the catalyst technical handbook

be selective

© 2008 Johnson Matthey Plc

Contents
1 2
2.1
INTRODUCTION
page 3

2.4

Smopex® – Metal Scavengers
2.4.1 2.4.2 General Description Smopex® Application

page 20

CATALYST RANGE

page 4

Heterogeneous Catalysts
Platinum Group Metal (PGM) Catalysts 2.1.1 2.1.2 2.1.3 2.1.4 2.1.5 2.1.6 2.1.7 2.1.8 2.1.9 General Description Liquid Phase Reactions Gas Phase Reactions Choice of Catalyst Support Choice of Metal Choice of Metal Location Catalyst Deactivation Safety and Handling Packaging and Storage

page 4

3

CATALYST SERVICES
3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8

page 21

Saving Time in Process Development Catalyst Kits Chemical Development and Optimization Metal Recovery Evaluation Service Supply of Catalysts Partnership in Catalyst Development/Production Technical Support for Catalytic Processes Refining of Catalyst Residues Smopex® Traditional Refining

2.1.10 Catalyst Recovery and Shipment Base Metal Catalysts 2.1.11 General Description and Applications Sponge Metal™ Catalysts 2.1.12 General Description 2.1.13 Liquid Phase Reactions 2.1.14 Choice of Metal 2.1.15 Choice of Catalyst Particle Size 2.1.16 Catalyst Deactivation 2.1.17 Safety and Handling 2.1.18 Packaging and Storage 2.1.19 Catalyst Recovery and Shipment 4.1.1 4.1.2 4.1.3 4.1.4 4.1.5 3.9

Metal Management

4
4.1

CHEMISTRIES

page 24

Hydrogenation
Carbon-Carbon Multiple Bonds Aromatic Ring Compounds Carbonyl Compounds Nitro and Nitroso Compounds Halonitroaromatics Reductive Alkylation Reductive Aminations Imines Nitriles Hydrogenolysis Debenzylations Hydrodehalogenations Rosenmund Reductions 4.1.12 Transfer Hydrogenations

page 24

2.2

Homogeneous Catalysts
2.2.1 2.2.2 2.2.3 2.2.4 2.2.5 2.2.6 2.2.7 2.2.8 General Description The Catalytic Cycle Choice of Catalyst Product/Catalyst Separation Catalyst Deactivation Safety and Handling Transport and Storage Catalyst Recovery and Shipment

page 15

4.1.6 4.1.7 4.1.8 4.1.9 4.1.11

4.1.10 Oximes

2.3

FibreCat Anchored Homogenous Catalysts
2.3.1 2.3.2 General Description Catalyst Leaching and Recycle

®

4.2
page 18

Dehydrogenation Hydroformylation Carbonylation Decarbonylation

page 41

4.3 4.4 4.5

page 43

page 45

page 46

2

© 2008 Johnson Matthey

2

4.6

Hydrosilylation

page 47

4.12.1 Organic Synthesis 4.12.2 Gas Purification

4.7

Cross-Coupling Reactions page 48
4.7.1 4.7.2 4.7 .3 4.7.4 4.7.5 4.7.6 4.7.7 Heck Reaction Suzuki-Miyaura Coupling Alpha-ketone Arylation Carbon-heteroatom coupling – e.g. Buchwald-Hartwig amination Organometallic Reactions Sonogashira Reaction Palladacycles

4.13 Chiral Catalysis
4.13.1 Asymmetric Hydrogenation 4.13.2 Enantioselective Hydroamination 4.13.3 Enantioselective Alkyne Addition 4.13.4 Asymmetric Michael Addition 4.13.5 CATAXA™ Anchored Catalysts

page 63

5
page 53

TABLE : HETEROGENEOUS CATALYSTS

page 69

4.8

Cyclopropanation and Carbene Reactions Isomerization

6
4.9
page 54

TABLE : HOMOGENEOUS CATALYSTS

page 73

4.10 Oligomerization and

7
page 55

Polymerization
4.11 Selective Oxidation
4.11.1 4.11.2 4.11.3 4.11.4

TABLE : SMOPEX ® METAL SCAVENGING PRODUCTS

page 86

page 56

8 9 10

GLOSSARY OF TERMS

page 87

Alcohols to Carbonyls or Carboxylic Acids Dihydroxylation of Alkenes Oxygen Insertion Reactions Acetoxylation

OTHER PUBLICATIONS

page 88

ADDRESSES OF LOCAL OFFICES

page 89

4.12 Particulate Catalysts

page 59

3

© 2008 Johnson Matthey Plc

3

1. Introduction
Johnson Matthey is a recognized world leader in precious and base metal catalysis. With staff in 38 countries, our extensive network of resources enables us to provide a full range of services and products. These include the development and manufacture of catalysts and chemicals, analytical and characterization techniques, and the recovery and refining of Platinum Group Metals (PGMs) from spent catalysts. We are committed to providing our customers with the best technology for optimizing catalytic processes. In this latest edition of our Catalyst Handbook, you will find our most recent developments in the areas of: • Chiral Catalysis • Coupling Catalysis • Metal Scavenging products – Smopex® • Anchored Homogeneous Catalysts – FibreCat® • Sponge Metal™ Catalysts • Precious Metal Recovery Technology We continue to invest in state-of-the-art equipment for manufacture, testing, recovery and refining of spent catalysts. Our staff offers a high level of technical support, including catalyst recommendations and design, catalyst handling and metal management. The Johnson Matthey name remains synonymous with accuracy, reliability and integrity. Let our catalysis knowledge and experience work for you to improve and optimize your manufacturing processes. The catalysts and technologies described herein are widely used in processes ranging from hydrogenation through carbonylations, coupling reactions and selective oxidations. In general, PGM catalysts combine high activity with milder reaction conditions to give high selectivities for specific transformations. Sponge metal catalysts (Ni, Cu, Co) offer our customers alternative process options, particularly in hydrogenation, reductive alkylation and dehydrogenation. Most importantly, we offer a range of solutions in chiral catalysis, including a unique range of ligands and anchored chiral catalysts.

4

© 2008 Johnson Matthey

4

2. Catalyst Range
2.1
HETEROGENEOUS CATALYSTS

2.1.2 Liquid Phase Reactions with PGM Catalysts
Liquid phase hydrogenations employing heterogeneous catalysts are multiple phase (gas – liquid – solid) systems containing concentration and temperature gradients. In order to obtain a true measure of catalytic performance, heat transfer resistances and mass transfer resistances need to be understood and minimized. Mass transfer effects can alter reaction times, reaction selectivity and product yields. The intrinsic rate of a chemical reaction can be totally obscured when a reaction is mass transport limited. For a reaction to take place in a multi-phase system, the

Johnson Matthey offers a full range of heterogeneous catalysts:• Platinum group metal catalysts (PGM) • Sponge metal (or skeletal) catalysts • Other base metal catalysts

Platinum Group Metal (PGM) Catalysts 2.1.1 General Description
Heterogeneous PGM catalysts are in a different phase to the reactants and can be easily separated at the end of the reaction. Examples are:• catalyst powder (Pd/C) slurried with liquid phase reactants in a batch or continuous process which can be separated by filtration. • catalyst granules – often called particulates – (Pt/Al2O3) as a bed through which reactants pass in the gas or liquid phase.

following steps must occur:(i) dissolution of gas (e.g. H2) into the liquid phase (ii) diffusion of dissolved gaseous reactant through the bulk liquid to the catalyst particle (iii) diffusion of the liquid reactants to the catalyst particle (iv) in-pore diffusion of the reactants to the catalyst surface (v) adsorption of reactants on the catalyst, chemical reaction and desorption of products (vi) diffusion of products from the catalyst pores

The key properties of a catalyst are :High activity: for fast reaction rate, low catalyst loading and a short reaction time to maximize production throughput. High selectivity: to maximize the yield, eliminate byproducts and reduce purification costs. High recycle capability: to minimize process costs. Fast filtration rate: to separate rapidly the catalyst and final product, ensuring maximum production rates.
STAGNANT GAS LAYER Concentration A (g) Concentration B (l) Concentration A (l) GAS

This figure illustrates the three potential mass transfer resistances in a multi-phase catalyst system.

A (gas) + B (liquid)
LIQUID STAGNANT LIQUID LAYERS

Products

A

A B

POROUS CATALYST PARTICLE

{
RESISTANCE TO LIQUID/SOLID MASS TRANSPORT

Heterogeneous catalysts are usually supported on a choice of materials such as activated carbon or alumina to improve metal dispersion, activity and catalyst durability. Supported PGM catalysts are used mainly in hydrogenation, dehydrogenation and selective oxidation reactions. Guidance is provided in Section 4 for the most appropriate catalyst for each specific reaction type. Section 2.1 indicates the most important technical and economic factors that will be of concern to the industrial user of these catalysts.

RESISTANCE TO GAS/LIQUID MASS TRANSPORT

{

Mass Transport
Rates of reaction will be affected by different process variables depending on which step is rate limiting. A reaction controlled by gas–liquid mass transport i.e. rate of mass transport of the gaseous reactant into the liquid, will be influenced mainly by reactor design, hydrogen pressure and agitation rate.

5

{
RESISTANCE TO DIFFUSION IN PORES OF CATALYST PARTICLE

© 2008 Johnson Matthey Plc

5

A reaction controlled by liquid–solid mass transport i.e. the rate of mass transport of either gaseous reactant or substrate from the bulk liquid to the external surface of the catalyst particle, will be influenced mainly by gas or substrate concentration, weight of catalyst in the reactor, agitation and catalyst particle size distribution. A reaction controlled by pore diffusion–chemical reaction i.e. the rate of reactant diffusion and chemical reaction within the catalyst particle, will be influenced mainly by temperature, reactant concentration, percent metal on the support, number and location of active catalytic sites, catalyst particle size distribution and pore structure. To evaluate and rank catalysts in order of intrinsic catalyst activity, it is necessary to operate under conditions where mass transfer is not rate limiting.

are preferred when the presence of water in the reaction system is not detrimental. Handling paste is much easier as it greatly reduces dusting and metal loss. The fire hazard, which occurs when organic vapors are present, is also reduced. When the use of a dry powder is unavoidable, adequate precautions should be taken during handling. (see section 2.1.8.) Ceramic-based catalysts such as those supported on alumina, silica or zeolites, are intrinsically safer and easier to handle because the support is denser than carbon and also is non-combustible. However, different supports may change the catalyst activity. For maximum economy in the use of PGM catalysts, it is important that the catalyst should be filtered from the reaction system without loss. Various types of leaf, cartridge and centrifuge filters are suitable for this operation, often in conjunction with a polishing filter. The recovery and refining of carbon-based catalyst residues is made easier if any filter precoat that may be required is of a combustible material such as cellulose. Many companies supply equipment suitable for filtering catalysts and Johnson Matthey can provide a list of contacts on request. Johnson Matthey also offers Smopex® metal scavenging fibers. (see section 2.4).

Reactors
A reactor used for liquid phase hydrogenations should provide for good gas–liquid and liquid–solid mass transport, heat transport and uniform suspension of the solid catalyst. To facilitate this, a well agitated reactor is essential. The most effective means of agitation at any scale is stirring in a reactor fitted with suitable baffles. Alternatively, the reactant gas stream may be used to agitate the system and this may be particularly effective when combined with a centrifugal or turbo impeller. Another very effective reactor design is the loop reactor. In this system the reactants are recirculated around a loop by means of a pump and the reaction occurs at the injection nozzle in the reactor. There is very effective gas/liquid/solid mixing at this nozzle. Many hydrogenation reactions are exothermic and it is necessary to remove the heat of reaction to maintain a constant reaction temperature. This can be achieved with an internal cooling coil or tubes, a cooling jacket or in the case of a loop reactor, an external heat exchanger. A loop reactor system is particularly suitable for highly exothermic reactions. Continuous liquid phase reactions may be carried out in trickle columns using granular or extrudate catalysts. The reactant, dissolved in a suitable solvent if necessary, is pumped to the column packed with catalyst. The reacting gas, generally hydrogen or oxygen, is passed co-currently or counter-currently through the catalyst bed. The product is collected continuously from the catalyst bed.

2.1.3 Gas Phase Reactions with PGM Catalysts
Granular and pelleted catalysts are used in fixed bed gas phase reactions. The disposition of the catalyst beds, the reactor design and the size and shape of the pellets are dictated by the requirements of the heat transfer, fluid flow and pressure drop in the system. For example, highly exothermic reactions are usually performed in multi-tubular reactors with a coolant fluid surrounding the tubes to remove the heat generated. Today, many industries demand high-purity gases for a wide range of uses. Besides chemical process feedstreams, other applications are in the electronics and nuclear industries. Contaminants, such as oxygen or hydrogen, frequently need to be reduced in order to prevent the occurrence of problems such as:(i) promotion of unwanted side reactions (ii) corrosion (or chemical attack) of reactor materials or components (iii) unwanted modification of semiconductor properties in electronic components. This has led to the development of a range of PGM catalysts on alumina supports for gas purification. These function by promoting catalytic combination of the contaminants within

Catalyst Handling and Recovery
Activated carbon-based powder and paste catalysts are both used for liquid phase reactions but paste catalysts, containing approximately 50–60% water within the pores,

6

© 2008 Johnson Matthey

6

the gas stream. For example, oxygen may be removed by combination with the stoichiometric quantity of hydrogen to form easily-removable water vapor. Section 4.12 provides detailed information on particulate catalysts and their use.

2.1.4 Choice of Catalyst Support for PGM Catalysts
Although the main function of the catalyst support is to extend the surface area of the metal, the selection of the best type of support for a particular catalytic metal is important as, in many reactions, the support can also substantially alter the rate and course of the reaction. The type of physical support is largely determined by the nature of the reaction system. When supported on a high surface area carrier, such as activated carbon, the catalytic metal is present in the form of discrete crystallites (typically a few nanometers diameter) and these give a very high catalyst area per unit weight of metal. For liquid phase reactions, powdered supports are invariably used, while in gas phase or continuous liquid phase reactions, a particulate support is used. The pore structure of the support may modify the role of the metal since the course of a reaction is often greatly influenced by the rates of diffusion of reactants and products within the catalyst pores. In addition, the surface area of a support can limit the PGM concentration that can be usefully employed. Many of the commonly used catalyst supports, particularly carbon and alumina, are available in a large range of particle sizes, each with a range of surface areas and pore size distributions.

Catalyst Charging
Care should be exercised when charging particulate catalysts to fixed bed reactors to minimize physical damage (generation of fines). Note that the catalyst should not fall more than 50–100cm. It should be evenly distributed as the bed is filled and not raked level. One of the best ways to fill a reactor evenly is with a canvas sock connected to an external hopper. The sock should be kept full and lifted slowly so that the catalyst flows out gently. The sock should be moved around the reactor to distribute the catalyst evenly and not left to discharge into a pile in one position. An alternative method is to fill the reactor with water and slowly add the catalyst such that it sinks gently down through the water.

Catalyst Activation
Fixed-bed catalysts are sometimes supplied in the unreduced form. These need to be activated before use in the following manner:(i) Load the catalyst carefully into the reactor and flush away air with flowing nitrogen (or other inert gas) at ambient temperature. (Ensure the volume of nitrogen exceeds 5 x the volume of the reactor) (ii) Introduce hydrogen at a concentration of 1% into the flowing nitrogen. Check for an exotherm in the catalyst bed. If it does not exceed 20˚C, then slowly increase the temperature (over >60 minutes) to the desired reaction temperature. The low hydrogen concentration will prevent a large exotherm when the catalyst species undergoes reduction. (iii) Check for any exotherm and gradually increase the hydrogen concentration until 100% hydrogen. (iv) Slowly introduce the feed to minimize any exotherms until the desired feed rate is achieved. Note: minimum temperatures of 100˚C for Pd, 120˚C for Ru and 200˚C for Pt catalysts are generally required to ensure complete reduction.

Reaction conditions may limit the choice of support. The support should be stable at the temperature used and should not react with the solvent, feedstock or reaction products.

2.1.4.1 Powdered Supports
A good powder catalyst will exhibit high attrition resistance to reduce catalyst losses by fines generation, good suspension characteristics for high catalyst activity and a fast filtration rate to minimize work–up time. These properties are functions of particle size and shape, pore volume, pore size distribution, surface area, activation procedure and material base. Values of these parameters may be optimum for one property but less good for another, e.g. a large catalyst particle size will produce a fast filtration rate but poor suspension characteristics.

7

© 2008 Johnson Matthey Plc

7

Thus, Johnson Matthey catalyst supports are selected to incorporate a compromise of properties to generate catalysts of fast filtration with high activity and selectivity. The following types of powder supports are most commonly used for PGM catalysts:

PGM supported on alumina may prove to be more selective than the same metal supported on carbon. Silica is sometimes used when a support of low absorptive capacity with a neutral, rather than basic or amphoteric character is required. Silica-alumina can be used when an acidic support is needed.

Carbon
Activated carbon powder is principally used as a support for catalysts in liquid phase reactions. As carbon is derived from naturally occurring materials there are many variations, each type having its own particular physical properties and chemical composition. These differences can often be related to how the carbon is activated. The two traditional methods in use are steam and chemical activation of the carbon char. In general, chemical-activated carbons tend to have higher BET surface areas than those of steamactivated carbons. By using different activation methods, the surface areas of different carbons can range from 500 m2g-1 to over 1500 m2g-1. Trace impurities that may be present in certain reaction systems can occasionally poison catalysts. The high absorptive power of carbons used as catalyst supports can enable such impurities to be removed, leading to longer catalyst life and purer products. Carbon catalysts are produced in two physical forms, dry powder or paste. The latter form contains approximately 50–60% by weight of water which is held within the pores of the carbon. There is no supernatant liquid and the ‘paste’ catalyst has the consistency of a friable powder.

Calcium Carbonate
Calcium carbonate is particularly suitable as a support for palladium, especially when a selectively poisoned catalyst is required. The surface area of calcium carbonate is low but it finds applications when a support of low absorption or of a basic nature is required. The carbonates of magnesium, strontium and zinc generally offer no advantage over calcium carbonate.

Barium Sulfate
Barium sulfate is another low surface area catalyst support. This support is a dense material and requires powerful agitation of the reaction system to ensure uniform dispersal of the catalyst. A palladium on barium sulphate catalyst was traditionally used for the conversion of acid chlorides to aldehydes (Rosenmund Reduction) together with an in situ partial poison to improve the selectivity. In this application, however, it is being replaced increasingly by palladium on carbon catalysts for more reproducible results.

2.1.4.2 Particulate Supports
The use of granular or pelleted supports enables catalytic reactions to be carried out continuously in fixed bed reactors. Vapor phase reactions have been carried out in this way, on an industrial scale, for many years. The advantages of this technique have been extended to liquid phase reactions by the use of trickle-column reactors. Since the formation of fine particles by attrition must be kept to the minimum, high mechanical strength is a basic requirement of these catalysts. Such supports are available in various forms, such as spherical or cylindrical pellets, extrudates or irregular shaped granules. The metal may be deposited on or near the surface, or it may be uniformly impregnated throughout the support. For most purposes, the diffusion of reactants into the pellet is slow, so that surface impregnation is generally preferred. The quantity of metal that may be deposited on the surface is dependent on the nature of the support. Catalyst life and performance are often affected by the method of preparation.

Graphite and Carbon Blacks
Graphite powder and carbon blacks have a lower surface area than activated carbon with graphite, generally in the range 5 m2g-1 to 30 m2g-1 (although special high surface area graphites are available in the range 100 m2g-1 to 300 m2g-1). Graphites and carbon blacks are made synthetically and are therefore of higher purity than activated carbons, which are manufactured from naturally-occurring feedstocks. They are used for selective hydrogenation reactions or when a low porosity support is required to minimize mass transfer problems or absorption of high value products.

Alumina and Other Oxides
Activated alumina powder has a lower surface area than most carbons, usually in the range 75 m2g-1 to 350 m2g-1. It is a more easily characterized and less absorptive material than carbon. It is also non-combustible. Alumina is used instead of carbon when excessive loss of expensive reactants or products by absorption must be prevented. When more than one reaction is possible, a

Alumina
The most commonly-used pelleted support, alumina, exists in several phases, but the type usually employed is gamma–alumina. The type and form of the alumina

8

© 2008 Johnson Matthey

8

support may play a vital role in determining the overall course of the reaction, as may certain ions, which may be deliberately added during catalyst manufacture. When a support of high mechanical strength is required, or when a much more inert support is necessary, alpha–alumina with a surface area of less than 10 m2g–1 is available. In some continuous vapor phase processes the catalyst may eventually become deactivated, due to masking of the catalytic sites by the deposition of carbonaceous matter. The catalyst may be regenerated in situ by the controlled oxidation of this carbon, taking care to avoid large exotherms in the catalyst bed.
ENLARGED SECTIONS EGGSHELL INTERMEDIATE UNIFORM SECTION THROUGH CATALYST PARTICLE CATALYST PARTICLE

Carbon
Carbon is usually not strong enough mechanically to withstand the arduous conditions encountered in an industrial gas phase reaction. However, granular carbon is particularly suitable for use as the support in trickle column reactors. Unlike alumina-based catalysts, carbon catalysts cannot be regenerated by a controlled oxidation process. Eggshell shows palladium located on the exterior surface. Intermediate shows palladium located deeper within the pore structure. Uniform shows palladium evenly dispersed throughout the support structure. Catalyst performance is determined mainly by the PGM component. A metal is chosen based both on its ability to complete the desired reaction and its ability not to perform unwanted side reactions. Palladium is the most versatile of the PGMs. It is typically the preferred metal for the hydrogenation of alkynes, alkenes, carbonyls in aromatic aldehydes and ketones, nitro compounds, reductive alkylations, hydrogenolysis and hydrodehalogenation reactions. Platinum is typically the preferred metal for the selective hydrogenation of halonitroaromatics and reductive alkylations. Rhodium is used for the ring hydrogenation of aromatics, while ruthenium is used for the higher pressure hydrogenation of aromatics and aliphatic carbonyl hydrogenation. The use of mixed-metal catalysts may also provide additional benefits in either selectivity and/or activity by a synergistic effect through the presence of both PGM metals. The Effect of Hydrogen Pressure on the Hydrogenation Activity of Catalyst
Uniform Intermediate Eggshell

CATALYTIC METAL PARTICULATES AND SUPPORT PORE STRUCTURE

CARBON METAL ATOMS

2.1.5 Choice of PGM

The catalysts are designed with different metal locations for reactions performed under different conditions of pressure and temperature. Hydrogenation reactions are generally first order with respect to hydrogen. Thus, the reaction rate is directly proportional to hydrogen pressure. With intermediate and uniform catalyst types, an increasing proportion of the metal becomes accessible as the pressure increases. When all the metal is available, the catalyst properties closely parallel those of an eggshell catalyst. Therefore at higher pressures, intermediate and uniform catalysts have a higher activity than eggshell ones because of their intrinsic greater metal dispersion due to metal located

2.1.6 Choice of PGM Location
Catalyst performance can be altered significantly by the appropriate choice of support material, metal location and dispersion within the pore structure of the support. Johnson Matthey has developed techniques to deposit the metal selectively in the desired location and this is illustrated for a 5% palladium on carbon catalyst in the schematic.
ACTIVITY

PRESSURE (PH 2 )

9

© 2008 Johnson Matthey Plc

9

deeper within the support pore structure. Thus, eggshell catalysts would be chosen for high activity at low hydrogen pressure and uniform catalysts at high pressure. The location of catalytic metal deep into the support may lead to large in–pore diffusion resistance to reactants. This will result in increases in residence time and possible changes in selectivity. Thus the variation of the metal location can be used to adjust the selectivity of the catalyst. Eggshell catalysts have high activity at low reaction pressures in systems substantially free from catalyst poisons. If a catalyst poison is present, this can be overcome by locating the catalytic metal deeper into the support structure and hence increasing the metal dispersion. Such a catalyst will exhibit greater poison resistance because:(i) the poison molecules often have high molecular weights and, unlike the smaller reactants, are unable to penetrate the pores where the catalytic metal is located. (ii) the increased metal area counteracts the constant area of metal rendered inactive by the poison. Variation of metal location, metal dispersion, metal loading (0.5–10%), catalyst pH and pore structure of the support has enabled the development of a large range of catalysts which are widely used in numerous liquid–phase and vapor–phase industrial processes.

“coking” on fixed-bed particulate catalysts. Fixed-bed (except carbon supported) catalysts can be reactivated by the controlled combustion of the coke using an inert gas stream and/or steam with a low concentration of air. The combustion exotherm should be controlled not to exceed 20˚C. Powder catalysts can sometimes be reactivated by washing with suitable solvents, treating with oxidizing agents to breakdown the polymeric materials to smaller, more soluble species, and reducing to metal. Sintering occurs when crystallite growth of the catalytic metal decreases the metal surface area. This can arise by thermal sintering, particularly when operating above the Hüttig Temperature (see table below) or by a metal dissolution/re–precipitation mechanism. Thermal sintering can sometimes cause the collapse of the support pore structure e.g. a phase transition from gamma to alpha-alumina resulting in encapsulation of the metal crystallite. Catalyst deactivation by sintering is usually irreversible. Catalyst deactivation by physical loss of metal can arise in several ways. Metal may dissolve in the reaction medium and be stripped from the support. Metal may volatilize in high temperature gas phase reactions. The support material may be attacked and start to dissolve in some liquid-phase reactions and the insoluble catalyst fines pass through the filter system. Excessive movement of fixedbed catalysts due to pressure fluctuations can cause loss of catalyst fines by abrasion. The above forms of catalyst deactivation can be overcome by a more suitable choice of catalyst and/or reaction conditions.

2.1.7 PGM Catalyst Deactivation
There are four main mechanisms for catalyst deactivation, namely poisoning, fouling, sintering and physical loss of metal. Poisoning is caused by the irreversible adsorption of species on the catalyst surface. Such species include heavy metals such as lead, copper and zinc; sulfurcontaining species such as hydrogen sulfide and mercaptans; arsenic; amines and carbon monoxide. In general, it is not possible to remove the poisons by a washing or oxidation procedure (an exception is carbon monoxide). Fouling occurs when the catalyst surface is masked by polymeric materials or tars, and is often referred to as

2.1.8 Safety and Handling of Supported PGM Catalysts
Carbon-supported dry powder catalysts can undergo dust explosions in the same manner as carbon itself – and other carbonaceous powdered materials, such as flour or stearic acid. The problem is minimized by avoiding dust formation during handling operations. Dusting is a bad practice in any case, giving rise to metal losses. As stated earlier, most of the platinum group metal catalysts supported on activated carbon can be used as water-wet pastes, which nevertheless behave as free

Table: The Hüttig Temperature of the Platinum Group Metals Metal Hüttig Temperature (°C) Pd 275 Pt 340 Rh 398 Ru 484 Ir 542 Os 718

10

© 2008 Johnson Matthey

10

flowing powders. Paste catalysts are intrinsically safer and easier to handle and use than their dry powder analogues. Pastes should always be used in preference to powders unless the presence of water is incompatible with the reaction system. The pastes are often more active catalysts than the corresponding powders. Fresh PGM catalysts are essentially non–pyrophoric and can safely be exposed to air (in the absence of organic vapors).

