Novel triazole-based ligands and their zinc(II) and nickel(II) complexes with a nitrogen donor environment as potential structural models for mononuclear active sites

Article abstract of DOI:10.1039/c4nj01642d

Three new 1,2,3-triazole-based ligands with an N,N,N coordination core were prepared using a convergent synthetic protocol starting from racemic 2-amino-1-phenylethanol. They were tested as chelators for biorelevant Zn^II or Ni^II ions. An N,N,N ligand with a terminal amino functionality coordinated the Zn^II in a bidentate fashion, not including the triazole nitrogen. The ligand with two pendant 2-pyridyl groups acted as a tridentate ligand without an N2-triazole coordination to Zn^II, while the ligand containing one 2-pyridyl group acted as an inverse-click chelator for Ni^II ions.

Full text of DOI:10.1039/c4nj01642d

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Novel triazole-based ligands and their zinc(II)
and nickel(II) complexes with a nitrogen donor
environment as potential structural models for
mononuclear active sites†
Cite this:DOI: 10.1039/c4nj01642d
ab
Bogdan Stefane, Franc Perdih,ab Aleksandar Visnjevac*c and Franc Pozgan*ab
ˇ
ˇ
ˇ
Three new 1,2,3-triazole-based ligands with an N,N,N coordination core were prepared using a convergent
synthetic protocol starting from racemic 2-amino-1-phenylethanol. They were tested as chelators for
biorelevant ZnII or NiII ions. An N,N,N ligand with a terminal amino functionality coordinated the ZnII in a
bidentate fashion, not including the triazole nitrogen. The ligand with two pendant 2-pyridyl groups acted
as a tridentate ligand without an N2-triazole coordination to ZnII, while the ligand containing one 2-pyridyl
group acted as an inverse-click chelator for NiII ions.
Received (in Victoria, Australia)
23rd September 2014,
Accepted 29th October 2014
DOI: 10.1039/c4nj01642d
www.rsc.org/njc
they can be relatively easily prepared and modified.10,11 Reinaud
and coworkers reported, in many papers over the past decade, on
Introduction
Mimetics of the active site of an enzyme are useful to better calixarene- and resorcinarene-based supramolecular biomimetic
understand the structural features and how a donor array models of the trihistidine mononuclear active site, which not only
modulates the chemistry around the metal centre in the mimic the first, but also the second and third coordination spheres
catalytic site.1 For instance, Rivas et al. have designed ligands of the catalytic metal.12 A triazole ring, on the other hand, can be
that provide N4O, N2S2O and N2O coordination spheres for zinc regarded as an aza-analogue of imidazole, a nitrogen donor
and have observed that a nitrogen coordination environment is present in the histidine-containing active sites of many metallo-
more efficient than mixed nitrogen/sulphur ligation in promoting enzymes. 1,2,3-Triazoles also act as N-donors and thus effectively
the amide cleavage,2 which would explain the predominant coordinate metals, creating coordination materials with attrac-
N-donating ligand environment in many catalytic zinc sites.3 tive physico-chemical properties.13 Of particular interest are the
Besides zinc, other late-first-row transition metals, such as iron, 1,4-disubstituted 1,2,3-triazole-based mono-, bi- or multidentate
copper and nickel, are frequently encountered as metals in chelating ligands, which are employed in many fields, such as
metalloproteins.4 Thus, the complexes of ZnII, NiII, FeII, CoII drug therapy, bioimaging and sensing, fluorescence, and cata-
and CuII with tris(pyrazolyl)methane sulfonate (Tpms),5 bis- lysis.14 This is mainly because both the N2 and N3 atoms of the
(3,5-dialkylpyrazol-1-yl)acetic acid6 or 3,3-bis(1-methylimidazol-2-yl) triazole nucleus can participate in metal coordination, while
propionate7 ligands served as structural models for the N,N,O additional coordination sites can be readily introduced into 1- or
binding in 2-His-1-carboxylate metalloenzymes. Namely, the facial 4-substituents using very efficient and selective ‘‘click reac-
motif of the triad histidine, histidine and aspartate (or glutamate) is tions’’.15 The majority of the 1,4-disubstituted 1,2,3-triazole
assumed to be essential for the activity of several metalloenzymes.8 ligands use their more Lewis basic N3 atom together with the
Although a great contribution has been made to the design of N,N,O pendant pyridyl group at position 4 (regular click chelators) to
facially coordinating ligands,9 tris(pyrazolyl)borate scorpionate form planar or nonplanar pockets for the complexation of
ligands with N,N,N ligation have frequently been used to mimic transition metals, such as ReI,16 PdII,17 FeII,18 CuII,19 ZnII,20 and
the 2-His-1-carboxylate active site of several metalloenzymes because RuII.18,21 There are few 1,2,3-triazole-based chelating ligands that
coordinate to the metal through the triazole N3 atom and the
sp3N donor (e.g., sec-amino) in the side chain at position 4.20,22
Despite the fact that the N2 atom in a 1,2,3-triazole has a much
lower electron density compared to N3,23 numerous stable com-
plexes with the coordinating N2 atom have been prepared using
suitable bi(or multi)dentate ligands with the 2-pyridyl group as the
nitrogen donor, directly or remotely attached to the N1 atom of
the 1,2,3-triazole ring (inverse click chelators).24 When instead of
a Faculty of Chemistry and Chemical Technology, University of Ljubljana,
ˇ
ˇ
Askerceva 5, 1000 Ljubljana, Slovenia
b EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1000 Ljubljana,
Slovenia. E-mail: franc.pozgan@fkkt.uni-lj.si
c
ˇ
´
ˇ
Physical Chemistry Division, ‘‘Ru:er Boskovic’’ Institute, Bijenicka 54,
10000 Zagreb, Croatia. E-mail: aleksandar.visnjevac@irb.hr
† CCDC 1011293–1011295. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/c4nj01642d
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the pyridyl group, an aminoalkyl group is grafted at the N1
position of the 1,2,3-triazole ring, no complexation with metal
occurs.22b Kuang et al. reported on utility of pyridyl or quinolinyl
containing azides to accelerate the Cu-catalyzed cycloaddition
with alkynes. The resulting 1,2,3-triazole ligands were demon-
strated to chelate CuII or ZnII ions in a multidentate manner,
including the N2 nitrogen of the triazolyl group.25 The successful
complexation of pyridyl-containing inverse chelators can be
explained by the enhanced electrophilicity of the metal centre,
caused by the coordination with the p-acceptor pyridyl group,26
which consequently enables coordination, even of the less-electron-
rich N2 atom of the 1,2,3-triazole ring. No such effect occurs
involving an amino functionality as a donor.
Scheme 1 Synthesis of 1,2,3-triazole 6. (i) ClCO2Bn (1.2 equiv.), NEt3
(1.5 equiv.), CH2Cl2, r.t., overnight, 81%; (ii) MeSO2Cl (1.2 equiv.), NEt3
(1.5 equiv.), CH2Cl2, 0 1C 0.5 h and r.t., 1 h, 97%; (iii) NaN3 (5 equiv.), DMF,
r.t, 3 h, 92%; (iv) PhCRCH (1.5 equiv.), CuSO4 (0.01 equiv.), Na-ascorbate
(0.1 equiv.), t-BuOH/H2O (1 : 1), r.t., 20 h, 70%; (v) H2 (60 psi), Pd/C
(20 mol%), MeOH, r.t., 8 h, 96%.
