Phosphonics Catalogue 2011 Full

Functionalised Silicas: Scavengers & Catalysts
Powerful Multi-purpose Metal Scavengers By-product and Impurity Removers Green Catalysts
2011-2012
Contents
2 3-4 5 6 Introduction Welcome Technology Product Application Map Formats Solid Phase Extraction (SPE) 42 Introduction 43 SPE Materials and Formats 44 Typical Purification Procedure using Cation Exchange Materials 45-46 Case Studies with PhosphonicS SPE Materials Catalysts 47 Introduction 48 Properties & Benefits of PhosphonicS Heterogeneous Catalysts 48 Heterogeneous Catalyst Kits 49 Heterogeneous Palladium Catalysts 49 Heterogeneous Palladium Catalyst Kit 50-51 Suzuki and Heck Reactions 52 General Suzuki Reaction Conditions 52 Flow Chemistry 53 Immobilised Phosphines 54 Heterogeneous Metal Oxidation Catalysts 55 Heterogeneous Metal Oxidation Catalyst Kit 55 General Oxidation Conditions 56 Summary of Oxidation Transformations 57 Heterogeneous Acid Catalysts 57 Heterogeneous Acid Catalyst Kit 57 Summary of Acid Transformations 58 General Acid-Catalysed Reaction Conditions 58 Case Studies with Acid Catalysts 59 Immobilised Enzymes 60 61-74 75 76 77 77 78 BC
Services 7 Screening Services 8 Development Services 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25-27 28 29 30-31 32 33 34 35 36 37 38 39 40 41 Metal Scavengers Introduction Properties & Benefits of PhosphonicS Metal Scavengers Metal Scavenger Selection Table Dosage Calculator Usage Introduction to Metal Scavenger Kits Kit A : General Metal Kit Kit B : Palladium Kit Scavenging of Palladium from APIs Kit C : Copper Kit Kit D : Chromium Kit Kit E : Ruthenium Kit Kit F : Platinum Kit Kit G : Tin Kit Kit H : Osmium Kit Kit I : Rhodium Kit Options on Process Scale Metal SPE Centrifuge Screening Tubes Metal Scavenging Case Studies Organic Scavengers Introduction Properties & Benefits of PhosphonicS Organic Scavengers Usage Organic Scavenger Kits Kit A : Electrophile Kit Kit B : Cation & Anion Exchange Kit Kit C : H-Bond Formation/Boronic Acid Removal Kit Kit D : Portfolio Kit Organic Scavengers in SPE Cartridge Format Organic Scavenging Case Studies
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Product Listing Pricing Notes Index by Functional Group Index by Application Bibliography/Publications Health and Safety Warranties & Disclaimers Ordering Information Contacts
New Updated 2011
PhosphonicS Ltd 44c Milton Park, Abingdon, Oxon, OX14 4RU www.phosphonics.com
Immobilised Reagents and Catalysts

PhosphonicS is a privately owned technology company specialising in metal scavenging and recovery agents, trace organic impurity removal, heterogeneous catalysts and supported bio-products. This catalogue contains the latest listing of our products and also includes useful information on their application and use. Using new chemical methodology we have developed an elegant and practical approach to the immobilisation of functional groups onto inorganic supports that allows us to generate materials optimised for a specific application. All of the materials in this catalogue are produced to ISO quality standards and are manufactured to a consistent specification whatever the scale and in addition benefit from the economies of scale associated with larger batch production. Custom products (including libraries for screening) sharing these same technical and economic benefits can also be designed and produced. Metal and Organic Scavenging, Metal Recovery Predominantly silica-based, these unique and highly effective functionalised materials give manufacturers and researchers advantages such as: New cost-effective options for the removal of toxic metals or organic fragments from high value products such as APIs, fine and speciality chemicals Materials for the efficient recovery of valuable Precious Metals from waste and process streams Chemical, physical, thermal and mechanical stability Compatibility with a wide range of solvents, pH and temperature conditions Minimal scavenger extractables Fast action and ease of use Availability in a wide variety of formats for use from small scale to bulk manufacture Green Catalysis Homogeneous metal or acid-based catalysts can be effective but often give rise to serious environmental concerns and product contamination issues. Supported heterogeneous systems offer a number of advantages including ease of isolation and removal from the reaction medium but traditionally suffer from a limited range of attached functionality and reduced activity. This catalogue contains details on a new range of supported heterogeneous systems for use in a wide range of commonly used reactions including Cross-coupling and other C-X bond formations Selective oxidations at carbon and sulfur Lewis acid-catalysed reactions and rearrangements Acid-catalysed reactions By tightly tethering the metal or active functionality to the support PhosphonicS has developed a range of heterogeneous catalytic systems that remain highly active through the catalytic cycle. The metal catalysts in particular can be used in a wide range of applications without transfer of the metal to the product or reaction medium. Application information Based on over 20 years experience of working in this area PhosphonicS has built a considerable knowledge base on the use of scavengers and heterogeneous catalysts in a variety of applications. This information is freely available and can be accessed via the website, the application guides contained in this catalogue or directly from PhosphonicS. We welcome comments on our products and new ideas as to how they can be applied, and are happy to share information on how they can be used effectively.
Welcome to PhosphonicS
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OH
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Technology
PhosphonicS exclusive immobilisation technology provides the platform for the design and manufacture of the high performance materials illustrated in this catalogue. The simplicity and elegance of this process offers the benefits of economy of scale combined with consistent product quality and performance. Fundamental to this technology is the strong chemical bond linking the active functionality to the support, with extensive tests revealing no breakdown in a wide range of challenging environments. Utilising predominantly silica frameworks, families of novel materials containing different functional groups have been produced for a wide range of applications. Alumina frameworks are also available as required.
Heteroatom typically S or P can act as additional FG Immobilised Functional group(s) combinations can be varied & optimised
The range of products in this catalogue illustrate our expertise in the following areas Metal Scavenging and Recovery Heterogeneous Catalysis particularly suited to Green Chemistry Organic Fragment Removal and Product Purification Solid Phase Extraction (SPE) and Separation We also have a range of custom products and are constantly developing new materials for different applications and are happy to discuss these with interested parties. Enzyme immobilisation applications have recently been developed and successfully tested externally. Some examples of this functionality are illustrated on page 4. These give a flavour of the diversity of functionality, and available spacer linkages not offered by competitor products. PhosphonicS through its technology has opened up a new area of multi-functional materials not accessible by existing technology, which tends to offer mono-functional or simple materials. This capability allows complex, high activity materials to be designed specific to the target application. The advantages of being able to readily scale the production and deliver reproducible quality and performance make the materials highly commercially attractive. This combination of functional diversity and spacer variability enables PhosphonicS to offer a design service for the immobilisation of specific functional groups, biological entities and polymeric species. Please contact us for further details.
Si
( )n ( )m
Spacer can be varied as application requires
FG
Inorganic support key properties readily tunable
Silica in particular by virtue of its ready availability, chemical and physical stability, variable pore and particle size is an excellent choice of support, however existing synthetic methods have restricted both the range and scale of available functionalised products. The technology developed by PhosphonicS overcomes these difficulties and affords a focused diversity of functionality that can be produced at a consistent quality whatever the scale.
Technology
S S SH S N H N H S NH 2
O S N H
H N
O NH2 S N
OH
OH OH
OH O
OH O
S S PdCl2PPh3 OH
OH OH O O P O O
P OH OH
O O
Ce(IV) O O O
O O O
S Pd(OAc)2
Co(II)
Fast, Efficient, Cost-Effective Solutions The products generated by this advanced technology offer the benefits of: Fast kinetics in purification and catalytic processes No product loss High effective functional group loading Tolerance of a wide range of solvents and reaction conditions High chemical, thermal, physical and mechanical stability Traceless operation, with no product or solution contamination Tuneable products optimised for specific applications leading to significant cost reductions in materials and operating time High quality silica with defined particle size distribution, very low fines level and low trace metal content Variation in particle and pore size according to application
Please contact us for further information on how this range of products can help with your problems.
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Product Application Map

To assist you in finding the appropriate section in this catalogue, a simple application map showing appropriate sections and pages in the catalogue is given below. Application / Product information Metal Scavenging Organic Scavenging Case Studies and Synthetic Examples Pages 17, 25-27, 30-31 Special Formats Process Cartridges Full Product Index
Kits
Pages 15-24
Pages 6, 25-28
Pages 6, 25
Pages 61-74
Pages 36-39
Pages 6, 40
Pages 6, 25
Page 41
Pages 61-74
SPE
Page 43
Page 6, 43
Pages 45-46
Pages 61-74
Heterogeneous Catalysts Palladium Catalysts Oxidation Catalysts
Pages 49, 55, 57
52
Pages 66-70, 72
Page 49
52
Pages 50-52
Pages 68-69
Page 55
Pages 55-56
Pages 66-67
Acid Catalysts
Page 57
Pages 57-58
Pages 66, 70, 72
Immobilised Enzymes
Page 59
Precious Metal scavenged by a PhosphonicS Metal Scavenger, ready for recovery.
Formats
PhosphonicS multi-functionalised materials are available in a wide range of easy to use formats, from loose powder to the pre-packaged systems shown below. The syringe and centrifuge systems are particularly useful for Discovery and Medicinal Chemistry and the cartridge formats have been used successfully at Process Scale.
All pre-packaged formats are available in pharmaceutical grade polypropylene. For the Process Development cartridge, also available in stainless steel, a wide range of O ring and end cap options are offered to fit existing hardware requirements. Format Centrifuge Tubes Scavenger Quantity 50 mg (in 2 mL volume tube) 1 g (in 6 mL volume cartridge) up to 10 g (in 75 mL volume cartridge) ~ 200 g (in 10 cartridge) or ~ 500 g (in 20 cartridge) Application Scavenger screening SPE Metal SPE Organic Scavenging Process Scale Metal or Organic Scavenging
Small SPE Cartridges
Large Process Cartridges
In these new, convenient formats, PhosphonicS materials offer: High scavenging affinity & selectivity for the contaminant (metal, organic), with good product recovery Excellent product purity, with issues of extractable impurities eliminated Tailored sensitivity, allowing key functionalities to be retained Ease of use and avoidance of vessel clean-up issues Good stability, high quality cartridge packing & reproducible results Faster problem-solving, reduced development time & enhanced process productivity Larger formats, including various filter options and vessels for Metal Recovery from waste streams, are also available. For further information or recommendations on any of the product formats described here please contact us.
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Screening Services
Digestion Microwave and ICP Spectrophotometer.
PhosphonicS has developed a number of Metal Screening Services to assist clients in their projects and help identify solutions for purification problems
The standard Metal Screening Service Programs are as follows: PhosphonicS QuickLook What is it? A confidential, fast turnaround service offering an initial look at a metal removal problem. We take a product sample and run a simple, focused scavenging program with a PhosphonicS Metal Scavenger kit. We report pre- & postscavenging results following a defined digestion and ICPOES metal measurement. What does it cover? Measurement of unscavenged sample to establish metal contamination level in the control Scavenging with PhosphonicS materials from the appropriate metal kit, and optional commercial standards, under agreed conditions Work-up, digestion and ICP measurements on scavenged samples plus control Report and recommendations We also offer other metal and organic scavenging testing services: PhosphonicS Scout : a full screening program on a metal removal or recovery problem, or an organic scavenging problem, using a broader range of PhosphonicS Metal or Organic Scavengers to identify preferred scavenger(s) and outline scavenging conditions - this is run as a confidential service. Costed on basis of program but typically 5-10 days duration. PhosphonicS Optimiser : an optimisation program taking a selected/preferred scavenger and working with you to design a process to run on full Process Scale either as a slurry/filtration or via a cartridge/flow design this is run as a confidential service. Costed on basis of program but typically 3-4 weeks duration. Scavenger screening programs seek to timeeffectively & cost-efficiently address the key project decision point of removal of metal contamination from API samples. Clear program objectives are agreed with the client upfront and typically seek to address: Preparative & Analytical Method Development Metal Scavenger Screening Metal Scavenger Optimisation Stages Scale-up Scavenging Experiments Future Recommendations for the Project Team
Development Services
Services
Development Programs Based on its proprietary immobilisation technology, PhosphonicS undertakes commercial development programmes to develop, for example, novel catalytic, purification and recovery processes in collaboration with major pharmaceutical, chemical and catalyst companies. Programme objectives are clearly agreed upfront with the client, progress is regularly communicated and flexibility to modify the programme focus is also allowed within our versatile approach to problem-solving. All client development work is completely confidential and the company has a flexible approach to the commercial structure of a development project and to the use of its intellectual property. Please contact us to discuss any potential applications of PhosphonicS technology. Laboratory Capabilities All PhosphonicS development and screening service activities are carried out in our Oxford laboratories by a dedicated and professional Technical team backed up by a comprehensive analytical service, including ICP-OES capability for metals analysis, HPLC, UV, NMR and solid phase analysis techniques. Engineering PhosphonicS has strategic partnerships with several engineering companies, allowing us to offer fully engineered solutions designed to get the very best from our products when used in commercial scale applications. We can offer advice on the design of process scale and waste management systems based on processes using PhosphonicS materials. In some instances, this extends to assistance in waste management and metal recovery through working with other specialist partners. We can design and build equipment suitable for use at pilot and full commercial scale. We can also supply our products pre-packaged in a variety of standard cartridge (plastic and stainless steel) and column formats, ready to plug straight into your existing process.
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Introduction
Metal Scavengers
Metal catalysts are extensively used to generate a wide range of products across a variety of industries. In the Pharmaceutical and Fine Chemical industries, metal catalysts play an important role in operations from early Discovery through Development to full Manufacture. Precious Metal catalysts in particular are used to promote many key transformations towards the synthesis of new Active Pharmaceutical Ingredients (APIs). In Medicinal Chemistry, palladium is perhaps the most-widely utilised Precious Metal, for reactions such as deprotections and hydrogenations, as well as carbon-carbon bond formations by Heck, Suzuki and Sonogashira couplings and carbonnitrogen bond formations by Buchwald-Hartwig aminations. The mild reaction conditions, high functional group tolerance and high yields offered by these now highly-advanced crosscoupling technologies also means that metal-catalysed reactions are now being used increasingly later on in complex pharmaceutical synthetic routes. Up until now the major drawback of metalcatalysed chemistry has been that toxic metal residues are invariably left bound to the desired reaction product, which will typically contain a number of functional groups, often in close proximity, and capable of strongly binding to Precious Metal catalyst residues. Traditional methods for the removal of metals from APIs include distillation, extraction, adsorption onto activated charcoals and crystallisation. However, these methods suffer from severe disadvantages including significant product loss; performance issues, primarily an inability to achieve the very low levels of residual metal content required by regulators; time and practicality issues. Indeed the leading references reported below describe the challenge of metal removal from APIs as requiring considerable development time, often for each individual product. PhosphonicS multi-functionalised silicas, designed containing ligands with an overall higher affinity for the metal compared to the pharmaceutical product, successfully overcome these metal removal issues and provide an attractive, reliable, practical and cost-effective first option for scavenging residual metals from all pharmaceutical products.
Useful References on Metal Removal from Pharmaceuticals Garrett, C. E.; Prasad, K. Adv. Synth. Catal., 2004, 346, 889 Welch, C. J. et al Org. Process Res. Dev., 2005, 9, 198 Bien, J. T. et al Organomet. Chem., 2004, 6, 263 Girgis, M. J. et al Org. Process Res. Dev., 2008, 12, 1209 Barbaras, D. et al Org. Process Res. Dev., 2009, 13, 1068 Describing the Use of PhosphonicS Scavengers:Galaffu, N. et al Org. Process Res. Dev., 2007, 11, 406 (application to APIs) Grosjean, C. et al Org. Process Res. Dev., 2009, 13, 434 (Suzuki Couplings) Salome, C. et al J. Med. Chem., 2010, 53, 1288 & 3756; Kohn, H. L. et al US Patent 20110021483 (Sonogashira & Heck Couplings)
Properties & Benefits

Properties of PhosphonicS Metal Scavengers
High affinity for a wide range of metals, in different oxidation states High selectivity for the metal, meaning minimal loss of the API/compound Enhanced performance, due to multiple functional groups and higher effective loadings Broad solvent and pH compatibility with both organic and aqueous formulations, reducing the requirements for time-consuming and costly solvent switches No swelling of the materials are required Availability on Process Scale Availability in a variety of formats and scales (loose powder and Process scale cartridges) Excellent stability - thermal, physical, chemical and mechanical Very high purity - eliminating issues of extractable impurities Fast kinetics - highly active at ambient temperatures Metal recycling options
Performance Benefits of PhosphonicS Metal Scavengers

