Structural variety of zinc and copper complexes based on a 2,3-disubstituted 1,2,3,4-tetrahydroquinazoline ligand

Article abstract of DOI:10.1039/c2dt30550j

The ring-chain tautomerism of 2-(3-tosyl-1,2,3,4-tetrahydroquinazolin-2-yl) quinolin-8-ol (H₂L^ring) has been exploited to produce mononuclear complexes or, alternatively, dinuclear complexes, as desired, by varying the stoichiometry of the ligand. Cu²⁺ and Zn²⁺ stabilise the ring tautomeric form of the ligand in their mononuclear complexes M(HL^ring)₂. The structural characterisation of Zn(HL ^ring)₂·2MeOH·0.5H₂O shows O,N-donor behaviour of the ring tautomer. The 1,2,3,4-tetrahydroquinazoline undergoes a ring-opening reaction upon formation of phenoxo-bridged dinuclear complexes M₂(L^chain)₂ in which the chain tautomer is acting as O,N,N,N-donor. The crystal structure of Cu ₂(L^amide)(L^quinazoline)(MeOH)·2MeOH evidenced the sensitivity of H₂L^ring to the copper-mediated aerobic oxidation, which results in two derivatives of the ligand, a quinazoline and an amide. The quinazoline ligand is acting as monoanionic and mononucleating through its O,N,N binding site, while the amide ligand behaves as a trianionic and binucleating through its O,N,N,N and O,O binding sites in Cu₂(L^amide)(L^quinazoline) (MeOH)·2MeOH.

Full text of DOI:10.1039/c2dt30550j

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PAPER
Structural variety of zinc and copper complexes based on a 2,3-disubstituted
1,2,3,4-tetrahydroquinazoline ligand†
Jesús Sanmartín-Matalobos,*a Cristina Portela-García,a Luis Martínez-Rodríguez,a
Concepción González-Bello,*b Emilio Lence,b Ana M. García-Deibea and Matilde Fondoa
Received 7th March 2012, Accepted 3rd April 2012
DOI: 10.1039/c2dt30550j
The ring-chain tautomerism of 2-(3-tosyl-1,2,3,4-tetrahydroquinazolin-2-yl)quinolin-8-ol (H2Lring) has
been exploited to produce mononuclear complexes or, alternatively, dinuclear complexes, as desired, by
varying the stoichiometry of the ligand. Cu2+ and Zn2+ stabilise the ring tautomeric form of the ligand in
their mononuclear complexes M(HLring)2. The structural characterisation of Zn(HLring)2·2MeOH·0.5H2O
shows O,N-donor behaviour of the ring tautomer. The 1,2,3,4-tetrahydroquinazoline undergoes a ring-
opening reaction upon formation of phenoxo-bridged dinuclear complexes M2(Lchain)2 in which the chain
tautomer is acting as O,N,N,N-donor. The crystal structure of Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH
evidenced the sensitivity of H2Lring to the copper-mediated aerobic oxidation, which results in two
derivatives of the ligand, a quinazoline and an amide. The quinazoline ligand is acting as monoanionic
and mononucleating through its O,N,N binding site, while the amide ligand behaves as a trianionic and
binucleating through its O,N,N,N and O,O binding sites in Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH.
Introduction
Quinazoline compounds have been under active study and as a
result it has been found that many alkaloids quinazoline-based
exhibit anticonvulsant, antibacterial, antidiabetic and anticancer
activities.1–3 A number of conventional methods for the
synthesis of substituted quinazolines are known,4–6 but very
recently a convenient one-pot procedure has been reported from
condensation of 2-aminobenzylamines with aryl aldehydes to
form 2-aryl-1,2,3,4-tetrahydroquinazolines, which were aerobi-
cally oxidised by employing Cu+/DABCO/4-HO-TEMPO as the
catalysts (Scheme 1).7
Ring-chain tautomerism is known to occur in 2- and 3-substi-
tuted 1,2,3,4-tetrahydroquinazolines,8,9 which is the reason why
metal complexes of ring tautomers have seldom been
described,10,11 while complexes of chain tautomers are the
common ones.12,13 Our previous studies11 suggest that the ring-
chain equilibrium is controlled by the coordinative requirements
aDepartamento de Química Inorgánica, Facultad de Química,
Universidad de Santiago de Compostela, 15782 Santiago de
Scheme 1 A route to synthesise 2-aryl quinazolines via oxidation
Compostela, Spain. E-mail: jesus.sanmartin@usc.es; Fax: +34 981
of 2-aryl-1,2,3,4-tetrahydroquinazolines, which exhibit ring-chain
528073
bCentro Singular de Investigación en Química Biológica y Materiales
tautomerism.
