Catalytic production of bio-based amines and derivatives

The continuous growth of world’s population and the increasing economic industrialization has led to an ever increasing demand to energy and goods. Simultaneously, we are confronted with a foreseeable depletion of cheap oil and sustainability issues for gas and coal conversion. These facts have stimulated the quest for renewable resources. Perhaps their major role as energy supplier may be questioned on the long term, but renewable feedstock for the manufacture of chemicals is not unrealistic. Keeping or using the original chemical functionality of the bio-based molecules may be advantageous in many cases, especially when the atom economy of the reaction to form the desired product is very high, or, in other words, when waste formation can be neglected. Besides the design and development of novel reaction technologies, chemo- and bio-catalysis will play a major role in that coming feedstock transition.

This thesis focuses on the catalytic synthesis of short amines from renewable feedstock. Amines are a group of chemical compounds that contain nitrogen atoms. Their functionality such as polarity and nucleophilicity can be exploited in various ways, which is why they are produced on a large industrial scale. For instance, they are building blocks of polymers, surfactants, pharmaceuticals and agrochemicals, and they are used as CO2 absorbents or as catalysts, for instance for polyurethane synthesis. So far, industrial amines are produced from petrochemical resources like methanol (e.g. in case of MMA, DMA and TMA) and ethylene (e.g. in case of ethanolamines and ethylenediamines). Moreover, their synthesis procedures involve toxic, explosive and/or expensive chemicals and intermediates, therefore not in line with the green chemistry principles of tomorrows chemical industry.

In this research, we looked for new, innovative catalytic processes for the safe and efficient production of short amines from carbohydrates. From a chemical point of view, these sugar structures are highly functional and therefore suitable as alternative carbon source for the production of chemicals. The cellulose building block, glucose, for instance contains one oxygen atom per carbon atom, comprising five alcohol groups and one carbonyl functional group. These C-O bonds, especially the carbonyl, are reactive towards a selectively transformation into C-N bonds via the different technologies that are available hereto. Catalysis plays a key role in achieving the reactions’ high selectively. Notwithstanding the undeniable importance of homogeneous catalysis in today’s chemical industry, solid catalysts offer several advantages, when compared to dissolved catalysts. They are separated more easily from the product mixture and allow for continuous processing. This research therefore focused on the exploration of heterogeneous catalytic processes.

The first goal was to develop a new reaction route to produce short amines from carbohydrates. This process implies a cleavage of C-C bonds besides the formation of novel C-N bonds. Classic reaction types to split C-C bonds, like retro-aldol condensation and hydrogenolysis, are known to require a high reaction temperature, typically well above 200 °C, which leads to thermal degradation and thus low product selectivity. Inspired by the working mechanism of Aldolase enzymes, an efficient low-temperature chemocatalytic process was therefore developed. This process requires an amine (as the nitrogen source) and a metal catalyst and is carried out under hydrogen pressure at temperatures well below 150 °C. The amine is essential to cleave the C-C bond at the low temperature, while the metal activates hydrogen to hydrogenate unsaturated intermediates. This reductive aminolysis process thus converts reducing sugars efficiently into acyclic ethylenediamines, like N,N,N’,N’-tetramethylethylenediamine (TMEDA), and ethanolamines, like N,N-dimethylaminoethanol (DMAE). It was demonstrated that different primary and secondary amines reagents can be used in this novel catalytic process. The main reaction product was always the corresponding ethylenediamine. Selectivity up to 84% could be achieved at full sugar conversion, even in absence of solvent. As an example, one of the obtained ethylenediamines, viz.N,N’-bis(2-hydroxyethyl)-N,N’-dimethylethylenediamine (BHEDMEDA), was successfully esterified and quaternized. The resulting “diester diquat” surfactant has potential applications as detergent or fabric softener.

The second part of this research unraveled the complex mechanism behind the reductive aminolysis process. The reaction mechanism was initially proposed, based on a kinetics and reactivity study and was further validated by a Density Functional Theory (DFT) study. The C-C cleavage that is observed occurs in a controlled fashion and is initiated after electron rearrangement within a zwitterionic iminium intermediate that is formed after nucleophilic amine attack at the reductive sugar end. DFT calculations confirmed that the reaction route involving the amine facilitated C-C scission is energetically the most favorable one. After scission, the commercial redox catalyst ensures an efficient hydrogenation of the resulting reactive, unsaturated retro-aldol fragments into stable short amines. This way, the thermodynamic equilibria are directed towards the desired intermediates and the targeted amines are ultimately obtained with high selectivity. To our delight, a (cheap) commercial silica supported nickel catalyst showed excellent performance to this end. Optimization of the process parameters afforded an excellent ethylenediamine product yield of 92% at full sugar conversion, using the supported nickel catalyst. The reductive aminolysis is impacted by a peculiar solvent effect. The ethylenediamine yield increased significantly when the reductive aminolysis was carried out in methanol instead of tetrahydrofuran. This observation was confirmed by DFT calculations, demonstrating that the presence of methanol considerably lowers the energy barriers of the desired reaction steps, resulting in a faster and thus more selective formation of the desired ethylenediamine product.

Reductive aminolysis thus allows for the efficient conversion of reducing sugars into the corresponding ethylenediamine at low temperature. However, the formation of corresponding ethanolamines via a similar mechanism is difficult, since selective enaminol hydrogenation mainly led to the corresponding glucamine, instead of the ethanolamine. The use of stoichiometric amount of the amine reagent on the other hand lowered the selectivity of the process. In the third part of this research, we therefore aimed for the development of an alternative, selective route to produce DMAE from a renewable carbon source, viz. ethylene glycol (EG), by using heterogeneous transition metal (TM) catalysts. DMAE is currently produced on an industrial scale from the reaction of dimethylamine (DMA) with ethylene oxide (EO) for its use as a surfactant building block. There are recent reports that describe excellent progress in the direct synthesis of EG from glucose and even cellulose. This motivates the strategy to produce of DMAE from EG. Recent technologies for the amination of EG as described in research literature use (expensive) homogeneous TM complexes that are difficult to separate from the product mixture. The use of heterogeneous TM catalysts (in the gas phase) mostly requires high reaction temperatures (> 200 °C) in order to activate the unreactive EG substrate. This ultimately results in low selectivity towards the corresponding ethanolamine. This work therefore proposes the use of a base (KOH) to stimulate the dehydrogenation of EG, allowing the conversion of EG into DMAE with high selectivity (94%) at strongly reduced temperature, viz. 150 °C, using a commercial silica-alumina supported nickel catalyst. On top of the facilitation effect on dehydrogenation, the KOH directs the reaction to DMAE at the expense of TMEDA, resulting in the unique selectivity for this base-catalyzed process.