As a part of our joint interest in designing biomimetic catalyst
systems12 and nitrogen ligand-transition metal architectures,27
we noticed the enormous potential of the 1,2,3-triazole-based
inverse-click chelators for the formation of NNX (where X stands
for O, N) type biometal complexes with one or two free coordina-
tion sites for the reversible guest binding. Here we present the
synthesis of new ligands containing a 1,2,3-triazole moiety with
potential N,N,N coordination sites and their chelation ability for
ZnII and NiII ions.
The identity of compound 6 was confirmed by NMR and
IR spectroscopy, high-resolution mass spectrometry, and
elemental analysis. The diastereotopic methylenic protons of
6 show in the 1H NMR spectrum in DMSO-d6 two well-
separated doublets of doublets at 3.33 and 3.58 ppm. Corre-
spondingly, the signal of the proton at the chiral centre
appears as a doublet of doublets. The characteristic signal of
the triazole ring appears at 8.79 ppm.
In the next step, the ligand arm of the triazole 6 was elongated
in order to introduce the third coordination donor. Since the
direct reaction of 6 with 2-bromoethylamine hydrobromide as an
aziridine precursor under basic conditions led to a complex
mixture of products, the phthalate-protected reagent 7 was used.
The heating of 6 with 7 in the presence of diisopropylethylamine
(DIPEA) yielded N-substituted phthalimide 8, which after hydra-
zinolysis gave the target compound 9 in a 33% yield over two
steps (Scheme 2).
Due to the positive effect of pyridyl groups in inverse-click 1,2,3-
triazole-based chelators, a potential hybrid sp2N^sp3N^sp2N ligand
was also designed. When triazole 6 was reacted with a slight excess
of 2-picolyl bromide hydrobromide, both the dipyridyl and mono-
pyridyl products 10 and 11 were obtained, together with starting
triazole 6, while the employment of 2.1 equivalents of 2-picolyl
bromide hydrobromide selectively afforded the dipyridyl product
10 (Scheme 3). The selective synthesis of 11 was achieved by the
reductive amination of 6. An in situ formed imine of 6 and
pyridine-2-carboxaldehyde was reduced with sodium cyanoboro-
hydride and the desired product 11 was isolated by chromato-
graphy in a low yield of 22% (Scheme 3). The NMR spectroscopy
investigation in DMSO-d6 revealed that both picolyl groups in the
ligand 10 are equivalent and that their methylenic protons display
a well-resolved AB spin system (two doublets at 3.81 and 3.92 ppm,
J = 14.5 Hz). Similarly, the methylenic protons of the picolyl group
in 11 in DMSO-d6 are also magnetically nonequivalent.
Results and discussion
Ligand design
On the basis of geometrical preferences we envisaged that
ligands comprising a 1,2,3-triazole N2 donor and two additional
coordination sites in the substituent attached to the N1 atom of the
triazole unit could be suitable ligands for coordination to metals in
a tridentate fashion. The retrosynthetic approach to the tridentate
1,2,3-triazole-based ligands with non-planar coordination pockets
containing three nitrogens or mixed nitrogen/oxygen donors is
depicted in Fig. 1. The embedment of a chiral centre is designed for
the potential use of these edifices in asymmetric transformations.
2-Amino-1-phenylethanol (1) was used as a starting material
for the synthesis of triazole ligands. First, the hydroxyl group of
amino alcohol 1 was transformed into the azido group. This
was achieved via carbamate-protected methane sulphonate 3,
which underwent a smooth substitution with sodium azide to
yield the organic azide 4. A well-established Cu-catalyzed [3+2]
cycloaddition of 4 with phenylacetylene selectively furnished
1,4-disubstituted 1,2,3-triazole 5, which was catalytically hydro-
genated under a hydrogen pressure to remove the carbamate
protection. Thus, the aminoalkyl-1,2,3-triazole 6 with two potential
coordination sites (N2 atom of triazole and NH2) was formed in a
5-step synthesis and isolated in an overall yield of 49% (Scheme 1).
Fig. 1 Retro-synthesis of potential tridentate 1,2,3-triazole-based ligands.
Scheme 2 Synthesis of N,N,N ligand 9.
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Scheme 3 Synthesis of the triazole-based ligands with the pendant
2-pyridyl group.
Scheme 5 Synthesis of metal complexes.
Scheme 4 Synthesis of the N,N,O ligand.
In order to extend the above-mentioned methodology, the
synthesis of the potential heteroleptic N,N,O-donor ligand 13
was also derived from aminoalkyl-1,2,3-triazole 6. The pendant
hydroxyl group with geometry suitable for tridentate ligation,
together with two nitrogen donors, was installed by the reaction
of 6 with 2-chloroethyl chloroformate. A basic hydrolysis of the
resulting carbamate 12 gave the desired product 13 in a good
isolated yield (70% from 6) (Scheme 4).
Metal complexes
The reaction of ligand 9 with 1 equivalent of ZnCl2 in the
mixture of methanol and dichloromethane at room tempera-
ture over 24 hours, followed by the recrystallization of the crude
Fig. 2 Crystal structure of 14. Selected bond lengths [Å] and angles [1]:
Zn1–N23 2.029(6), Zn1–N20 2.110(6), Zn1–Cl2 2.221(2), Zn1–Cl1 2.227(2),
residue from the EtOH/MeOH 1 : 1 mixture led to the formation N23–Zn1–N20 87.0(3), N23–Zn1–Cl2 110.9(2), N20–Zn1–Cl2 109.98(17),
N23–Zn1–Cl1 115.9(2), Cl1–Zn1–N20 107.97(18), Cl1–Zn1–Cl2 119.93(9).
of white crystals of product 14 (Scheme 5). The elemental
analysis indicated that ligand 9 formed a zinc(II) complex with
a 1 : 1 metal : ligand stoichiometry, and the formation of the
complex was additionally confirmed by the Maldi-Tof HRMS hydrogen bond N20–H20ꢀ ꢀ ꢀN2 [2.32 Å, 2.951 (5) Å, 1261] forming
study (m/z = 406.1). In the 1H NMR spectrum of 14 in DMSO-d6 a hydrogen-bonded six-membered ring. In addition to this
all three amino protons appear as one broad singlet at approxi- intramolecular H-bond, there is the intermolecular hydrogen
mately 4 ppm, strongly (for about 2 ppm) shifted downfield bond N23–H23Bꢀ ꢀ ꢀN3 [2.29 Å, 3.109 (4) Å, 1511] observed in the
compared to the free ligand 9, indicating that both the primary structure of 14, connecting two molecules related by a crystallo-
and secondary amino groups undergo an interaction with the graphic inversion centre, and thus forming the molecular dimers
metal atom. In addition, recognizable downfield shifts in as the basic molecular building blocks of the crystal structure.
