FAQ

Why is the level of fines important?

The amounts of fines are important whether you are running a column or using a scavenger in a batch reactor. In a columns flash and SPE, fines will cause channeling, backpressure and clogging. When you are working in a batch reactor, fines can clog your filter or slip through and contaminate your final product. Our silica gel has the lowest level of fines in the industry. We maintain strict quality control to ensure excellent lot-to-lot reproducibility.

What is the difference between silica and polymer?

Both are made from the linkage of repetitive units. In the case of polymers it is the repetition of monomer units and for silica it is the repetition of SiO₄ tetrahedrons. Therefore the polymer is an organic backbone whereas the silica gel is an inorganic one. That makes the polymer more susceptible to leaching which happens when the polymer condensation is not complete and parts of it can get dissolved in organic solvents.

With the polymer the active sites are inside the matrix so the rate of scavenging is largely dependent on the rate of diffusion through the polymer. This is why it must be used in solvents that swell it (DCM, THF, CHCl₃). This also means that product can get trapped inside the polymer greatly affecting the yield.

With silica the active sites are on the surface where they are accessible giving fast kinetics and high yields. We use very porous irregular silica to maximize our loading. Silica gel is not affected in any way by any organic solvent since the pore structure is rigid and permanent.

How should the functionalized silica be handled?

Handling functionalized silica is easy; it has a high level of mechanical and thermal stability. Unlike polymer, it does not carry any static charge, which makes it easier to weigh and dispense. They can be wet or dry packed and are easily formatted. For the functionalized silicas that carry a moisture or air sensitive function, it is recommended that, like all products of that nature, they should be handled under an inert atmosphere to keep the products' freshness. Click here to view “Working with Silica Bound Scavengers”.

What are the storage conditions for the functionalized silica?

It depends on the functional group we provide the storage conditions for maximum shelf life on the PDS (Product Data Sheet) for each specific product. In general, products with reactive hydroscopic functional groups they should be stored under an inert atmosphere and in the refrigerator at 4°C for maximum shelf life. Please remember that products that are stored in the refrigerator should be allowed to come to room temperature before they are opened to minimize condensation. Products with stable functional groups should be stored in airtight containers to avoid moisture build up.

What is endcapping and why do you do it?

When we functionalize our silica it is impossible to react with all available silanol groups (free OH groups on the silica surface) so we “endcap” the residual ones with a capping agent such as trimethylsilylchloride to form Si-O-Si(CH₃)₃. There are two main benefits of end capping.

First, it renders the silica non-acidic and non-polar. Bare silica gel for chromatography with all its free silanols is polar and somewhat acidic (pKa~5). In chromatography this polar interaction is the basis for the separation, but for functionalized silica that is used as a scavenger or a reagent, the only interaction that should occur is the one with the grafted function and not a non-specific binding with the surface.

The second reason is that when functionalized silica is used in harsh conditions, the end?capping prevents the surface from being attacked and destroyed. The figure below represents what the surface structure looks like.

 

Are all functionalized products endcapped?

Most products are end capped but there are a few exceptions. The oxidants, Si-KmnO₄, Si- PCC and Si-PDC are not end capped for the simple reason that the silanols (free OH groups on the silica surface) are needed to ensure optimal efficiency of the material. They retain the by-products generated during the reaction, considerably simplifying the work-up step.

Does functionalized silica dissolve in methanol or any of the other standard organic solvents?

No, end-capped silica is insoluble in all standard organic solvents.

Does functionalized silica dissolve in water?

Bare silica will start to dissolve in aqueous solutions, albeit very slowly, at pH 9. Lower than 9 it is stable. Over 9, the dissolution will speed up as the pH is increased. For functionalized silica, the pH stability range is increased to between 2 and 12 because the residual OH's are endcapped.

Can different functionalized silicas be mixed?

Yes if you don’t need them to interact. One of the key benefits of using supported reagents and scavengers is that you can mixed incompatible functional groups such as acids and bases together because they can’t interact. This is due to two reasons the relative size of the functional group is very small compared to the size of the particle to which it is attached (roughly 100 000 orders of magnitude difference), and at least 95% of the moieties are grafted inside the pore structure. For some reactions such as an amide coupling with Carbodiimde and HOBt you need the reagents to interact so only one of them can be solid supported.

