A New Ether Process Solvent : Cyclopentyl Methyl Ether (CPME) for green Chemistry & Process Innovation

Transcription

1 IGCW th Oct A New Ether Process Solvent : Cyclopentyl Methyl Ether (CPME) for green Chemistry & Process Innovation The Bronze prize in CPhI Innovation Awards 2010 Sustainability Awards in Informex 2011 ZEON CORPORATION 1

2 Contents 1 Introduction of Zeon Corporation 2 Background of Development 3 Physical Properties of CPME 4 Matching of CPME for the 12 Principles of Green Chemistry 5 CPME for Process Innovation 6 Conclusion 2

3 1 Introduction of Zeon Corporation 3

4 1-1 Corporate Profile, Business Segment & Products Corporate Profile Date of Establishment 12 th April, 1950 Capital JPY 24.1 billion Employees 3,090 Crude oil Naphtha Ethylene(C2) Propylene(C3) C4 C5 Business Segment & Products C4 & C5 Chemistry GPB Geon Process of Butadiene Licenced to 49 plants in 19 countries GPI Geon Process of Isoprene Butadiene Isoprene Piperylene DCPD Dicyclopentadiene 2-Butyne Synthetic Rubbers Latex Petroleum Resins Elastomers RIM Reaction Injection Molding Specialty Plastics Specialty Chemicals Application Tires Belts Automobile parts Traffic paint Adhesives Paint Ink Combined septic tank Housing materials Lenses Light-guide plates Light dispersion plates Optical films Perfumes Pharmaceuticals Solvents Segment Elastomer Business Others Specialty Materials Business 4

5 1-2 Specialty Chemicals - Derivatives Cyclopentene Derivatives Halogenated Hydrocarbons Alcohol & their derivatives Carboxylic acid & their derivatives Hydrocarbons Ketones Cyclopentene Others Metallocene Aroma products CPME 2-Butyne Derivatives Norbornene derivatives 2-Butyne Leaf Alcohol & Leaf Esters 5

6 2 Background of Development 6

7 2-1 Back Ground of Development Common Ether Solvent # Very soluble in water # Easy peroxide formation # Low boiling point # Moderately soluble in water # Unstable to acid Sales Started from Nov CPME has : High hydrophobicity Wide range liquid state Low peroxide formation Stable to acids & bases 7

8 3 Physical Properties of CPME 8

9 3-1 Physical Properties CPME THF MeTHF Et 2 O Dioxane MTBE Density (20 C) [g/cm 3 ] Vapor specific gravity (air = 1) Boiling point [ C] Melting point [ C] < Viscosity (20 C) [cp] (25 C) Surface tension (20 C) [mn/m] Unknown Vaporization energy (bp) [Kcal/kg] Specific heat (20 C) [Kcal/kg K] Unknown Refractive index (20 C) Wide Range Liquid State Low Vaporization Energy Solubility parameter [cal/ml] Unknown Unknown Dielectric constant (25 C) Dipole moment [D] 1.27 (calcd.) 1.7 Unknown Azeotropic temperature with water [ C] 83 (a) (b) (c) Solubility of solvent in water (23 C) [g/100g] 1.1 Infinite Infinite 4.8 Solubility of water in solvent (23 C) [g/100g] 0.3 Infinite Infinite 1.5 High Hydrophobicity Flash point [ C] Auto Ignition Temperature [ C] ~ LogPow Unknown Explosion range [vol%] Lower limit Upper limit

10 3-2 Positioning Among Other Solvents 180 Glycol-ethers DMSO Boiling Point 100 Toluene Dioxane MTBE IPE CPME AcOEt MeTHF THF DMF Appropriate Boiling Point, Polarity Et2O Low Polarity (Dielectric Constant) High 10

11 3-3 Summary of CPME Benefits 1. Green Chemistry High Recovery Rate > 90% --- High Hydrophobicity Reduces amount of wastes and CO 2 Diverse uses as reaction, extraction and crystallization solvents --- Solvent unification, Reduction of solvent amount Low peroxide formation Manufactured by atom economical process Makes Azeotrope with water : 16% water at Process Innovation Diverse uses as reaction, extraction and crystallization solvents --- Reduction of solvent exchange Process simplification and shortening One-pot synthesis and telescoping Stable under acidic and basic conditions 11