Moleculares (CIQUS), Universidad de Santiago de Compostela, calle
Jenaro de la Fuente s/n, 15782 Santiago de Compostela, Spain.
E-mail: concepcion.gonzalez.bello@usc.es
of the metal, which provides the sulfonamide N atom in an appro-
priate conformation and promotes an intramolecular cyclisation
reaction by activation of the imine C through N coordination.
In this work we report the structural variety of mono- and
dinuclear zinc and copper complexes based on a 2,3-disubsti-
tuted 1,2,3,4-tetrahydroquinazoline ligand (H2Lring) emanating
†Electronic supplementary information (ESI) available: Gibbs free
energy details and coordinates of the most stable conformers tetrahedral
Zn(II) complex as well as representative bidimensional spectra of dinuc-
lear complexes. CCDC 860095 and 860096. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c2dt30550j
6998 | Dalton Trans., 2012, 41, 6998–7004
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proportion of Zn(HLchain
)
was detected in the spectra of the
2
Zn2+/H2Lring system. In contrast, a negligible proportion of Zn-
(HLchain)2 is observed when the reaction was performed at room
temperature.
Slow evaporation of the mother liquor of Cu2(Lchain)2 during a
three day period at room temperature yielded brown crystals of
Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH as by-product, in which
derivatives of both tautomeric forms of the ligand are present,
an amide and a quinazoline (Scheme 2). The formation of
HLquinazoline can be explained as due to the hydrolysis or metha-
nolysis of the tosylamide group, which is supported by the
1
identification of p-TsOH (p-toluenesulfonic acid) by H NMR
spectroscopy on the mother liquor of Cu2(Lchain)2. Then, a Cu2+-
mediated oxidation of the resulting 2-substituted tetrahydroqui-
nazoline could occur. The oxidation of both 1,2,3,4-tetrahydro-
quinazolines to quinazolines6,7 and imines to amides14 are topics
that have received attention in the last years. An investigation
leading to preparation of 2-substituted quinazolines from the
one-pot reaction of aldehydes with 2-aminobenzylamines by
employing CuCl/DABCO/4-HO-TEMPO as the catalysts and
oxygen as the terminal oxidant7 (Scheme 1) showed that the
process also occurs by using Cu2+ instead of Cu+. Control
experiments showed that the presence of 4-HO-TEMPO is useful
to improve the yield, but not essential for achieving aerobic oxi-
dation. In this study, we provide evidence that the oxidative reac-
tion of a tetrahydroquinazoline occurs even if only Cu2+ is
present, i.e. without the use of oxidation promoters.
Scheme 2 Monodeprotonated HLring and Lquinazoline, bisdeprotonated
Lchain and trisdeprotonated Lamide in the complexes of this work. The
binding sites are indicated by arrows. The numbering scheme was used
for the assignment of the NMR signals. An asterisk has been used to
label the chiral atom (C9) of HLring
.
The characterisation by X-ray crystallography of Cu2(Lamide)-
(Lquinazoline)(MeOH)·2MeOH also evidenced the formation of
the amide ligand H3Lamide, which was isolated from the mother
liquor and spectroscopically characterised (see Experimental
section). Since the starting reagents were only H2Lring and
Cu(OAc)2·H2O, the formation of H3Lamide can be explained as
due to a transformation of the initial ligand that can occur either
as a chain (imine) or as a ring (1,2,3,4-tetrahydroquinazoline).
Several methods have been described for the synthesis of
amides,14 but none of them use 1,2,3,4-tetrahydroquinazolines
as precursors and few of them start with imines. Two methods
for amide formation from imines stand out because of their
simplicity. The straightforward method was reported by Ghaffar-
zadeh and co-workers14a who use a silicon-based reducing
agent, Et3SiH, in the presence of zinc dust, and the method
reported by Rhee and co-workers14b uses BF3·OEt2 in conjunc-
tion with a strong oxidising agent, 3-chloroperoxybenzoic acid.
Here, we show that the reaction can occur by air and in the
presence of Cu2+ ions.
from both its ring-chain tautomerism and its sensitivity to
copper-mediated aerobic oxidation. The structural characteri-
sation of Zn(HLring)2·2MeOH·0.5H2O and Zn2(Lchain)2 revealed
the O,N-donor behaviour of the ring tautomer while the chain
tautomer is acting as O,N,N,N-donor, as depicted in Scheme 2.
