Siliceous Mesocellular Foam (MCF) for Green Chemistry Jaehong Lim, Su Seong Lee and Jackie Y. Ying Institute of Bioengineering and Nanotechnology, Singapore 12th Annual Green Chemistry and Engineering Conference   June 25, 2008 Washington, DC

IBN, Biopolis, Singapore IBN @ The Nanos Chromos Centros Matrix Genome Proteos Nanos Helios

Heterogenization of Catalysts Shortcomings of Homogeneous Catalysts High cost Low stability Difficulties in reuse Toxic residues in product Benefits of Heterogenization Cost-effective Good stability Easy purification Reduced toxicity in product Recycling use of expensive material Feasible for scale-up Potential application as a continuous flow process

Spherical Mesocellular Foam (MCF) Conventional MCF - Effective for catalysis and separation - Easy to prepare Robust Uniform particle size Large pores Large surface area - Potential scale-up Spherical MCF Particle size: ~5 mm Pore size: ~25 nm Window size: ~15 nm Wall width: ~5 nm Pore volume: 2.0-2.5 cm3/g BET surface area: 500-600 m2/g

Design of Immobilized Catalysts Support Mesocellular Foam Inert Robust Well dispersed in solvents Synthesizable Catalyst Organometallic Organo- Stable Active Reusable Linker Hydrocarbon Triazole, etc. Inert Flexible Synthesizable

Fabrication of Immobilized Catalysts <1eq. HMDS O H TMS T M S OH O H OH MCF Procedure 1 – Precapping 2 – Grafting 3 – Postcapping 4 – Incorporation Ligand O H L T M S TMS OH Catalyst Well dispersed! C T M S TMS excess HMDS L T M S TMS

Ring-Closing Metathesis + Catalyst = Mo, Ru, etc. X = C, O, N, etc. Ring size = 5 ~ >15 BILN 2061 Anti-HCV agent Boehringer Ingelheim

Synthesis of Catalysts 2nd gen. Grubbs Cat. CuCl, 50°C DCM Catalyst n Ligand (mmol/g) Ruthenium Ru / Lig PC-1 0.44 0.17 0.42 PC-2 0.24 0.13 0.57 BC-1 1 0.22 0.18 0.91 BC-2 0.36 0.21 0.64

Catalytic Activity PC-1 PC-2 Conversion (%) HG-II BC-1 Homog. BC-2 Homogeneous Time (hr)

Recyclability Conversion (%) Run # BC-1, DCM PC-1, DCM PC-1, Toluene BC-2, Toluene Run #

Substrates 100-94% up to 7 runs: 25°C, DCM 88% - run 1 75% - run 2 80°C, Toluene 100-94% up to 7 runs 25°C, DCM

Enhanced Recyclability SH-oct 0.15 mmol/g Conversion (%) SH-oct SH-tms SH-tms 0.21 mmol/g Run #

Leaching Study Recyclability ICP-MS Temp. pre-BC-1 Ru residue [ppm] Run 1 Run 3 Run 5 25°C - 35 30 20 5 mol% 23 18 15 50°C 13 9 7 10 Conversion (%) 25°C, 1 hr / run 50°C, 0.5 hr / run 25°C, 5 mol% pre-BC-1, 2 hr / run 50°C, 5 mol% pre-BC-1, 1 hr / run Run #

RCM Catalysts via “Click” Chemistry 1 mol% CuI DIPEA, THF Room Temp 2nd-gen Grubbs Cat. CuCl, DCM, 50oC Catalyst Linker Ligand (mmol/g) Ruthenium RCM-Pr n-Propyl 0.19 0.16 RCM-Bn Benzyl RCM-Pn n-Pentyl 0.15 0.14

Activity & Recyclability 5 mol% catalyst; DCM; RT; C = 0.05M RCM-Pr RCM-Bn RCM-Pn Linker-Carb Linker-Alkyl Run # Conversion (%) Conversion (%) RCM-Pr RCM-Bn RCM-Pn Linker-Carb Linker-Alkyl Time (hr)

More Catalysis Cyclopropanation Organocatalysts “Click” MCF L-Tyr-OMe.HCl L-Phe-OMe.HCl

Magnetic Micro-catalyst for RCM Synthesis Fe2O3 SiO2 Fe2O3 SiO2 Fe2O3 SiO2 Easy recycle Images 10nm 200nm

Acknowledgments Prof. Jackie Y. Ying and Ms. Noreena AbuBakar Dr. Su Seong Lee Ms. Siti Nurhanna Riduan IBN, BMRC and A*STAR, Singapore