1
the H NMR resonances of all the methylenic protons and of This means that both available triazole nitrogens (N2 and N3) act
the proton at the chiral centre were observed. However, the as hydrogen-bond acceptors rather than being involved in the
resonance of the proton of the triazole unit of the complex 14 Zn(II) coordination.
remained virtually unchanged, suggesting that the triazole ring
We assumed that the dipyridyl compound 10 could act as a
is not involved in the zinc coordination. Indeed, a single-crystal scorpionate-like tridentate ligand involving a triazole N2 atom
X-ray diffraction study of 14 revealed that the zinc ion is and two pyridine nitrogens as the donors. Ligand 10 was mixed
embedded in a tetrahedral coordination sphere formed by with 1 equivalent of ZnCl2 in methanol and after cooling,
two nitrogen donors from the ligand side chain and two chlorine colourless crystals of 15 were formed (Scheme 5). While the
anions (Fig. 2). The overall conformation of the potentially HRMS of the product gave only the signal for dissociated ligand
tridentate ligand molecule is defined by a strong intramolecular 10, its coordination to the zinc centre was well supported by the
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NMR analysis. The 1H NMR spectrum in DMSO-d6 of 15 shows a amino N3 atom [2.418(3) Å]. The Zn–Cl bonding distances
single set of resonances for all pyridine hydrogen atoms are 2.2630(11) and 2.3110(12) Å. The N–Zn–N angles are
appearing as broadened signals (without a fine structure) and 117.56(14)1, 75.90(11)1 and 74.78(12)1 and these deviate from
are all shifted downfield relative to the free ligand 10. More- the values expected for an ideal trigonal bipyramid. The lattice
over, methylenic protons of the 2-picolyl group appear as two structure is stabilized by weak CHꢀ ꢀ ꢀCl and CHꢀ ꢀ ꢀp inter-
very broad singlets, also slightly shifted at 3.87 and 4.08 ppm, actions. Although the compound 15 has five aromatic rings,
respectively. These results indicate that the two picolyl groups no significant p–p interactions can be observed in the crystal
are equivalent and thus both bind to the metal in a symmetric structure.
fashion. Similarly, the 13C NMR signals of pyridyl carbons
The nickel complex with ligand 11 was formed by reacting
(except 60-C) and the methylenic carbon of the picolyl group the ligand with 1 equivalent of NiCl2ꢀ6H2O (Scheme 5). Blue
are broadened. The broadening of the 1H and 13C picolyl crystals, separated from the mother liquor by filtration, revealed a
signals suggests a fluxional structure, probably due to the weak broad and ill-defined H NMR spectrum, which is in agreement
1
interaction between the pyridyl nitrogens and the zinc ion. with the paramagnetic nature of the 3d8 species. The evidence for
Interestingly, the signal of a proton at the chiral centre in the formation of a nickel complex with the ligand 11 was provided
ligand 10 changed its fine structure from a doublet of doublets by the IR spectrum, significantly altered with respect to the one
to a not-well-resolved doublet once 10 coordinated to zinc and obtained for the free ligand. The metal coordination was further
is also remarkably shifted downfield (Dd E 0.3 ppm) in supported by mass spectrometry (ESI+), which showed a signal
comparison to the free ligand. On the other hand, the reso- corresponding to a [(11)NiCl]+ ion. The coordination of ligand 11
nance of the triazole proton in complex 15 is practically the to Ni was finally confirmed by the single crystal X-ray analysis. The
same as that for the proton in the free ligand 10 (8.72 and asymmetric unit consists of two crystallographically independent
8.71 ppm), indicating the absence of triazole coordination to complexes (molecule A and B) and two methanol solvate mole-
the metal atom. A detailed insight into the geometry and the cules (Fig. 4). The octahedral geometry in both molecules (A, B) is
binding mode of the zinc atom to ligand 10 was obtained by slightly distorted, with maximum deviations from the ideal angles
single crystal X-ray analysis.
of 90 and 1801 ranging from 0.08(5)1 to 10.71(6)1 and from 2.94(5)1
The complex 15 is monomeric and features a five coordi- to 9.60(6)1, respectively. Ligand 11 is tridentately coordinated to
nated zinc centre in a distorted trigonal bipyramidal geometry the Ni metal centre in the mer-geometry with Ni–N bonding
(Fig. 3). The distortion of a trigonal bipyramid can be best
described by the structural parameter t (0 for an ideal square
pyramid and 1 for an ideal trigonal bipyramid),28 which in our
case adopts the value of 0.72. The ligand 10 is tridentatly
coordinated to the Zn metal centre in fac-geometry with Zn–N
bonding distances with N1 and N2 pyridyl atoms of 2.068(3)
and 2.074(4) Å, respectively, and one longer distance with the
Fig. 4 Crystal structure of [16(MeOH)]ꢀMeOH, only molecule A is pre-
sented. Selected bond lengths [Å] and angles [1] for molecule A: Ni(1)–N(2)
2.0733(15), Ni(1)–N(4) 2.0488(15), Ni(1)–N(5) 2.0718(15), Ni(1)–O(1) 2.0902(13),
Ni(1)–Cl(1) 2.4311(5), Ni(1)–Cl(2) 2.4289(5), N(2)–Ni(1)–O(1) 92.92(5), N(2)–
Ni(1)–Cl(1) 89.92(5), N(2)–Ni(1)–Cl(2) 88.22(5), N(4)–Ni(1)–N(2) 91.11(6), N(4)–
Ni(1)–N(5) 79.29(6), N(4)–Ni(1)–O(1) 174.97(6), N(4)–Ni(1)–Cl(1) 92.36(5),
N(4)–Ni(1)–Cl(2) 89.94(5), N(5)–Ni(1)–N(2) 170.40(6), N(5)–Ni(1)–O(1)
96.66(6), N(5)–Ni(1)–Cl(1) 90.49(5), N(5)–Ni(1)–Cl(2) 91.73(5), O(1)–Ni(1)–
Cl(1) 84.65(4), O(1)–Ni(1)–Cl(2) 93.18(4), Cl(2)–Ni(1)–Cl(1) 177.063(18);
selected bond lengths [Å] and angles [1] for molecule B: Ni(2)–N(7)
2.0465(15), Ni(2)–N(9) 2.0492(15), Ni(2)–N(10) 2.0457(15), Ni(2)–O(2)
2.0858(13), Ni(2)–Cl(3) 2.4353(5), Ni(2)–Cl(4) 2.4698(5), N(7)–Ni(2)–N(9)
Fig. 3 Crystal structure of 15. Selected bond lengths [Å] and angles [1]:
Zn1–N1 2.068(3), Zn1–N2 2.074(4), Zn1–N3 2.418(3), Zn1–Cl1 2.2630(11),
Zn1–Cl2 2.3110(12), N1–Zn1–N2 117.56(14), N1–Zn1–N3 75.90(11), N2–Zn1–N3
74.78(12), N1–Zn1–Cl1 109.38(10), N1–Zn1–Cl2 101.94(9), N2–Zn1–Cl2
96.45(10), N2–Zn1–Cl1 124.94(10), Cl1–Zn1–N3 91.10(8), Cl2–Zn1–N3
168.12(8), Cl1–Zn1–Cl2 100.58(5).
