Synthesis, characterization, catalytic activity, and DFT calculations of Zn(II) Hydrazone complexes

Article abstract of DOI:10.3390/molecules25184043

Two new Zn(II) complexes with tridentate hydrazone-based ligands (condensation products of 2-acetylthiazole) were synthesized and characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy and single crystal X-ray diffraction methods

Full text of DOI:10.3390/molecules25184043

molecules
Article
Synthesis, Characterization, Catalytic Activity, and
DFT Calculations of Zn(II) Hydrazone Complexes
3
Temiloluwa T. Adejumo 1, Nikolaos V. Tzouras 2, Leandros P. Zorba 2, Dušanka Radanovic´
,
3
5
1
Andrej Pevec 4, Sonja Grubišic´ , Dragana Mitic´ , Katarina K. And¯elkovic´ ,
Georgios C. Vougioukalakis 2,
*
, Božidar Cobeljic´
*
and Iztok Turel 4,
*
1,
ˇ
1
Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade, Serbia;
adejumo.temiloluwa@gmail.com (T.T.A.); kka@chem.bg.ac.rs (K.K.A.)
2
3
4
5
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens,
Panepistimiopolis, 15771 Athens, Greece; nitzouras@gmail.com (N.V.T.); leozor888@gmail.com (L.P.Z.)
Center for Chemistry, ICTM, University of Belgrade, Njegoševa 12, P.O. Box 815, 11001 Belgrade, Serbia;
radanovic@chem.bg.ac.rs (D.R.); sonja.grubisic38@gmail.com (S.G.)
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Vecˇna pot 113,
1000 Ljubljana, Slovenia; Andrej.Pevec@fkkt.uni-lj.si
Innovation Centre of Faculty of Chemistry, University of Belgrade, Studentski trg 12–16,
11000 Belgrade, Serbia; dmitic@chem.bg.ac.rs
ˇ
*
Correspondence: vougiouk@chem.uoa.gr (G.C.V.); bozidar@chem.bg.ac.rs (B.C.);
Iztok.Turel@fkkt.uni-lj.si (I.T.); Tel.: +30-210-727-4230 (G.C.V.); +381-69-262-8978 (B.C.);
+386-1-479-8525 (I.T.)
ˇ
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editors: Andreas A. Danopoulos and Georgios C. Vougioukalakis
Received: 13 August 2020; Accepted: 3 September 2020; Published: 4 September 2020
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: Two new Zn(II) complexes with tridentate hydrazone-based ligands (condensation
products of 2-acetylthiazole) were synthesized and characterized by infrared (IR) and nuclear
magnetic resonance (NMR) spectroscopy and single crystal X-ray diffraction methods. The
complexes
1
,
2
and recently synthesized [ZnL3(NCS)2] (L3 = (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-
were tested as potential catalysts
(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium) complex
3
for the ketone-amine-alkyne (KA2) coupling reaction. The gas-phase geometry optimization of newly
synthesized and characterized Zn(II) complexes has been computed at the density functional
theory (DFT)/B3LYP/6–31G level of theory, while the highest occupied molecular orbital and
lowest unoccupied molecular orbital (HOMO and LUMO) energies were calculated within the
time-dependent density functional theory (TD-DFT) at B3LYP/6-31G and B3LYP/6-311G(d,p) levels of
theory. From the energies of frontier molecular orbitals (HOMO–LUMO), the reactivity descriptors,
such as chemical potential (
) have been calculated. The energetic behavior of the investigated compounds (
examined in gas phase and solvent media using the polarizable continuum model. For comparison
reasons, the same calculations have been performed for recently synthesized [ZnL3(NCS)2] complex
DFT results show that compound has the smaller frontier orbital gap so, it is more polarizable and
is associated with a higher chemical reactivity, low kinetic stability and is termed as soft molecule.
µ
), hardness (
η), softness (S), electronegativity (
χ) and electrophilicity index
(
ω
1
and ) has been
2
3.
1
Keywords: Girard’s T reagent; hydrazone ligand; Zn(II) complexes; XRD; ketone-amine-alkyne
coupling reaction; catalysis; DFT calculation
1. Introduction
Hydrazone ligands are one of the most important classes of flexible and versatile polydentate
ligands which show very high efficiency in chelating various metal ions [1–13]. The coordination
behavior of hydrazones is known to depend on the pH of the medium, the nature of the
Molecules 2020, 25, 4043; doi:10.3390/molecules25184043
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Molecules 2020, 25, 4043
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substituents and on the position of the hydrazone group relative to other moieties [
2–
4]. Moreover,
deprotonation of the –NH group, which is readily achieved in the complexed ligand in particular,
results in the formation of tautomeric anionic species (=N–N−–C=O or =N–N=C–O−), having
different coordination properties.
ligands is partly due to their potential applications as catalysts [
Hydrazone ligands, obtained from Girard’s T reagent (trimethylammoniumacetohydrazide
chloride) and 2-acetylpyridine or 2-quinolinecarboxaldehyde
HL3Cl
Our interest in metal complexes with hydrazone-based
5
,6
] and molecular magnets [ ].
7
(
=
(E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride
and HL4Cl = (E)-N,N,N-trimethyl-2-oxo-2-(2-(quinolin-2-ylmethylene)hydrazinyl)ethan-1-aminium
chloride) are tridentate ligands which show the potential to form mononuclear and binuclear
structures with metal ions [
) [
], [CdHL3(NCS)2(SCN)] [
[CdL4(NCO)1.64Cl0.36] [10] and [CoHL4(N3)3] [
3
,
4
8
,
6
,
8
–
10]. In the mononuclear complexes (e.g., [ZnL3(NCS)2]
], [ZnL4(N3)2] [ ], [ZnL4(NCO)2] [ ], [ZnL4(N3)1.65Cl0.35] [10],
]) with one hydrazone ligand being coordinated in a
(3
8
9
9
4
tridentate fashion to the central metal ion, the vacant coordination sites are filled by monodentate
ligands (pseudohalides/halides) and in some cases by counter anions of starting metal salts [11]. In the
other type of mononuclear structures two hydrazone ligand molecules occupy the coordination sphere
of the central metal ion forming an octahedral coordination geometry (e.g., [CoL32][Co(NCS)4]BF4 [12
]
and Zn(II) complex with the 2-acetylthiazole (N4)-phenylthiosemicarbazone ligand (CCDC
1059843) [13]). In the binuclear [M2(L4)2(µ1,1-N3)2(N3)2]
H2O CH3OH (M = Ni(II) and Co(II)) [ ] and
[Cu2(L3)2(µ1,1-N3)2](ClO4)2 [
] complexes, the hydrazone-based ligands show the same tridentate
·
·
3,4
6
N,N,O-coordination mode forming the octahedral structure in the former two complexes cooperatively
with two bridging and one terminal azide anion per metallic center and the square pyramidal in the
latter with two bridging azides.
On the other hand, the propargylamines are a unique family of organic compounds, which has
received ample attention by the wider scientific community [14
these compounds is partly due to the bioactive nature of certain members of their family [14
Furthermore, propargylic amines are frequently encountered as intermediates in organic synthesis,
providing facile access to a variety of structurally complex organic compounds [14 15]. Among
,
15]. The profound interest surrounding
–
17].
,
these compounds, the subgroup of tetrasubstitutedpropargylamines is particularly interesting, as it
comprises the least studied family of propargylamines. The most straightforward approach towards
such molecules is the ketone-amine-alkyne (KA2) multicomponent coupling reaction, for which a
significant number of catalytic systems has been reported during the past decade [18
the work of some authors focusing on sustainable organic transformations, multicomponent reactions
and sustainable metal catalysis [19
33], the first zinc-based homogeneous catalytic system for the KA2
–28]. As part of
–
coupling was disclosed very recently [34]. Since the use of ligands in these catalytic systems is rare, we
were interested in testing well-defined zinc complexes as potential catalysts for the reaction operating
under air.
Herein, we report the synthesis and characterization of two new Zn(II) complexes
[ZnL1(NCS)2]
·
2H2O (
trimethylammoniumacetohydrazide chloride (Girard’s T reagent) and thiosemicarbazide, respectively.
The structures of and were characterized by infrared (IR) and nuclear magnetic resonance
(NMR) spectroscopy and single crystal X-ray diffraction methods. The catalytic activity of and
and the previously characterized [ZnL3(NCS)2]
0.5MeOH [ ] complex has been evaluated in the
ketone-amine-alkyne (KA2) coupling reaction. The experimental studies on the catalytic activities
of 0.5MeOH [ ] ( ) complex have been accompanied
and recently synthesized [ZnL3(NCS)2]
1 2)with the condensation products of 2-acetylthiazole and
) and [Zn(L2)2] (
1
2
1
2
·
8
3
1,
2
·
8
3
by density functional theory (DFT) calculations. We used B3LYP, a density functional theory-based
approach, to describe the structures and molecular properties of the compounds of interest. The global
reactivity descriptors, namely, chemical potential (µ), hardness (η), softness (S), electronegativity (χ),
and electrophilicity index (ω) have been evaluated from highest occupied molecular orbital (HOMO)
and lowest unoccupied molecular orbital (LUMO) energy values.

