Design and synthesis of thiazole and thiazolidine metallo-supramolecular networks

Article abstract of DOI:10.1080/10426507.2010.530327

A mild and selective procedure for the synthesis of 4-carboxy thiazoles and thiazolidines starting from naturally occurring cysteine by condensation with aldehydes is described. The optimized procedure, taking advantage of the positive effect of microwave

Full text of DOI:10.1080/10426507.2010.530327

Phosphorus, Sulfur, and Silicon, 186:1312–1315, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.530327
DESIGN AND SYNTHESIS OF THIAZOLE
AND THIAZOLIDINE METALLO-SUPRAMOLECULAR
NETWORKS
Barbara Di Credico, Luca Gonsalvi, Maurizio Peruzzini,
Gianna Reginato, and Andrea Rossin
Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti
Organometallici (ICCOM-CNR), Sesto Fiorentino, Firenze, Italy
Abstract A mild and selective procedure for the synthesis of 4-carboxy thiazoles and thiazo-
lidines starting from naturally occurring cysteine by condensation with aldehydes is described.
The optimized procedure, taking advantage of the positive effect of microwave irradiation on the
MnO2-mediated oxidation step, is suitable for multigram scale. Coordination of these ligands
towards a variety of transition metal ions gave new interesting metallorganic supramolecular
architectures in which an extensive 3D network is created through hydrogen bonding.
Keywords Amino acid; coordination complexes; thiazoles; thiazolidines
INTRODUCTION
Nitrogen-containing heterocycles have been widely used as ligands as they may easily
support, via chelation or multimetallic coordination, the assembly of polymeric, polydi-
mensional architectures. In particular they are able to establish a variety of noncovalent
interactions, such as dipole–dipole and hydrogen-bonding.1 Mixed N,S-heterocycles such
as thiazolidines or thiazoles have received much attention in this area and, for instance,
nicotinate and isonicotinate derivatives were recently chosen as promising organic con-
nectors in crystal engineering, because they are able to provide both highly directional
coordinative metal-to-ligand bonds and flexible complex-to-complex hydrogen bonds.2 In
consideration of that, we decided to screen some new carboxy thiazole–based ligands in
order to obtain a better insight on the substituent effects to direct the 3D self-assembly
of coordination complexes with transition metals. Thus we we turned our attention to the
optimization of synthetic methodologies for the large-scale preparation of thiazole-based
carboxylates.3 In this article we report our results in this area, together with the first studies
on the coordination chemistry of such ligands with Co(II) and Zn(II), which lead to the
Received 14 September 2010; accepted 5 October 2010.
The authors thank Ente Cassa di Risparmio–Firenze through the motu proprio FIRENZE HYDROLAB
project (www.iccom.cnr.it/hydrolab/) for supporting this research activity.
Address correspondence to Barbara Di Credico, Consiglio Nazionale delle Ricerche, Istituto di Chimica dei
Composti Organometallici (ICCOM-CNR), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Firenze, Italy.
E-mail: barbara.dicredico@iccom.cnr.it
1312

METALLO-SUPRAMOLECULAR NETWORKS
1313
synthesis of a new family of complexes with interesting supramolecular assemblies in the
solid state, mainly due to extensive 3D hydrogen-bonded networks.
RESULTS AND DISCUSSIONS
Cyclization of cysteine side-chains onto carbonyl groups yielding thiazole five-
membered heterocycles is a well established procedure4 that has found many applications.5
Following this approach, l-cysteine ethyl ester 1 was reacted with different pyridyl- or
carboxaldehydes 2a–d to afford the corresponding thiazolidine derivative 3a–d as shown
in Scheme 1.
N
a
R =
SH
S
KHCO3
H2O/MeOH
R
b
c
R =
R =
N
+
RCHO
N
H
EtOOC
EtOOC
NH2.HCl
2a-d
1
3a-d
87-91%
COOEt
COOEt
d R =
Scheme 1
Thus thiazolidines 3a–d were converted into the corresponding thiazoles 4a–d via
oxidative dehydrogenation. Several methods are described to perform this transformation
(CBrCl3/DBU,6 DDQ,7 NiO25a,8), albeit drawbacks such as low yields and harsh and
hazardous reaction conditions often hamper large scale synthesis. In our case, oxidation
was conveniently performed using the commercially available activated MnO2,4a,9 which
provided the desired thiazoles in very good yields, although under rather harsh conditions,
namely benzene as solvent in the presence of pyridine for 24 h at 55◦C, using a 25-fold
excess of oxidant.
In order to find milder and more general reaction conditions, we decided to investigate
the effect of microwave irradiation10 on this oxidation and, in keeping with our expectations,
the use of this technique shortened the reaction time significantly, leading to the quantita-
tive formation of thiazoles 4a–d. Although an excess of MnO2 was still necessary under
optimized conditions (30 s, 300 W MW, 100◦C), this was reduced to 5 eq., toluene was used
instead of benzene, and the use of pyridine was not necessary (Scheme 2). Ester saponifica-
tion with Cs2CO3 in aqueous methanol afforded the corresponding carboxythiazoles 5a–d,
which were isolated after crystallization from acid water.3
MnO2 (5eq)
toluene
MW
Cs2CO3
S
S
MeOH/H2O
HOOC
3a-d
R
R
N
N
EtOOC
5a-d
98-99%
4a-d
Scheme 2
Complexation ability of 5a towards different transition metals was studied. The
simultaneous presence of an acid and a basic site within the same molecule makes this ligand
very interesting from a supramolecular point of view, engaging in multiple coordination