2.1.10 PGM Catalyst Recovery and Shipment
When the catalyst has come to the end of its active life, the spent material can be sent back to Johnson Matthey for recovery of the PGM values. Each batch of residues received is rendered into a form suitable for evaluating the exact metal content. After use, the filtered supported catalyst should be

After use, all catalysts containing absorbed hydrogen may ignite if dried in air, especially in the presence of organic materials. A used, filtered catalyst should therefore be kept water-wet and out of contact with combustible solvents and vapors. PGM catalysts are extremely efficient at catalyzing the oxidation of low flash point organic compounds and can cause spontaneous combustion in the presence of these organic liquids (or their vapors) and oxygen (or air). Care should always be taken when mixing catalysts and organic materials. The risk of spontaneous ignition can be reduced by cooling both the catalyst and the organic material(s) before mixing and performing the mixing operation under a blanket of inert gas, such as nitrogen. It is much safer to add solvent to catalyst than catalyst to solvent.

washed with a suitable solvent, followed by water (to reduce the organics content to a minimum) and returned as damp cake to the bags and drums. These should be sealed and stored away from any combustible vapors. Since many supported catalysts are more pyrophoric after use in hydrogenation reactions due to hydrogen adsorption, they should ideally be filtered under an inert atmosphere. If this is not possible then the filter cake should not be allowed to ‘dry out’ during filtration, such that air is drawn through the cake before it is washed thoroughly with water (to minimize the organics content) and transferred as a damp cake to the drums for storage. Other materials contaminated with PGMs, such as wipes, filter cloths or distillation residues should be returned in a separate marked drum for metal reclamation.

2.1.9 Packaging and Storage of PGM Catalysts
Johnson Matthey catalysts are normally supplied in polyethylene bags (sealed with plastic clips) which are packed in heavy-duty fiberboard drums. If required, steel or plastic drums can be employed. Also, on request, the catalysts can be packaged in pre–weighed quantities for batch-type processing requirements. PGM heterogeneous catalyst samples for laboratory evaluation are available packed in glass or plastic bottles. The catalysts should be stored in their sealed drums to prevent ingress of air and foreign gases until required for use. The drums should be kept in a cool, dry place under reasonable conditions (not exposed to the elements of weather and extremes of temperature – ideally keep between 5 to 30°C). They should not be stored near oils or flammable liquids or exposed to combustible vapors. After use, the empty bags and drums should be retained for return of the spent supported catalyst.

Gas-phase pelleted catalysts can usually be returned without any pretreatment for recovery of metal values. Spent catalyst residues returned to Johnson Matthey are classed as materials for recycling and the transport of these residues is subject to current waste regulations. Johnson Matthey can offer advice about the regulations that apply to different materials, but the classification of any waste material is dependent upon the composition and characteristics of that material and is the responsibility of the originator of the waste. In addition to the regulations governing waste shipments, all movements of catalyst residues must be classified and labeled according to current international transport regulations. Material originating within the European Union should be classified and labelled for supply in accordance with Directive 1999/45/EC (as amended). To ensure safe treatment of the residues, Johnson Matthey requires a Material Safety Data Sheet for each residue returned. Further information and assistance on procedures for the return of residues and on the refining service can be obtained by contacting Johnson Matthey. The refining service is described in Section 3.8.

© 2008 Johnson Matthey Plc

11

Base Metal Catalysts 2.1.11 General Description and Applications PRICAT® Supported Base Metal Catalysts
Johnson Matthey’s PRICAT® products are supported base metal catalysts for applications in the agrochemical, fine chemical, pharmaceutical intermediate and flavor & fragrance markets. These base metal catalysts are utilized in a vast range of reactions. The varying types and applications include copper based catalysts for dehydrogenation in slurry phase or fixed bed, powdered nickel for miscellaneous hydrogenations and alumina powders for dehydration . The main PRICAT® products are kieselguhr and silica supported Ni, Cu and Co catalysts functionalized with dopants. Most of the catalysts in the PRICAT® range come in tablet and powdered form. This allows the products to be applied in slurry phase, trickle bed and fixed bed reactors. The powdered catalysts are easy to handle since they are non-pyrophoric, free flowing and have excellent filtration qualities. The PRICAT® tablets, used in trickle and fixed-bed applications, usually come in the following sizes: 3 x 3 mm 5 x 4 mm 6 x 5 mm 6 x 10 mm

and loading of additives, the selectivity and activity of the catalyst can be further tuned by altering the support, metal depositioning technique, and reduction and passivation method. The table below shows some typical compositions and physical appearances of the main catalysts in the PRICAT® range. The table shows only the most widely used PRICAT® catalysts, and thus does not reflect the full range. Custom catalysts are available on request. Reactions performed by PRICAT®‚ catalysts include: Hydrogenation of sterically-hindered olefins Hydrogenation of phenols Ammonolysis of alcohols Selective hydrogenation of phenol to cyclohexanol Hydrogenation of mono nitro-aromatics to the amine Ring hydrogenation of alkyl-substituted phenols and aromatics Hydrogenation of aldehydes, ketones and aldoses to the corresponding alcohols Reduction of nitriles to primary and secondary amines Selective dehydrogenation of alcohols to the corresponding aldehydes and ketones

All PRICAT® catalysts are reduced and air passivated, allowing for ease of use. In general, activation can be done in situ under mild process conditions and low hydrogen partial pressures. PRICAT® catalysts are doped with cocatalytic metals and other additives in order to enhance performance in specific reactions. In addition to the type

PRICAT Powder Ni 52/35 Ni 55/5 Ni 56/5 Ni 62/15 Ni 60/15 Cu 51/8 Cu 60/35 Co 40/55 x x x x x x x x x x x Tablet x x

Metal % 50 55 55 60 60 51 62 40

Support

Promotors MgO ZrO2 Cr2O3 x Al2O3 MnO

Kieselguhr Kieselguhr Kieselguhr Kieselguhr Kieselguhr Silica Silica Kieselguhr

x x x x x

x x

x x

x x

12

© 2008 Johnson Matthey Plc

Sponge Metal Catalysts 2.1.12 General Description

Sponge Metal Catalyst Handling and Recovery
Typically, Sponge Nickel catalysts are provided as a powder

Sponge Metal

TM

catalysts are used for many of the same

covered in water (a slurry). The slurry contains approximately 58-60% catalyst solids by weight. Catalyst weight can be accurately determined using displacement. Information on this method can be provided on request. Activated Sponge Metal catalyst is shipped as an aqueous slurry, packaged in steel drums. The material is pyrophoric and classified as hazardous. All packaging meets UN performance packaging guidelines for UN 1378. Proprietary Johnson Matthey AMCAT® catalysts are

heterogeneous chemistries as PGM catalysts. The most common type of reaction are three phase, gas-liquid-solid, reactions. Sponge Metal catalysts can be easily separated at the end of the reaction. For slurry phase Sponge Metal catalysts, settling, filtration and decantation are common ways to separate the catalyst. Other methods less commonly used in the industry are centrifugation and magnetic separation. (activated Sponge Nickel are magnetic). Sponge Metal catalysts are prepared from alloys of transition metals and aluminum. The aluminum is leached from the alloy structure, leaving behind an active metal surface covered in adsorbed hydrogen. The activated catalysts are stored under water to protect them from oxidation. Sponge Metal catalysts are in the fully active form when shipped and require no preactivation prior to use. Sponge Metal catalysts are used mainly in hydrogenation, reductive alkylation and dehydrogenation reactions.
TM

catalysts

activated powdered encapsulated catalysts in which water has been displaced by an aliphatic amine. AMCAT catalysts are in the form of solid 1/2 inch (13mm) cubes that are nonpyrophoric. The active catalyst powder is released after charging into the desired feedstock and/or solvent. In some reactions, to gain maximum catalyst efficiency, the catalyst is allowed to settle after reaction and the product is decanted off the top using a dip tube. When this is not appropriate, the entire reaction mixture including product, solvent and catalyst can be fed to a filter or other separation device. If the catalyst will remain in the reactor for re-use, it may also be possible to incorporate filters into the reaction vessel to prevent downstream catalyst carryover. The filtering of Sponge Metal catalysts after use is recommended for maximum economy. Various types of leaf, cartridge, magnetic and centrifugal filters and separators are suitable for this operation. Downstream polishing filters are often used. If the catalyst settling and product decantation steps are efficient, it may be possible to use only a polishing filter.

2.1.13 Sponge Metal Liquid Phase Reactions
The principles which govern the use of Sponge Metal catalysts are very similar to those described in Section 2.1.1 for heterogeneous PGM catalysts.

Considerations in the Industrial Use of Catalyst Reactors
Sponge Nickel catalysts are most often utilized in slurryphase, batch, stirred tank reactors. Reactant, solvent (if present) and catalyst are charged to the vessel, air is replaced with an inert gas and the vessel is put under hydrogen pressure. The mixture is mechanically agitated, then heated to reaction temperature. After reaction, the mixture is cooled, agitation stopped and the catalyst allowed to settle. Product can be removed via diptube. Slurry-phase Sponge Metal catalysts are sometimes used in continuous stirred reactors with continuous catalyst separation and recycle. Continuous stirred reactors are beneficial for very fast reactions (e.g.dinitro and dinitrile reductions) prone to by-product formation.

© 2008 Johnson Matthey Plc

13

Sponge Metal Catalyst Charging
Catalyst can be charged to the reaction vessel by several methods. In the simplest process, the catalyst drum is placed in proximity to the opening of the reactor, the lid is removed and the entire contents are poured into the vessel. Alternately, the slurry is stirred with a shovel or scoop and metered into the vessel. If a drum is overturned into another vessel, it is recommended that a sturdy 2 inch to 4 inch steel grating be placed over the opening to prevent the drum or drum liner from falling into the vessel.

2.1.15 Choice of Sponge Metal Catalyst Particle Size
Sponge Metal catalyst performance can be altered significantly by varying the particle size of the grind. The standard mean particle size for Sponge Metal catalysts is 35 microns, however, other particle sizes are available upon request. Smaller catalyst particle size will, in general, increase catalyst activity but will reduce the ease of catalyst filtration or separation.

2.1.16 Sponge Catalyst Deactivation
Alternatively, the catalyst drum is emptied into an intermediate mechanically-stirred charge tank. The stirred slurry would then be pumped or educted into the reaction vessel in a separate step. Rather than overturning a drum and pouring catalyst from the drum to a vessel, it is also possible to stir the catalyst mechanically in the drum and then pump or educt the slurry into another vessel. There are four main mechanisms for Sponge Metal catalyst deactivation, namely poisoning, fouling, sintering and chemical and physical degradation. Poisoning is caused by the irreversible adsorption of species on the catalyst surface. Such species include heavy metals such as lead, iron or mercury; sulfur containing species such as hydrogen sulfide and mercaptans; arsenic; amines and carbon monoxide. Most poisoning is irreversible, i.e. it is not possible to remove the poisons by washing or other Since activated Sponge Metal catalysts are already provided in the reduced state, no further pre-activation or pre-reduction treatments are necessary prior to the actual reaction step. Sponge Metal active surfaces can be fouled by polymeric materials such as tars or “heavies” . Powder (slurry phase) catalysts can sometimes be reactivated by washing with suitable solvents. The most common primary base metals formulated into Sponge Metal catalysts are nickel, cobalt and copper. Other base metals can be made into Sponge Metal catalyst formulations. Sponge Metal catalysts often contain other base metal promoters. Catalyst deactivation by chemical degradation can occur in Sponge Nickel catalysts, used mainly for hydrogenations, are supplied in both unpromoted and promoted forms. The most common promoters are molybdenum (A-7000 series) and iron and chromium (A-4000 series). Sponge Cobalt™ catalysts find application in selective hydrogenation, e.g. hydrogenation of nitriles to primary amines without the addition of ammonia as selectivity enhancer, or nitro group reduction in the presence of other functional groups such as halide. Sponge Cobalt catalysts can also be unpromoted and promoted. Copper is also incorporated into Sponge Metal catalysts as a primary component. Sponge Copper™ catalysts are more commonly used in dehydrogenation rather than reduction chemistries. two ways. The active metal may dissolve in the reaction medium, or the residual aluminum in the catalyst structure can be leached away to the point where the activity decreases unacceptably. It may also be possible for catalysts to mechanically abrade in high-shear reaction systems. Loss of metallic surface area via sintering is more prevalent in copper catalysts than with nickel catalysts. Catalyst deactivation by sintering is irreversible. treatment. However, catalyst poisoning by carbon monoxide can be reversible.

Sponge Metal Catalyst Activation

2.1.14 Choice of Sponge Metal

14

© 2008 Johnson Matthey Plc

2.1.17 Safety and Handling
Activated Sponge Metal catalysts are all potentially pyrophoric. Fresh catalyst is shipped under a protective layer of water to prevent immediate oxidation by air. In the event of a splash or spill, immediately flush with water to prevent catalyst drying. Dry catalyst can selfheat and serve as an ignition source for other flammable materials. Contaminated cleaning materials should be disposed of in a safe place where they cannot cause a fire. Sponge Metal catalysts contain adsorbed hydrogen on their surfaces. Depending on the history and storage conditions of the catalyst, small amounts of hydrogen can evolve from the catalyst into the drums. Even though the drums are equipped with a self-venting mechanism, care must be taken when opening containers. No ignition sources should be present in areas where drums are stored, handled and opened. After use, all catalysts containing absorbed hydrogen may ignite if dried in air, especially in the presence of organic materials. A used, filtered catalyst should therefore be kept water-wet and out of contact with combustible solvents and vapors. Please refer to the Material Safety Data Sheet for detailed up-to-date information about hazards and safe handling recommendations.

2.1.19 Catalyst Recovery and Shipment
When the catalyst has come to the end of its active life, Johnson Matthey offers services for reclamation of metal value. Each batch of residues received is rendered into a form suitable for evaluating the exact metal content. After use, the filtered supported catalyst should be washed with a suitable solvent, followed by water to reduce organics content to a minimum. Spent catalysts should be sealed and stored away from any combustible vapors. Many supported catalysts are more pyrophoric after use in a hydrogenation reaction due to hydrogen absorption. Catalyst filtration should be done under an inert atmosphere and the filter cake should not be allowed to ‘dry out’. The filter cake should be washed thoroughly with water. Other materials contaminated with base metals, such as wipes, filter cloths, distillation residues etc., should be returned in a separate marked drum for metal reclamation. Spent catalyst residues returned to Johnson Matthey are classed as materials for recycling and the transport of these residues is subject to current waste regulations. Johnson Matthey can offer advice about the regulations that apply to different materials, but the classification of any waste material is dependent upon the composition and characteristics of that material and is the responsibility of the originator of the waste.

2.1.18 Packaging and Storage
In addition to the regulations governing waste shipments, Sponge Metal catalysts are typically supplied in open-head steel drums. For high-purity requirements, custom drums are available with a polyethylene insert. To accommodate customers’ particular processes, the catalyst is available in a variety of drum sizes, from 3-gallon (11 litre) to 55-gallon (208 litre). Also, on request, catalysts can be packaged in pre–weighed quantities to match batch size requirements. Sponge Metal heterogeneous catalyst samples for laboratory evaluation are available packed in plastic bottles. Catalyst should always be stored in sealed containers to prevent ingress of air and foreign gases until required for use. Drums should be kept in a cool, dry place under reasonable conditions (not exposed to the elements of weather and extremes of temperature – (ideally keep between 5 to 30°C). Drums should not be stored near oils or flammable liquids or exposed to combustible vapors due to the risk of fire. After use, empty drums can often be retained for shipment of spent catalyst. Further information and assistance on the procedures for the return of residues and on the refining service offered can be obtained by contacting your local Johnson Matthey office. (see section 10). To ensure safe treatment of the residues and to meet European Health and Safety legislation Johnson Matthey requires a Material Safety Data Sheet for each residue returned. all movements of catalyst residues must be classified and labeled according to current international transport regulations. Material originating within the European Union must also be classified and labeled for supply in accordance with Directive 1999/45/EC.

© 2008 Johnson Matthey Plc

15

2.2

HOMOGENEOUS CATALYSTS

For example, a reaction with reagent 1 (R1) reacting with reagent 2 (R2) in the presence of a catalyst (M) to form product (P), where P=R1R2, could be written as

2.2.1 General Description
A homogeneously-catalyzed reaction contains the catalyst in the same phase as the reactants. Almost invariably the catalyst is dissolved in a liquid phase. Homogeneous catalysis is an area of increasing importance within the chemical industry both for the manufacture of large-scale industrial chemicals and complex fine chemicals. Examples of large-scale applications are:• acetic acid manufacture by methanol carbonylation using a rhodium complex and the more advanced technology using an iridium catalyst. • butyraldehyde and plasticizer alcohol (2–ethylhexanol) production by the hydroformylation of propylene using a rhodium catalyst. For PGM-catalyzed reactions, the advantages of a homogeneous system over a heterogeneous process are:(i) better utilization of metal – all of the catalytic metal is equally available to the reactants and hence a lower catalyst loading is required. (ii) exploitation of different metal oxidation states and ligands – offering a wide range of activity and, in particular, selectivity in a complex molecule. (iii) elimination of in–pore diffusion allowing kinetic rather than mass transfer control of reaction rates – ease of process scale–up. (iv) easy exotherm removal – no localized overheating and hence long catalyst lifetime.

R1 + R2

[M] → P

The following scheme describes the catalytic cycle

The reaction intermediates involved in the catalytic cycle may or may not be capable of being isolated. The catalyst [M] is a metal atom with various chemical species bonded to it. These are called ligands. If the coordination number of the central metal atom is maintained during the catalytic cycle, it may be necessary for ligands to become detached during the course of the reaction. This is called ligand dissociation. In this example, the central metal atom has two ligands (L) which dissociate and then reattach later on in the catalytic cycle:
P [ML2 ] R
1

2.2.2 The Catalytic Cycle
For materials to act in a catalytic, as opposed to a stoichiometric mode, the catalyst must be recycled whilst reactants are continuously forming product(s).
[R MR ]
2 1

L L [LMR ]
1

R

2

16

© 2008 Johnson Matthey Plc

The ligands (L) may be the same, or different, and could include the solvent in which the reaction is being performed. In such cases, the solvent forms part of the catalyst cycle and hence choice of solvent can be crucial in homogeneous catalysis. Platinum Group Metals and all transition metals can form such intermediates in which the nominal oxidation state and coordination number can be systematically varied. Transition metals have partially filled d–electron shells which can form hybridized bonding orbitals between the central metal atom and the ligand. Suitable ligands are those capable of forming bonds with σ – and π – character such as carbonyls, alkenes and organophosphines. These ligands play a crucial role in homogeneous catalytic chemistry. Much academic research has focused on the interaction of transition metal complexes with organic molecules. Many spectroscopic techniques have been used to identify the transient catalytic intermediates. Precise knowledge of the intermediates and mechanisms involved can often help process optimization. In some cases it has been possible to construct molecular models of reaction intermediates whose conformation will lead to the formation of one particular product. This is particularly applicable to the synthesis of enantiomericallypure isomers.

For example, compounds such as Rh4(CO)12, Rh6(CO)16, Rh2Cl2(CO)4, Ru3(CO)12 and RuCl2(CO)6 are not readily available in bulk quantities. In industry, stainless steel reactors are commonplace, so the addition of halide, even at ppm levels, can sometimes cause plant corrosion. Hence, halide free catalysts or precursors might well be preferred in practice even though the catalytic performance of the halide containing and non–halide containing materials may be identical, e.g. • Pd(acac)2, Pd-70 or [Pd(OAc)2]3, Pd-111 rather than palladium chloride solution • RhH(CO)(PPh3)3, Rh-42 rather than RhCl(CO)(PPh3)2, Rh-40 • Ruthenium nitrosyl nitrate solution rather than ruthenium chloride solution Although a specific reaction may be catalyzed by one particular compound, it is often more convenient to use a precursor and produce the actual catalyst in situ. Johnson Matthey can offer specific advice in reagent choice based on extensive experience in catalyst selection.

Precursor

Catalyst

Reason for using precursor rather than catalyst
Pd-101 is heat, light & air sensitive

Pd-111, [Pd(OAc)2]3 + PPh3

Pd-101, Pd(PPh3)4

The homogeneous catalyst (or its precursor) is supplied as a chemical compound whose characteristics, i.e. purity, can be readily determined and controlled. It is dissolved in the reaction medium, hence its original physical form is less important than that of a heterogeneous catalyst.

or Pd-92, Pd(dba)x + PPh3

RhI3

[Rh(CO)2I2]-

catalyst not readily available

RuCl3xH2O + oxidant

RuO4

RuO4 not commercially available dba = dibenzylideneacetone

2.2.3 Choice of Catalyst
Many factors affect the selection of a particular homogeneous catalyst (or precursor). Reactions reported in the chemical literature will not necessarily have been optimized with respect to reagent choice or operating conditions. Reagents will have been chosen because they were readily available to the researcher and not because they were most suitable, e.g. • use of argon instead of oxygen-free nitrogen • use of PGM catalysts or precursors which do not lend themselves to economic scale-up • use of expensive reagents when cheaper ones would be just as effective

PPh3 = triphenylphosphine;

OAc = acetate ;

For a complete list of homogenous catalysts mentioned in this handbook, see Section 6.

© 2008 Johnson Matthey Plc

17

2.2.4 Product/Catalyst Separation
A key consideration for homogeneous catalyst users is product/catalyst separation with subsequent product work–up and catalyst recycling. All common separation techniques have been employed in full-scale commercial operations as well as on the laboratory scale. These include :(i) product distillation, usually under reduced pressure (ii) liquid-liquid solvent extraction, particularly in applications where the spent catalyst is rendered soluble in water. (iii) crystallization of the product by addition of a precipitating solvent, such as diethyl ether, or a hydrocarbon, such as hexane. (iv) flash chromatography on neutral alumina or silica gel, using various solvents including acetone, hexane, ethyl acetate and mixtures of these. The spent catalyst is retained on the column while the desired product passes through. (v) catalyst adsorption followed by removal by filtration.

Poisoning is where the catalyst reacts irreversibly with an impurity e.g. the presence of carbon oxysulfide in carbon monoxide will eventually deactivate the catalyst. Cluster formation can occur when there is insufficient ligand present to stabilize the catalyst, particularly when in a low oxidation state. Eventually the catalyst activity will decline, but if the reason for this is known, it may be possible to reactivate in situ. In other cases this will not be possible. In extreme cases of cluster formation the catalyst may be precipitated. Also, when operating at high temperatures (above 100˚C) the catalyst may become unstable and decompose, resulting in precipitation. The fourth mechanism for deactivation is due to changes occurring to the ligand e.g. exposure of the catalyst to air, oxidizing triphenylphosphine (TPP) ligands to triphenyl phosphine oxide (TPPO).

2.2.6 Safety and Handling
Johnson Matthey has always been concerned to ensure that those products which are intrinsically hazardous are provided with sufficient information to permit safe handling and usage. Users should note that there is an obligation upon

(vi) selective precipitation of the catalyst and removal from the reaction medium by filtration. The desired product is then further purified by vacuum distillation or recrystallization. In addition to the separation techniques listed above, Johnson Matthey offers Smopex©, a unique metal scavenging system where metal binding functionality has been grafted onto fibers allowing the effective recovery of a range of precious metals. For more information on Smopex© see section 2.4.

everyone involved in the use and handling of these materials to acquaint themselves with the potential hazards involved. Johnson Matthey will be pleased to offer specific advice as necessary. Some of the compounds listed in this handbook have only been prepared on a relatively small scale for research purposes, and a complete investigation of their chemical, physical and toxicological properties has not been made.

2.2.7 Transport and Storage
Johnson Matthey will dispatch these compounds in a manner which conforms to all transport regulations. Steps will be taken to ensure their secure transportation. Each batch of product is accurately sampled and analyzed to ensure batch to batch consistency. Johnson Matthey can dispatch material in pre–packed lots – either a fixed weight of compound or PGM per package. This can be done for both solid and liquid products. The materials should be kept in their original containers, protected from extremes of temperature until just before use. The containers should be resealed after dispensing.

To be reused, a catalyst has to be rendered soluble again, so further processing is essential. Such systems can be quite complex, but the chemical transformations that are made possible with homogeneous catalysis may justify this extra processing. In some cases, the PGM homogeneous catalyst is so active that there is no economic need to recover the metal values due to the very low catalyst loading.

2.2.5 Catalyst Deactivation
All catalysts will eventually deactivate. There are four main mechanisms for deactivation namely: poisoning, cluster formation, precipitation and changes to the ligands.
18

© 2008 Johnson Matthey Plc

2.2.8 Catalyst Recovery and Shipment
When the catalyst has come to the end of its active life, the spent material can be sent back to Johnson Matthey for recovery of the platinum group metal values. It is in the catalyst user’s interest to concentrate any catalyst containing liquors as much as possible before shipment, thereby:• reducing freight charges • reducing residue treatment charges However, in some instances, material can be more dilute and processed in AquaCat®. (see section.3.8). Spent catalyst materials returned to Johnson Matthey are classed as materials for recycling and the transport of these residues is subject to current waste regulations. Spent homogeneous catalyst residues typically contain over 50% organic compounds. Johnson Matthey has considerable experience in handling these types of materials. It is advisable that Johnson Matthey is consulted at the earliest possible opportunity to ensure that the material can be transported with a minimum of delay. In addition to the regulations governing waste shipments, all movements of catalyst residues must be classified and labeled according to current transport regulations. Material originating within the European Union must also be classified and labeled for supply in accordance with Directive 93/21/EEC (as amended).

lengths, (0.3mm) is standard) giving materials with different physical characteristics suited to a variety of reactor and filter combinations. For all fiber lengths, recovery and recycle of the fiber-supported catalyst after reaction is readily achieved. Anchoring of the active polymer chain to an inert polymer support ensures excellent accessibility of the catalytic sites. This allows easy diffusion of the starting materials and products to and from the catalytic sites, in contrast to conventional polystyrene bead technology where slow diffusion can often reduce the reaction rate. Additionally, the polyethylene fiber is extremely robust and is not degraded by stirring, again in contrast to polystyrene beads. Johnson Matthey has tested these catalysts in a number of representative cross-coupling, hydrogenation, oxidation and hydrosilylation reactions There are currently 4 series of FibreCat® catalysts grouped according to the reactions they are used in: 1000 series: 2000 series: 3000 series: 4000 series: Cross-coupling reactions Hydrogenation reactions Oxidation reactions Hydrosilylation reactions

The full list of products is shown in Section 6.

Comparison of FibreCat® Catalysts with Homogeneous Catalysts: 1000 series – Cross-coupling reactions Suzuki Reaction

To ensure safe treatment of the residues and to meet local regulations, Johnson Matthey requires a Material Safety Data Sheet for each residue returned. The refining service is described in Section 3.8. Suzuki (or Suzuki-Miyaura) reactions involve the coupling of organoboron compounds with aryl, alkenyl and alkynyl halides or triflates. This reaction is a very useful and generally high yielding method for cross-coupling of aromatic and heterocyclic aromatics.

2.3 F IBRE C AT ®
2.3.1 General Description1
FibreCat® is a new range of polymer-anchored homogeneous catalysts offering the selectivity benefits of homogeneous catalysts with the filtration/ separation benefits of heterogeneous catalysts. The active metal species are covalently bound to a polymer chain. This active polymer is further linked to an inert polyolefin fiber, which is insoluble in all common organic solvents. The fiber can be prepared in a variety of

O Br + B(OH) 2 Catalyst, toluene

O K 2 CO 3 (2 equivalents), N 2 , 70C, 2h

FibreCat® technology offers a more active catalyst than the homogeneous equivalent.

FibreCat® 1001 Pd: 4-bromoacetophenone molar ratio % Yield 1 : 120

[Pd(OAc)2]3 + 12 PPh3 1 : 100

99.9

76.5

1 S Collard et al, Catalysis of Organic Reactions (proceedings of 19th ORCS conference) 2002, 49-60 19

© 2008 Johnson Matthey Plc

2000 series - Hydrogenation Reactions
The hydrogenation of carbon-carbon double bonds using organometallic complexes of rhodium is widely used in organic synthesis. By anchoring coordination complexes to polymer supports, it should be feasible to combine the high selectivity and mild reaction conditions of the analogous homogeneous system with the ease of separation and recyclability of heterogeneous catalysts. The fiber supports can also exert an influence on the selectivity and activity of the catalyst. In the selective hydrogenation of geraniol to citronellol1 and the selective hydrogenation of carvone to 7 ,8dihydrocarvone2, Rh FibreCat® catalysts exhibit similar selectivities to their homogeneous counterparts.