Molecules 2020, 25, 4043
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2. Results and Discussion
2.1. Synthesis
The ligand (HL1Cl), (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)
ethan-1-aminium chloride, was obtained from the condensation reaction of 2-acetylthiazole and Girard’s
T reagent. By the reaction of ligand HL1Cl with Zn(OAc)2
·
4H2O and NH4SCN in excess in solvent
, with the composition [ZnL1(NCS)2]
2H2O,
, Zn(II) is pentacoordinated with the thiazole nitrogen,
mixture of water/methanol, mononuclear Zn(II) complex
was obtained (Scheme 1a). In complex
1
·
1
the azomethine nitrogen, and the carbonyl oxygen atoms from the deprotonated hydrazone ligand
and two thiocyanate ligands coordinated through the nitrogen atoms. Reaction of ligand HL2
((E)-2-(1-(thiazol-2-yl)ethylidene)hydrazine-1-carbothioamide) with Zn(BF4)2
1:1:2.3 molar ratios, in a mixture of acetonitrile/water, gives mononuclear Zn(II) complex
composition [Zn(L2)2] (Scheme 1b). Two deprotonated ligands L2 are coordinated to Zn(II) ion through
·
6H2O and NaN3 in a
, with
2
the thiazole nitrogen, the imine nitrogen, and the thiolate sulfur atoms, forming a distorted octahedral
complex. Complex
similar structure to complex 1 (Scheme 1c).
3
, with composition [ZnL3(NCS)2]
0.5MeOH was previously reported [8] and has a
·
Scheme 1. Synthesis of:
(
a
) [ZnL1(NCS)2] ) [Zn(L2)2] (
2H2O (1) complex; (b 2) complex; (c)
·
[ZnL3(NCS)2]·0.5MeOH (3) complex.
2.2. Crystal Structures of [ZnL1(NCS)2]·2H2O (1) and [Zn(L2)2] (2) Complexes
The molecular structure of
1 is shown in Figure 1. Selected bond distances and angles are given in
Table 1. The neutral complex [ZnL1(NCS)2] crystallizes as dihydrate in the triclinic crystal system with
space group P 1. In 1
, Zn1 has fivefold coordination with tridentate ligand L1 and two nitrogen atoms
−
(N5, N6) from thiocyanate ligands. L1 is coordinated to Zn1 in the zwitterionic form through NNO-set
of donor atoms forming two fused five-membered chelate rings (Zn–N–C–C–N and Zn–N–N–C–O).
The dihedral angle of nearly 4.0◦ between two five-membered chelate rings shows the non-coplanar

Molecules 2020, 25, 4043
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nature of metal-ligand system. Generally, the distortion in the five coordinated systems is described
by an index of trigonality is the greatest basal angle and is the second
= (β − α)/60, where
greatest angle [35]. The parameter is 0 for regular square based pyramidal forms and 1 for trigonal
bipyramidal forms. The value of 0.36 calculated for , indicates that the irregular coordination
geometry about Zn1 is 36% trigonally distorted square-based pyramidal. The greatest basal angles
O1 Zn1 N1 and N2 Zn1
N5 are 149.20(7)◦ and 127.42(10)◦, respectively. The Zn1 is lifted out of the
plane of the four in-plane ligand atoms (O1, N1, N2 and N5) by a distance of 0.6091(3) Å. The complex
shows slightly greater degree of trigonal distortion from ideal square-based pyramidal configuration,
τ
β
α
τ
τ
1
−
−
−
−
ρ
1
in comparison with the other five-coordinate Zn(II) complexes with N-heteroaromaticmonohydrazones
of Girard’s T reagent and pseudohalide or halide ligand (N3−, NCO−, NCS− or Cl−) as monodentate for
which the calculated
Materials) [ 10]. The
Zn(II)complexes [36 40] (complexes
is more strongly bound to the imine nitrogen atom of the ligand L1 than to the 1,3-thiazole nitrogen,
τ
values are in the range 0.31–0.34 (complexes
values for complexes fit into the range of values obtained for related
15, Table S1 in the Supplementary Materials). The Zn(II) ion in
3–6, Table S1 in the Supplementary
8–
τ
1, 3–6
–
7–
1
as indicated by the Zn1–N2, 2.058(2) Å and Zn1–N1, 2.212(2) Å bond lengths (Table 2). Similar to this,
in analogous Zn(II) complexes with Girard’s T hydrazone-based ligands and N3−, NCO−, NCS− or Cl−
as monodentate ligands [
Zn–N(pyridine/quinoline), 2.206(6)/2.240(2)–2.344(2) Å bond lengths, indicating that Zn(II) ion is more
tied to the imine nitrogen atom than to the pyridine or quinoline nitrogen atoms. In complexes , the
Zn O(enolic) bond distances are in the range from 2.146(5) to 2.222(2) Å. The shortest Zn O(enolic) bond
length is found in the [ZnL3(NCS)2] ] complex and the longest in [ZnL4(N3)1.65Cl0.35] [10
0.5MeOH [
L3 = condensation product of 2-acetylpyridine and trimethylammoniumacetohydrazide chloride and
L4 = condensation product of. 2-quinolinecarboxaldehyde and trimethylammoniumacetohydrazide
chloride). The thiocyanate ligands in are coordinated to Zn(II) ion in bent mode, with Zn
angles of 168.5(3) and 171.7(2)◦. In the crystals of the complex molecules [ZnL1(NCS)2] are assembled
8–
10] the Zn
−
N(imine), 2.049(3)–2.088(6) Å bond lengths are shorter than
1, 3–6
−
−
·
8
]
(
1
−
N−C
1
into supramolecular layers parallel with the (0 0 1) lattice plane by means of moderate O1W–H1W···O1
and weak C8–H8A···S2 and C10–H10B···O1W intermolecular hydrogen bonds [41] (Table S2, Figure
S1a in the Supplementary Materials). In addition, the solvent water molecules O1W and O2W assists
in joining the neighboring layers related by the center of symmetry by means of weak intermolecular
hydrogen bonds C–H···OW (Table S2, Figure S2b in the Supplementary Materials). The shortest
separations of 4.467(2) and 4.666(2) Å between the centers of gravity of the 1,3-thiazole rings are
observed along the [−1 1 0] direction.
Figure 1. ORTEP presentation of the molecular structure of [ZnL1(NCS)2]
2H2O (1). Thermal ellipsoids
·
are drawn at the 30% probability level.

