Water is a safe, harmless, and environmentally benign solvent. From an eco-sustainable chemistry
perspective, the use of water instead of organic solvent is preferred to decrease environmental
contamination. Moreover, water has unique physical and chemical properties, such as high dielectric
constant and high cohesive energy density compared to most organic solvents. The different interactions
between water and substrates, make water an interesting candidate as a solvent or co-solvent from an
industrial and laboratory perspective. In this regard, organic reactions in aqueous media are of current
interest. In addition, from practical and synthetic standpoints, a great advantage of using water is
immediately evident, since it does not require any preliminary drying process.
This thesis was found on this aspect of chemical research, with particular attention to the mechanisms
which control organo and bio-catalysis outcome. The first part of the study was focused on the aldol
reaction. In particular, for the first time it has been analyzed for the first time the stereoselectivity of the
condensation reaction between 3-pyridincarbaldehyde and the cyclohexanone, catalyzed by morpholine
and 4-tertbutyldimethylsiloxyproline, using water as sole solvent. This interest has resulted in countless
works appeared in the literature concerning the use of proline derivatives as effective catalysts in organic
aqueous environment. These studies showed good enantio and diastereoselectivities but they did not
present an in depth study of the reaction mechanism. The analysis of the products diastereomeric ratios
through the Eyring equation allowed to compare the activation parameters (ΔΔH≠ and ΔΔS≠) of the
diastereomeric reaction paths, and to compare the different type of catalysis. While morpholine showed
constant diasteromeric ratio at all temperatures, the O(TBS)-L-proline, showed a non-linear Eyring diagram,
with two linear trends and the presence of an inversion temperature (Tinv) at 53 ° C, which denotes the
presence of solvation effects by water. A pH-dependent study allowed to identify two different reaction
mechanisms, and in the case of O(TBS)-L-proline, to ensure the formation of an enaminic species, as a keyelement
in the stereoselective process. Moreover, it has been studied the possibility of using the 6-
aminopenicillanic acid (6-APA) as amino acid-type catalyst for aldol condensation between cyclohexanone
and aromatic aldehydes. A detailed analysis of the catalyst regarding its behavior in different organic
solvents and pH, allowed to prove its potential as a candidate for green catalysis. Best results were
obtained in neat conditions, where 6-APA proved to be an effective catalyst in terms of yields. The catalyst
performance in terms of enantio- and diastereo-selectivity, was impaired by the competition between two
different catalytic mechanisms: one via imine-enamine mechanism and one via a Bronsted-acid catalysis.
The last part of the thesis was dedicated to the enzymatic catalysis, with particular attention to the use of
an enzyme belonging to the class of alcohol dehydrogenase, the Horse Liver Alcohol Dehydrogenase
(HLADH) which was selected and used in the enantioselective reduction of aldehydes to enantiopure
arylpropylic alcohols. This enzyme has showed an excellent responsiveness to this type of aldehydes and a
good tolerance toward organic solvents. Moreover, the fast keto-enolic equilibrium of this class of
aldehydes that induce the stereocentre racemization, allows the dynamic-kinetic resolution (DKR) to give
the enantiopure alcohol. By analyzing the different reaction parameters, especially the pH and the amount
of enzyme, and adding a small percentage of organic solvent, it was possible to control all the parameters
involved in the reaction. The excellent enatioselectivity of HLADH along with the DKR of arylpropionic
aldehydes, allowed to obtain the corresponding alcohols in quantitative yields and with an optical purity
ranging from 64% to >99%.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:1467 |
| Date | 27 April 2009 |
| Creators | Emer, Enrico <1979> |
| Contributors | Giacomini, Daria |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | Italian |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/restrictedAccess |
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