Faster : purification, batch processing, problem-solving, market introduction Reduced : Development time, valuable API losses, total manufacturing costs, environmental burden Enhanced : process, productivity, compliance Regulatory Support : successfully used in commercial applications
Before and after treatment with a PhosphonicS Metal Scavenger. Dichloromethane solutions of Pd(II) and Pd(0) triphenylphosphine complexes respectively Pd levels reduced to <1 ppm in 30 seconds.
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10
Metal Scavengers
Selection Table
Metal Scavengers
The choice of metal scavenger for your reaction and reaction product depends upon the: Particular metal to be removed, as well as its oxidation state(s) Structural nature and functional groups within the desired product/API Environment (solvent and pH) in which the metal is contained Residual reagents and by-products present Potential interaction of the scavenger with the functional groups present in the API
Product Code Pd Cu Cr Ru Pt Sn Os Rh STA3 SEM26 SPM32 SPM36 MTCf SEA SCYT1 PO1 SET STMS SPA5 SPAf POH1 SDEA SPM3 SPM32f SPM36f POH1g SEM26f SPM32g SEAg PMISf Preferred Kit Material (generally very high affinity)
Metals Removed Others Ag, V, Mn, Fe, Co, Ni, Zn, Cd, Pb, Hg, Al, Ga, U, Ir Ag, Fe, Ni, Cd, Pb, Hg, Ir, Au Ag, Fe, Cd, Pb, Hg, Ir, Au Ag, Fe, Ni, Cd, Pb, Hg, Ir, Au Ir Ag, V, Fe, Ni, Zn, Cd, Pb, Hg, Ir, Au Ag, V, Mn, Fe, Co, Ni, Zn, Cd, Pb, Hg, Al, Sr, Mg, Ca, La, Ce, U Ag, Fe, Ni, Cd, Pb, Hg, Ga, Au Ag, V, Mn, Fe, Co, Ni, Zn, Cd, Pb, Hg, Al, Sr, Ga, Cs Ag, V, Mn, Co, Ni, Cd, Pb, Hg, Al, Ga, U, Ir Ag, Mn, Fe, Ni, Hg, Al, U, Ir Fe, Zn, Cd, Pb, Hg, Al, Sr, Ga, Cs, U Ag, Mn, Fe, Co, Ni, Zn, Cd, Sr, Ga, U Ag, Ni, Cd Ag, Fe, Cd, Pb, Hg, Ir, Au Ag, Fe, Ni, Cd, Pb, Hg, Ir, Au Fe, Zn, Cd, Pb, Hg, Al, Sr, Ga, Cs, U Ag, Fe, Ni, Cd, Pb, Hg, Ir, Au Ag, Fe, Cd, Pb, Hg, Ir, Au Ag, V, Fe, Ni, Zn, Cd, Pb, Hg, Ir, Au Ag, Fe, Ni, Zn, Pb Kit Material (generally high affinity) Non-Kit Material (generally with affinity)
11
Dosage Calculator
Calculating how much PhosphonicS Scavenger to Use:
Initial screening During initial screening of a scavenger, the objective is to identify the best scavenger type(s) for the specific problem. Optimising the treat rate for the application is best run as a separate and subsequent step. For this reason, PhosphonicS normally recommends that initial scavenging experiments are run on small scale with 0.5-1 weight equivalents of the scavenger to the API or chemical intermediate /product. Example A 0.5 g sample of an API product is available in a reaction solvent after initial work-up. The Pd metal level in solution is expected to be in the range 100-1000 ppm. Add 0.25 g scavenger (0.5 weight equivalent) to each sample for the initial scavenging test. Measure metal levels in solution pre- and postscavenging to establish the best scavenger. Optimisation screening In the optimisation step, it is normal to start at the initial screening treat rate, and then repeat screening with reduced levels of scavenger. It is often possible to reduce the scavenger treat rate down towards a range of 2-4 molar equivalents of scavenger to metal. This does depend on the specific problem and conditions that are used. Note, the calculation of the molar equivalents of scavenger being used requires a knowledge of the metal level in the solution to be scavenged or in the product that is to be treated to remove the metal. Note: PhosphonicS scavengers are rated on their metal removal capacity denoted in mmol/g. The molar equivalents of scavenger are calculated as follows: Example A Assume the scavenger of choice has a rating of 1.0 mmol/g The Palladium (Pd) metal level in an 2000 mL (2 L) API solution has been measured as 200 ppm in solution (mg/L). Pd atomic weight = 106.42 This equates to a Pd content = 200 x 2 = 400 mg Pd = 0.4 g Pd = 3.759 mmoles The amount of scavenger required for a treat rate = 1 molar equivalent = 3.759/1.0 = 3.759 g The amount of scavenger required for a treat rate = 4 molar equivalents = 4 x 3.759 = 15.035 g Example B Assume the scavenger of choice has a rating of 1.0 mmol/g The Palladium (Pd) metal level in a 1000 g (1 kg) sample of API has been measured as 4000 mg/kg. The product is to be scavenged after dissolution in 20 L of solvent. Pd atomic weight = 106.42 This equates to a Pd content after dissolution= 4000 x 1 = 4000 mg Pd = 4 g Pd = 37.59 mmoles The amount of scavenger required for a treat rate = 1 molar equivalent = 37.59/1.0 = 37.59 g The amount of scavenger required for a treat rate = 4 molar equivalent = 4 x 37.59 = 150.35 g
H Li Be Na Mg K Ca Rb Sr Cs Ba Fr Ra
Extracted metal B Al Sc Ti Y V C Si N P
Cr Mn Fe Co Ni Cu Zn Ga Ge As
Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Pt Au Hg Ti Pb Bi
Lu Hf Ta W Re Os Ir Lr
Rf Db Sg Bh Hs Mt Ds Rg Uub Uut Uuq Uup
La Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Ac Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No
Range of Metals Scavenged by PhosphonicS to Date.
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12
Metal Scavengers
Usage
Metal Scavengers Using PhosphonicS Metal Scavengers
Step 1 Choose Functionalised Materials for Metal 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. Step 2 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 page 12 - 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 C 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. Step 3 Typical Experimental Procedure The solid scavenger can be added directly to the solution of API or synthetic intermediate. No prewetting 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. Step 4 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 sample to facilitate throughput during early screenings stage see pages 6 and 28.
13
Introduction to Kits
To support Research and Development programs a set of product kits has been created. These allow the trial of different PhosphonicS products, providing the assessment of different scavenging mechanisms, and the identification and selection of the optimum product for a specific application. Kits are designed for the removal of particular metals and contain materials that can be used under both acidic and basic conditions. Additional custom kits to address the removal of particular metals are available on request; please contact PhosphonicS to discuss your particular requirements. Typically 10 g of each scavenger is included in the kit. Alternatively we can offer 25 g or 100 g formats. Materials within kits can be ordered individually on larger scale by reference to their product code. For kit pricing please contact PhosphonicS Kits Available Kit A: General Metal Removal Kit (a range of base, heavy & Precious Metal removal agents) 10 g format (SP-05-KIT A4 10) (9 x 10 g samples); 25 g format (SP-05-KIT A4 25) (9 x 25 g samples) Kit B: Palladium Removal Kit (a range of scavenging agents for palladium and other Precious Metals) 10 g format (SP-05-KIT B7 10) (9 x 10 g samples); 25 g format (SP-05-KIT B7 25) (9 x 25 g samples); 100 g format (SP-05-KIT B7 100) (9 x 100 g samples) Kit C: Copper Removal Kit (a full range of scavenging agents for copper removal) 10 g format (SP-05-KIT C6 10) (9 x 10 g samples) Kit D: Chromium Removal Kit (a wide range of scavenging agents for chromium removal) 10 g format (SP-05-KIT D4 10) (6 x 10 g samples) Kit E: Ruthenium Removal Kit (a wide range of scavenging agents for ruthenium removal) 10 g format (SP-05-KIT E4 10) (8 x 10 g samples) Kit F: Platinum Removal Kit (a full range of scavenging agents for platinum removal) 10 g format (SP-05-KIT F2 10) (9 x 10 g samples) Kit G: Tin Removal Kit (a full range of scavenging agents for tin removal) 10 g format (SP-05-KIT G3 10) (9 x 10 g samples) Kit H: Osmium Removal Kit (a full range of scavenging agents for osmium removal) 10 g format (SP-05-KIT H2 10) (7 x 10 g samples) Kit I: Rhodium Removal Kit (a variety of scavenging agents for rhodium removal) 10 g format (SP-05-KIT I4 10) (8 x 10 g samples) In some cases, customers may however prefer to screen less materials initially. To aid selection for this advanced screening, within kits B-I, four materials have been highlighted as top screening candidates. When adopting this approach, the remaining materials should be used to provide a second tranche of scavengers as required based on the first round screening results, to probe different scavenging mechanisms and spatial arrangements of functional groups. Within kits, scavengers are not listed in any order of preference and it is recommended to trial initially at least all four top materials against a particular Precious Metal scavenging problem. Key to Kits on pages 15-24
Top Candidate for Metal Screen
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14
Metal Scavengers
Kit A: General Metal Kit

Metal Scavengers
Structure Name Metals treated Loading Particle Size Pore Diameter Product Code
Kit A: General Metal Removal Kit. 10 g format (SP-05-KIT A4 10) 25 g format (SP-05-KIT A4 25)
O S N H H N
NH 2
Triamine ethyl sulfide amide Silica

S
Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Fe(III), Ni(0), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.8 mmol/g 60-200 m 60
STA3
SH
0.8 mmol/g 60-200 m 60
SEM26
2-Mercaptoethyl ethyl sulfide Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Fe(III), Ni(II), Cu(II), Ga(III), Ru(II), Ru(III), Rh(I), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 60 (low cross-linking)
SH
SPM32
3-Mercaptopropyl ethyl sulfide Silica

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 60
SPA5
Pentaamine ethyl sulfide amide Silica

O S O O
(
O
SH
0.75 mmol/g 60-200 m 60
SET
Pentaerythritol 2-mercaptoacetate ethyl sulfide Silica

S ONa ONa O
Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(III), Ag(I), Cd(II), Sn(II), Sn(IV), Cs(I), Hg(II), Pb(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Mg(II), Al(III), Ca(II), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Sr(II), Ag(I), Cd(II), Sn(II), Sn(IV), La(III), Ce(III), Ce(IV), Hg(II), Pb(II), UO2(II)
0.6 mmol/g 60-200 m 60
STMS
Disodium succinate ethyl sulfide Silica 0.8 mmol/g 60-200 m 60
NH2
SEA
2-Aminoethyl sulfide ethyl Silica

O P ONa ONa
1 mmol/g 60-200 m 60
PO1
Disodium ethyl/butyl phosphonate Silica

S S N H N H
Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Os, Ir(I), Ir(III), Pt(II)
0.6 mmol/g 60-200 m 90
MTCf
Methyl thiourea ethyl sulfide ethyl Silica
15
Kit B: Palladium Kit

Structure Name Metals treated
O S N H
H N
NH 2
Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Fe(III), Ni(0), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.8 mmol/g 60-200 m 60
STA3
SH
0.8 mmol/g 60-200 m 60
SEM26
2-Mercaptoethyl ethyl sulfide Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 60 (low cross-linking)
SH
SPM32
3-Mercaptopropyl ethyl sulfide Silica Fe(III), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 60 (high cross-linking)
SH
SPM36

S S N H N H
0.6 mmol/g 60-200 m 90
MTCf
Methyl thiourea ethyl sulfide ethyl Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 90 (low cross-linking)
SH
SPM32f
3-Mercaptopropyl ethyl sulfide Silica Fe(III), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 90 (high cross-linking)
SH
SPM36f
3-Mercaptopropyl ethyl sulfide Silica 0.8 mmol/g 60-200 m 60
NH2
SEA

NHAc S O OH
Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Pt(II)
0.6 mmol/g 60-200 m 60
SCYT1
N-Acetyl-L-cysteine ethyl Silica
T: +44 (0)1235 834466
F: +44 (0)1235 835566
16
Metal Scavengers
Loading Product Particle Size Code Pore Diameter Kit B: Palladium Removal Kit. (covering palladium and other precious metals) 10 g format (SP-05-KIT B7 10) 25 g format (SP-05-KIT B7 25) 100 g format (SP-05-KIT B7 100)
Scavenging of Palladium from APIs

Metal Scavengers
PhosphonicS materials show a high affinity for metal scavenging, which it has been demonstrated in many cases is sufficient to overcome the strong affinity of polar functional groups within APIs for metal ions. Metal removal from APIs containing hydroxyl groups, amines, amides, carboxylic acids and esters, ethers, nitriles and amino acids have all been successful and we have reported the scavenging of palladium residues from a range of highly functionalised synthetic intermediates and APIs, generated from palladium-catalysed deprotection reactions and cross-coupling reactions.
O HO HN O OH O O-Debenzylation Catalyst Pd(OH)2

HO
O NH2 N-CBz Removal Catalyst Pd(OH)2 HN N-Alloc Removal Catalyst PdCl2(PPh3)2
HN O
N H
Before : 300 ppm Pd After : <1 ppm Pd
O N H Sonogashira coupling Buchwald coupling Catalyst PdCl2(PPh3)2 O2N Before : 30 ppm Pd After : <1 ppm Pd Anti-oxidant precursor H N Catalyst PdCl2(PPh3)2
Before : 700 ppm Pd After : <5.0 ppm Pd Calcium entry Blocker analogue O O N O O O NH
O HN N N N Catalyst Pd2dba3
Suzuki coupling
CN Catalyst Pd(PPh3)4
Heck coupling
Before : 2100 ppm Pd After : <5.0 ppm Pd Valsartan precursor Bioorg. Med. Chem. Lett., 1994, 4, 29
Before : 307 ppm Pd After : 4.8 ppm Pd Oncology Candidate CP-724,714 Org. Process Res. Dev., 2005, 9, 440
Highly Functionalised Sulfur-based Silica Scavengers for the Efficient Removal of Palladium Species from Active Pharmaceutical Ingredients (APIs) Galaffu, N.; Man, S.; Wilkes, R. D.; Wilson, J. R. H. Org. Process Res. Dev., 2007, 11, 406.
17
Kit C: Copper Kit

Kit C: Copper Removal Kit. 10 g format (SP-05-KIT C6 10)

O P ONa ONa
Mg(II), Al(III), Ca(II), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Sr(II), Ag(I), Cd(II), Sn(II), Sn(IV), La(III), Ce(III), Ce(IV), Hg(II), Pb(II), UO2(II) Fe(III), Ni(0), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
1 mmol/g 60-200 m 60
PO1
SH
0.8 mmol/g 60-200 m 60
SEM26
2-Mercaptoethyl ethyl sulfide Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Fe(III), Ni(II), Cu(II), Ga(III), Ru(II), Ru(III), Rh(I), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 60 (low cross-linking)
SH
SPM32

O S N H H N
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S O O
(
O S
SH
0.75 mmol/g 60-200 m 60
SET

ONa ONa O
Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(III), Ag(I), Cd(II), Sn(II), Sn(IV), Cs(I), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), Cr(III), Mn(II), Fe(III), Ni(0), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), UO2(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.6 mmol/g 60-200 m 60
STMS
Disodium succinate ethyl sulfide Silica

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 60
SPA5

O S N H H N
NH 2
0.8 mmol/g 60-200 m 90
SPAf
Polyamine ethyl sulfide amide Silica 0.8 mmol/g 60-200 m 60
NH2
SEA
T: +44 (0)1235 834466
F: +44 (0)1235 835566
18
Metal Scavengers
Kit D: Chromium Kit

Metal Scavengers
Kit D: Chromium Removal Kit. 10 g format (SP-05-KIT D4 10)

O P OH OH
Al(III), Cr(III), Fe(III), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III), Rh(I), Rh(III), Cd(II), Cs(I), Hg(II), Pb(II), UO2(II)
1 mmol/g 60-200 m 60
POH1
Ethyl/butyl phosphonic acid Silica

