Accepted Manuscript

Research paper

Synthesis of Heteroleptic Copper(I) Complexes with Phosphine-Functionalized

Thiosemicarbazones: Efficient Catalyst for Regioselective N-Alkylation Reac-
tions

Rangasamy Ramachandran, Govindan Prakash, Paranthaman Vijayan,

Periasamy Viswanathamurthi, Jan Grzegorz Malecki

PII: S0020-1693(16)30900-8
DOI: http://dx.doi.org/10.1016/j.ica.2017.05.003
Reference: ICA 17571

To appear in: Inorganica Chimica Acta

Received Date: 18 November 2016

Revised Date: 31 March 2017
Accepted Date: 2 May 2017

Please cite this article as: R. Ramachandran, G. Prakash, P. Vijayan, P. Viswanathamurthi, J. Grzegorz Malecki,
Synthesis of Heteroleptic Copper(I) Complexes with Phosphine-Functionalized Thiosemicarbazones: Efficient
Catalyst for Regioselective N-Alkylation Reactions, Inorganica Chimica Acta (2017), doi: http://dx.doi.org/
10.1016/j.ica.2017.05.003

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 Synthesis of Heteroleptic Copper(I) Complexes with Phosphine-
Functionalized Thiosemicarbazones: Efficient Catalyst for Regioselective N-
Alkylation Reactions

Rangasamy Ramachandran,a Govindan Prakash,a Paranthaman Vijayan,a, † Periasamy

Viswanathamurthi,*a Jan Grzegorz Maleckib

a
Department of Chemistry, Periyar University, Salem-636 011, India.
b
Department of Crystallography, Silesian University, Szkolna 9, 40-006 Katowice, Poland.

† Present address: Department of Chemistry, University of Delhi, Delhi, India.

*To whom correspondence should be made, e-mail: viswanathamurthi72@gmail.com;

Fax: +91 427 2345124

1
Abstract

Three new heteroleptic copper(I) complexes [Cu(PPh3)(PNS-H)] (1) (PNS-H = 2-(2-

(diphenylphosphino)benzylidene) thiosemicarbazone), [Cu(PPh3)(PNS-Me)] (2) (PNS-Me = 2-
(2-(diphenylphosphino)benzylidene)-4-methyl-3-thiosemicarbazone) and [Cu(PPh3)(PNS-Et)]
(3) (PNS-Et = 2-(2-(diphenylphosphino)benzylidene)-4-ethyl-3-thiosemicarbazone) have been
synthesized and characterized by various spectral and analytical technique. The single-crystal X-
ray diffraction study of complexes 2 and 3 confirmed the formation of complexes with Cu(I) ion,
coordinated through P,N,S-donor atoms from the phosphino-thiosemicarbazone ligands. All the
copper(I) complexes have been demonstrated as highly efficient catalysts for the synthesis of N-
alkylated heterocyclic amine by the coupling of primary amines with alcohols at low catalyst
loading, and the maximum yield was obtained up to 99%. The N-alkylation reactions were
readily carried out under moderate conditions, and release of water was the only by-product. In
addition, the effects of substituent’s on the ligand, solvents, base and catalyst loading on the
catalytic activity of the complexes have also been investigated. Advantageously, only one
equivalent of the alcohol was consumed in the process.

Keywords: Phosphine ligands; Thiosemicarbazones; Copper(I) complexes; Heterocyclic

amines; Regioselective N-alkylation.

2
Introduction
There is continued interest in research into the coordination chemistry of CuI-phosphine
complexes due to their wide application in homogeneous catalysis.1-3 In particular, heteroleptic
copper(I) complexes have been attracted much interest due to their rich structural chemistry, high
reactivity and unusual redox properties.4-7 Such complexes often contain weakly-bonded ligands
making them highly suitable in mechanistic studies. They are also very useful as precursors in
synthesis and they may readily give active sites in catalysis.8 In this regard, a vast number of
CuI-phosphine complexes have been prepared including very few reports on heteroleptic CuI
phosphorus-donor complexes.9

In recent years, the chemistry and properties of metal thiosemicarbazone complexes have
been extensively reported.10 On the other hand, the coordination behaviour of thiosemicarbazone
ligands toward M(I) ions is still a partially explored field. Owing to their insolubility in different
solvents, structural studies involving M(I) thiosemicarbazones are mainly focused in Cu(I)
complexes.11,12 Tertiary phosphines are known for their solubilising effect in heterocyclic
copper(I) thioamide complexes and therefore it is being useful ligands to construct M(I)
heteroleptic complexes.13 In spite of their synthetic versatility and practical utility, studies on the
heteroleptic complexes of CuI with phosphino-thiosemicarbazone and phosphane ligands are
scarce.