Molecules 2020, 25, 4043
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Table 1. Selected bond lengths (Å) and angles (◦) for 1 and 2.
1
2
Zn1–N6
Zn1–N5
Zn1–N2
Zn1–O1
Zn1–N1
O1–C6
S2–C11
S3–C12
N2–C4
N2–N3
N3–C6
N5–C11
N6–C12
1.955(3)
1.959(2)
2.058(2)
2.1778(19)
2.212(2)
1.265(3)
1.626(3)
1.624(3)
1.285(3)
1.389(3)
1.317(3)
1.146(3)
1.149(4)
Zn1–N6
Zn1–N5
Zn1–N2
Zn1–N1
Zn1–S2
Zn1–S4
S2–C6
S4–C12
N2–C4
N2–N3
N6–N7
N3–C6
N4–C6
N6–C10
N7–C12
N8–C12
N2–Zn1–N6
N2–Zn1–N5
N6–Zn1–N5
N2–Zn1–N1
N6–Zn1–N1
N5–Zn1–N1
N2–Zn1–S4
N6–Zn1–S4
N5–Zn1–S4
N1–Zn1–S4
N2–Zn1–S2
N6–Zn1–S2
N5–Zn1–S2
N1–Zn1–S2
S4–Zn1–S2
C6–S2–Zn1
C12–S4–Zn1
2.149(2)
2.1869(19)
2.147(2)
2.318(2)
2.4516(7)
2.4109(7)
1.716(3)
1.712(3)
1.290(3)
1.370(3)
1.364(3)
1.327(3)
1.360(3)
1.301(3)
1.332(3)
1.360(3)
166.84(8)
103.08(7)
75.28(7)
73.63(8)
93.21(8)
84.54(8)
101.19(5)
79.42(5)
154.65(6)
95.42(6)
79.08(6)
113.88(6)
91.66(6)
150.76(6)
100.03(3)
95.20(9)
95.96(8)
N6–Zn1–N5
N6–Zn1–N2
N5–Zn1–N2
N6–Zn1–O1
N5–Zn1–O1
N2–Zn1–O1
N6–Zn1–N1
N5–Zn1–N1
N2–Zn1–N1
O1–Zn1–N1
C6–O1–Zn1
C11–N5–Zn1
C12–N6–Zn1
N5–C11–S2
N6–C12–S3
110.73(11)
121.74(10)
127.42(10)
96.93(10)
97.85(9)
74.02(8)
101.94(10)
97.92(9)
75.37(8)
149.20(7)
109.97(16)
168.5(3)
171.7(2)
179.0(3)
179.2(3)
Table 2. Optimization of the reaction conditions.
Entry
Catalyst
Mol%
Temp.(◦C)
Solvent
Additive (0.5 eq.)
% Isolated Yield 1
1
2
3
4
5
6
7
8
9
1
10
10
10
10
10
5
10
10
5
120
120
120
120
120
110
110
110
130
130
130
toluene (1 M)
toluene (1 M)
toluene (1 M)
toluene (1 M)
toluene (1 M)
neat
-
-
-
-
-
-
-
-
85
0
67
0
56
51
65
57
91
61
33
HL1Cl
3
HL3Cl
2
1
1
3
1
3
1
neat
neat
neat
neat
MgSO4
MgSO4
MgSO4
10
5
5
11 2
neat
1
All reactions were performed on a 0.5 mmol scale and the reaction time was 16 h unless otherwise noted. The
progress of the reaction was monitored by gas chromatography/mass spectroscopy (GC/MS) analysis, using n-octane
as the internal standard and the isolated yields reported correspond to the pure product after chromatographic
2
purification. The reaction was stopped after 3 h.
The molecular structure of
given in Table 1. The neutral complex molecule [Zn(L2)2] crystallizes in the monoclinic crystal
system with space group P21/c. In complex
, two deprotonated ligand molecules L2 coordinate
2 is shown in Figure 2. Selected bond distances and angles are
2

Molecules 2020, 25, 4043
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the Zn(II) ion in a meridional fashion, forming a distorted octahedral complex by chelation through
two NNS donor atom sets. Each ligand coordinates to metallic center through thiazole nitrogen,
imine nitrogen and thiolate sulfur atoms. The tridentate coordination of each ligand implies the
formation of two fused five-membered chelate rings Zn–N–C–C–N and Zn–N–N–C–S. The chelate
rings (Zn1–N5–C9–C10–N6 and Zn1–N6–N7–C12–S4) are nearly coplanar, while the other pair
(Zn1–N1–C3–C4–N2 and Zn1–N2–N3–C6–S2) deviates significantly from coplanarity, as indicated by
the dihedral angles of 2.2◦ and 7.1◦, respectively. In addition, the two chelation planes comprising
the atoms N–N–S–Zn are practically perpendicular (dihedral angle = 89.7◦). The octahedral complex
molecule of
2 is comparable with the Zn(II) complex containing a similar ligand (2-acetylthiazole
(N4)-phenylthiosemicarbazone) (CSD refcode KUMPEP) [13], although the latter is much more distorted
due to the presence of the phenyl group at the terminal nitrogen atom of the thiosemicarbazone ligand,
as evidenced by the smaller dihedral angle between chelation planes (N–N–S–Zn) compared to that
observed in
defined as the mean deviation of 12 octahedral angles from ideal 90◦. The complex
octahedral strain in comparison to that observed in analogous Zn(II) complex with 2-acetylthiazole
(N4)-phenylthiosemicarbazone. The calculated
Oh values are 10◦ for the former and 12◦ for the latter
complex. The mean Zn– bond lengths (Zn–N1,3-thiazole 2.2525 Å, Zn–Sthiolate 2.4313 Å and Zn–Nimine
2.148 Å) observed in complex are similar to those found in its structural analogue (Zn–N1,3-thiazole
2
(83.9◦ vs. 89.7◦). One of the measures of the octahedral strain is average
∆
Oh value,
2
shows less
∆
L
2
2.2310 Å, Zn–Sthiolate 2.4331 and Zn–Nimine 2.1877Å).
Figure 2. ORTEP presentation of the molecular structure of [Zn(L2)2] (
2). Thermal ellipsoids are drawn
at the 30% probability level.
In the crystals of complex 2, molecules self-assemble within the layer parallel with the (1 0 0)
lattice plain by means of intermolecular hydrogen bonds between terminal NH2 groups (N4 and
1
N8) serving as hydrogen bond donors and thiolate sulfur atoms S4 at 1
S2 at 1 x, 2 y,
−
x,
−
1/2 + y,
−
z and
2
−
−
−
z serving as acceptors (Table S3, Figure S2a in the Supplementary Materials).
The complex molecules belonging to neighboring layers are linked through weak π···π interactions
involving heteroaromatic 1,3-thiazole rings to form a 3D supramolecular structure (Table S4 and Figure
S2b in the Supplementary Materials). In addition, the molecules of 2 are linked along a crystallographic
axis by weak Caromatic–H···Nhydrazone contacts.