2.

Oxidation of alcohols to aldehydes FibreCat® catalyst can selectively oxidize alcohols to aldehydes without over-oxidation to carboxylic acid. For example, FibreCat® 3002 gives 70% conversion of benzyl alcohol to benzaldehyde with no over-oxidation to benzoic acid:
OH 10 mol% Ru as FibreCat 3002 Toluene 3 bar 60 C, 6 hours O

4000 series - Hydrosilylation Reactions
Platinum complexes are commonly used in hydrosilylation reactions as the exceptional activity of the catalyst allows the Pt to be used at very low levels. There can be issues, though, with Pt being left in the product. This often needs to be removed, depending on the end application. These issues are overcome by using a supported homogeneous catalyst.

OH 1

OH

O

O

In the reaction of trichlorosilane with tetradecene, the
2

FibreCat® catalyst gives 85% conversion to product and a colorless product, indicating that there is no Pt in the product.

The hydrogenation of the least hindered double bond in these substrates is faster with homogeneous and FibreCat® systems than other double bonds in the molecule meaning that the selective hydrogenation can be achieved.
SiCl C12 H 25 + Cl 3 SiH C12 H 25

3000 series - Oxidation Reactions
1. The catalytic cis-dihydroxylation of olefins has traditionally been achieved with the use of osmium complexes such as OsO4 and K2OsO2(OH)4. The use of homogeneous OsO4 is limited due to the hazards associated with its volatility and toxicity. FibreCat lowers the volitility of the OsO4. In the cis-dihydroxylation of 1,2-cyclooctene to cis-1,2cyclooctane diol, FibreCat® 3003 gives 85% conversion to product and <5ppm Os metal is leached into solution.
OH 0.1mol% Os-FibreCat 3:1t BuOH/H 2O 1.3 equiv amine-N-oxide 60C, 24 hours OH
®

2.3.2 Catalyst Leaching and Recycle
Covalent linking of the metal catalyst to the polymer support ensures that there is only very low leaching of metal into solution during the course of the reaction. As an example, analysis of the reaction liquor from the Suzuki coupling of 4–bromoanisole with phenyl boronic acid indicated that only ca 0.2% of the palladium was lost to solution (less than 1 ppm palladium in solution). Furthermore, the sample of catalyst recovered was reused numerous times in this reaction and remained active throughout. The minimal leaching of the metal into the reaction product is particularly relevant when manufacturing pharmaceutical intermediates.

20

© 2008 Johnson Matthey Plc

2.4 SMOPEX®
2.4.1 General Description
Smopex® is a new metal scavenging system for the recovery of low levels of precious metals (PM) from catalytic processes. Metal binding properties are introduced into thin polyolefin base fibers allowing fast metal recovery at high metal loadings giving vast improvements in process economics. Smopex® fibers have a unique advantage over traditional polymer beads in that the active groups are almost exclusively located on the surface of the fiber. This allows for the efficient recovery of PMs from a wide range of process solutions, and offers users the opportunity to overcome many of the issues associated with existing recovery techniques. The fibers are robust and do not degrade while stirring, In addition, they are insoluble in a wide range of commonly used solvents and are able to be used in both aqueous and organic media. The main benefits of Smopex include: • Smopex® selectively removes ionic and non-ionic precious metal complexes from both aqueous and organic solutions • Smopex® can be used as a filter aid to remove colloidal precious metal particles from process liquors • Smopex® can remove metal from both homogeneously and heterogeneously catalysed reactions • Liquors containing low levels of PMs may not be • The Smopex® system offers benefits including fast reaction kinetics and high precious metal loading on the fiber • The diffusion rate of the metal species to the active groups is often slow in alternative products • Smopex® fibres can be used to remove metal from the product stream. • Smopex® fibres can recover metal down to ppb levels, for discharge to effluent. See section 7 for a listing of the available Smopex® products. • Material composition confidentiality retention In these instances, Smopex® can be used at customer sites to remove the metal before shipment, making the shipment possible, non-hazardous, and cost effective. cost effective to transport and treat • Hazardous materials under shipment legislation The transportation of certain precious metal containing process material can be restricted, or simply not possible, for a number of reasons: For application in the Pharmaceutical and Fine Chemical sector, Smopex® has been filed with the US Food and Drug Administration (FDA) in order that it can be used in pharmaceutical applications for the removal of metal from the product stream containing the Active Pharmaceutical Ingredient (API). In addition, Johnson Matthey has further DMF numbers filed with the US FDA. Smopex-111, a thiol functionalised fiber, can now be used within the product stream containing the Active Pharmaceutical Ingredient (API). The DMF number is 18099.

2.4.2 Smopex® Application
Precious metal (PM) catalysts have a wide range of applications in fine and bulk chemical manufacturing processes and provide clean and efficient routes to products in very high yields. The recovery of these PMs from process solutions is essential for improving process economics and enabling product purification. For their recovery, traditional techniques such as distillation and precipitation are being superseded by more sophisticated techniques, from solvent extraction to ion- or ligandexchange. In addition, environmental considerations almost always dictate low levels of PMs in effluent discharge, which makes Smopex the perfect recovery solution.

© 2008 Johnson Matthey Plc

21

3. Catalyst Services – how we work with you
Johnson Matthey offers much more than the supply of a range of catalysts. Johnson Matthey looks to support customers from the start of the development of a new process or route, through its scale-up and on for the full production life of the process. We support the supply of catalyst with a complete management system for precious metal, including the refining of catalyst residues. We provide a comprehensive, cost-effective and timeefficient package for all aspects of the development, implementation and execution of catalytic processes. These services are described below. For details of any of these services, please contact your local Johnson Matthey office. (section 10).

3.2 CATALYST KITS
Catalyst kits are available for a variety of research, development and screening applications. Johnson Matthey offers the following kits: Cross Coupling Asymmetric Hydrogenation Heterogeneous PGM Catalysts – 40 samples FibreCat® – Anchored homogeneous catalysts Smopex® – PGM metal scavengers Selective Oxidation Hydrogenation

3.3 CHEMICAL DEVELOPMENT
AND OPTIMIZATION
Johnson Matthey has developed high throughput screening equipment and techniques, which are available for evaluating catalyst systems for customer reactions. These techniques can be used to identify suitable catalyst systems, and larger scale equipment is available to optimize the systems once identified. This work is done with customer–supplied feedstock to ensure that the catalyst system is the best for the profile of the material with which it will be used. This high throughput screening equipment is suitable for all reactive gas chemistries, as well as reactions under an inert atmosphere.

3.1 SAVING TIME IN
PROCESS DEVELOPMENT
When alternative process routes are being identified and evaluated, Johnson Matthey can provide advice as to which catalyst types and reaction conditions are most likely to give the desired activity and selectivity. Section 4 of this Handbook and the Catalytic Reaction Guide can be used to identify the catalyst systems suggested for particular transformations. For specific reactions, a full catalyst recommendation can be provided by Johnson Matthey chemists, giving suitable catalysts, solvents, additives and process conditions. A catalyst recommendation from Johnson Matthey is the quickest route to a process with the desired activity and selectivity. Time and effort may also be saved later in the process as Johnson Matthey can at this stage advise on process issues such as catalyst recovery, or the selection of catalysts that are easy to handle at plant scale. A list of standard catalysts is given in sections 5 and 6. Many catalysts have been developed through in-house programs for specific reactions and Johnson Matthey is also able to formulate catalysts optimized for individual reaction conditions. Samples of catalysts are available to customers. By working with us, you will ensure that the same catalysts that are used in the laboratory are available for use in the plant.

All development work for customers at Johnson Matthey is conducted within a framework ensuring total confidentiality and the customer’s freedom to operate the process.

3.4 METAL RECOVERY
EVALUATION SERVICE
A key element of the efficiency of metal–catalyzed processes is the recovery of the metal from the process and the refining of the process residues. Johnson Matthey has developed methods for recovering metal in different forms from process streams. When a process is in development, Johnson Matthey will evaluate the recovery of the metal from the process and identify a refining route for the residues. This ensures that the process that is put into production is as clean, efficient and cost–effective as possible.

22

© 2008 Johnson Matthey Plc

3.5 SUPPLY OF JOHNSON
MATTHEY CATALYSTS
By working with Johnson Matthey as the process is developed, you will ensure that your chosen catalyst is available at scale to use in your process. Any catalyst supplied as a sample can be supplied at pilot and then at full production scale, to the same exacting standards.

3.8 REFINING OF PGM CATALYST
RESIDUES
As the largest refiner of secondary (i.e. recycled) platinum group metal materials in the world, Johnson Matthey is ideally placed to ensure the efficient recovery of the metal values in your residues. Traditionally, the recovery of metal has been through

All catalysts or catalyst precursors from Johnson Matthey are supplied with full quality and health and safety documentation. All can be packed to individual customer requirements. Our export department can arrange for the delivery of catalyst across the world.

incineration. (see Traditional Refining). Johnson Matthey has now introduced novel technologies for the recovery of precious metals. These are detailed below:

Smopex®
Smopex® is a unique metal ‘scavenging’ system where chemical groups are attached to fibers, which are then used to attract the required metal. These functionalized fibers can be placed directly into the

3.6 PARTNERSHIP IN CATALYST
DEVELOPMENT AND PRODUCTION
In addition to producing a range of catalysts developed in our own laboratories, Johnson Matthey can manufacture catalysts to customers’ chemical and physical specifications. Johnson Matthey works with customers to ensure that, from first samples to full plant production, the catalyst meets the customers’ performance requirements. The customer benefits from Johnson Matthey’s experience in the development, scale–up and manufacture of catalysts. Johnson Matthey will develop catalysts and manufacturing methods with customers for supply into their own processes, or with partners for supply to a third party.

process stream to remove the metal via an ion exchange process. Once recovery is complete, the Smopex® (with the metal attached to it) can simply be filtered off leaving a pure process liquor behind. Smopex fibers are easy to handle and filter. They can remove metal from both homogeneously and heterogeneously catalyzed reactions, and selectively remove ionic and non-ionic precious metal complexes from both aqueous and organic solutions. The use of Smopex® allows recovery from liquors containing low levels of precious metal even down to parts per billion (ppb) levels.

3.7 TECHNICAL SUPPORT FOR
CATALYTIC PROCESSES
Johnson Matthey technical support continues when the process is in production. Full technical advice is available, supported by analytical services. This service can be used to enhance the performance of catalytic processes. If, for example, a catalyst is being poisoned in a process, Johnson Matthey can work to identify the mechanism of deactivation by characterizing the poisoned catalyst and investigating potential solutions. Shipping: The ways in which the residues of different types of catalyst should be returned are

Traditional Refining
Quotation: From the composition of your residues, Johnson Matthey can identify the best route for the residues in the refinery and quote in advance for all costs.

© 2008 Johnson Matthey Plc

23

24

© 2008 Johnson Matthey Plc

4. Chemistries
4.1
HYDROGENATION
substituted double bonds. Asymmetric hydrogenations are possible using chiral ligands. (see section 4.13.1). Alkynes can be readily hydrogenated to alkenes or alkanes under mild conditions using Pt or Pd supported catalysts. Typical operating conditions are temperatures of 20 –100˚C and hydrogen pressures of 1–10 bar. Palladium is the most selective metal for the conversion The ease of hydrogenation decreases with increasing substitution at the double bond. In molecules containing more than one double bond, the least hindered will be hydrogenated preferentially, and exocyclic double bonds more easily hydrogenated than endocyclic double bonds. A complication in the hydrogenation of alkenes can be double bond migration and cis–trans isomerisation. The tendency of the PGMs to promote these reactions is generally in the order Pd > Rh > Ru > Pt = Ir Hence platinum catalysts are useful when double bond migration is to be avoided. Homogeneous (Rh and Ir) catalysts are particularly useful for selective alkene hydrogenations. For example in the rhodium-catalyzed hydrogenation of carvone to dihydrocarvone: of alkynes to alkenes without further hydrogenation to the corresponding alkane. Modifiers such as amines or sulfur-containing compounds can be added to the reaction system to improve the selectivity to the alkene. Alternatively, Pd catalysts can be modified with a second metal such as Pb, Cu or Zn. The best known and most widely used catalyst of this type is Lindlar’s catalyst which is a mixed Pd/Pb catalyst on a calcium carbonate support. Selectivity to the alkene can also be improved by limiting the hydrogen availability.

4.1.1 Carbon–Carbon multiple bonds
Alkynes and alkenes are readily hydrogenated to alkanes over supported catalysts with the following general order of activity Pd > Rh > Pt >> Ru

O Br + B(OH) 2

Neither the carbon–carbon double bond in the ring nor the ketone function is hydrogenated. Similarly, in the manufacture of the pharmaceutical Ivermectin, only one of several carbon-carbon double bonds is hydrogenated in the presence of Wilkinson’s catalyst, Rh-100 RhCl(PPh3)3. Rh-100 is normally selective for the least substituted double bond. Arene, carboxylic acid, ester, amide, nitrile, ether, chloro, hydroxy, nitro and sulfur groups are all tolerated. Catalysts such as Ir-90 [Ir(COD)(py)PCy3]PF6, Ir-93 [IrCl(COD)]2, Rh-93 [RhCl(COD)]2 or Rh-97 [Rh(nbd)2]BF4 are used for hydrogenating highly
24

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)
50–100

Pressure (bar)
1–10

Solvent

Catalyst

-C≡C- → -CH2.CH2-

None or alcohols

Pd/C A402002-5, A405028-5, Pd/c A503023-5, A102023-5, Pd/c A470085-5, A470129-5 Pd/C A102038-5, Ni A-5000d/C Ni/Mo A7063 Pd(S)/C A103038-5 Pd/CaCO3 A303060-5 Pd,Pb/CaCO3 A305060-5, A306060-5

-C≡C- → -CH=CH-

5–50

1–3

Alcohols, acetic acid, ethyl acetate or vapor phase

-CH=CH- → -CH2.CH2-

5–100

3–10

None, alcohols, acetic acid or ethyl acetate

Pd/C A402002-5,A405028-5, Pd/c A503023-5, A102023-5, Pd/c A470085-5, A470129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

Selective hydrogenation of least substituted alkene

25–75

1–5

Methanol, ethanol, acetone, THF or toluene Dichloromethane, toluene or ethanol

Rh-100 FibreCat® 2003, 2006

Hydrogenation of substituted double bonds

25–75

1–5

Ir-90, Ir-93, Rh-93 or Rh-97

4.1.2 Aromatic ring compounds
The activity of the catalysts, both heterogeneous and homogeneous, for the hydrogenation of aromatic rings are in the order Rh > Ru > Pt > Pd The rate of hydrogenation of the aromatic ring with PGM catalysts varies with the nature, number and position of the substituents. Typical operating conditions for heterogeneous Rh catalysts would be 20–60°C and 1–4 bar hydrogen pressure. In general, homogeneous catalysts offer no advantages and are very rarely used for ring hydrogenations.

For the hydrogenation of alkyl-substituted polycyclic aromatics Rh and Pt catalysts are generally less selective than Ru unless the aromatic ring is highly substituted. Benzene is readily hydrogenated to cyclohexane. Industrially this reaction is performed in the vapor phase with a Pt/alumina fixed bed catalyst. Partial hydrogenation of benzene to cyclohexene can be effected at 25–200°C and 10–70 bar with a heterogeneous Ru catalyst. Ru is often recommended if C–O or C–N bond hydrogenolysis is to be avoided. Basic additives may be used to suppress unwanted hydrogenolysis or coupling reactions and to increase the hydrogenation rate. There is considerable interest in the ring hydrogenation of

Carbocycles
Rhodium is the most active catalyst, but cost may count against its large scale use in some cases. Pt and Ru catalysts usually require more extreme operating conditions but the performance of Ru catalysts can often be improved by the addition of small amounts of water.

4-t-butylphenol to the cis-isomer (as opposed to the transisomer). Choice of a specific Rh/carbon catalyst together with the use of a non-polar solvent (e.g. hexane) can yield >90% of the desired cis-isomer. Increased solvent polarity (e.g. isopropanol) results in the production of increasing quantities of the trans product.

© 2008 Johnson Matthey Plc

25

Reaction

Temperature (°C)

Pressure (bar)

Solvent

Catalyst

Carbocyclic ring

5–150

3–50

None or alcohols

Rh/C C101023-5,C101038-5 Rh/AI2O3 C301011-5 Ru/C D101023-5,D101038-5, Rh/c D170201-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5 Pd/C A503023-5, A102023-5, Pd/c A102038-5, A470085-5 Ni A-5000

Phenol →Cyclohexanone

30–200

1–10

None

Pd/C A102023-5, A105023-5

In summary, selectivity is affected by:• choice of catalyst (including bimetallics) • solvent polarity and pH • reaction conditions (temperature and pressure). A reaction of considerable commercial importance is the one step Pd-catalyzed conversion of phenol to cyclohexanone (a precursor of Nylon 6), with minimal over hydrogenation to cyclohexanol. This reaction can be performed in either the liquid or vapor phase at 30–200°C and 1–10 bar hydrogen pressure.

Rh is the most active catalyst under mild conditions and is recommended when hydrogenolysis is to be avoided. Pd is an effective catalyst especially for the hydrogenation of acyl- or acyloxy- pyridines. Generally, Pd is the preferred catalyst for selective hydrogenation of nitrogen-containing heterocyclic rings in the presence of carbocylic rings.

Heterocycles
In general, heterocycles are easier to hydrogenate than carbocycles. Heterocyclic compounds such as pyridines, quinolines, isoquinolines, pyrroles, indoles, acridines and carbazoles can be hydrogenated over Pd, Pt, Rh and Ru catalysts. Hydrogenation of furans and other oxygen-containing Acidic solvents, such as acetic acid, and aqueous HCl solutions are often used to facilitate hydrogenation. Pt catalysts have been successfully used in the hydrogenation of many nitrogen containing heterocycles at 25–50°C and 3–4 bar hydrogen pressure, e.g. Specific requirements should be examined on a case by case basis. heterocycles becomes more complex due to hydrogenolysis and ring cleavage possibilities. Hydrogenolysis is generally promoted by high temperature and acidic solvents. Ru is an excellent catalyst at elevated temperatures and pressures where N–dealkylation or deamination is to be avoided.

26

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)
30-150

Pressure (bar)
3-50

Solvent

Catalyst

Pyridines

None or alcohols

Pt/C B102022-5, B103032-5, Pt/c B501032-5, B170147-5 Ni A-5000 Rh/C C101023-5, C101038-5

Furans

30-100

5-60

None, alcohol or water

Pd/C A503023-5, A102023-5 Pd/c A102038-5, A570147-5 Pd/c A570129-5 Rh/C C101023-5, C101038-5 Ru/C D101023-5, D101038-5

Pyrroles

30-100

3-50

Acetic acid or alcohol/acid

Pd/C A503023-5, A102023-5, Pd/c A570129-5 Pt/C B102022-5, B103032-5, Pt/c B501032-5, B170147-5 Rh/C C101023-5, C101038-5

4.1.3 Carbonyl compounds
Aldehydes

1

Ether formation, which may occur as an alcohol dehydration product, can be reduced using a Ru catalyst. Pd is the preferred catalytic metal for the hydrogenation of aromatic aldehydes. Typical reaction conditions are 5–100°C and 1–10 bar hydrogen pressure. Pd will also catalyze the production of hydrocarbon formed from the hydrogenolysis of the alcohol intermediate. Acidic conditions and polar solvents promote the formation of the hydrocarbon by-product.

In general, saturated aliphatic aldehydes can be hydrogenated over Pt, Ru or Ir catalysts to the corresponding primary alcohols at 5–150°C and 1–10 bar hydrogen pressure. Pd tends to be an ineffective catalyst for aliphatic aldehydes but is the metal of choice for aromatic aldehydes. Ru is the catalytic metal of choice for hydrogenation of aliphatic aldehydes. A well known example is the hydrogenation of glucose to sorbitol in aqueous solution. This reaction is traditionally performed industrially with a Ni catalyst, but there are advantages to be gained by using a Ru catalyst. These are:-

Although Pt and Ru can be considered for this application, there is the possibility of simultaneous ring hydrogenation. To some extent, this side reaction can be inhibited by the addition of either salts of Zn, Ag or Fe (typically <1 mol % with respect to the catalytic PGM) or low molecular weight aliphatic nitriles. In the special case of haloaromatic aldehydes to the

• lower operating temperatures, hence less caramelization of the product • lower operating pressures, hence lower plant capital costs • unlike Ni, Ru is not leached into the sugar solution so this particular product purification step/environmental hazard is eliminated.

corresponding haloaromatic alcohols, Pt is the metal of choice. Extensive hydrodehalogenation will occur with Pd catalysts.

© 2008 Johnson Matthey Plc

27

Of particular interest is the selective reduction of α–ß unsaturated aldehydes such as crotonaldehyde and especially cinnamaldehyde.2 A generalized reaction scheme is shown above. Carbonyl hydrogenation is generally less facile than olefins thus making selective hydrogenation of the α–ß unsaturated aldehyde to the α–ß unsaturated alcohol quite difficult. Reaction Temperature (°C)
5–150

Pt/C is used commercially to produce cinnamyl alcohol from cinnamaldehyde. Cinnamyl alcohol has also been produced in the laboratory from cinnamaldehyde using water soluble Ru and Ir homogeneous catalysts. Pd/C is used to produce dihydrocinnamaldehyde. Dihydrocinnamyl alcohol is the product when both reducible functions are hydrogenated.

Pressure (bar)
1–10

Solvent

Catalyst

to aliphatic alcohols

Alcohols, ethyl acetate or water

Ru/C D101023-5, D101038-5, Ru/c D170201-5 Pt/C B103032-5, B103018-5, Pt/c B501032-5, B170147-5 Pd/C A503023-5,A102023-5, Pd/c A470085-5, A570129-5 Pd/c A570201-5 Pd/C A503023-5, A503038-5, Pd/c A102023-5, A470085-5 Pd/c A470129-5, A470201-5 Ru/C D101023-5, D101038-5, Ru/c D170201-5 Pt/C B103032-5, B103018-5, Pt/c B501032-5, B170147-5

to aromatic alcohols

5–100

1–10

Neutral: benzene, hexane, DMF or ethyl acetate Acidic: alcohol or acetic acid

RR’C=O →RR’CH2

5–100

1–10

Glucose → Sorbitol α,ß unsaturated aldehyde to unsaturated alcohol

100–120

20–30

Water

50–120

5–15

Isopropanol

1 R.A. Sheldon and H. van Bekkum Fine Chemicals Through 1 Heterogeneous Catalysis Wiley – VCH 2001 363-369 2 P Gallezot and D. Richard Catal Rev - Sci Eng (1998) 40 81-126 . 28

© 2008 Johnson Matthey Plc

Ketones
Ketone hydrogenation is similar to that of aldehyde hydrogenation, but is usually less facile due to increased steric hindrance at the carbonyl group. Saturated aliphatic ketones can be hydrogenated over Pt or Ru to the corresponding secondary alcohol at 5–150˚C and 1–10 bar hydrogen pressure. Aromatic ketones are best hydrogenated over Pd catalysts. Ru is the catalytic metal of choice for the hydrogenation of water soluble ketones and for hydrogenations in alcohol solvents (since ether formation is minimized). Aromatic ketones can be hydrogenated to the corresponding alcohol or alkyl aromatic (hydrogenolysis) over a variety of catalysts. Hydrogenolysis is favored by acid conditions, elevated temperatures and polar solvents.

The selective hydrogenation of an α–ß unsaturated ketone to the corresponding α–ß unsaturated alcohol is much more difficult than is the case for the α–ß unsaturated aldehydes. However, hydrogenation of the α–ß unsaturated ketone to the saturated ketone is relatively trivial with a Pd catalyst as would be expected. Ketones can be hydrogenated to alcohols using homogeneous catalysts such as Ru–100. The reaction is promoted by base. Homogeneous catalysts are particularly attractive for performing enantioselective hydrogenations on functionalized ketones. Please see section 4.13 for information on asymmetric ketone reduction.

Reaction

Temperature (°C)
5-150

Pressure (bar)
1-10

Solvent

Catalyst

to aliphatic alcohols

Alcohols, ethyl acetate or water

Ru/C D101023-5, D101038-5, Ru/c D170201-5 Pt/C B103032-5, B103018-5, Pt/c B501032-5, B170147-5

to alcohols

15-100

1-50

Toluene, THF , methanol, ethanol or propan-2-ol

Ru-100

to aromatic alcohols

5-100

1-10

Neutral: benzene, hexane, DMF or ethyl acetate

Pd/C A503023-5, A102023-5, Pd/c A470085-5, A570129-5, Pd/c A570201-5

RR’C=O → RR’CH2

5-100

1-10

Acidic: alcohol or acetic acid

Pd/C A503023-5,A503038-5, Pd/c A102023-5,A470085-5, Pd/c A470129-5, A470201-5

© 2008 Johnson Matthey Plc

29

4.1.4 Nitro and nitroso compounds
Aromatic nitro and nitroso groups are hydrogenated to the corresponding amine over palladium and platinum catalysts. The analogous aliphatic compounds are less easily hydrogenated as the resulting amine tends to inhibit the catalyst. In this case, higher catalyst loadings and more vigorous reaction conditions are required. To some extent the inhibiting effect can be decreased by operating under acidic conditions. Nitro/nitroso hydrogenations are usually performed with heterogeneous catalysts. Intermediate hydroxylamines, oximes, azo compounds or p–aminophenol can be obtained depending upon the reaction conditions.

p–Amino phenols can be obtained in good yield by the hydrogenation of aromatic nitrobenzenes in dilute sulfuric acid under carefully controlled conditions. The yield is usually improved by the presence of a water soluble quaternary ammonium compound. Hydrogenation of nitro compounds is a very exothermic reaction RNO2 + 3H2 ➝ RNH2 + 2H2O ΔH = –431 kJ/mole It is therefore often desirable to use a solvent as a heat sink. Although it is possible to hydrogenate a dinitroaromatic to a nitroaminoaromatic, such reactions are generally difficult. It has been reported1 that this reaction can be achieved using the Ru-100, RuC12(PPh3)3 homogenous catalyst. Pd–111, [Pd(OAc)2]3 and Rh–120, [RhCl2Cp*]2 have been used for the hydrogenation of nitro and nitroso compounds

Reaction pathways for the hydrogenation of the nitro group

1 J.F Knifton J. Org. Chem. (1975) 40 519 . 30

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)

Pressure (bar)

Solvent*

Catalyst

From Nitro Compounds to aromatic amine

5-50

1-5

Neutral or acidic alcohols, ethyl acetate

Pd/C A401102-5, A405028-5, Pd/c A503023-5, A503032-5, Pd/c A102023-5, A470085-5, Pd/c A470129-5, A470201-5 Ni A-5000 Pt/C B103032-5, B501032-5, Pt/c B170147-5 Pd/C A401102-5, A405028-5, Pd/c A503023-5, A503032-5, Pd/c A102023-5, A470085-5, Pd/c A470129-5, A470201-5 Ni/Mo A-7000 Ni/Mo A-7063 Pt/C B103032-5, B501032-5, Pt/c B170147-5 Rh/C C101023-5

to aliphatic amine

50-150

3-25

Alcohols. Base causes inhibition. Acid sometimes improves activity

to haloamines

90-150

8-12

Alcohols, ethyl acetate

Pt/C Pt/c Pt/c Pt/c

B101032-3, B103032-3, B170147-3, B102032-1, B101038-1, B105047-1, B170147-1

to p-aminophenols From Nitroso Compounds to aromatic amine

50-150

<1

Dilute H2SO4

Pt/C B102032-1, B105047-1, Pt/c B170058-1 Pd/C A503023-5, A503032-5, Pd/c A505085-5, A102023-5, Pd/c B570147-5, A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

5-100

1-10

Neutral or acidic alcohols, ethyl acetate

to aliphatic amine

5-100

1-10

Alcohol/HCl or acetic acid

Pd/C A503023-5, A503032-5, Pd/c A505085-5, A102023-5, Pd/c A570147-5, A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

* Many processes are operated commercially without solvent, using molten substrate at temperatures higher than those indicated above

4.1.5 Halonitroaromatics
The hydrogenation of halonitroaromatics to the corresponding haloaminoaromatic is a reaction of considerable industrial importance. Traditionally, Fe/HCl catalyst has been used to obtain the desired yield of the haloamine (Béchamp Process) but it is increasingly being replaced by Pt catalysts because of several inherent disadvantages:-

I > Br > Cl > F and its position on the aromatic ring with respect to the nitro group being hydrogenated:ortho > para > meta Acidity in the form of acid addition or an acidic catalyst will tend to inhibit hydrodehalogenation. Typical operating conditions are 90–150°C and 8–12 bar

• a steam distillation step is needed to separate the product haloamine from the iron oxide sludge – an operation which is energy intensive and therefore expensive • environmental problems with the disposal of the iron sludge. These problems can be successfully overcome using a Pt supported catalyst; Pd catalysts cause high levels of hydrodehalogenation. The ease of halogen removal (as the hydrohalic acid) depends on the particular halogen:© 2008 Johnson Matthey Plc

hydrogen pressure, as more severe conditions promote hydrodehalogenation. The reaction can be effectively carried out with or without the use of a solvent. A solvent, while facilitating temperature control (acting as a heat sink for the exotherm) may have a marked influence on the rate and selectivity to the haloamine. Generally, aprotic solvents inhibit hydrodehalogenation whereas protic solvents tend to increase reaction rates.

