Polymer supported chemistry has been used widely in industrial applications for over fifty years. Biotage supported reagents and scavengers are based on functionalized polystyrene or silica polymers. They are inert, specifically-reactive and clean additives deployed to achieve a specific purpose.
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:
... or pack them into columns and flow through for fixed-bed applications. There are numerous applications – from reaction catalysis to stoichiometric reagent delivery.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Accelerate a wide range of solution-phase reactions and work-ups with Biotage's scavenger resins and solid supported reagents.
Biotage® MP-Borohydride is a versatile reducing agent used for the reduction of carbonyl compounds and imines, and the reductive amination of aldehydes and ketones.
Biotage® MP-Cyanoborohydride is a macroporous polymer supported cyanoborohydride. It is a versatile reducing agent for the reductive amination of carbonyl compounds and reduction of imines. The reaction work-up protocol is greatly simplified by using the solid supported reagent. Specifically, compared with the small molecule sodium cyanoborohydride, it is reported that toxic cyanide is not released on reaction workup and therefore does not contaminate the product or pose a danger towards the user.
Biotage® MP-Triacetoxyborohydride is a macroporous polystyrene-supported equivalent of tetraalkylammonium triacetoxyborohydride. Its primary applications in the reductive amination of aldehydes and ketones under neutral or mildly acidic reaction conditions. This resin was developed to perform in a manner similar to that of the well-established sodium triacetoxyborohydride, while simplifying reagent handling and product purification. Moreover, for many of these reactions, a scavenger resin may be added for one-pot purification of the product.
Biotage® PS-Carbodiimide is a neutral, bound carbodiimide that can be used for the synthesis of amides and esters. In general, PS-Carbodiimide was found to synthesize amides in high yield and purity without evidence of residual amine or carboxylic acid. Unreacted carboxylic acid, normally used in excess relative to the amine, remains bound to the resin during workup.
Biotage® PS-HOBt(HL) is a sulfonamide-linked, polymer supported equivalent of 1-hydroxybenzotriazole (HOBt). PS-HOBt(HL) is used to generate bound HOBt active esters, which can either be made and used in situ, or isolated and stored as stable intermediates for the synthesis of high purity amides.
Biotage® PS-PPh3-Pd resin is a polystyrene-supported equivalent of the small molecule catalyst tetrakis(triphenylphosphine) palladium(0) [Pd(Ph3P)4]. The primary application for the resin is as a catalyst for Suzuki-Miyaura coupling reactions between arylboronic acids and aryl halides. PS-PPh3-Pd may also have applications in other types of palladium-catalyzed processes in which Pd(Ph3P)4 is used. The Suzuki reaction is one of the most widely practiced coupling protocols for the preparation of symmetrical and unsymmetrical biaryl compounds. The resin was developed to perform in a manner similar to that of the well-established catalyst, while facilitating reagent handling and simplifying workup, product isolation, and removal of palladium.
Biotage® PS-TBD is a polymer-supported bicyclic guanidine moiety (1,5,7-triazabicyclo[4.4.0]dec-5-ene) base. PS-TBD applications include alkylation of phenols and amines; esterification of carboxylic acids using alkyl halides; alkylation of activated methylene compounds; de-halogenation of organic halides; high throughput synthesis of aryl triflates and aryl nonaflates, and the regioselective synthesis of lysophospholipids.
Biotage® PS-TEMPO is a novel polymer bound oxidant, based on a polystyrene bound, sulfonic ester linked 2,2,6,6-tetramethylpiperidine-1-oxyl species (PS-TEMPO),. It allows rapid and efficient access to often unstable ketone or aldehyde reactive species, and displays a visual indication of its oxidation state. The color change observed as the oxidation state of the reagent changes, can give an indication of the extent to which the reagent has been used. PS-TEMPO can be regenerated and reused for multiple oxidation reactions.