Can functionalized silica be packed?

Yes, because it has a rigid structure that does not swell in organic solvent it is well suited for packing in cartridges, SPEs and HPLC columns. We offer a wide range of prepacked formats and can provide many more on a custom basis.

What is the preferred method of agitation?

Functionalized silica has a high level of mechanical stability and can be agitated by all of the standard methods including stirring, shaking, vertical oscillation and sonication. Using a magnetic stirrer bar where the magnetic is coupled through the bottom of the flask can result in some shearing and grinding of the silica which over time can lead to an increased levels of fines. We have verified with a scanning electron microscope that fine particles start to appear after 4hrs of agitation with a magnetic stirrer. These fine particles are not detrimental to the reactivity of the silica gel but they can cause issues with filtration such as clogging and slow filtration. For reactions that last less than 4 hours, you can use a magnetic stirrer. For reactions that last more than 4 hours you should use an overhead stirrer or a magnetic stirrer that does not couple through the bottom.

What are the conditions that lead to leaching or cleavage?

The leaching or cleavage of the organic function from the silica gel can be caused by extremely high or low pH, HF, and to a certain extent by long exposure to Na+ and F- in high concentrations.

How is the loading determined for the functionalized silica gels?

We want to determine the loading of a Si-piperidine silica gel. The CNS gives a percentage of N of 1.825%. Knowing there is only one nitrogen atom per molecule of piperidine, what is the loading?

For certain functional groups, determination of the loading by CNS is not enough. This is especially true for highly reactive products such as Si-Carbodiimide for which the loading is determined by a test reaction.

Can silica-based products be used in scale-up operations?

Yes definitely, since functionalized silica has an inert non-swelling matrix unlike the polymeric products. Our products have been used in development to the pilot plant scale.

Can the functionalized silica be recycled?

It depends on the functional group and how it is used. C18 is obviously easily recycled but Si-Isocyanate is not. As a general rule products that are undergo a structural change during use such as Si-Isocyanate being converted to urea are going to be very difficult to recycle. In developing a recycling protocol a lot depends on how the products were used which is why SiliCycle does not offer more than the most general guidelines for recycling.

Do you do custom synthesis?

Yes we provide a custom synthesis service based on silica products. If you are in need of a product that is not in our catalog, please complete the product request form and we will contact you to discuss your needs.

What is a supported scavenger?

A supported scavenger is a reactive functional group grafted onto an silica backbone. Once a reaction is complete, a supported scavenger can be introduced in the reaction flask or the reaction solution can be passed through a packed SPE column packed with the chosen scavenger. The scavenger will react with and bind excess reagent and/or by-products achieving a chemically driven separation. Purification is now a simple filtration and evaporation.

 

How do you choose a scavenger?

Please refer to our two scavenger selection guides. One specifically for the removal of metals and another more general scavenger selection guide. These are designed to act as a general guide however, in some cases, especially metals, its may be necessary to try a few different scavengers, for this purpose we have developed a selection of scavenger kits. If you have any questions please contact our technical support department.

What is "catch and release" with silica scavengers?

“Catch & release” is a term used when a molecule is temporarily bound either ionically or covalently to a silica scavenger and then subsequently released. This is either done to facilitate purification or synthesis.

A very popular example of “Catch &Release” purification is the purification of amines with Si- Tosic acid (TsOH) also known as SCX. TsOH will scavenge the basic amines out of the reaction mixture allowing all other impurities to be washed away with a neutral solvent such as MeOH or DCM. The amines are released by switching to a basic solvent such as 5% ammonia in MeOH or triethylamine in DCM. “Catch & Release” purification normally involves an ionic interaction, and is readily adapted to a SPE format for automation.

“Catch & Release” synthesis is the interface between solution and solid phase synthesis. The scavenger may function as an activating, or a protecting group, For example Si-TsCl can act as a bound tosylate to activated alcohols and Si-Diol can protect ketones and aldehydes by forming the acetal or ketal. Once bound additional transformation maybe performed before the molecule is finally cleaved. The solid support facilitates purification through multiple transformations.

How do you determine how much scavenger to use?

It depends on the compound scavenged. For highly favored reactions, such as acid-base reactions, 1-2 equivalents are enough to ensure completion. For slower reactions, 4-6 equivalents are recommended. Sample procedures are provided with our scavengers.