31

Reaction

Temperature (°C)
90-150

Pressure (bar)
8-12

Solvent

Catalyst

Halonitro → haloamine

Alcohols or cyclohexane

Pt/C B101032-3, B103032-3, Pt/c B102032-1, B101038-1, Pt/c B105047-1, B170147-1 Pt/c

4.1.6 Reductive Alkylation

R1 R NH2

+

O

C R
2

R

N

C

R1 R2

+

H2O

Pt H2 or Pd R1 R NH CH R2
Reductive alkylation involves the reaction of a primary or secondary amine with an aldehyde or ketone to form a secondary or tertiary amine respectively. Formation of the imine intermediate is favored by acidic conditions. The imine intermediate is seldom isolated in such cases. The amines formed are also suitable substrates for further alkylation. A catalyst of high selectivity is required to minimize Thus, when wanting to produce a secondary amine (with a minimum of tertiary amine) from a primary amine feedstock, the primary amine to carbonyl molar ratio should not exceed one. hydrogenation of the carbonyl compound to the alcohol prior to imine formation via condensation. Sulfided platinum catalysts can be used to minimize alcohol formation but generally require more severe operating conditions. Non-sulfided Pt catalysts are effective under mild reaction conditions (10 bar, 100°C). Aldehydes are generally more reactive than ketones because they tend to be less sterically hindered. Pt or Pd catalysts are preferred for reductive alkylations. Typical reaction conditions are 50–300°C and 1–50 bar pressure. In some cases, the amine may be produced in situ from the corresponding nitro or nitroso compound. Similarly the carbonyl may, in some circumstances, be produced in situ from the appropriate acetal, ketal, phenol or alcohol.

R1 R NH CH R2

R1

R1

+

O

C R2

+ H2

R

N CH

R2 2

+ H2O

32

© 2008 Johnson Matthey Plc

CH3 NH NH2

+

CH CH2 CH3 C CH3 O

NH

NH CH

CH2 CH3

CH

CH3 CH3

The manufacture of the rubber antioxidant 6-PPD

A reductive alkylation of commercial significance in the rubber chemicals industry is the reaction of 4–aminodiphenylamine with MIBK (methyl isobutylketone) to produce 6PPD. Homogeneous Ir catalysts (exemplified by Ir–93, [IrCl(COD)]2 plus ligand) are effective for reductive alkylations (as well as imine hydrogenations – see section 4.1.8).

Typical operating conditions are 25–50°C and 1–80 bar pressure. A wide variety of solvents can be used – such as dichloromethane, alcohol, toluene and tetrahydrofuran (THF). For example N–cyclohexylaniline can be formed in 98% yield at atmospheric pressure in methanol.

Ir O

+ H2N

+ H2

N H

Reaction

Temperature (°C)
20–100

Pressure (bar)
1–50

Solvent

Catalyst

from aldehyde

Alcohol or the aldehyde

Pd/C A109047-5, A503032-5, Pd/c A503023-5, A102023-5, Pd/c B570147-5, A570129-5 Ni A-5000 Ni/Mo A-7000 Pt/C B102032-3, B104032-3, Pt/c B170147-3, B105032-3, Pt/c B106032-3, B171147-3 Pd/C A109047-5, A503032-5 Pd/c A503023-5, A102023-5, Pd/c B570147-5, A570129-5 Ni A-5000 Ni/Mo A-7000 Pt/C B102032-3, B104032-3, Pt/c B170147-3, B105032-3, Pt/c B106032-3, B171147-3

from ketone

50–150

1–50

Alcohol or the ketone

© 2008 Johnson Matthey Plc

33

4.1.7 Reductive Aminations

R1 C R2 O

R1

+

NH3

R2 Pd

C

N

H

+

H2O

H2

R1 R2
This reaction is essentially the same as a reductive alkylation except that the “amine” feedstock employed is ammonia. The catalyst of choice is almost invariably Pd. Excess ammonia is employed to suppress hydrogenation of the carbonyl to the corresponding alcohol.

CH NH2

Reaction

Temperature (°C)
50–300

Pressure (bar)
1–50

Solvent

Catalyst

from aldehyde

None or alcohol

Pd/C A109047-5, A503032-5, Pd/c A503023-5, A102023-5, Pd/c A570147-5, A570129-5 Pd/C A109047-5, A503032-5, Pd/c A503023-5, A102023-5, Pd/c A570147-5, A570129-5

from ketone

50–300

10–50

None or alcohol

4.1.8 Imines
Reductive alkylations/aminations involve the condensation of a carbonyl compound with an amine to form an imine intermediate, which undergoes hydrogenation to the amine. In some cases, the imine is the feedstock for hydrogenation. Pd and Pt heterogeneous catalysts are typically used although homogeneous Ir catalysts are also effective, particularly for enantioselective hydrogenations. Pd and Pt catalysts can be used under relatively mild operating conditions of 20–100°C and 1–10 bar pressure. Alcohols are usually the solvents of choice and acidic conditions often promote the reaction.
Ph Ph Ph N Me Me HN HN Me

+

34

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)
20–100

Pressure (bar)
1–10

Solvent

Catalyst

Imine → amine

Alcohol or toluene

Pd/C A109047-5, A503023-5, Pd/c A503032-5, A102023-5, Pd/c A570147-5, A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

4.1.9 Nitriles
Hydrogenation of nitriles can be carried out over Rh, Pt or Pd catalysts at 5–150°C and 1–100 bar hydrogen pressure. Primary, secondary or tertiary amines can be formed via the intermediate imine RCH2NH2 R C N RCH NH (RCH2)2NH

In neutral media, Pd is also effective for the production of tertiary amines. For aliphatic nitriles, with proper selection of conditions, either Rh, Pt or Pd may be effective for the formation of primary amines, whereas Rh catalysts yield secondary amines as the predominant product and Pt or Pd catalysts favor the formation of tertiary amines – especially in the hydrogenation of short chain aliphatic nitriles. Dinitriles, either aliphatic or aromatic, usually need (RCH2)3N considerably higher operating pressures (100–220 bar) to effect the hydrogenation.

For example, veratrylnitrile can be readily hydrogenated to the corresponding primary amine with a Pd catalyst at 10–50°C and 3–5 bar In acidic aqueous media, nitriles can undergo reductive hydrolysis to aldehydes and/or alcohols by hydrolysis of the imine intermediate.

CH3O

CN Pd

CH3O

CH2 NH2
R C N R CH NH

H 2O RCHO

+

NH3

CH3O

CH3O

Pd is the catalyst of choice for this reaction which can be For the formation of the primary amines, either acidic solvent conditions (at least 2–3 moles of acid/mole of nitrile) or excess ammonia (>2 moles/mole nitrile) are required. Formation of secondary amines is facilitated by neutral conditions while tertiary amines are usually produced predominantly only in the presence of a low molecular weight secondary amine. For aromatic nitriles in ammonia or acidic media, Pd and Pt are preferred for the production of primary amines. Pt and Rh are preferred for the formation of secondary amines in neutral solvents. effected at 30–100°C and 1–5 bar. The aqueous solvent is made acidic with H2SO4, HCl or CH3COOH. The acid promotes the hydrolysis of the imine and acts as a scavenger for the ammonia. In order to force the reaction to the desired aldehyde, phenylhydrazine or semicarbazide can be added. The aldehyde forms the respective condensation phenylhydrazone or semicarbazone product. At least 1–2 moles of additive/mole of aldehyde needs to be added. Reductive cyclization may also be an important reaction pathway when a suitable second reactive functional group is available.

© 2008 Johnson Matthey Plc

35

Reaction

Temperature (°C)

Pressure (bar)

Solvent

Catalyst

to Aliphatic Amine
1°–amine RNH2 5–100 1–10 Alcohol/ammonia or alcohol/min. acid or acetic anhydride Pd/C A503023-5, A503032-5, Pd/c A102023-5, A570147-5, Pd/c A570129-5 Pt/C B103032-5, B501032-5, Pt/c B570147-5 Rh/C C101023-5, C101038-5 Ni A4000, A5000, Ni A7000, A7063 AMCAT 5 AMCAT 7 2°–amine R2NH 50–100 2–5 Alcohols. neutral conditions Rh/C C101023-5, C101038-5 Pd/C A503023-5, A503032-5 Pd/c A102023-5, A570147-5, Pd/c A570129-5 3°–amine R3N 50–100 2–5 Alcohols, or DMF with 2°–amine Pd/C A503023-5, A503032-5 Pd/c A102023-5, A570147-5, Pd/c A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5 to Aromatic Amine 1°–amine ArNH2

50–100

1–10

Alcohol/ammonia or alcohol/min. acid or acetic anhydride

Pd/C A503023-5, A503032-5 Pd/c A102023-5, A570147-5, Pd/c A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

2°–amine Ar2NH 3°–amine Ar3N

5–100

2–5

Alcohol/water

Pt/C B103032-5, B501032-5, Pt/c B170147-5 Pd/C A503023-5, A503032-5 Pd/c A102023-5, A570147-5, Pd/c A570129-5 Pt/C B103032-5, B501032-5, Pt/c B170147-5

50-100

2–5

Alcohol or DMF with 2°–amine

to Aldehyde 30–100 1–5 Alcohol/acid or water/acid Pd/C A402002-5, A109047-5, Pd/c A503023-5, A570129-5 Pd/c A570201-5

36

© 2008 Johnson Matthey Plc

4.1.10 Oximes
Hydrogenation of oximes can give rise to primary, secondary or tertiary amines, hydroxylamines or imines. The imines are rarely isolated as such, since condensation coupling can readily occur as well as the possibility of reductive hydrolysis to the aldehyde. Acetylation of the oxime facilitates hydrogenation. Rh is the preferred catalytic metal for the formation of primary amines usually producing less secondary amine product than Pd.

Rh is also the catalyst of choice if reductive coupling is to be minimized. Acidic (H3PO4 or H2SO4) or ammoniacal solvents favor the formation of primary amines by suppressing reductive coupling side reactions. Acidic conditions are recommended to minimize reaction rate inhibition caused by the amine products. With a Rh catalyst, the amount of acid is not critical, but with a Pd catalyst, there should be at least 2–3 moles of acid per mole of oxime. Pt or Pd catalysts are generally preferred for the partial hydrogenation of oximes to the corresponding hydroxylamine (or imine precursor).

RCH2NH2 RCH N OH

+

H2O

RCH2NHOH

RCH

NH

+

H2O

RCHO

+

NH3

Reaction

Temperature (°C)
30–60

Pressure (bar)
1–5

Solvent

Catalyst

oxime → amine

Alcohol/acid

Pd/C A109047-5, A503023-5, Pd/c A503032-5, A102023-5, Pd/c A570147-5, A570129-5 Rh/C C101023-5, C101038-5

© 2008 Johnson Matthey Plc

37

4.1.11 Hydrogenolysis
Debenzylations
Benzyl groups and related structures (e.g. carbobenzyloxy) are often used to protect amine and hydroxyl functional groups. Catalytic hydrogenolysis for the removal of these protecting groups occurs under mild conditions. Typical operating conditions are 5–100°C and 1–10 bar hydrogen pressure. Hydrogenolysis is promoted by high temperatures and low pressures. In most cases Pd/carbon is the catalyst of choice, but there are differences between O–debenzylation (cleavage of carbon–oxygen bonds) and N–debenzylation (cleavage of carbon–nitrogen bonds).

(b) N–Debenzylation
For N–debenzylations exemplified by the general scheme

CH2NR1R2

Pd

CH3

+

R1R2NH

both reduced and unreduced Pd/C can be effective. Acidic solvents such as acetic acid, ketones with acid addition, or even acid buffered solvents are desirable to prevent inhibition of the catalyst by the amine products. The amine adsorption characteristics are pH dependent. Typically, N-debenzylations are more difficult to perform than O-debenzylations. The slower N-debenzylation reaction rate can often be improved by using higher palladium content in the catalysis design.

(a) O–Debenzylation
The classical Pd/C catalyst used for this reaction is Pearlman’s catalyst (a 20% palladium hydroxide on carbon catalyst), but in most cases it is possible to use a catalyst with a much lower Pd content. Best results are invariably obtained with an unreduced (oxidic) Pd/carbon catalyst. The best solvent for this reaction is THF (tetrahydrofuran) although acetic acid or alcohol have also been used successfully.

(c) Removal of Carbobenzyloxy Group
In practical terms, operating conditions are very similar to those of N–debenzylation described above. Acidic conditions are desirable, not only to avoid amine inhibition of the catalyst, but also to avoid poisoning by the liberated CO2.

CH2 CH2OR Pd CH3

OCONR1R2 Pd

CH3

+

+ R1R2NH + CO2
ROH

Reaction

Temperature (°C)
5–100

Pressure (bar)
1–10

Solvent

Catalyst

Debenzylation

Alcohols, THF , acetic acid or alcohol/mineral acid

Pd/C A402002-5, A405028-5, Pd/c A405032-5, A503023-5, Pd/c A503032-5, A470129-5, Pd/c A402028-10, A402032-10, Pd/c A501023-10, A501032-10,

Pd/c A470129-10 Carbon–oxygen cleavage 50–150 3–50 Alcohol/mineral acid, THF or acetic acid Pd/C A402002-5, A405028-5, Pd/c A405032-5, A503023-5, Pd/c A503032-5, A470129-5, Pd/c A402028-10, A402032-10, Pd/c A501023-10, A501032-10, Pd/c A470129-10, A401002-20, Pd/c A470129-20 Pd/C A402002-5, A405028-5, Pd/c A405032-5, A503023-5, Pd/c A503032-5, A470129-5, Pd/c A402028-10, A402032-10, Pd/c A501023-10, A501032-10, Pd/c A470129-10

Carbon–nitrogen cleavage

50–150

3–50

Alcohol/mineral acid or acetic acid

38

© 2008 Johnson Matthey Plc

Hydrodehalogenations
Hydrodehalogenation occurs under relatively mild conditions (5–100°C and 1–10 bar) but is favored by increasing temperature rather than pressure. RX + H2 ➝ RH + HX

Rosenmund Reductions
The Rosenmund Reduction is the Pd catalyzed hydrogenation of an acyl chloride to the corresponding aldehyde

COCl

X = F Cl, Br, I , Pd is the most active and preferred catalytic metal. The ease of hydrogenolysis is in the order I > Br > Cl > F Selective hydrodehalogenation is possible in some cases e.g. removal of chlorine (as HCl) with fluorine retention. This is demonstrated by the fixed bed vapor phase conversion of CFC (chlorofluorocarbon) to HFC (hydrofluorocarbon).
R

Pd

CHO

+
R

HCl

The classical catalyst for this reaction is Pd/BaSO4, but in most cases Pd/carbon powders can be substituted with advantage. The operating conditions must be mild (temperatures of 5–50°C and pressures of 1–3 bar), otherwise overhydrogenation to the primary alcohol will occur. In order to preserve the selectivity to the aldehyde, nitrogen or sulfur-containing compounds are often added to modify the catalyst. Typical additives include thiourea or thioquinanthrene. These well-defined compounds have largely eclipsed the use of the variable “quinoline/sulfur” reagent. The reaction

The reaction rate also depends on molecular structure and neighboring functional groups. Cleavage of aryl halides is more facile than alkyl halides. The reaction rate is often adversely affected by the release of halide ion, therefore an addition of basic halide acceptors is often made. Typical additives include aliphatic amines (e.g. triethylamine), sodium carbonate, magnesium oxide etc. At least 2 equivalents of base per equivalent of halide should be added. Suitable choice of solvent can also help minimize the effect of catalyst inhibition by halide. Alcohols or esters (such as ethyl acetate) can be used as solvents, often with the addition of up to about 10% water, which can help to maintain catalyst activity.

must be carried out in the absence of water, otherwise hydrolysis of the feedstock to the corresponding carboxylic acid will occur. Dry powder Pd/C catalyst must therefore be used (as opposed to water-wet pastes) to maintain the anhydrous conditions. As with other hydrodechlorinations, a basic chloride acceptor is often utilized. Examples include 1,2-butylene oxide, aliphatic amines, sodium carbonate, magnesium oxide, 2,6–dimethylpyridine etc. (again at least 2 equivalents per equivalent of halide). Sometimes, due to the ease of acid chloride hydrodechlorinations, it is possible to remove the liberated HCl with a nitrogen sparge or by operating at subatmospheric pressures so that the addition of specific chloride acceptors is not necessary.

© 2008 Johnson Matthey Plc

39

Reaction

Temperature (°C)
5–100

Pressure (bar)
1–10

Solvent

Catalyst

Hydrodehalogenation

Alcohols, ethyl acetate or vapor phase

Pd/C A402002-5, A405028-5 Pd/c A503023-5, A503038-5, Pd/c A102023-5, A570129-5, Pd/c A570201-5 Pd/C A302023-5, A302038-5, Pd/c A701023-5 Pd/BaSO4 A308053-5, A201053-5, A201053-10

Rosenmund Reduction (acyl chloride → aldehyde)

5–50

1–3

Toluene, xylene, acetone or THF

4.1.12 Transfer Hydrogenations1
When hydrogen gas and/or hydrogenation plant is not readily available, then the hydrogenation may be achieved using a chemical hydrogen donor. In effect the catalyst dehydrogenates the donor molecule to generate hydrogen to carry out the hydrogenation. The donor molecule and catalyst should be selected with care so that the rate of hydrogen release is comparable to the rate of hydrogenation of the feedstock. Typical donor molecules include cyclohexene, formates, phosphinates, propan–2–ol and indolene. Pd and Pt are the heterogeneous catalysts of choice. Transfer hydrogenations are often performed under reflux but it is possible to operate at lower temperatures when required. Different selectivities are sometimes achieved by transfer hydrogenation rather than H2 gas.

Transfer hydrogenation can be accomplished using homogeneous catalysts. For example, tetralone has been hydrogenated with Rh-120 with an amine ligand in the presence of a hydrogen donor, propan-2-ol. Examples of PGM precursors of homogeneous catalysts used for transfer hydrogenations in the literature are Iridium (Ir-93 [IrCl(COD)]2), Rhodium (Rh-93 [RhCl(COD)]2), (Rh-120 [RhCl2(CP*)]2) and Ruthenium (Ru-120 [RuCl2(pcymene)]2). Please refer to section 4.13 for information on asymmetric hydrogenation.

O

OH

+

(CH3)2CHOH

+

(CH3)2CO

1 R.A.W. Johnstone et al. Chem. Rev. (1985) 85 129–170 40

© 2008 Johnson Matthey Plc

Reactant

Product

Donor

Solvent

(˚C)

Temperature

Catalyst

Nitro

Amine

Formic acid, phosphinic acid, sodium formate, sodium phosphinate, tetraethyl ammonium formate Formic acid, phosphinic acid, sodium phosphite

Methanol, ethanol or THF

50–80

Pd/C A503023-5, A503038-5, Pd/c A102023-5, A102038-5, Pd/c A570129-5

Halonitro

Haloamine

Methanol, ethanol or water

60–80

Pt/C B101032-3, B103032-3, Pt/c B170147-3, B102032-1, Pt/c B101038-1, B105047-1, Pt/c B170147-1 Ir–93 Rh–93, Rh–120

Imine

Amine

Formic acid & Et3N, propan–2–ol Cyclohexene, indolene, triethyl ammonium formate Cyclohexene, phosphinic acid, sodium phosphinate Formic acid & Et3N, propan–2–ol

None or acetonitrile

0–60

Alkene

Alkane

None

Reflux

Pd/C A503023-5, A503038-5, Pd/c A102023-5, A102038-5, Pd/c A570129-5

Carbonyl

Alcohol

Ethanol or THF

Reflux

Pd/C A503023-5, A503038-5, Pd/c A102023-5, A102038-5, Pd/c A570129-5 Ir–93 Rh–93, Rh–120

Ketone

Alcohol

None or acetonitrile

0–60

Debenzylation

Formic acid, sodium formate

Ethanol, methanol or THF

50–80

Pd/C A503023-5, A503032-5, Pd/c A470129-5, A402028-10, Pd/c A501023-10, A501032-10, Pd/c A470129-10

4.2 DEHYDROGENATION
Dehydrogenation is an endothermic process, and hence high operating temperatures (up to 250°C) and high catalyst loadings (3–10% with respect to feedstock) are often necessary. At such high temperatures, most PGM complexes decompose, so homogeneously catalyzed dehydrogenations in the liquid phase are usually not feasible. Traditionally, nitrogen has been used to purge the liberated hydrogen from the reaction, but increasingly the use of hydrogen acceptors is finding favor.

Hydrogen Acceptor Nitrotoluene Nitrobenzene Maleic acid Dimethylmaleate α–methylstyrene trans–stilbene Tetralin Indene

Product Toluidine (+ water) Aniline (+ water) Succinic acid Dimethylsuccinate Cumene Dibenzyl Decalin Indane

© 2008 Johnson Matthey Plc

41

Hydrogen acceptors should be used in 0.5–2.0 molar quantities with respect to the liberated hydrogen. Where the products include water, care should be taken, because the steam which is liberated can cause bumping of the reactor contents in liquid phase reactions.

Very small additions (2–10 ppm with respect to the feedstock) of organic sulfur compounds such as diphenyl sulfide can promote some dehydrogenation reactions. Such additions have to be very carefully optimized. A particular dehydrogenation of industrial importance is

For the same reason it is desirable to use dry powder catalysts for liquid phase reactions and dry pelleted catalysts for gas phase reactions.

the formation of iminostilbene from iminodibenzyl

Pd/C

It is highly desirable to use a hydrogen acceptor if at all possible, thus permitting lower temperature operation than would be possible without a hydrogen acceptor. The operating temperature should be as low as possible, consistent with acceptable product yields in order to minimize:• metal crystallite sintering – see section 2.1.7 • product decomposition and/or by–product formation Typical high boiling point solvents used include biphenyl and polyglycol ethers. It is possible sometimes to use the hydrogen acceptor as the solvent. The ease of dehydrogenation is dependent on the substrate and operating conditions. However, the following general comments can be made:• easier if at least one double bond is close to the dehydrogenation site A common problem with operating catalysts at high • easier if the end product is a fully aromatic compound • 6 and 7-membered or larger ring systems are easier to dehydrogenate than 5-membered rings1. temperatures in the vapor phase for extended periods is that coking may occur (see section 2.1.7). This has the effect of masking individual metal crystallites. One way of reducing this effect on the Pd or Pt pelleted catalysts is to introduce a small quantity of hydrogen into the feedstock. The catalysts of choice for liquid phase dehydrogenations are Pd > Pt > Rh Catalyst performance can be enhanced by the addition of inorganic bases such as Na2CO3, MgO (up to about 5% by weight with respect to the catalyst). Addition of base neutralizes any acidic sites on the catalyst, which if left untreated, could cause by–product formation. R OH Pd/C α-methyl styrene R OH For the dehydrogenation of cyclohexanols and cyclohexanones, the favored hydrogen acceptors are olefins e.g. α−methylstyrene. The product is an intermediate in the preparation of Carbamazepine – a treatment for epilepsy.
N H nitrotoluene N H

1 M. Bartok Stereochemistry of Heterogeneous Metal Catalysis 1 Wiley Interscience (1985) 35–37 42

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)
180–275

Solvent

H2 Acceptor

Catalyst

Cyclohexanones/anols to Phenols

biphenyl

Olefinic (e.g. α−methylstyrene, tetralin)

Pd/C A503023-5, A503038-5, Pd/c A102023-5, A102038-5, Pd/c A570129-5, A501023-10, Pd/c A501038-10, A101023-10, Pd/c A101038-10 Pd/C A503023-5, A503038-5, Pd/c A102023-5, A102038-5, Pd/c A570129-5, A501023-10, Pd/c A501038-10, A101023-10, Pd/c A101038-10 Pt/C B103032-5, B103018-5, Pt/c B501032-5 Ni/Mo A-7000 Ni/Mo A-7200

Alkane to Alkene

180–250

Glycol, PEG

Nitrotoluene, nitrobenzene

Alcohol to Carbonyl

>200

None (vapor phase)

None

4.3 HYDROFORMYLATION
Hydroformylation is the largest and oldest homogeneously catalyzed industrial process, in which the simultaneous addition of one mole of CO and H2 is made across a carbon–carbon double bond to produce an aldehyde. Industrially, the most important alkene feedstock is propene.

The butyraldehyde is either reduced directly to n-butanol, or aldolized and dehydrated to 2-ethylhexenal and then reduced to 2-ethylhexanol – a well known plasticizer alcohol. For terminal alkene hydroformylation, the Rh homogeneous catalyst is used together with a large excess (50-100 x molar with respect to the catalyst) of a tertiary phosphine such as triphenylphosphine. Many different Rh catalysts (or precursors) can be used. Typical Rh compounds include Rh-40 Rh(PPh3)2(CO)Cl, Rh-42 RhH(CO)(PPh3)3, Rh-43 Rh(acac)(CO)(PPh3) and Rh-50 Rh(acac)(CO)2. Provided the Rh compound selected can enter into the

CH 3 + CO + H2 CHO +
straight chain

CHO
branched chain

The original cobalt-catalyzed high pressure process was discovered in Germany over 60 years ago. The replacement of Co by Rh in the mid 1960’s provided a major breakthrough in the history of homogeneous catalysts. The main advantages are:• higher straight chain: branched chain product ratios (the straight chain product usually being the more commercially desirable) • lower operating pressures, hence lower plant capital costs

catalytic cycle, the precise form of the precursor is of little importance. The factors affecting the choice of a particular precursor usually involves such “practical” properties as:• absence of halogen (important for long term stability in steel reactors – but not in glass equipment) • ease of storage/handling in air • minimal health hazards • solubility in the reaction medium • cost of conversion of the Rh metal to the

• lower operating temperatures, hence less formation of oligomeric by-products • lower feedstock consumption per tonne of product, hence increased yield These more than compensate for the higher cost of Rh. A consortium of three companies (Davy McKee/Johnson Matthey/Union Carbide) commercialized the Rh catalyzed process, now known as the L.P (Low Pressure) Oxo . Process and licensed it world-wide. Well over 1 million tonnes of n–butanol is now made annually from propene using the L.P Oxo Process. .

particular complex The propene hydroformylation process operated by Hoechst (Ruhrchemie) is interesting in that the reaction medium is a two phase aqueous/organic system in which the Rh catalyst is solubilized in the aqueous phase using a sodium sulfonate substituted triphenylphosphine as the ligand. Since the Rh is confined to the aqueous phase, product/catalyst separation is straightforward with minimal loss of Rh into the organic phase.