Molecules 2020, 25, 4043
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2.3. Evaluation of the Zinc Complexes’ Catalytic Activity in the KA2 Coupling Reaction
We chose cyclohexanone, pyrrolidine and phenylacetylene as a model substrate triad. A promising
result was obtained when complex was used in 10 mol% loading in toluene, affording the product
in 85% isolated yield after 16 h (Entry 1, Table 2). As expected, when ligand HL1Cl was used as a
possible catalyst in a control experiment, the desired propargylamine was not formed. Complex
led to a 67% yield under the same conditions, while complex also displayed moderate catalytic
1
3
2
activity (Entries 3 and 5, Table 2), suggesting that the zinc center is no longer fully coordinated under
the reaction conditions. Removing the solvent while reducing the temperature and catalyst loading
also led to moderate yields in the cases of both
water-scavenging additive, in combination with an increase in temperature, led to the highest yield,
when complex was used in 5 mol% loading (Entry 9, Table 2). Under the same conditions, complex
1 and 3 (Entries 6–8, Table 2), while using MgSO4 as a
1
3
led to moderate yield, while reducing the reaction time to 3 h led to incomplete conversion and low
yield (Entries 10 and 11 respectively, Table 2), suggesting that the reaction conditions outlined in entry
9 of Table 2 were optimal. Of note, when taking into account the reactivity of simple zinc salts, complex
1
performs comparably well in this reaction. However, lower catalyst loading is required under the
conditions described herein, while, in the case of zinc acetate, 10 mol% was essential in order to reach
yields above 90%, in combination with dry/inert conditions.
Several substrate combinations were coupled under the aforementioned conditions, as shown
in Scheme 2. Piperidine led to compound 4b in high yield, as was the case in the parent, Zn-based,
ligand-free system and the more recently reported Mn-based system [34,42]. Propargylamine 4c was
obtained in moderate yield, while using a linear ketone in combination with pyrrolidine afforded
compound 4d in 72% yield. Propargylamine 4e, bearing an ester moiety that can be used for further
functionalization, was synthesized in good yield, while the primary amine-derived compound 4f was
also successfully synthesized, albeit in moderate yield because of the stability of the intermediate imine.
When the steric bulk of the linear ketone was increased, the yield dropped significantly, highlighting
the crucial effect of steric hindrance in the outcome of this reaction (compound 4g). When an aliphatic
alkyne was used in combination with N-phenylpiperazine, propargylamine 4h was obtained in 37%
isolated yield. In order to assess the effect of a less functionalized aliphatic alkyne, 1-octyne was
used and compound 4i was isolated in 70% yield. Finally, cyclopentanone was chosen as a coupling
partner and, as anticipated based on known reactivity trends, compound 4j was obtained in moderate
yield [34,42]. Overall, complex 1 allows for lower catalyst loading when compared to simple zinc salts
and is more robust under harsh, ambient conditions [34]; however, the limitations of this coupling
reaction and the generally observed trends regarding substrate scope persist in this case as well.
2.4. Density Functional Theory (DFT) Optimized Structures and Highest Occupied Molecular Orbital-Lowest
Unoccupied Molecular Orbital (HOMO-LUMO) Analysis
In order to calculate the ground-state geometries of the complexes, DFT calculations of
[ZnL1(NCS)2] ( ) and [Zn(L2)2] ( ), as well as [ZnL3(NCS)2] (
1 2 3) complexes have been performed,
as described below. DFT calculations predict five-fold coordination for both [ZnL1(NCS)2] and
[ZnL3(NCS)2] complexes with tridentate ligands HL1Cl and HL3Cl and two nitrogen atoms from
thiocyanate ligands (Figure 3), thereby supporting the experimental X-ray diffraction (XRD) results. In
complex
2
DFT results show that two tridentate ligand molecules L2 coordinate the Zn(II) ion through
thiazole nitrogen, imine nitrogen and thiolate sulfur atoms, forming an octahedral complex with four
fused five-membered chelate rings, in agreement with experimental data. Selected bond lengths and
values of valence angles are summarized in Table S5. The calculated geometric parameters of mixed
ligand complexes are compared with the X-ray diffraction structures and show good agreement.

Molecules 2020, 25, 4043
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Scheme 2. Substrate scope of the reaction system under the optimal conditions. All reactions
were performed on a 0.5 mmol scale and isolated yields after column chromatography are shown
in parentheses.
Figure 3. Density functional theory (DFT) optimized geometries of: (
(2); and (c) [ZnL3(NCS)2] (3).
a 1); (b
) [ZnL1(NCS)2] ( ) [Zn(L2)2]

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The HOMO-LUMO energies of the complexes provide information about energetic behavior and
stability of the complexes. The energy gap between HOMO and LUMO, determines reactivity and
kinetic stability of molecules [43–45]. The chemical hardness (η) is a good indicator of the chemical
stability. The molecules having a large energy gap are known as hard and having a small energy gap
are known as soft molecules. The soft molecules are more polarizable than the hard ones because they
need little energy for excitation [46
,47]. The chemical potential (µ), hardness value (η), softness (S),
electronegativity (χ) and electrophilicity index (ω) of molecules are formulated by the equations [47]:
µ = −(−EHOMO − ELUMO)/2,
(1)
η = (−EHOMO + ELUMO)/2,
S = 1/2η,
(2)
(3)
(4)
(5)
χ = (−EHOMO − ELUMO)/2,
ω = µ2/2η,
where EHOMO and ELUMO are the energies of the HOMO and LUMO orbitals. The negative chemical
potential indicates complex to be stable in such a way that does not decompose spontaneously into its
elements. Hardness measures the resistance to change in the electron distribution in a molecule.
The HOMO-LUMO energy calculations were performed within the time-dependent density
functional theory (TD-DFT) approach at the B3LYP/6-31G level of theory in vacuum and toluene. This
functional has been employed with a great success in reactivity studies, with a good compromise
between accuracy and computational cost [48]. To examine the basis set dependence of the DFT HOMO
and LUMO energies, we also performed TD-DFT calculations on the investigated systems using the
B3LYP functional with a larger basis set such as 6-311G(d,p). Results are presented in the Table S6.
We obtained small differences between the HOMO and LUMO energies calculated at B3LYP level of
theory by using the 6-31G and 6-311G(d,p) basis sets, ranging from 0.07 to 0.22eV. It has been already
found that HOMO energies, negative values of LUMO energies and TD-DFT HOMO-LUMO gaps are
generally less sensitive to the basis set [49].
The HOMO and LUMO and their energies were calculated to locate the high- and low-density
1
regions in all complexes and are shown in Figure 4. The HOMOs of [ZnL1(NCS)2] ( ) and [ZnL3(NCS)2]
(3
) complexes are delocalized mainly at the linear monodentate ligands NCS– and metal centers,
whereas the LUMOs are delocalized on the planar ring of Schiff base in equatorial plane (Figure 4).
The HOMOs of the complex [Zn(L2)2] (
) are delocalized mainly at the five-membered heterocyclic
rings with terminal NH2 groups. The LUMOs of the complex [Zn(L2)2] (
) are delocalized at the
2
2
five-membered heterocyclic chelate rings of the two tridentate ligands. The calculated values of
reactivity descriptors of complexes are given in Table 3. The negative values of chemical potential
(
−
3.886,
into their components. As shown in Table 3, the compound that has the lowest energy gap in
comparison to the two other complexes is the compound Egap is 2.167 eV in vacuum and 2.977 eV
in toluene). This lower energy gap allows it to be the softest molecule. The magnitude of chemical
hardness, supported by the HOMO–LUMO energy gap, for complexes and have been found to
be: 1.083, 1.456, and 1.232 eV, respectively (Table 3). Chemical hardness (softness) value of complex
is lower (greater) among all the investigated complexes, both in the gas phase and toluene. Hence,
complex is found to be more reactive than all the compounds which is in agreement with experimental
catalytic data. The compound that has the lowest LUMO energy is the compound 1 (E = 2.803 eV)
which signifies that it can be the best electron acceptor [50]. Besides, the electrophilicity index values
−
3.597 and
−
3.670 eV) show their stability suggesting that these do not undergo decomposition
1 (∆
1,
2
3
1
1
−
ω
given in Table 3 for complexes (6.971, 4.443 and 5.466 eV, respectively) related to chemical potential and
hardness indicate that compound 1 is the strongest electrophile among all compounds. Compound 1
possesses a higher electronegativity value (χ = 3.886 eV) than all compounds, a characteristic that could
explain its superior activity in catalysis, when compared to the other complexes evaluated herein [34].