91.77(6), N(7)–Ni(2)–O(2) 93.04(6), N(7)–Ni(2)–Cl(3) 89.67(5), N(7)–Ni(2)–
Cl(4) 86.60(5), N(9)–Ni(2)–O(2) 173.74(6), N(9)–Ni(2)–Cl(3) 89.30(5), N(9)–
Ni(2)–Cl(4) 91.57(5), N(10)–Ni(2)–N(7) 171.60(6), N(10)–Ni(2)–N(9) 81.42(6),
N(10)–Ni(2)–O(2) 93.42(6), N(10)–Ni(2)–Cl(3) 95.13(4), O(2)–Ni(2)–Cl(3)
94.72(4), N(10)–Ni(2)–Cl(4) 88.66(5), O(2)–Ni(2)–Cl(4) 84.73(4), Cl(3)–Ni(2)–
Cl(4) 176.195(19).
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metal complexes is currently ongoing and will be the subject of
our forthcoming report.
Conclusions
The synthesis of potential tridentate ligands containing a
1,2,3-triazole moiety with either nitrogen or mixed nitrogen
and oxygen donor sites was achieved by employing the con-
vergent protocol starting from 2-amino-1-phenylethanol. Their
coordination ability was tested with two biorelevant metals to
mimic a histidine-carboxylate active site of metallopeptidases.
An all-nitrogen-donor ligand containing a terminal amino
functionality was coordinated to the ZnII ion in a bidentate
fashion, not including a triazole N2 atom. A 1,2,3-triazole-based
ligand containing two 2-picolyl groups was coordinated to the
ZnII ion through tertiary and two pyridine nitrogens, while the
N,N,N ligand with one 2-picolyl arm acted as an inverse-click
chelator for the NiII ion, since an N2 atom of the triazole ring
together with the amino and pyridyl nitrogens was successfully
coordinated to the metal. However, the coordination of the
N,N,O ligand with a terminal hydroxyl group was not achieved
under neutral or under basic conditions. The synthesized
complexes may have potential as bioinspired catalysts and due
to the possibility of introducing a chiral centre they may also be
used in asymmetric transformations.
Fig. 5 Chain formation of molecules A in [16(MeOH)]ꢀMeOH. Dashed
lines indicate the hydrogen bonds. Hydrogen atoms that are not involved
in the motif shown have been omitted for clarity [symmetry codes (i) x + 1,
y, z; (ii) x ꢁ 1, y, z].
Experimental section
General considerations
The reagents and solvents were used as received from commercial
suppliers. The reagent 7 was prepared according to the reported
procedure.29 Melting points were determined on a Kofler micro
hot stage. The NMR spectra were recorded at 302 K either on a
Bruker Avance DPX 300 or Avance III 500 MHz spectrometer
operating at 300 MHz (or 500 MHz) and 75.5 MHz (or 125 MHz)
for 1H and 13C. The 1H NMR spectra are referenced with respect to
TMS as the internal standard. The 13C NMR spectra are referenced
against the central line of the solvent signal (DMSO-d6 septet at d =
39.5 ppm, CDCl3 triplet at d = 77.0 ppm). The coupling constants
(J) are given in Hz. The multiplicities are indicated as follows: s
(singlet), d (doublet), t (triplet), m (multiplet) and br (broadened).
IR spectra were obtained with a Bruker ALPHA FT-IR spectro-
photometer or Bio-Rad FTS 3000MX. MS spectra were recorded
with an Agilent 6224 Accurate Mass TOF LC/MS instrument, VG-
Analytical AutoSpec Q instrument or 4800 MALDI TOF/TOF
Analyzer, Applied Biosystems. Elemental analyses (C, H, N) were
performed using a Perkin-Elmer 2400 Series II CHNS/O Analyzer.
TLC was carried out on Fluka silica gel TLC-cards. Merck silica gel
60 PF254 containing gypsum was used to prepare chromatotron
plates. Radial chromatography was performed using a Harrison
Research, model 7924T chromatotron.
distances 2.0488(15)–2.0733(15) for molecule A and 2.0457(15)–
2.0492(15) for molecule B. The Ni–O bonding distances are
2.0858(13)–2.0902(13) Å and the Ni–Cl distances are 2.4289(5)–
2.4698(5) Å for both molecules. Hydrogen bonding between the
coordinated methanol molecule and the NH group with the
chlorido ligand connects molecules A to a 1D chain (Fig. 5), as
well as molecules B (Table 1). The chains are mutually connected
by p–p stacking [3.827(2) and 3.8765(12) Å] and weak CHꢀ ꢀꢀN and
CHꢀꢀꢀp interactions.
Finally, chelation of N,N,O ligand 13 was also attempted, but
we did not succeed in preparing and isolating the Zn or Ni
complexes of the ligand 13 so far, regardless of the environ-
ment (basic or neutral) that was used in the preparation or the
counteranion (chloride or acetate). The study of the coordina-
tion ability of the ligand 13 as well as potential utility of our
Table 1 Hydrogen bonds for [16(MeOH)]ꢀMeOH; distances [Å] and angles
[1], [symmetry codes (i) x + 1, y, z; (ii) x ꢁ 1, y, z]
D–Hꢀ ꢀ ꢀA
d(D–H)
d(Hꢀ ꢀ ꢀA)
d(Dꢀ ꢀ ꢀA)
+(DHA)
O1–H1Aꢀ ꢀ ꢀCl2i
N4–H4Bꢀ ꢀ ꢀCl1ii
O2–H2Aꢀ ꢀ ꢀCl3ii
N9–H9Bꢀ ꢀ ꢀCl4i
N9–H9Bꢀ ꢀ ꢀCl3
O3–H3Aꢀ ꢀ ꢀCl2
O4–H4Aꢀ ꢀ ꢀCl4
0.836(9)
0.93
0.828(10)
0.93
0.93
0.84
2.491(15)
2.38
2.513(14)
2.43
2.77
2.36
3.2271(14)
3.2123(16)
3.2643(14)
3.2205(16)
3.1636(16)
3.196(2)
147(2)
148.5
151(2)
142.4
106.7
173.6
165.6
X-ray diffraction analysis
Single-crystal X-ray diffraction data were collected using a
Agilent Technologies SuperNova Dual diffractometer with an
0.84
2.34
3.1577(19)
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Atlas detector and Mo-Ka radiation (l = 0.71073 Å) at room 1H NMR (300 MHz, CDCl3): d = 2.66 (br, 1H, OH), 3.32 (m, 1H,
temperature (14 and 15) and 150 K ([16(MeOH)]ꢀMeOH). The CHaHb-CH), 3.56 (m, 1H, CHaHb-CH), 4.84 (dd, J = 3.1, 7.5 Hz,
data were processed using CrysAlis Pro.30 The structures were 1H, CH), 5.11 (s, 2H, CH2-Ph), 5.13 (br, 1H, NH), 7.28–7.41
solved by direct methods using the program SHELXS-97 (m, 10H, Ar) ppm.
