Screening Process
Choose Functionalised Materials for Scavenging
The metal scavenger selection table provides information on scavenger affinity for each metal. It is recommended that a number of materials or an established metal kit are screened against a particular metal removal problem. The removal kit selected will contain a number of functionalised materials which have demonstrated high affinity for the metal to be removed. Within each precious metal kit, four materials have been highlighted as top screening candidates, to allow screening of the kit in two stages if required.
Select Experimental Design Factors
Equivalents of scavenger to use
In initial experiments we suggest using 0.5 – 1 weight equivalents of scavenger to the API or synthetic intermediate. Once the preferred
scavenger is identified, the process can be quickly optimised and the number of equivalents of scavenger reduced down to typically 2-4 molar equivalents of scavenger : metal residue in the API - subject to each particular problem. See the dosage calculator to help calculate how much PhosphonicS™ Scavenger to use and for further guidance on initial screening and optimisation. Any potential interaction between the functional groups on the scavenger and any other reactive reagents or by-products present should also be
considered at this stage.
Temperature
In initial experiments we suggest using a starting temperature of 50 ºC for scavenging investigations. Whilst many scavenging processes can be operated successfully at room temperature within reasonable timescales, higher scavenging rates can often be achieved by warming the solution. PhosphonicS™ materials can be added directly to warm reaction mixtures and heated to elevated temperatures without degradation.
pH of Aqueous Reaction Mixtures
For best results, PhosphonicS™ materials should be used in the pH range 2 to 10. Outside of this pH range, care should be exercised.
Agitation Rate
Higher agitation rates can enhance scavenging performance, although typically gentle to moderate agitation rates will suffice. Use of orbital shaking or gentle stirrer bar stirring is recommended on small screening scales, proceeding to overhead stirring upon scale-up.
Solvent
PhosphonicS™ materials can be used in a wide range of aqueous and organic solvents, including typical solvents such as THF, DMF, ethyl acetate, methanol, toluene, ethers and chlorinated solvents. Changing solvent can be considered if scavenging is slow.
In initial experiments we suggest using 0.5 – 1 weight equivalents of scavenger to the API or synthetic intermediate. Once the preferred
scavenger is identified, the process can be quickly optimised and the number of equivalents of scavenger reduced down to typically 2-4 molar equivalents of scavenger : metal residue in the API - subject to each particular problem. See the dosage calculator to help calculate how much PhosphonicS™ Scavenger to use and for further guidance on initial screening and optimisation. Any potential interaction between the functional groups on the scavenger and any other reactive reagents or by-products present should also be
considered at this stage.
Temperature
In initial experiments we suggest using a starting temperature of 50 ºC for scavenging investigations. Whilst many scavenging processes can be operated successfully at room temperature within reasonable timescales, higher scavenging rates can often be achieved by warming the solution. PhosphonicS™ materials can be added directly to warm reaction mixtures and heated to elevated temperatures without degradation.
pH of Aqueous Reaction Mixtures
For best results, PhosphonicS™ materials should be used in the pH range 2 to 10. Outside of this pH range, care should be exercised.
Agitation Rate
Higher agitation rates can enhance scavenging performance, although typically gentle to moderate agitation rates will suffice. Use of orbital shaking or gentle stirrer bar stirring is recommended on small screening scales, proceeding to overhead stirring upon scale-up.
Solvent
PhosphonicS™ materials can be used in a wide range of aqueous and organic solvents, including typical solvents such as THF, DMF, ethyl acetate, methanol, toluene, ethers and chlorinated solvents. Changing solvent can be considered if scavenging is slow.
Typical Experimental Procedure
The solid scavenger can be added directly to the solution of API or synthetic intermediate. No pre-wetting of the scavenger is required. The mixture should be agitated for at least one hour for initial investigations. Scavenging progress can be followed by normal analytical techniques such as ICP. A strong indication of the progress of metal removal can sometimes be gained by the loss of colour from the solution, or by colouration of the normally white scavenger. If metal removal is not complete then the process can be continued or
parameters such as temperature adjusted, with residual metal content measured at additional suitable periods.
parameters such as temperature adjusted, with residual metal content measured at additional suitable periods.
Optimisation
In exceptional cases the scavenging process may need to be extended to several hours or overnight with the use of additional scavenger and/or an increase in temperature. Mixtures of scavengers might also be employed. At the end of this period the scavenger is removed by filtration, the scavenger washed with additional solvent and the combined solutions concentrated. After selection of the best scavenger(s), optimisation of the scavenger quantity (typically down to between 2-4 molar equivalents of scavenger to metal residue in the API can be achieved), temperature, scavenging time and solvent type can be undertaken if required. Cartridge formats and pre-weighed centrifuge tubes are available as alternatives to loose scavenger to facilitate throughput during early screening stages.