12 4 Matching of CPME for the 12 Principles of Green Chemistry 12

13 4-1 Matching of CPME for the 12 Principles of Green Chemistry 1. Prevention Significant reduction of water and solvent waste CPME matches 8 principles 2. Atom Economy We manufacture CPME by the atom economical reaction. 3. Less Hazardous Chemical Syntheses 4. Designing Safer Chemicals 5. Safer Solvents and Auxiliaries CPME makes slight peroxides. We manufacture CPME with minimum auxiliaries. 6. Design for Energy Efficiency CPME can save energy by simplification and shortening of production processes. 7. Use of Renewable Feedstocks 8. Reduce Derivatives We manufacture CPME in the one-step continuous system without derivatizations. 9. Catalysis We manufacture CPME in the catalytic process in the presence of the solid acid. 10. Design for Degradation 11. Real-time analysis for Pollution Prevention The flow reaction process is continuously monitored. 12. Inherently Safer Chemistry for Accident Prevention CPME has lower formation of peroxides in comparison with common ethers. 13

14 4-2 Examples of CPME for Green Chemistry - Reduction of Wastes & CO 2 Emissions - 1. Prevention THF Process CPME Process In CPME process, big reduction of CO 2 would be possible. 14

15 4-3 Examples of CPME for Green Chemistry - Manufacturing Process - 1. Prevention 8. Reduce Derivatives 2. Atom Economy 9. Catalysis 5. Safer Solvents and Auxiliaries 11. Real-time Analysis 6. Design for Energy Efficiency for Pollution Prevention Molecular Weight = Continuous catalytic addition reaction by solid acid catalyst : No atom waste, energy saving 15

16 4-4 Examples of CPME for Green Chemistry - Low Peroxide Formation Inherently Safer Chemistry for Accident Prevention 16

17 5 CPME for Process Innovation 17

18 5-1 Process Simplification & Cost Reduction - Fixed Cost Reduction - THF Process Reaction Simple process! CPME Process Reaction Ethyl acetate Much water Water Concentration Extraction Washing THF Much waste water Waste water Water Washing CPME : Reaction & Extraction solvent Waste water Concentration Ethyl acetate Concentration CPME Product Product 18

19 5-2 Process Simplification & Cost Reduction - Cost Reduction Example Including solvent recovery - Extraction solvent: unnecessary! CPME recovery rate = 90% recovery rate = 70% recovery rate = 60% $6 x 10 x 0.1 = $6//kg - product $5x 10 x 0.3 = $15/kg - product $3 x 10 x 0.4 = $12/kg - product equal weight of water to Product A Reaction Solvent Cost Solvent/Product = 10/1(by weight) ($6/kg) MeTHF ($5/kg) THF ($3/kg) 4 weight times of water to Product AcOEt ($1.2/kg) $1.2 x 10 x 0.1 = $1.2 4 weight times of water to Solvent B Extraction Solvent Cost AcOEt ($1.2/kg) $1.2 x 10 x 0.1 = $1.2 equal weight of water, aqnacl to Product 2 weight times of water, aqnacl to Solvent C Waste Disposal Cost ($0.5/kg) CPME: $0.5 x 10 x 0.1 = $0.5 water: $0.5 x 3 = $1.5 MeTHF: $0.5 x 10 x 0.3 = $1.5 AcOEt: $0.5 x 10 x 0.1 = $0.5 water: $0.5 x 6 = $3 Total Variable Cost (A+B+C) (Waste solvent, Waste water) THF: $0.5 x 10 x 0.4 = $2.0 AcOEt: $0.5 x 10 x 0.1 = $0.5 water: $0.5 x ( ) = $40 CPME MeTHF THF $8.0/kg-product $21.2/kg-product $55.7/kg-product * The prices used here are only to demonstrate their cost reduction with CPME. The actual prices would vary according to conditions such as quality, quantity, location, time, etc. 19

20 5-3 Potential Applied to Wide Range ph - High Resistance to Strong Acid & Base - CPME : Very Stable to Acid & Base 20

21 5-4 Example of Process & Green Chemistry Innovation - Pinner Reaction - R-CN solution solvent yield (%) 1,4-Dioxane Et 2 O 86 a) CPME CPME 90 b) CPME CPME 89 b) Solvent Requirements - stability to acid - solubility of raw materials - insolubility of product CPME CPME 91 b) a) U.S.Pat. No.: US B2 b) Work-up of CPME process is only filtration and washing. THF : Impossible to use! K. Watanabe, N. Kogoshi, H. Miki, Y. Torisawa, Synth. Commun. 2009, 39,

