNS-H)] (4). A suspension of [RuHCl(CO)- 2H, J = 8.8 Hz, Ar H). 13C NMR (100 MHz, DMSO-d6): δ (ppm)
(AsPh3)3] (0.100 g, 0.105 mmol) in ethanol (15 mL) was treated = 206.45 (CuO), 170.73 (C–S), 155.68 (–CHvN), 135.48 (Ar C),
with PNS-H (0.038 g, 0.105 mmol) and the mixture was gently 135.27 (Ar C), 133.84 (Ar C), 132.35 (Ar C), 131.17 (Ar C),
refluxed for 8 h. During this time, the colour changed to 129.95 (Ar C), 124.40 (Ar C), 123.71 (Ar C), 123.61 (Ar C),
yellow. Then the solvent was removed under reduced pressure, 123.55 (Ar C), 123.38 (Ar C), 123.27 (Ar C), 122.65 (Ar C),
and the solid was washed thoroughly with cold ethanol and 122.51 (Ar C), 122.36 (Ar C), 122.11 (Ar C), 121.89 (Ar C),
diethyl ether, affording a shiny yellow crystalline solid. Yield 121.53 (Ar C), 121.20 (Ar C), 121.11 (Ar C), 120.73 (Ar C),
82% (0.11 g), mp: 110–112 °C. Anal. Calcd for C39H32AsClN3O- 120.45 (Ar C), 119.02 (Ar C), 116.81 (Ar C), 115.82 (Ar C). 31P
PRuS: C, 56.22; H, 3.87; N, 5.04; S, 3.85. Found: C, 56.49; H, NMR (162 MHz, DMSO-d6): δ (ppm) = 31.38 (s, PPh2). MS (ESI,
3.79; N, 5.14; S, 3.66. IR (KBr disks, cm−1): 3392 (ms, νNH); m/z): 873.0 [M − Cl]+. Single crystals suitable for an X-ray deter-
1962 (s, νCuO); 1592 + 1496 (s, νCvN + νC–N); 738 (s, νC–S); 1433, mination were grown by slow evaporation of dichloromethane–
1092, 694 (s, for AsPh3). UV-Vis (CH2Cl2), λmax (nm): 231, 245, ethanol solution of 6 at room temperature.
350, 427. 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 8.86 (d, 1H,
J = 8.3 Hz, –CHvN), 8.48 (s, 1H, –NH2), 7.86 (t, 1H, J = 7.2 Hz,
Catalysis
Ar H), 7.75–7.02 (m, 23H, Ar H), 6.89 (t, 3H, J = 7.2 Hz, Ar H),
6.70 (t, 1H, J = 8.8 Hz, Ar H), 6.57 (m, 2H, J = 7.2 Hz, Ar H). 13
C
Catalytic N-alkylation of (hetero)aromatic amines and amide
NMR (100 MHz, DMSO-d6): δ (ppm) = 206.02 (CuO), 176.04 with alcohols. A typical procedure is as follows. To a stirred
(C–S), 154.59 (–CHvN), 138.91 (Ar C), 136.53 (Ar C), 134.41 (Ar suspension of ruthenium(II) catalyst (0.5 mol%) and KOH
C), 134.02 (Ar C), 133.92 (Ar C), 133.52 (Ar C), 133.19 (Ar C), (4 mmol) in toluene (5 mL) were added alcohol (2.0 mmol)
133.11 (Ar C), 132.08 (Ar C), 131.81 (Ar C), 131.16 (Ar C), and amine/amide (2.0 mmol) at room temperature and then
130.64 (Ar C), 130.39 (Ar C), 130.02 (Ar C), 128.84 (Ar C), the temperature was raised to 100 °C for 12 h. Upon com-
128.66 (Ar C), 128.51 (Ar C), 128.17 (Ar C), 128.08 (Ar C), pletion (as monitored by TLC), the reaction mixture was cooled
125.21 (Ar C). 31P NMR (162 MHz, DMSO-d6): δ (ppm) = 32.13 at ambient temperature, H2O (3 mL) was added and the
(s, PPh2). MS (ESI, m/z): 767.6 [M − Cl]+.
