1 / 15

Application of Porous Scavengers for High Throughput Purification Cory Szafranski, Qunjie Wang, Joseph J. Kirkland, Timo

Application of Porous Scavengers for High Throughput Purification Cory Szafranski, Qunjie Wang, Joseph J. Kirkland, Timothy Langlois Agilent Technologies Inc. Lorin A. Thompson DuPont Pharmaceuticals. APPLICATION OF POROUS SCAVENGERS FOR HIGH THROUGHPUT PURIFICATION

nerina
Download Presentation

Application of Porous Scavengers for High Throughput Purification Cory Szafranski, Qunjie Wang, Joseph J. Kirkland, Timo

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Application of Porous Scavengers for High Throughput Purification Cory Szafranski, Qunjie Wang, Joseph J. Kirkland, Timothy Langlois Agilent Technologies Inc. Lorin A. Thompson DuPont Pharmaceuticals

  2. APPLICATION OF POROUS SCAVENGERS FOR HIGH THROUGHPUT PURIFICATION Cory Szafranski, Qunjie Wang, Joseph J. Kirkland and Timothy Langlois, Agilent Technologies Inc., 2850 Centerville Road, Wilmington, DE 19808; Lorin A. Thompson, DuPont Pharmaceuticals, Wilmington, DE 19880-0500 ABSTRACT To overcome practical difficulties related to gel-type polystyrene-based scavengers, i.e. large wet volume, significant swelling, solvent incompatibilities, and low flow-through efficiencies, we have recently developed silica and macroporous polymer based scavengers (CombiZorb). This presentation describes the advantages and usefulness of these scavengers, and applications of them in various reaction protocols.

  3. Introduction • Solid scavengers are increasingly used in parallel organic synthesis to remove excess reactants or by-products. However, most scavengers are based on gel-type poly- styrene, which features: 1) very high swelling in some solvents - cannot be pre-packed and stored in a cartridge or column format; 2) necessity of swelling - narrow range of compatible solvents. • New macroporous scavengers - CombiZorb has been developed based on ultra-pure, spherical silica and low swelling macroporous polystyrene/DVB, to overcome these drawbacks.

  4. Macroporous Scavengers • Based on ultra-pure, spherical silica: S-Monoamine(NH2), S-Triamine(NH, NH2), S-TertiaryAmine, S-Sulfonic Acid, S-Aldehyde, S-Epoxide, S-Mercaptan, S-Diphenylethylphosphine. • Based on low-swelling macroporous polystyrene/DVB: MP-Isocyanate, MP-Aldehyde, MP-Mercaptan, MP-Trisamine(NH, NH2), MP-Piperidinomethyl, MP-Sulfonyl Hydrazide(-NHNH2), MP-Sulfonyl Chloride

  5. Features and Advantages (vs. gel-type polystyrene based scavengers) • Silica-based: Ultra pure silica - no interference with reactions. Spherical silica - easy to handle, good flow-through properties. No-swelling, high density - larger amount for available volume; possible incorporation into different formats (membrane, column). Porous structure - solvent independent, good mass transfer of reactants. • Low-swelling macroporous polystyrene/DVB-based: Low swelling (30% vs. 500% for gels) - larger capacity per vol., easy to handle, possible in different formats (membrane, column). Porous structure - broad solvent compatibility.

  6. Performance Comparison

  7. Performance Comparison (cont’d) Scavenging aldehyde/ketones by polymer-SO2NHNH2 (3 eq., 2h, RT, in MeOH). residue (%) MP-: Macroporous CombiZorb Scavengers Gel-: Gel polystyrene based Scavengers

  8. Scavenging Test of S-Triamine

  9. Scavenging Test of MP-Isocyante(2.5 equiv.)

  10. Rxn run in 2 mL of Ethyl Acetate, THF, or DMF. Added 200 mL of water, stirred 16 h at RT. • The solution is forced through a plug of 450 mL of scavenger in a 2.0 mL tube, and is then rinsed with 1.0 mL of solvent. • Eluents are conc., redissolved in 4.0mL solvent, and analyzed by HPLC. Sequestering of Carboxylic Acids % Acid Remaining

  11. Acylation of Benzylamine - Benzylamine, chlorobenzoyl chloride and S-Tertiary Amine were mixed with 2 mL CH2Cl2 at RT and shaken for 1 hour. - S-Triamine plus 1 mL acetonitrile was added to the mixture and shaken for 1 h, the solid was filtered off and washed with CH2Cl2 (twice, 0.5 mL each). - Benzyl chlorobenzamide was obtained as a pure product upon solvent evaporation.

  12. Synthesis of Pyrazoles

  13. Summary • Two types of porous scavengers (ultra pure silica, low-swelling polystyrene) have been developed with a variety of functionalities. • The preliminary studies demonstrate the major advantages of the new scavengers: - higher capacity for available volume; - broad solvent compatibility; - compatible with different application formats.

  14. References For general application of scavengers

  15. Stability of Silica-based Scavengers safety zone - Non-aqueous solution: 1< pH<14 , >24 h - 10% H2O: 1<pH<10, >5h - > 50% H2O: 1<pH<10, >2h

More Related