Using acetal functionalization for the design of safer chemicals.

Compelling evidence shows the toxicity of several bulk chemicals encountered in daily life, including bisphenol A (BPA) and N,N-dimethylformamide (DMF). As regulations tighten, these substances are often replaced with closely related "regrettable alternatives", underscoring the need for truly safer options. In parallel, valorization of lignocellulosic biomass offers a path toward a more circular chemical industry. In this context, aldehyde-assisted fractionation (AAF) has emerged as a promising biomass fractionation strategy, stabilizing reactive intermediates via cyclic acetal formation. Recent insights into the additional advantages of these functionalized preserved natural structures (e.g., rigidity, polarity...) support expanding this strategy to the design of indirect substitutes for petrochemicals. This dissertation further explores how biogenic motifs can be functionalized through acetalization and tuned to produce safer alternatives to BPA and DMF. First, we replaced BPA as a monomer in epoxy resins. A xylose-based diol was synthesized via carbohydrate functionalization and catalytic hydrogenation under mild conditions, achieving up to 85% yield from xylose. Despite its distinct structure, this diol closely mimicked BPA's reactivity, rigidity, and connectivity in epoxy resins, while offering comparable formulation properties. Built on a xylose core that appears to minimize toxicity signals, the diol derived diglycidyl ether showed nearly identical curing kinetics and comparable thermomechanical properties to conventional systems. Importantly, the labile acetal bonds enabled resin degradability, allowing recovery of carbon fiber or adherends and up to 80 % xylose. Second, we replaced BPA as a color developer in thermal paper, with a light-colored lignin polymer obtained through Sequential AAF (SAAF), which lowered chromophore concentration through multiple extraction cycles, improving printing contrast. Good performance was achieved with SAAF lignin (color density at 120 °C ~ 0.8 - 1.1) when combined with xylan-based diformylxylose (DFX) as a sensitizer. Coatings remained stable for over a year under ambient conditions. Lignin based developers showed estrogenic activity two to three orders of magnitude lower than BPA, while lignin's high molecular weight avoids skin penetration. Third, we expanded the acetalization strategy to glycerol. We developed a family of dipolar aprotic solvents as substitute for DMF, the solvent of choice in many pharmaceutical processes. We introduced trioxa-3,6,8-bicyclo[3.2.1]octanes (TBOs) as tunable solvents, made in two steps from bio-glycerol and tested them in solid-phase peptide synthesis (SPPS) as a case study. The lead TBO solvent accelerated couplings and enabled reducing amino acid equivalents from 2.0 to 1.1, while maintaining performance. In the synthesis of difficult sequences in batch (Barstar[75-90], 68% vs 65% in DMF) and in flow (Neurokinin A, 68% vs 51% in DMF), crude purities improved compare