The synthesis of oxime-and-amide bis-chelate ligands.
Date
2014
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Abstract
In this part of the thesis our intention was to pave the way for the synthesis of pentadentate ligands
with the bis-chelate methyl-hydroxyacetamide binding centre augmented with a flexible pendant arm
that may provide additional coordination from an axial direction (scorpionate action), Fig. 4.
Analysis of the possible synthetic approaches revealed that to realise a variety of ligands with the
above features, a class of key intermediate compounds will have to be prepared, namely, 1,3-
diaminopropanes with a flexible arm of variable length bearing terminal nucleophile and grafted on
the C2-carbon, Figure 5. In principle, the synthesis of substituted 1,3-diaminopropanes can be achieved
through a number of routes, Schemes 1A-6A, of which in present work we explored two.
In total, we have synthesised eleven compounds, five of them new: 2,2’-(2-hydroxypropane-1,3-
diyl)bis(1H-isoindole-1,3(2H)-dione) (2), 2,2’-(2-bromopropane-1,3-diyl)bis(1H-isoindole-1,3(2H)-dione)
(3), [2-(benzyloxy)ethyl]propanedinitrile (22a), [3-(benzyloxy)propyl]propanedinitrile (22b) and
2-(2-hydroxyethyl)propane-1,3-diaminium dichloride (24a). Previously known compounds were
characterised by 1H and 13C NMR spectroscopy. New compounds were characterised by complete
range of instrumental techniques described in Chapter A.
Pivotal 2-(2-hydroxyethyl)alkyl-1,3-diaminium dichloride precursor (24a) was synthesised via benzylic
mono-protection of diols, followed by bromo-de-hydroxylation, alkylation of malononitrile at the C2
carbon with the intermediate prepared, deprotection, and catalysed hydrogenation. The reduction
proved to be persistently difficult, and highly hydroscopic diamine hydrochloride salt formed in rather
low yield.
An alternative route, emanating from bromo-de-hydroxylation of (2) into (3), was briefly explored but
abandoned due to a regrettable oversight. As a matter of fact, the synthesis of (3) was accomplished
successfully, and the routes that rely on this or similar Boc-protected intermediate (13), in retrospect,
are probably the most promising ones.
Abstract for Chapter B
In this part of the thesis we set out to synthesise new class of the bis-chelate N,N'-alkane-
1,x-diylbis[2-cyano-2-(hydroxyimino)ethanamide] ligands, Fig. 6, with a variable length and nature of
polymethylene bridge (ethyl, methyl, butyl and 1,3-diaminopropyl-2-ol) between the two
cyanohydroxyiminoacetamide moieties. Prior to our work only one such ligand was reported in
literature. These new compounds were synthesised for future studies of their thermodynamics of
protonation and metallation with a range of transition metals.
In total, we have synthesised nine compounds in this chapter, of which three are new (5a, 5c, and 5d).
Previously known compounds were characterised by 1H and 13C NMR spectroscopy. All new
compounds were characterised by complete range of instrumental techniques described in Chapter B.
Two routes towards the synthesis of desired ligands were explored, and the path that relies on the
intermediate bis-amides, Scheme 15 path A, turned out to be successful.
In particular,
a) three of the four bis-cyanoamide precursors were synthesised in solvent medium, with the yield
of 67% (4a), 76 % (4b) and 66 % (4d); the remaining bis-cyanoamide (4c) was synthesised in 87 %
yield using a solvent-free procedure,
b) all four desired bis-cyanoxime-and-amide ligands (5a-d) were prepared successfully in 3.6, 24, 6.6
and 6.2 % yield, respectively.
For two representative compounds, N,N’-ethane-1,2-diylbis(2-cyanoacetamide) (4a) and N,N’-ethane-
1,2-diylbis[2-cyano-2-(hydroxyimino)ethanamide] (5a), we were able to obtain suitable single crystals
and to determine their molecular and crystal structure by X-ray diffraction. Both crystals structures are
the first of their kind.
Description
M. Sc. University of KwaZulu-Natal, Pietermaritzburg 2014.
Keywords
Chelates., Ligands., Oximes., Amides., Theses--Chemistry.