(ref. 31) (15) or SIR97 (ref. 32) (14 and [16(MeOH)]ꢀMeOH)
2-[(Benzyloxycarbonyl)amino]-1-phenylethylmethane sulfonate
and refined on F2 using full-matrix least-square procedures (3). To the cooled (0 1C) mixture of 2 (3.772 g, 13.90 mmol),
(SHELXL-97).31 Single crystals of 14 were of an extremely poor triethylamine (2.9 mL, 20.78 mmol) and CH2Cl2 (70 mL), methane-
quality and the data collection was difficult. Hence the some- sulfonyl chloride (1.3 mL, 16.80 mmol) was slowly added. The
what ill-refined structure. However, the main goal was to resulting mixture was stirred at the same temperature for 0.5 h and
establish the zinc binding mode which is undoubtedly and then at r.t. for 1 h. Then water (100 mL) was added and after
fully achieved. All our later attempts to produce the better separation, the organic phase was successively washed with HCl
quality single crystals were unsuccessful. All non-hydrogen (40 mL, 1 M), NaHCO3 (50 mL, sat.), and brine (50 mL) and then
atoms were refined anisotropically. The hydrogen atoms were dried (Na2SO4). After removal of volatiles, 4.695 g (97%) of yellow
1
treated as riding atoms in geometrically idealized positions, oil was obtained. H NMR (500 MHz, CDCl3): d = 3.55 (m, 1H,
except the hydrogen atoms attached to O1 and O2 atoms in CHaHb-CH), 3.69 (m, 1H, CHaHb-CH), 5.10 (d, J = 12 Hz, 1H,
[16(MeOH)]ꢀMeOH that were refined fixing the bond lengths CHaHb-Ph), 5.13 (d, J = 12 Hz, 1H, CHaHb-Ph), 5.24 (s, 3H, Me), 5.65
and isotropic temperature factors. Crystallographic data are (m, 1H, CH), 6.07 (br, 1H, NH), 7.30–7.48 (m, 10H, Ar) ppm. IR
listed in Table 2.
(neat): n = 1743, 1350, 1233, 1216, 1170, 966, 914, 698 cmꢁ1
.
HRMS (ESI+) calcd for C16H16O2N ([M-OSO2Me]+): 254.1181;
found: 254.1177.
Syntheses
Benzyl (2-azido-2-phenylethyl)carbamate (4). The mixture of
3 (4.695 g, 13.44 mmol), used directly from the previous
reaction, NaN3 (4.369 g, 67.21 mmol) and DMF (15 mL) was
stirred at r.t. for 3 h. Then water (100 mL) was added and
extracted with Et2O (3 ꢂ 80 mL). The combined organic layers
were washed with brine (2 ꢂ 80 mL) and dried (Na2SO4). After
removal of volatiles, 3.674 g (92%) of orange oil was obtained.
Rf = 0.59 (3 : 5 petroleum ether/EtOAc). 1H NMR (300 MHz,
CDCl3): d = 3.32 (m, 1H, CHaHb-CH), 3.55 (m, 1H, CHaHb-CH),
4.70 (dd, J = 3.0, 6.0 Hz, 1H, CH), 5.02 (br, 1H, NH), 5.10 (d, J =
12.3 Hz, 1H, CHaHb-Ph), 5.14 (d, J = 12.3 Hz, 1H, CHaHb-Ph),
7.30–7.40 (m, 10H, Ar) ppm. 13C NMR (75.5 MHz, CDCl3): 46.3,
Benzyl (2-hydroxy-2-phenylethyl)carbamate (2). To the cooled
(0 1C) mixture of 2-amino-1-phenylethanol (7.36 g, 53.65 mmol),
triethylamine (11.2 mL, 80.24 mmol) and CH2Cl2 (80 mL),
solution of benzyl chloroformate (9.2 mL, 64.45 mmol) in CH2Cl2
(20 mL) was slowly added. The resulting mixture was allowed to
warm to r.t. and stirred over night. Then water (100 mL) was
added and after separation, the aqueous phase was extracted
with CH2Cl2 (50 mL). Combined organic layers were washed with
water (100 mL) and dried (Na2SO4). After removal of the solvent,
the solid residue was suspended in petroleum ether and filtered
off to give 11.717 g (81%) of a white crystalline product. Rf = 0.61
(1: 10 MeOH/CH2Cl2); m.p. 109–111 1C (ref. 33, 120–121 1C).
Table 2 Crystal-data and structure-refinement details of 14–16
14
15
[16(MeOH)]ꢀMeOH
Formula
Mr
T (K)
C
18H21Cl2N5Zn
C28H26Cl2N6Zn
582.82
293(2)
C24H29Cl2N5NiO2
549.13
150(2)
443.67
293(2)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
a (1)
b (1)
Triclinic
P1
Monoclinic
P21/c
8.8955(9)
14.5691(11)
21.5718(19)
90
91.451(8)
90
2794.8(4)
4
Triclinic
P1
%
%
7.927(1)
10.6150(11)
12.920(2)
78.84(1)
74.08(2)
70.62(1)
979.90(17)
2
6.42170(10)
11.6331(2)
34.4621(8)
89.715(2)
85.211(2)
82.580(2)
2543.95(8)
4
g (1)
Volume (Å3)
Z
Dc [Mg mꢁ3
]
1.504
1.538
456
1.385
1.098
1200
1.434
1.004
1144
m [mmꢁ1
F(000)
]
Crystal size (mm)
Reflections collected
Reflections unique (Rint
Parameters
0.60 ꢂ 0.30 ꢂ 0.20
0.50 ꢂ 0.10 ꢂ 0.10
0.40 ꢂ 0.15 ꢂ 0.10
10 999
20 508
20 188
)
6397 (0.060)
235
0.0989, 0.3133
0.1881, 0.3425
1.049
6399 (0.0581)
334
0.0595, 0.1418
0.1035, 0.1641
1.071
11 625 (0.0170)
625
0.0348, 0.0764
0.0399, 0.0793
1.110
R, wR2 [I 4 2s(I)]a
R, wR2 (all data)b
GOF, Sc
P
P
P
P
P
a
b
2
c
2
R = ||Fo| ꢁ |Fc||/ |Fo|. wR2 = { [w(Fo ꢁ Fc2)2]/ [w(Fo2)2]}1/2
.
S = { [(Fo ꢁ Fc2)2]/(n/p)}1/2 where n is the number of reflections and p is the
total number of parameters refined.
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65.5, 66.9, 126.9, 128.0, 128.1, 128.5, 128.7, 128.9, 136.2, 136.8, (m, 2H, Ar), 7.73–7.82 (m, 5H, Ar and CH triazole) ppm. 13C NMR
156.2 ppm. IR (NaCl) n = 3419, 3334, 3063, 3033, 2939, 2103, (75.5 MHz, CDCl3): 37.3, 47.2, 52.7, 65.3, 119.8. 123.2, 125.7, 126.9,
1708, 1522, 1455, 1250, 1147, 1067, 989, 755, 699 cmꢁ1. HRMS 128.0, 128.6, 128.7, 129.0, 130.6, 132.0, 133.8, 137.5, 147.5,
(ESI+) calcd for C16H17N4O2 ([M + H]+): 297.1352; found 297.1346. 168.4 ppm. IR (KBr): n = 3419, 1770, 1713, 1612, 1396, 767,
Benzyl [2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl]carbamate 719 cmꢁ1. HRMS (ESI+) calcd for C26H24N5O2 ([M + H]+):
(5). To the mixture of 4 (1.689 g, 5.70 mmol), phenylacetylene 438.1925; found 438.1918.
