1,3-Dihydroxypropan-2-one (DHA) synthesis from Glycerol for pharmaceutical applications

In the last century the amino alcohol serinol (2-amino-1,3-propanediol) has become a common intermediate for several chemical processes. Since the 40's serinol was used as precursor for synthesis of antibiotics (e.g. chloramphenicol). In the last years, new scopes of application were discovered. Serinol is used as building block in the synthesis of X-ray contrast agents, pharmaceuticals (anti-inflammatory or analgesic drugs) or in the cosmetics industry. It can either be obtained by chemical processes based on 2-nitro-1,3-propanediol, dihydroxiacetone (1,3-Dihydroxypropan-2-one or simply DHA) and ammonia [59]. One way to synthesize Serinol, in fact, is reacting DHA in a catalyzed reaction using Pt supported on carbon as catalyst. The DHA can be synthesized from Glycerol (1,2,3-propanetriol or glycerine) with a selective oxydation of the secondary carbon. The reaction from Glycerol to DHA must be catalyzed and nowadays only one method is well known. The method to obtain DHA uses gluconobacter oxydans as catalyst for the selective glycerol oxydation. Anyway the method presents many drawbacks cost not yet solved such as low productivity and high production. It is fundamental to underline how nowadays glycerol plants are closing and others are opening that use glycerol as a raw material as a result of the large surplus of glycerol that is formed as a byproduct in manufacturing biodiesel fuel by transesterification of seed oils with methanol. Over the last twenty years, indeed, biodiesel emerged as a viable fuel and as a fossil diesel additive to replace sulfur, whose content is being progressively lowered according to tighter environmental legislation. However, the increasing production of biodiesel is not artificially sustained and is predicted to spread and increase, as biodiesel provides sufficient advantages to merit subsidy. Besides the closure of production plants, industry reacted to this situation stimulating research to find new applications of glycerol as a low-cost feedstock for functional derivatives either for mass consumption, such as additives for concrete, or as a precursor of valued fine chemicals [60]. One investigated application of glycerol is exact its possible use as starting material for DHA synthesis (figure 1.4, chapter 1). The aim of this work was to investigate for new possibilities to transform glycerol into DHA, avoinding gluconobacter oxydans utilisation. In particular the attention was posed on new catalytic solutions investigating inorganic catalysts for the selective oxydation of glycerol. Two catalytic system were investigated. An heterogenous solution using noble metal nanoparticles supported on carbonious supports (mono- and bi-metallic systems) and an homogeneous one using an organometallic catalyst based on Pd. The study was approach from experimental and theoretical point of view becasue the reaction mechanism is not still clear. The research bring us to investigate deeply many weakness of the reaction and not still clear in literature, such as an efficient analytical method, problems linked to the catalysts aging, their deactivation and synthesis.