N-Alkylated heterocyclic amines are ubiquitous structural motifs of many natural

products and pharmaceutically active compounds. In particular,
2-N-(alkylamino)azoles exhibit a wide range of pharmacological and physiological activities.14
Traditionally, 2-N-(alkylamino)azoles are prepared by cyclocondensation reactions of two
functionalized precursors (e.g. Hantszch aminothiazole synthesis). Transition metal-catalyzed
cyclization reactions have been developed for the preparation of 2-N-(alkylamino)azoles,
including cyclizations of o-halobenzothioureas,15 benzothioureas,16 or domino
condensation/coupling/cyclization of o-haloanilines, carbon disulfide and alkylamines. However,
these procedures are only available for the synthesis of benzo-fused 2-N-(alkylamino)azoles.17
Transition metal-catalyzed direct oxidative couplings of azoles with amines,18 chloramines19 or
formamides20 provide another access to 2-N-(alkylamino)azoles. These procedures generally
suffer from high catalyst loadings, more stoichiometric amounts of oxidants or other additives,

3
and low yields. It was well documented that the N-alkylation of amino-azoles with alkyl halides
occurs on the most basic endocyclic nitrogen, affording N-endosubstituted 3-alkyl-2-
iminobenzothiazolines as products (Scheme 1, left).21 Recently, much attention has been paid to
the N-alkylation of amines with alcohols as environmentally benign alkylating agents instead of
alkyl halides based on a transition metal-catalyzed ‘‘hydrogen auto transfer (or hydrogen-
borrowing) process’’.22 In this article, the regioselective N-alkylation of 2-aminobenzothiazoles
to N-exosubstituted 2-(N-alkylamino)benzothiazoles using alcohols as alkylating agents have
been described (Scheme 1, right).

In continuation of our ongoing research in the utility of transition metal complexes

incorporated with thiosemicarbazone ligands for various organic transformations,23 the Cu(I)
have been selected as the catalytic system here because it is cost-effective and has emerged for
the N-alkylation of amines and sulfonamides with alcohols.24 Influenced by the above facts, it
was considered worthwhile to undertake the synthesis, structural characterization and study of
the catalytic properties of three new heteroleptic copper(I) complexes containing flexible
phosphine-functionalized thiosemicarbazone ligands together with PPh3 as coligands.

Experimental section
General considerations. All reagents were purchased from Aldrich as high-purity products and
generally used as received; all solvents were used as received as technical-grade solvents. The
starting complex [Cu(PPh3)2(CH3COO)]25 and phosphino-thiosemicarbazones26 were prepared
according to published procedures. Elemental analyses were performed using a Vario EL Series
III CHNS analyzer. IR spectra were collected on a Nicolet Avatar model FT-IR
spectrophotometer. NMR spectra were recorded on a Bruker AV400 spectrometer (1H, 400
13 31
MHz; C, 100 MHz and P, 162 MHz). The melting points were checked with a Lab India
melting point apparatus. Crystals of 2 and 3 were mounted on glass fibers and used for data
collection. Crystal data were collected at 293(2) K (2 and 3) using a Gemini A Ultra Oxford
Diffraction automatic diffractometer Graphite monochromated Mo-Kα radiation
(λ = 0.71073 Å) was used throughout. The absorption corrections were performed by the multi-
scan method. Corrections were made for Lorentz and polarization effects. The structures were
solved by direct methods using the program SHELXS-97.27 Refinement and all further
calculations were carried out using SHELXL-97.27 The H atoms were included in calculated

4
positions and treated as riding atoms using the SHELXL default parameters. The non-hydrogen
atoms were refined anisotropically, using weighted full-matrix least squares on F2. Atomic
scattering factors were incorporated in the computer programs. Structures 2 and 3 have solvent
accessible voids which rise alert level A. In structure 3, the alert level B is due to the water
molecule in the crystal structure.

Synthesis of heteroleptic copper(I) phosphino-thiosemicarbazone complexes (1-3)

[Cu(PNS-H)PPh3] (1): A suspension of [Cu(CH3COO)(PPh3)2] (0.194 g, 0.3 mmol) in CH2Cl2
(10 mL) was treated with PNS-H (0.109 g, 0.3 mmol) in ethanol and the mixture was gently
refluxed for 3 h. During this time the color changed to yellow. The solvent was reduced to half of
the volume on a rotary evaporator, and the suspension was filtered, washed thoroughly with cold
ethanol (10 mL) and diethyl ether (2 х 5 mL). The product was finally dried under vacuum,
affording a yellow solid in 79% yield. Mp: 216 °C. Anal. Calcd for C38H32CuN3P2S: C, 66.32; H,
4.69; N, 6.11; S, 4.66%. Found: C, 66.43; H, 4.62; N, 6.02; S, 4.56%. IR (KBr discs, cm−1): 3423
(m, νNH); 1542 + 1513 (s, νC=N + νC−N); 743 (s, νC−S), 1434, 1093, 693 (s, PPh3). 1H NMR (400
MHz, DMSO-d6, ppm): 6.55−6.51 (m, 4H, Ar H), 6.67 (t, 7H, J = 8.0 Hz, Ar H), 7.13−7.09 (m,
4H, Ar H), 7.49−7.19 (m, 11H, Ar H), 7.71−7.53 (m, 4H, Ar H), 8.23 (s, 1H, CH=N), 8.41 (s,
−NH2). 13C NMR (100 MHz, DMSO-d6): 121.17 (Ar C), 119.33 (Ar C), 125.26 (Ar C), 125.55
(Ar C), 127.44 (Ar C), 128.01 (Ar C), 128.78 (Ar C), 128.85 (Ar C), 129.01 (Ar C), 129.12 (Ar
C), 129.87 (Ar C), 132.94 (Ar C), 133.36 (Ar C), 133.50 (Ar C), 144.60 (−CH=N), 146.12
(C−S). 31P NMR (162 MHz, DMSO-d6, ppm): −1.03 (PPh3), −3.62 (PPh2).