O P ONa ONa

O S N H H N
Mg(II), Al(III), Ca(II), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Sr(II), Ag(I), Cd(II), Sn(II), Sn(IV), La(III), Ce(III), Ce(IV), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Os, Pt(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(III), Ag(I), Cd(II), Sn(II), Sn(IV), Cs(I), Hg(II), Pb(II)
1 mmol/g 60-200 m 60
PO1
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S N H H N
OH
0.8 mmol/g 60-200 m 60
SDEA
2-Hydroxyethyldiamine ethyl sulfide amide Silica

O S N H
(
O
H N
NH 2
0.8 mmol/g 60-200 m 60
SPA5

S ONa ONa O
0.6 mmol/g 60-200 m 60
STMS
19
Kit E: Ruthenium Kit

Kit E: Ruthenium Removal Kit. 10 g format (SP-05-KIT E4 10)

O P OH OH
Al(III), Cr(III), Fe(III), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III), Rh(I), Rh(III), Cd(II), Cs(I), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), Cr(III), Mn(II), Fe(III), Ni(0), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), UO2(II)
1 mmol/g 60-200 m 60
POH1

O S N H H N
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S H N
( N
H
NH 2
0.8 mmol/g 60-200 m 90
SPAf
Polyamine ethyl sulfide amide Silica

S S N H N H
0.6 mmol/g 60-200 m 90
MTCf

NHAc S O OH
Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Pt(II)
0.6 mmol/g 60-200 m 60
SCYT1

O S N H H N
OH
Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Os, Pt(II), UO2(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.8 mmol/g 60-200 m 60
SDEA
2-Hydroxyethyldiamine ethyl sulfide amide Silica 0.8 mmol/g 60-200 m 60
NH2
SEA
SH
0.8 mmol/g 60-200 m 60 (low cross-linking)
SPM32
T: +44 (0)1235 834466
F: +44 (0)1235 835566
20
Metal Scavengers
Kit F: Platinum Kit

Metal Scavengers
Kit F: Platinum Removal Kit. 10 g format (SP-05-KIT F2 10)

S
SH
2-Mercaptoethyl ethyl sulfide Silica
Fe(III), Ni(0), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.8 mmol/g 60-200 m 60
SEM26
SH
Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
SPM32f
SH
SPM36f
3-Mercaptopropyl ethyl sulfide Silica Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Pt(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) 0.8 mmol/g 60-200 m 60 (higher cross-linking)
SPM3

O S N H H N
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 60
SPA5

S S N H N H
0.6 mmol/g 60-200 m 90
MTCf

O S N H H N
OH
Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Os, Pt(II), UO2(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
0.8 mmol/g 60-200 m 60
SDEA
2-Hydroxyethyldiamine ethyl sulfide amide Silica 0.8 mmol/g 60-200 m 60
NH2
SEA
21
Kit G: Tin Kit

Kit G: Tin Removal Kit. 10 g format (SP-05-KIT G3 10)

O P ONa ONa
Mg(II), Al(III), Ca(II), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Sr(II), Ag(I), Cd(II), Sn(II), Sn(IV), La(III), Ce(III), Ce(IV), Hg(II), Pb(II), UO2(II) Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II)
1 mmol/g 60-200 m 60
PO1
SH
SPM32f
SH
SPM36f

O S O O
SH
Fe(III), Ni(II), Cu(II), Ga(III), Ru(II), Ru(III), Rh(I), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Sr(II), Ru(III), Ag(I), Cd(II), Sn(II), Sn(IV), Cs(I), Hg(II), Pb(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), Cr(III), Mn(II), Fe(III), Ni(0), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), UO2(II)
0.75 mmol/g 60-200 m 60
SET

O S N H H N
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S N H H N
(
O
NH 2
0.8 mmol/g 60-200 m 60
SPA5

S ONa ONa O
0.6 mmol/g 60-200 m 60
STMS

S
NH2
0.8 mmol/g 60-200 m 60
SEA

O S
( N
H
H N
NH 2
0.8 mmol/g 60-200 m 90
SPAf
T: +44 (0)1235 834466
F: +44 (0)1235 835566
22
Metal Scavengers
Kit H: Osmium Kit

Metal Scavengers
Kit H : Osmium Removal Kit. 10 g format (SP-05-KIT H2 10)

S SH

S
Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), VO(II), Cr(III), Mn(II), Co(II), Ni(0), Ni(II), Cu(II), Ga(III), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), Cr(III), Mn(II), Fe(III), Ni(0), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), UO2(II)
0.8 mmol/g 60-200 microns 60
SPM32
NH2
SEA

O S N H H N
NH 2
STA3

O S
( N
H
H N
NH 2
SPA5

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 90
SPAf

S S N H N H
MTCf

S N N
Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Os, Pt(II), Pb(II)
PMISf
Pyridylmethylimino ethyl sulfide ethyl Silica
23
Kit I: Rhodium Kit

Kit I: Rhodium Removal Kit. 10 g format (SP-05-KIT I4 10)

O P OH OH
Al(III), Cr(III), Fe(III), Zn(II), Ga(III), Sr(II), Ru(II), Ru(III) Rh(I), Rh(III), Cd(II), Cs(I), Hg(II), Pb(II), UO2(II)
1 mmol/g 300-500 m 150
POH1g
Ethyl/butyl phosphonic acid Silica Fe(III), Ni(0), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 90
SH
SEM26f
2-Mercaptoethyl ethyl sulfide Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 60-200 m 90 (low cross-linking)
SH
SPM32f
SH
SPM36f
3-Mercaptopropyl ethyl sulfide Silica Fe(III), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) Al(III), VO(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), Ru(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), Pb(II), UO2(II) Al(III), Cr(III), Mn(II), Fe(III), Ni(0), Ni(II), Cu(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Hg(II), UO2(II) VO(II), Fe(III), Ni(II), Cu(II), Zn(II), Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Ag(I), Cd(II), Sn(II), Sn(IV), Os, Ir(I), Ir(III), Pt(II), Au(I), Au(III), Hg(II), Pb(II) 0.8 mmol/g 300-500 m 150 (low cross-linking)
SH
SPM32g

O S N H H N
NH 2
0.8 mmol/g 60-200 m 60
STA3

O S
( N
H
H N
NH 2
0.8 mmol/g 60-200 m 90
SPA10f

S
NH2
0.8 mmol/g 300-500 m 150
SEAg
T: +44 (0)1235 834466
F: +44 (0)1235 835566
24
Metal Scavengers
Options on Process Scale

Metal Scavengers
Process Development scale cartridges prepacked with PhosphonicS established metal scavenger range1 are now readily available. This versatile cartridge format offers significant project time-savings to the Process chemist, reducing both scavenging times and unit operations, including vessel cleaning and removing manual handling of the scavenger. The single PhosphonicS cartridge format was successfully tested in AstraZenecas large scale labs, progressing to the Pilot plant where a flexible, scale-out approach has allowed multiple cartridges to be used at different scales as required for a variety of metal removal API projects,2 recently being applied at commercial product scale.
From the Vessel
To the Receiver
100% Virgin polypropylene or Stainless Steel options Compatible with most process streams Fits existing plant equipment; scale-out equipment readily available Available in 10 (~0.2 kg) & 20 (~0.5 kg) & larger options, with scale-out option for multiples
25

Using PhosphonicS Process Development Cartridges Pd Removal from a Cross-coupling Reaction on Large Scale (7.6 kg) A crude reaction product was generated via a Pd-mediated cross-coupling reaction in toluene. After work-up the solution was found to contain 600 ppm of palladium. Metal Scavenging : A prior screening2 exercise incorporating a range of polymer and silicabased adsorbents and extractants identified the most suitable palladium scavenger as SPM32. Small scale cartridge testing had implied the use of up to 4 cartridges may be required for effective Pd removal down to the target level of 50 ppm (92% Pd removal). The process solution was processed in two 63 L batches, each containing 3.8 kg of intermediate, and was pumped at room temperature at a flow rate of ~40 L/hr consecutively through four 20 PhosphonicS scavenger cartridges, each containing ~0.5 kg of PhosphonicS mercaptosulfide scavenger SPM32. Analysis showed the Pd content to be 217 ppm after cartridge 1: (64% Pd removal) down to 11 ppm after cartridge 4 (>98% Pd removal in total). After use of a fifth cartridge the final product was found to contain just 5 ppm Pd. This result was comparable with a control batch slurry scavenging experiment stirred at room temperature overnight. Process Result : Multi-kg quantities of the reaction stream were efficiently processed through the PhosphonicS scavenger cartridge in times which make cartridge processing a viable alternative to batch processing for large scale laboratory work targeting initial kg quantities of an API or an earlier intermediate. The intermediate was advanced to the next stage of the synthesis within the allowed production timeframe and well within specification in terms of metal content. Housings to hold large multiples of PhosphonicS pre-packed cartridges for further Process scale-up using a scale-out approach are readily available and results from use of this multiple cartridge approach in conjunction with AstraZeneca will be reported fully in the near future.2 An earlier, alternative option to scale-up processes is: Using Plant Filter Housings packed with PhosphonicS Metal Scavengers On pilot plant scale efficient metal removal from process streams can also be achieved by packing PhosphonicS metal scavengers into existing larger filter housings. As required, recirculation of the solution can be performed until the desired target metal level is achieved for that particular synthetic step. AstraZeneca have employed this process for metal removals from several API intermediates including:
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26
Metal Scavengers

Metal Scavengers
Pd Removal from Buchwald-Hartwig Reaction on Large Scale (40+ kg)
Rh content (ppm) 600 500 400 300 200 100 0 0 5 10 15 Time (hrs) 20 25
A crude heterocyclic highly-functionalised reaction product was generated using Pd2dba3/XPhos in a mixed organic solution and after work-up of this step the solution was found to contain 720 ppm of palladium. The intermediate was generated on 44 kg scale and ~50% by weight of PhosphonicS SPM36f was packed into the filter housing. Recirculation of the solution of the API intermediate at 80 C resulted in a reduction in Pd content over 36 hours to just 75 ppm in solution/40 ppm in the intermediate (equating to 90% Pd removal), meeting the specification required for this stage of the process within the allowed production timeframe. After further synthetic steps this allowed the API batch to be delivered on time and within regulatory guidelines for metal content.
Rh removal from an AstraZeneca API intermediate on 4 x 30 kg scale in a packed filter housing using PhosphonicS SPM32f scavenger.
SH
Rh Removal from Addition Reaction on Large Scale (120+ kg)

800 700 Pd content/ppm 600 500 400 300 200 100 0 0 10 20 Time/hrs 30 40
solution/72 ppm in the intermediate (equating to >92% Rh removal), meeting the specification required for this stage of the process within the allowed production timeframe. As with the Pd removal case study above, further synthetic steps allowed the API batch to be delivered on time and within regulatory guidelines for metal content.
References
1
Scavenger screening kits for Pd, Cu, Cr, Ru, Pt, Sn, Rh & other metals are available from PhosphonicS 2 Presented by G. Reginato at Organic Process Research & Development Conference, Barcelona, September 2010; Reginato, G.; Sadler, P Wilkes, R. D. manuscript in .; preparation
Pd removal from an AstraZeneca API intermediate on 44 kg scale in a packed filter housing using PhosphonicS SPM36f scavenger.
A crude heterocyclic addition reaction product containing multiple functional groups was generated using a Rh catalyst in a mixed organic solution and after work-up the solution was found to contain up to 686 ppm of rhodium. Under similar conditions to those outlined above, rhodium was removed from the API intermediate, generated on 30 kg scale in each of 4 batches using 30% by weight of PhosphonicS SPM32f metal scavenger. Recirculation of the solution of the API intermediate resulted in a reduction in Rh content over 20-24 hours to <50 ppm in
27
Metal SPE
Metal Scavenging SPE
PhosphonicS multi-functionalised silica scavengers are available in pre-packed polypropylene cartridges for efficient metal removal from organic reaction mixtures and synthetic intermediates on laboratory scales during the early stages of Process Development campaigns or from Discovery reactions. The cartridges are available containing metal scavenger quantities of 1 g (6 mL volume cartridge) and 10 g (75 mL volume cartridge). The functionalised silica scavengers have a particle size range of 35 - 70 m, pore diameter of 60 and typical functional group loadings of 0.8 mmol/g.
Structure Name
S SH
Product Code
SPM32d
Metals Removed
Fe, Cu, Ru, Rh, Pd, Ag, Cd, Sn, Os, Ir, Pt, Au, Hg, Pb

S
(low cross-linking)
SH
SPM36d 3-Mercaptopropyl ethyl sulfide Silica

O S N H
(high cross-linking)
Fe, Ni, Cu, Ru, Rh, Pd, Ag, Cd, Sn, Os, Ir, Pt, Au, Hg, Pb
(
O P OH OH
H N
NH 2
SPA5d
Al, V, Cr, Mn, Co, Ni, Cu, Ga, Ru, Rh, Pd, Ag, Cd, Sn, Os, Ir, Pt, Hg, Pb, U
Pentaamine ethyl sulfide amide Silica Al, Cr, Fe, Zn, Ga, Sr, Ru, Rh, Cd, Cs, Hg, Pb, U
POH1d

O S OH OH
STMAd
Al, Cr, Mn, Fe, Co, Ni, Zn, Ga, Cd, Hg, Pb, U
Succinic acid ethyl sulfide Silica

S
NH2
SEAd
V, Fe, Ni, Cu, Zn, Ru, Rh, Pd, Ag, Cd, Sn, Os, Ir, Pt, Au, Hg, Pb

S S N H N H
MTCd
Ru, Rh, Pd, Os, Ir, Pt
Experimental Steps for Metal Removal by SPE 1. Pre-condition the Metal SPE cartridge by passing methanol followed by the reaction solvent through it (typically 1 cartridge volume of each). 2. Load the reaction mixture onto the top of the cartridge and allow the solution to pass through under gravity. 3. Wash the cartridge with further portions of methanol (typically 2-3 cartridge volumes) and collect. 4. Evaporate the combined solvents to give the metal-free reaction product.
For SPE Format pricing please contact PhosphonicS

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28
Metal Scavengers
Centrifuge Screening Tubes

Metal Scavengers
Centrifuge Screening Tubes To facilitate the screening of our metal scavengers, the scavenger kits outlined on pages 15-24 are available in capped polypropylene centrifuge tubes. Each tube contains 50 mg of scavenger and the tube volume is 2 mL. This approach to adsorbent screening has been adopted by a number of pharmaceutical companies and was recently described in detail by Merck for the removal of both metals1 and coloured impurities2 from APIs. In this format, the functionalised silica scavengers typically have a particle size range of 60 - 200 m and a pore diameter of 60 , though this varies according to the particular metal of interest (see pages 15-24 for complete details on each of the scavengers contained within screening kits) and typically functional group loadings are 0.8 mmol/g.
References
1 Welch, C. J.; Albaneze-Walker, J.; Leonard, W. R.; Biba, M.; DaSilva, J.; Henderson, D.; Laing, B.; Mathre, D. J.; Spencer, S.; Bu, X.; Wang, T. Org. Process Res. Dev., 2005, 9, 198 2 Welch, C. J.; Leonard, W. R.; Henderson, D. W.; Dorner, B.; Childers, K. G.; Chung, J. Y. L.; Hartner, F. W.; Albaneze-Walker, J.; Sajonz, P Org. Process Res. . Dev., 2008, 12, 81
For Centrifuge Screening Tube pricing please contact PhosphonicS
29
Case Studies
Metal Scavenging Case Studies
PhosphonicS materials are being used by pharmaceutical companies in the manufacture of APIs and API intermediates at full process scale. Details of these processes are generally confidential, but we are able to summarise the experience of some of our customers:
Client : Exelixis
Pd Removal : Delivering 16 kgs of an API within Regulatory Levels (<5 ppm) Synopsis : Crude API sample containing >100 ppm of palladium, introduced by a Pd(0)-catalysed coupling reaction performed at the final stage of the synthetic process. Conventional metal scavenging protocols were not readily adaptable to this compound due to its very poor solubility. Key Issue : Speed to initial 100 g quantities of API and then kg quantities for testing. Process Target : Isolation of the API without any significant loss and with Pd content reduced to within regulatory guidelines (<5 ppm). Process Step : Treatment of the existing process stream, consisting of a solution of the crude API sample in an organic-aqueous solvent mixture at >80 C for 1 hour in slurry mode with PhosphonicS multi-functionalised silica-based thiol scavenger SPM32 (unoptimised, 0.1 weight equivalents compared to the API used). Process Result : API isolated with minimal loss of material, without the introduction of any further impurities (as determined by full gradient HPLC) and with regulatoryacceptable Pd content of <5 ppm. Process Scale-up : API produced on 16 kg scale using this process step.
S SH
SPM32
Client : DuPont Chemoswed