22 5-5 Example of Process & Green Chemistry Innovation - Process Simplification at Pinner Reaction - Original Process CPME Process 1. Solvent : Et 2 O-Dioxane 1. Solvent : CPME 2. Cooling Reaction 3. Warmed at N 2 Bubbling HCl Telescoping Steps 9 to 4 Solvents 2 to 1 2. Cooling Reaction 5. Removal of solvent in vacuo 6. Precipitated by cooling 7. Addition of Et 2 O 8. Filtration Et 2 O Dioxane Waste Waste Et 2 O Greener Process Without Dangerous Solvents Reduce wastes 3. Filtration 9. Drying 4. Drying Product Product 22

23 5-6 Example of Process & Green Chemistry Innovation - Amino Acid Anhydride Synthesis - Original Process 1. Raw Material / Ethyl Acetate 2. Phosgene Dimer Charge (Dropwise), Reaction / N 2 Bubbling 4. Removal of Ethyl Acetate 5. Addition of n-hexane 6. Filtration 7. Drying Telescoping Steps 7 to 6 Solvents 2 to 1 Greener Process Without Dangerous Solvents Yield : 70 79% Purity : % n-hexane CPME Process 1. Raw Material / CPME 2. Phosgene Dimer Charge (Dropwise), Reaction / N 2 Bubbling 4. Removal of CPME 5. Filtration 6. Drying Product Hodogaya Chemical Co., Ltd., Japan Patent Product 23

24 5-7 Example of Process & Green Chemistry Innovation - Grignard Reaction - Solvent Yield of Products (%) Selectivity of Products (%) Alcohol Olefin Alcohol Olefin THF THF + CPME CPME *Grignard reagent concentration : 1mol/L Selectivity & Yield of Alcohol : Dramatically Changed 24

25 5-8 Example of Process & Green Chemistry Innovation - Crystallization Solvent - Recrystallization of the Intermediate in the Tamiflu synthesis Recrystallization from CH 2 Cl 2 /CPME (1:2) 80% yield, 95%ee 99%ee! K. Yamatsugu, L. Yin, S. Kamijo, Y. Kimura, M. Kanai, M. Shibasaki, Angew. Chem. Int. Ed. 2009, 48,

26 5-9 CPME as Green Alternative Solvent - ACS / GCI Solvent Selection Guide - CPME is one of green solvent Candidates in discussion of ACS / Green Chemistry Institute. 26

27 6 Conclusion 27

28 6-1 Conclusion CPME contributes to: 1. Green Chemistry Reduction of water, wastes and CO 2 Avoid dangerous solvent Extraction solvent is not necessary by hydrophobicity High recovery rate Lower peroxide formation 2. Process Innovation Fixed cost reduction Reduce process time, vessels and apparatus by solvent unification Variable cost reduction Process Simplification by telescoping Extraction solvent is not necessary by hydrophobicity High recovery rate Better Stability to acid and base 28

29 6-2 CPME Won Awards Bronze Prize in Innovation Awards 2010 Product Category Profiles in Sustainability

30 Thank You for Listening 30

31 Appendix-1 CPME Specifications Specifications Purity (GC) min % Water (KF) max. 100ppm Peroxide (Titration) max. 50wtppm Color (Hazen No.) max

32 Appendix-2 CPME Toxicological & Ecological Data 32

33 Appendix-3 ICH Guideline for Residual Solvents (Zeon) CPME has not yet classified in ICH guideline for residual solvents (Q3C). However, it is assumed to be in Class 2 according to Zeon's own calculation. 1) Formula PDE = (NOEL x Weight Adjustment)/(F1+F2+F3+F4+F5) Concentration Limit (PPM) = 1000 x PDE / dose *PDE: Permitted Daily Exposure 2) Calculation PDE = (15x50) / (5 x 10 x 10 x 1 x 1)=1.5mg/day Concentration Limit = 1000 x 1.5/10 = 150ppm 3) Conclusion According to the above, Zeon assume CPME would be classified in Class 2. 33

34 Appendix-4 : Toxicological Assessment of 2-Methyltetrahydrofuran and Cyclopentyl Methyl Ether in support of Their use in pharmaceutical Chemical process Development PDE (mg/day) CPME 7.4 MeTHF 6.2 THF 7.2* Toluene 8.9* *ICH Guideline Antonucci, V et al.: Org. Process Res. Dev., Article ASAP, /op100303c, March 18,