On the other hand, the X-ray crystal structure of Cu2(Lamide)-
(Lquinazoline)(MeOH)·2MeOH revealed the sensitivity of this
system to copper-mediated aerobic oxidation, which results in
two derivatives of the ligand, a quinazoline and an amide. The
quinazoline ligand Lquinazoline is acting as monoanionic and
mononucleating through its O,N,N binding site in the dinuclear
copper complex, while the amide ligand Lamide behaves as
trianionic and binucleating through its O,N,N,N and O,O binding
sites (Scheme 2). To the best of our knowledge, Cu2(Lamide)-
(Lquinazoline)(MeOH)·2MeOH is the first case reported in which
the Otosyl,Ophenoxo donor set of this type of N-tosyl ligands forms
a second binding site for an outer metal ion.
Results and discussion
Crystal structure of Cu2(Lamide)(Lquinoline)(MeOH)·2MeOH
A reactivity study on Zn2+/H2Lring and Cu2+/H2Lring systems
showed that mononuclear complexes of the ring tautomer are the
main products obtained at methanol reflux temperature when a
1 : 2 molar ratio was used. The characterization by X-ray diffrac-
tion techniques of Zn(HLring)2·2MeOH·0.5H2O supports this.
However, if the molar ratio is varied from 1 : 2 to 1 : 1, the
course of this reaction can be fundamentally altered to produce
phenoxo-bridged dinuclear complexes of the chain tautomer,
such as Cu2(Lchain)2 and Zn2(Lchain)2·2MeOH. Regardless of the
molar ratio used, at methanol reflux temperature, a low
An ORTEP representation of the dinuclear complex is shown in
Fig. 1. Both coordination environments that can be described as
distorted square-based pyramids are rather similar. The most sig-
nificant geometric data are given in Table 1 along with selected
data for the H bonding scheme.
Cu2(Lamide)(Lquinoline)(MeOH) is formed by [Cu(Lquinoline)]+
and [Cu(Lamide)(MeOH)]− moieties, which are linked together
through both a μ-phenoxo bridge and an unusual coordination of
an Otosyl atom of trisdeprotonated Lamide. Thus, the amide ligand
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behaves as binucleating through its O,N,N,N and O,O binding
sites. The O,N,N,N donor set occupies the base of a distorted
square-based pyramid, the apex of which is occupied by a coor-
dinated methanol molecule (Fig. 1). The apical vertex and one of
the basal positions of the square-based pyramid in the
coordination sphere of an outer Cu2+ion are occupied by the
O
tosyl and Ophenoxo atoms of Lamide, respectively. The outer metal
ion completes its coordination sphere through the O,N,N donor
set of the monodeprotonated Lquinoline
.
A true coordination (i.e. not secondary interaction) of Otosyl
atoms is rather unusual, but a few mono- and dinuclear com-
plexes of N-tosyl substituted ligands have been reported
in which one of the O atoms of the sulphonamide group is co-
ordinated in a monodentate mode.15,16 To the best of our
knowledge, Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH is the first
case reported in which the Otosyl,Ophenoxo donor set of this type
of N-tosyl substituted ligands forms a second binding site for an
outer metal ion.
Crystal structure of Zn(HLring)2·2MeOH·0.5H2O
The unit cell of Zn(HLring)2·2MeOH·0.5H2O consists of mol-
ecules of the neutral complex (Fig. 2), each of which interacts
with two molecules of solvated methanol, and disordered water
molecules with low occupation sites. The main geometric par-
ameters of the metal complex are listed in Table 1, which
includes the H bonding scheme.
In the crystal, the metal center is coordinated to two monoa-
nionic units of the ring ligand, which behaves as a bidentate
system through the N,O donor set of the 8-hydroxyquinoline
Fig. 1 Ellipsoid representation at the 40% probability level of the
molecular structure of Cu2(Lamide)(Lquinoline)(MeOH).