How do you choose a metal scavenger?

Please refer to our metal scavenger selection guide. In addition to the metal itself there are a number of factors that affect the scavengers effectiveness. Please refer to our case study on Pd which illustrates some of the other variables that may effect the scavenger. In some cases it may be necessary to try a few different scavengers, for this purpose we have developed a metal scavenger kit. If you have any questions please contact our tech support department.

How do you calculate how much metal scavenger to use, starting from ppm concentration of the metal?

If we take the example where the palladium (Pd²⁺) level in 10 kg of active compound is 3000 ppm. This amounts to 30 g of Pd that needs to be scavenged.

3000ppm = 3000/10⁶
grams of Pd = 3000/10⁶ * 10 kg * 1000g/1kg = 30g of ionic palladium

Our choice of scavenger would be the Si-thiol

So 235 g of Si-Thiol need to be used in order to scavenge 30 g of ionic palladium. This is only valid for 1 equivalent. If a higher ratio is desired, the quantity needs to be multiplied by the same factor. (2 eq. = 470 g; 4 eq. = 940 g).

What is a supported reagent?

A supported reagent like a scavenger is a reactive functional group grafted onto insoluble silica. Unlike a scavenger, which is added once a reaction, is complete, a supported reagent is added at the beginning of the reaction and replaces the solution phase reagent and allows the reagent to be used in greater excess driving the reaction to completion. It also facilitates multiple step one pot reactions. The spent reagent is easily removed by filtration. Bound reagents are an excellent alternative in cases where the reagent is used in excess and can by difficult to remove such as triphenyl phosphines. Purification is now a simple filtration and evaporation.

 

Won’t the supported oxidants leach since they are adsorbed and not bound?

It depends on how they are used. To be effective, the supported oxidants such as Si-KMnO₄ should be used in a solvent where the free reagent is not soluble. This way, the reagent stays on the silica for which it has more affinity. If large amount of water is present, the reagent will be completely washed off or destroyed. For example, when working with Si-KMnO₄, an organic solvent such as cyclohexane should be used (see SynLett 2001, 10, 1555-1556). Unbound PCC and PDC are nearly always used as a suspension in DCM, adsorbing it onto silica facilitates its removal. The reagent cannot technically leach since it is not soluble in the first place.

Do you do custom packing?

Yes we provide a variety of custom packing services and can pack any of our functionalized gels into any format.

What is SPE?

SPE stands for Solid Phase Extraction, which is a form of “digital chromatography”, meaning it works in an on/off manner, compared to regular liquid chromatography where the elution on the peaks or components occurs gradually. SPE uses a sorbent that has a strong affinity for the desired compound and solvent changes to collect the individual components as single fractions rather than gradient elution used in normal chromatography which yields multiple fractions of the same component. After applying the sample to a pre conditioned column the column is eluted with a solvent that has a weak affinity for the desired product to removed impurities it is then eluted with a solvent that has a strong affinity for the desired product thereby displacing it from the sorbent. This makes SPE much more amenable to automation. Common SPE formats for include syringe barrels and 96 well plates.

What type of SPEs do you offer?

We offer a variety of SPE formats, mainly pre packed syringe barrels in a variety of sizes from 1ml to 150ml. 96 well plates are available on a custom basis. In terms of sorbent we can pack any of our bare or functionalized gels we have a variety of reverse, normal and ion exchange gels available as std products in addition to flash silica. Please go to the SPE section in our catalog.

How do you choose your sorbent for SPE?

For the standard types of SPE you need to consider two things your solvent (aqueous or non aqueous) and the mechanism for interaction (polar, non polar or ion exchange) and then consult the SPE flow diagrams. If your are interested in using a scavenger in SPE you should consult our selection guide.

How do select what size of SPE to use?

There are no hard and fast rules for selecting the size of SPE. Our sorbents have a higher loading than comparable silica based material and have a nominal loading of 1 mmol/g. For organic and metal scavenging applications the sorbent should be used in at least a 4 fold excess. The sample volume should be kept small ideally it should be completely adsorbed into the bed the volume of a silica bed is approximately 120 µL per 100 mg. Residence time is key for scavenging.