Doctoral dissertation
Transformations of oxygen functional groups in organic molecules mediated by molecular iodine or/and N-halo compounds
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Abstract
The increasing demand for the sustainable world and consequently for environmentally
friendlier technology in the last decades is a driving force towards the exploration of greener
methodologies in the field of organic chemistry. In this context, the purpose of this
dissertation lays in the development of effective and metal-free catalytic approaches for
significant and established reactions, such as dehydrative C−C coupling, esterification and
aldol condensation. Accordingly, the goal of the presented research was to explore and
exploit the capabilities of certain halogen compounds as metal-free mediators in
transformations of some oxygen functional groups in organic molecules.
Firstly, a method for direct dehydrative C–C coupling between benzylic alcohols and
phenyl-substituted alkenes was developed, using molecular iodine as an ecologically
acceptable metal-free catalyst, which presumably acts as a Lewis acid. The method allows
solvent-free reaction conditions as well as the scale-up, furnishing polysubstituted olefins
in high yields and thereby confirming the synthetic applicability of the presented
methodology. Furthermore, the reaction pathway was proposed, suggesting the
involvement of a carbocation intermediate. Finally, the possibility of the direct coupling
between tertiary and secondary benzyl alcohols was examined and confirmed.
Further on, methodology for direct esterification of carboxylic acids and alcohols was
developed, using a convenient, easily-handled, low-priced bench-top mediator –
N-bromosuccinimide (NBS). The approach includes mild neat reaction conditions and
relatively low temperatures (70 °C), providing comprehensive esterification of substituted
benzoic acids as well as of mono-, di- and tri-carboxy alkyl derivatives. In addition, the
efficacy of the method was elaborated also on more complex structural backbones of bile
acids, such as cholic acid and dehydrocholic acid. The method is metal-free and proved to
be air- and moisture-tolerant, allowing for a simple synthetic and isolation procedure as
well as for the scale-up of aromatic and alkyl esters with yields up to 100%. In addition, a
protocol for the catalyst recycling has been suggested.
Finally, the esterification protocol was furtherly upgraded by using 1,3-dibromo-5,5-
dimethylhydantoin (DBDMH) as a widely available, inexpensive, and metal-free
precatalyst. The method allows the use of an even broader scope of carboxylic acids than
the N-bromosuccinimide mediator, while maintaining all other advantages of the NBSmediated
reaction system. Moreover, the reaction pathway for esterification was proposed
and a scale-up of certain industrially important derivatives performed. Lastly, to show a
general ability of DBDMH acting as the activator of the carbonyl functionality, the
methodology was expanded also on the aldol condensation of aldehydes.