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Results were confirmed by using another DFT model denoted as BVP86/6-311G(d,p) with the lowest
HOMO-LUMO energy gap for complex . The differences between TD-DFT gaps calculated with
1
selected different functionals are small. For instance, B3LYP and BVP86 predict relatively good HOMO
and LUMO energies for investigated complexes with errors ranging from 0.56 to 0.73 eV.
Figure 4. Molecular orbital plots and energy levels of the highest occupied molecular orbital (HOMO),
the lowest unoccupied molecular orbital (LUMO) and HOMO-LUMO transitions of: (a
) [ZnL1(NCS)2]
(1); (b) [Zn(L2)2] (2); and (c) [ZnL3(NCS)2] (3).
Table 3. Quantum chemical descriptors for complexes in vacuum and toluene (in brackets).
[ZnL1(NCS)2] (1)
[Zn(L2)2] (2)
[ZnL3(NCS)2] (3)
EHOMO (eV)
ELUMO (eV)
∆Egap(eV)
µ (eV)
−4.970 (−5.692)
−2.803 (−2.695)
2.167 (2.977)
−3.886 (−4.193)
1.083 (1.488)
0.461 (0.336)
3.886 (4.193)
6.971 (5.908)
−5.054 (−5.268)
−2.141 (−2.252)
2.913 (3.016)
−3.597 (−3.76)
1.456 (1.508)
0.343 (0.331)
3.597 (3.760)
4.443 (4.687)
−4.903 (−5.645)
−2.438 (−2.330)
2.465 (3.315)
−3.670 (−3.987)
1.232 (1.657)
0.405 (0.301)
3.670 (3.987)
5.466 (4.797)
η (eV)
S (eV)
X (eV)
ω (eV)
3. Materials and Methods
2-Acetylpyridine ( 99%), 2-acetylthiazole (99%), thiosemicarbazide (99%) and Girard’s T reagent
≥
(99%) were obtained from Aldrich. IR spectra were recorded on a Nicolet 6700 Fourier transform
infrared (FT-IR) spectrometer using the attenuated total reflectance (ATR) technique in the region
1
4000
−
400 cm−1 (vs-very strong, s-strong, m-medium, w-weak, bs-broad signal). H- and 13C-NMR
spectra were recorded on a Bruker Avance Ultrashield 500 plus spectrometer (1H at 500 MHz; 13C at
125 MHz) at room temperature using TMS as internal standard in DMSO-d6, or on a Varian Mercury
200 MHz spectrometer (1H at 200 MHz; 13C at 50 MHz) or a Brucker Avance 400 MHz instrument
(1H at 400 MHz; 13C at 101 MHz) using CDCl3 as the solvent. Chemical shifts are expressed in ppm

