On the synthesis of tetradentate ligands [Elektronische Ressource] / von Martin Schulz

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• Publié par: friedrich-schiller-universitat_jena
• Publié le: 01 janvier 2009
• Nombre de lectures: 34
• Langue: English
• Poids de l'ouvrage: 10 Mo

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On the Synthesis of Tetradentate Ligands
Dissertation
zur Erlangung des akademischen Grades doctor rerum naturalium
(Dr. rer. nat.)
vorgelegt dem Rat der Chemisch-Geowissenschaftlichen Fakultät der
Friedrich-Schiller-Universität Jena
von Diplomchemiker Martin Schulz
geboren am 11.12.1980 in Bad Salzungen1. Gutachter: Prof. Dr. Matthias Westerhausen, FSU Jena
2. Gutachter: Prof. Dr. Rainer Beckert, FSU Jena
Tag der öffentlichen Verteidigung: 16. Dezember 2009Contents
List of Abbreviations 4
1 Introduction 6
1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.2 Preparatory work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3 Aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2 Results and Discussion 16
2.1 Ligand design via nitroaldol reaction with pyridine-2-carbaldehyde . . . 16
2.1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.1.2 Synthesis and reactivity of 2-nitro-1,3-di(pyridine-2-yl)propane-
1,3-diol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.1.3 Synthesis of 2-nitro-1,3-di(pyridin-2-yl)propane-1,3-diolato zinc
dichloride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.1.4 Development of macromolecular catalysts for nitroaldol reactions 32
2.1.5 O-Trialkylsilyl protection of 2-nitroalcohols . . . . . . . . . . . . 34
2.1.6 Reduction of the nitro group . . . . . . . . . . . . . . . . . . . . 42
2.1.7 Synthesis of a N-salicylaldimine ligand, its vanadium(v) complex
and catalytic activity . . . . . . . . . . . . . . . . . . . . . . . . 46
2.2 N-(Pyridine-2-ylmethylidene)amines as ligands and ligand precursors . 57
2.2.1 Synthesis of N-(pyridine-2-ylmethylidene)amines . . . . . . . . . 57
2.2.2 Synthesis and structural diversity of 2-pyridylmethylideneamine
complexes of zinc(II) chloride . . . . . . . . . . . . . . . . . . . 58
2.2.3 Synthesis of 1,4-diamino-2,3-di(2-pyridyl)butane and its zinc(II)
chloride complex . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2.2.4 Synthesis of a tetraaryl substituted piperazine (ZnCl ) complex2 2
with unexpected stereoselectivity . . . . . . . . . . . . . . . . . 75
2.2.5 Miscellaneous reactions . . . . . . . . . . . . . . . . . . . . . . . 81
3 Summary 84
4 Zusammenfassung 87
5 Experimental 91
References 111A Crystallographic Data 119
Acknowledgment 124
Declaration of Originality 124List of Abbreviations
δ ................. Chemical shift
Δν .............. Line width
................. Extinction coefficient
λ ................ Wavelength
eν ................ Wave number
a ................ Coupling constant (EPR)
aibn ............. 2,2’-Diazo-bis(2-methylpropanenitrile)
bipy ............. 2,2’-Bipyridine
Bu ............... Butyl
1d ................ Doublet ( H NMR)
1dd ............... of doublets ( H NMR)
1ddd .............. Doublet of of doublets ( H NMR)
de ............... Diastereomeric excess
DEI ............. Direct electron impact
DEPT ........... Distortionless enhancement by polarization transfer
dmap ............ N,N-Dimethylpyridine-4-amine
dmf ..............ylformamide
dmso ............ Dimethyl sulfoxide
ee ................ Enantiomeric excess
EI ............... Electron impact
EPR ............. Electron paramagnetic resonance
ESI .............. Electron spray ionization
FAB ............. Fast atom bombardment
GC .............. Gas chromatography
HMBC ........... Heteronuclear multiple bond correlation
HSQC ...........uclear single quantum coherence
IR ............... Infrared spectroscopy
J ................ Coupling constant (NMR)
LMCT ........... Ligand to metal charge transfer
1m ................ Mass, multiplet ( H NMR), medium (IR)
Me ............... Methyl
MS .............. Mass spectrometry
nba .............. 3-Nitrobenzyl alcohol
NMR ............ Nuclear magnetic resonance
NOE ............. Overhauser effectNOESY .......... Nuclear Overhauser and exchange spectroscopy
13p ................ Primary ( C NMR)
Prop ............. Propyl
pyr .............. Pyridyl
1 13q ................ Quartet ( H NMR), quaternary ( C NMR)
1quint ............ Quintet ( H NMR)
r.t. .............. Room temperature
1 13s ................. Singlet ( H NMR), secondary ( C NMR)
st ................ Strong (IR)
1 13t ................. Triplet ( H NMR), tertiary ( C NMR)
tbd .............. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene
TBDMS ......... Tert-butyldimethylsilyl
thf ............... Tetrahydrofuran