© 2008 Johnson Matthey Plc

43

RhH(CO)L3 C3H7CHO L CH2 CHCH3

RhH(CO)L2 H L2Rh H H2 O L2Rh C CO C3H7 CO L2Rh CO C3H7 O C CO C3H7

H L2Rh CO

CHCH3 CH2

CH2CH2CH3 L2Rh CO

CO
The catalytic cycle for the rhodium catalyzed hydroformylation of propene (L = triphenylphosphine)

There have been many studies of the mechanism of hydroformylation. Suitable choice of operating conditions and ligand can drive the reaction to form the straight chain aldehyde, or the branched chain product. Thus the tailormaking of ligands to favor the formation of a particular product has become a practical proposition. For example, Union Carbide has developed a phosphite ligand to give very high straight chain to branched chain ratios. Other industrial processes incorporating a Rh catalyzed hydroformylation step include:• production of vitamin A The BASF process involves the hydroformylation of a terminal alkene, whereas the Hoffmann–La Roche process hydroformylates an internal alkene • production of 1,4-butanediol The Kuraray process (operated by Lyondell) involves the hydroformylation of allyl alcohol

The vast majority of (and certainly all of the industrially important) processes use Rh as the catalytic metal of choice. The literature indicates that Pt has some activity as a hydroformylation catalyst, often used together with a SnCl2 promoter.

44

© 2008 Johnson Matthey Plc

Reaction

Temperature (°C)
50–150

Pressure (bar)
10–50

Solvent

Catalyst

Hydroformylation

Toluene or ethyl acetate

Rh–40, Rh–42, Rh–43, Rh–50, Rh–112 Rh 2–ethylhexanoate

4.4 CARBONYLATION
The carbonylation of methanol to acetic acid is one of the largest industrial processes using homogeneous catalysis.

Methyl methacrylate can thus be obtained from the carbonylation of methyl acetylene in a methanol solvent, thereby avoiding the classical cyanohydrin route. By analogy, when water is used as the solvent, acids are formed (hydrocarboxylation). For example one step in a DuPont/DSM route to adipic acid involves the

Rh/I CH3OH + CO CH3COOH

hydrocarboxylation of butadiene with an Ir catalyst.

Ir

+ CO

+

H2O

HOOC

COOH

The original process, developed by Monsanto and subsequently purchased by BP used an iodide-promoted , Rh catalyst. More recent work by BP Chemicals has shown that an iodide-promoted Ir homogeneous catalyst (Cativa™ process) can be used with carbonylation. Pd is the catalytic metal of choice for the carbonylation of alkynes and alkenes. In alcohol solvents esters are formed.
O CH2 CH2

Under different conditions, Shell and others have shown that polyketones can be formed from the carbonylation of alkenes in the presence of cationic Pd complexes derived from palladium acetate or PdCl2.2 Chelating diphosphines, such as diphenylphosphinopropane or 1,1’-bis(diphenylphosphino)ferrocene have been shown to be very effective ligands for this type of reaction.

advantage.1

Over 60%

of the world’s acetic acid is now made by methanol

+

CO n O O n

CH

CR

+ CO

+ R’OH

CH2

C R

COOR’

CH2

CHR +

CO

+ R’OH

RCH2CH2COOR’

These polymers find use as engineering thermoplastics.

1 J.H. Jones Platinum Metals Rev. (2000) 44(3) 94 2 E. Drent and P .H.M. Budzelaar Chem. Rev. (1996) 96 663 45

© 2008 Johnson Matthey Plc

Pd is also the catalyst of choice for the base-catalyzed hydrocarboxylation of aryl or benzyl halides. Base acts as a scavenger for the liberated HX.

ArX

+

CO

+

H2O

ArCOOH

+

HX

(X = halide)
®

Anchored homogeneous catalysts (FibreCat ) are under development for carbonylation reactions (see section 2.3).

Reaction
Alkene, alkyne or secondary alcohol carbonylation Primary alcohol carbonylation

Temperature (°C)
50–150

Pressure (bar)
10–50

Solvent
Toluene or alcohol

Catalyst
Pd–62, Pd–100, Pd–103, Pd–111, PdCl2 Rh–110, Rh–112, RhCl3.xH2O, RhI3

25–200

1–50

None

4.5 DECARBONYLATION
Both Pd and Rh catalysts have been used to decarbonylate aldehydes (to produce alkanes) and acyl chlorides (to produce chloroalkanes or chloroarenes).

The decarbonylation reaction can be used to advantage in classical carbohydrate chemistry, exemplified by the one–step synthesis of arabinitol from glucose.

CHO H HO OH H OH OH CH2OH HO H H CH2OH H OH OH CH2OH Arabinitol

+

CO

RCOX

RX

+

CO

(X = H, Cl)

H H

There are also reports of the effective decarbonylation of carboxylic anhydrides, ketones and ketenes. Dihydrocinnamaldehyde can be decarbonylated with Rh (Rh–40 [RhCl(CO)(PPh3)2] or Rh–100 [RhCl(PPh3)3]) to form ethylbenzene1 in 96% yield.

Glucose

Yields of 90% can be achieved with Rh-100 in N–methylpyrrolidone at 130°C in 30 minutes.2

Reaction
Decarbonylation of aldehydes, acyl chlorides, carboxylic acid anhydrides, ketones and ketenes

Temperature (°C)
110–145

Pressure (bar)
1

Solvent
N–methylpyrrolidone, toluene, benzonitrile or xylene

Catalyst
Rh–100, Rh–40, Rh–93 + chelating diphosphine

1 J.M. O’Connor and J. Ma J. Org. Chem. (1992) 57 5075 2 M.A. Andrews and S.A. Klaeren Chem. Comm. (1988) 1266 46

© 2008 Johnson Matthey Plc

4.6 HYDROSILYLATION
Hydrosilylation (often referred to as hydrosilation) is the addition of an H–Si bond across a carbon-carbon double bond.

Rh catalysts can selectively hydrosilylate alkynes to the alkene, but the regiochemistry is very dependent on the solvent used.2

RC

CH

+

Et3SiH

Rh-100

R H

SiEt3

R

H SiEt3 trans

+
H cis H

CH2

CHR’

+

R3SiH

R3Si

CH2CH2R’

The reaction finds practical application in the “curing” or hardening of silicone polymers effected by the cross coupling of different silicone fragments. Benzene
O Si O H R

Solvent

% cis 86 3

% trans 12 95

others 2 2

+
CH2

R’

O Si CH O

O Si O

R CH2

R’

O Si CH2 O

Acetonitrile

Platinum compounds are extremely active catalysts for this reaction.1 The catalyst can be used at such low levels that it is not necessary to separate it from the silicone product. Originally, chloroplatinic acid (Speier’s catalyst) was used as the most readily available and cheapest hydrosilylation catalyst. However there are two problems:• chloroplatinic acid is a potent sensitizer and hazardous to health, so great care must be taken during its handling • chloroplatinic acid contains platinum in oxidation state IV which must be reduced to Pt(0) before it becomes catalytically active. This results in a variable induction period. A more reliable/reproducible catalyst is Karstedt’s catalyst which is made from chloroplatinic acid by the addition of an appropriate siloxane and reducing agent. The Pt is in the Pt(0) oxidation state when used. Johnson Matthey supplies a variety of custom Karstedt’s catalyst. In some cases, specific Pt(II) precursors are used rather than Karstedt’s catalyst. Compounds which have been used in this way include Pt-92 [PtCl2(cyclohexene)]2, Pt-96 [PtCl2(COD)] and Pt-112 [PtCl2(SEt2)2]. Although homogeneous catalysts are commonly used, heterogeneous Pt/C catalysts are effective in some cases.

Rh catalysts can also catalyze some hydrosilylation reactions that cannot be catalyzed by Pt complexes3. Rh catalysts have also been used to prepare chiral silanes.4

1 L.N. Lewis et al. Platinum Metals Rev. (1997) 41 6 2 R. Takenchi and N. Tanonchi J. Chem. Soc. Perkin Trans. (1994) 2909 3 A.G. Bessmertnykh et al. J. Org. Chem. (1997) 62 6069 4 K. Tamao et al. J. Am. Chem. Soc. (1996) 118 12469

© 2008 Johnson Matthey Plc

47

Reaction
Hydrosilylation of alkenes

Temperature (°C)
25–75

Pressure (bar)
1

Solvent
None or hydrocarbons

Catalyst
Chloroplatinic acid, Pt–92, Pt–96, Pt–112, Pt–114, Pt/AI2O3 B301013-5, B301099-5 Rh–93, Rh–100

Hydrosilylation of alkyne to cis-alkene Hydrosilylation of alkyne to trans-alkene

25

1

Ethanol or propan-2-ol Acetonitrile

25

1

Rh–93 + PPh3 or Rh–100

4.7 CROSS-COUPLING REACTIONS
Cross-coupling reactions are among the most important chemical processes in the fine chemical and pharmaceutical industries. These reactions represent the key steps in building complex molecules from simple precursors. Recently, there has been a burgeoning of interests in this area, mainly due to interest in coupling challenging substrates, such as electron rich aryl chlorides, triflates, nitriles, etc. Steric effect as well as the presence of sulfur on the substrate can play an adverse role in coupling reactions. One of the key mechanistic steps in coupling reactions is the oxidative addition of the aryl halide, Ar-X to Pd(0) (see below).

The ease of C-X bond cleavage is in the order I > Br > Cl. The relative reactivities of Ar-X can be correlated to their respective bond dissociation energy: Ph-Cl: 96 kcal/mol Ph-Br: 81 kcal/mol Ph-I: 65 kcal/mol

In some cases, the iodide system is active enough for coupling to occur in the absence of a ligand. Typically, a Ph3P-based Pd complex is suited for Ar-Br coupling, while Ar-Cl coupling is practically impossible, although there has been some success with activated aryl chlorides. Electron withdrawing substituents on the Ar ring activates the Ar-X

reductive elimination Ar-R

LnPd

0

oxidative addition ArX

bond, while electron donating groups have a deactivation effect on the Ar-X bond. During the late 1990’s several academic groups (eg: Koie,

LnPd M B Sn Si Zn Mg

Ar R

LnPd

Ar X

Fu, Buchwald, Hartwig, Beller, etc.) found that electronrich phosphines (aliphatic) in the presence of a Pd precursor favor the Ar-Cl addition to Pd(0). The bulkiness of the ligand (cone angle measures bulkiness) is also

transmetallation MX MR

important, as it facilitates the reductive elimination step. In this regard, t-Bu3P acts as an excellent electron rich, bulky

General Mechanism of Coupling

base-HX

LnPd 0

oxidative addition ArX

base LnPd β- hydrogen elimination R Ar
Mechanism of Heck Coupling
48

H X R LnPd X Ar R H LnPd

Ar X

Mehanism of Heck Coupling

© 2008 Johnson Matthey Plc

monodentate ligand. However, t-Bu3P is a pyrophoric waxy solid and therefore difficult to handle in a conventional production environment. Our research indicates that bidentate ligands are equally effective in coupling chemistry. It is well documented that the large bite angle of a bidentate ligand enhances the reductive elimination step. From a handling perspective, a fully formed, relatively air-stable yet active catalyst is a preferred choice. Johnson Matthey offers advanced technology for coupling reactions. Several examples of these electron rich bulky monodentate and bidentate phosphine based “third generation” catalysts are given below.

P(t-Bu)2

Ph

Fe

Ph

Ph Ph Q-Phos

Ph

These catalysts have been successfully scaled up and tested in commercial processes.

4.7.1 Heck Reaction
A Japanese scientist, Mizoroki (1971) and an American scientist, Heck (1972) developed independently a protocol to couple an aryl or alkenyl halide with an olefin in the presence of a Pd based catalyst. These reactions can occur both inter- and intra-molecularly. The application of this chemistry includes the synthesis of hydrocarbons,

P

Pd

P

Pd(t-Bu 3 P)2
Pd-116

conducting polymers, light emitting electrodes, dyes and enantioselective synthesis of natural products. An example of classical Heck reaction is demonstrated for the synthesis of anti-inflammatory agent- LTD4 antagonists1,2.

Br P Pd Br [Pd(μ-Br)t-Bu3P]2
Pd-113
Cl N

O

CO2 Me 3 mol% Pd(OAc) 2 9 mol% P(o -Tol) 3 Et 3 N / DMF / 100°C / 1.5 hr (91%)

Pd

P
Cl N

Br +

O

CO 2Me

>95% trans -isomer

Me Cl N

CO 2 H CO 2 Me

P

Cl Pd

P Pd

Cl

L-699,392 (Merck-Frosst)

Fe
P

These reactions are promoted by a base, which neutralizes
Cl

Cl

the liberated acid. Pd(0), stabilized with an aromatic phosphine ligand, is the active catalytic species (LnPd) and the favored reaction media are dipolar aprotic solvents such as acetonitrile, DMF DMSO and DMA. ,

P

di-t-bpfPdCl2

FibreCat 1032

Pd-118

Recently Heck coupling has been applied to challenging substrates with the aid of the next generation catalysts. An example of such reaction for the synthesis of an API intermediate (actual substrate is disguised) is demonstrated below, where Pd(0) catalyst, Pd(t-Bu3P)2 is the best catalyst of choice.
1 V. Snieckus, Cross Coupling Strategies and methods in Aromatic and Heteroaromatic Synthesis (Scientific Update Course), New Orleans, November 12-14, 2002 2 A.O. King et.al. (Merck), J. Org. Chem., 1993, 58, 3731-3735

© 2008 Johnson Matthey Plc

49

R'' Cl R + R
R''

For challenging aryl chloride conversions several of Johnson Matthey’s third generation catalysts, including
R

Pd-cat DMF/ 120 oC/Et3N

Pd-116, Pd-118 and Pd 119, provide significant advantages.
R

The di-tert-butylphosphinoferrocene palladium dichloride (Pd-118) is an air stable, yet highly active catalyst, which has been proven to be effective in Suzuki coupling. The following table illustrates the generality of the catalyst in Suzuki coupling towards a wide variety of substrates.3

Pd-catalyst Pd(Ph3P)2Cl2 Pd(OAc)2/TPP Pd(t-Bu3P)2 Pd2dba3/(o-tolyl)3P Pd(PPh3)4 Pd(PCy3)2Cl2 Pd2dba3/t-Bu3P

Conversion 0 0 100 95 0 0 100

Selectivity 95 2.5 82

ArX

+

PhB(OH)2

Pd-118/ 120oC K2CO3/DMF

Ar-Ph

Entry Substrate

Catalyst loading 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01 equiv 0.01equiv

yield (%)

Pd(0) (t-Bu3P)2 can be also used for indole and azaindole syntheses by direct annulation.1 In the following example, enamine formation followed by intra molecular Heck coupling of an aryl chloride is speculated, rather than alpha ketone arylation followed by enamine.
R4 R4

1 2 3 4 5 6 7

4-chlorotoluene 4-bromoanisole 4-chloroanisole 4-bromo-3-methylanisole 2-chlorothiophene 2-bromo-4-fluoroanisole 2-chloro-4-fluoroanisole 2-chloro-3-methylpyridine 2-chloro-4, 6-dimethoxytriazine Bromomesitylene

98 100 100 96 84 95 95 89 100 85

Cl R1 NH R2

+
O R3

Pd(t-Bu 3P)2 , K 3PO4 HOAc, MgSO4, DMA

R1 N R2

R3

8 9 10

4.7.2 Suzuki-Miyaura Coupling
For moderately challenging substrates, such as Currently, Suzuki coupling is the most widely utilized Pd catalyzed coupling reaction in the Pharmaceutical and Fine Chemical industries. The coupling reaction involves the reaction of a substituted aryl boronic acid (nucleophile) with a substituted aryl halide, diazonium salt or triflate (electrophile) to produce biaryls. In general, Suzuki coupling reactions require milder conditions than the Heck reactions and are favored due to the non toxicity of the boron reagents.
B(OH)2

bromothiophenes, chloropyridines, etc., the polymer supported Pd catalyst, FibreCat 1032 has shown good results. Following our preliminary report4, additional research from Abbott Laboratories 5, indicates that these are practical catalysts for conventional and microwave assisted Suzuki coupling. An example of the microwave assisted Suzuki coupling reaction is given below.

Commercial examples include antihypertensive drug Valsartan (Novartis) and the fungicide Boscalid
O N N COOH O NH Cl

+

3 % FibreCat 1032 K 2 CO3, EtOH, MW

(BASF)2.

N

Cl
Me

N

Me

Yield: 89% (100%)

N N N Valsartan (Novartis) Boscalid (BASF) NH Cl

1 Nazare, et.al., Angew. Chem. Int. Ed., 2004, 43, 4526-4528. 2 Rouhi, Chemical and Engineering News, 2004, 82, 49-58 3 Colacot & Shea, Org. Lett., 2004, 21, 3731. 50

4 Colacot et. al., Organometallics, 2002, 21, 3301. 5 Sauer et.al., Org. Lett., 2004, 6, 2793.

© 2008 Johnson Matthey Plc

4.7.3 Alpha-ketone Arylation
Alpha-ketone arylation is a relatively new type of carboncarbon coupling reaction, where an aryl halide is added to the alpha position of a carbonyl group by activating the CH. Early studies indicate that catalyst choice is critical in accomplishing this type of coupling. Initial results show that Pd-118 is a very good catalyst for such transformations. An example is given below.
X + X

Simple Pd(0) compounds such as Pd-101 Pd(PPh3)4 or catalysts made from precursors such as Pd-111 [Pd(OAc)2]3, Pd-110 [Pd(allyl)Cl]2 and Pd-94 Pd2(dba)3 with suitable phosphine ligands can also be used, depending on the substrate.

Ar-X

di-tbpfPdCl 2 alcoxide base Toluene
O Ar

4.7.5 Organometallic Reactions
In some reactions, a prerequisite is the production of an organometallic intermediate containing metals such as magnesium, tin, zinc or lithium. These organometallic compounds can react with an aryl halide with the elimination of the metal halide and the subsequent formation of a coupled product. The best known general example of this type of reaction is probably the Grignard reaction.

O

Yield 70-95%

4.7.4 Carbon-heteroatom Coupling – e.g. Buchwald-Hartwig Amination
Carbon–heteroatom coupling can be effected by a Pdcatalyzed reaction. This can include forming C-N, C-O, C-S and C-P bonds. The C-N bond forming process (amination) is often referred to as the Buchwald–Hartwig, although initial work was carried out by Koie and co workers in Japan. A general scheme of amination and ether formation is shown below. As there is an acid by-product, a base is used, often a strong organic base such as NaOtBu to drive the reaction.

ArX + Ar1MgX

Ar

Ar1

+ MgX2

In some cases these reactions proceed satisfactorily. However, in other cases, the presence of a homogeneous palladium catalyst may dramatically improve the yield of the coupled product. The relative positions of the substituents on the aromatic rings determine the point at which coupling occurs, i.e.
Br MgBr

Pd R

+
R

+ MgBr2

Heterocyclic ring coupling is also possible, e.g. A wide variety of homogeneous Pd(0) catalysts can be used for the above reactions. The new range of highly active Pd-catalysts are very suitable for this difficult coupling reaction. Pd-113 and Pd116 have been shown to catalyze a wide range of substrates including aryl chlorides and triflates. Air stable catalysts such as Pd-118 (Pd(dtbpf)Cl2) and Pd-107 (Pd(dppf)Cl2) show good activity for aryl chlorides and bromides, respectively. The following example show the fast rates achieved with Pd-113 (strong base)6 and the stable turnover available with Pd-116 (cheaper base)7.
CH2Br Pd CH2CH CH2 CH3 ZnCl Br Pd CH3

+
S S

+ ZnClBr

The organometallic reagent may in some cases be completely aliphatic, but coupling can still occur, e.g.

+ CH2 CHSnBu3
Bu = butyl

+ Bu3SnBr

Palladium-catalyzed reactions of this type, involving the use of tin-based reagents, are often referred to as Stille coupling reactions. Similar reactions involving zinc-based reagents are referred to as Negishi couplings.

6 J. Hartwig et al, Angew. Chem. Int. Ed., 2002, 41, 4746 7 J. Hartwig et al, J. Org. Chem., 2002, 67, 6479 51

© 2008 Johnson Matthey Plc

4.7.6 Sonogashira Reaction
Palladium catalysts can also be employed in the coupling of terminal alkynes with aryl or alkyl halides. The reaction, known as the Sonogashira reaction, generally involves the use of a palladium catalyst in conjunction with copper iodide, the copper reacting with the alkyne to form an alkynylcuprate. Mild conditions are usually used for this reaction, often room temperature, allowing a large number of functional groups to be tolerated.

The generic structure of such species is

X = halide, acetate L = P or N C Pd L X X Pd C L

Many of these complexes show not only increased activity over the more traditional catalysts, but also exhibit very good thermal and air stability. In the case of the phosphite catalysts developed by Bedford1 (see below) these reactions can be performed in air without the drying of

R X + R’

Pd/CuI base

R R’

solvents or reagents – a major advance over the more conventional catalysts. Their main advantage is activity – catalyst loadings as low as 10-4 mol % have been successfully used in reactions of aryl bromides.
The Bedford bridging chloro palladacycle containing the tris (2,4-di-t-butyl phenyl) phosphite ligand – Pd 109.

If the reaction is performed on an alkene, the geometry about the double bond is usually preserved, making this an extremely useful reaction for the synthesis of ene-yne molecules with specific geometry.
R' X Pd/CuI

+
R

R' base R

t-Bu ArO OAr P Pd Cl ArO t-Bu Cl Pd P O OAr t-Bu

4.7.7 Palladacycles
The use and versatility of coupling reactions has increased recently with the advent of new Pd catalysts known as palladacycles.

O t-Bu

Reaction
Heck

Temperature (°C)
25–100

Solvent
Various (e.g. toluene, THF)

Catalyst
Pd–62, Pd–100, Pd–101, Pd–106, Pd–108, Pd–109, Pd–111, Pd-116, Pd-119 FibreCat®–1001, 1002 Pd/C A109047-5, A405028-5, A503023-5, A102023-5, A470085-5 Pd–101, Pd–109, Pd–111, Pd-113 Pd-118 FibreCat®–1001, 1002, 1032 Pd–106, Pd–107 Pd–113 , Pd–111, Pd–116, Pd–118 ®–1001, 1002 FibreCat

Suzuki

25–100

Various

Buchwald–Hartwig

80–100

THF or toluene

Organometallic reactions

25–100

THF dioxane, toluene or DMF ,

Pd-62, Pd-100, Pd–101, Pd-103, Pd-106 Pd-100, Pd-101 FibreCat® 1032

Sonogashira reaction

25–120

THF or DMF

1 D.A. Aldisson, R.B. Bedford, S.E. Lawrence and P Scully .N. 2 Chem. Comm. (1998) 2095 52

© 2008 Johnson Matthey Plc

4.8 CYCLOPROPANATION AND
CARBENE REACTIONS
The generation of carbenes from the decomposition of diazo compounds can be catalyzed by metal complexes. The carbene binds to the metal and can subsequently be transferred to an alkene (cyclopropanation), to an alkyne (cyclopropenation) or even inserted into a C–H bond depending on the choice of catalyst, substrate and conditions.
RCH CHR + CR1R2N2 RCH C R1 R2 CHR

One of the best known applications is in the synthesis of chiral methylphenidate. The racemic form of methylphenidate is sold as Ritalin™, widely prescribed for the treatment of hyperactive children. However, the d-threo isomer is 13 times more active than its mirror image.2
Dirhodium(II) tetrakis[methyl-2-pyrrolidone 5(S) carboxylate] Rh2(5S-MEPY)4

+

N2

CH3OOC

N Rh

O

O N Rh

COOCH 3

RC

CR

+ CR R N2

1 2

RC C R1

CR R2

+

N2

N CH3OOC O

O

N

COOCH3

The original catalysts were based on Cu complexes, but more recent work has involved the use of Rh catalysts. For non-stereoselective cyclopropanations or cyclopropenations, the catalysts of choice are based on dimeric Rh(II) carboxylates e.g. Rh-110 [Rh(OAc)2]2 Pd catalysts such as Pd-111 [Pd(OAc)2]3 have been used, but their application seems to be restricted to reactions involving terminal olefins and α,β unsaturated carbonyls.
N2

The process involves a highly selective intermolecular asymmetric insertion at the α position of N–Boc piperidine with methyl phenyldiazoacetate followed by removal of the Boc protecting group.
O OCH3 O OCH3 NBoc

It is in the area of enantioselectivity that the Rh(II) carboxamidate1 complexes really demonstrate their effectiveness. These catalysts are characterized by four bridging amide ligands bound to the di–rhodium core, with two oxygens and two nitrogens bonded to each Rh atom, and each pair of nitrogen atoms adjacent to one another.

NBoc Rh2(5S-MEPY)4 Cyclohexane/ 500C/ 4h

69%

HCl

O OCH3 NH.HCl

d-threo-methylphenidate

Reaction
Carbene insertion into terminal alkene or α,β unsaturated carbonyl Cyclopropanation, cyclopropenation, carbene insertions

Temperature (°C)
0-10

Pressure (bar)
1

Solvent
Ether or dichloromethane

Catalyst
Pd–70, Pd–111

0–50

1

Cyclohexane, pentane or dichloromethane

Rh–110, Rh–115

1 M.P Doyle and D.C. Forbes Chem. Rev. (1998) 98 911-935 . 2 T. Colacot Proc. Indian Acad. Sci. (Chem. Sci.) (2000) 112 197 53

© 2008 Johnson Matthey Plc

4.9 ISOMERIZATION
Isomerization of olefins can be carried out effectively using homogeneous catalysts. Wilkinson’s catalyst (Rh-100 RhCl(PPh3)3) has been used in the synthesis of several natural products and can be used in the isomerization of allyl alcohols to enols.

Olefin isomerization processes can also be catalyzed by Pd or Ru. The Pd(II) catalysts are well suited for industrial application because of their stability to air and moisture. Here the trans-isomer is favored kinetically as well as thermodynamically.