Table 1 Main bond distances [Å] and angles [°] for the coordination environments of Zn(HLring)2·2MeOH·0.5H2O and Cu2(Lamide)(Lquinazoline
)
(MeOH)·2MeOH
Zn(HLring)2·2MeOH·0.5H2O
Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH
Distance
Distance
Distance
Zn1–N101
Zn1–O101
Zn1–N201
Zn1–O201
Zn1⋯N102
Zn1⋯N202
1.994(2)
1.998(2)
2.035(3)
2.038(3)
2.699(3)
2.717(3)
Cu1–N101
Cu1–N102
Cu1–O101
Cu1–N103
Cu1–O1S
1.902(2)
1.998(2)
2.145(2)
1.908(2)
2.325(2)
Cu2–N201
Cu2–N202
Cu2–O101
Cu2–O201
Cu2–O103
1.915(3)
2.058(3)
1.909(2)
2.000(2)
2.2929(19)
Angle
Angle
Angle
O201–Zn1–O101
O201–Zn1–N101
O101–Zn1–N101
O201–Zn1–N201
O101–Zn1–N201
N101–Zn1–N201
108.25(9)
115.39(10)
83.26(10)
83.66(10)
115.30(10)
148.90(11)
N101–Cu1–N103
N101–Cu1–N102
N103–Cu1–N102
N101–Cu1–O101
N103–Cu1–O101
N102–Cu1–O101
N101–Cu1–O1S
N103–Cu1–O1S
N102–Cu1–O1S
O101–Cu1–O1S
163.17(10)
81.50(10)
95.81(10)
79.20(9)
100.99(9)
159.84(9)
89.58(9)
107.23(9)
94.69(10)
90.93(9)
O101–Cu2–N201
O101–Cu2–O201
N201–Cu2–O201
O101–Cu2–N202
N201–Cu2–N202
O201–Cu2–N202
O101–Cu2–O103
N201–Cu2–O103
O201–Cu2–O103
N202–Cu2–O103
175.94(10)
101.65(9)
82.28(11)
97.20(10)
78.77(11)
159.38(10)
89.90(8)
90.64(9)
96.88(8)
91.40(8)
H bond scheme for Zn(HLring)2·2MeOH·0.5H2O
N202–H2A⋯O2S
N102–H2B⋯O1S
O1S–H1S⋯O201
O2S–H2S⋯O101
0.83(4)
0.89(4)
0.84
2.25(4)
2.30(4)
1.90
2.935(4)
3.007(4)
2.674(3)
2.669(3)
140(3)
135(3)
154
0.84
1.88
157
H bond scheme for Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH
O(1S)–H(1S)⋯O(3S)
O(2S)–H(2S)⋯O(102)
O(3S)–H(3S)⋯O(201)
0.91(4)
0.76(4)
0.84
1.77(5)
2.01(4)
1.81
2.674(4)
2.759(3)
2.632(3)
173(4)
171(4)
167
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Fig. 2 Ellipsoid representation at the 50% probability level of the mol-
ecular structure of Zn(HLring)2·2MeOH·0.5H2O. Some labels have been
omitted for clarity. The figure shows the Λ-C(S,S) enantiomer of the
complex.
Fig. 3 Comparison of calculated (green) and found (violet) structures
of Zn(HLring)2.
residue. This arrangement gives rise to a distorted tetrahedral
coordination environment, the deformation of which appears to
be mainly related to two secondary interactions with the two pro-
tonated amine N atoms of the tetrahydroquinazoline moieties.
Zn(HLring)2·2MeOH·0.5H2O is chiral, not only because it con-
tains a chiral ligand (Scheme 2) but also because it is helical.
This spatial disposition combined with the planarity of the con-
jugated 8-hydroxyquinoline residues leads to a typical double-
bladed propeller arrangement around the zinc ion, a situation that
gives rise to helical chirality (Δ,Λ) for the global molecule.
As the crystal structure corresponds to the centrosymmetric
P21/c group, a (Δ,Λ)-racemate can be considered for this
complex in the unit cell. For the nomenclature of this helicate,
the helicity (Δ,Λ) is indicated first, and this is followed by the
configurations (R,S) of the two ligand units arranged in accord-
ance with their numbering scheme for chiral atoms C109 and
C209, respectively. Since each Δ and Λ enantiomer of Zn
(HLring)2·2MeOH·0.5H2O involves two ligands of identical chir-
ality, the racemate could be named as Λ-(S,S),Δ-(R,R)-Zn-
(HLring)2·2MeOH·0.5H2O.
Fig. 4 Relative Gibbs free energy for the most stable conformers cal-
culated (in methanol) for tetrahedral zinc complexes. Only Λ-isomers of
helical Zn(HLring)2 are represented.
but similar trends were found (see ESI†). Then, calculation of
the relative Gibbs free energy difference was also performed
(Fig. 4). These results show that Zn(HLring)(HLchain) and Zn-
(HLchain)2 are the least stable isomers of the series and there is
almost no difference between them. In contrast, the difference in
Theoretical studies
Computational studies were undertaken in order to gain an
insight into both the relative energies of the most stable possible
isomers of mononuclear zinc complexes and the type of bridge
involved in Zn2(Lchain)2. Geometry optimizations and energy
calculations were performed using the Gaussian 09W17 program
package at the density functional theory (DFT) level by means
of the hybrid M06 functional18 using the standard 6-31G(d)
basis set. A polarizable continuum19 solvation model was used
for energy minimisations to take into account the solvent (metha-
nol) effect. The very good agreement between the geometric par-
ameters found and those estimated by using DFT calculations is
clear in Fig. 3, which shows both the found molecular structure
and the calculated model by using Gaussian 09W.17
the relative Gibbs free energy between Zn(HLchain
) and the
2
experimentally obtained Λ-(S,S)-Zn(HLring)2 is near to 10 kcal
mol−1. This could explain the temperature-dependent formation
of Zn(HLchain)2 (vide supra).