(0.873 g, 8.55 mmol), and t-BuOH/H2O (20 mL, 1 : 1), freshly
N-[2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl]ethane-1,2-
prepared aqueous solutions of sodium ascorbate (570 mL, 1 M) diamine (9). The mixture of 8 (115 mg, 0.263 mmol), hydrazine
and CuSO4ꢀ5H2O (57 mL, 1 M) were added. The resulting mixture hydrate (107 mg, 2.137 mmol), and ethanol (8 mL) was refluxed
was stirred at r.t. for 20 h, then evaporated, and water (50 mL) for 3 h. Then volatiles were evaporated and 1 M aqueous
was added and extracted with CH2Cl2 (3 ꢂ 50 mL). Combined solution of HCl (5 mL) was added. Upon cooling 2,3-dihydro-
organic layers were dried (Na2SO4). After removal of volatiles, the phathalazine-1,4-dione was filtered off. The filtrate was basified
solid residue was suspended in Et2O (50 mL) and filtered off to with 40% aqueous solution of NaOH to pH E 12 and extracted
give 1.59 g (70%) of the product. Rf = 0.41 (1: 1 petroleum ether/ with Et2O (3 ꢂ 10 mL). Combined organic layers were washed
1
EtOAc); m.p. 152–154 1C. H NMR (300 MHz, CDCl3): d = 4.09 with water (5 mL) and dried (Na2SO4). After the removal of the
(m, 1H, CHaHb-CH), 4.22 (m, 1H, CHaHb-CH), 5.05 (d, J = 12.3 Hz, solvent 52 mg (64%) of a white solid was obtained. Rf = 0.26
1H, CHaHb-Ph), 5.11 (d, J = 12.3 Hz, 1H, CHaHb-Ph), 5.45 (br, 1H, (1 : 5 MeOH/CH2Cl2); m.p. 113–115 1C (petroleum ether/EtOAc).
NH), 5.76 (dd, J = 4.2, 9.0 Hz, 1H, CH), 7.26–7.44 (m, 13H, Ar), 1H NMR (500 MHz, DMSO-d6): d = 1.96 (br, 3H, NH, NH2), 2.54
7.68 (s, 1H, CH triazol), 7.79 (m, 2H, Ar) ppm. 13C NMR (75.5 MHz, (m, 4H, CH2-CH2), 3.24 (dd, J = 5.0, 13.0 Hz, 1H, CHaHb-CH),
DMSO-d6): 44.4, 63.5, 65.3, 120.8, 125.1, 127.0, 127.5, 127.7, 127.8, 3.57 (dd, J = 9.5, 13.0 Hz, 1H, CHaHb-CH), 5.87 (dd, J = 5.0,
128.2, 128.5, 128.6, 128.9, 130.7, 136.9, 137.3, 146.4, 156.2 ppm. IR 9.5 Hz, 1H, CH), 7.30–7.47 (m, 8H, Ar), 7.86 (m, 2H, Ar), 8.81
(KBr) n = 3395, 3078, 2934, 1699, 1523, 1458, 1425, 1261, 1204, (s, 1H, CH triazole) ppm. 13C NMR (125.7 MHz, DMSO-d6): 41.2,
1157, 1076, 998, 932, 909, 854, 745, 693, 544, 515 cmꢁ1. HRMS 51.8, 52.9, 64.4, 120.8, 125.1, 126.9, 127.8, 128.1, 128.7, 128.8,
(ESI+) calcd for C24H23N4O2 ([M + H]+): 399.1821; found 399.1835. 130.8, 138.7, 146.2 ppm. IR (KBr): n = 3409, 3338, 3087, 2936,
C24H22N4O2 (398.46): calcd C 72.34, H 5.57, N 14.06; found C 1618, 1559, 1458, 766, 697 cmꢁ1. HRMS (ESI+) calcd for C18H22N5
72.15, H 5.50, N 13.97.
2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethan-1-amine (6). 70.33, H 6.89, N 22.78; found C 70.30, H 6.67, N 22.57.
The mixture of 5 (2.22 g, 5.57 mmol), MeOH (250 mL), and Pd/C 2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-N,N-bis(pyridin-2-
([M + H]+): 308.1875; found 308.1888. C18H21N5 (307.39): calcd C
(1.18 g, 1.11 mmol; 10 wt%) was hydrogenated under H2 (60 psi) ylmethyl)ethanamine (10). The mixture of 6 (100 mg, 0.378 mmol),
at r.t. for 8 h. Then the catalyst was filtered off, the filtrate was 2-picolylbromide hydrobromide (200 mg, 0.791 mmol), DIPEA
concentrated and the residue was passed through a short column (195 mg, 1.509 mmol), and MeCN (5 mL) was stirred at 80 1C for
of silicagel with MeOH as the eluent. After the removal of the 5 h. Then volatiles were evaporated, water was (10 mL) added and
solvent, 1.41 g (96%) of a white product was obtained. Rf = 0.35 extracted with DCM (3 ꢂ 10 mL). Combined organic layers were
1
(1 : 10 MeOH/CH2Cl2); m.p. 108.5–110.5 1C. H NMR (300 MHz, dried (Na2SO4) and evaporated. The solid residue was subjected
DMSO-d6): d = 3.22 (br, 2H, NH2), 3.33 (dd, J = 5.1, 13.5 Hz, 1H, to column chromatography (SiO2, MeOH/CH2Cl2 1 : 20) to give
CHaHb-CH), 3.58 (dd, J = 9.3, 13.5 Hz, 1H, CHaHb-CH), 5.74 (dd, J = 101 mg (60%) of a white product. Rf = 0.55 (1: 10 MeOH/CH2Cl2);
5.4, 9.2 Hz, 1H, CH), 7.29–7.48 (m, 8H, Ar), 7.86 (m, 2H, Ar), 8.79 m.p. 127.5–129 1C (petroleum ether/EtOAc). 1H NMR (500 MHz,
(s, 1H, CH triazole) ppm. 13C NMR (75.5 MHz, DMSO-d6): 46.1, DMSO-d6): d = 3.33 (m, 1H, CHaHb-CH), 3.67 (dd, J = 10 Hz,
67.5, 120.8, 125.1, 126.8, 127.7, 128.0, 128.7, 128.8, 130.8, 138.6, 13.5 Hz, 1H, CHaHb-CH), 3.81 (d, J = 14.5 Hz, 2H, 2 ꢂ Py-CHaHb),
146.3 ppm. IR (KBr) n = 3451, 3366, 3283, 1607, 1456, 1218, 1075, 3.92 (d, J = 14.5 Hz, 2H, 2 ꢂ Py-CHaHb), 5.93 (dd, J = 5 Hz, 10 Hz,
760, 691 cmꢁ1. HRMS (ESI+) calcd for C16H17N4 ([M + H]+): 1H, CH), 7.07 (m, 2H, Py), 7.22 (ddd, J = 1, 5, 7.5 Hz, 2H, Py),
265.1453; found 265.1459. C16H16N4 (264.33): calcd C 72.70, H 7.31–7.41 (m, 6H, Ar), 7.46 (m, 2H, Ar), 7.59 (ddd, J = 2, 7.5,
6.10, N 21.20; found C 72.50, H 6.14, N 20.99.