1314
B. DI CREDICO ET AL.
modes that are related to its pH-dependent protonation–deprotonation equilibria in water
(Scheme 3).
X
H
N
S
N
N
S
N
N
S
N
OH-
H+
OH-
H+
O
O
O
5a
O
HO
HO
pKeq
O
N
N
H
O
S
Scheme 3
Theregio-isomer of 5a containinga para- or meta-pyridyl substituent in the2-position
is known to be capable of generating 3D coordination polymers with silver(I), zinc(II), and
copper(II).11 In our case, discrete complexes are formed, where the o-pyridyl substituent
(either protonated or deprotonated) is involved in intramolecular hydrogen bonding. This is
shown in Figure 1, where the crystal structures of Zn(II) and Co(II) complexes are reported.
In acid medium, a protonated nitrogen atom on the pyridyl substituent is present
and complex A is formed. The zinc atom is six-coordinated, with the ligand occupying
the equatorial plane and two water molecules trans to each other complete the octahedral
coordination geometry. The “pyridinium-like” ring is involved in a N(2)-H(2)···O(2)#
Figure 1 Crystal structure of Zn(II) complex A and Co(II) complex B with 5a and their solid state packing
evidencing the hydrogen bonding network. H atoms on the organic ligands are omitted for clarity. Weak interactions
are shown in dotted lines. The crystallographic data files (CIFs) for complexes A and B have been deposited (CCDC
Numbers 781930-781932). (Color figure is available online.)

METALLO-SUPRAMOLECULAR NETWORKS
1315
hydrogen bonding. Additional interactions between the aquo ligands, C O groups of
neighboring molecules, and the disordered perchlorate ions are present, leading to a complex
network of embedded H-bonds that holds all the components together in a compact assembly
(Figure 1).
The reaction of cobalt(II) acetate tetrahydrate with 5a at pH = 5 produces purple
crystals of complex B. The coordination geometry around Co(II) is octahedral (Figure 1),
with the same ligand disposition seen in complex A. The O(3)-H(3B)···O(1)# hydrogen
bond between the aquo ligands and the carboxylic groups of neighboring molecules in the
lattice is still present. The not protonated N(pyridyl) engages a trans-(N,N) disposition,
which is the most energetically stable, and an additional O(3)-H(3A)···N(2)# hydrogen
bond with the other proton on the aquo ligands. In both cases, the presence of an extended
hydrogen bonding network due to the presence of several polar groups in the asymmetric
unit confers a “pseudo-polymeric” nature to these solids, being insoluble in all solvents.
CONCLUSIONS
We have reported a selective and general procedure for the synthesis of 4-
carboxythiazoles, showing that both reaction time and the need of polluting reagents can be
dramatically reduced by MW irradiation during the oxidation step. The coordination ability
of 5a in aqueous environment has been analyzed, leading to new complexes in which
an extensive 3D network is created through hydrogen bonding. Under this perspective,
this study can to be considered as the first step towards the synthesis of thiazole-based
metal-organic frameworks (MOFs) for potential applications in the field of gas storage.
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