FAQ

Chromatography

1. Why is the level of fines important?

The amount of fines is important whether you are running a column or using a scavenger in a batch reactor. Whether in SPE or Flash cartridges, fines will cause channeling, backpressure and clugging. When you are working in a batch reactor, fines can clug your filter or pass through and contaminate your final product. Our silica gel has the lowest level of fines in the industry and we maintain strict quality control to ensure excellent lot-to-lot reproducibility.

General Functionalized

1. 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 (Styrene, ethylene, glycol, etc.) and for silica, it is the repetition of SiO4. Therefore the polymer has an organic backbone whereas the silica gel has an inorganic one. The polymer is more susceptible to leaching which happens when the polymer condensation is not completed and parts of it can dissolved in organic solvents.

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

The silica active sites are on the surface where they are accessible giving fast kinetics and high yields. Silica gel is not affected in any way by any organic solvent since the pore structure is rigid, permanent, and consequently is mechanically and thermally stable.

2. How should functionalized silica be handled?

Handling functionalized silica is easy. Unlike polymer, it does not carry any static charge, which makes it easier to weigh and dispense. They can be wet or dry packed. For all functionalized silica gels with a moisture and/or air sensitive functionality, they should be handled under an inert atmosphere in order to preserve their reactivity.

3. What are the storage conditions for the functionalized silica?

It will vary depending on the storage conditions and approximated shelf life of grafted functional groups. These informations are written on the PDS (Product Data Sheet) sent with every product. In general, products with reactive hygroscopic functional groups should be stored under inert atmosphere at 4°C. Products stored at 4°C should be allowed to warm to room temperature before opening to minimize condensation. Products with stable functional groups should be stored in closed containers to avoid moisture.

4. What is endcapping and why do you do it?

When functionalizing silica, it is impossible to react with every silanol groups (free OH groups of the silica) so we “endcap” the residual ones with a capping agent.

There are two main benefits to endcapping: First, it makes silica non-acidic and non-polar. Bare silica gel used for chromatography has all its silanols free. That is what makes it polar and somewhat acidic. In chromatography, polar interactions are the basis of separation. But for functionalized silica 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 being used in harsh conditions, the endcapping prevents the surface from being attacked and destroyed. The figure below represents what the surface structure looks like.

5. Are all functionalized products endcapped?

Most products are endcapped but there are a few exceptions. The oxidants, Si-KMnO4, Si-PCC and Si-PDC are not endcapped 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.

6. Does functionalized silica dissolve in methanol or any other standard organic solvents?

No, endcapped silica is insoluble in all standard organic solvents.

7. 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 silanols are endcapped.

8. Can different functionalized silicas be mixed?

Yes, if you don’t need them to interact together. One of the key benefits of using supported reagents and scavengers is that you can mix incompatible functional groups such as acids and bases together and they won’t interact with each other. 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 amide coupling with Carbodiimide and HOBt, you need the reagents to interact so only one of them can be supported.

9. 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.

10. 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 stir bar in contact with the bottom of the flask can result in some shearing and grinding of the silica which over time can lead to an increased level of fines. We have confirmed with a scanning electron microscope that fine particles start to appear after 4 hours of agitation with a magnetic stirrer. These fine particles are not detrimental to the reactivity of the silica gel but they can cause filtration issues such as clugging 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 consider using an overhead mechanical stirrer or a supended magnetic stirrer in order to avoid indesirable grinding.

11. 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.

12. 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 some 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 active loading is determined by a test reaction.

13. 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). SiliCycle’s products have been used from development to pilot plant scale.

14. Can 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 undergo a chemical change during use, such as Si-Isocyanate (being converted to urea), are going to be very difficult to recycle as the transformation cannot be inverted.

15. Do you do custom synthesis?

Yes, we provide a custom synthesis service based on silica products. If you need a product that is not in our catalog, please contact us to discuss about your product request.

Scavengers

1. What is a supported scavenger?

A supported scavenger is a reactive functional group grafted onto a silica backbone. Once a reaction is completed, a supported scavenger can be introduced in the reaction flask or the reaction solution can be passed through a SPE cartridge 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 process.

2. How do you choose a scavenger?

Please refer to the scavenger selection guides: one specifically for the removal of metals and the other for more general scavenger. These are designed to act as a general guide, however, in some cases, it may be necessary to try a few different scavengers. For this purpose, you can refer to the selection of scavenger kits. If you have any questions, please contact our technical support department.