Theoretical calculations predicted that O-bridged isomers are
clearly more stable than N-bridged isomers of Zn2(Lchain)2. The
Gibbs free-energy difference between the most stable O-bridged
and the less stable N-bridged isomers is up to 16 kcal mol−1
(see ESI†). The structure of the most stable O-bridged dinuclear
zinc complex is shown in Fig. 5. The observed NOE cross-peaks
(see ESI†) between protons H-9 and H-10, which are separated
by 2.2 Å, as well as between H-9 and H-3, which are separated
by 2.6 Å, indicate that the imine N atom must be oriented to the
same side of the metal and participate in the coordination.
Morever, the observed NOE cross-peaks between H-14⋯H-16/
H-20, which are separated by 3.2 Å, indicate close proximity of
the benzylidene ring to the tosyl ring. All this is in agreement
Because both chirality and ring-chain tautomerism in the
ligand are known to occur, the minimum energy for (S,S)-Zn-
(HLring)2, (R,R)-Zn(HLring)2, (R,S)-Zn(HLring)2, Zn(HLchain)2 and
Zn(HLring)(HLchain) with tetrahedral geometries has been calcu-
lated. These studies were performed in vacuum and methanol,
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complexes, as desired, through varying ligand stoichiometry.
Mononuclear complexes of the ring tautomer, which are the
thermodynamically favourable forms, are the products obtained
when a 1 : 2 molar ratio was used. We have discovered that by
decreasing the stoichiometry of the ligand, the course of this
reaction can be fundamentally altered to produce phenoxo-
bridged dinuclear complexes of the chain tautomer. The chain
tautomeric form behaves as dianionic O,N,N,N-donor, while the
ring form is acting as monoanionic O,N-donor.
The sensitivity of the 2,3-disubstituted 1,2,3,4-tetrahydroqui-
nazoline to the copper-mediated aerobic oxidation led us to
Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH containing two new
ligands, a quinazoline and an amide. The quinazoline ligand acts
as mononucleating through its O,N,N donor set, while the amide
ligand behaves as binucleating through its O,N,N,N and O,O
binding sites. To the best of our knowledge, Cu2(Lamide)(Lquina)-
Fig. 5 The DFT-predicted most stable form of Zn2(Lchain)2. This struc-
ture is consistent with the NOE experiment. Relevant distances between
NOE peaks observed are indicated as dashed red lines.
with the DFT-predicted most stable form of O-bridged
Zn2(Lchain)2.
(MeOH)·2MeOH is the first case reported in which the Otosyl
,
Ophenoxo donor set of this type of N-tosyl substituted ligands
Spectroscopyc characterisation of the complexes
forms a second binding site for an outer metal ion.
The structures of mono- and dinuclear complexes that do not
crystallise or give poorly diffracting crystals were elucidated on
the basis of FT-IR, UV-Vis, NMR and mass spectroscopies.
Thus, the MALDI-TOF mass spectra clearly show the mono-
nuclear, or alternatively, dinuclear nature of the complexes.
The chain tautomeric form of the ligand in Zn2(Lchain2) was
easily identified from the imine proton signal (about 9 ppm) and
the magnetically equivalent methylene protons (about 4 ppm).9
The absence of the signals corresponding to the most acidic
protons, i.e. the corresponding to OHphenol and NHsulphonamide
groups, demonstrates the dianionic behavior of the ligand.
Experimental
General
All starting materials and reagents were commercially avail-
able and were used without further purification. Elemental
analyses were performed on a Carlo Erba EA 1108 analyzer.
MALDI-TOF mass spectra were recorded on a Bruker Ultraflex
III TOF/TOF using methanol as solvent and DCTB as matrix.
FAB mass spectra were recorded on a Micromass Autospec
spectrometer employing m-nitrobenzyl alcohol as matrix.
1H NMR and 13C NMR spectra were recorded on a BRUKER
AMX-500 spectrometer in deuterated solvents. The J values are
given in Hertz. NMR assignments were made by a combination
of COSY, NOESY, DEPT-135 and NOE experiments. Infrared
spectra were recorded as KBr pellets either on a Bio-Rad FTS
135 or a Jasco FT/IR-410 spectrophotometer in the range
NMR assignment of the signals in the spectrum of Zn2(Lchain
)
2
was made by a combination of NOE, NOESY and COSY experi-
ments (see ESI†). We have detected NMR spectroscopically
Zn(HLchain
)
2
[δH (500 MHz; dmso-d6) 9.54 (s, 1H, H-9),
8.18 (d, J = 8.2 Hz, 1H, H-4), 8.10 (d, J = 8.2 Hz, 1H, H-3),
4.23 (d, J = 5.8 Hz, 2H, H-14) and 2.32 (s, 3H, H-18)] as a minor
product on the mother liquors of Zn(HLring)2 and Zn2(Lchain2).