TLC ............. Thin layer chromatography
tmb .............. Trimethoxybenzene
tmeda ........... N,N,N’,N’-Tetramethylethylene-1,2-diamine
TMS ............. Trimethylsilyl
TOF ............. Turnover frequency
TON ............ Turnover number
TSA ............. Transition state analogue
w ................ Weak (IR)
w% .............. Weight percent
z ................. Charge
IUPAC Naming was realized using ACD/ChemSketch Freeware, version 11.02, Ad-
vanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com, 2008.1 Introduction
1.1 Background
The activation of small molecules such as CO , CO, NO, CH , H O and others has2 4 2
1been a field of research for decades. And research in this area is of growing interest,
since for example small molecules such as H , N and O are an ubiquitous reservoir2 2 2
of chemical energy. But they also serve as synthons for (bio)chemical processes or sig-
naling agents in biological systems. CO for example is used in biological systems as2
C1 synthon for the production of glucose, malonic acid, oxaloacetate and others. This
is accomplished by enzymes such as ribulose-1,5-bis(phosphate)-carboxylase-oxidase
(RuBisCO), acetyl-CoA carboxylase or phosphoenolpyrovat carboxykinase. Artificial
processes use CO for the carboxylation of phenol or production of organic and inor-2
ganic carbonates. NO is an example for a signaling agent in biological systems and
its chemistry is of medical importance. Since the early days of chemistry it has been
known that metals or metal ions are able to catalyze reactions of these often thermo-
dynamically stable molecules. Thus, researchers were concerned with the coordination
behavior of small molecules towards metal centers, the reasons for their activation, the
basis of selectivity of metal/small-molecule interactions and the transfer of knowledge
for laboratory and industrial or medical use. Activation of small molecules by metal
ions or complexes is a process that occurs in every organism. Hence, investigations on
biocatalysts help to gain deeper insights into activation mechanisms, while contrari-
wise, fundamental inorganic, organic and theoretical research can help to understand
the enzyme’s mode of action. Research in this field is strongly interdigitated and has
been forwarded by recent advances in synthetic and theoretical methods as well as
spectroscopic techniques. Gathering information of the enzyme’s mode of action is
approached by mimicking the active center of a metalloenzyme. Since biocatalysts
often comprise of huge proteins, their spectroscopic examination is strongly hampered
and smaller model compounds are desired. These model complexes are divided into
structural mimics and functional mimics. Structural models mimic the coordination
site, for instance donor atoms, conformation, bond lengths and angles. They do not
necessarily mimic the catalytic function but provide useful comparative data for spec-
troscopic studies of the natural counterpart. Functional mimics often have little re-
semblance with the binding sites of its natural analogue but have similar catalytic
properties like activity or selectivity. The challenging task when modeling parts of
a biocatalyst was summarized by Parkin: "The construction of accurate synthetic
analogues is therefore nontrivial, and considerable attention must be given to ligand
61.1 Background
design in order to achieve a coordination environment, which is similar to that enforced
2by the unique topology of a protein.". This challenge was addressed in the collabo-
rative research center "Metal-mediated reactions modeled after nature" (SFB 436) at
the university of Jena, where our group was also involved. Parts of these investigations
were focused on functional mimics of homo- and heterodinuclear zinc containing met-
alloenzymes in order to develop catalysts for the activation of small molecules. Natural
examples are metallo-β-lactamase (Zn(ii), Zn(ii)), bovine lens leucine amino peptidase
(Zn(ii), Zn(ii)), alkaline phosphatase (Zn(ii), Zn(ii)), kidney bean purple acid phos-
3,4phatase (Zn(ii), Fe(iii)) and DNA polymerase I (Zn(ii), Mg(ii)). Although these
enzymes catalyze the cleavage of peptide or phosphate ester bonds or the transfer of
nucleotides to DNA, the underlying mechanisms also apply for the activation of small
molecules. A selection of published dinuclear zinc enzyme models is given in Figure
1. They comprise phenolate, phthalazine or pyrazolyl linkers as well as cryptands and
4calix[4]arenes. Their common feature are N and O donor sites, while the two metal
centers are bridged via water, hydroxide, carboxylate, or phosphate moieties.
Figure 1: Selection of published structural and functional models of dinuclear zinc-