7.5 Hz, 2H, Py), 7.83 (m, 2H, Ph), 8.48 (ddd, J = 1, 2, 5 Hz, 2H, Py),
2-{2-[2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethylamino]- 8.72 (s, 1H, CH triazole) ppm. 13C NMR (75.5 MHz, CDCl3): d =
ethyl}isoindoline-1,3-dione (8). A solution of 6 (622 mg, 58.5, 60.6, 63.1, 118.9, 122.2, 123.4, 125.6, 127.0, 128.0, 128.5,
2.353 mmol), N-(2-bromoethyl)phthalimide (598 mg, 2.354 mmol), 128.7, 128.9, 130.7, 136.5, 137.4, 147.3, 148.8, 158.8 ppm. IR
DIPEA (608 mg, 4.70 mmol), and DMSO (5 mL) was stirred at (neat): n = 3144, 3061, 3011, 2829 1590, 1432, 1362, 1028, 767,
100 1C for 14 h. To the cold reaction mixture brine (30 mL) was 696 cmꢁ1. HRMS (ESI+) calcd for C28H27N6 ([M + H]+): 447.2297;
added and extracted with EtOAc (3 ꢂ 30 mL). Combined organic found 447.2292. C28H26N6 (446.55): calcd C 75.31, H 5.87,
layers were washed with brine (2 ꢂ 30 mL) and dried (Na2SO4). N 18.82; found C75.58, H 5.68, N 18.87.
After removal of volatiles, the oily residue was subjected to radial
2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-N-(pyridin-2-ylmethyl)-
chromatography (SiO2; MeOH/CH2Cl2 1 : 100, then 50 : 1, then ethanamine (11). To the mixture of 6 (106 mg, 0.401 mmol) and
20 : 1) giving 532 mg (52%) of orange oil. 1H NMR (300 MHz, MeOH/CH3CO2H (3 mL/0.1 mL), a solution of 2-pyridine-
CDCl3): d = 1.40 (br, 1H, NH), 2.98 (t, J = 6.0 Hz, 2H, CH2), 3.38 carboxaldehyde (86 mg, 0.803 mmol) in MeOH (1 mL) was
(dd, J = 5.1, 12.9 Hz, 1H, CHaHb-CH), 3.81 (m, 3H, CHaHb-CH and added. The resulting mixture was stirred at r.t. for 0.5 h, then
CH2), 5.72 (dd, J = 5.1, 8.7 Hz, 1H, CH), 7.24–7.43 (m, 8H, Ar), 7.65 NaCNBH3 (101 mg, 1.607 mmol) was added portion wise over a
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period of 1 h and afterwards stirred for additional 0.5 h. The found 309.1706. C18H20N4O (308.38): calcd C 70.11, H 6.54,
reaction mixture was evaporated and the mixture of NaOH N 18.17; found C 70.18, H 6.41, N 17.87.
(2 mL, 35%) and water (10 mL) was added, and extracted with
Complex [Zn(9)Cl2] (14). The mixture of 9 (134 mg,
DCM (4 ꢂ 10 mL). Combined organic layers were dried 0.44 mmol) in CH2Cl2 (6 mL) and ZnCl2 (63 mg, 0.46 mmol)
(Na2SO4) and evaporated. The residue was purified by radial in MeOH (5 mL) was stirred at room temperature. The white
chromatography (SiO2; MeOH/CH2Cl2 50 : 1) giving 32 mg precipitate was filtered off, washed with cold MeOH and dried
(22%) of a yellowish product. Rf = 0.63 (1 : 10 MeOH/CH2Cl2); to give 165 mg (85%) of an analytically (CHN and NMR) pure
1
m.p. 116–119 1C (petroleum ether/EtOAc). H NMR (500 MHz, complex. Colourless crystals suitable for the single crystal X-ray
DMSO-d6): d = 2.58 (br, 1H, NH), 3.28 (dd, J = 5, 13 Hz, 1H, analysis were obtained by a slow evaporation from the aceto-
1
CHaHb-CH), 3.61 (dd, J = 9.5, 13 Hz, 1H, CHaHb-CH), 3.87 nitrile solution at the room temperature. H NMR (500 MHz,
(AB, 2H, Py-CH2), 5.96 (dd, J = 5, 9.5 Hz, 1H, CH), 7.22 (ddd, DMSO-d6): d = 2.58–2.78 (m, 4H, CH2-CH2), 3.35 (m, 1H, CHaHb-CH),
J = 1, 4.5, 7.5 Hz, 1H, Py), 7.31–7.47 (m, 9H, Py and Ar), 7.70 3.85 (dd, J = 10, 13.5 Hz, 1H, CHaHb-CH), 4.05 (br, 3H, NH, NH2),
(ddd, J = 2, 7.5, 7.5 Hz, 1H, Py), 7.86 (m, 2H, Ar), 8.47 (ddd, J = 1, 2, 6.13 (dd, J = 3.5, 10 Hz, 1H, CH), 7.32–7.47 (m, 8H, Ar), 7.87
5 Hz, 1H, Py), 8.82 (s, 1H, CH triazole) ppm. 13C NMR (125.7 MHz, (m, 2H, Ar), 8.82 (s, 1H, CH triazole) ppm. 13C NMR (125.7 MHz,
DMSO-d6): d = 52.6, 53.9, 64.3, 120.9, 121.8, 121.9, 125.1, 126.9, DMSO-d6): d = 38.7, 48.5, 52.5, 63.3, 121.7, 125.1, 126.6, 127.9,
127.8, 128.2, 128.7, 128.9, 130.8, 136.5, 138.6, 146.2, 148.8, 159.9 128.5, 128.90, 128.92, 130.7, 138.0, 146.6 ppm. IR (neat): n =
ppm. IR (neat): n = 3299, 3120, 3085, 2907, 2821, 1589, 1478, 1428, 3321, 3231, 3149, 1593, 1457, 1442, 1431, 1226, 1153, 1122, 1078,
841, 759, 688 cmꢁ1. HRMS (ESI+) calcd for C22H22N5 ([M + H]+): 1016, 983, 761, 727, 694 cmꢁ1. MALDI-TOF [C18H21ClN5Zn]+
356.1870; found 356.1870. C22H21N5 (355.44): calcd C 74.34, ([M ꢁ Cl]+): (406.07); found 406.07. C18H21Cl2N5Zn (443.71):
H 5.96, N 19.70; found C 73.94, H 6.11, N 19.49.
calcd C 48.72, H 4.77, N 15.78; found C 48.73, H 4.71, N 15.52.