Pd

OH

Rh CH3

1-pentene OH

trans-2-pentene

Heterogeneous catalysts are also effective for olefin isomerization, with Pd/C being the best when used under acidic conditions at elevated temperatures. Rearrangements can also be performed with Pd catalysts. Optically active cyanohydrin can be stereoselectively isomerized to the α,β–unsaturated nitrile1 in 89% ee using Pd-62 PdCl2(CH3CN)2.
OAc PdCl2(CH3CN)2 C5H11 OAc 83% yield C5H11

* CN

*

CN

Reaction
Allylic rearrangements

Temperature
(°C) 25–90

Pressure
(bar) 1

Solvent
THF xylene, benzene , or no solvent

Catalyst
Pd–111 + PPh3, Pd–101, Pd–62 Pd/C A109047-5, A503023-5, Pd/c A503038-5, A570147-5, Pd/c A570129-5 Rh–100, RhCl3.xH2O

1 H. Abe, H. Nitta, A. Mori and S. Inoue Chem. Lett. (1992) 2443 54

© 2008 Johnson Matthey Plc

4.10 OLIGOMERIZATION AND
POLYMERIZATION
Rh, Pd and Ru are the main metals used in PGM-catalyzed polymerization reactions. Low molecular weight oligomers can be produced and are dependent on the type of catalyst used. These catalysts were first developed by Grubbs2 in 1993. Tricyclohexylphosphine is the preferred ligand as bulky groups make the catalyst more active. These catalysts are active without rigorous exclusion of water
CH2 Rh PPh3 CH2 CH2 CH2 CH2 CH2 CH2 C CH2 allene Rh CH2 CH2

or oxygen, and are more tolerant of functional groups than Zeigler–Natta catalysts. ROMP reactions with norbornene derivatives can be catalyzed by vinylidine Ru complexes.3 These carbene complexes can be prepared from Ru-100 RuCl2(PPh3)3 by reaction with terminal alkynes followed by phosphine ligand exchange.

Polyketones can be made by the Pd-catalyzed copolymerization of carbon monoxide and an olefin (ethylene or propylene). The Pd(II) catalyst is made from palladium acetate or palladium chloride and a diphosphine ligand.1 Polymerization of simple alkenes such as polyethylene is normally carried out using Ziegler–Natta catalysts (W, Ti, Ni). However, recent advances in Ru carbene chemistry have lead to new interest in PGM-catalyzed polymerization. Ring Opening Metathesis Polymerization (ROMP) can be efficiently catalyzed by Ru carbene complexes of the type shown.

Cl Cl

PCy3 Ru C

Bu H

PCy3
Similar Ru(II) carbene catalysts can be prepared from Ru–120 [RuCI2(p–cymene)]2 without using phosphine ligands. These catalysts enable high stereoregularity in the polymerization of substituted norbornadienes.

Reaction

Temperature (°C)
25–100

Pressure (bar)
1–10

Solvent

Catalyst

Polymerization

Alcohols, toluene, biphasic systems (water/hexanol), or no solvent

Ru–100, RuCl3.xH2O + ligand, Ru–120 + ligand, Pd–101, Pd–111 + PPh3, RhCl3.xH2O, Rh–100

Copolymerization

25–150

1–150

CH2Cl2 or methanol

Pd–62, Pd–101, Pd–111 or PdCl2 + ligand Pd–101, Pd–111 + PPh3 + nucleophile

Telomerization

25–80

1

Acetonitrile or methanol

1 K. Nozaki, N. Sato and H. Takaya J. Am. Chem. Soc. (1995) 117 9911 2 S.T. Nguyen, R.H. Grubbs and J.W. Ziller J. Am. Chem. Soc. (1993) 115 9858 3 H. Kitayama and F Ozaura Chem. Lett. (1998) 67 . 55

© 2008 Johnson Matthey Plc

4.11

SELECTIVE OXIDATION

In contrast to hydrogenation systems, sulfur-containing moieties do not appear to poison PGM catalysts under oxidation conditions. For example, 2-thienylmethanol can be readily oxidized to the corresponding aldehyde in >90% yield with a Pt/C catalyst in toluene. Furthermore, the catalyst can be reused quite effectively.
1/

Supported PGMs are very good oxidation catalysts and this property is used to effect the total oxidation of pollutants to CO2 , H2O and N2 in industrial fume abatement and automotive anti–pollution applications. Pt catalysts are used for the oxidation of the fuel (hydrogen, lower aliphatic alcohols and some other fuels) in fuel cells and other electrochemical devices.

2

O2
S CHO

+ H 2O

S

CH 2OH

In order to effect selective oxidations, it is necessary to operate under relatively mild conditions to minimize CO2 formation; typically 20–60°C and up to 5 bar air pressure. If flammable solvents are required then low O2 concentrations (typically 3%O2 or 5%O2 in N2) can be used as a safe replacement for air. The longer reaction times can be compensated for by increasing the pressure within the reactor. Johnson Matthey has also shown that H2O2 (typically 30%) is an effective oxidant. The PGM catalysts will rapidly decompose H2O2, therefore efficient use requires a continuous feed over the course of reaction. When using H2O2 as oxidant it must be noted that water by-product is also being introduced, the presence of which can enhance the selectivity to the carboxylic acid.
1/ 2

4.11.1(b) Secondary Alcohol to Ketone
For aliphatic alcohols, Pt-Bi catalysts exhibit the highest activity. The Pt-Bi catalysts can be run under neutral or basic conditions. For example, 2-octanol can be readily oxidized to the corresponding ketone in >90% yield with Pt-Bi/C in water with 0.5 molar equivalent of NaOH added. The catalyst can be used for at least three reaction cycles with negligible loss in activity.
OH O

O2

+ H 2O

For aromatic alcohols the mixed metal catalyst Pd-Pt-Bi/C has shown the highest activity followed by Pd/C and Ru/C.

4.11.1(a) Primary Alcohol to Aldehyde
The selective oxidation of primary alcohols to the aldehyde functionality can be performed in the liquid phase. For aliphatic alcohols the Bi-promoted Pt catalysts have shown the highest activity. Ru/C is more aldehyde-selective but higher catalyst loadings are required to attain desirable conversions. Selectivity to the aldehyde is enhanced by the use of organic solvents which are immiscible with water, e.g. toluene, xylene, dichloroethane etc. For example, geraniol can be converted to citral in toluene or xylene solvent at 60ºC and 3 bar air using Pt-Bi/C, Pt/C or Ru/C catalysts.

These catalysts require the presence of base (as with primary aromatic alcohol oxidation). The selective oxidation of secondary alcohols can be conducted in the presence of water, such that H2O2 is a suitable oxidant in these reactions.

4.11.1(c) Primary Alcohol or Aldehyde to Carboxylic Acid
The selective oxidation of primary alcohols and aldehydes to the carboxylic acid functionality can be achieved using Bi-promoted Pt catalysts and trimetallic Pd-Pt-Bi/C. Under neutral conditions Pt-Bi/C can give high carboxylic acid yields, whereas Pt-Pd-Bi/C catalyst requires basic

OH + 1/ 2 O 2

O

conditions to attain high activity (which can also lead to
+ H 2O

the formation of condensation by-products). Water is a good solvent for this reaction due its promotional effect on the oxidation of aldehyde to carboxylic acid.

For aromatic alcohols the Pd-Pt-Bi/C, Pd/C and Ru/C catalysts all display high activity under basic conditions. These conditions can be achieved by running the reaction in the presence of base such as an aqueous solution of NaOH or NaHCO3.
56

© 2008 Johnson Matthey Plc

Pd-Pt-Bi/C has been used in aqueous solutions at 40–60ºC for the air oxidation of sugars to the corresponding monoacid, e.g. glucose ➝ gluconic acid. The reaction is favoured by alkaline conditions, typically pH 8–10.

• careful control of the oxygen availability (often achieved by operating the reaction with partial oxygen pressures as low as 10 mbar) • pH optimization

Premature poisoning of the Pt catalyst can occur by complete coverage of the surface by oxygen to form a Pt oxide species. This effect can be minimized by: Reaction Temperature (ºC)
30-60

• periodic regeneration of the catalyst by a washing/reduction treatment

Pressure (bar)
1-3

Solvent

Catalyst

Primary Alcohol to Aldehyde

Toluene, xylene, acetonitrile

Pt/C B103032-5, B103018-5 B501032-5, B101002-5, B112002-5, B170201-5 Ru/C D101023-5, D101038-5 D170201-5, D103002-5 Pd/C A503023-5, A102023-5 A570129-5, A102038-5 Pt, Bi/C B503032-5, B111022-5 FibreCat® 3002

Secondary Alcohol to Ketone

30-80

1-3

Water, water + base, toluene, stylene acetonitrile

Pt/C B103032-5, B103018-5 B501032-5, B101002-5, B112002-5, B170201-5 Ru/C D101023-5, D101038-5 D170201-5, D103002-5 Pd/C A503023-5, A102023-5 A570129-5, A102038-5 Pt, Bi/C B503032-5, B111022-5 FibreCat® 3002

Alcohol or Aldehyde to Acid

30-60

1-2

Water, water + base

Pt/C B103032-5, B103018-5 B501032-5, B101002-5 B112002-5, B170201-5 Pd/C A503023-5, A102023-5 A570129-5, A102038-5

Glucose to Gluconic Acid

40-50

1

Water + base

Pt/C B103032-5, B103018-5 B501032-5, B101002-5 B112002-5, B170201-5 Pd/C A503023-5, A102023-5 A570129-5, A102038-5 Pt, Bi/C B503032-5, B111022-5

4.11.2 Dihydroxylation of Alkenes
The cis-dihydroxylation of alkenes has been traditionally catalyzed by osmium tetroxide in combination with a variety of co-oxidants including hydrogen peroxide, sodium hypochlorite, air (oxygen), N-methylmorpholine-N-oxide and t-butylhydroperoxide.
H RCH CHR' H C R' Os

Osmium tetroxide is extremely hazardous and great care must be exercised when using this reagent. There are two user-friendly alternatives to using the tetroxide. The first consists of osmium tetroxide anchored onto a polymeric support (FibreCat 3003). Supporting the osmium in this manner renders it non-volatile and nonhazardous.

+ 1/2O2 + H2O

R

C

OH OH

© 2008 Johnson Matthey Plc

57

Reaction

Temperature (°C)

Pressure (bar)

Solvent

Catalyst

Dihydroxylation

0–50 0-60

ca 1 ca 1

t–Butanol, water or THF t–Butanol/Water

OsO4 or K2[OsO2(OH)4] FibreCat™ 3003

This material is best used in conjunction with Nmethylmorpholine-N-oxide and at temperatures of 60°C or less which ensures that minimal levels (<5%) of the metal leaches from the support. Supporting the osmium in this manner also allows it to be easily removed from the reaction and allows for its possible reuse.
Pd(0)
CH2 CH2 + Pd(II) + H2O

+ CH3CHO + Pd(0) + 2H

The process was rendered catalytic and commercialized by Wacker Chemie. The role of the Cu is to reoxidize the Pd(0) back to Pd(II).

+ +

2Cu(II) 2H+

Pd (II) +

2Cu(I)

The other alternative is “potassium osmate dihydrate” (dipotassium trans-dioxotetra(hydroxo)osmium (VI)). This can be used as an air-stable user-friendly source of homogeneous osmium for dihydroxylations in aqueous solvents.

2Cu(I)

+

2

2Cu(II)

+

H2O

There are several versions of this process, both single and two stage. Some are based on Pd/Cu/Cl and some are halide free. Ruthenium tetroxide, although not available commercially, can be generated in situ from a suitable Ru precursor such as RuCl3.xH2O and one of the oxidizing agents included in section 4.11.2. Ruthenium tetroxide is considerably more reactive than osmium tetroxide and is capable of oxidatively cleaving alkenes to form carboxylic acids.

4.11.3 Oxygen Insertion Reactions
Over 85% of the world’s acetaldehyde is made by the selective oxidation of ethene with a mixed Pd/Cu homogeneous catalyst.
Pd/Cu CH2 CH2

+

2

CH3CHO
’RuO4’ C8H17CH CHC7H14COOH

The fact that Pd salts can oxidize ethene to acetaldehyde stoichiometrically, has been known for over 100 years.

+ 2O2

C8H17COOH pelargonic acid

+

HOOCC7H14COOH azelaic acid

oleic acid

Reaction

Temperature (°C) 20–50

Pressure (bar) 1–5

Solvent

Catalyst
recommended catalyst type shown in parenthese

CH2=CH2 → CH3CHO

Acetic acid or alcohol

Pd–111, PdCl2 + Cu2+

Oxidative olefin cleavage

25–70

1

Various

Ru-100, RuCl3

4.11.4 Acetoxylation
A key step in the Mitsubishi process for the production of 1,4-butanediol from butadiene involves a Pd-catalyzed acetoxylation step.

The acetoxylation step was originally researched with a homogeneous Pd catalyst, but commercially a Te-modified Pd heterogeneous catalyst is used to obtain a higher selectivity to 1,4-diacetoxybutene and easier product/metal separation.

+

CH3COOH

+

2

CH3COO

OOCCH3

+

H2O

HO
58

OH

+

2CH3COOH

© 2008 Johnson Matthey Plc

4.12 PARTICULATE CATALYSTS
Particulate catalysts are used in fixed-bed continuous gas phase or liquid phase reactions. The dimensions of the catalyst bed (area of cross section and length), reactor design, and size and shape of the individual particulate (sphere, cylindrical tablet, ring, extrudate etc) are dictated by the requirements of heat transfer, fluid flow and pressure drop in the system. For liquid phase reactions, the reactant, dissolved in a suitable solvent if necessary, is pumped into the column packed with catalyst. The reactant gas, usually hydrogen (or air-oxygen) can be passed co-currently or countercurrently through the catalyst bed. The product is collected continuously from the catalyst bed and no filtration of catalyst is involved. For gas phase reactions, only co-current flow is possible. Since the formation of fine particles by attrition must be kept to a minimum, high mechanical strength is a fundamental requirement of all particulate catalysts. The most commonly used particulate support in the fine chemicals industry is γ-alumina. Although not as strong as α-alumina, the relatively high surface area (100–350 m2g-1) makes γ-alumina a more useful catalyst support than α-alumina (typical surface area 1–10 m2g-1). In some continuous gas phase reactions, the catalyst may become deactivated due to the deposition of coke on the active sites. In such cases the catalyst can be regenerated in situ by the controlled oxidation of the deposited material (to CO2 and H2O). However, great care must be taken to avoid excessive exotherm generation in the bed to prevent irreversible metal crystallite sintering with subsequent loss of catalyst activity. Although not as strong as alumina, carbon can be used as a granular support in fixed bed reactors. It is used in cases where the aggressive/corrosive nature of the reactants makes the use of γ-alumina impossible, e.g.

The catalytic metal may be deposited on the outer surface of the shaped particulate support (eggshell deposition) or may be homogeneously impregnated throughout the bulk of the support (uniform deposition). For most purposes, the diffusion of reactants into the particulate bulk is slow, so eggshell catalytic metal loading is generally preferred. Catalytic metal loadings on particulate supports are usually in the range 0.2-2% by weight with respect to the weight of support (as opposed to 1-10% for powdered catalysts). Care should be exercised when charging particulate catalysts to fixed bed reactors to minimize physical damage and the generation of fines with increased pressure drop and metal loss consequences. Details of catalyst loading procedures are given in Section 2.1.3. If catalyst to be used for a hydrogenation is supplied in an unreduced form, it needs to be activated in the reactor before use according to the following procedure: (i) load the catalyst carefully into the reactor and flush away air with flowing nitrogen (or other inert gas) at ambient temperature. (Ensure the volume of nitrogen exceeds 5 x the volume of the reactor.) (ii) introduce hydrogen at a concentration of 1% into the flowing nitrogen. Check for an exotherm in the catalyst bed. If it does not exceed 20˚C, then slowly increase the temperature (over 60 minutes) up to the desired reaction temperature. The low hydrogen concentration will prevent a large exotherm when the catalyst species undergoes reduction. (iii) check for any exotherm and gradually increase the hydrogen concentration to 100% hydrogen. (iv) slowly introduce the feed to minimize any exotherms until the desired feed rate is achieved. When the catalyst is finally discharged from the reactor, the above sequence should be reversed. It is very important to ensure that all traces of H2 are removed and that the catalyst has fully cooled to ambient temperature

Cl2CHCOOH

ClCH2COOH

+ HCl

before exposure to air.

© 2008 Johnson Matthey Plc

59

4.12.1 Organic Synthesis
Like their powdered catalyst counterparts, particulate PGM catalysts are used for a variety of reactions including hydrogenation, amination, dehydrogenation, hydrodehalogenation and isomerization. Applications For Johnson Matthey Particulate Catalysts in Organic Synthesis Catalyst Type 47 48 49 50 50A 50B 54 Support Material Carbon Alumina Alumina Alumina Alumina Alumina Alumina Nominal Size/Shape 2–5mm Granules 3mm Tablets 3mm Tablets 3mm Tablets 4–8mm Spheres 2–4mm Spheres 3mm Tablets PGM Pd Pd Pd Pd Pd Pd Pd Loading (%wt) 0.5, 1.0 0.5 2 0.5 0.5 0.5 0.5 Applications Hydrogenation of Olefins Hydrogenation/Dehydrogenation Hydrodehalogenation Hydrogenation/Dehydrogenation Hydrogenation/Dehydrogenation Hydrogenation/Dehydrogenation Hydrogenation of Phenol to Cyclohexanone Amination of Ketones Hydrogenation of Olefins Aromatic Ring Hydrogenation Hydrogenation of Alkynes and Alkenes to Alkanes Hydrodehalogenation Hydrogenation / Dehydrogenation Hydrogenation / Dehydrogenation Hydrogenation of Olefins Hydrogenation of Olefins Alkene to Alkane Hydrogenation Reductive Alkylation Hydrogenation / Dehydrogenation Hydrogenation / Disproportionation Hydrogenation of Olefins Hydrogenation of Phenol to Cyclohexanone Dehydrogenation Aromatic Ring Hydrogenation Benzene to Cyclohexane Decomposition of Hydrogen Peroxide Amination of Carbonyls Dehydrogenation of Alcohols to Carbonyls Hydrogenation of Aliphatic Carbonyls Aromatic Ring Hydrogenation Hydrogenation of Aliphatic Carbonyls Hydrogenation of Olefins Aromatic Ring Hydrogenation Hydrogenation of Carbonyls Hydrogenation of Aromatics Typical applications using Johnson Matthey particulate catalysts for organic synthesis are shown below.

86

Carbon

3mm Extrudate

Pd

0.8

300 301 354 355 360 375 382 385 386 454 73

Alumina Alumina Alumina Alumina Alumina Carbon Carbon Carbon Carbon Alumina Alumina

3mm Extrudate 3mm Extrudate 4–6mm Spheres 2–4mm Spheres 3mm Tablets 3mm Extrudate 2mm Extrudate 0.6–0.85mm Granules 2–5mm Granules 4mm Ring Extrudate 3mm Tablets

Pd Pd Pd Pd Pd/Ru Pd Pd Pd Pd Pd Pt

0.5 0.5 0.2 0.5 0.1/0.1 1 2 5 1 1 0.3, 0.5

176

Alumina

4–8mm Spheres

Pt

1

146

Alumina

3mm Tablets

Ru

0.5

642

Carbon

2mm Extrudate

Ru

3

660 520

Silica Alumina

1.5mm Extrudate 3mm Tablets

Ru Rh

3 0.5

60

© 2008 Johnson Matthey Plc

4.12.2 Gas Purification
There is a growing requirement for very high purity gases in a wide variety of applications. In addition to the purification of chemical feedstreams, there are requirements for ultra–pure gases in the electronic and nuclear industries. Contaminants such as O2 or H2 frequently need to be removed to single ppm levels in order to prevent such problems as:• promotion of unwanted side reactions • corrosion (or chemical attack) of the reactor itself or of the catalyst • unwanted modifications to the semiconducting properties of electronic components. This has led to the development of a range of PGM catalysts on γ-alumina supports for gas purification. Essentially, the reaction is:-

Such poisons typically include:• carbon monoxide (in industrial H2 derived from syngas) • sulfur compounds • halogen compounds • oil mists (from compressors) • acid and alkaline sprays (from gas scrubbers) • heavy metals such as Pb or Hg (in industrial H2 derived by electrolysis) The use of an elevated temperature may be beneficial if significant quantities of carbon monoxide or sulfur are present or if the gas stream is saturated with water vapor. The inlet temperature must always be at least 10°C above the dew point of the gas stream to avoid the possibility of liquid water condensing on the active site and reducing the catalyst’s overall activity. Operation at elevated pressures will also improve catalyst efficiency. The volumetric gas flow per unit time divided by the overall volume of the catalyst bed is known as the Unit Space Velocity. The most common unit of time quoted is the hour. Therefore:

2H2

+ O2 ΔH = - 241.8 kJ/mol

2H2O

Gas Hourly Space Velocity = Volume of gas flowing/hour (GHSV) Volume of catalyst bed The GHSV which is required in any specific situation will depend on:• impurity levels present in the inlet gas • maximum allowable impurity level in the outlet gas

Thus, for example, O2 may be removed from an inert gas (e.g. N2, He etc) by combination with the stoichiometric amount of hydrogen to form the easily removable water vapor. These catalysts are simple to use, involving merely the passage of the gas stream through the catalyst bed supported between grids in a suitable reactor vessel. The catalytic combination of H2 and O2 is an extremely facile reaction. The reaction is exothermic, and the actual temperature increase will depend on the concentration of gas component to be removed and the size and thermal insulation of the catalyst bed in use. To preserve catalyst activity, the maximum operating temperature in any such gas phase reaction should be no more than about 600˚C. The water vapor formed can readily be removed downstream from the reactor either cryogenically or using a conventional dryer containing a desiccant such as molecular sieve. Ideally, catalyst poisons should be eliminated from the process gas stream to maximize catalyst performance and life.

(i.e. percentage conversion required) • concentration of poisons present • gas to be purified. The pressure drop across a catalyst bed is determined by a number of factors:• GHSV • aspect ratio of the catalyst bed for a given overall bed volume i.e. length to diameter ratio • temperature and pressure • gas viscosity • shape and size of the individual catalyst particulate.

© 2008 Johnson Matthey Plc

61

It is essential that attrition loss and dust formation be kept to a minimum, in order to minimize an increase in pressure drop over time.

Pressure drop as a function of particulate size and shape is shown below.

3mm Tablets

3.5mm Ring Extrudate Pressure Drop 5mm Tablets 4-8mm Spheres

7mm Tablets

Superficial Velocity (Hydrogen) Typical Gas Purification Applications Catalyst Type 48 49 50 50A Nominal Size & Shape of Alumina 3 mm Tablets 3 mm Tablets 3 mm Tablets 4–8 mm Spheres PGM Pd Pd Pd Pd Loading (% Wt) 0.3, 0.5 5 0.3, 0.5 0.3, 0.5 Applications O2 from H2, N2, Ar, CO2 by combination with H2 H2 removal getter O2 from H2, N2, Ar, CO2 by combination with H2 O2 from H2, N2, Ar, CO2 by combination with H2 O3 from air or water O2 from H2, N2, Ar, CO2 by combination with H2 O3 from air or water O2 from H2, N2, Ar, CO2 by combination with H2 H2 from O2, Ar, N2, CO2, air, He, He/Ar by combination with O2. O2 from N2 by reaction with CH4. Hydrocarbons from O2, N2, CO2, air, He, Ar by reaction with O2. CO from CO2, N2, air by combination with O2 CO or CO2 from H2 by methanation to CH4 VOC removal from vent streams by reaction with O2 VOC removal from vent streams by reaction with O2 O2 from H2, N2, Ar, CO2 by combination with H2 O2 from H2, N2, Ar, CO2 by combination with H2 Reduction of nitrogen oxides to N2 with H2 in the presence of CO and CO2 Decomposition of N2O Decomposition of N2O

50B

2–4 mm Spheres

Pd

0.3, 0.5

54 73

3 mm Tablets 3 mm Tablets

Pd Pt

0.5 0.3, 0.5

146 256 257 300 301 360

3 mm Tablets 4-6 mm Spheres 2–4 mm Spheres 3 mm Tablets 3 mm Tablets 3 mm Tablets

Ru Pt Pt Pd Pd Pd/Ru

0.5 0.1, 0.3 0.1 0.3, 0.5 0.3, 0.5 0.12/0.12

519 520 630

2-4 mm Spheres 3 mm Tablets 3 mm Tablets

Rh Rh Ru

0.5 0.5

0.3, 0.5, 1 CO or CO2 from H2 by methanation to CH4

62

© 2008 Johnson Matthey Plc

4.13

HOMOGENEOUS CHIRAL CATALYSIS

+

N2CHCO2Me

Cat* CO2H 92% ee R R R=

Cilastatin

In 1992 the Food and Drug Administration in the U.S. introduced guidelines to encourage the commercialization of single-enantiomers drugs. This has driven the discovery of new and efficient methods to access enantiomerically pure compounds.
Cat* =

N Cu O O 2

OC8H7

Knowles, Horner and Kagan3 independently reported the Traditionally, enantiomerically pure compounds have been obtained by classical resolution of racemates or transformation of naturally occurring chiral compounds, and more recently by chromatographic separation technologies. Biocatalysis is another important tool for the production of single enantiomers, but its applicability is limited by the inherent single-handed, lock-and-key specificity of enzymes. Since the late 1960s, asymmetric organometallic catalysis has become a very powerful strategy and is now recognized in industry as a costeffective means of producing chiral intermediates and products.
AcHN Ph H2 Rh/L* AcHN Ph O H DIOP AcHN CO2H H2 Rh/L* AcHN CO2H O H PPh2 PPh2

first examples of homogeneous-catalyzed asymmetric hydrogenation of olefins employing Rh complexes bearing chiral phosphines. This novel methodology proved to be very successful and Monsanto used it in the preparation of the drug L -DOPA, in what became the first industrial asymmetric synthesis.

72% ee

Asymmetric catalysis is achieved by the combination of a chiral ligand, a metal atom and, in some cases, an achiral additive or other auxiliary ligands. The chosen chiral ligand must have a suitable combination of structure and functionalities to modify the metal atom, generating reactivity and stereoselectivity. The first examples of enantioselective organometallic catalysis can be traced back to 1966, when Noyori et al. described the cyclopropanation of alkenes using a salencopper complex.1 Although very low enantioselectivities (~10% ee) were initially reported, fine-tuning of the copper catalyst allowed Aratani to improve them to 92% ee.2 This methodology was applied later on to the industrial preparation of cilastatin.