[Cu(PNS-Me)PPh3] (2): The red color complex 2 was prepared and isolated by adopting the
same method as described for 1 and using PNS-Me (0.113 g, 0.3 mmol). Yield, 78%. Mp: 229
°C. Anal. Calcd for C39H34CuN3P2S: C, 67.70; H, 4.88; N, 5.98; S, 4.57%. Found: C, 67.84; H,
4.93; N, 5.91; S, 4.52%. IR (KBr discs, cm−1): 3441 (m, νNH); 1540 + 1478 (m, νC=N + νC−N); 745
(s, νC−S), 1434, 1093, 694 (s, PPh3). 1H NMR (400 MHz, DMSO-d6, ppm): 2.88 (d, 3H, J = 4.4
Hz, −CH3), 6.79 (s, 1H, Ar H), 7.07−7.22 (m, 27H, Ar H), 7.33 (t, 1H, J = 3.6 Ar H), 7.35 (s,
13
1H, −NHterminal), 8.14 (s, 1H, −CH=N). C NMR (100 MHz, DMSO-d6, ppm): 18.35 (−CH3),
128.20 (Ar C), 128.30 (Ar C), 129.26 (Ar C), 129.50 (Ar C), 132.45 (Ar C), 132.67 (Ar C),
133.50 (Ar C), 133.62 (Ar C), 134.18 (−CH=N), 147.22 (C−S). 31P NMR (162 MHz, DMSO-d6,

5
ppm): −1.02 (PPh3), −3.84 (PPh2). Single crystals suitable for an X-ray determination were
grown by slow evaporation of dichloromethane-ethanol solution of 2 at room temperature.

[Cu(PNS-Et)PPh3] (3): The red color complex 3 was prepared and isolated by adopting the same
method as described for 1 and using PNS-Et (0.117 g, 0.3 mmol). Yield 82%, Mp: 265 °C, Anal.
Calcd for C40H36CuN3P2S: C, 67.07; H, 5.07; N, 5.87; S, 4.48%. Found: C, 67.01; H, 5.12; N,
5.80; S, 4.40%. IR (KBr discs, cm−1): 3229 (m, νNH); 1558 (m, νC=N) 1534, 1478 (s, νC−N); 745 (s,
νC−S). 1433, 1093, 694 (s, PPh3) 1H NMR (400 MHz, DMSO-d6, ppm): 1.15−1.24 (m, 3H,
−CH3), 1.90 (s, 2H, −CH2), 7. 38 (t, 1H, J = 7.2 Ar H), 7.25−7.29 (m, 28H, Ar H), 7.16 (t, 1H, J
13
= 7.2 Hz, Ar H), 8.19 (s, IH, −CH=N). C NMR (100 MHz, DMSO-d6, ppm): 14.52 (−CH3),
34.12 (−CH2), 119.33 (Ar C), 121.18 (Ar C), 128.07 (Ar C), 128.14 (Ar C), 128.28 (Ar C),
128.66 (Ar C), 129.18 (Ar C), 129.39 (Ar C), 129.46 (Ar C), 131.57 (Ar C), 131.77 (Ar C),
132.46 (Ar C), 132.59 (Ar C), 133.32 (Ar C), 133.45 (Ar C), 133.70 (Ar C),140.90 (−CH=N),
149.70 (C=S). 31P NMR (162 MHz, DMSO-d6, ppm): −1.07 (PPh3), −3.78 (PPh2). Single crystals
suitable for an X-ray determination were grown by slow evaporation of dichloromethane-ethanol
solution of 3 at room temperature.

Typical procedure for N-alkylation of (hetero)aromatic amines with alcohols

In a 25 mL round bottomed flask were placed 0.1 mol% of copper(I) catalyst, 1 mmol of
alcohol, 1 mmol of amine, 0.2 mmol of KOH and 2 mL of toluene. The reaction flask was heated
at 100 °C for 12 h in an oil bath. Upon completion (as monitored by TLC), the reaction mixture
was cooled at ambient temperature, H2O (3 mL) was added and the organic layer was extracted
with CH2Cl2 (3 х 10 mL). The combined organic layers were dried with magnesium sulphate and
concentrated. The crude product was purified by column chromatography (ethyl acetate/hexane)
and conformed by 1H NMR spectroscopy (S11−S17, ESI†). Reported isolated yields are an
average of two runs.