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(δ) values and coupling constants (J) in Hz. Elemental analyses (C, H, N and S) were performed by
standard micro-methods using the ELEMENTARVario ELIII C.H.N.S.O analyzer. Molar conductivities
were measured at room temperature (25 ◦C) on a digital conductivity-meter JENWAY-4009. GC/MS
spectra were recorded with a Shimandzu R GCMS-QP2010 Plus Chromatograph Mass Spectrometer
using a MEGAR (MEGA-5, F.T: 0.25 µ
m, I.D.: 0.25 mm, L: 30 m, Tmax: 350 ◦C, Column ID# 11475)
column, using n-octane as the internal standard.
3.1. Synthesis of (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium
Chloride (HL1Cl)
The ligand HL1Cl was synthesized by the reaction of Girard’s reagent T (1.676 g, 10 mmol) and
2-acetylthiazole (1036 µL, 10 mmol) in water (20 mL). Reaction mixture was acidified with 3–4 drops of
2 M HCl and refluxed for 3 h. After cooling to the room temperature, white precipitate was filtered
and washed with water. Yield: 2.54 g (92%). Anal. Calcd. (%) for C10H17N4OSCl: C, 43.40; H, 6.19; N,
20.24; S, 11.58. Found (%): C, 43.45; H, 6.21; N, 20.20; S, 11.52. IR (ATR, cm−1): 3387w, 3129w, 3092m,
3018m, 2955s, 1702vs, 1612w, 1550vs, 1487s, 1401m, 1300w, 1201s, 1135w, 976w, 945w, 914m, 787w,
1
748w, 684w, 585w, 552w. H-NMR (500 MHz, DMSO-d6),
δ (ppm): 2.41, (s, 3H, C5-H); 2.53, (s, 3H,
C5-H); 3.30, (s, 9H, C8-H); 3.34, (s, 9H, C8-H); 4.60, (s, 2H, C7-H); 4.82, (s, 2H, C7-H); 7.848, (d, 1H,
C2-H/C3-H = 5 Hz, C2-H); 7.854, (d, 1H, JC2-H/C3-H = 5 Hz, C2-H); 7.926, (d, 1H, JC2-H/C3-H = 5 Hz, C3-H);
7.932, (d, 1H, JC2-H/C3-H = 5 Hz, C3-H); 11.61, (s, 1H, N-H); 11.86, (s, 1H, N-H). 13C-NMR (125 MHz,
DMSO-d6), (ppm): 13.9, (C5); 15.05, (C5); 53.6, (C8); 53.9, (C8); 63.0, (C7); 63.8, (C7); 123.3, (C2); 123.6,
J
δ
(C2); 143.9, (C3); 144.00, (C3); 147.00, (C4); 150.8, (C4); 161.2, (C1); 166. 8, (C1); 167.0, (C6); 167.3, (C6).
3.2. Synthesis of [ZnL1(NCS)2]·2H2O (1)
The Zn(II) complex
HL1Cl (83 mg, 0.30 mmol) and NH4SCN (60 mg, 0.78 mmol) in a solvent mixture of water/methanol
(10/10 mL). The solution was refluxed for 4 h. After refrigeration of the reaction solution at
8 ◦C for
1
was synthesized by the reaction of Zn(OAc)2
·
2H2O (75 mg, 0.30 mmol), ligand
−
two weeks pale yellow crystals suitable for X-ray analysis were formed. Yield: 0.11 g (83%). Anal.
Calcd. (%) for C12H20N6O3S3Zn: C, 36.71; H, 5.13; N, 21.41; S, 24.51. Found (%): C, 36.55; H, 5.15; N,
21.27; S, 24.31. IR (ATR, cm−1): 3502s, 3383s, 3123m, 3055w, 2959w, 2088vs, 1610s, 1536s, 1475s, 1424s,
1
1402s, 1341m, 1290w, 1237w, 1151w, 1095w, 1064w, 1012w, 988w, 923w, 880w, 746w, 556w. H-NMR
(500 MHz, DMSO-d6),
JC2-H/C3-H = 2.2 Hz, C2-H); 8.16, (d, 1H, JC2-H/C3-H = 2.2 Hz, C3-H). 13C-NMR (125 MHz, DMSO-d6),
(ppm): 15.4, (C5); 53.8, (C8); 66.7, (C7); 125.7, (C3); 134.3, (C9); 142.5, (C2); 147.3, (C4); 166.2, (C1);
δ (ppm): 2.54, (s, 3H, C5-H); 3.27, (s, 9H, C8-H); 4.20, (s, 2H, C7-H); 8.06, (d, 1H,
δ
171.7, (C6).
3.3. Synthesis of Ligand HL2 (E)-2-(1-(thiazol-2-yl)ethylidene)hydrazine-1-carbothioamide
The ligand HL2 was synthesized by the reaction of thiosemicarbazide and 2-acetylthiazole in
water according to the previously described method [12]. Yield 1.82 g (91%). IR (ATR, cm−1): 3436s,
3248s, 3188s, 3099m, 3071m, 2983m, 2066w, 1648w, 1589s, 1510s, 1482s, 1452m, 1425s, 1365m, 1282m,
1166m, 1107m, 1069m, 1039m, 958w, 881w, 847w, 755w, 712w, 638w. Anal. Calcd. (%) for C6H8N4S2: C,
1
35.98; H, 4.03; N, 27.98; S, 32.02. Found (%): C, 35.74; H, 4.26; N, 27.88; S, 31.98. H-NMR (500 MHz,
DMSO-d6), δ
(ppm): 7.89, (C4-H, d J3 = 5 Hz); 7.80, (C5-H, d, J3 = 5 Hz); 2.43, (C7-H3, s); 10.67, (N-H, s);
8.53 and 7.69, (N-H2, bs). 13C-NMR (125 MHz, DMSO-d6),
δ (ppm): 14.1, (C7); 144.7, (C2); 179.4, (C8);
167.5, (C6); 143.7, (C4); 123.1, (C5).
3.4. Synthesis of [Zn(L2)2] (2)
The Zn(II) complex
2
was synthesized by the reaction of Zn(BF4)2 6H2O (72 mg, 0.20 mmol),
·
ligand HL2Cl (40 mg, 0.20 mmol) and NaN3 (30 mg, 0.46mmol) in solvent mixture of acetonitrile/water
(15/5 mL). The solution was refluxed for 4 h. After refrigeration of the reaction solution at –8 ◦C for
one-week yellow crystals suitable for X-ray analysis were formed. Yield: 0.08 g (87%). Anal. Calcd.

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(%) for C12H14N8S4Zn: C, 36.16; H, 3.54; N, 28.12; S, 32.18. Found (%): C, 36.04; H, 3.56; N, 28.02; S,
32.07. IR (ATR, cm−1): 3571w, 3496w, 3436m, 3308vs, 3169s, 3109s, 2925w, 2255w, 2185w, 2078m, 1632m,
1589m, 1569m, 1496s, 1425vs, 1375vs, 1298s, 1198vs, 1162s, 1097s, 1029m, 882w, 783m, 726w, 677m,
1
644w, 596w, 547w, 480w. H-NMR (500 MHz, DMSO-d6),
δ (ppm): 2.43, (s, 3H, C5-H); 7.45, (s, 2H,
NH2); 7.88, (d, 1H, C2-H); 7.94, (d, 1H, C6-H). 13C-NMR (125 MHz, DMSO-d6),
δ (ppm): 15.9, (C5);
122.5, (C3); 139.2, (C4); 142.4, (C2); 167.3, (C1); 181.7, (C6).
3.5. Synthesis of Ligand HL3Cl (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)
ethan-1-aminium Chloride
The HL3Cl ligand was synthesized by the reaction of 2-acetylpyridine and Girard’s T reagent
according to the previously described method [8
]. Yield 2.36 g (87%). IR (ATR, cm−1): 3387w, 3127m,
3090m, 3049m, 3016m, 2950s, 1700vs, 1612w, 1549s, 1485m, 1400m, 1300w, 1253w, 1200s, 1153w, 1135m,
1095w, 1073m, 975w, 944w, 914m, 748w, 683w.
3.6. Synthesis of [ZnL3(NCS)2]·0.5CH3OH Complex (3)
The Zn(II) complex
NH4SCN according to the previously described method [
3
was synthesized by the reaction of ligand HL3Cl, Zn(OAc)2
·
2H2O and
8
]. Yield 0.08 g (94%). IR (ATR, cm−1): 3030w,
2067vs, 1639w, 1620w, 1592w, 1566m, 1535s, 1464m, 1437m, 1397m, 1366m, 1339m, 1302m, 1200w,
1145w, 1074m, 1019m, 975w, 914w, 782w, 749 (w). λM = 28 Ω−1cm2mol−1
.
3.7. X-Ray Crystallography
The molecular structures of complexes
Crystallographic data and refinement details are given in Table S7. The X-ray intensity data for
were collected at room temperature on a Nonius Kappa CCD diffractometer equipped with
graphite-monochromator utilizing MoK radiation ( = 0.71073 Å). Data reduction and cell refinement
was carried out using DENZO and SCALPACK [51]. Diffraction data for were collected at room
temperature with an Agilent SuperNova dual source diffractometer using an Atlas detector and
equipped with mirror-monochromated MoK radiation ( = 0.71073 Å). The data were processed
1 and 2 were determined by single-crystal X-ray diffraction.
1
α
λ
2
α
λ
by using CrysAlis PRO [52]. All the structures were solved using SIR-92 [53] and refined against
F2 on all data by full-matrix least-squares with SHELXL–2014 [54]. All non-hydrogen atoms were
refined anisotropically. The water bonded hydrogen atoms in 1 was located in a difference map and
refined with the distance restraints (DFIX) with O–H = 0.96 Å and with Uiso(H) = 1.5Ueq(O). All
other hydrogen atoms were included in the model at geometrically calculated positions and refined
using a riding model. Crystallographic data for the structures reported in this paper have been
deposited with the CCDC 2021000 (for 1) and 2021001 (for 2). CCDC 2021000 and 2021001 contain
the supplementary crystallographic data for this paper. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2
1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk).
3.8. Catalysis General Procedure
A Teflon sealed screw-cap pressure tube equipped with a stirring bar and a rubber septum or a
screw-cap vial, was charged with x mol% of the catalyst and 0.5 eq. of the additive (MgSO4) unless
otherwise noted. Under air, 0.5 mmol of the amine were added and the mixture was stirred until the
solid was partially dissolved. 0.5 mmol of the alkyne were added and the mixture was stirred at room
temperature. Finally, 0.5 mmol of the ketone were added and the reaction was allowed to stir in a
preheated oil bath, for the appropriate time. After cooling to room temperature, ethyl acetate was
added (2
×
5 mL) and the mixture was stirred for 5 min. The mixture was filtered through a short
silica gel plug, in order to remove inorganic impurities, concentrated under vacuum and loaded atop a
silica gel column. Gradient column chromatography with ethyl acetate/petroleum ether furnished the
desired products. All products were characterized by 1H-NMR, and 13C{1H}-NMR which were all in