88% ee

These first achievements stimulated further investigations, and in 1980 Noyori published his first article on asymmetric hydrogenation of aminoacids employing chiral BINAP based on the C2 symmetric binaphthyl backbone. , The high chiral-recognition ability of BINAP-based metal complexes boosted the synthetic applications of asymmetric hydrogenation. Soon these complexes were also used in other catalytic reactions such as the asymmetric isomerization of allylic amines, a reaction employed by Takasago in the industrial synthesis of (-)menthol from myrcene since 1985. Even more successful has been the use of BINAP-Ru

Ph CO2Me 1 mol% Cat* + N2CHCO2Me CO2Me 6% ee 10% ee + Cat* = N O Cu O N Ph

complexes in the asymmetric hydrogenation of functionalized olefins and ketones. This reaction has been applied to the preparation of several drugs and natural products, including isoquinilone alkaloids.4

1 Nozaki, H.; Moruiti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1966, 22, 5239 2 Aratani, T.; Yoneyoshi, Y.; Nagase, T. Tetrahedron Lett. 1975, 31, 1707 . 3 Dang, T. P Kagan, H. B. J. Chem. Soc. Chem. Commun. 1972, 481. .; 4 Noyori, R., Nobel Lecture, Angew. Chemie. Int. Ed., 2002, 41, 2008 63

© 2008 Johnson Matthey Plc

Prof. K. B. Sharpless also shared this 2001 Nobel Prize
PO(OCH3)2 PPh2 PPh2 R NHCHO (S)-BINAP-Ru dicarboxylate R PO(OCH3)2 NHCHO

thanks to his innovative work in the asymmetric epoxidation of olefins. In 1980 Katsuki and Sharpless discovered the titanium-catalyzed asymmetric epoxidation of olefins bearing allylic hydroxy groups.6

BINAP

NEt2

[Rh (R)-BINAP]+

NEt2 OH > 98% ee (-)-Menthol

R2 R1

R3 OH + t-BuO2H

Cat*

R2 R1

R3 O

OH

HO O NCH3 H Morphine H3CO Naproxen

Cat* = diethyl tartrate + Ti(Oi-Pr)4
CO2H OH Citronellol

often > 95% ee

HO

The osmium-catalyzed asymmetric dihydroxylation was subsequently discovered in 1987 7 Mechanistic . investigations and ligand engineering allowed the application of this second Sharpless reaction to any given class of alkenes, making it a very useful technology in organic synthesis.
HO O OH AE (+)-DET OH Geraniol OH AD-β OH

The asymmetric hydrogenation of simple, unfunctionalized ketones remained an unresolved problem until 1995. There Noyori et al. found a general solution based on the use of a [RuCl2(bisphosphine)(diamine)] complex in the presence of an alkaline base.5 The newly devised bisphosphine/diamine complex proved to be very active and selective in the hydrogenation of a range of aromatic, heteroaromatic and olefinic ketones in 2-propanol containing t-BuOK or KOH. This method has been applied to the asymmetric synthesis of several drugs, including (R)-denopamine, the antidepresant (R)-fluoxetine and the antipsychotic (S)duloxetine.
OH CF3 O HO denopamine hydrochloride OCH3 OCH3 NHCH3.HCl precursor of α-damascone OH

AE (-)-DET O OH HO

AD-α

OH OH

AE - asymmetric epoxydation AD - osmium-catalyzed asymmetric dihydroxylation
OH

H.HCl N

During the 1990s, Jacobsen and Katsuki independently developed chiral manganese-salen ligands for the catalytic epoxidation of alkenes in combination with cheap oxygen sources (i.e. NaClO), enantioselectivities often reaching 98% ee. During the last decade many new enantioselective reactions have been discovered (aminohydroxylation, aziridination, hydroformylation). Catalysis by palladium complexes has been actively developed, particularly in the areas of enantioselective allylic substitution and asymmetric Heck reaction.

fluoxetine hydrochloride OH O S NHCH3 duloxetine precursor of α-tocopherol

OCH3

OCH3 precursor of anthracyclins

Following the first discoveries in asymmetric hydrogenation, the search for new families of chiral phosphorous ligands with improved stereo-electronic characteristics has become an on-going effort both in academia and industry. Dr. Knowles and Prof. Noyori were awarded the Nobel Prize in Chemistry in 2001 for their outstanding contributions in this subject.

5 6 6 7 7 64

Noyori, R.; Ohkuma, T., Angew. Chemie. Int. Ed., 2001, 40, 1 Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974. Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. . Crispino, G. A.; Sharpless, K. B. Synthesis 1993, 8, 777 . Johnson, R. A.; Sharpless, K. B. in Catalytic Asymmetric Synthesis, Ed. Ojima, I., VCH, Weinheim, 1993, p.101 and p. 227

© 2008 Johnson Matthey Plc

4.13.1 Asymmetric Hydrogenation
Homogeneous asymmetric hydrogenation is one of the most important chiral technologies Johnson Matthey offers to its customers in the Pharmaceutical and Fine Chemicals industry through its business unit, Catalysis and Chiral Technologies (CCT). This portfolio has been developed by combining in-licensed asymmetric ligands from companies and academic institutions with in-house developed catalytic systems. A range of technologies has been assembled that allows, a priori, the coverage of all the known application of asymmetric hydrogenation (C=C, C=O and C=N bonds).
Rh-catalyzed hydrogenation of α-ketoesters R O CO2R'

R Rh-catalyzed hydrogenation of dehydroaminoacids

CO2R'' NHR'

R N Fe PR2 PR2

R

CO2R' CO2R'

Rh-catalyzed hydrogenation of itaconates

Boaz, N. W.; Debenham, S. D.; Mackenzie, E. B.; Large, S. E. Org. Lett. 2002, 4, 2421. Boaz, N. W.; Debenham, S. D.; Large, S. E.; Moore, M. K. Tetrahedron: Asymmetry 2003, 14, 3575.

P-Phos and Xyl-P-Phos
P-Phos, licensed from Prof A. Chan, is a biaryl phosphine with the unique feature of incorporating two methoxysubstituted pyridine rings in the backbone.8 This contributes to the balance of electronic and steric properties that make the P-Phos ligand very active and selective in a series of reactions such as rutheniumcatalyzed hydrogenation of ß-ketoesters and dehydroaminoacids, and ruthenium-catalyzed hydrogenation of non-functionalized ketones.
O R Ru-catalyzed hydrogenation of β-ketoesters OMe Ru-catalyzed hydrogenation of unsaturated acids CO2H R R' MeO MeO N OMe Ar = Ph, Xyl O N PAr 2 PAr 2 Ru-catalyzed hydrogenation of aromatic ketones CO2Me

ParaPhos® and PhanePhos
PhanePhos was first reported in 1997 and has since found , applications in rhodium-catalyzed hydrogenation of dehydroaminoacids, palladium catalyzed amination, ruthenium-catalyzed hydrogenation of ß-ketoesters, and ruthenium-catalyzed hydrogenation of non-functionalized ketones. Johnson Matthey obtained a licence to PhanePhos in 2002. Investigations into the reactivity of the common precursor 4,12-dibromo[2.2]paracyclophane towards electrophilic aromatic substitution has recently led to the introduction of the new paracyclophane-based ligands, ParaPhos. This research has improved the efficiency of the ligand synthesis and has expanded the range of available phosphines by introducing substituents with different electronic effects on the paracyclophane backbone while breaking with the requirement for C2 symmetry. Both rhodium and ruthenium catalysts bearing the PhanePhos and ParaPhos ligands show an exceptionally high activity in most homogeneous hydrogenation reactions and a surprising high “tunability” associated with the use of different derivatives.9
R1 R3HN R2 CO2Me O R CO2Me Ru-catalyzed hydrogenation of β-ketoesters PAr 2 O Boc N N Ac CO2Me PhanePhos ParaPhosTM R=H CH2OTIPS, OMe PAr 2

™ Bophoz™
Bophoz™ is a phosphine-aminophosphine ligand based on the ferrocene backbone. It presents exceptional reactivity in rhodium-catalysed hydrogenations. The Bophoz™ range of ligands display a rather unique combination of activity and selectivity in the hydrogenation of C=C and C=O bonds (such as in -ketoesters). A commercial agreement with the Eastman Chemical Company for the use of Bophoz™ has been in place since November 2003.

Rh-catalyzed hydrogenation dehydroaminoacids

R

Ru-catalyzed hydrogenation of aromatic ketones

R = CH2OH, CH2OTrityl

8 Pai, C. -C.; Lin, C. -W.; Lin, C. -C.; Chen, C. -C.; Chan, A. S. C.; Wong, W. T. J. Am. Chem. Soc. 2000, 122, 11513. 9 Rossen, K.; Pye, P J.; Reamer, R. A.; Tsou, N. N.; Volante, R. P Reider, P J. J. Am. Chem. Soc. 1997, 119, 6207 . .; . . 9 Domínguez, B.; Hems, W. P Zanotti-Gerosa, A. Org. Lett. 2004, 6,1927. .;

© 2008 Johnson Matthey Plc

65

BINAM-P and Spiro-P
These structurally diverse ligands have been developed by Professor Chan of Hong Kong Polytechnic University. Johnson Matthey obtained a licence in 2002. BINAM-P is an amino-phosphine ligand with axial chirality characterized by a larger than usual dihedral angle that is a consequence of the partially reduced binaphthyl backbone. Spiro-P is a phosphinite ligand based on the concept of a spiro-bicyclic backbone.10 Both ligands have found excellent applications in the rhodium-catalyzed hydrogenation of dehydroaminoacids.

suited to provide the best ligands for this catalysis when used in combination with diamine ligands such as DPEN, DACH and DAIPEN.

Transfer hydrogenation technology
Ruthenium transfer hydrogenation catalysts bearing tosylated diamine ligands were developed by Noyori and Ikariya, and are included in the license agreement between JST and Johnson Matthey. The reduction of C=O groups in presence of i-PrOH and a base or in the presence of a mixture of formic acid and triethylamine must be considered complementary to hydrogenation technology.12 Transfer hydrogenation gives

NHPAr 2 NHPAr 2

Ar2P PAr 2 O O

excellent selectivity on “difficult” substrates such as cyclic ketones, acetylenic ketones and imines.
Ts Ph Ph N Ru N Cl H2

O

i-PrOH / t-BuOK or HCO2H/Et3N, 5/2 R

OH

BINAM-P

Spiro-P

R

Asymmetric Ketone Reduction Ketone hydrogenation technology
The discovery by Professor Noyori’s group that nonfunctionalized aromatic ketones can be efficiently reduced by ruthenium catalysts was a dramatic leap forward in the field of asymmetric homogeneous hydrogenation. The broad applicability of the technology and the exceptionally high activity of these catalysts makes asymmetric ketone hydrogenation the route of choice to chiral alcohols.11 The Japan Science and Technology Corporation (JST) licensed this technology to Johnson Matthey in 2003. Two families of ligands, P-Phos and ParaPhos, are perfectly
Ar P P O R t-BuOK, H2 Ar

Typical products obtained

In i-PrOH / t-BuOK
OH

Dynamic kinetic resolution in i-PrOH / t-BuOK
OH OH

In HCO2H/Et3N
OH OH

NHCbz OH

OH

H3CO H3CO R NH

4.13.2 Enantioselective Hydroamination
This technology has been exclusively in-licensed from Yale (Professor John Hartwig). Johnson Matthey is optimizing the system for each particular substrate.

Ar Cl Ru Ar Cl

NH2 NH2 OH R ee > 98% Typical products obtained OH OH Fe

NHAr Potential Intermediate [(R)-P-Phos)Pd(OTf) 2] arylamine, toluene, 25o C NHAr Pd H L L F3C F3C high yield and high ee

H2N

NH2

Diamines

Me

NH2 DPEN H2N NH2 NH2 DACH OMe Me2N OMe DAIPEN OH OH O OH MeO

OMe

OH

10 10 11 11 12 66

Zhang, F .-Y.; Pai, C. -C.; Chan, A. S. C. J. Am. Chem. Soc. 1998, 120, 5808. Chan, A. S. C.; Hu, W.; Pai, C. -C.; Lau, C. -P Jiang, Y.; Mi, A.; Yan, M.; Sun, J.; Lou, R.; Deng, J. J. Am. Chem. Soc. 1997, 119, 9570. .; Noyori, R.; Ohkuma, T. Angew. Chem. Int. Ed. 2001, 40, 1. Noyori, R. Nobel Lecture, Angew. Chem. Int. Ed. 2002, 41, 2008. Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem. Int. Ed. 1997, 36, 285 and 288.

© 2008 Johnson Matthey Plc

4.13.3 Enantioselective Alkyne Addition
Developed by Professor Erick Carreira of ETH (Zurich).
HO H R2 R1

4.13.5 CATAXA™ Anchored Catalysts
Rhodium CATAXATM catalysts
The hydrogenation of prochiral carbon-carbon double bonds using enantioselective organometallic complexes of rhodium is widely used in chiral organic synthesis. However, extensive purification of the products is often necessary to remove the rhodium, and/or expensive phosphine ligands from the product. Johnson Matthey has anchored a range of rhodium catalysts on alumina, CATAXATM/ Rh, which are easily collected by filtration after the reaction and show

O H R1

H

R2

R1 = H or alkyl/aryl

(+)-N-methyl ephedrine Zn(OTf) 2, Et3N

R1 can be aryl or alkyl - linear or branched sterically crowded. Enantiomeric excesses are generally above 98%. This methodology can be applied to the synthesis of 1,4-diols
Ph O (+)-N-Methylephedrine Ph O Me Me O O Me Me O Me (-)-N-Methylephedrine Me OH 99% ee 92:8 diastereoselectivity H Ph O Me Me Me Me O Me Me

negligible amounts of leaching into the reaction mixtures. By attaching chiral homogeneous catalysts onto an alumina via a heteropolyacid, the high enantioselectivity and mild reaction conditions of the analogous homogeneous system can be combined with the ease of separation and simple method of recycle which is observed with heterogeneous catalysts. In addition, the support can add an extra dimension by exerting a positive influence on the enantioselectivity of the catalyst. In many instances, CATAXATM catalysts can be reused. The ability of the catalyst to recycle will depend on a number of factors including:

OH 99% ee 93:7 diastereoselectivity

4.13.4 Asymmetric Michael Addition
The La-BINOL complex for asymmetric Michael reaction is a highly stable powder. It has application for a broad range of substrates: cyclic enones (5-9 membered ring), acyclic enones and ß-dicarbonyl compounds.13 The homogeneous asymmetric complex can easily be recovered (ee > 98%) even after 4 recycles).

• The conditions under which they are used (whether the catalyst is exposed to air, moisture etc before/during/after the reaction); • The solvent in which the catalyst is used (some solvents, particularly alcohols, can themselves help to stabilize low co-ordinate metal complexes).

O O R= CO2Et O CO2Et R O O La O HO

All the ligands and catalysts discussed in this review are available through Alfa Aesar, a Johnson Matthey Company.

13 Matsunaga, S.; Das, J.; Roels, J.; Vogl, E. M.; Yamamoto, N.; Lida, T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 2252. Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc 1999, 121, 4168. Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chemie Int. Ed. Engl. 1997, 36, 1236.

© 2008 Johnson Matthey Plc

67

A variety of CATAXATM supported rhodium catalysts are available. These are based on the general structure shown below. The complexes can be chiral or achiral. Each catalyst will exhibit different rates dependent on the solvents and substrate used. Examples of diphosphine ligands: -dppb (1,4-bis(diphenylphosphine)butane). -(S,S)-BDPP (SkewPhos). -(S,S)-DIPAMP . Examples of dienes: -Cyclooctadiene. -Norbornadiene.

A precursor version of CATAXATM/ Rh catalysts is also available, CATAXATM/ Rh(COD)2. This material will allow the in-situ preparation of supported Rh catalysts by a simple ligand exchange reaction with the desired diphosphine ligand. The resultant catalysts generally require a prehydrogenation step for the pre-formed CATAXATM/ Rh/ Phosphine catalysts.

CATAXA™/ Rh(COD)2

Choice of solvent
CATAXATM/ Rh/ Phosphine catalysts Many different solvents can be used in conjunction with The CATAXATM/ Rh catalysts exhibit similar or often higher enantioselectivity or selectivity to their homogeneous counterparts in reactions such as hydrogenation of dimethylitaconate (DMIT), to acetamido cinnamate (below) and geraniol. CATAXA™/ Rh catalysts. The choice of solvent will depend largely on the substrate and the type of supported catalyst being used. Solvents such as ethanol and toluene have been used successfully with this material. As the material is air and moisture sensitive, we also recommend the use of dried and degassed solvents. Note: - Like many organometallic complexes, CATAXATM/ Rh samples are prone to oxidation and hence deactivation. To increase the shelf life of these materials they must be stored and handled under an inert atmosphere.

H H +

S

R

68

© 2008 Johnson Matthey Plc

5.
Catalyst Type

Table: Heterogeneous Catalysts
Support Material Metal Loading % Typical Applications

PALLADIUM A101023-10 A101023-5 A101038-10 A102023-5 Carbon Powder Carbon Powder Carbon Powder Carbon Powder 10 5 10 5 Dehydrogenation Hydrogenation of aliphatic nitro compounds Dehydrogenation Hydrogenation of alkynes, alkenes, aromatic rings, nitro and nitroso compounds, imines, nitriles, aromatic carbonyls, reductive alkylation, reductive amination, hydrogenolysis, debenzylation, selective oxidation, dehydrogenation, C-C coupling Hydrogenation of alkynes, alkenes, aromatic rings, aromatic carbonyls, hydrogenolysis, debenzylation, selective oxidation, dehydrogenation Selective hydrogenation where lower activity is required Conversion of phenol to cyclohexanone Hydrogenation of aromatic nitriles, imines, oximes, reductive amination, reductive alkylation, C-C coupling Selective hydrogenation where lower activity is required Selective hydrogenation where lower activity is required Rosenmund Reduction Rosenmund Reduction Selective hydrogenation where lower activity is required Selective hydrogenation of alkynes to alkenes Selective hydrogenation of alkynes to alkenes Selective hydrogenation where lower activity is required Hydrogenolysis, debenzylation Hydrogenation of aromatic and aliphatic nitro compounds Hydrogenation of alkynes, alkenes, hydrogenolysis, hydrodehalogenation, debenzylation Hydrogenolysis, debenzylation Hydrogenolysis, debenzylation Hydrogenolysis, debenzylation Hydrogenation of alkynes, alkenes, aromatic and aliphatic nitro compounds, hydrogenolysis, hydrodehalogenation, debenzylation, C-C coupling Hydrogenolysis, debenzylation Hydrogenation of alkynes, alkenes, aromatic rings, aromatic and aliphatic nitro compounds, aromatic carbonyls, hydrogenolysis, debenzylation, C-C coupling Hydrogenolysis, debenzylation Hydrogenolysis, debenzylation Hydrogenation of alkynes, alkenes, aromatic and aliphatic nitro compounds, aromatic carbonyls, hydrogenolysis, debenzylation Hydrogenation of aromatic and aliphatic nitro compounds, aromatic carbonyls Hydrogenolysis, debenzylation, dehydrogenation

A102038-5

Carbon Powder

5

A103038-5 A105023-5 A109047-5 A201053-10 A201053-5 A302023-5 A302038-5 A303060-5 A305060-5 A306060-5 A308053-5 A401002-20 A401102-5 A402002-5 A402028-10 A402028-5 A402032-10 A405028-5

Carbon Powder Carbon Powder Carbon Powder Barium Sulfate Barium Sulfate Carbon Powder Carbon Powder Calcium Carbonate Calcium Carbonate Calcium Carbonate Barium Sulfate Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder

5 5 5 10 5 5 5 5 5 5 5 20 5 5 10 5 10 5

A405032-5 A470085-5

Carbon Powder Carbon Powder

5 5

A470129-10 A470129-20 A470129-5

Carbon Powder Carbon Powder Carbon Powder

10 20 5

A470201-5 A501023-10

Carbon Powder Carbon Powder

5 10

© 2008 Johnson Matthey Plc

69

Catalyst Type A501032-10 A501038-10 A503023-5

Support Material Carbon Powder Carbon Powder Carbon Powder

Metal Loading % 10 10 5

Typical Applications Hydrogenolysis, debenzylation Dehydrogenation Hydrogenation of alkynes, alkenes, aromatic rings, nitro and nitroso compounds, imines, nitriles, aromatic carbonyls, reductive alkylation, reductive amination, hydrogenolysis, debenzylation, selective oxidation, dehydrogenation, C-C coupling, isomerization Hydrogenation of nitro and nitroso compounds, imines, nitriles, oximes, reductive alkylation, reductive amination, hydrogenolysis, debenzylation Hydrogenation of aromatic carbonyls, hydrogenolysis, hydrodehalogenation, isomerization Hydrogenation of aromatic and aliphatic nitroso compounds Hydrogenation of nitro and nitroso compounds, imines, nitriles, oximes, reductive alkylation, reductive amination, isomerization Hydrogenation of alkynes, alkenes, aromatic rings, nitro and nitroso compounds, imines, oximes, aromatic carbonyls, nitriles, reductive alkylation, reductive amination, hydrogenolysis, hydrodehalogenation, selective oxidation, dehydrogenation, isomerization Hydrogenation of aromatic carbonyls, nitriles, hydrogenolysis, hydrodehalogenation Rosenmund Reduction

A503032-5

Carbon Powder

5

A503038-5 A505085-5 A570147-5

Carbon Powder Carbon Powder Carbon Powder

5 5 5

A570129-5

Carbon Powder

5

A570201-5 A701023-5 PLATINUM B101002-5 B101032-3 B101038-1 B102022-5 B102032-1 B102032-3 B103018-5 B103032-3 B103032-5

Carbon Powder Carbon Powder

5 5

Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder

5 3 1 5 1 3 5 3 5

Selective oxidation Hydrogenation of halonitroaromatics Hydrogenation of halonitroaromatics Hydrogenation of heterocyclic compounds Hydrogenation of halonitroaromatics, p-aminophenol production Reductive alkylation Hydrogenation of aliphatic carbonyls, dehydrogenation, selective oxidation Hydrogenation of halonitroaromatics Hydrogenation of alkenes, aromatic rings, heterocyclic compounds, aromatic and aliphatic nitro and nitroso compounds, imines, nitriles, aliphatic carbonyls, dehydrogenation, selective oxidation Reductive alkylation Reductive alkylation Hydrogenation of halonitroaromatics, p-aminophenol production Reductive alkylation Selective oxidation Selective oxidation p-Aminophenol production Hydrogenation of halonitroaromatics Hydrogenation of halonitroaromatics, reductive alkylation

B104032-3 B105032-3 B105047-1 B106032-3 B111022-5 B112002-5 B170058-1 B170147-1 B170147-3

Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder

3 3 1 3 5 5 1 1 3

70

© 2008 Johnson Matthey Plc

Catalyst Type

Support Material

Metal Loading %

Typical Applications

PLATINUM – continued B170147-5 Carbon Powder 5 Hydrogenation of alkenes, aromatic rings, heterocyclic compounds, aromatic and aliphatic nitro and nitroso compounds, imines, nitriles, aliphatic carbonyls Selective oxidation Reductive alkylation Hydrosilylation Hydrosilylation Hydrogenation of alkenes, aromatic rings, heterocyclic compounds, aromatic and aliphatic nitro and nitroso compounds, imines, nitriles, aliphatic carbonyls, dehydrogenation, selective oxidation Selective oxidationIRIDIUM

B170201-5 B171147-3 B301013-5 B301099-5 B501032-5

Carbon Powder Carbon Powder Alumina Powder Alumina Powder Carbon Powder

5 3 5 5 5

B503032-5

Carbon Powder

5

RHODIUM C101023-5 Carbon Powder 5 Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic nitro compounds, aliphatic nitriles, alkenes Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic nitro compounds, aliphatic nitriles, alkenes Hydrogenation of aromatic rings

C101038-5

Carbon Powder

5

C301011-5

Alumina Powder

5

RUTHENIUM D101023-5 Carbon Powder 5 Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic carbonyls, sugar hydrogenation, selective oxidation Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic carbonyls, sugar hydrogenation, selective oxidation Selective oxidation Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic carbonyls, sugar hydrogenation, selective oxidation

D101038-5

Carbon Powder

5

D103002-5 D170201-5

Carbon Powder Carbon Powder

5 5

MIXED METAL E101049-4/1 E101023-4/1 F101023-4.5/0.5 F101038-4.5/0.5 G101038-5/0.25 Carbon Powder Carbon Powder Carbon Powder Carbon Powder Carbon Powder 4% Pd 1% Pt 4% Pd 1% Pt Hydrogenation of alkenes, nitro and nitroso compounds, imines, selective oxidation Hydrogenation of alkenes, nitro and nitroso compounds, imines, selective oxidation

4.5% Pd 0.5% Rh Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic nitriles, oximes 4.5% Pd 0.5% Rh Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic nitriles, oximes 5% Ru 0.25% Pd Hydrogenation of aromatic rings, heterocyclic compounds, aliphatic carbonyls NOTE The foregoing lists of catalysts and applications are not exhaustive

NOTE Paste catalysts are free flowing, powder–like materials, usually containing approximately 50–60% w/w water.

© 2008 Johnson Matthey Plc

71

PRICAT® Catalysts
PRICAT Powder Ni 52/35 Ni 55/5 Ni 56/5 Ni 62/15 Ni 60/15 Cu 51/8 Cu 60/35 Co 40/55 x x x x x x x x x x x Tablet x x Metal % 50 55 55 60 60 51 62 40 Kieselguhr Kieselguhr Kieselguhr Kieselguhr Kieselguhr Silica Silica Kieselguhr x x x x Support Promotors MgO x x x x x x x ZrO2 Cr2O3 x Al2O3 MnO

SPONGE METAL

Product A-5000 A-5B00 A-5200 A-4000 A-7000 A-7200 A-7063 A-7B63 A-7B73 A-2000 A-3B00 A-8000 A-8B46 AMCAT-5 AMCAT-5343 AMCAT-7 AMCAT-2

Primary Metal Nickel Nickel Nickel Nickel Nickel Nickel Nickel Nickel Nickel Nickel Copper Cobalt Cobalt Nickel Nickel Nickel Nickel

Promoters Non-promoted Non-promoted Non-promoted Fe & Cr Mo Mo Mo Mo Mo Fe Non-promoted Non-promoted Cr & Ni Non-promoted Non-promoted Mo Fe

Particle Size, median (u) 35 50 175 35 35 175 35 50 50 35 50 35 50 35 35 35 35

Typical applications General hydrogenation General hydrogenation General hydrogenation Diamine hydrogenation Polyol hydrogenation General hydrogenation Polyol hydrogenation Polyol hydrogenation Polyol hydrogenation Nitro group hydrogenation Dehydrogenation Selective hydrogenation Selective hydrogenation In In In In primary fatty amine tertiary fatty amine primary fatty amine primary fatty amine

72

© 2008 Johnson Matthey Plc

6. Table: Homogeneous Catalysts
Our range of PGM homogeneous catalysts and precursors is listed in the tables below. We have also listed some simple PGM chloride salts which are the starting materials for most co–ordination compounds.

An explanation of the European Union (E.U.) hazard codes is given below:

E.U. Code Xi

Hazard Irritant –

Nature of the Hazard Non-corrosive substances which, through immediate, prolonged or repeated contact with the skin or mucous membrane may cause inflammation. Substances which may, on contact with living tissues, destroy them. Substances which give rise to a highly exothermic reaction in contact with other substances, particularly flammable substances. Solid substances which may readily catch fire after brief contact with a source of ignition and which continue to burn or to be consumed after removal of the source of ignition. Substances which may cause death or acute or chronic damage to health when inhaled, swallowed or absorbed via the skin. Substances which in low quantities cause death or acute or chronic damage to health when inhaled, swallowed or absorbed via the skin. Substances which in very low quantities cause death or acute or chronic damage to health when inhaled, swallowed or absorbed via the skin. New substance – not the subject of a full notification.

C O F

Corrosive Oxidizing Highly flammable Harmful Toxic

– – –

Xn T

– –

T+

Very toxic

CSNYFT

Caution Substance not yet fully tested. Dangerous for the Environment

N

Chemicals that may present an immediate or delayed danger to one or more components of the environment.