2-Chloroethyl 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl-
Complex [Zn(10)Cl2] (15). The mixture of 10 (150 mg,
carbamate (12). To a solution of 6 (368 mg, 1.392 mmol) and 0.336 mmol), ZnCl2 (46 mg, 0.337 mmol), and MeOH (3 mL) was
pyridine (156 mL, 1.94 mmol) in CH2Cl2 (10 mL), 2-chloroethyl stirred for 1 day at r.t. and then cooled. After approximately 1 week
chloroformate (157 mL, 1.52 mmol) was added. The resulting white crystals were filtered off, washed with MeOH and dried to give
mixture was stirred at r.t. for 2.5 h, afterwards water (15 mL) was 165 mg (84%) of an analytically (CHN and NMR) pure complex.
added. Layers were separated and the water phase was extracted Crystals suitable for X-ray analysis were obtained from methanol
with CH2Cl2 (3 ꢂ 10 mL). Combined organic layers were dried solution at 4 1C. 1H NMR (500 MHz, DMSO-d6): d = 3.29 (dd, J = 3.5,
(Na2SO4) and evaporated to give 467 mg (90%) of a white solid. 15 Hz, 1H, CHaHb-CH), 3.90 (dd, J = 9, 14.5 Hz, 1H, CHaHb-CH), 3.98
Rf = 0.59 (1 : 20 MeOH/CH2Cl2); m.p. 138–140 1C. 1H NMR (br, 2H, 2 ꢂ Py-CHaHb), 4.13 (br, 2H, 2 ꢂ Py-CHaHb), 6.46 (d, J = 6 Hz,
(300 MHz, CDCl3): d = 3.61 (t, J = 5.7 Hz, 2H, CH2), 4.09 1H, CH), 7.27 (br, 2H, Py), 7.29–7.39 (m, 6H, Ar), 7.48 (m, 2H, Ar),
(m, 1H, CHaHb-CH), 4.21 (m, 1H, CHaHb-CH), 4.28 (m, 2H, CH2), 7.47 (br, 2H, Py), 7.84 (m, 2H, Ar), 7.95 (br, 2H, Py), 8.72 (s, 1H, CH
5.58 (t, J = 4.7 Hz, 1H, NH), 5.75 (dd, J = 4.7, 9.3 Hz, 1H, CH), 7.23– triazole), 8.92 (br, 2H, Py) ppm. 13C NMR (125.7 MHz, DMSO-d6): d =
7.45 (m, 8H, Ar), 7.70 (s, 1H, CH triazole), 7.79 (m, 2H, Ar) ppm. 13
C
55.8 (br), 56.4 (br), 60.4 (br), 121.1, 124.1 (br), 124.2 (br), 125.2, 126.7,
NMR (75.5 MHz, CDCl3): d = 41.8, 45.2, 64.7, 64.9, 120.5, 125.7, 128.1, 128.5, 128.9, 129.0, 130.4, 138.5, 140.0 (br), 146.9, 148.6, 154.7
126.7, 128.3, 128.8, 129.0, 129.2, 130.2, 136.8, 148.1, 156.0 ppm. (br) ppm. IR (neat): n = 3127, 3103, 3064, 3035, 2940, 1607, 1572,
IR (KBr): n = 3401, 1710, 1520, 1263, 1240, 764, 692 cmꢁ1. HRMS 1486, 1444, 1429, 1025, 764, 697, 648 cmꢁ1. HRMS (ESI+) calcd for
(ESI+) calcd for C19H20ClN4O2 ([M + H]+): 371.1269; found C28H27N6 ([M
ꢁ
ZnCl2 +
H]+): 447.2292; found 447.2290.
371.1270.
C28H26Cl2N6Zn (582.86): calcd C 57.70, H 4.50, N 14.42; found
2-{[2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl]amino}ethan- C 57.61, H 4.27, N 14.55.
1-ol (13). To the mixture of 12 (467 mg, 1.26 mmol), directly used
Complex [Ni(11)Cl2] (16). The mixture of 11 (77 mg,
from the previous reaction, and EtOH (20 mL), solution of KOH 0.217 mmol), NiCl2ꢀ6H2O (52 mg, 0.219 mmol), and MeOH
(680 mg, 12.12 mmol) in water (6 mL) was added and refluxed for (2 mL) was stirred for 1 day, then treated with Et2O (1 mL) and
1.5 h. Afterwards the mixture was evaporated under reduced cooled. After approximately one week blue crystals were filtered
pressure and the solid residue was suspended in water (15 mL) off, washed with MeOH/Et2O (2 : 1) and dried to give 56 mg (53%)
and vigorously stirred. The white solid was filtered off, thoroughly of the product. Crystals suitable for X-ray analysis were obtained
washed with water and dried to give 302 mg (78%) of the product. from MeOH/Et2O (2 :1) solution at 4 1C. IR (neat): n = 3160, 2918,
Rf = 0.18 (1 : 20 MeOH/CH2Cl2); m.p. 109–112 1C (MeOH/H2O). 1608, 1481, 1456, 1441, 1333, 1160, 1083, 1024, 975, 961, 932, 769,
1H NMR (300 MHz, DMSO-d6): d = 1.82 (br, 1H, NH), 2.64 (m, 2H, 724, 696 cmꢁ1. HRMS (ESI+) calcd for C22H21ClN5Ni ([M ꢁ Cl]+):
CH2), 3.28 (dd, J = 4.9, 13.1 Hz, 1H, CHaHb-CH), 3.41 (dt, J = 4.9, 4.9 448.0833; found 448.0833. C22H21Cl2N5NiꢀH2Oꢀ0.5MeOH: calcd
Hz, 2H, CH2-OH), 3.60 (dd, J = 9.6, 13.1 Hz, 1H, CHaHb-CH), 4.44 C 52.06, H 4.85, N 13.49; found C 52.08, H 4.41, N 13.72.
(t, J = 4.9 Hz, 1H, OH), 5.89 (dd, J = 4.9, 9.6 Hz, 1H, CH), 7.25–7.50
(m, 8H, Ar), 7.86 (m, 2H, Ar), 8.79 (s, 1H, CH triazole) ppm. 13C
NMR (75.5 MHz, DMSO-d6): 51.1, 53.0, 60.3, 64.4, 120.8, 125.1,
126.9, 127.8, 128.1, 128.7, 128.8, 130.8, 138.7, 146.2 ppm. IR (KBr):
Acknowledgements
n = 3409, 3273, 3081, 2896, 2870, 1487, 1457, 1230, 1076, 913, 764, We thank the Ministry of Higher Education, Science and
693 cmꢁ1. HRMS (ESI+) calcd for C18H21N4O ([M + H]+): 309.1710; Technology of the Republic of Slovenia and the Slovenian
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Research Agency for financial support (P1-0230-0103, P1-0230-
0175) and Ministry of Science, Education and Sports of the
Republic of Croatia (grant 098-1191344-2943) for financial
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support. Dr D. Zigon (Center for Mass Spectroscopy, ‘‘Joˇzef
Stefan’’ Institute, Ljubljana, Slovenia) is gratefully acknow-
ledged for the mass measurements. This work was partially sup-
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