Title: Application of Porous Scavengers for High Throughput Purification
1Application of Porous Scavengers for High
Throughput Purification Cory Szafranski, Qunjie
Wang, Joseph J. Kirkland, Timothy
Langlois Agilent Technologies Inc. Lorin A.
Thompson DuPont Pharmaceuticals
2APPLICATION 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.
3Introduction
- 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.
4Macroporous 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
5Features 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.
6Performance Comparison
7Performance Comparison (contd)
Scavenging aldehyde/ketones by polymer-SO2NHNH2
(3 eq., 2h, RT, in MeOH).
residue ()
MP- Macroporous CombiZorb
Scavengers Gel- Gel polystyrene based
Scavengers
8Scavenging Test of S-Triamine
9Scavenging Test of MP-Isocyante(2.5 equiv.)
10Sequestering of Carboxylic Acids
- 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.
Acid Remaining
11Acylation 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.
12Synthesis of Pyrazoles
13Summary
- 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.
14References
For general application of scavengers
15Stability of Silica-based Scavengers
- safety
zone - - Non-aqueous solution 1lt pHlt14 , gt24 h
- - 10 H2O 1ltpHlt10, gt5h
- - gt 50 H2O 1ltpHlt10, gt2h