Project Goal: to deliver 2 kg of API with Palladium content within regulatory levels (<10ppm) Synopsis : Crude heterocyclic API prepared from Suzuki coupling with Pd(dppf) in DMF containing up to 1000 ppm residual Palladium. Unsuccessful Metal Removal Attempts : Due to the extremely poor solubility of the API conventional metal removal protocols such as treatment with activated charcoal, treatment with silica gel or extraction with various aqueous solutions proved unsuccessful. Key Issue : Reduction of Palladium content to within specification (<10 ppm) without loss of heterocyclic API product. Scavenger Screening : Initially Palladium removal with a number of different PhosphonicS scavengers was evaluated in various solvents and at different temperatures. From the results achieved and in collaboration with PhosphonicS a combination of two different scavengers were recommended and successfully afforded API containing the desired level of <10 ppm Palladium. Process Step : Treatment of 2.4 kg crude API in Me-THF and DMF at 60 C for 12 hours with a 1:1 combination of PhosphonicS scavengers SPM32 and SEM26 in slurry mode (1 weight equivalent in total compared to the API). The process was continuously monitored by Pd analysis. Process Result : After removal of PhosphonicS scavengers by filtration and crystallization of the API from solution, 2 kg of heterocyclic API was delivered in >99% purity containing just 4 ppm Palladium.
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30
Metal Scavengers
Case Studies
Metal Scavengers Client : AstraZeneca
Rh Removal from Addition Reaction on Large Scale (120 kg in total) Synopsis : Crude heterocyclic addition reaction product containing multiple functional groups. Initial metal content : up to 686 ppm of rhodium in organic solution. Key Issue : Reduction of metal content to set specification within timescale (24 hours) allowed for this process step. Process Target : Within the 24-hour timescale allowed for this process step, Rh content of the solution was required to be <100 ppm (<75 ppm in the intermediate), allowing further reduction to within ICH guidelines upon subsequent synthetic steps. Scavenger Screening : PhosphonicS multi-functionalised silica-based thiol scavenger SPM32f was identified as the optimum scavenger for this process stream following a metal adsorbent screening campaign including activated carbons /charcoals, polymer-based adsorbents and competitor silica scavengers. Process Step : PhosphonicS SPM32f metal scavenger (30 wt% to starting material) was packed into a standard filter housing and the process stream at 60 C was circulated through the filter bed, with periodic monitoring of the Rh content. Rapid and effective Rh removal was achieved quickly and the process was allowed to continue for between 20 and 24 hours per batch to maximise metal removal. Process Result : Metal content of the isolated API-intermediate was found to be reduced down to <50 ppm in solution (72 ppm in the intermediate) within the 24-hour process step timescale, with no loss of intermediate indicated by appropriate analytical assays. Metal removal was consistent for each of the four 30 kg batches run. The API-intermediate was advanced to the next process step, without any delays, allowing the API batch to be delivered on time and within regulatory guidelines for metal content.
SH
SPM32f
Client : Clauson Kaas

Pd Removal : Delivering first kg quantities of API within Regulatory Levels (<5 ppm) Synopsis : Crude API sample prepared by Suzuki and Sonogashira couplings containing up to 3000 ppm of palladium. Key Issue : Speed to initial kg quantities of API for testing. Process Target : Isolation of the API without any significant loss and with Pd content reduced to within ICH guidelines (<5 ppm). Scavenger Screening : PhosphonicS recommended and previously successfully screened and utilised scavenger employed directly. Process Step : Treatment of the crude API sample in methanol at reflux for 1 hour in slurry mode with PhosphonicS multi-functionalised silica-based thiol scavenger SPM32 (0.5 weight equivalents compared to the API used). Process Result : API isolated with minimal loss of material and with regulatory-acceptable Pd content of <5 ppm. Process Scale-up : API produced on multi-kg scale using this process step.
31
Introduction
The benefits of using excess reagents for organic synthesis in order to drive reactions to completion and maximise product yield can often be outweighed by the requirement to effectively remove the excess, often highly reactive, reagent in order to ensure subsequent screening results and product testing are not compromised. These reactive reagents, some with potential toxic and genotoxic activities, include electrophiles and nucleophiles, acids and bases, anions and cations. Even when used in substoichiometric amounts and thereby largely consumed in the desired reaction, such highly reactive reagents still need to be safely removed from products, often down to low ppm or even ppb levels. The use of functionalised materials as scavengers of organic molecules has been widely embraced by High-Throughput Chemistry groups in order to simplify solution-phase reaction work-ups and allow arrays of compounds to be generated quickly and in high purity, replacing more traditional and timeconsuming methods for the removal of excess reagents including aqueous work-ups and chromatography. There is still a need for effective organic scavengers, particularly those available on scales to fulfil scavenging operations for a particular drug candidate/API right the way from early Discovery through Development to full Manufacture.
Scavenger Impurities Substrate Impurities
PhosphonicS has designed a portfolio of multifunctionalised silicas which possess optimum ligands and functionalities for the removal of a broad range of reactive organic impurities and reagents from pharmaceutical products, and provide an attractive, reliable, practical and costeffective first option for scavenging organics from all pharmaceutical products.
Useful References on Organic Scavenging and SPE Cork, D.; Hird, N. Drug Discovery Today, 2002, 7, 56 Ripka, W. C.; Barker, G.; Krakover, J. Drug Discovery Today, 2001, 6, 471 Weinbrenner, S.; Tzschucke, C. C. In Combinatorial Chemistry, Bannwarth, W., Hinzen B. Eds.; Wiley-VCH: Weinheim, 2006, Chapter 1, pages 1 31 Wipf, P Coleman, C. M. Drug Discovery World, Winter .; 2003/4, 62 Brown, J.; Chighine, A.; Colucci, M. A.; Galaffu, N.; Hirst, S. C.; Seymour, H. M.; Shiers, J. J.; Wilkes, R. D.; Williams, J. G.; Wilson, J. Tetrahedron Lett., 2008, 49, 4968 Kennedy, J. P Williams, L.; Bridges, T. M.; Daniels, R. .; N.; Weaver, D.; Lindsley, C. W. J. Comb. Chem., 2008, 10, 345
+
Product
+
Reagent
in excess
Scavenger Scavenger
Filter off
Product
Filter off
+
Reagent
unreacted excess
High purity
Scavenger
Reagent
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Organic Scavengers
Properties & Benefits

Organic Scavengers Properties of PhosphonicS Portfolio of Organic Scavengers
High affinity for a wide range of organic impurities. Fast kinetics - highly active even at ambient temperatures. High selectivity for reactive organic impurities, meaning minimal loss of the API/compound. Broad solvent and pH compatibility with both organic and aqueous formulations. No swelling of the materials is required. Excellent stability - thermal, physical, chemical and mechanical. Very high purity = negligible extractable impurities. Enhanced performance, due to multiple functional groups and higher effective loadings. Availability from Discovery to Process Scale, in loose & cartridge formats. Complete compatibility with other PhosphonicS scavengers as scavenging functionalities are completely immobilised, functionalities which would be incompatible as solution phase reagents can be mixed in onepot for scavenging; e.g. PhosphonicS immobilised acids and amine scavengers can be used together to purify amide formation reactions in which both acidic and basic reagents remain.
Performance Benefits of PhosphonicS Organic Scavengers

Faster : purification, batch processing, problem-solving, market introduction. Reduced : Discovery/Development time, valuable material losses, manufacturing costs. Enhanced : process, productivity, compliance.
33
Usage
Selecting & Using PhosphonicS Organic Scavengers
Step 1 - Choose Functionalised Materials for Organic Scavenging The Organic Scavenger kit lists provide information on scavenger affinity for particular impurities. It is recommended that a number of materials or an established Organic Scavenger kit are screened against a particular impurity. Step 2 - Select Scavenging Format Slurry Batch or Cartridge Loose scavengers for slurry batch processing are available at all scales. Easy-to-use cartridge formats are also available to enhance throughput and processing time. Step 3 - Select Experimental Design Factors and Run Scavenging Process Equivalents of scavenger to use - In initial slurry scavenging experiments we suggest using up to 6 molar equivalents of scavenger to the reagent or reactive impurity to be removed. This may be increased for cartridge applications. - Once the preferred scavenger is identified, the process and the number of equivalents of scavenger can often be quickly optimised to 2 molar equivalents or less. - Any potential interactions between the functional groups on the scavenger and any other reactive reagents or by-products present should also be considered at this stage. Temperature - We suggest using a starting temperature of up to 50 C for initial scavenging investigations. In cartridge formats, the solution may need to be recycled. - Many scavenging processes can be operated successfully at room temperature within reasonable timescales, but 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. As an alternative, warm solutions may be added directly to PhosphonicS cartridges. Agitation Rate/Cartridge Flow 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. - For cartridge operations, we recommend initially performing scavenger operations under gravity. Subsequently, positive pressure or vacuum might be applied to optimise flow rate, whilst maintaining full scavenging efficiency. 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. 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. Time In slurry format, solutions should be agitated for at least one hour for initial investigations. Scavenging progress can be followed by normal analytical techniques such as HPLC. If removal is not complete the process can be continued or parameters adjusted, such as increasing the temperature or adding further scavenger. In cartridge formats, flow rates and solution recycling should be considered to optimise scavenging performance. Step 4 Work-up and Product Isolation From slurry operations the scavenger is removed by simple filtration. In both slurry and cartridge format, the scavenger should be washed with additional solvent and the combined solution concentrated in vacuo to provide the purified product.
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34
Organic Scavengers
Introduction to Kits
Organic Scavengers
To support Research and Development programs a set of product kits has been created. These allow the trial of different PhosphonicS products and the identification and selection of the optimum product for a particular organic impurity. Kits are available containing from 10 g -100 g of each scavenger Individual materials within kits can be ordered on larger scale by reference to their product code Additional custom kits to address the removal of particular organic impurities are available on request Organic scavengers are also available in easyto-use cartridges: SPE cartridges for small scale, rapid, highthroughput applications (1-10 g) (see page 39) (the particle size of the functionalised silicas contained within these cartridges is 35 70 m, to provide flow rates more suited to SPEtype applications) PhosphonicS Process Development cartridge (~0.5 kg or 0.2 kg) (see pages 6 and 25) Kits Available Kit A: Electrophile Removal Kit Consisting of 6 loose PhosphonicS materials (SPM32, SEA, SPA5, SPAf, MTCf and 4MPAE) 10 g format (OS-08-KIT A2 10) (6 x 10 g samples) 25 g format (OS-08-KIT A2 25) (6 x 25 g samples) 100 g format (OS-08-KIT A2 100) (6 x 100 g samples) Kit B: Cation and Anion Exchange Kit Consisting of 5 loose PhosphonicS materials (SEA, SPA5, SPAf, POH1 and STMA) 10 g format (OS-08-KIT B2 10) (5 x 10 g samples) 25 g format (OS-08-KIT B2 25) (5 x 25 g samples) 100 g format (OS-08-KIT B2 100) (5 x 100 g samples) Kit C: H-Bond Formation Removal Kit for Boronic Acids & Other Impurities Consisting of 2 loose PhosphonicS materials (SDOL and SMG) 10 g format (OS-08-KIT C1 10) (2 x 10 g samples) 25 g format (OS-08-KIT C1 25) (2 x 25 g samples) 100 g format (OS-08-KIT C1 100) (2 x 100 g samples) Kit D: Organic Scavenger Portfolio Kit Consisting of 10 loose PhosphonicS materials from kits A - C 10 g format (OS-08-KIT D2 10) (10 x 10 g samples) 25 g format (OS-08-KIT D2 25) (10 x 25 g samples) 100 g format (OS-08-KIT D2 100) (10 x 100 g samples) Materials are available in various particle sizes, pore diameters and functional group loadings, in addition to those shown in the kits, in order to address particular applications where the adjustment of these properties of the functionalised silica may prove beneficial, for example for flow chemistry applications.
35
Electrophile Kit
Structure Name Particle Size Pore Diameter Loading Product Code
Kit A: Electrophile Removal Kit. For the effective removal of: Alkyl halides, mesylates and tosylates Acyl & sulfonyl halides Chloroformates Carboxylic & sulfonic acids Isocyanates & isothiocyanates -Halo esters, ketones, amides 10 g format (OS-08-KIT A2 10) 25 g format (OS-08-KIT A2 25) 100 g format (OS-08-KIT A2 100)
SH
60-200 m 60
0.8 mmol/g
SPM32
NH2
60-200 m 60
0.8 mmol/g
SEA

O S N H
H N
NH 2
60-200 m 60
0.8 mmol/g
SPA5

O S N H
H N
NH 2
60-200 m 90
0.8 mmol/g
SPAf

S S N H N H
60-200 m 90
0.6 mmol/g
MTCf

O S N H SH
Electrophiles
0.3-0.5 mmol/g 60-200 m 60
4MPAE
4-Mercaptophenyl amidoethyl sulfide ethyl Silica

Conversion of 4MPAE into the potassium thiophenolate salt can be readily achieved and can often further increase performance for electrophile removal
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Organic Scavengers
Cation and Anion Kit

Organic Scavengers
Kit B: Cation and Anion Exchange Kit. For the effective removal of: Weak anions, acids and phenols Cations, bases and amines Additional uses include: Free-basing of amines by removal of salts such as HCl or TFA (anion exchangers) Free-basing of amines generated as acetate salts in Reductive Amination procedures or TFA salts by solid-phase procedures or Boc deprotection (by cation exchange catch and release) 10 g format (OS-08-KIT B2 10) 25 g format (OS-08-KIT B2 25) 100 g format (OS-08-KIT B2 100)
S
NH2
60-200 m 60
0.8 mmol/g
SEA

O S N H
H N
NH 2
60-200 m 60
0.8 mmol/g
SPA5

O S N H
H N
NH 2
60-200 m 90
0.8 mmol/g
SPAf

O P OH OH
60-200 m 60
1.0 mmol/g
POH1

O S OH OH
60-200 m 60
0.6 mmol/g
STMA
37
Boronic Acid Kit

Kit C: H-Bond Formation Removal Kit for Boronic Acids & other impurities. For the effective removal of: Boronic acids from cross-couplings and Petasis multi-component reactions Impurities capable of participating in a H-bond forming removal mechanism 10 g format (OS-08-KIT C1 10) 25 g format (OS-08-KIT C1 25) 100 g format (OS-08-KIT C1 100)
OH S OH
60-200 m 60
0.8 mmol/g
SDOL
2,3-Dihydroxypropyl ethyl sulfide Silica

O S N OH OH OH OH OH
60-200 m 60
0.8 mmol/g
SMG
N-methyl-D-glucamine ethyl sulfide amide Silica
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Organic Scavengers
Portfolio Kit
Organic Scavengers
Structure Name For removal of Loading Particle Size Pore Diameter Product Code
Kit D: Organic Scavenger Portfolio Kit. All 10 materials contained in kits A, B & C 10 g format (OS-08-KIT D2 10) 25 g format (OS-08-KIT D2 25) 100 g format (OS-08-KIT D2 100)
O S N H SH
Electrophiles
0.3-0.5 mmol/g 60-200 m 60
4MPAE

S SH
Electrophiles
0.8 mmol/g 60-200 m 60
SPM32

S
NH2
Electrophiles Weak anions
0.8 mmol/g 60-200 m 60
SEA

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 60
SPA5

O S N H
H N
NH 2
0.8 mmol/g 60-200 m 90
SPAf

S S N H N H
Electrophiles
0.6 mmol/g 60-200 m 90
MTCf

O P OH OH
Cations Basic compounds, amines
1 mmol/g 60-200 m 60
POH1

O S OH OH
0.6 mmol/g 60-200 m 60
STMA

OH S OH
Boronic acids Impurities by H-bond formation
0.8 mmol/g 60-200 m 60
SDOL

Boronic acids Impurities by H-bond formation
0.8 mmol/g 60-200 m 60
SMG
N-methyl-D-glucamine ethyl sulfide amide Silica
39
SPE Formats
Organic Scavengers Available in SPE Cartridge Format
For Discovery scale purifications, PhosphonicS organic scavengers are available in SPE cartridges. Cartridges available contain the following quantities of PhosphonicS SPE sorbent: 1 g (6 mL volume) 2 g (15 mL volume) 5 g (20 mL volume) 10 g (75 mL volume) The particle size of the functionalised silicas contained within these cartridges is 35 70 m, to provide flow rates appropriate for SPE applications
Organic scavenger cartridges.
Structure Name
For removal of
Loading Particle Size Pore Diameter