Molecules 2020, 25, 4043
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agreement with the assigned structures and the data reported in the literature ([34,42] and references
cited therein]).
Characterization Data for the Synthesized Propargylamines
1-(1-(Phenylethynyl)cyclohexyl)pyrrolidine (4a): Obtained as an orange/yellow oil in 91% yield (115 mg,
1
0.46 mmol). H-NMR (200 MHz, CDCl3)
δ 7.44 (dd, J = 6.7, 3.1 Hz, 2H), 7.30 (m, 3H), 2.82 (t, J = 5.9 Hz,
4H), 2.13–1.94 (m, 2H), 1.91–1.41 (m, 12H, overlapping peaks). 13C{1H}-NMR (50 MHz, CDCl3)
128.1, 127.6, 123.6, 90.3, 86.1, 59.3, 47.0, 37.8, 25.7, 23.5, 23.0.
δ 131.7,
1-(1-(Phenylethynyl)cyclohexyl)piperidine (4b): Obtained as a yellow oil in 87% yield (116 mg, 0.44 mmol).
1H-NMR (400 MHz, CDCl3)
δ 7.47–7.36 (m, 2H), 7.28–7.23 (m, 3H), 2.70 (m, 4H), 2.11–2.05 (m, 2H),
1.83–1.34 (m, 14H, overlapping peaks). 13C{1H}-NMR (101 MHz, CDCl3)
90.6, 86.3, 59.7, 47.3, 35.8, 26.6, 25.8, 24.9, 23.2.
δ 131.9, 128.4, 127.8, 124.0,
1-(1-(p-Tolylethynyl)cyclohexyl)piperidine (4c): Obtained as a yellow oil in 64% yield (91 mg, 0.32 mmol).
1H-NMR (400 MHz, CDCl3)
δ 7.33 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 2.73 (s, 4H), 2.34 (s, 3H),
2.12–2.09 (m, 2H), 1.78–1.42 (m, 14H, overlapping peaks). 13C{1H}-NMR (101 MHz, CDCl3)
131.7, 129.1, 120.6, 90.4, 86.7, 59.9, 47.3, 35.7, 26.4, 25.8, 24.7, 23.3, 21.5.
δ 137.9,
1-(3-Methyl-1-phenylpent-1-yn-3-yl)pyrrolidine (4d): Obtained as an orange/brown oil in 72% yield (82
1
mg, 0.36 mmol). H-NMR (400 MHz, CDCl3)
δ 7.45–7.38 (m, 2H), 7.32–7.26 (m, 3H), 2.80 (t, J = 5.8 Hz,
4H), 1.84–1.79 (m, 4H), 1.74–1.65 (m, 2H), 1.42 (s, 3H), 1.05 (t, J = 7.5 Hz, 3H). 13C{1H}-NMR (101 MHz,
CDCl3) δ 131.7, 128.2, 127.7, 123.5, 90.9, 84.7, 58.6, 47.8, 33.9, 25.1, 23.7, 8.9.
1-(1-(Phenylethynyl)cyclohexyl)piperidine-4-carboxylate (4e): Obtained as a yellow oil in 67% yield (114
1
mg, 0.34 mmol). H-NMR (200 MHz, CDCl3)
δ 7.42 (dd, J = 6.7, 3.0 Hz, 2H), 7.35–7.23 (m, 3H), 4.13 (q,
J = 7.1 Hz, 2H), 3.15 (d, J = 11.6 Hz, 2H), 2.42–2.18 (t, J = 11.0 Hz, 3H), 2.13–1.43 (m, 14H), 1.24 (t, J = 7.1
Hz, 3H). 13C{1H}-NMR (50 MHz, CDCl3)
41.6, 35.9, 28.9, 25.8, 22.9, 14.3.
δ 175.4, 131.7, 128.3, 127.8, 123.6, 90.4, 86.2, 60.3, 59.0, 45.8,
N-Octyl-1-(phenylethynyl)cyclohexanamine (4f): Obtained as a yellow oil in 53% yield (83 mg, 0.27 mmol).
1H-NMR (200 MHz, CDCl3)
δ 7.42 (dd, J = 6.7, 3.1 Hz, 2H), 7.33–7.23 (m, 3H), 2.79 (t, J = 7.1 Hz, 2H),
1.94 (d, J = 11.6 Hz, 2H), 1.74–1.07 (m, 20H), 0.88 (m, 3H). 13C{1H}-NMR (50 MHz, CDCl3)
δ 131.6,
128.1, 127.7, 123.6, 93.3, 84.6, 55.2, 43.2, 38.1, 31.8, 30.5, 29.5, 29.3, 27.5, 25.9, 23.1, 22.7, 14.1.
1-(3-Methyl-1-phenylhex-1-yn-3-yl)pyrrolidine (4g): Prepared according to the general procedure and
obtained as an orange/brown oil in 31% yield (37 mg, 0.16 mmol). 1H-NMR (200 MHz, CDCl3)
δ
7.45–7.36 (m, 2H), 7.28–7.25 (m, 3H), 2.79 (t, J = 5.4 Hz, 4H), 1.85–1.74 (m, 4H), 1.73–1.47 (m, 4H), 1.43
(s, 3H), 0.95 (t, J = 7.1 Hz, 3H). 13C{1H}-NMR (50 MHz, CDCl3)
δ 132.0, 128.4, 127.9, 123.8, 91.5, 84.7,
58.3, 48.0, 44.0, 26.1, 23.9, 18.0, 14.8.
2-Methyl-4-(1-(4-phenylpiperazin-1-yl)cyclohexyl)but-3-yn-2-ol (4h): Obtained as an orange solid in 37%
1
yield (60 mg, 0.19 mmol). H-NMR (400 MHz, CDCl3)
δ 7.26 (m, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.89–6.80
(m, 1H), 3.31–3.15 (m, 4H), 2.88–2.73 (m, 4H), 2.25 (br. s, 1H), 2.04–1.38 (m, 16H). 13C{1H}-NMR (50
MHz, CDCl3) δ 151.3, 129.2, 119.7, 116.0, 91.6, 81.9, 65.4, 58.2, 49.6, 46.1, 35.7, 32.1, 25.7, 22.9.
1-(1-(Oct-1-yn-1-yl)cyclohexyl)piperidine (4i): Prepared according to the general procedure and obtained
1
as a yellow oil in 70% yield (96 mg, 0.35 mmol). H-NMR (400 MHz, CDCl3)
δ 2.70–2.50 (m, 4H), 2.22
(t, J = 6.7 Hz, 2H), 1.93 (d, J = 11.2 Hz, 2H), 1.78–1.70–1.24 (m, 22H), 0.95–0.79 (m, 3H). 13C-NMR (101
MHz, CDCl3) δ 85.8, 80.7, 58.9, 47.0, 36.0, 31.4, 29.3, 29.3, 25.9, 24.9, 23.2, 22.7, 18.7, 14.1.