Results and discussion

Synthesis and characterization of heteroleptic copper(I) complexes
The phosphino-thiosemicarbazone ligands (PNS-H, PNS-Me and PNS-Et) were
synthesized from the condensation reaction of 2-diphenylphosphinebenzaldehyde with
thiosemicarbazide, 4-N-methylthiosemicarbazide and 4-N-ethylthiosemicarbazide respectively,

6
following the published procedure.26 The heteroleptic complexes [Cu(PPh3)2(PNS-X)] (X = H,
Me, Et) were prepared by treating an ethanolic solution of the phosphino-thiosemicarbazone
ligands and dichloromethane solution of [Cu(PPh3)2(CH3COO)] in 1:1 molar ratio (Scheme 2).
All the complexes are found air-stable, with melting point ranging from 229–286 °C. They are
soluble in dichloromethane, chloroform, N,N-dimethylformamide (DMF) and dimethyl sulfoxide
(DMSO). The compounds were characterized by elemental analyses, spectral (IR and NMR)
(Fig. S1 and S7, ESI†) and single-crystal X-ray analysis.

Crystal structure

The structures of 2 and 3 were determined by X-ray diffraction. The ORTEP diagrams of 2 and 3
are given in Figs. 1-2. The selected bond lengths, angles, and their refinement data are
summarized in Table 1-2. The single crystal X-ray studies revealed that the complexes 2 and 3
are crystallized in an orthorhombic system with the space group Pccn. The coordination
geometry around the Cu(I) ion in complexes 2 and 3 is distorted tetrahedron, the copper atom
being bounded to uninegative tridentate PNS donor molecules in such a way that five and six
membered ring formed. The remaining site is occupied by triphenylphosphine. In the complexes
2 and 3 the coordination sphere is same and the general structural motifs differ only in the
terminal substitution (R = Me and Et). Thus the structure of one of the Cu(I) complex 2 (Fig. 1)
will be described in detail here. The bond length Cu(1)-N(1); 2.101(2), Cu(1)-S(1); 2.3045(9),
Cu(1)-P(1); 2.2521(8) of four and five membered ring and Cu(1)-P(2); 2.2606(9) Å, which agree
very well with those that are reported for copper(I) complexes.28 The tetrahedron angles of
P(1)−Cu(1)−P(2); 125.24(3)o and N(1)−Cu(1)−P(1); 86.10(7)o, which showed a deviation from
the expected angles, suggesting distortion in the tetrahedral coordination geometry. The large
deviation of the [P(1)−Cu(1)−P(2)] angle [~125o] from 109o may be ascribed to the steric
repulsion between the two adjacent bulky phosphine molecules. In addition, complexes 2 and 3
contains two types of intermolecular hydrogen bond N(3)−H(3)····N(2) and C(32)−H(32)···S(1)
with bond distance of 2.166, 2.938 Å, respectively, and one intramolecular hydrogen bond
C(23)−H(23)···S(1) with bond distance of 2.963 Å (Fig. S8 and S9, ESI†).

Spectroscopy studies

7
 A strong band observed at 1594−1583 cm-1 in the ligands corresponding to νC=N was
shifted to 1558−1540 cm-1 in all the complexes indicating the participation of azomethine
nitrogen in bonding.26b A sharp band observed at 758−742 cm-1, ascribed to νC=S in the ligands,
has completely disappeared in the spectra of all the new copper complexes and the appearance of
a new band around 745 cm-1 due to νC−S indicated the coordination of the sulfur atom after
enolization followed by deprotonation.29 In addition, vibrations corresponding to the presence of
PPh3 also appeared in the expected region. The 1H NMR spectra of the ligands and their
complexes (1−3) show the signals in the expected regions. The singlets that appeared for the N–
NH–C=S proton of the free ligands at 11.94−11.53 ppm are absent in the complexes, supporting
the enolization and coordination of the thiolate sulphur to the Cu(I) ion. A singlet due to
azomethine proton (8.23−8.14 ppm) in the complexes are slightly downfield compared to the
free ligands (8.79−8.64 ppm), suggesting deshielding upon coordination to Cu(I) ion. The
spectra of the complexes showed a singlet at 8.41−8.13 ppm, which has been assigned to NH−R
protons. Further, the spectra of all the complexes showed a series of signals for aromatic protons
at 7.53−6.51 ppm. The terminal methyl proton peak appeared at 2.88 ppm for complex 2. In
addition, two peaks appeared at 1.15−1.24 and 1.90 ppm corresponding to terminal ethyl group
13
protons for complex 3. The C NMR spectra show the expected signals in the appropriate
regions. For the uncoordinated ligands, the C=N and C=S signals appear in the regions around
141.41−140.25 and 178.93−175.81 ppm respectively. Upon coordination and formation of the
new Cu(I) complexes, the C=N and C−S carbon signals appeared in the region between
144.60−134.18 and 149.70−146.12 ppm. This is consistent with the P, N, S coordination and
thioenolization of the C=S of thiosemicarbazone moieties. In all the complexes (1−3), aromatic
carbon atoms of the phenyl group observed around 133.70−119.33 ppm are comparable to the
literature values.30 The presence of PPh3 and PPh2 moieties coordinated to Cu(I) is also
confirmed by 31P NMR, where two singlets are observed in the region −1.02 to −1.07 ppm and
−3.78 to −3.84 ppm.