0.8 mmol/g 35-70 m 60
Product Code
SH
Electrophiles 3-Mercaptopropyl ethyl sulfide Silica

S NH2
SPM32d
0.8 mmol/g 35-70 m 60
SEAd

O S N H
H N
NH 2
0.8 mmol/g 35-70 m 60
SPA5d

S S N H
O P OH OH
N H
Electrophiles
0.6 mmol/g 35-70 m 60
MTCd
Methyl thiourea ethyl sulfide ethyl Silica Cations Basic compounds, amines 1 mmol/g 35-70 m 60
POH1d

O S OH OH
0.6 mmol/g 35-70 m 60
STMAd
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Organic Scavengers
Case Studies
Organic Scavengers Organic Scavenging Case Studies
Amine Scavenging Preparation of Medicinal Chemistry Intermediate 3-(2-Bromophenyl)propanoyl chloride (2.28 g, 9.23 mmol), was dissolved in dichloromethane (20 mL), cooled to 0 C and phenethylamine (excess, 5.8 mL, 30 mmol) was added dropwise over 15 minutes. The reaction mixture was warmed to r.t. and stirred for an additional 4 hours. The solution was passed through a plug of heterogeneous phosphonic acid POH1 (1.5 g), which effectively removed the excess amine. The resultant solution was evaporated under reduced pressure to give the desired amide product (2.8 g, 94 % yield, >95% purity).
O Cl Br (i) NH2 (ii) O P OH OH POH1
DCM, r.t.
O N H Br
Scavenger Screening for Removal of Commonly Problematic Electrophiles Three PhosphonicS scavengers were screened against example substrates from classes of problematic electrophiles: alkyl halides, -haloacyl derivatives and sulfonic acids. Scavenging was generally effective using just 2 equivalents of scavenger at 50 C in THF. PhosphonicS scavengers allowed rapid optimisation of the impurity removal, often resulting in >98% scavenging of the electrophile, and eliminated the need to use problematic additives such as tertiary amines often employed with other scavengers.
100 80 60 40
Scavenger A
20 0
Scavenger B Scavenger C
O S N Cl N O O Cl OH
41
Introduction
Solid Phase Extraction (SPE) is now well established as an essential tool in Discovery Medicinal Chemistry, offering considerable operational benefits and time savings over traditional extractive work-up and chromatographic methods. This simple technique is ideally suited to purifying milligrams through to multiple grams of product, and has found application at the various project stages of Lead Discovery (larger compound arrays/libraries) to Hit-to-Lead and Lead Optimisation (small focused compound arrays and high value single compounds).
Direct Filtration
Reaction mixture Wash solvent (MeOH)
Catch and Release

Reaction mixture Wash solvent (MeOH) Eluting solvent (eg NH3 in MeOH)
Whilst often highly effective, SPE materials based on such strong sulfonic acid functionality can present problems for instance when acidsensitive moieties are present - sulfonic acid sorbents have been used for the removal of common protecting groups such as Boc and TBDMS - or by catalysing side reactions of the basic compounds to be purified, resulting in either product loss or a reduction in purity. Sulfonic acid SCX materials also generally fail to differentiate between the different basicities of reaction components such as 2 and 3 amines, mixtures which are frequently generated by common reactions such as reductive aminations or deprotection steps. PhosphonicS offers a number of silicaimmobilised acids with reduced acidities, covering a pKa range from 1 to 6 and featuring phosphonic acid and carboxylic acid functionalities. These materials allow the clean purification of basic compounds containing acidsensitive groups such as Boc, OtBu and TBDMS, and can also be used for selective separations of basic reaction components including 2 and 3 amines, and saturated and unsaturated nitrogen heterocycles. PhosphonicS immobilised amines act as weak anion exchangers, circumventing the problems of irreversible retention and product loss often associated with stronger anion exchangers. The inherent high stability, selectivity and excellent solvent compatibility of PhosphonicS functionalised silicas make the materials ideally suited to SPE purifications in Medicinal Chemistry.
PhosphonicS SPE sorbent
PhosphonicS SPE sorbent
Impurities retained
Product retained
Product eluted
Impurities eluted
Product eluted
Strong cation exchange (SCX) is the most widely used method of SPE purification. Basic reaction products are typically retained by the SCX material, allowing non-basic impurities to be washed away, before the desired basic product is eluted. This purification protocol is termed catch and release and has traditionally been performed using cation exchange materials featuring strongly acidic sulfonic acid functionalities of pKa <1. Product purification can also be performed by the retention of basic impurities by the SCX material, with the non-retained, non-basic reaction product washed off and collected. This can be considered a non-retained method of purification or direct filtration of impurities from the product.
O S S O O OH P OH OH
O S OH OH O S
O OH
Strongly acidic Low pKa
PhosphonicS SPE products Fewer side reactions Retained acid sensitive groups Selective catch and release
Less acidic Higher pKa
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SPE
SPE Materials and Formats

SPE PhosphonicS SPE Cartridges
For Discovery scale purifications, PhosphonicS Organic Scavengers are available in SPE cartridges. Cartridges available contain the following quantities of PhosphonicS SPE sorbent: 1 g (6 mL volume) cartridge 2 g (15 mL volume) cartridge 5 g (20 mL volume) cartridge 10 g (75 mL volume) cartridge The particle size of the functionalised silicas contained within these cartridges is 35 70 m, to provide flow rates appropriate for SPE applications. Cartridges are made from polypropylene. Frits are made from polyethylene. Both are compatible with commonly-used organic and aqueous solvents. For scale-up purposes where slurry processing is more appropriate, PhosphonicS SPE materials are available in larger particle sizes for easy filtration. Structure Name
S
SPE cartridges.
For removal of
Particle Size Pore Diameter
Product Code
NH2
Weak anions
35-70 m 60
SEAd

S O H N
NH
NH 2
Weak anions
35-70 m 60
SPA5d

O P OH OH
Cations
35-70 m 60
POH1d

O S OH OH O
Cations
35-70 m 60
STMAd
43
Typical Purification Procedure

Using PhosphonicS Cation Exchange Materials 1. Choose the appropriate PhosphonicS SPE cation exchange material POH1d or STMAd. 2. Select the appropriate size cartridge loading onto the cartridge should typically start at 5% by weight (reaction mixture : functionalised silica), though much higher loadings are often possible. 3. Condition the cartridge by passing MeOH followed by the loading solvent of choice through it. 4. Load the reaction mixture onto the top of the cartridge in the solvent of choice (~1 mL solvent/50 mg product). 5. Allow the reaction mixture layer to elute through. Pass further MeOH through the cartridge. This load fraction will contain unretained reaction components. 6. Wash the cartridge with further MeOH. These wash fractions will contain any further traces of unretained reaction components. 7. Basic product elution is dependent on the modified cation exchange material used. Elute the product with triethylamine in MeOH solution (5% v/v) and collect the fraction. If necessary, elute the cartridge further with ammonia in MeOH solution (~1.2% v/v; ~0.7 M) and collect the fraction. Fractions from these two elution steps will contain any retained or caught reaction components. 8. Rinse the cartridge finally using MeOH. 9. Analyse fractions to confirm that the desired separation has been achieved. 10. Concentrate appropriate fractions in vacuo to afford the purified product(s).
SPE experimental set-up.
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SPE
Case Studies
SPE
PhosphonicS new cation exchange materials offer: Complete Retention of Acid-sensitive Functionalities These materials allow the clean purification of basic compounds containing acid-sensitive groups such as Boc, OtBu and TBDMS. Additionally compounds containing THP groups have been passed through the materials without cleavage, allowing purifications by non-retained mechanisms to be considered.
Basic molecules containing acid-sensitive groups successfully subjected to cation exchange catch and release with PhosphonicS functionalised silicas.
O HN O O NH2
O
HN
H N Si O
NH2 O Si
N O
H2 N
CO2H
'Catch & release' with
POH1d
POH1d
STMAd
STMAd
STMAd
Piperazine amide formation without protecting group removal.

O
O O N H O
OH
O P OH OH
O Caught 0.7 M. NH3 in MeOH Released N N H N O
N NH
(xs.)
O O
DIC, HOBt (1.5 eq.) DCM
Washed off xs. Acid DCU Urea By-Product HOBt
96% yield 98% purity
45
Case Studies
Highly Selective Separations of Basic Compounds PhosphonicS SPE products also allow the effective separation of basic reaction components including 2 and 3 amines, and saturated and unsaturated nitrogen heterocycles. Reaction mixture components are either both caught and then selectively released by use of appropriate eluants or one of the reaction mixture components is selectively retained, allowing the second component to be washed through and collected. An example separation along with associated analytical data is shown below:
N N H2, Pd/C EtOH NH
mAU
VWD1 A, Wavelength=215 nm (D:\EZXDATA\TSCREEN2\07-07\170707-129-054_MIX_2151.D)
600 500 400 300 200 100 0

mAU
1.9 min. Pyridine 2.2 min. Piperidine
1:1 pyridine : piperidine mixture
1.4 1.6 1.8 2 2.2 VWD1 A, Wavelength=215 nm (D:\EZXDATA\TSCREEN2\07-07\170707-129-054-PHOS31.D)
2.4
2.6
2.8
min
10.00 8.00 6.00 4.00 2.00

1.4 mAU 1.6 1.8 2 2.2 2.4 2.6
Et3N/MeOH wash
1.9 min. 98%
2.8
min
VWD1 A, Wavelength=215 nm (D:\EZXDATA\TSCREEN2\07-07\170707-129-054-PHOS41.D)
NH3/MeOH wash
300 200 100 0 -100

1.4 1.6 1.8 2 2.2
2.2 min. 97%
2.4
2.6
2.8
min
Accelerated Reaction Work-ups PhosphonicS SPE materials can be used to accelerate reaction work-ups and are then removed by simple filtration. In the example shown, the cation exchange catch and release feature is accompanied by effective imine deprotection, replacing the time-consuming normal acidic aqueous work-up.
Ph NH2 N Cl PhCHO (xs), Ph B(O H)2 (xs) Pd C l 2 ( PPh 3 ) 2 Na2CO 3, to luene N N
O P OH OH
Caught 0.7 M. NH3 in MeOH Released

N
NH2
Facile work-up and isolation of 2-phenyl-3-aminopyridine.
Washed off impurities
60% yield 98% purity
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SPE
Introduction
Catalysts
The use of heterogeneous catalysts for chemical production is growing in importance as chemical industries seek to demonstrate improved sustainability and reduced environmental impact. This drive towards the use of heterogeneous catalysts is based on the inherent process benefits offered. These include easier product isolation and purification, no undesired catalystderived contamination of the product, cost benefits from catalyst recycling and often improved activity and reaction selectivity over homogeneous catalysts, or even stoichiometric homogeneous reagents. Heterogeneous catalysts, which are highly suitable for either batch or continuous flow applications, can also be used as convenient tools for high-throughput Discovery Chemistry, reducing and often removing the need for laborious product purifications. PhosphonicS has developed a range of novel heterogeneous catalysts for a wide range of applications including metal-mediated crosscouplings, oxidations and acid-promoted reactions in the pharmaceutical, fine chemical and petrochemical industries.
Useful References on Heterogeneous Catalysis Corma, A.; Garcia, H. Adv. Synth. Catal., 2006, 348, 1391 Leadbeater, N. E.; Marco, M. Chem. Rev., 2002, 102, 3217 Ley, S. V. et al, J. Chem. Soc., Perkin Trans. 1, 2000, 23, 3815 Uozumi, Y. Topics in Current Chemistry, 2004, 242, 77
47
Properties & Benefits/Kits

Properties of PhosphonicS Heterogeneous Catalysts
Wide variety of particle sizes available Average pore diameter of 60 -150 for most applications Particle sizes, pore sizes and functional group loading can be readily varied, as appropriate for the application Range of effective loadings available, as appropriate to application Pd catalysts: 0.01 0.4 mmol/g Oxidation catalysts: 0.2 0.5 mmol/g Acid catalysts: 0.2 1.0 mmol/g No swelling of the catalysts are required Broad solvent compatibility Excellent stability - thermal, physical, chemical and mechanical Performance Benefits High selectivity. Clean reactions, fewer by-products Easy product isolation; catalysts simply filtered off Removal of problematic ligands such as phosphines avoided High yields of product Catalyst recycling High purity - no leaching of metal or organic fragments into products Faster, more economic processes Heterogeneous Catalyst Kits To support Research and Development programs, a set of catalyst kits have been created. These allow the trial of different PhosphonicS catalysts and the identification and selection of the optimum catalyst for a specific application. Catalysts can also be supplied as individual samples. Kits contain selections of highly effective catalysts with widely-appropriate properties such as particle and pore sizes and functional group loadings. These properties of functionalised silicas can however be readily varied and their modification may prove useful for optimisation of a particular process. PhosphonicS can provide catalyst features tailored to individual clients needs, please contact us to discuss your particular requirements.
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Catalysts
Heterogeneous Palladium Catalysts

Catalysts
Compared to traditional synthetic methods, palladium-catalysed cross-coupling reactions offer increased synthetic convergence and shorter routes into products. As these methods allow highly functionalised molecules to be coupled together under relatively mild conditions, metal-catalysed reactions are extremely widely used for Discovery Medicinal Chemistry efforts and are becoming increasingly used by Process Chemistry groups, even at later stages of candidate synthesis. In spite of the excellent performance of metal scavengers such as functionalised silicas, the potential for metal contamination of final products by homogeneous catalysts, alongside some of the other benefits outlined previously, has led to much synthetic attention being devoted to the search for efficient heterogeneous palladium catalysts. PhosphonicS immobilised heterogeneous palladium catalysts have been successfully utilised in cross-coupling reactions including Suzuki and Heck reactions and are highly effective for a wide range of different substrates giving the coupled products in very high yields.
Structure Name
Product Code
Heterogeneous Palladium Catalyst Kit. 1 g format (CP-06-KIT D3 1) (5 x 1 g samples) 5 g format (CP-06-KIT D3 5) (5 x 5 g samples), 10 g format (CP-06-KIT D3 10) (5 x 10 g samples)
O S O Pd(OAc)
0.1-0.4 mmol/g 60-200 m 60
SCRPd
Palladium acetate ethanoate ethyl sulfide Silica

S S Pd(OAc)2
Palladium acetate 2-mercaptoethyl ethyl sulfide Silica

S S Pd(OAc)2
0.1-0.4 mmol/g 60-200 m 60
SEM2Pd
Palladium acetate 3-mercaptopropyl ethyl sulfide Silica

PdCl2PPh3 P O
0.1-0.4 mmol/g 60-200 m 60
SPM3Pd
O O
0.01-0.03 mmol/g* 60-200 m 110
PAPd1r
Triphenylphosphine palladium dichloride phosphaadamantane ethyl Silica

Pd(dba)
O O
P O
0.01-0.03 mmol/g* 60-200 m 110
PAPd2r
Dibenzylideneacetone palladium(0) phosphaadamantane ethyl Silica * higher loadings of 0.05 0.14 mmmol/g are also routinely available H-PAPd1r and H-PAPd2r products
49
Suzuki and Heck Reactions

With SCRPd
Br R
R = H, Me, OMe, Cl
B(OH)2
K2CO3, xylene, 90 C, 2 hrs

O S O Pd(OAc)
R
>90% yield (for each of 3 recycles)
SCRPd (up to 5 mol%) Br R

R = H, OMe, Cl
K2CO3, NMP, 110 C, 24 hrs
R
>97% yield (for each of 3 recycles)
Al-Hashimi, M.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2007, 273, 298
With SEM2Pd or SPM3Pd
)n
S
Pd(OAc) 2
SEM2Pd n = 1 or SPM3Pd n = 2 a.1.5 mol%; b. 3 mol% Br R

R = H, Me, OMe, Cl
B(OH)2
a. K2CO3, xylene, 110 C, 2-7 hrs or b. NaOtBu, iPrOH, 25 C, 6 hrs
generally >90% yield (for each of 3 recycles)
Al-Hashimi, M.; Qazi, A.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2007, 278, 160
With PAPd1r or PAPd2r
PdL
O O
PAPd1r L = Cl2PPh3 or PAPd2r L = dba 0.1 mol% Ar X + Ar'B(OH)2