4000–600 cm−1. UV-Vis spectra were obtained on 10−4–10−5
methanol solutions with a CECIL CE 2021 spectrophotometer.
M
The ring form of the ligand in Cu(HLring)2 and Zn(HLring
)
2
was easily identified from a fairly strong infrared band in the
region 3346–3327 cm−1, which is attributed to the ν(N–H)
vibration of the tetrahydroquinazoline ring.13,20 Moreover, the
absence of a very strong infrared band at about 1595 cm−1 due
to the vibrational stretching mode of CvNimine, which is a
Theoretical studies
All calculations were performed using the Gaussian 09W17
program package at density functional theory (DFT) level by
means of the hybrid M06 functional.18 The standard 6-31G(d)
basis set was used for C, H, O, S and N and the LANL2DZ rela-
tivistic pseudopotential was used for Zn. The starting point of
these calculations was the crystallographic structure described in
this article, Zn(HLring)2. Firstly, the crystallographic structures
obtained were minimised at a DFT level. The resulting energy
value was taken as a reference for all subsequent calculations.
On the optimised geometries a DFT minimisation in methanol
solution was performed by means of the polarisable continuum
solvation model.19 Harmonic frequencies were calculated at the
same level of theory to characterise the stationary points and to
determine the zero-point energies (ZPE). All calculations were
first performed in vacuum, and then in methanol to compare the
solvent effect (see ESI†).
characteristic feature of the spectra of Cu2(Lchain
)
and
Zn2(Lchain)2, allowed us to observe the νCvNquinoline medium
band at about 1598 cm−1
The coordination geometries of Cu2+ ions can be described as
2
.
square-planar21 and square pyramidal22 in Cu(HLring
)
and
2
Cu2(Lchain)2, respectively. This is deduced from the UV-Vis
spectra of Cu(HLring)2 and Cu2(Lchain)2, which exhibit a broad
band characteristic of a d–d transition at 670 and 524 nm,
respectively.
Conclusions
The ring-chain tautomerism of a 2,3-disubstituted 1,2,3,4-tetra-
hydroquinazoline has been explored to produce mono-
nuclear complexes or, alternatively, phenoxo-bridged dinuclear
7002 | Dalton Trans., 2012, 41, 6998–7004
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To explore the conformational preference of the metal com-
plexes, the dihedral angles C3–C2–C9–N3 in H2Lring as well as
C9–N2–C9a–C10 and C13a–C14–N3–S in H2Lchain were pro-
gressively incremented from 0 to 360°, and the resultant geo-
metries were minimised using PM6. The most stable conformers
were further minimised by DFT. It was considered that the con-
formation around the metal might not change significantly.
Therefore, changes were not made around the metal coordination
environment from a defined geometry. A tetrahedral coordination
was used for zinc complexes. For the four most stable confor-
mers of each complex the harmonic frequencies were calculated
in vacuum and methanol solution. As a result, three possible
atoms that are potentially involved in the H bonding scheme
were located in Fourier maps and were treated isotropically.
Zn(HLring)2·2H2O
This compound was obtained from a methanol solution (40 mL)
containing H2Lring (200 mg, 0.46 mmol) and Zn (OAc)2·2H2O
(51 mg, 0.23 mmol) under reflux for 1 h. Alternatively, this reac-
tion could be performed by stirring at room temperature over-
night. The solid in the resulting yellow suspension was filtered
off, washed with methanol and diethyl ether and dried under
vacuum to yield Zn (HLring)2·2H2O (137 mg, 62%) as a
stereoisomers of Zn(HLring)2, one conformer for Zn(HLchain
)
2
and one for Zn(HLring)(HLchain) were obtained (see ESI†).
1
yellow powder. H NMR (250 MHz, dmso-d6, in ppm): δ 8.53
(d, J = 8.5 Hz, 1H, H-4), 5.76 (d, J = 5.9 Hz, 1H, H-9), 4.36
(d, J = 15.9 Hz, 1H, H-14eq) and 3.94 (d, J = 15.9 Hz, 1H,
H-14ax) 2.23 (s, 3H, H-18). νmax (KBr)/cm−1 3423 (br,m) (OH),
3346 (sh,m) (NH), 1597(m) (CvNquin), 1336(s) (SO2) and 1164
(vs) (SO2); MS (FAB, disulfide): m/z (%): 925.1 (72) [M+];
elemental analysis: found: C, 60.4; H, 4.4; N, 8.8; S, 6.8. Calcd
for C48H40N6O6S2Zn·2H2O: C, 60.0; H, 4.6; N, 8.8; S, 6.7%.