Regioselective N-alkylation of amino-azoles

Initial studies were performed using 2-aminobenzothiazole and benzyl alcohol as

building blocks and toluene as the solvent, under various reaction conditions and the results are
depicted in table 3. To ensure its catalytic role, a control experiment was performed in the

8
absence of base or copper catalyst and, as expected, there was no reaction even after a prolonged
reaction time of 12 h (entries 1 and 9). Weak bases such as K2CO3 and Cs2CO3 were ineffective
(entries 2 and 3). The reaction was considerably accelerated by the addition of a strong base.
Strong bases, such as KOtBu and NaOH were found effective (entries 4 and 8). When the
reaction was carried out in the presence of KOH, N-alkylated amine was formed in an excellent
yield (upto 99%), which we considered to be the choice of the base (entry 5−7, 10 and 11).
Furthermore, considering the results when 0.1 mol% of catalyst was used, it is clear that copper
catalyst lead to higher yields (entries 5-7). The results also indicate that the catalyst 2 is the
efficient catalyst among all, because of the presence of the least electron donating moiety (+I
effect), which appears to lead to an improvement in activity (entries 6, 10 and 11). However,
lower yield was observed in the case of [Cu(CH3COO)(PPh3)2] complex as a catalyst for this
reaction (Entry 12).

With the optimized conditions in hand, we sought to explore the scope of N-alkylation of
various heterocyclic amines, diamines with alcohols to afford the corresponding secondary
amines; the results are summarized in table 4. The reactions of 2-aminopyridine with benzyl
alcohols bearing electron-donating and -withdrawing substituent’s at the aromatic ring proceeded
smoothly to give the corresponding N-alkylated amines in good to high yields (4a−4d). The
reaction was also applied to 2-pyridylmethanol, affording the desired product 4e with 85% yield.
In the case of the aliphatic alcohol with 2- aminobenzothiazoles, the desired product 4f was
successfully obtained in 84% yield. The N-alkylation of different substituted 2-
aminobenzothiazoles was then studied. N-akylation of 2-aminobenzothiazoles bearing p-Cl and
p-OMe groups afforded the corresponding N-alkylated products in 99 and 98% yields (4g and
4h). The result showed that the presence of electron releasing group on the aromatic ring
proceeded higher yield. Unsubstituted benzylic alcohol also provided the desired products in
excellent yield (4i). Remarkably 4,5-diphenyl-2-aminothiazole also gave the required products in
good yields (4j, 4k and 4l). The compatibility of the catalytic system with heterocycles diamine
was demonstrated, and very good result (4m) was obtained for the N,N’-dialkylation of 2,6-
diaminopyridine with benzylalcohol using the catalyst 2. Reaction of o-phenylenediamine with
benzyl alcohol afforded the desired 2-substituted benzimidazole in 76% isolated yield (4n). 4-
Methoxylbenzyl alcohol could also be alkylated, revealing the formation of solely 2-(4-
methoxyphenyl)-1H-benzimidazole in 83% yield after 12 h of reaction time (4o).

9
Conclusion

Three new heteroleptic CuI phosphino-thiosemicarbazone complexes (1-3) have been

designed and synthesized by the reactions of [Cu(CH3COO)(PPh3)2] with deprotonated
diphenylphosphinobenzaldehyde 4N-substituted thiosemicarbazones. The structures of the
complexes 2 and 3 were established by X-ray crystallography. Single crystal XRD upshots of
complexes revealed a distorted tetrahedral geometry around the copper ion with
thiosemicarbazone acts as a monoanionic tridentate PNS donor fashion. The catalytic study of
the complexes 1-3 towards regioselective N-alkylation reactions of amines was completed, which
shows that all catalysts are active toward catalytic transformations. Notably, the complex 2 was
found to be very efficient catalyst towards N-alkylation of a wide range of heterocyclic amines
with alcohols. This catalysis provides a clean, convenient and practical route for the direct N-
alkyl amine synthesis in view of the following advantages: (1) The reaction proceeds smoothly
and effectively under moderate conditions. (2) The catalyst is readily available, cheap and stable
that offers easy handling and ready work-up. (3) The present method is applicable in the
synthesis of various N-alkyl amines, including useful aromatic and heteroaromatic amines, in
high yields.