3. What is "Catch and Release" technique?

“Catch & release” is a term used when a molecule is temporarily bound either ionically or covalently to a functionnalized silica and 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 Strong Cation Exchanger (SCX). TsOH will catch 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 act as an activating, or a protecting group. For example, Si-TsCl can act as a bound tosylate to activate 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.

4. 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.

Metal Scavengers

1. How do you choose a metal scavenger?

Please refer to the metal scavenger selection table. In addition to the metal itself, there are a number of parameters that affect the scavengers’ effectiveness. Please refer to the case study on Pd which illustrates some of the variables that may affect the scavenger or the Metal Scavenger brochure. In some cases, it may be necessary to try a few scavengers. For this purpose, we have developed a metal scavenger kit. If you have any questions, please contact our technical support department.

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

To get an effective metal removal, the amount of SiliaMetS Metal Scavenger used is very important. You can determine by two different ways how much scavenger will be needed;

• from the residual concentration (more accurate method)
• from the amount of metal catalyst used (when the residual metal concentration is unknown)

From residual metal concentration (ppm)

Knowing the palladium (Pd) level in 800 g of material is 500 ppm, (the oxidation state does not affect the calculation).

Data needed:
• Loading of the scavenger (SiliaMetS Thiol): 1.2 mmol/g
• Metal molecular weight: Ex. Pd = 106.42 g/mol
• Amount of product to be treated containing the Pd: Ex. 800 g
• Residual concentration of metal: Ex. 500 ppm of Pd

1. Determine the amount of palladium to be scavenged

2. Calculate the amount of scavenger (SiliaMetS Thiol) to use (1 equivalent)

To scavenge 400 mg of palladium, 3.13 g of SiliaMetS Thiol is needed if ­using only one equivalent. However, it is highly recommend trying a minimum of 4 equivalents at first. In this case, the amount of SiliaMetS Thiol will be 4 times higher (4 x 3.13 g = 12.40 g).
Sometimes, the metal residual concentration is unknown. In such a case, the amount (g) of palladium to be scavenged can be replaced by the amount of metal catalyst used for the ­reaction:

From amount of metal catalyst used

Data needed:
• Amount of metal catalyst used: Ex. 10 g of Pd(PPh₃)₄
• Metal catalyst molecular weight: Pd(PPh₃)₄ = 1155.56 g/mol

1. Determine the amount of palladium to be scavenged

The amount of SiliaMetS Thiol to be used can then be determined as stated above (see point 2. above). In this particular case, one equivalent of SiliaMetS Thiol ­corresponds to 7.20 g.­

Reagents

1. What is a supported reagent?

A supported reagent is a reactive functional group grafted onto insoluble silica. Unlike a scavenger, which is added once a reaction is completed, a supported reagent is added at the beginning of the reaction; it replaces the homogeneous 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 be difficult to remove such as triphenylphosphines. Purification is now a simple filtration and evaporation process.

2. Won’t the supported reagents leach since they are adsorbed and not bound?

It depends on how they are used. To be effective, the supported reagents such as Si-KMnO4 should be used in a solvent where the free reagent is not soluble. By doing so, 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 almost always used as a suspension in DCM, adsorbing it onto silica facilitates its removal. The reagent cannot technically leach since it is not soluble.

Formatted Silica: TLC, Flash Cartridges and SPE

1. Do you do custom formats?

Yes, we provide a variety of custom packing formats and can pack any of our functionalized gels into any format. (Flash cartridges or SPEs)

2. 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 easily applied to automation. Common SPE formats include syringe barrels type and 48, 96, 384 well plates.

3. What type of SPEs do you offer?

We offer a variety of SPE formats, mainly pre packed barrels in a variety of sizes from 1ml to 377ml. 48, 96, 384 well plates are also available. In terms of sorbent, any type of silica or functionalized silica that we offer are available for packing . Please see the SPE section of our site for more information.

4. How do you choose your sorbent for SPE?

For standard types of SPE, you need to consider two things: the solvent (aqueous or non aqueous) and the mechanism of interaction (polar, non polar or ion exchange). Then, consult the SPE flow diagrams to make your selection. If you are interested in using a scavenger in SPE, you should consult the scavenger selection guides: one specifically for the removal of metals and the other for more general scavenger.

5. How do select what size of SPE to use?

There are no strict rules for selecting the size of SPE. SiliCycle sorbents have a higher loading than comparable silica based material from other manufacturer. For organic and metal scavenging applications, we recommend using at least a 4 fold excess of SiliaBond® Metal Scavenger. The sample volume should be kept small; ideally it should be completely adsorbed into bed (approximately 120 µL per 100 mg). Residence time is the key for a good scavenging efficiency.