Novel Solvents for Sustainable Technology

1. CHEMRAWN-XVII and ICCDU-IX GREENHOUSE GASES – Mitigation and Utilization, Kingston, ON, Canada, 11 July, 2007 Novel Solvents for Sustainable Technology Prof. Charles A. Eckert, Prof. Charles L. Liotta Georgia Institute of Technology, Atlanta, GA and Prof. Philip G. Jessop Queen’s University, Kingston, Ontario

2. “Sustainable” is not just hugging a tree…

3. It’s getting everyone to hug a tree

4. Sustainable Chemical Process Reactor • Major Cost: Separation and Purification • Systems Approach • Modify Reaction to Facilitate Separation • Applications: Chemicals Pharmaceuticals Microelectronics Biotechnology Products Separator RawMaterial Recycle

5. Novel Solvents Using CO2 • Supercritical CO2 • Gas-Expanded Liquids • Reversible Acids • Reversible Ionic Liquids

6. C H 7 15 - CN- + N C H C H 7 15 7 15 C H 7 15 Supercritical CO2for Phase Transfer Catalysis • Reaction of Species of Different Polarity • Not Both Soluble in Most Common Solvents • Involves Reaction Between Phases, i.e. Toluene-Water • Alternative: PTC • Tetraheptyl Ammonium Bromide • ‘Greasy” Counterion -- Brings CN- into Toluene

7. Phase Transfer Catalysis in SCFs:Typical Reactions

8. Three-Phase PTC System with Catalyst-Rich Surface Phase Supercritical CO2 Phase C H C l C H C N 2 2 Catalyst Phase + N KCN Solid Phase

9. Benefits of SCFs for PTC • Environmentally Friendly • Favorable Transport Properties • Tunable with Density • Tunability with Cosolvents • Easy Solvent Removal • Catalyst Recycling Opportunities

10. GAS GAS Liquid Liquid Liquid Add CO2 Gas-Expanded Liquids (GXLs)Tunable Organic-CO2 Mixtures • Good Organic Solvents Miscible with CO2 • Solubility is Pressure Tunable • Solvent properties are pressure tunable • Separation by Depressurization

11. Properties of GXLs:Phenanthrene Sol’y in Acetone, 25 °C Liquid Acetone Liquid CO2

12. Acid Properties of GXLs CO2 Methanol + Reichardt’s Dye (Indicator) Same Flask after CO2 Introduction

13. In Situ Formation of Acids from CO2 Water + CO2 Methanol + CO2 Hydrogen Peroxide + CO2 (for oxidation reactions)

14. β-Pinene to α-Terpineol in GXL/MeOH • Fragrances, Intermediates • Current Process • Aqueous, Acidic • Neutralization, Waste Salt • Limited Solubility of β-Pinene (10-15 ppm) • Reactants Much More Soluble in Methanol • Forms Methylcarbonic Acid • No Need to Add or Neutralize Acid • Reversible Acid Forms In Situ • Product Separation Tunable with CO2 Pressure • No Waste Salt

15. + CO2 Vapor Vapor GXL Organic H2O Catalyst Aqueous Catalyst - CO2 Organic Aqueous Tunable Solvents (OATS)for Homogeneous Catalysis • Homogeneous Reaction • Organic/Aqueous Solution • Ambient Pressure • CO2 Induces Phase Split • Heterogeneous Separation • GXL Poor Solvent for • Ionic Catalysts • Enzymes • Decant, Depressurize • Catalyst Recycle • Product Purification

16. Organic-Aqueous Tunable Solvent: OATSCO2 Effect on LLE for THF/Water

17. Water-THF-CO2 Equilibria Left: No CO2 Single Liquid Phase Water Soluble Dye Right: 20 Bars CO2 Two Liquid Phases, Dye Partitioning > 105 Cover Picture, J. Phys. Chem. B, 2004

18. OATS Reaction: Hydroformylation • Water-soluble catalyst • Minimal Rh loss • Industrial Process for Propylene • Mass transfer inhibited for larger olefins • THF improves solubility • TON improved 50 – 100 Fold • Isomerization Problems

19. Hydroformylation Reaction Rate

20. OATS for Biocatalytic Synthesis and Purification of Hydrophobic Drugs • Enantioselective Biocatalysis • Water Insoluble Substrates • Facile Product Isolation and Catalyst Recycle • OATS Mixture • Benign Alternative for Organics • Higher Enantioselectivity • Higher Efficiency • Higher Stability of Enzymes • Facile Purification of Pharmaceuticals

21. Biocatalytic Synthesis of Chiral Alcohols NADH-dependent enzymatic reduction of less-water soluble ketones Enzymes: ADH (alcohol dehydrogenase), FDH (formate dehydrogenase); Cofactor: NAD(H) — hydrogen transfer agents; Buffer: 0.1 M ammonia formate, pH  6.5

22. Recovery Efficiency of (s)-(-)-sec-Phenylethyl Alcohol in OATS Acetonitrile/Water (50:50), 40 °C. (0.2 mol/L NH4HCO3 buffer, pH 5)

23. CO2 out CO2 in Product/ Organic (GXL) Homogeneous Biocatalysis Product Purification Reactants Products Enzyme/ Aqueous Aqueous/Enzyme Recycle Organic Solvent Recycle OATS: Homogeneous Reaction/Heterogeneous Recovery

24. Difficult Separation Product Contamination Variation in Activity or Selectivity Catalyst Leaching off Support Mass Transfer Limitations Best of Both Worlds Homogeneous Catalysis Heterogeneous Catalysis OATS Facile Separation Increased: - Selectivity - Yields - ee’s

25. Reversible Ionic LiquidCO2 (1 atm.) Acts as “Switch” • DBU(1,8-diazabicyclo-[5.4.0]-undec-7-ene) Non-Polar Chloroform Polar (Ionic Liquid) Dimethylformamide or Propanoic Acid Jessop, Heldebrant, Li, Eckert, Liotta, Nature2005, 436, 1102.

26. Guanidine Cased ILs • Guanidines + MeOH + CO2 RTILs • Reverses Readily • With Inert Gas Sparge, Heat Polarity like Chloroform Significantly More Polar than [bmim][BF4]

27. Hydrocarbon TMBG/MeOH Reversible IL as a Solvent • Soluble in DBU and TMBG • Octane, Heptane, Pentane • Phase separation upon formation of IL • Negligible Cross-contamination CO2 Hydrocarbon Phase N2 or Heat TMBGH+/ MeOCO2-

28. DBU or TMBG Ionic Liquid Pentane Reaction/Separation in Reversible ILs 1- Pentane 2-MeOH/CO2 Product C A + B Product C SEPARATION REACTION Heat or N2 REFORMATION RECYCLE

29. Novel CO2-Based Solvents to Couple Reaction and Separation • Build Separation Scheme into Reaction • Tunable Solvents • Supercritical • Nearcritical • Gas-Expanded Liquid • “Smart” Solvents • Sustainable Processes