Chemical Synthesis

ChemDose

Convenient Dosing of Catalysts and Reagents:

 


Introduction
ChemDose® is a novel technology allowing for the use of chemical reagents and catalysts in the form of tablets.1-2 The ~5 millimeter tablets are composed of a chemically inert magnesium aluminosilicate matrix, together with an adsorbed reagent or catalyst. Upon exposure to solvents, the reagent or catalyst readily dissolves out, leaving behind an easily removed insoluble tablet. Co-developed with Reaxa, Ltd, ChemDose® technology allows for fast, accurate, and consistent dispensing of milli- and micromolar quantities of chemicals to reaction vessels, thus saving time while minimizing waste. ChemDose® tablets are particularly useful for handling sensitive catalysts and reagents, which can be difficult to weigh and are prone to degrade in the presence of air or moisture. Importantly, there is no "learning curve" with ChemDose®— the tablets can simply be substituted for the classical ligand, catalyst, or reagent in a given chemical reaction.

ChemDose® Tablets

ChemDose® tablets are well-suited for parallel solution phase synthesis where rapid optimization of reaction parameters is desired, and are compatible microwave reactor technology. The image below illustrates a screening experiment designed to optimize a Suzuki-Miyaura cross-coupling reaction performed under microwave conditions. Six different palladium catalysts were employed in the form of ChemDose® tablets, and product yields were determined after 5 minutes of reaction time.



ChemDose inert matrix mechanism

Sigma-Aldrich offers a growing portfolio of palladium catalysts and ligands in the form of ChemDose® tablets, for use in cross-coupling and other reactions (e.g., Suzuki, Sonogashira, and amination reactions), as well as three peptide coupling reagents in tablet form. Each ChemDose® product is available in units of 10 or 100 tablets.

Catalysts (Loading)* Ligands (Loading) Coupling Reagents (Loading)
Pd(OAc)2 (2 or 10 µmol) X-Phos (2 µmol) DCC (0.15 mmol)
Pd2(dba)3 (0.5 µmol) S-Phos (2 µmol) DIC (0.15 mmol)
Pd(dppf)Cl2•CH2Cl2 (2 µmol)   HATU (0.02 mmol)
Pd(PPh3)4 (2 µmol)  

 

Pd(PPh3)2Cl2 (1 µmol)    
PEPPSI-IPr (2 µmol)

 

 

* All loadings given on a per tablet basis

References:
(1) Ruhland, T. et. al. J. Comb. Chem., 2007, 9, 301.
(2) ChemDose® is a registered trademark of Reaxa Ltd. and is covered by international patent application no. PCT/DK05/000428 and related patent applications, including European patent application no. 05753717.7.

 

Advantages

 

  • Convenient handling and dispensing of reagents and catalysts
  • Eliminates the tedious weighing process for small chemical quantities
  • Reduction of waste
  • Compatible with parallel automation and microwaves: rapid reaction optimization
  • Simple reaction work-up: inert tablet easily removed upon completion of reaction
  • Consistent chemical loadings of tablets, controlled release rates
  • Reaction kinetics closely parallel conventional reagent
  • Virtually no "learning curve" in using ChemDose® products


 

Representative Applications

Suzuki Coupling

Suzuki Coupling

Suzuki Coupling

Sonogashira Coupling

Sonogashira Coupling

Sonogashira Coupling

Amide Bond Formation

Amide Bond Formation

     Chromatograms after 1 hour:

Amide Bond Formation

Frequently Asked Questions (FAQs)

  1. What are the ChemDose® tablets made from? How big are the tablets?

    The tablets themselves are composed of a chemically inert magnesium aluminosilicate matrix, along with the adsorbed reagent or catalyst. All tablets are approximately 5 millimeters in diameter.

  2. Where do I find information on the exact loading for a given lot of a ChemDose® product?

    The certificate of analysis (C of A) contains lot specific loading information, along with the method used for the loading determination.

  3. How should I dispose of spent ChemDose® tablets?

    They should be treated as solid waste, contaminated with reaction species. The matrix is non-toxic and environmentally benign.

  4. How should I store ChemDose® tablets?

    As with most catalysts and ligands, as a general precaution it is best to store them in a refrigerator and/or under an inert atmosphere to maintain activity. Some catalysts, such as Pd(dppf)Cl2·CH2Cl2, are more robust and can be handled in air without issue. Please refer to the ChemDose® label for specific handling of a given catalyst, ligand, or reagent.

  5. Can I use them in any solvent?

    Yes, including aqueous solvents.

  6. Do the tablets disintegrate during the course of the reaction?

    They are normally recovered intact, however, they may disintegrate somewhat in aqueous reactions. Any disintegrated tablets can be removed from the reaction via filtration.

  7. What is the pH stability of the ChemDose® tablets?

    The ChemDose® tablets are mildly basic and will dissolve in the presence of mineral acids.

  8. Can I use them in a microwave or pressure vessel?

    Absolutely. Please see the Technical Information for Download section (below) for additional examples of cross-coupling reactions involving the use of microwaves.

Technical Information for Download (PDF format):

1) ChemDose® Presentation (2.8 MB PDF)
2) ChemDose® Technical Flyer (563 KB PDF)

 

Product Information


 

  Product Number Product Name Synonym Loading
(per tablet)
Add to Cart
684929 Palladium(II) acetate, ChemDose® tablets Pd(OAc)2 2 μmol
685593  Palladium(II) acetate, ChemDose® tablets Pd(OAc)2 10 μmol
685135 Tris[dibenzylideneacetone]dipalladium(0), ChemDose® tablets Pd2(dba)3 0.5 μmol
(1.0 μmol Pd)
685127  [1,1'-Bis(diphenylphosphino)ferrocene]-dichloropalladium(II)–dichloromethane complex, ChemDose® tablets Pd(dppf)Cl2 ·CH2Cl2 2 μmol
685364 Tetrakis[triphenylphosphine]palladium(0), ChemDose® tablets Pd(PPh3)4 2 μmol
685607  Bis(triphenylphosphine)palladium(II) dichloride, ChemDose® tablets Pd(PPh3)2Cl2 1 μmol
685143 PEPPSI-IPr, ChemDose® tablets   2 μmol
685585  S-Phos, ChemDose® tablets   2 μmol
685151 X-Phos, ChemDose® tablets   2 μmol
685178 N,N'-Dicyclohexylcarbodiimide, ChemDose® tablets DCC 0.15 mmol
685666 N,N'-Diisopropylcarbodiimide, ChemDose® tablets DIC 0.15 mmol
685739  O-(7-Azabenzotriazol-1-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, ChemDose® tablets HATU 0.02 mmol