Acknowledgment

The authors are grateful to Indian Institute of Technology, Chennai, Indian Institute of Science,
Bangalore and Punjab University, Chandigarh, for providing instrumental facilities.

Appendix A. Supplementary material

Synthesis and spectral data for ligands and complexes. Experimental procedures and spectral
data for N-alkylated products. CCDC reference number 1517368 and 1517367 for complex 2 and
3. This data can be obtained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.

10
 References

1. (a) S. Lal, H. S. Rzepa, S. Díez-Gonzlez, ACS Catal. 4 (2014) 2274-2287; (b) S-L. Zhang,
W-F. Bie, L. Huang, Organometallics 33 (2014) 5263-5271; (c) Campbell-Verduyn, L. S.;
Mirfeizi, L.; Dierckx, R. A.; Elsinga, P. H.; Feringa, B. L. Chem. Commun. 2009, 2139-2141.
2. (a) S.S. Chavan, S.K. Sawant, S.B. Pawal, M.S. More, Polyhedron 105 (2016) 192-199; (b)
F. Perez-Balderas, M. Ortega-Munoz, J. Morales-Sanfrutos, F. Hernandez-Mateo, F. G.
Calvo-Flores, J. A. Calvo-Asin, J. Isac-Garcia, F. Santoyo-Gonzalez, Org. Lett. 5 (2003)
1951-1954.
3. (a) D. Wang, M. Zhao, X. Liu, Y. Chen, N. Li, B. Chen, Org. Biomol. Chem. 10 (2012) 229-
231; (b) L. Li, P. S. Lopes, V. Rosa, C. A. Figueira, M. A. N. D. A. Lemos, M. T. Duarte, T.
Aviles, P. T. Gomes, Dalton Trans. 41 (2012) 5144-5154; (c) Z. Gonda, Z. Novak, Dalton.
Trans. 39 (2010) 726-729; (d) D. Wang, N. Li, M. Zhao, W. Shi, C. Ma, B. Chen, Green
Chem. 12 (2010) 2120-2123; (e) S.-Q. Bai, L.L. Koh, A. Hor, Inorg. Chem. 48 (2009) 1207-
1213.
4. D. R. McMillin, K.M. McNett, Chem. Rev. 98 (1998) 1201-1220.
5. N. Armaroli, Chem. Soc. Rev. 30 (2001) 113-124.
6. N. Armaroli, G. Accorsi, F. Cardinali, A. Listorti, Top. Curr. Chem. 280 (2007) 69-115.
7. R. Peng, M. Li, D. Li, Coord. Chem. Rev. 254 (2010) 1-18.
8. I.P. Beletskaya, A.V. Cheprakov, Organometallics 31(2012) 7753-7808.
9. (a) S. Guo, M- H Lim, H- V Huynh, Organometallics, 32 (2013) 7225-7233; (b) L. Li, P. S.
Lopes, C. A. Figueira, C. S. B. Gomes, M. T. Duarte, V. Rosa, C. Fliedel, T. Avilés, P. T.
Gomes, Eur. J. Inorg. Chem. (2013) 1404-1417; (c) F. Lazreg, A. M. Z. Slawin, C. S. J.
Cazin Organometallics, 31 (2012) 7969-7975; (d) L. Li, P. S. Lopes, V. Rosa, C. A.
Figueira, M. A. N. D. A. Lemos, M. T. Duarte, T. Avilés, P. T. Gomes, Dalton Trans., 41
(2012) 5144-5154.
10. J.S. Casas, M.S. Garcıa-Tasende, J.Sordo, Coord. Chem. Rev. 209 (2000)
197-261.
11. T.S. Lobana, S. Rekha, R.J. Butcher, A. Castineiras, E. Bermejo,
P.V. Bharatam, Inorg. Chem. 45 (2006) 1535-1542.