(X = Br or Cl) K2CO3, xylene, reflux, 2 hrs
Page 50 shows specific Suzuki examples with PAPd1r and PAPd2r.
Ar Ar'
Guino, M.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2008, 293, 25
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Catalysts
Suzuki Reactions with PAPd1r & PAPd2r

Catalysts
Aryl halide, Ar Product Conversion with PAPd1r Conversion with PAPd2r
Br OH O O
CH3
92%1
OH
95%2; 98%
Br N
>99%
N
>99%
Br
CH3
CH3
69%
70%
Br H3CO
CH3
87%
H3CO
84%; 67%
N O
Me Br
N O
Me
68%
66%
Br
81%
N Cl N Cl
85%
Br
CH3
CH3
91%3
90%4
Cl NO2 NO2
49%; 73%
50%
Conversions calculated by HPLC. Reaction conditions: General Procedure 1; Microwave Procedure (as described on page 51). Catalyst recycles: 1 99%; 2 95-99%; 3 92-93%; 4 95-97%. Similarly successful results for a diverse range of Suzuki reactions were obtained with SEM2Pd and SPM3Pd catalysts.
51
General Suzuki Reaction Conditions

For each substrate efficient reaction conditions have invariably to be determined and variations in the choice of catalyst, catalyst and reagent concentrations, solvents and temperature may have to be investigated. Catalyst variations such as particle size, surface area and pore diameters can subsequently be explored to optimise a particular reaction. These general reaction conditions can vary slightly depending on the catalyst used. For catalysts PAPd1r and PAPd2r, 0.1 mol% of catalyst is typically used and for SCRPd, SEM2Pd and SPM3Pd catalysts a typical amount of 1-5 mol% is employed. General Procedure 1 : An aryl halide (1 mmol), a boronic acid (1.5 mmol), K2CO3 (2 mmol) and the appropriate catalyst were refluxed in xylene (4 mL) for 2 hours. General Procedure 2 : An aryl halide (1 mmol), a boronic acid (1.1 mmol), NatOBu (1.2 mmol) and catalyst were stirred in ipropanol (4 mL) at r.t. for 6 hours. Microwave Procedure : An aryl halide (1 mmol), a boronic acid (1.5 mmol), K2CO3 (2 mmol) and the appropriate catalyst were stirred in a mixture of EtOH:H2O:DME (1:2:4) (2.5 mL) at 130 C for up to 30 minutes in a microwave reactor. Product Isolation and Catalyst Recycling : The crude reaction product was isolated by filtration of the catalyst followed by drying in vacuo. The catalyst was washed with water and methanol and dried in vacuo and can then be re-used. Flow Chemistry PhosphonicS heterogeneous palladium catalysts can be packed into glass reactor columns and applied to Suzuki reactions such as that shown below under continuous flow conditions. Flow process benefits such as the ability to use high substrate concentrations, high substrate conversions, good catalyst capacity and short residence times were all observed. For full details see Application Note 13 at www.vapourtec.com.
S B(OH)2 Br + N R + DIPEA
S Pd(OAc)2 R
SPM3Pd
ethanol:water:DME (2:1:2)
PhosphonicS full range of heterogeneous catalysts are now being explored for flow chemistry applications.
Typical Reaction and HPLC Data for Crude Reaction Product.

published with the kind permission of Sygnature Chemical Services Ltd.
Pd(dba)
P O
Br B(OH)2
PAPd2r (0.04 mol%) Na2CO3, DME/EtOH (4 :1) MW, 135 oC, 30 mins
+
N .HCl
mAU 2.083 100
Diode Array
80
60
92% yield, 98% purity
40
20
0 0 1 2 3 4 5 6 min
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Catalysts
Immobilised Phosphines
Catalysts
PhosphonicS has successfully immobilised onto silica a range of specialised phosphine ligands found to demonstrate enhanced performance in cross-couplings. Structure Name Loading Particle Size Pore Diameter Product Code
O O
P O
0.5 mmol/g 60-200 m 110
PAr
Phosphaadamantane ethyl Silica
0.5 mmol/g 60-200 m 60
DCP
Dicyclohexylphosphine ethyl Silica
0.5 mmol/g 60-200 m 60
NP
Dinorbornylphosphine ethyl Silica
A variety of metal complexes have been attached to these ligands to give novel catalysts. A selection of the palladium and platinum catalyst variants prepared to date are shown - the inclusion of other metal species and the immobilisation of specific phosphine ligands is available upon request.
L M
O O O
P L M
L M
PAPd1r PAPd2r
ML = PdCl2PPh3 ML = Pd(dba)
DCPPd4 DCPPd3 DCPPt4
ML = PdCl2(CH3CN) ML = PdCl2(C6H 5CN) ML = PtCl2(CH3CN)
NPPd4 NPPd3 NPPt4
ML = PdCl 2(CH 3CN) ML = PdCl 2(C6H5CN) ML = PtCl2(CH3CN)
Product codes shown in bold
53
Heterogeneous Metal Oxidation Catalysts

Allylic and benzylic oxidations, alcohol oxidations, sulfoxidations and epoxidations are key chemical transformations. However these reactions, generally conducted by the use of stoichiometric concentrations of inorganic oxidants, suffer from significant environmental and safety drawbacks which have restricted their use on process and manufacturing scale. Widely-used oxidising reagents include potassium permanganate, manganese dioxide, chromium trioxide, potassium chromate, potassium dichromate and peracids. These hazardous reagents produce large volumes of toxic waste that is becoming increasingly costly to treat and dispose of in an environmentallyfriendly manner. Difficulties in the work-up of these oxidation reactions as well as in the purification of the products, particularly from metal residues, are also typically encountered. Whilst highly efficient metal scavenging technologies such as functionalised silicas are now available, the removal of metal species from APIs can often be a complex problem, with increasingly strict regulatory metal content targets to be addressed. In addition to generating large quantities of hazardous and toxic waste, this means that reaction products whose synthesis involves a traditional homogenous metal-promoted oxidation are often taken forward into initial screens or further synthetic steps with large metal contamination, thereby severely affecting result reliability. There is clearly an increasing need for new heterogeneous oxidation catalysts that are not only effective and available across a range of scales but also possess advantages such as ease of use, facile product isolation, produce reduced hazardous waste and allow catalyst recovery and recycling. Under mild conditions in the presence of a re-oxidant, PhosphonicS heterogeneous oxidation catalysts cleanly, efficiently and selectively perform key oxidative transformations, including alcohol oxidations, benzylic and allylic oxidations, epoxidations and sulfoxidations. The catalysts can be simply and effectively recycled.
PhosphonicS Heterogeneous Metal Oxidation Catalysts.
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Catalysts
Metal Oxidation Catalyst Kit & Conditions

Catalysts
Structure Name Loading Particle Size Pore Diameter Heterogeneous Metal Oxidation Catalyst Kit. 10 g format (CP-06-KIT B 10) (5 x 10 g samples) 25 g format (CP-06-KIT B 25) (5 x 25 g samples)
O P
Product Code
O O
VO(II)
0.2-0.5 mmol/g 60-200 m 60
POVO
Vanadyl(II) ethyl/butyl phosphonate Silica

O P
O O
Co(II)
0.2-0.5 mmol/g 60-200 m 60
POCo
Cobalt(II) ethyl/butyl phosphonate Silica

O P
O O
Mn(II)
0.2-0.5 mmol/g 60-200 m 60
POMn
Manganese(II) ethyl/butyl phosphonate Silica

O P
O O
Cr(III)
0.2-0.5 mmol/g 60-200 m 60
POCr
Chromium(III) ethyl/butyl phosphonate Silica

O P
O O
Ce(IV)
0.2-0.5 mmol/g 60-200 m 60
POCe
Cerium(IV) ethyl/butyl phosphonate Silica
For each substrate reaction conditions have to be initially validated and variations in catalyst and reagent concentrations, solvents and temperature have to be investigated to fine-tune the reaction outcome. PhosphonicS publications provide useful guidance for most oxidation substrates. Variations in particle size, surface area and pore diameters are factors which can subsequently be explored to further optimise a particular process. Allylic Oxidation: A mixture containing the substrate (1 mmol) dissolved in acetonitrile (6 mL), catalyst POCo (60 mg) and tert-butyl hydroperoxide (6 mmol in decane) was heated and stirred under an atmosphere of nitrogen. Alcohol Oxidation: The alcohol (1 mmol) dissolved in acetonitrile (4 mL) was added to catalyst POCe (40 mg). The mixture was stirred and sodium bromate (2 mmol) and water (0.5 mL) were added. The resultant mixture was refluxed under an atmosphere of nitrogen. Sulfoxidation: The POCe catalyst (30 mg) and
sulfide (1 mmol) were added to acetonitrile (3 mL). Sodium bromate (1.5 mmol) and water (0.5 mL) were added. This mixture was stirred with heating. As an alternative POVO catalyst can be used with 30% aqueous hydrogen peroxide employed as the re-oxidant. Epoxidation: A mixture containing the substrate (1 mmol) dissolved in acetonitrile (6 mL), POVO (60 mg) and tert-butyl hydroperoxide (6 mmol in decane) was heated and stirred under an atmosphere of nitrogen. Reaction Work-up and Product Isolation: On completion of the reaction, the catalyst was filtered off and washed with a suitable solvent. The catalyst can be dried in vacuo and re-used if appropriate. The combined filtrate was washed if appropriate (e.g. with 10% aqueous sodium sulfite solution followed by water for POCo allylic oxidations), dried over MgSO4 and concentrated under reduced pressure. Purification where necessary, to remove traces of starting material, was by recrystallisation or column chromatography.
55
Summary of Oxidation Transformations

Oxidation Catalyst Product Code Substrate Product Re-oxidant Leading References
O P
O O
Co(II)
POCo
Allylic/Benzylic CH2 Allylic alcohols
Ketones Enones
BuOOH
Tet. Lett., 2003, 44, 4283; 2004, 45, 4465 Tet. Lett., 2004, 45, 4465; 2006, 47, 8017
O P
O O
VO(II)
POVO
Allylic alcohols Sulfides
Epoxides Sulfoxides
BuOOH or NaBrO3 or H2O2
O P
O O
Mn(II)
POMn
Allylic CH2 or Benzylic CH2
Ketones
BuOOH
Unpublished results
O P
O O
Ce(IV)
POCe
1 Alcohols 2 Alcohols Sulfides
Acids Ketones Sulfoxides
NaBrO3 or t BuOOH
Tet. Lett., 2003, 44, 769; 2005, 46, 4365
O P
O O
Cr(III)
POCr
Sulfides
Sulfoxides
NaBrO3 or t BuOOH
Unpublished results
Alternative metals immobilised to the phosphonate silica, including Cu, Ni, Ti and Zn, are available on request, for a variety of applications.
A range of transformations are shown in the scheme below.
O S R
O
O
S R
R = CN; CH2OH; CH=CH2 (i)

OH
(viii)
O
OH
O P O O MLn
(ii)
OH F
(vii)
OH
(iii)
(vi)
N N OH S N
O
OH
(iv)
(v)
N O O N N S O OH
For (i) & (ii) MLn = Co(II) (POCo); (iii) & (iv) MLn = VO(II) (POVO); (v) - (viii) MLn = Ce(IV) (POCe)
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Catalysts
Heterogeneous Acid Catalysts

Catalysts
A large number of chemical processes are acidcatalysed and typically these have been performed with quantities of mineral acids, which can be hazardous to use, corrosive, and necessitate reaction work-ups generating inorganic waste requiring appropriate, environmentally-friendly disposal. Side-products are also common and often require removal. On Process Scale the costs for these tasks can be high and have a significant impact on overall Structure Name process costs. On Discovery Scale the aqueous work-up is time-consuming and inconvenient. Heterogeneous acid catalysts remove these issues, can be easily removed by simple filtration and are now being used increasingly for chemical reactions. PhosphonicS offer a number of immobilised acid catalysts, available from R&D quantities up to full Process Scale. Loading Particle Size Pore Diameter
Product Code
Heterogeneous Acid Catalyst Kit. 10 g format (CP-06-KIT A3 10) (3 x 10 g samples) 25 g format (CP-06-KIT A3 25) (3 x 25 g samples) 100 g format (CP-06-KIT A3 100) (3 x 100 g samples)
O P OH OH
1.0 mmol/g 60-200 m 60
POH1

S OH S O O
0.7 mmol/g 60-200 m 60
SPhSA
Phenyl sulfonic acid ethyl sulfide Silica

O P
O O
Ti
O O
0.2-0.5 mmol/g 60-200 m 60
POTi
Diisopropyl titanium ethyl/butyl phosphonate Silica Pore sizes from 60-150 available for application optimisation. Particle sizes of 60-200, 315-500, 500-1000 and 1000-2000 m available.
Summary of Acid Tranformations Strong phenyl sulfonic acid SPhSA and the milder phosphonic acid POH1 are effective catalysts for a range of widely-utilised chemical reactions, including esterifications, transesterification, dehydrations, cyclisations, condensations, rearrangements, isomerisations and polymerisations, and for the introduction of a variety of commonly-used protecting groups by reactions such as acetalisation, ketalisation and etherification. Diisopropyl titanium phosphonate POTi has also been used as a catalyst for esterifications and trans-esterifications, as well as polymerisations. The catalysts can be simply and effectively recycled.
R R' Si OR
RCH2CHR'OH
RCO2R'
RCO2H R'OH
tBuSi(Me)2OMe
X = S-C6H4-pSO3H
ROH
RCO2R' R2OH
RCO2R2
OR X = PO(OH)2
RC(O)R' RCHO
Diols
O ( )n
O O R O
R R'
57
Acid-Catalysed Reactions & Case Studies

