Supported Reagents

Polymer Supported Reagents

Polymer supported reagents are functional polymers designed to perform synthetic transformations in same way as their solution counterparts. Excess reagent and by-products remain attached to the resin, while the end product is purified by simple filtration. Their application is very simple:

1. Add resin/silica to reaction
2. Stir for desired time
3. Filter as usual to purify

... or pack them into columns and flow through for fixed-bed applications. There are numerous applications – from reaction catalysis to stoichiometric reagent delivery.  

Types of Polymer

Biotage® uses two different resin types for its reagents, 1% crosslinked poly(styrene-co-divinylbenzene) and highly crosslinked, macroporous polystyrene. The 1% crosslinked polystyrene is designated by PS-. MP- designates highly crosslinked, macroporous resin. Highly crosslinked macroporous resins swell significantly less in solvent so they are not dependent on swelling to be effective. Instead, reagents diffuse through the pore structure to reach reactive sites. For this reason, MP- resins can be used in confined volumes where swelling would be a problem. They can also be used with a much wider variety of solvents. Alternatively, the use of silica based scavengers has increased significantly in recent years. Also heterogeneous, silica confers the advantage of being amenable to flow / fixed bed applications.

Efficient Delivery to Reactions

Polymer supported reagents are functionalized polymers that perform synthetic transformations in a similar manner to their small molecule, non-bound counterparts, however, they provide the added advantage of heterogeneity, meaning that they are very easy to remove from reactions afterwards for example by simple filtration techniques. 

Non-Toxic, No Smells and Easier To Handle

Once bound to the resin (or silica) there vapor pressure of volatile or toxic reaction components is virtually eliminated and many chemical moieties become more stable, as in the case of MP-Triacetoxyborohydride or the supported tetrakis palladium triphenylphosphine catalyst PS-PPh₃-Pd, for example.

Reduce Processing Steps and Mitigate Impurity Risks

Even if by-products are not toxic or do not have a stench, they may still be difficult to separate, co-elute, or mask other target products in a mixture. PS-Triphenylphosphine resin for example performs the chemistry you would expect, but the PS-Triphenylphosphine oxide by-product is 100% resin bound, and is thus easily removed by filtration afterwards. No more issues with large UV signals masking the intended product, giving false reaction performance indicators. Similarly the dicyclohexylurea urea by-product from PS-Carbodiimide resin coupling reactions is also 100% resin bound and can never interfere with products in solution and further downstream reactions.

Drive Reactions with Excess Reagent/Scavenger

Adding more reagents will drive a reaction to completion, but the excess reagents will need to be separated afterwards, involving additional purification steps. With a resin bound strategy, the resin (or silica) supported reagent is heterogeneous, it does ‘see’ the solution, but it is completely insoluble, so removing excess after the reaction is just a case of filtering using simple and inexpensive laboratory items. 

Re-cycle and Re-use

Easy to recover after a reaction, many resins and supported products are also additionally compliant with the principles of green chemistry, being recyclable or operating in a catalytic mode. While many resins are used once, for reasons of industry preference or regulation, Biotage can support clients who need guidance on how to re-use, by providing technical guidance.

Making the Impossible – Possible

Resins and silicas are heterogeneous, meaning that we can lock away products and completely selectively release them later (or lock away by-products, and only let product through). Processes that are energy and labor intensive, such as solvent switching, can be achieved in a matter of seconds at room temperature and at normal atmospheric pressure. High boiling point solvents such as DMF and DMSO can be removed from amine mixtures and replaced with more volatile solvents.

Thermally and Mechanically Stable

Resin reagents work well with overhead stirring or mechanical shaking. They withstand temperatures up to approx. 150 °C (i.e. microwave chemistry heating conditions). Silica supported reagents are mechanically stable, and may also be stirred but are more often packed into fixed bed formats for flow through applications. Silicas can withstand 150–200 °C temperatures, so as long as the intended chemistry is compatible, the resin or silica option is an efficient delivery vehicle for the chemistry of the project.

Scale-Up and Formats

Additionally, Biotage has a flexible cartridge packing facility to accommodate many scale-up paths and options, from grams to multi-kg and in a variety of formats for processing.

Long Shelf-Life

Polymer supported reagents are stable. By definition they only take part in the reactions they were designed for, so side reactions and degradation is much less of an issue compared to small molecule chemistry. In real terms the shelf-life of a functionalized polymer may be indefinite, so we recommend a nominal 1 year expiry when the product is stored in cool dry conditions.