Molecules 2020, 25, 4043
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1-(1-(Phenylethynyl)cyclopentyl)piperidine (4j): Prepared according to the general procedure and obtained
1
as a yellow oil in 67% yield (339 mg, 1.34 mmol). H-NMR (400 MHz, CDCl3)
δ
7.41 (dd, J = 6.5, 3.2 Hz,
2H), 7.31–7.25 (m, 3H), 2.75–2.60 (m, 4H), 2.15–2.10 (m, 2H), 1.87–1.44 (m, 12H, overlapping peaks).
13C{1H}-NMR (101 MHz, CDCl3) δ 131.8, 128.3, 127.7, 123.9, 91.6, 85.4, 67.7, 50.4, 39.9, 26.3, 24.5, 23.5.
3.9. DFT Calculations
Density functional theory was used to determine the optimized geometries of complexes
[ZnL1(NCS)2] (
for [ZnL3(NCS)2] (
Gaussian 09 [55] program at B3LYP/6–31G level [56
1
) and [Zn(L2)2] (
2
8
). For comparison reasons the same calculations have been performed
]. All the DFT calculations were performed in gas phase with the
59] of theory. In order to evaluate the energetic
3) complex [
–
behavior of complexes, the HOMO-LUMO energy calculations were performed within the TD-DFT
approach using B3LYP/6-31G, B3LYP/6-311G (d,p) and BVP86/6-311G(d,p) methods in vacuum. In
addition, HOMO-LUMO energy investigations were also conducted in toluene by using TD-DFT/PCM
(polarizable continuum model) [60] calculations at B3LYP/6-31G level of theory. Calculations were
carried on the PARADOX supercomputing facility [61].
4. Conclusions
In
the
reactions
of
Zn(II)
with
chloride
(E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-
HL1Cl)
and (E)-2-(1-(thiazol-2-
yl)ethylidene)hydrazinyl)ethan-1-aminium
yl)ethylidene)hydrazine-1-carbothioamide (HL2) in the presence of NH4SCN and NaN3, respectively,
two different structural types of Zn(II) complexes were obtained and characterized by spectroscopic
(
methods (IR and NMR) and single crystal X-ray diffraction methods. In
1 the Zn(II) ion is
pentacoordinated with tridentate ligand L1 and two thiocyanate anions forming a distorted square
pyramidal structure. In
octahedral structure.
2
the Zn(II) ion is hexacoordinated with two L2 molecules forming a distorted
The DFT calculations of newly synthesized
complex have been carried out for their structural determination, HOMO, LUMO study and to
calculate reactivity descriptors. The lower kinetic stability and higher reactivity of complex compared
to the other two complexes have been found from the lower HOMO–LUMO energy gap value, in
agreement with experimental data. The electrophilicity index value (6.971 eV in gas phase and 5.908
eV in toluene) indicates that compound is the strongest electrophile than all investigated compounds.
In addition, compound possesses higher electronegativity value ( = 3.886 eV) than all compounds.
1 and 2 3)
complexes, as well as [ZnL3(NCS)2] (
1
ω
1
1
χ
Therefore, it is the best electron acceptor and that feature can plausibly explain its better performance
as a Lewis acid catalyst in the ketone-amine-alkyne coupling.
Supplementary Materials: The following are available online: Figure S1: (a) A view of the crystal packing of
1
showing complex molecules connected by means of OW-H···O, CMe-H···S and CMe-H···OW hydrogen bonds
(dashed blue lines) into layer parallel with the (0 0 1) lattice plain; (b) A side view of the layers parallel with the
(0 0 1) lattice plain related by the centers of symmetry showing the function of O1W in joining the neighboring
layers, Figure S2: (a) A view of the crystal packing of
2 showing complex molecules connected by means of
N–H···S hydrogen bonds (dashed blue lines) into layer parallel with the (1 0 0) lattice plain; (b) A side view of
the layers showing intermolecular π···π contacts involving 1,3-thiazole rings. Hydrogen atoms not involved
in hydrogen bonding are omitted for clarity, Figure S3–S22: 1H- and 13C{1H}-NMR spectra of the synthesized
propargylamines, Table S1. Structural parameters correlating the geometry of five-coordinate [ZnLX2] complexes
(
L
= tridentate hydrazone-based ligand; X = pseudohalde, halide or DMSO), Table S2. Hydrogen-bond parameters
for [ZnL1(NCS)2] ), Table S3. Hydrogen-bond parameters for [Zn(L2)2] (
2H2O (
), Table S4. Intermolecular π···π
interaction parameters for complex , Table S5. DFT calculated and experimental average values of selected bond
lengths (Å) and angles (◦) for [ZnL1(NCS)2] ( ), [Zn(L2)2] ( ) and [ZnL3(NCS)2] (
), Table S6. EHOMO, ELUMO and
·
1
2
2
1
2
3
their energy gaps calculated by using TD-DFT in vacuum at different levels of theory. Table S7. Crystal data and
structure refinement details for 1 and 2.
ˇ
Author Contributions: T.T.A., D.M., and B.C. contributed towards the syntheses, crystallization and
characterization of the ligand and complexes, as well as the interpretation of the relevant results. A.P. collected
single-crystal X-ray crystallographic data, solved the structures and performed their refinement. D.R. wrote the
relevant XRD part of the paper. S.G. performed the DFT calculations and interpreted the results. N.V.T. and L.P.Z.

Molecules 2020, 25, 4043
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carried out the catalytic evaluation experiments. G.C.V., K.K.A., and I.T. coordinated the research and wrote
the final manuscript based on the reports of their collaborators. All authors exchanged opinions concerning the
progress of the project and commented on the preparation of the manuscript at all stages. All authors have read
and agreed to the published version of the manuscript.
Funding: This research was funded by the Ministry of Education, Science and Technological Development of
the Republic of Serbia grant numbers 451-03-68/2020-14/200168 and 451-03-68/2020-14/200026 and by Slovenian
Research Agency grant number P1-0175. The present work was co-funded by the European Union and Greek
national funds through the Operational Program “ Human Resources Development, Education and Lifelong
Learning “ (NSRF 2014-2020), under the call “Supporting Researchers with an Emphasis on Young Researchers -
Cycle B” (MIS: 5047938). The APC was funded by MDPI, St. Alban-Anlage 66, 4052 Basel, Switzerland.
Acknowledgments: We thank the EN-FIST Centre of Excellence, Ljubljana, Slovenia, for the use of the
SuperNova diffractometer.
Conflicts of Interest: The authors declare no conflict of interest.
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