11
12. T.S. Lobana, S. Kanna, G. Hundal, P. Kaur, B. Thakur, S. Attri, R. J. Butcher, Polyhedron,
28 (2009) 1583-1593.
13. T. S. Lobana, A. Castineiras, Polyhedron, 21 (2002) 1603-1611.
14. Z.Y. Sun, Z. Zhu, Y. Ye, B. McKittrick, M. Czarniecki, W. Greenlee,
D. Mullins, M. Guzzi, Bioorg. Med. Chem. Lett. 19 (2009) 6801-1805.
15. L.L. Joyce, G. Evindar, R.A. Batey, Chem. Commun. (2004) 446-447.
16. L.L. Joyce, R.A. Batey, Org. Lett. 11 (2009) 2792-2795.
17. D. Ma, X. Lu, L. Shi, H. Zhang, Y. Jiang, X. Liu, Angew. Chem., Int. Ed. 50 (2011)1118-
1121.
18. J.Y. Kim, S.H. Cho, J. Joseph, S. Chang, Angew. Chem., Int. Ed. 49 (2010) 9899-9903.
19. T. Kawano, K. Hirano, T. Satoh, M. Miura, J. Am. Chem. Soc. 132 (2010) 69001.
20. S.H. Cho, J.Y. Kim, S.Y. Lee, S. Chang, Angew. Chem., Int. Ed. 48 (2009) 9127-9130.
21. J.V. Metzger, in Thiazoles and their Benzo Derivatives. Comprehensive Heterocyclic
Chemistry, Pergamon Press Ltd, New York, 6 (1984) 235-331.
22. (a) G. E. Dobereiner, R. H. Grabtree, Chem. Rev. 110 (2010) 681-703; (b) G. Guillena, D.
Ramon, M. Yus, Chem. Rev. 110 (2010) 1611-1641.
23. (a) S. Selvamurugan, R. Ramachandran, G. Prakash, M. Nirmala, P. Viswanathamurthi, S.
Fujiwara, A. Endo. Inorg. Chim. Acta. 454 (2017) 46-53; (b) R. Ramachandran, G. Prakash,
M. Nirmala, P. Viswanathamurthi, J. G. Malecki, J. Organomet. Chem. 791 (2015) 130-140;
(c) R. Ramachandran, G. Prakash, S. Selvamurugan, P. Viswanathamurthi, J. G. Malecki, W.
Linert, A. Gusev, RSC Adv., 2015, 5, 11405-11422; (d) R. Manikandan, P. Anitha, G.
Prakash, P. Vijayan, P. Viswanathamurthi, R. J. Butcher, J. C. Malecki, J. Mol. Catal. A:
Chem. 398 (2015) 312-324; (e) R. Ramachandran, G. Prakash, S. Selvamurugan, P.
Viswanathamurthi, J. G. Malecki, V. Ramkumar. Dalton Trans. 43 (2014) 7889-7902
24. A. J. A. Watson, J. M. J. Williams, Science 329 (2010) 635-636.
25. M.B. Ferrari, F. Bisceglie, E. Buluggiu, G. Pelosi, P. Tarasconi, Polyhedron 29 (2010) 2134-
2141.
26. (a) A. Castineiras, R. Pedrido, Dalton Trans., 41 (2012) 1363-1372; (b) A. Castineiras, R.
Pedrido, Inorg. Chem., 48 (2009) 4847–4855.

27. G. M. Sheldrick, Acta Crystallogr. A64 (2008) 112-122.

28. A. Castineiras, R. Pedrido, Dalton Trans. 39 (2010) 3572-3584.

12
29. P. Kalaivani, R. Prabhakaran, P. Poornima, F. Dallemer, K. Vijayalakshmi, V. Vijaya Padma,
K. Natarajan, Organometallics 31 (2012) 8323-8332.
30. A. Castineiras, R. Pedrido, Inorg. Chem. 47 (2008) 5534-5536.

Y Y R OH Y R
R X
NH NH2 NH
N -H2O -H2O N
N
R
X = Halide, Y = S/O, R = alkyl/aryl This work
Previous reports

Scheme 1 Regioselective N-alkylation of heterocyclic amines with alkyl halides and

alcohols.

13
 S
N R
N N O PPh3
H H C2H5OH/CH2Cl2
P P N
+ Cu N
Reflux, 3h Cu
O PPh3 S NH
PPh3 R
R = H, HLPH
R = Me, HLPMe R = H, (1)
R = Et, HLPEt R = Me, (2)
R = Et, (3)

Scheme 2 Synthesis of heteroleptic Cu(I) phosphino-thiosemicarbazone (1-3) complexes.

14
Fig. 1 ORTEP plot of complex 2. Thermal ellipsoids have been drawn at the 50% probability
level.

15
Fig. 2 ORTEP plot of complex 3. Thermal ellipsoids have been drawn at the 50% probability
level. Water molecule has been omitted for clarity.

Table 1 Crystal data and structure refinement parameters for complexes 2 and 3.

2 3
Empirical formula C39H34CuN3P2S C40H36CuN3P2S.H2O
Formula weight 702.23 734.31
T (K) 293(2) 293(2)
Wavelength (Å) 0.71073 0.71073

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Crystal system Orthorombic Orthorombic
Space group Pccn Pccn
Unit cell dimensions
a (Å) 10.0489(11) 10.1781(4)
b (Å) 30.210 (3) 30.5954(13)
c (Å) 25.6646 (19) 25.4095(10)
α (ᵒ) 90 90
β (ᵒ) 90 90
γ(ᵒ) 90 90
Volume (Å3) 7791.3 (12) 7912.6 (6)
Z 8 4
Density (calculated)
1.192 1.216
Mg m-3
Absorption coefficient
0.725 0.717
mm-1
F(000) 2912 3008
scan range for data
3.450 to 24.996 3.696 to 25.049
collection (deg)
-11< = h< = 10 -11< = h< = 12
Index ranges -34< = k< = 35 -35< = k< = 36
-30< = l< = 28 -30< = l< = 22
Reflections
26445/6789,0.0407 26759/9600,0.0430
collected/unique, Rint
Completeness to
0.991 0.996
thetamax
Data/restraints/
6789/0/416 6990/0/430
Parameters
Goodness-of-fit on F2 0.979 0.999
Final R indices [I R1 = 0.0455, R1 =0.0523,
>2σ(I)]a wR2 = 0.1318 wR2 = 0.1651
R1 = 0.0561, R1 = 0.0788,
R indices (all data)
wR2 = 0.1318 wR2 = 0.1651

Table 2 Selected geometrical parameters for complexes 2 and 3.

