Regioselective synthesis, isomerisation, in vitro oestrogenic activity, and copolymerisation of bisguaiacol F (BGF) isomers

• Published in: Green chemistry : an international journal and green chemistry resource : GC 2019, Vol.21 (24), p.6622-6633
• Main Authors: Koelewijn, Steven-Friso, Ruijten, Dieter, Trullemans, Laura, Renders, Tom, Van Puyvelde, Peter, Witters, Hilda, Sels, Bert F.
• Format: Article
• Language: English
• Subjects: Addition polymerization; Alcohol; Alkylation; Biopolymers; Bisphenol A; Byproducts; Chemical synthesis; Copolymerization; Green chemistry; Guaiacol; Isomerization; Isomers; Lignin; NMR; Nuclear magnetic resonance; Organic chemistry; Petrochemicals industry; Phenols; Physicochemical properties; Regioselectivity; Substitution reactions; Thermoplastic resins; Vanillyl alcohol
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/C9GC02619C

Bisguaiacol F (BGF), a potentially safer and renewable bisphenol A (BPA) replacement made from lignin-derivable vanillyl alcohol ( p -VA), is a promising building block for future aromatic biopolymers. Unfortunately, like BPA synthesis, this electrophilic condensation reaction is also prone to regioselectivity issues, giving rise to m , p ′- and o , p ′-BGF byproducts. In this work, the hitherto unconsidered influence of m , p ′-BGF, viz . the main isomeric byproduct of p , p ′-BGF synthesis, on the physicochemical properties of poly(BGF carbonate) (BGF-PC) was systematically investigated by random copolymerisation with different fractions of pure m , p ′-BGF (25, 50 and 75 wt%). To do so, the elusive m , p ′-isomer was made in unparalleled regioselectivity (72%) by alkylation condensation of isovanillyl alcohol ( m -VA) with guaiacol. Surprisingly, no isomeric scrambling due to acid-catalysed isomerisation was encountered for pure BGF isomers, which strongly facilitates their synthesis in contrast to petrochemical bisphenol F (BPF). Furthermore, to ensure safer chemical design, an in vitro human oestrogen receptor α (hERα) transactivation assay was performed. Both pure m , p ′- and p , p ′-BGF displayed a significantly reduced oestrogenic potency (∼426–457 times lower affinity than BPA) and oestrogenic efficacy (∼39–50% of BPA's maximum induction). Interestingly, mutual comparison between p , p ′-BPF and p , p ′-BGF reveals and proves for the first time the direct link between ortho -methoxy substitution and reduced in vitro oestrogenic activity (for transactivation of hERα). In contrast to o , p ′-BPA, viz . the main byproduct of p , p ′-BPA synthesis, m , p ′-BGF was proven suitable for utilization in thermoplastics, thereby avoiding time-consuming and labour-intensive (re)crystallizations to obtain regioisomerically pure p , p ′-BGF.