Safety by natural design: benign bisphenols from biomass

Synthetic polymers are crucial in maintenance of our high standard of living. While delivering many benefits, our current plastics economy has also led to one of the greatest environmental scourges of our time. Plastic pollution is now widespread and leads to substantial chemical exposure to humans and the environment. Within this context, especially endocrine-disrupting chemicals with high production volumes, such as bisphenols, are a major concern.

Bisphenols, and especially bisphenol A (BPA), are a unique class of bifunctional polymer precursors that are pivotal for manufacturing polymers with superior thermal and physico-mechanical properties. Important examples include polycarbonate water bottles, epoxy resin food can linings, and resin-based dental composites. Despite this crucial role, unfortunately, BPA is highly controversial. Namely, its ability to interfere with the natural oestrogen receptor (ER) has been long known, but came back into disrepute when its leaching from polymers was found. Ever since, BPA is highly scrutinized and linked to a myriad of adverse effects on human health and the environment. This instigated a quest for safer BPA alternatives. However, the required intrinsic rigidity and stiffness, makes BPA almost irreplaceable for polymer chemistry. Although a plethora of so-called ‘BPA-free’ alternatives has been proposed, ultimately they have not yet been able to meet the performance standards exhibited by BPA-based polymers, or were controversial from a safety point of view as well.

Moreover, common BPA production requires phenol, which is derived from fossil benzene. Unfortunately, (i) the large discrepancy between the phenol and acetone markets (due to the strong growth in BPA demand), and (ii) the volatility of the benzene market are expected to pose a significant threat to the economics of phenol (and strongly related BPA) production. In reaction to prior issues, literature has proposed several methods for benzene-free synthesis of phenol from renewable feedstock. Yet, due to BPA’s large scale of production, only abundant (aromatic) renewable feedstock are worth considering to substantially replace fossil phenol, and hence to support future industrial production of renewable BPA replacements.

In this doctoral work, the potential of rational safety-driven molecular design is investigated in the synthesis of benign bisphenols from biomass. Herein, the crux of the matter is to find common ground between safety and functionality by eliminating the structural features that instigate oestrogenic activity, while retaining the structural requirements for performance. A very promising strategy to design minimal oestrogenic bisphenols involves the incorporation of o-methoxy moieties. Luckily, not only does the natural design of the aromatic biopolymer lignin – the second most abundant constituent of terrestrial plant biomass – contains such a favorable substitution pattern, but the recent selective valorisation of (native) wood lignin also gives prospects that such methoxyphenols will become accessible from future biorefineries. In this way, renewable resources do not function merely as a goal to replace fossil resources, but also serve as a means to produce less toxic molecules. To realize not only safer but also functional designs, at least the methylenediphenol scaffold should be retained to impart performance. Hence, a new platform of o-methoxylated methylenediphenols is developed.