TRANSENZYMEX TRANsposition à l échelle semi-pilote de la Synthèse ENZYmatique de nouveaux macrobisphénols biosourcés et leur incorporation dans des Matrices polymères par EXtrusion réactive Dr. Pierre Ferchaud (CVG) Pr. Florent Allais (Chaire ABI)
Today: bisphenol-based copolymers TXIC Bisphenol A (BPA) Co-monomer Aliphatic/aromatic copolymers 2
Tomorrow: macrobisphenol-based copolymers Phenolic compound from lignin Aliphatic diols Enzymatic catalysis Bio-based Macrobisphenol Co-monomer Metal-free polymerization Aliphatic/aromatic copolymers 3
Bio-based starting materials Ferulic acid Lignocelullose degradation C 2 H Isosorbide Double dehydration of sorbitol H H H Me Ethylene glycol From bioethanol through successive dehydration/oxidation/hydrolysis H H H H 1,3-propanediol Fermentation of sugars H H 1,4-butanediol E. Coli-mediated fermentation of sugars H H 4
Biocatalysis via Candida antarctica lipase B (CAL-B, Novozyme 435 ) Lipase = hydrolysis/formation of esters Biocatalysis under mild conditions (65-90 C) High selectivity Active in bulk or in-solvent Active on acids, methyl/ethyl esters Immobilized on resin: elimination by filtration, reusable Inactive on phenols 5
Biocatalysis via Candida antarctica lipase B (CAL-B, Novozyme 435 ) CAL-B Inactive towards phenols Et R R H H Me CAL-B H Me R = non-aromatic, primary or secondary alcohol Benefits No protection of phenol required No homopolymerization issues Sun, S. et al., J. Mol. Catal. B: Enzym. 2009, 57, 104-108 Cassani, J. et al., Electron. J. Biotechnol. 2007, 10, 508-513 6
Chemo-enzymatic synthesis of macrobisphenols Bulk or in- solvent (Hexanes) H C 2 H Me i) HCl/EtH, ii) Pd/C, H 2 H Et Me CAL-B 75 C H H H H H H H H Me H Me H H Me H H H Me H Me Me H H «ne- pot» H H H Me H Me H Me Pion, F.; Reano, A.; Ducrot, P.-H. and Allais,* F. RSC Adv. 2013, 3, 8988-8997 7
Kinetic study of the condensation in-bulk 100 Me H H Me 80 60 H Me p2mal yield reached a:er 5 hours (primary alcohols) Me H % conversion 40 Isosorbide 1,4-butanediol Me H H H H Me H 20 1,3-propanediol Glycerol Me 0 0 10 20 30 40 50 60 70 Time (h) p2mal yield reached a:er 2 days (secondary alcohols + steric hindrance) Pion, F.; Reano, A.; Ducrot, P.-H. and Allais,* F. RSC Adv. 2013, 3, 8988-8997 Me H H Me 8
Kilolab transfert Equipment 5- Liters reactor From - 40 to + 170 C Reduced or atm. Pressure (inert) ATEX Reac2on, reflux, dis2lla2on, crystalliza2on Büchner filter From 0 to + 70 C Reduced or atm. Pressure (nitrogen) 9
Laboratory Labscale vs. Kilolab-scale Et Kilolaboratory (x 44) 22.9 g 1000 g H Me 3.7 g H H 162 g 2 g CAL-B 75 C 87.4 g 4 heures 20 heures Me H H Me 10
Comparison: catalyst separation Laboratory Kilolaboratory Crude mixture solubilizaaon Dichloromethane : 11 L Acetone : 3 L FiltraAon ver Celite, rince with DCM (2 L) 24 µm, rince with acetone (2 L) ConcentraAon Rotary evaporator Dis2lla2on (acetone/ethanol) in the reactor 11
Comparison: purification Laboratory Kilolaboratory CrystallizaAon MeH, 70 C, 8.7 L 502 g EtH, 70 C, 3 L + 2 L (wash) 680 g Chromatography Silica gel DCM + AcEt (Unknow volumes) 218 g CrystallizaAon For the 2 frac2ons MeH (6.5 L) 656 g 12
Conclusion benchscale vs. Kilolab-scale Recovered yields (85%) and purity (95%) are strictly identical Solvant consumption for 1 kg of bisphenol: 40 L for the benchscale 8.8 L for the kilolab-scale Highly simplified purification Benchscale to micro-pilot scale transposition : validated! 13
Solvent Resistant DiaNanofiltration, a greener alternative to recrystallization? Diafiltration Technique Removal of contaminants 3 rd Stage 1 st Stage 2 nd Stage 14
1 st Stage Diananofiltration Borsig NF1 35 bar 2 nd Stage 100 100 80 80 % 60 40 % 60 40 20 20 0 0,0 2,0 4,0 6,0 8,0 10,0 12,0 VD Purity = 99.2 % Loss = 44.2 % (To be recovered in the second stage) 0 1,0 3,0 5,0 7,0 9,0 11,0 VD Purity = 96.9 % Global Purity = 97.9% Global loss = 16.3 % Good agreement between experimental data and the model prediction 15
Solvent Recycling 3 rd Stage Loss of Reagents (%) 16 14 12 10 8 6 4 2 0 2,0 1,5 1,0 0,5 0,0 1 6 11 Concentration factor, f Loss (exp) Loss (model) Impurities (model) Impurities (exp) Acetone impurities (%) Global Performance of the membrane-based process: BDF Recovery = 85% (similar to crystallization) Purity = 98% (vs. 95% w/ recrystallization) Solvent Recovery = 90% (impurities < 1%) EtDFe + BDF Recovery in last step = 86% 9x of volume reduction Impurity < 1% Losses = 14% 16
Acknowledgements Dr. Andreia Teixera (M.C.) Gaëlle Willig (TR) Julien Couvreur (TR) Aurélien Peru (AI) Dr. Pierre Ferchaud Dr. Hélène Ducatel Funding