The choice of catalyst, either the strong sulfonic acid SPhSA or the milder phosphonic acid POH1, is dependent on the substrate and preferred reaction conditions. For each substrate reaction conditions have to be initially validated and variations in catalyst and reagent concentrations, solvents and temperature have to be investigated to enhance the reaction outcome. Variations in particle size, surface area and pore diameters are factors which can subsequently be explored to further optimise a particular process. The following examples illustrate the use of these heterogeneous catalysts for a number of typical acid-catalysed reactions. Further synthetic protocols including dehydrations and aldol condensations are described in J. Mol. Catal. A: Chem., 2008, 280, 96. Esterification: A solution of oleic acid (5 g, 1.8 mmol) in ethanol (25 mL) was added to the sulfonic acid catalyst SPhSA (1 g) and the mixture refluxed for 6 hours. Following the work-up described below oleic acid ethyl ester (5.5 g, 99%) was isolated in >99% purity. Alcohol Protection Tetrahydropyranylation: A mixture of an alcohol (5 mmol), dihydropyran (4 fold molar excess) and catalyst POH1 (50 mg) was stirred in ether (15 mL). Following the work-up described below the tetrahydropyran derivative was isolated cleanly and in >98% yield. Carbonyl Protection Ketalisation: A mixture of the ketone (40 mmol), ethylene glycol (6 mL) and catalyst POH1 (0.4 g) in toluene (30 mL) was refluxed under Dean and Stark conditions for 4 hours. Following the work-up described below the 1,3 dioxolane product was generally obtained in high purity and in >98% yield. Reaction Work-up and Product Isolation: On completion of the reaction, the reaction was cooled and the catalyst filtered off and washed with a suitable solvent. The combined filtrate was dried over MgSO4 and concentrated under reduced pressure. The catalyst was washed with methanol, dried and reused. Case Studies with PhosphonicS Heterogeneous Acid Catalysts Ketal Deprotection Preparation of a Medicinal Chemistry Intermediate N-Alloc-4-piperidone ethylene acetal (0.7 g, 3.3 mmol) was dissolved in acetone (10 mL) and water (0.5 mL). Heterogeneous phosphonic acid POH1 was added, and the mixture was stirred at reflux for 6 hours. The reaction was filtered through a sintered funnel and the clear filtrate evaporated in vacuo to give the piperidone product (0.6 g, quantitative yield, >95% purity).
O
P OH OH
POH1
N O O
acetone/H2O reflux, 6 hour Quantitative yield O
N O
Esterification of Fatty Acids with Catalyst SPhSA Esterification of both lauric and oleic acid with a variety of alcohols was performed in very high yields with primary alcohols using typically 5 mol% S of acid catalyst SPhSA, which can be recycled. Yields are generally better than those achieved with homogeneous and other heterogeneous sulfonic acid catalysts and with secondary alcohols the reaction remained clean and effective, though initial, unoptimised yields were reduced.
O R
S
OH
R'OH
SPhSA
OH S O O
O R O R'
R Me Et n Pr i Pr n C8H17 Bn
R = nC8H17CH=CHyield/% 98 97 97 49 89 67
R = nC4H9 yield/% 96 94 95 na na na
na = reaction not performed
Esterification of Fatty Acids in the Presence of Triglycerides The SPhSA catalyst is also highly efficient for the esterification of free fatty acids in the presence of triglycerides, having application for the production of biodiesel.
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Catalysts
Immobilised Enzymes
Bio Catalysts
Biocatalysis is now established as a key technology in many chemistry-focused industries, offering greener, cleaner, shorter and more costeffective production steps. Immobilised enzymes (IEs) offer further enhanced benefits over their soluble counterparts in terms of stability, recycling/reuse and selectivity. These performance traits have resulted in widespread applications for IEs from heterogeneous biocatalysts to protein purification tools to analytical devices and beyond. As a further extension of our technology, we have recently undertaken the immobilisation of a variety of enzymes to our silica frameworks, within which key elements such as framework properties including particle size, pore size and hydrophobic character can all be readily varied, as can the nature of the linker employed for covalent attachment of the enzyme. The stability benefits of our IEs, where no enzyme leaching was observed even at elevated temperatures over long processing times, and even in organic solvent mixtures, were confirmed, meaning the biocatalysts could be recycled with reproducible results. These functionalised silica IEs have subsequently been used for a range of chemo-enzymatic synthesis applications to generate high-value chiral ligands of broad synthetic application. For example, chiral diones,1 precursors of chiral diene ligand metal complexes used as highly effective catalysts for asymmetric reactions such as additions to enones2 and arylations of tosylimines,3 were generated by the Carnell group in high enantioselectivity from resolution of an enol acetate by use of a lipase immobilised onto our PhosES silica supports. In this application, the benefit of hydrophobic modification of the IEs was clearly demonstrated by PhosES-03 outperforming unmodified variants in terms of enantioselectivity achieved, as well as a range of industry-standard methods for IE generation.
PhosES silica supports for enzyme attachment, featuring a range of linker functionalities and hydrophobic surface modifications as required, are available upon request please contact us directly for further information. In addition to the various applications described in this catalogue, we have applied our leading edge immobilisation skills to a range of challenging problems where use of our customised silica supports can present key performance benefits. We encourage companies to challenge us with their immobilisation requirements, allowing us to present positive, economically viable and workable solutions for application testing.
References
1 2
Luo, Y.; Carnell, A. J. J. Org. Chem., 2010, 75, 2057 Tokunga, N.; Hayashi, T. Adv. Synth. Catal., 2007, 249, 513; Paquin, J.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett., 2005, 7, 3821 and references therein 3 Nishimura, T.; Yasahura, Y.; Hayashi, T. J. Org. Lett., 2006, 8, 979 and references therein.
59
Pricing Notes
In addition to the kits detailed previously, scavengers and catalysts are available as individual items or can be assembled into custom kits relevant to the problem in question. The prices below refer to all of the items in the list that follows, as supplied in loose powder format. Prices shown are on FCA basis they exclude delivery charges which are charged at cost, and will be advised at time of order Packaging charges are included products are normally supplied in plastic containers Payment terms 30 days from invoice Paperwork supplied as standard: delivery note and invoice Safety Data Sheets are provided with first order Sample products are normally available for shipment within 2 working days Sample prices are valid until further notice For R&D/small test samples, pricing is available on request.
Key
Silica framework FP KM DP Frontline Product (Top 4 from kits) Material from Metal Scavenger or Organic Scavenger kit Development Product
SPE Solid Phase Extraction Product, generally supplied in cartridges CAT Catalysis Product
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Product Index
By Terminal Functional Group
Structure Name Mainstream Applications Loading Particle Size Pore Diameter Product Code Product Category
Alcohols, Diols and Polyols

S OH
Metal Scavenger
0.8 mmol/g 60-200 m 60
SOL
DP
2-Hydroxyethyl ethyl sulfide Silica

OH S OH
Metal Scavenger Organic Scavenger
0.8 mmol/g 60-200 m 60
SDOL
KM

Organic Scavenger
0.8 mmol/g 60-200 m 60
SMG
KM
N-Methyl-D-glucamine ethyl sulfide amide Silica

O S N H H N
OH
Metal Scavenger
0.8 mmol/g 60-200 m 60
SDEA
KM
2-Hydroxyethyldiamine ethyl sulfide amide Silica 1 mmol/g 60-200 m 60
OH
Linker
POL
DP
3-Hydroxypropyl Silica
Amines
S NH2
0.8 mmol/g 60-200 m 60
SEA
FP

S
NH2
Metal SPE SPE
0.8 mmol/g 35-70 m 60
SEAd
SPE

S
NH2
Metal Scavenger Organic Scavenger Metal Scavenger

NH 2
0.8 mmol/g 300-500 m 150
SEAg
FP

O S N H H N
Organic Scavenger
0.8 mmol/g 60-200 m 60
STA3
FP
61
Product Index
Structure Name Mainstream Applications Amines
O S N H H N NH 2
Product Code
Product Category
N H
0.8 mmol/g 60-200 m 60
STA4
DP
Tetraamine ethyl sulfide Silica

O S
( N
H
H N
NH 2

O S N H
Organic Scavenger
0.8 mmol/g 60-200 m 60
SPA5
FP
H N
Metal SPE
NH 2
SPE
0.8 mmol/g 35-70 m 60
SPA5d
SPE

O S N H
H N
NH 2 .(2HCl)
Ion Exchange
0.8 mmol/g 60-200 m 60
SPA5Cl
DP
Pentaamine ethyl sulfide amide Silica Chloride

O S
( N
H
H N
Metal Scavenger
NH 2

O S N H N H NH 2
Organic Scavenger Metal Scavenger Organic Scavenger
0.8 mmol/g 60-200 m 90
SPAf
KM
0.8 mmol/g 60-200 m 60
STPA
DP
Bis-Aminopropylamine ethyl sulfide amide Silica
Polyamines such as SPAf are depicted as linear structures, though are likely to consist additionally of branched and cyclic amine components
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Product Index
Structure Name Mainstream Applications Amines
O S N H N
Product Code
Product Category
Supported Base
0.8 mmol/g 60-200 m 60
SDME
DP
N,N-Dimethylethylamine ethyl sulfide amide Silica

O S N H N
Supported Base
0.8 mmol/g 60-200 m 60
SDMP
DP
3-Dimethylamino-1-propylamine ethyl sulfide amide Silica

S O H N NH 2
N H
Metal Scavenger Organic Scavenger Metal Scavenger Organic Scavenger Metal Scavenger Organic Scavenger Metal Scavenger Organic Scavenger
0.8 mmol/g 60-200 m 60
S2TA3
DP
Triamine ethyl sulfide ethyl amide Silica

S O H N
NH
NH 2
0.8 mmol/g 60-200 m 60
S2TA4
DP
Tetraamine ethyl sulfide ethyl amide Silica

S O H N
NH
NH 2
0.8 mmol/g 60-200 m 60
S2PA5
DP
Pentaamine ethyl sulfide ethyl amide Silica

S O H N
NH
NH 2
0.8 mmol/g 60-200 m 90
S2PA10f
DP
Polyamine ethyl sulfide Silica
N H
H N
NH 2
Organic Scavenger
0.7 mmol/g 60-200 m 60
P3N5
DP
Pentamine propyl Silica

O S N H
NH2
Organic Scavenger
0.5-0.7 mmol/g 60-200 m 60
AMB
DP
4- Aminomethyl benzylamidoethyl sulfide ethyl Silica
63
Product Index
Amino Acids & Derivatives

NHAc S O OH
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCYT1
KM

NH2 S O O
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCYE
DP
Ethyl L-Cysteine ethyl Silica

NH2 S O OH
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCY
DP
L-Cysteine ethyl Silica

NHAc S O ONa
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCYTNa
DP
Sodium N-Acetyl-L-cysteine ethyl Silica
Carboxylic Acids, Esters and Carboxylates

O S OH
0.6 mmol/g 60-200 m 60
SCA
DP
Ethanoic acid ethyl sulfide Silica

O S OH
Metal SPE SPE
0.6 mmol/g 35-70 m 60
SCAd
SPE/DP
Ethanoic acid ethyl sulfide Silica

O S O
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCMe
DP
Methyl ethanoate ethyl sulfide Silica
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Product Index
Carboxylic Acids, Esters and Carboxylates

O S ONa
Metal Scavenger
0.6 mmol/g 60-200 m 60
SCR
DP
Sodium ethanoate ethyl sulfide Silica

O S OH OH
0.6 mmol/g 60-200 m 60
STMA
KM

O S OH OH
Metal SPE SPE
0.6 mmol/g 35-70 m 60
STMAd
SPE

O S ONa ONa
Metal Scavenger
0.6 mmol/g 60-200 m 60
STMS
FP
Imidazoles
O S N H N N
Metal Scavenger Supported Base
0.8 mmol/g 60-200 m 60
SIA
DP
Imidazole propyl ethyl sulfide amide Silica
65
Product Index
Metal Phosphonates and Carboxylates

O P
O O
Ti
O O
Acid Catalyst
0.2-0.5 mmol/g 60-200 m 60
POTi
CAT
Diisopropyl titanium ethyl/butyl phosphonate Silica

O P
O O
VO(II)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POVO
CAT
Vanadyl(II) ethyl/butyl phosphonate Silica

O P
O O
Co(II)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POCo
CAT
Cobalt(II) ethyl/butyl phosphonateSilica

O P
O O
Mn(II)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POMn
CAT
Manganese(II) ethyl/butyl phosphonate Silica

O P
O O
Cr(III)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POCr
CAT
Chromium(III) ethyl/butyl phosphonate Silica

O P
O O
Ce(IV)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POCe
CAT
Cerium(IV) ethyl/butyl phosphonate Silica

O P
O O
Ca(II)
Ion Exchange
0.2-0.5 mmol/g 60-200 m 60
POCa
DP
Calcium(II) ethyl/butyl phosphonate Silica

O P
O O
Ca(II) Cl
Ion Exchange
0.2-0.5 mmol/g 60-200 m 60
POMeCa
DP
Calcium(II) methyl ethyl/butyl phosphonate Silica

O P
O O
Cu(II)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POCu
CAT
Copper(II) ethyl/butyl phosphonate Silica

O P
O O
Cu(II)
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 90
POCuf
CAT
Copper(II) ethyl/butyl phosphonate Silica
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Product Index
Metal Phosphonates and Carboxylates

O P
O O
Cu(II)Br
Oxidation Catalyst
0.2-0.5 mmol/g 60-200 m 60
POMeCuBr
DP
Copper(II) bromide methyl ethyl/butyl phosphonate Silica

O S O O O Cu(II)
Oxidation Catalyst
0.4-0.6 mmol/g 60-200 m 60
STMCu
DP
Copper(II) succinate ethyl sulfide Silica

O S O Cu(II)Br
Oxidation Catalyst
0.3-0.5 mmol/g 60-200 m 60
SCRCuBr
DP
Copper(II) bromide ethanoate ethyl sulfide Silica

O P
O O
Ni(II)
Cross-Coupling Catalyst
0.2-0.5 mmol/g 60-200 m 60
PONi
DP
Nickel(II) ethyl/butyl phosphonate Silica

O P
O O
Zn(II)
Lewis Acid Catalyst
0.2-0.5 mmol/g 60-200 m 60
POZn
CAT
Zinc(II) ethyl/butyl phosphonate Silica
67
Product Index
Structure Name
PdCl2PPh3 P O
Mainstream Applications
Product Code
Product Category
Palladium Catalysts
Cross-Coupling Catalyst 0.01-0.03 mmol/g 60-200 m 110
O O
PAPd1r
CAT

PdCl2PPh3 P
O O O

Pd(dba)
0.05-0.14 mmol/g 60-200 m 110 (High Loading)
H-PAPd1r
CAT
O O
P O Pd(dba)
Cross-Coupling Catalyst Dibenzylideneacetone palladium(0) phosphaadamantane ethyl Silica
0.01-0.03 mmol/g 60-200 m 110
PAPd2r
CAT
O O
P O
Cross-Coupling Catalyst Dibenzylideneacetone palladium(0) phosphaadamantane ethyl Silica

O S O Pd(OAc)
H-PAPd2r
CAT
0.1-0.4 mmol/g 60-200 m 60
SCRPd
CAT
Palladium acetate ethanoate ethyl sulfide Silica 0.1-0.4 mmol/g 60-200 m 60
S Pd(OAc)2
SEM2Pd
CAT
Palladium acetate 2-mercaptoethyl ethyl sulfide Silica 0.1-0.4 mmol/g 60-200 m 60
S Pd(OAc)2
SPM3Pd
CAT
Palladium acetate 3-mercaptopropyl ethyl sulfide Silica

PdCl2PPh3
Cross-Coupling Catalyst Triphenylphosphine palladium dichloride dicyclohexylphosphine ethyl Silica
0.015-0.03 mmol/g 60-200 m 60
DCPPd1
CAT
PdCl2PPh3
DCPPd1
CAT
PdCl2PPh3
Triphenylphosphine palladium dichloride dicyclohexylphosphine ethyl Silica
0.015-0.03 mmol/g 60-200 m 110
DCPPd1r
CAT
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Product Index
Structure Name
PdCl2PPh3
Mainstream Applications
Product Code
Product Category
Palladium Catalysts
DCPPd1r
CAT
Pd(dba)
Cross-Coupling Catalyst Dibenzylideneacetone palladium(0) dicyclohexylphosphine ethyl Silica

PdCl2C6H5CN
0.08-0.15 mmol/g 60-200 m 110
DCPPd2r
CAT
Cross-Coupling Catalyst Benzonitrile palladium dichloride dicyclohexylphosphine ethyl Silica
0.10-0.15 mmol/g 60-200 m 60
DCPPd3
CAT
PdCl2CH3CN
Cross-Coupling Catalyst Acetonitrile palladium dichloride dicyclohexylphosphine ethyl Silica
0.15-0.3 mmol/g 60-200 m 60
DCPPd4
CAT
PdCl2PPh3
Cross-Coupling Catalyst Triphenylphosphine palladium dichloride dinorbornylphosphine ethyl Silica
0.01-0.025 mmol/g 60-200 m 60
NPPd1
CAT
PdCl2PPh3
Cross-Coupling Catalyst Triphenylphosphine palladium dichloride dinorbornylphosphine ethyl Silica

Pd(dba)
0.04-0.1 mmol/g 60-200 m 110 (High Loading) 0.07-0.18 mmol/g 60-200 m 110 (High Loading)
NPPd1r
CAT
Cross-Coupling Catalyst Dibenzylideneacetone palladium(0) dinorbornylphosphine ethyl Silica

PdCl2C6H5CN
NPPd2r
CAT
Benzonitrile palladium dichloride dinorbornylphosphine ethyl Silica

PdCl2CH3CN
0.1-0.2 mmol/g 60-200 m 60
NPPd3
CAT
Cross-Coupling Catalyst Acetonitrile palladium dichloride dinorbornylphosphine ethyl Silica
0.15-0.3 mmol/g 60-200 m 60
NPPd4
CAT
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Product Index
Structure Name Mainstream Applications Phosphines
O O P O
Product Code
Product Category
Immobilised Ligand
0.5 mmol/g 60-200 m 110
PAr
CAT
Phosphaadamantane ethyl Silica

P
Immobilised Ligand
0.5 mmol/g 60-200 m 60
DCP
CAT
Dicyclohexylphosphine ethyl Silica

P
Immobilised Ligand
0.5 mmol/g 60-200 m 60
NP
CAT
Dinorbornylphosphine ethyl Silica
Phosphonic Acids and Phosphonates

O P OH OH

O P OH OH
Metal Scavenger Organic Scavenger Acid Catalyst Metal Scavenger Organic Scavenger Acid Catalyst
1 mmol/g 60-200 m 60
POH1
FP
1 mmol/g 300-500 m 150
POH1g
KM

O P OH OH
Metal SPE SPE
1 mmol/g 35-70 m 60
POH1d
SPE

O P ONa ONa
Metal Scavenger
1 mmol/g 60-200 m 60
PO1
FP
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Product Index
Structure Name Mainstream Applications Pyridines
S S N
Product Code
Product Category
Supported Base Organic Scavenger
0.6 mmol/g 60-200 m 60
SPMEP
DP
(2-Pyridylethylsulfide 3-propyl) ethyl sulfide Silica
0.8 mmol/g 60-200 m 60
P3DP
DP
3-(Bis-2-Pyridylethyl)amino propyl Silica