Crystal structure analysis data
Diffraction data for Zn(HLring)2·2MeOH·0.5H2O and [Cu2-
(Lamide)(Lquinazoline)(MeOH)]·2MeOH were collected at 100(2) K,
using graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å)
from a fine focus sealed tube. Some significant crystal para-
meters and refinement data are summarised in Table 2. Data
were processed and corrected for Lorentz, polarisation effects.
Multi-scan absorption corrections were performed using the
SADABS routine.23 Structures were solved by standard direct
methods24 and were then refined by full matrix least squares on
F2.25 All non-hydrogen atoms were anisotropically refined,
except for a solvated and disordered water molecule with three
different occupation sites for Zn(HLring)2·2MeOH·0.5H2O.
Hydrogen atoms were mostly included in the structure factor cal-
culation in geometrically idealised positions, with thermal para-
meters depending of the parent atom, by using a riding model.
In the case of Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH, the H
Cu(HLring
)
2
This compound was obtained from a methanol solution (40 mL)
containing H2Lring (200 mg, 0.46 mmol) and Cu(OAc)2·H2O
(47 mg, 0.235 mmol) under reflux for 1 h. Alternatively, this
reaction could be performed by stirring at room temperature
overnight. A dark green powdery solid was isolated by filtration,
washed with diethyl ether and dried under vacuum. Yield =
176 mg (81%). νmax (KBr)/cm−1 3327(br,m) (NH), 1599(m)
(CvNquin), 1335(s) (SO2) and 1163(vs) (SO2). Elemental analy-
sis: found: C, 62.1; H, 4.3; N, 9.1; S, 6.6. Calcd (%) for
C48H40CuN6O6S2: C, 62.3; H, 4.4; N, 9.1; S, 6.9%.
Table 2 Diffraction data for Cu2(Lamide)(Lquinazoline)(MeOH)·2MeOH
and Zn(HLring)2·2MeOH·0.5H2O
Zn
(HLring)2·2MeOH·0.5H2O (MeOH)·2MeOH
Cu2(Lami)(Lquin
)
Zn2(Lchain)2·2MeOH
A solution of H2Lring (80 mg, 0.18 mmol) and Zn(OAc)2·2H2O
(28 mg, 0.18 mmol) in methanol (80 mL) was heated under
reflux for 4 h. Filtration of the resulting orange suspension
yielded an orange powder, which was washed with methanol
and diethyl ether, and dried under vacuum. Yield = 82 mg
(50%). δH (500 MHz; dmso-d6) 8.90 (s, 1H; H-9), 8.60 (1 H, d,
J = 8.1 Hz, H-4), 7.98 (1 H, d, J = 8.1 Hz, H-3), 7.75 (2 H, d,
J = 8.1 Hz, H-16 and H-20), 7.50 (1 H, t, J = 8.0 Hz, H-6),
7.46 (1 H, d, J = 8.2 Hz, H-10), 7.36 (1 H, t, J = 8.0 Hz, H-11),
7.21 (1 H, t, J = 8.0 Hz, H-12), 7.16 (2 H, d, J = 8.1 Hz, H-17
and H-19), 7.08 (1 H, d, J = 8.0 Hz, H-13), 6.98 (1 H, d, J = 8.0
Hz, H-5), 6.81 (1 H, d, J = 8.0 Hz, H-7), 4.06 (2 H, s, H-14) and
2.29 (3 H, s, H-18); λmax(MeOH)/nm 214, 234, 268, 341 and
398; νmax (KBr)/cm−1 3408(br,m) (OH), 1597(s) (CvNimi),
1332(s) (SO2) and 1164(vs) (SO2); MS (MALDI-TOF, DCTB):
m/z (%): 991.1 (100) [M+], 494.1 (13) [12M+]; Elemental analy-
sis: found: C, 56.6; H, 3.9; N, 7.6; S, 5.7. Calcd (%) for
C48H38N6O6S2Zn·2MeOH: C, 56.9; H, 4.4; N, 8.0; S, 6.1%.
Formula
Mr
Crystal system
Space group
Unit cell
C50H48N6O8S2Zn
998.43
Monoclinic
P21/c
a = 25.385(4)
b = 10.0122(13)
c = 17.570(2)
α = 90
β = 94.269(2)
γ = 90
4628.6(11)
4
1.433
0.685
2080
C44H40Cu2N6O8S
939.96
Triclinic
ˉ
P1
a = 11.372(3)
b = 11.437(3)
c = 16.766(4)
α = 76.947(11)
β = 84.836(12)
γ = 72.451(11)
2025.0(9)
Volume (Å3)
Z
2
Dc (g cm−3
)
1.542
1.166
968
1.88–26.02
48 645/7916
0.0475
7916/0/563
0.0394, 0.0823
0.0656, 0.0920
0.962, −0.520
μ (mm−1
F(000)
)
θ range (°)
Ref. col./Ref. Ind
Rint
Data/restr./param.