organic layer was extracted with CH2Cl2 (3 × 10 mL). The com-
[RuCl(CO)(AsPh3)(PNS-Me)] (5). It was prepared as bined organic layers were dried with magnesium sulfate and
described for 4 by suspension of [RuHCl(CO)(APh3)3] (0.100 g, concentrated. The crude product was analyzed by GC-MS or
0.092 mmol) with PNS-Me (0.034 g, 0.092 mmol). Yield 78% purified by column chromatography (n-hexane–EtOAc). The
(0.10 g), mp: 120–122 °C. Anal. Calcd for C40H34AsClN3OPRuS: reported isolated yields are the average of two runs.
C, 56.71; H, 4.05; N, 4.96; S, 3.78. Found: C, 56.87; H, 4.31; N,
Direct amination of 2-nitropyridine with benzyl alcohol. To
4.81; S, 3.26. IR (KBr disks, cm−1): 3423 (ms, νNH); 1945 (s, a stirred suspension of ruthenium(II) catalyst (0.5 mol%) and
νCuO); 1585 + 1490 (s, νCvN + νC–N); 747 (s, νC–S); 1432, 1091, KOH (4 mmol) in toluene (5 mL) were added benzyl alcohol
695 (s, for AsPh3). UV-Vis (CH2Cl2), λmax (nm): 235, 257, 356, (12.0 mmol) and 2-nitropyridine (2.0 mmol) at room tempera-
1
435. H NMR (400 MHz, DMSO-d6): δ (ppm) = 8.77 (d, 1H, J = ture and then the temperature was raised to 100 °C for 12 h.
8.0 Hz, –CHvN), 8.15 (s, 1H, –NH), 7.63–7.10 (m, 24H, Ar H), Upon completion (as monitored by TLC), the reaction mixture
6.89–6.86 (m, 1H, Ar H), 6.72 (t, 1H, J = 7.6 Hz, Ar H), 6.55 (t, was cooled at ambient temperature, H2O (3 mL) was added and
2H, J = 8.0 Hz, Ar H), 1.22 (s, 3H, –CH3). 13C NMR (100 MHz, the organic layer was extracted with CH2Cl2 (3 × 10 mL). The
DMSO-d6): δ (ppm) = 206.42 (CuO), 176.03 (C–S), 154.27 combined organic layers were dried with magnesium sulphate
(–CHvN), 138.91 (Ar C), 134.00 (Ar C), 133.90 (Ar C), 133.79 and concentrated. The crude product was analyzed by GC-MS or
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purified by column chromatography (n-hexane–EtOAc). The
reported isolated yields are the average of two runs.
Acknowledgements
Catalytic N-alkylation of heteroaromatic diamine with alco- The authors wish to record grateful thanks to Prof. Bruno
hols. To a stirred suspension of ruthenium(II) catalyst (0.1 mol%) Therrien, Institute of Chemistry, University of Neuchatel,
and KOH (4 mmol) in toluene (5 mL) were added alcohol Switzerland for crystal data collection of structure 2. The
(4 mmol) and diamine (2.0 mmol) at room temperature and authors also acknowledge the Indian Institute of Technology,
then the temperature was raised to 120 °C for 12 h. Upon com- Chennai and Indian Institute of Science, Bangalore for provid-
pletion (as monitored by TLC), the reaction mixture was cooled ing instrumental facilities.
at ambient temperature, H2O (3 mL) was added and the
organic layer was extracted with CH2Cl2 (3 × 10 mL). The com-
bined organic layers were concentrated in vacuo and the crude
product was analyzed by GC-MS or purified by column chrom-
atography over silica-gel (n-hexane–ethyl acetate). The reported
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7902 | Dalton Trans., 2014, 43, 7889–7902
This journal is © The Royal Society of Chemistry 2014