S
N N
Metal Scavenger
0.8 mmol/g 60-200 m 90
PMISf
FP

O S N H N
0.7 mmol/g 60-200 m 60
PMES
DP
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Product Index
Sulfonic Acids
S
Acid Catalyst
SO3H
0.7 mmol/g 60-200 m 60
SPhSA
CAT
Phenyl sulfonic acid ethyl sulfide Silica 0.7 mmol/g >315 m 60
Acid Catalyst
SO3H
SPhSAe
CAT
Phenyl sulfonic acid ethyl sulfide Silica
Thiols and Sulfides

S
Metal Scavenger
SH
Organic Scavenger
0.8 mmol/g 60-200 m 60 (Low Cross-Linking) 0.8 mmol/g 60-200 m 60 (High Cross-Linking) 0.8 mmol/g 60-200 m 90 (High Cross-Linking) 0.8 mmol/g 60-200 m 60 (Low Cross-Linking) 0.8 mmol/g 60-200 m 90 (Low Cross-Linking) 0.8 mmol/g 300-500 m 150 (Low Cross-Linking) 0.8 mmol/g 35-70 m 60 (Low Cross-Linking) 0.8 mmol/g 60-200 m 60 (High Cross-Linking)
SEM22
KM
SH
Metal Scavenger
SEM26
FP
2-Mercaptoethyl ethyl sulfide Silica Metal Scavenger
SH
SEM26f
KM
2-Mercaptoethyl ethyl sulfide Silica Metal Scavenger Organic Scavenger
SH
SPM32
FP
SH
Metal Scavenger
SPM32f
FP
SH
Metal Scavenger
SPM32g
FP

S SH
Metal SPE SPE
SPM32d
SPE
SH
Metal Scavenger
SPM36
FP
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Product Index
Thiols and Sulfides

S SH
Metal Scavenger

S SH
0.8 mmol/g 60-200 m 90 (High Cross-Linking) 0.8 mmol/g 35-70 m 60 (High Cross-Linking) 0.8 mmol/g 60-200 m 60 (Low Cross-Linking) 0.8 mmol/g 60-200 m 60 (High Cross-Linking)
SPM36f
FP
Metal SPE SPE
SPM36d
SPE

S
SH
Metal Scavenger
SBM42
DP
4-Mercaptobutyl ethyl sulfide Silica

S
SH
Metal Scavenger
SBM46
DP
4-Mercaptobutyl ethyl sulfide Silica

S
SH
Metal Scavenger
0.8 mmol/g 60-200 m 60
SHM
DP
6-Mercaptohexyl ethyl sulfide Silica

S O
SH
Metal Scavenger
0.8 mmol/g 60-200 m 60 (Low Cross-Linking) 0.8 mmol/g 60-200 m 60 (High Cross-Linking)
SMEE12
DP
2-(2-Mercaptoethoxy)ethoxyethyl ethyl sulfide Silica

S O
SH
Metal Scavenger
SMEE15
DP
2-(2-Mercaptoethoxy)ethoxyethyl ethyl sulfide Silica

O S O O
SH
Metal Scavenger
0.75 mmol/g 60-200 m 60
SET
KM

O S O O
SH
Metal Scavenger
0.75 mmol/g 300-500 m 150
SETg
DP

O S O O
SH
Metal Scavenger
0.75 mmol/g 60-200 m 90
SETf
DP
73
Product Index
Thiols and Sulfides

O S O O O
SH 3
Metal Scavenger
0.75 mmol/g 60-200 m 60
SPT
DP
Pentaerythritol 2-mercaptopropionate ethyl sulfide Silica 0.8 mmol/g 60-200 m 60
Metal Scavenger
SEM2
DP

S S
Metal Scavenger
0.8 mmol/g 60-200 m 60
SPM3
KM
Thiophenols
O S N H SH
Organic Scavenger
0.3-0.5 mmol/g 60-200 m 60
4MPAE
KM
Thioureas
S S N H N H

N H
0.6 mmol/g 60-200 m 60
MTC
DP

S S N H

S S
Organic Scavenger
0.6 mmol/g 60-200 m 90
MTCf
FP
Metal SPE
N H N H
SPE
0.6 mmol/g 35-70 m 60
MTCd
SPE
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Product Index
By Application
Application Page Acid Catalysts 57-58 Alcohol Oxidation 55-56 Allylic Oxidation 55-56 Amine Scavenging 37,41 Anion Exchange 37,43 API, Scavenging from 17 Benzylic Oxidation 56 Bibliography 76 Biocatalysts 59 Boronic acid Scavenging 38 Buchwald Reactions 17,27 Cartridges, for Process Scale 25-26 Case Studies, Acid Catalysis 58 Case Studies, Metal Scavenging 26-27,30-31 Case Studies, Organic Scavenging 41 Case Studies, SPE 45-46 Catch and Release 42-46 Cation Exchange 37,42-46 Copper Scavengers 18 Chromium Scavengers 19 Cross-coupling Catalysts 49-52 Deprotection 57-58 Electrophile Scavenging 36,41 Epoxidation 55-56 Esterification 57-58 Flow Chemistry 52 Heck Reactions 17,49-50 Heterogeneous Catalysts 47-58 ICP Metal Analysis 7 Immobilised Enzymes 3,59 Immobilised Phosphines 53 Metal Scavenging 9-31 Metal SPE 28 Nucleophile Scavenging 37,41 Organic Scavenging 32-41 Osmium Scavengers 23 Oxidation Catalysts 54-56 Palladium Catalysts 49-52 Application Page Palladium Scavengers 16 Platinum Scavengers 21 Process Scale Scavenging 25-27 Product Formats 6,25,29,40,43 Publications 76 Reaction Procedures, Pd Couplings 52 Reaction Procedures, Oxidations 55 Ruthenium Scavengers 20 Rhodium Scavengers 24 Scavenging Protocols, Metals 12-13,28 Scavenging Protocols, Organics 34 Screening Kits, Metal Scavenging 14-24,29 Screening Kits, Organic Scavenging 35-39 Screening Services 7 Separation of Basic Compounds 46 Solid Phase Extraction (SPE) 40,42-46 SPE Protocols 44 Sonogashira Reactions 17 Strong Cation Exchange (SCX) 42-46 Sulfoxidation 55-56 Supported Bases 63,65,71 Suzuki Reactions 17,50-52 Tin Scavengers 22 Weak Anion Exchange 37,39,40,43
75
Bibliography/Publications
Metal Scavenging Highly functionalised sulfur-based silica scavengers for the efficient removal of palladium species from active pharmaceutical ingredients (APIs) Galaffu, N.; Man, S.; Wilkes, R. D.; Wilson, J. R. H. Org. Process Res. Dev., 2007, 11, 406 Functionalised Silicas: Addressing the Industrial and Environmental Challenges of API Synthesis Wilson, J.; Wilkes, R. Innovations in Pharmaceutical Technology, 2007, Spring edition, 86 Organic Scavenging and Solid Phase Extraction New Functionalised Silicas for Highly Selective Cation Exchange Purification in Medicinal Chemistry Brown, J.; Chighine, A.; Colucci, M. A.; Galaffu, N.; Hirst, S. C.; Seymour, H. M.; Shiers, J. J.; Wilkes, R. D.; Williams, J. G.; Wilson, J. Tetrahedron Lett., 2008, 49, 4968 Heterogeneous Catalysts Palladium Catalysts Palladium ethylthioglycolate modified silica a new heterogeneous catalyst for Suzuki and Heck cross-coupling reactions Al-Hashimi, M.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2007, 273, 298 Dithio palladium modified silicas - New heterogeneous catalysts for Suzuki cross-coupling reactions Al-Hashimi, M.; Qazi, A.; Sullivan, A. C. Wilson, J. R. H. J. Mol. Catal. A: Chem., 2007, 278, 160 Silicaethylphosphatrioxaadamantane a new support for palladium catalysts and evaluation in Suzuki coupling reactions Guino, M.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2008, 293, 25 Oxidation Catalysts Oxidation of alcohols using cerium (IV) alkyl phosphonate modified silica Al-Haq, N.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett., 2003, 44, 769 Allylic and benzylic oxidation using cobalt (II) alkyl phosphonate modified silica Jurado-Gonzalez, M.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett., 2003, 44, 4283 Selective oxidations of allylic alcohols using vanadyl and cobalt (II) alkyl phosphonate modified silicas Jurado-Gonzalez, M.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett., 2004, 45, 4465 Selective oxidations of sulfides to sulfoxides using immobilised cerium alkyl phosphonate Al-Hashimi, M.; Roy, G.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett., 2005, 46, 4365 Selective oxidations of sulfides to sulfoxides using a silica immobilised vanadyl alkyl phosphonate catalyst Al-Hashimi, M.; Fisset, E.; Sullivan, A. C.; Wilson, J. R. H. Tetrahedron Lett., 2006, 47, 8017 Acid Catalysts A new solid acid catalyst : the first phosphonate and phosphonic acid functionalised microporous polysilsesquioxanes Jurado-Gonzalez, M.; Ou, D. L.; Ormsby, B.; Sullivan, A. C.; Wilson, J. R. H. Chem. Commun., 2001, 67 Covalently linked ethylmercaptophenyl sulfonic acid and ethylmercaptobenzyl sulfonic acid silica materials Synthesis and catalytic activity Bugrayev, A.; Al-Haq, N.; Okopie, R. A.; Qazi, A.; Suggate, M.; Sullivan, A. C.; Wilson, J. R. H. J. Mol. Catal. A: Chem., 2008, 280, 96 Flow Chemistry Suzuki Couplings with a Heterogeneous Palladium Catalyst In conjunction with Vapourtec, see www.vapourtec.co.uk Review Articles Solid phase catalysts : Novel functionalised silicas offering new synthetic methods Wilson, J.; Sullivan, A. Speciality Chemicals Magazine, 2006, June edition, 28 Functionalised Silicas: Addressing the Industrial and Environmental Challenges of API Synthesis Wilson, J.; Wilkes, R. Innovations in Pharmaceutical Technology, 2007, Spring edition, 86 Novel Heterogeneous Metal Oxidation Catalysts. Environmentally Friendly Catalysts for Laboratory to Process Scale Applications Wilkes, R. D.; Wilson, J. R. H. Chemistry Today, 2007, 25 (4), 22 Heterogeneous Catalysis Gets Greener Wilkes, R.; Wilson, J. Manufacturing Chemist, 2007, July/August edition, 29 Immobilisation Technology for Green Chemistry Applications Colman, R. Speciality Chemicals Magazine, 2007, July/August edition, 38
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Health and Safety

Health, Safety and Environment Essential HSE information is provided on all of our products. All of our products are supplied together with an appropriate Safety Data Sheet. Regulatory Information PhosphonicS products are produced in compliance with standard regulations governing the production and supply of chemical products. Regulatory Support Files are supplied to support the regulatory process in respect of Pharmaceutical Applications. Enquiries Enquiries regarding the HSE or regulatory status of our products should be made as follows: PhosphonicS Ltd 44c Milton Park Abingdon OXON United Kingdom OX14 4RU Tel: +44 (0) 1235 834466 Fax: +44 (0) 1235 835566 Email: contact@phosphonics.com Warranties and disclaimers PhosphonicS warrants that products shall conform to the description of products as provided by PhosphonicS through this catalogue, analytical data or other literature. This warranty is exclusive and PhosphonicS makes no other warranty, express or implied, including any implied warranty of merchantability or fitness for any other purpose. PhosphonicS warranties made in connection with any sale shall not be effective if PhosphonicS has determined, in it sole discretion, that the Buyer has misused the products in any manner, has failed to use the products in accordance with industry standards and practices, or has failed to use the products in accordance with instructions, if any, furnished by PhosphonicS. PhosphonicS sole and exclusive liability and Buyers exclusive remedy with respect to product proved to PhosphonicS satisfaction to be defective or non-conforming shall be replacement of such products without charge or refund of the purchase price, at PhosphonicS sole discretion, upon the return of such products in accordance with PhosphonicS instructions. PhosphonicS shall not in any event be liable for incidental, consequential, or special damages of any kind resulting from any use or failure of the products, even if PhosphonicS has been advised of the possibility of such damage including, without limitation, liability for loss of use, loss of work in progress, down time, loss of revenue or profits, failure to realise savings, loss of products of Buyer or other use or any liability of Buyer to a third party on account of such loss, or for any labour or other expenses, damage or loss occasioned by such product including personal injury or property damage unless such personal injury or property damage is caused by PhosphonicS gross negligence. All claims must be brought within one (1) year of shipment, regardless of their nature. For more information about PhosphonicS terms and conditions of sale, refer to the section opposite.
77
Ordering Information & Customer Service

To place an order or inquire about an existing order To place an order or kits or bulkexisting about an for samples, inquirebulk orders:orders: order for samples, kits or
Address: PhosphonicS Ltd 44c Milton Park Abingdon OXON OX14 4RU United Kingdom Tel: +44 (0) 1235 834466 Fax: +44 (0) 1235 835566 Email: contact@phosphonics.com To order products you will need to provide us with a minimum amount of information on your company and your application. We normally send a customer registration form to all of our new customers. Once completed this will allow us to set you up as a customer in our systems. Technical Service To discuss product specific questions: Tel: +44 (0) 1235 834466 Email: contact@phosphonics.com Quotation Requests Tel: +44 (0) 1235 834466 Fax: +44 (0) 1235 835566 Email: contact@phosphonics.com or sales@phosphonics.com To Make a Payment (by mail) Address: PhosphonicS Ltd 44c Milton Park Abingdon OXON OX14 4RU United Kingdom Terms & Conditions Products and services are supplied according to PhosphonicS standard terms and conditions of sale. Please apply for a copy by e-mail to contact@phosphonics.com
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Phosphonics Catalogue 2011 Full

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Functionalised Silicas: Scavengers & Catalysts

New Updated 2011

Immobilised Reagents and Catalysts

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Inorganic support key properties readily tunable

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Product Application Map

Heterogeneous Catalysts Palladium Catalysts Oxidation Catalysts

Pages 49, 55, 57

Pages 66, 70, 72

Precious Metal scavenged by a PhosphonicS Metal Scavenger, ready for recovery.

Small SPE Cartridges

Large Process Cartridges

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Digestion Microwave and ICP Spectrophotometer.

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Properties & Benefits

Performance Benefits of PhosphonicS Metal Scavengers

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Rf Db Sg Bh Hs Mt Ds Rg Uub Uut Uuq Uup

Range of Metals Scavenged by PhosphonicS to Date.

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Top Candidate for Metal Screen

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Kit A: General Metal Kit

Triamine ethyl sulfide amide Silica

0.8 mmol/g 60-200 m 60

0.8 mmol/g 60-200 m 60

3-Mercaptopropyl ethyl sulfide Silica

0.8 mmol/g 60-200 m 60

Pentaamine ethyl sulfide amide Silica

0.75 mmol/g 60-200 m 60

Pentaerythritol 2-mercaptoacetate ethyl sulfide Silica

0.6 mmol/g 60-200 m 60

Disodium succinate ethyl sulfide Silica 0.8 mmol/g 60-200 m 60

2-Aminoethyl sulfide ethyl Silica

Disodium ethyl/butyl phosphonate Silica

Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Os, Ir(I), Ir(III), Pt(II)

0.6 mmol/g 60-200 m 90

Methyl thiourea ethyl sulfide ethyl Silica

Kit B: Palladium Kit

Triamine ethyl sulfide amide Silica

0.8 mmol/g 60-200 m 60

0.8 mmol/g 60-200 m 60

3-Mercaptopropyl ethyl sulfide Silica

Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Os, Ir(I), Ir(III), Pt(II)

0.6 mmol/g 60-200 m 90

3-Mercaptopropyl ethyl sulfide Silica 0.8 mmol/g 60-200 m 60

2-Aminoethyl sulfide ethyl Silica

Ru(III), Rh(I), Rh(III), Pd(0), Pd(II), Pt(II)

0.6 mmol/g 60-200 m 60

N-Acetyl-L-cysteine ethyl Silica

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Scavenging of Palladium from APIs

O HO HN O OH O O-Debenzylation Catalyst Pd(OH)2