R1, wR2 [I > 2σ(I)] 0.0480, 0.1183
0.77–26.02
37386/9114
0.0565
9114/0/630
R1, wR2 (all data)
0.0830, 0.1363
1.059, −0.674
Residuals (e Å−3
)
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 6998–7004 | 7003

View Online
Cu2(Lchain
)
2
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A solution of H2Lring (100 mg, 0.23 mmol) and Cu(OAc)2·H2O
(38 mg, 0.23 mmol) in methanol (50 mL) was heated under
reflux for 4 h. The resulting dark solution was concentrated to
dryness under vacuum and the resulting solid was washed with
diethyl ether and dried under vacuum. Yield = 70 mg (61%).
λmax(MeOH)/nm 210, 236, 270, 312 and 384, 524; νmax
(KBr)/cm−1 1594(s) (CvNimi), 1349(s) (SO2) and 1167(vs)
(SO2); MS (MALDI-TOF, DCTB): m/z (%): 984.0 (100) [M+],
493.1 (23) [12M+]; Elemental analysis: found: C, 58.8; H, 4.2; N,
8.3; S, 6.2. Calcd (%) for C48H38Cu2N6O6S2: C, 58.5; H, 3.9; N,
8.5; S, 6.5%.
11 A. M. García-Deibe, J. Sanmartín-Matalobos, C. González-Bello,
E. Lence, C. Portela-García, L. Martínez-Rodríguez and M. Fondo,
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8-Hydroxy-N-{2-[(4-methylphenylsulfonamido)methyl]phenyl}-
quinoline-2-carboxamide (H3Lamide
)
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This compound was obtained from the mother liquor of Cu2-
(Lchain)2. Purification by flash chromatography over silica gel
eluting with (75 : 25) diethyl ether–hexane gave amide H3Lamide
as a beige solid. δH (500 MHz; acetone-d6) 10.69 (1 H, br s,
NHCO), 9.34 (1 H, br s, OH), 8.60 (1 H, d, J = 8.5 Hz, H − 4),
8.32 (1 H, d, J = 8.5 Hz, H − 3), 7.69 (2 H, d, J = 8.5 Hz,
H − 16), 7.65 (1 H, d, J = 8.0 Hz, H − 7), 7.62 (1 H, br d,
J = 8.0 Hz, H − 10), 7.59 (1 H, dd, J = 8.5 and 0.5 Hz, H − 5),
7.49 (1 H, dd, J = 8.0 and 0.5 Hz, H − 13), 7.37 (1 H, dt,
J = 7.5 and 1.5 Hz, H − 11), 7.27 (2 H, dt, J = 7.5 and 1.0 Hz,
H-6 + H-12), 7.13 (2 H, d, J = 8.5 Hz, H-17 and H-19), 6.83
(1 H, br s, NHCH2), 4.17 (2 H, d, J = 4.2 Hz, CH2) and 2.15
(3 H, s, CH3); δC (125 MHz; acetone-d6) δ 164.0 (C; C9), 154.6
(C; C8), 148.7 (C; C2), 143.8 (C; C15), 138.9 (CH; C4), 138.3
(C; C18a), 137.8 (C; C8a), 136.5 (C; C9a), 133.1 (C; C13a),
131.2 (C, C4a), 131.1 (CH, C13), 130.1 (CH, C7), 130.6
(2 × CH, C16 + C20), 129.1 (CH, C11), 127.7 (2 × CH, C17 +
C19), 127.3 (CH, C12), 127.1 (CH, C5), 120.4 (CH, C3), 118.8
(CH, C10), 112.7 (CH, C6), 44.6 (CH2, C14) and 21.1 (CH3,
C18); νmax (KBr)/cm−1 3460 (O–H), 3363 (NH), 3259 (NH) and
1672 (CvO); MS (FAB): m/z (%): 448 (MH+, 100%); HRMS
calcd for C24H22O4SN3 (MH+): 448.1331; found, 448.1331.
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Acknowledgements
Financial support from the Ministerio de Ciencia e Innovación
(CTQ2010-19191 to JSM and SAF2010-15076 to CGB) and the
Xunta de Galicia (10PXIB2200122PR and GRC2010/12 to
CGB) is gratefully acknowledged. We are also grateful to the
Centro de Supercomputación de Galicia (CESGA) for the use of
the Finis Terrae computer.
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7004 | Dalton Trans., 2012, 41, 6998–7004
This journal is © The Royal Society of Chemistry 2012