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Abstract:

Decarboxylation refers to a chemical reaction in which a carboxylic acid functional group is removed from an organic backbone by C-C bond scission, with release of carbon dioxide. This reaction is particularly attractive for the selective defunctionalisation of renewable carbon feedstocks, and may facilitate their entry in the bio-based chemical industry. The main focus of this dissertation was on the decarboxylation of amino acids into useful nitrogenous compounds, which may find applications in the production of bulk and fine chemicals. The availability of amino acids will not be an issue, because they are nowadays produced from carbohydrates and ammonia by efficient large-scale fermentation processes. Alternative resources are provided by protein waste streams from the agro-industry and biofuel production. A case study was made on the production of glutamic acid and the potential applications of its derivatives, to illustrate the role of amino acids in the future bio-refinery. Two pathways for decarboxylation of amino acids can be distinguished: an oxidative route towards nitriles and a non-oxidative route towards amines and derivatives. In the context of protein waste valorisation, decarboxylation may contribute to the recycling of organic nitrogen from natural resources. Moreover, the downstream processing of protein hydrolysates may be facilitated as well, because the zwitterionic charge behaviour of amino acids will disappear upon decarboxylation. However, state-of-the-art methodologies are often associated with high waste loads. Therefore, three complementary catalytic strategies for decarboxylation of amino acids under mild conditions have been developed in this dissertation. The first strategy is based on catalytic halide oxidation and provides an improvement to the classical hypobromite-mediated oxidative decarboxylation of amino acids into nitriles. Hypobromite can be produced in situ by oxidation of ammonium bromide with hydrogen peroxide in the presence of a heterogeneous catalyst. Hydrogen peroxide is considered as a green oxidant, because it is converted into water during the reaction. The catalyst consists of tungstate immobilised on a layered double hydroxide-type material and can be recycled. Both halide oxidation and oxidative decarboxylation are facilitated by the catalyst in an aqueous one-pot reaction at room temperature. In this way, the bromide loading can be reduced to at least 50% of the stoichiometric amount required for oxidative decarboxylation. Nitriles are produced in good to excellent yield and the system tolerates a wide range of functional groups. The catalytic performance can be maintained on the level of crude protein hydrolysates, which was demonstrated for a wheat gluten sample. The second strategy for oxidative decarboxylation of amino acids is based on the transition metal-catalysed dehydrogenation of the amine moiety in the substrate. The reaction is facilitated by an alumina-supported ruthenium catalyst in the presence of molecular oxygen. This oxidant is also converted into water in the end. When the reaction is performed in water at 100 °C, several amino acids can be transformed into nitriles in good yield. Ruthenium-catalysed hydration of nitriles to amides is unfortunately an inherent side reaction. The system shows a lower functional group compatibility compared to the hypobromite-based reaction. However, the ability to perform this reaction with molecular oxygen and in the absence of any halide source is a major advantage of this methodology in terms of sustainability. Finally, the non-oxidative decarboxylation of amino acids into amines is based on Schiff base formation with a carbonyl compound, and proceeds in the absence of transition metal catalysts. Isophorone has been identified as a performant organocatalyst out of many structurally diverse aldehydes and ketones. The high activity of isophorone is attributed to the alpha,beta-unsaturated ketone motif with an electron-donating substituent on the C=C double bond. The charged reaction intermediate can be stabilised by the Schiff base by temporary electron delocalisation. When the reaction is performed in 2-propanol at 150 °C, catalyst loadings as low as 5 mol% are sufficient to convert many amino acids into the corresponding amines with good to excellent yield. Remarkably, amino acid-derived formamides are obtained in high yield when the solvent is switched from 2-propanol to N,N-dimethylformamide. Organocatalytic decarboxylation of amino acids proceeds with higher efficiency under mild conditions when the generated amines are converted in situ into an inert, non-nucleophilic derivative, which is not able to compete for Schiff base formation with the organocatalyst.