2 3
Interatomic distances (Å)
Cu(1)-P(1) 2.2521(8) Cu(1)-P(1) 2.2542(10)
Cu(1)-N(1) 2.101(2) Cu(1)-N(1) 2.109(3)
Cu(1)-S(1) 2.3045(9) Cu(1)-S(1) 2.3020(11)

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 C(8)-S(1) 1.724(3) C(8)-S(1) 1.728(5)
N(1)-N(2) 1.371(3) N(1)-N(2) 1.367(4)
Cu(1)-P(2) 2.2606(9) Cu(1)-P(2) 2.2509(11)
Bond angles(ᵒ)
P(2)-Cu(1)-P(1) 125.24(3) P(2)-Cu(1)-P(1) 123.76(4)
N(1)-Cu(1)-P(1) 86.10(7) N(1)-Cu(1)-P(1) 85.35(9)
N(1)-Cu(1)-S(1) 83.13(7) N(1)-Cu(1)-S(1) 83.14(9)
N(1)-Cu(1)-P(2) 115.66(7) N(1)-Cu(1)-P(2) 118.74(9)
S(1)-Cu(1)-P(1) 118.57(3) S(1)-Cu(1)-P(1) 117.45(4)
S(1)-Cu(1)-P(2) 113.75(3) S(1)-Cu(1)-P(2) 115.48(4)

Table 3 N-alkylation of 2-aminobenzothiazole with benzyl alcohol under various conditions.a

Catalyst Yield
Entry Catalyst Base
(mol%) (%)b
1 [Cu(LPH)PPh3](1) 0.20 - 0
2 [Cu(LPH)PPh3](1) 0.20 K2CO3 52

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 3 [Cu(LPH)PPh3](1) 0.20 Cs2CO3 72
4 [Cu(LPH)PPh3](1) 0.20 NaOH 80
5 [Cu(LPH)PPh3](1) 0.20 KOH 92
6 [Cu(LPH)PPh3](1) 0.10 KOH 94
7 [Cu(LPH)PPh3](1) 0.05 KOH 89
8 [Cu(LPH)PPh3](1) 0.10 NaOtBu 78
9 - - KOH 0
10 [Cu(LPMe)PPh3](2) 0.10 KOH 99
11 [Cu(LPEt)PPh3](3) 0.10 KOH 90
12 [Cu(CH3COO)(PPh3)2] 0.10 KOH 43
a
Reaction conditions: 2-aminobenzothiazole (1 mmol), benzyl alcohol (1 mmol), CuI catalyst,
base (0.2 mmol), toluene (2 mL), at 100 oC for 12 h. bIsolated yield.

Table 4 N-alkylation of amines with various alcohols.a,b

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 S OH S
2 (0. 10 mol%)
NH2 + R NH
KOH,toluene
N N R
100oC, 12h

S
S
NH S Cl
NH
N NH
N
N
O
4a, 94% 4b, 96% 4c, 98%

H
S Br S S N
NH NH N
N N N

4d, 89% 4e, 85% 4f, 84%

Cl S Cl S Cl S
NH NH NH
N Cl N O N

4g, 99% 4h, 98% 4i, 95%

Ph H
Ph S S N
S Ph
NH
NH N
Ph N Cl
Ph N
Ph
4j, 92% 4k, 96% 4l, 77%

H
HN N NH N S

N N

4m, 89% 4n, 75% 4o, 84%

a
Reaction conditions: 2-aminobenzothiazole (1 mmol), benzyl alcohol
(1 mmol), CuI (0.10 mol%), KOH (0.2 mmol), toluene (2 mL), at 100 oC for 12
h. bIsolated yield.
:
Highlights

 Heteroleptic copper(I) thiosemicarbazone complexes were designed and synthesized.

 The ligands coordinated to Cu(I) ion via PNS fashion.
 The catalytic efficiency towards N-alkylation of amines with alcohols has been reported.
 Maximum yield was obtained (up to 99%) for low catalyst loading.

20
Graphical Abstract Synopsis
Heteroleptic copper(I) complexes with phosphine-functionalized thiosemicarbazones were
designed, synthesized and applied to N-alkylation of amines with alcohols under moderate
condition.

Graphical Abstract Pictogram

21