Solubilities
The relative solubilities of the co–ordination compounds in different solvents are indicated in the tables. For guidance, the following abbreviations have been used:– v.s. s. f.s. sl.s. v.sl.s. i very soluble soluble fairly soluble slightly soluble very slightly soluble insoluble ca. 1000 g/l ca. 100 g/l ca. 15 g/l ca. 10 g/l ca. 1 g/l or less

© 2008 Johnson Matthey Plc

73

IRIDIUM COMPOUNDS
Catalog No. Ir-40 Compound Carbonylchloro bis (triphenylphosphine) iridium(l) [IrCl(CO) (PPh3)2] Carbonylhydrido tris (triphenylphosphine) iridium(l) [IrCl(CO)H(PPh3)3] (Cycloocta–1,5–diene) pyridyl tricyclohexyl– phosphine iridium(I) hexafluorophosphate [Ir(COD)py(PCy3)]PF6 Di -mu-chloro bis(cyclooctene) iridium (I) [Ir(C8H14)2Cl]2 Bis(1,5-cyclooctadiene)di- mumethoxydiiridium(I) [Ir(C8H12)2OCH3]2 Di μ–chloro bis (η4–cycloocta–1,5– diene) di–iridium(I) [IrCl(COD)]2 "Iridium(III) acetate" Hexa(acetato) μ3–oxo tris (aquo) tri–iridium acetate [Ir3(OAc)6μ3–O(H2O)3]OAc Iridium(III) chloride hydrate [IrCl3].H2O Color & Form lemon yellow crystals pale yellow powder orange crystals Mol Wt 780 % Metal Content 24.6 Stability air stable

Ir-42

1007

19.1

slowly decomposes in air air stable

Ir–90

804

23.9

Ir–91 Ir–92

yellow solid yellow solid red– orange solid dark green solid

896 651

42.9 58.0

slowly decomposes in air & moisture slowly decomposes in air & moisture air stable

Ir–93

671

57 .2

Ir–112

50–54

air stable

green/ black crystalline flakes black– brown crystals orange fiber yellow fiber

50–56

air stable hygroscopic

Chloroiridic acid; Hydrogen hexachloroiridate(IV) hydrate H2[IrCl6].H2O FibreCat® 4000-D11 FibreCat® 4000-D12 Ir(COD)Cl on triphenylphosphine fibers Ir(COD)Cl on pyridine fibers

38–45

air stable hygroscopic air stable air stable

4.0-5.0 4.0-5.0

OSMIUM COMPOUNDS
Catalog No. Compound Color & Form yellow crystals Mol Wt 254 % Metal Content 75 Stability

Osmium tetroxide Osmium (VIII) oxide [OsO4]

m.pt 41°C

“Potassium osmate dihydrate” Dipotassium trans dioxo tetra (hydroxy) osmium (VI) K2[OsO2(OH)4]

purple solid

368

51.6

air stable

FibreCat® 3003 FibreCat® 3004
74

OsO4 on pyridine fibers

yellow fiber violet fiber

7 .5 nominal 7 .5 nominal

store cold -20°C store cold -20°C

K2[OsO2(OH)4] on triethylamine fibers

© 2008 Johnson Matthey Plc

IRIDIUM COMPOUNDS
Solubilities sl.s Chloroform sl.s toluene E.U. Hazard Code CAS No. (EINECS No.) T 14871–4–1 (2389416) 17250–25–8 Use and Comments Hydrogenation Vaska’s compound Hydrogenation Catalogue No. Ir–40

s. chloroform s. toluene

Xn

Ir–42

sl.s acetone, dichloromethane, diethyl ether, ethanol

Xn CSNYFT

64536–78–3 ( –– )

Hydrogenation Crabtree's catalyst

Ir–90

i.water i. water

12246-51-4 12148-71-9

Imine Hydrogenation Chiral Hydrogenation Imine Hydrogenation Chiral Hydrogenation Hydrogenation

Ir–91 Ir–92

s. chloroform, toluene sl.s acetone, alcohol

Xi

12112–67–3 (2351707)

Ir–93

s. acetic acid, water

Xi CSNYFT

52705–52–9 ( –– )

Catalyst precursor Ir–112 Solid contains metal in more than one formal oxidation state Also available in solution in acetic acid Catalyst precursor

s. alcohol, water

Xn

14996–61–3 * (2330446)

f.s alcohol, water

C

16941–92–7 (2410128)

Catalyst precursor Also available as solution hydrosilylation and hydrogenation hydrosilylation and hydrogenation FibreCat® 4000–D11 FibreCat® 4000–D12

i. all known solvents i. all known solvents *CAS No. refers to a specific hydrate

OSMIUM COMPOUNDS
Solubilities v.s carbon tetrachloride s. water E.U. Hazard Code T+, C CAS No. (EINECS No.) 20816–12–0 (2440587) Use and Comments Catalog No.

Oxidation Can be readily sublimed. Should only be used in a well ventilated remote environment.

s. water

Xi

19718 – 36 – 6 (2432471)

Oxidation. A convenient substitute for OsO4

i. all known solvents

T+

Oxidation

FibreCat® 3003 FibreCat® 3004
75

i. all known solvents

Xi

Oxidation

© 2008 Johnson Matthey Plc

PALLADIUM COMPOUNDS
Catalog No. Pd–62 Compound Color & Form dark yellow powder pale yellow powder Mol Wt 263 % Metal Content 40.4 Stability

Dichloro bis(acetonitrile)palladium(II) [PdCl2(CH3CN)2]

air stable

Pd–63

Tetrakis(acetonitrile)palladium(II) tetrafluoroborate Pd(CH3CN)4(BF4)2

444

23.9

air, moisture & light sensitive air stable

Pd–70

Bis(acetylacetonato)palladium(II) [Pd(acac)2]

yellow orange solid purple brown

304

35.0

Pd–93

Bis(dibenzylideneacetone)palladium(0) Pd(C17H14O)2

575

18.5

slightly air & moisture sensitive slightly air & moisture sensitive slightly air & moisture sensitive air stable

Pd–94

Tris(dibenzylideneacetone)dipalladium(0) Pd2(C17H14O)3

dark purple solid

916

23.2

Pd–95

Tris(dibenzylideneacetone)dipalladium(0) chloroform adduct Pd2(C17H14O)3.CHCI3

purple powder 1035

20.6

Pd–100

Dichloro bis(triphenylphosphine) palladium(II); [PdCl2(PPh3)2] Tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4]

yellow solid yellow solid

701

15.2

Pd–101

1154

9.4

air, heat, light & moisture sensitive air stable moisture sensitive

Pd–102

Diacetato 1,3–bis(diphenylphosphino) propane palladium(II) [Pd(OAc)2(Ph2PCH2CH2CH2PPh2)]

cream solid

636

16.7

Pd–103

Dichloro 1,2–bis(diphenylphosphino) ethane palladium(II) [PdCl2(Ph2PCH2CH2PPh2)] Dichloro 1,4–bis(diphenylphosphino) butane palladium(II) [PdCl2(Ph2PCH2CH2CH2PPh2)]

off white powder

575

18.5

air stable

Pd–105

yellow solid

603

17 .6

air stable

Pd–106

Dichloro 1,1-bis(diphenylphosphino)ferrocene orange/red palladium(II) dichloromethane adduct solid [Pd(dppf)Cl2]. CH2CI2 Dichloro 1,1-bis(diphenylphosphino) ferrocene palladium(II) acetone adduct [Pd(dppf)Cl2]. (CH3)2O Di–μ–chloro–bis (tris(2,4–di–t–butylphenyl) phosphite–2–C,P) dipalladium(II) Di-μ-chlorobis(eta 3-2 propenyl) dipalladium [Pd(C3H5)Cl]2 Allylpalladium chloride dimer brick red solid white – off white powder yellow powder

816

13.0

air stable

Pd–107

789

13.4

air stable

Pd–109

1576

13.5

air stable

Pd–110

366

58.1

very slightly air & moisture sensitive

76

© 2008 Johnson Matthey Plc

PALLADIUM COMPOUNDS

Solubilities s. acetone, chloroform

E.U. Hazard Code Xn

CAS No. (EINECS No.) 14592–56–4 (2386373)

Use and Comments

Catalog No.

Coupling precursor, rearrangements, Pd–62 debromination.

s. water

21797-13-7

Coupling

Pd–63

s. chloroform, toluene

Xi

14024–61–4 (2378598)

Alkene dimerisation, cyclization, oxidation

Pd–70

sls. chloroform

32005-36-0

Coupling reactions

Pd-93

s. chloroform

51364-51-3 52409-22-0 60748-47-2 52522-40-4

Coupling reactions

Pd-94

Coupling reactions

Pd-95

v.sl.s acetone, chloroform

Xn

13965–03–2 (2377442) 14221–01–3 (2380869)

Carbonylation. Coupling reactions Coupling reactions. Store refrigerated

Pd–100

s. chloroform, toluene

Xn

Pd–101

s. acetic acid, chloroform, methanol sl.s acetone v.sl.s toluene

Xn CSNYFT

149796–59–8 (–)

Coupling reactions. Carbonylation

Pd–102

Xn CSNYFT

19978–61–1 (–)

Coupling reactions

Pd–103

sl.s DMF v.sl.s. acetonitrile, water

Xn CSNYFT

29964–62–3 (–)

Coupling reactions

Pd–105

i. water

95464-05-4

Coupling reactions

Pd-106

s. chloroform sl. s. dichloromethane

Xn CSNYFT

851232-71-8 (–)

Coupling reactions Carbonylation

Pd–107

i. water s. toluene, chloroform i. water

Xn CSNYFT

217189–40–7 (–) 12012-95-2

Coupling reactions especially Suzuki and Stille couplings of aryl bromides and iodides Coupling reactions

Pd–109

Pd-110

© 2008 Johnson Matthey Plc

77

PALLADIUM COMPOUNDS
Catalog No. Pd–111 Compound

– (CONTINUED)
Color & Form Mol Wt % Metal Content 47 .4 Stability

Palladium(II) acetate trimer Hexakis(μ–acetato) tripalladium(II) [Pd(OAc)2]3 Dibromo bis(tri-tert-butylphosphine) dipalladium (I) [Pd(μ-Br)t-Bu3P]2

orange/brown 673 needles

air stable

Pd-113

dark green/ black crystals

777

27 .4

air & moisture sensitive

Pd-114

Dichloro bis(tricyclohexylphosphine) palladium(II) PdCl2[(C6H11)3P]2 Dichloro bis(tri-ortho-tolylphosphine) palladium(II) PdCl2[P(o-tolyl)3]2 Bis(tri-tert-butylphosphine)palladium(0) Pd(t-Bu3P)2

yellow powder

738

14.4

air stable

Pd-115

yellow/orange 786 solid off white solid 510

13.5

air stable

Pd-116

20.9

air & moisture sensitive

Pd-117

Dichloro bis(diphenylphosphinophenyl)ether palladium(II) DPEPhos PdCl2 Dichloro 1,1-bis(di-tert-butylphosphino) ferrocene palladium(II) di-t-bpfPdCl2 Dichloro 1,1-bis(di-isopropylphosphino) ferrocene palladium di-isoppf PdCl2 Dibromo 1,1-bis(tri-ortho tolylphosphine)palladium(II) PdBr2[P(o-toly)3]2

light yellow solid

719

14.8

air stable

Pd-118

dark red/brown 651 solid

16.3

air stable

Pd-119

orange red solid

595

17 .8

air stable

Pd–120

orange/yellow 875 solid

12.0

Slowly decomposes in air & moisture air stable

Pd–121

Dibromo 1,1-bis(diphenylphosphino) ferrocene palladium(II) dppfPdBr2 Dibromo bis(triphenylphosphine) palladium (II) [Pd(PPh3)2Br2] Pd(OAc)2 on triphenylphosphine fibers

purple red solid

820

12.9

Pd-130

orange solid yellow/brown fiber orange fiber yellow fiber

791

13.5

air stable

FibreCat® 1001 FibreCat® 1026 FibreCat® 1032

2.7-4.0

air stable

PdCI2 on triphenylphosphine fibers

3.5-5.5

air stable

Pd(OAc)2/tri-tert-butylphosphine on tritertbutylphosphine fibers

4.5-5.5

air stable

Q Phos

1,2,3,4,5-Pentaphenyl-1’-(di-tert butylphosphino)ferrocene CTC-Q-PHOS (Use in conjunction with Pd precursor) Palladium(II) chloride [PdCl2]

pink-red solid

711

n/a

air & moisture stable

red– brown powder

177

59.6–60.0

air stable

78

© 2008 Johnson Matthey Plc

PALLADIUM COMPOUNDS

– (CONTINUED)
CAS No. (EINECS No.) 3375–31–3 (2584249) Use and Comments Carbonylation. Coupling precursor. Slowly decomposes in alcohol solutions Highly active for all coupling reactions especially amination and Suzuki couplings Coupling reactions Catalog No. Pd–111

Solubilities s. acetic acid, toluene

E.U. Hazard Code Xi

i. water

185812-86-6

Pd-113

i. water

29934-17-6

Pd-114

i. water

40691-33-6

Coupling reactions

Pd-115

i. water (but decomposes)

53199-31-8

Highly active for all coupling reactions especially amination and Heck couplings Coupling reactions Highly active for all coupling reactions especially Suzuki couplings Coupling reactions

Pd-116

i. water i. water

205319-06-08 95408-45-0

Pd-117 Pd-118

i. water

215788-65-1

Pd-119

i.water

24554-43-6

Coupling

Pd–120

s. chloroform, dichloromethane

124268-93-5

Coupling

Pd–121

v.sl. s. acetone, acetonitrile

25044-96-6 (-)

Coupling reactions

Pd-130

i. all known solvents

Bromo/iodo coupling reactions

FibreCat® 1001 FibreCat® 1026 FibreCat® 1032

i. all known solvents

Bromo/iodo coupling reactions

i. all known solvents

Highly active for all coupling reactions especially chloro coupling, amination 312959-24-3 Highly active for all coupling reactions especially Negishi couplings

i. water

s. dil mineral acids and aqueous alkali metal halides

Xi

7647–10–1 (2315962)

Catalyst precursor. Also available as H2PdCl4 solution

© 2008 Johnson Matthey Plc

79

PLATINUM COMPOUNDS
Catalog No. Pt–62 Compound trans–Bis(acetonitrile) dichloroplatinum(II) trans–[PtCl2(CH3CN)2] Color & form pale yellow micro– crystals lemon needles cream micro– crystals yellow powder Mol Wt 348 % Metal Content 56.0 Stability air stable

Pt–70

Bis(acetylacetonato) platinum(II); [Pt(C5H7O2)2] Dichloro (η4–norbornadiene) platinum(II) [PtCl2(nbd)] (η4–Cycloocta–1,5–diene) diiodoplatinum(II) [PtI2(COD)] Dichloro (η4 cycloocta–1,5–diene) platinum(II) [PtCl2(COD)] cis–Dichlorobis (triphenylphosphine) platinum(II) cis–[PtCl2(PPh3)2] trans–Dichlorobis(diethylsulfide) platinum(II) trans–[PtCl2(SEt2)2] Karstedt catalyst solution Approximate formula Pt2(divinyltetramethyldisiloxane)3 Chloroplatinic acid on pyridine fibers Platinum(II) chloride [PtCl2]

393

49.6

air stable

Pt–90

358

54.4

air stable

Pt–91

557

35.0

air stable

Pt–96

pale yellow solid white crystals

374

52.1

air stable

Pt–100

790

24.7

air stable

Pt–112

bright yellow crystals pale yellow solution orange fiber olive green powder orange –red crystals

446

43.7

air stable

Pt–114

3–4

air stable, store less than 50°C air stable

FibreCat® 4001

3.5-6.0

266

72.8 –73.6

air stable

Chloroplatinic acid; Hydrogen hexachloroplatinate(IV) hydrate H2[PtCl6].H2O

39 –42

air stable hygroscopic

RHODIUM COMPOUNDS
Catalog No. Rh–40 Compound Carbonylchloro bis (triphenylphosphine) rhodium(I) [RhCl(CO)(PPh3)2] Carbonyl hydrido tris (triphenylphosphine) rhodium(I) [RhH(CO)(PPh3)3] Acetylacetonatocarbonyltriphenylphosphine rhodium(I) (ROPAC) [Rh(acac)(CO)(PPh3)] Acetylacetonatodicarbonyl rhodium(I) [Rh(acac)(CO)2] Tris(acetylacetonato) rhodium(III) [Rh(acac3)] Color & Form yellow crystals yellow crystals yellow crystals Mol Wt 691 % Metal Content 14.9 Stability air stable

Rh–42

918

11.2

air stable

Rh–43

492

20.9

air stable

Rh–50

green flakey crystals yellow crystals

258

39.9

air stable

Rh–70
80

400

25.8

air stable

© 2008 Johnson Matthey Plc

PLATINUM COMPOUNDS
Solubilities v.sl.s acetone i. dichloromethane t.s. DMF E.U. Hazard Code CAS No. (EINECS No.) T 13869–38–0 (2376192) Use and Comments Catalog No. Pt–62

v.s chloroform

Xn

15170–57–7 (2392235) 12152–26–0 (2352716) Hydrosilylation

Pt–70

s. acetic acid

Xn

Pt–90

s. dichloromethane

Xn

12266–72–7 (2355387)

Hydrosilylation

Pt–91

sl.s. chloroform, dichloromethane v.sl.s. alcohols v.sl.s. chloroform, hexane, toluene

Xn

12080–32–9 (2351445)

Hydrosilylation

Pt 96

Xn

15604-36-1 (2334959)

Pt–100

v.s acetone s. ethyl acetate

Xn

15337–84–5 (2393731)

Hydrosilylation

Pt–112

Dictated by solvent used

68478–92–2 (2708444)

Hydrosilylation. Usually supplied in propan–2–ol/ divinyltetramethyldisiloxane. Hydrosilylation

Pt 114

i. all known solvents v.sl.s acetone, alcohol, water

C, T

FibreCat® 4001

Xn

10025–65–7 (2330341)

Hydrosilylation

v.s acetone, alcohol, ether, ethyl acetate, water

C, T

16941–12–1 (2410107)

Hydrosilylation. A powerful sensitiser and allergen

RHODIUM COMPOUNDS
Solubilities f.s chloroform, ethanol E.U. Hazard Code T CAS No. (EINECS No.) 13938–94–8 (2377128) 17185–29–4 (2412303) Xi 25470–96–6 (2470150) Use and Comments Decarbonylation Catalog No. Rh–40

f.s chloroform

Hydroformylation

Rh–42

s. chloroform f.s toluene

Hydroformylation. ROPAC

Rh–43

s. acetone sl.s alcohol, chloroform, toluene v.s chloroform s. alcohol © 2008 Johnson Matthey Plc

T, F

14874–82–9 (2389479) 14284–92–5 (2381925)

Hydroformylation. Dichromic green–red crystals when crushed

Rh–50

Rh–70
81

RHODIUM COMPOUNDS
Catalog No. Rh–92 Compound

– (CONTINUED)
Color & Form mustard yellow crystals orange crystals orange crystal red-brown solid dark red solid dark red crystals magenta crystals orange crystals Mol Wt 461 % Metal Content 44.7 Stability air stable

Di μ–chlorobis (η4–norbornadiene) dirhodium(I) [RhCl(nbd)]2 Di μ–chlorobis (η4–cycloocta–1,5– diene)dirhodium(I); [RhCl(COD)]2 Acetylacetonato(1,5-cyclooctadiene) rhodium(I) Rh(C8H12)(C5H7O2) Bis(cyclooctadiene)rhodium(I) tetrafluoroborate[Rh(C8H12)2]BF4 Bis(norbornadiene)rhodium(I) tetrafluoroborate [Rh(nbd)2]BF4 Bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate [Rh(C8H12)2]O3SCF3 Chloro tris(triphenylphosphine) rhodium(I) [RhCl(PPh3)3] Wilkinson’s catalyst Bromo tris(triphenylphosphine) rhodium(l) [RhBr(PPh3)3] Hydrido tetrakis(triphenylphosphine) rhodium(ll) [RhH(PPh3)4] Rhodium(II) acetate dimer [Rh(OAc)2]2 "Rhodium(III) acetate" Hexa(acetato) μ3–oxo tris(aquo) trirhodium acetate [Rh3(OAc)6μ3–O(H2O)3]OAc Rhodium(II) octanoate dimer [Rh(C8H15O2)2]2 Di μ–chloro dichloro bis (η5–pentamethylcyclopentadienyl) di–rhodium (I); [RhCl2(η5–Cp*)]2 Bis(norbornadiene)rhodium trifluoromethanesulfonate [Rh(C7H8)2]BF4

Rh–93 Rh–95 Rh-96

493 310 406

41.8 33.0 25.3

air stable air stable slightly air & moisture sensitive slightly air & moisture sensitive air sensitive

Rh–97

374

27 .5

Rh–98

468

22.0

Rh–100

925

11.1

slowly decomposes in air air sensitive

Rh–101

969

10.6

Rh–105 Rh–110

yellow powder emerald green powder brown solid

1152 442

8.9 46.6

air sensitive air stable

Rh–112

34–39

air stable

Rh–115

emerald green powder burgundy solid orange solid

778

26.4

air stable

Rh–120

618

33.3

air stable

Rh–125

436

23.6

stable at 0 deg C air stable air stable air sensitive air sensitive air stable

Rh–126 Rh–127 FibreCat® 2003 FibreCat® 2006

Bis(ethylene)(pentanedionato)rhodium yellow Rh(C2H4)2(C5H7O) solid (norbornadiene)(pentanedionato) rhodium Rh(C7H8)(C5H7O) Rh(nbd)2BF4 on triphenylphosphine fibers Rh(nbd)CI on triphenylphosphine fibers Rhodium (2–ethylhexanoate) in 2–ethyl hexanol Rhodium(III) chloride hydrate [RhCl3].nH2O Rhodium(III) iodide [RhI3] yellow solid orange fiber yellow fiber red/ brown solution dark red flakes black powder

257 294

39.9 34.9 3.0-4.0 2.0-3.5 3.0–4.0

39–43

air stable

484

21.3

air stable but hygroscopic

82

© 2008 Johnson Matthey Plc

RHODIUM COMPOUNDS
Solubilities v.sl.s most solvents

– (CONTINUED)
CAS No. (EINECS No.) 12257–42–0 (2355104) 12092–47–6 (2351576) 12245-39-5 35138-22-8 Use and Comments Hydrogenation. Isomerisation Hydroformylation. Hydrogenation. Isomerisation Hydroformylation Hydrogenation (Chiral and non-chiral) Hydrogenation, Isomerisation Catalog No. Rh–92

E.U. Hazard Code Xn

sl.s acetone, methanol s. chloroform sl s methyl ethyl ketone, dichloromethane i. water

Xi

Rh–93 Rh–95 Rh-96

CSNYFT

36620–11–8 (–) 99326-34-8

Hydrogenation, Isomerisation

Rh–97

s. chloroform

Hydrogenation (Chiral and non-chiral) Selective Hydrogenation. Decarbonylation. Store under inert gas Hydrogenation

Rh–98

v.s chloroform sl.s acetone, alcohol v.sl.s diethyl ether, toluene v.s. chloroform sl.s acetone, alcohol v.sl.s diethyl ether, toluene s. chloroform, toluene sl.s methanol v.sl.s acetone, acetic acid, chloroform, water s. acetic acid, water Xi Xn

14694–95–2 (2387445) 14973–89–8 (2390505)

Rh–100

Rh–101

CSNYFT

18284–36–1 (—) 15956–28–2 (2400848) 42204–14–8 (2557079) Cyclopropanation Carbene reactions Alcohol carbonylation catalyst precursor Available also in solution in acetic acid Cyclopropanation Carbene reactions Hydrogenation Chiral hydrogenation precursor Chiral Hydrogenation precursor Hydrogenation precursor Hydrogenation precursor Selective Hydrogenation Selective Hydrogenation

Rh–105 Rh–110

Rh–112

sl.s alcohol

CSNYFT

73482–96–9 ( –– ) 12354–85–7 ( –– ) 178397-71-2

Rh–115

s. chloroform, acetone sl.s. THF methanol , i. diethyl ether s. dichloromethane & chloroform s. dichloromethane & chloroform s. dichloromethane & chloroform i. all known solvents i. all known solvents s. propan–2–ol, acetone

CSNYFT

Rh–120

Rh–125

12082-47-2 32354-50-0

Rh–126 Rh–127 FibreCat® 2003 FibreCat® 2006

Xn

20845–92–5 (2440791) 20765–98–4 * (2331654) 15492–38–3 (2395215)

Catalyst precursor

s. alcohol, water sl.s acetone i. most solvents

Xn

Catalyst precursor

Alcohol carbonylation catalyst precursor
83

© 2008 Johnson Matthey Plc

RUTHENIUM COMPOUNDS
Catalog No. Ru–41 Compound Dicarbonyldichloro bis(triphenylphosphine) ruthenium(II) [RuCl2(CO)2(PPh3)2] Carbonylchlorohydrido tris (triphenylphosphine) ruthenium(II) [RuClH(CO)(PPh3)3] Tris(acetylacetonato) ruthenium(III) [Ru(acac)3] Dichloro (η4–cycloocta–1,5– diene) ruthenium(II) polymer [RuCl2(COD)]n Bis(2-methylallyl)(1,5cyclooctadiene)ruthenium (II) Ru(C8H12)(C4H7)2 Color & Form yellow white crystals Mol Wt 752 % Metal Content 13.4 Stability air stable

Ru–42

pale yellow crystals

952

10.6

air stable light sensitive

Ru–70

dark red– brown crystals dark brown powder off-white crystals

398

25.4

air stable

Ru–90

38.3

air stable

Ru–91

319

31.6

slowly decomposes in air & moisture as well as at warm conditions air stable

Ru–92

(1,5 cyclooctadiene) ruthenium trifloroacetate [Ru(C8H12) (CF3CO2)]2 (1,5-cyclooctadiene) ruthenium acetate Ru(C8H12) (CH3CO2)2 Dichloro tris (triphenylphosphine) ruthenium(II) [RuCl2(PPh3)3] "Ruthenium(III) acetate" Hexa(acetato)μ3–oxo tris (aquo)triruthenium acetate [Ru3(OAc)6μ3–O(H2O)3]OAc Tetrachloro bis (η6–p–cymene) diruthenium(II) [RuCl2(η6–C10H14)]2 Tetraiodobis (η6 p-cymene) ruthenium(ll) dimer [Rul2(η6-C10H14)]2 Tetra (n–propylammonium) perruthenate [NPr4][RuO4], TPAP

yellow powder

870

23.2

Ru–93

yellow powder black solid

327

30.9

air stable

Ru–100

958

10.5

air stable

Ru–112

dark green solid

40 – 45

air stable

Ru–120

dark red crystals brownishyellow solid very dark green/brown solid black crystals

612

33.0

air stable

Ru–121

978

20.7

stable at room temperature

Ru–130

351

28.7

air stable but hygroscopic air stable but hygroscopic air stable

Ruthenium(III) chloride hydrate [RuCl3].xH2O

38–43

FibreCat® 3001 FibreCat® 3002

TPAP on triethylamine fibers

5 nominal

Na2RuO4 on triethylamine fibers

grey black fiber

3.0-4.5

air stable

84

© 2008 Johnson Matthey Plc

RUTHENIUM COMPOUNDS

Solubilities v.sl.s acetone chloroform, toluene

E.U. Hazard Code Xn

CAS No. (EINECS No.) 14564–35–3 (2386059)

Use and Comments

Catalog No. Ru–41

insoluble in most solvents

T

16971–33–8 (2410510)

Disproportionation and silyl transfer. Transfer hydrogenation

Ru–42

s. chloroform sl.s acetone, ethyl acetate, methanol, toluene, water i. most solvents

T

14284–93–6 (2381930)

Hydrogenation

Ru–70

Xn

50982–13–3 (2568892)

Hydrogenation

Ru–90

i. water

12289-94-0

Chiral Hydrogenation Ru–91 Reduction of CO groups

s. chloroform

133873-70-8

Chiral Hydrogenation Ru–92 Reduction of CO groups

s. chloroform

133519-03-6

Chiral Hydrogenation Ru–93 Reduction of CO groups Hydrogenation Dehydrogenation Oxidation Ru–100

v.sl.s acetone, alcohol, chloroform, ethyl acetate, toluene vs. acetic acid, water sl.s. acetone Xi, N

15529–49–4 (2395697)

55466–76–7 (2596537)

Available also in solution in acetic acid

Ru–112

s. alcohol, chloroform Xn CSNYFT

52462–29–0 ( –– )

Hydrogenation Ru–120 Transfer hydrogenation Chiral hydrogenation precursor Chiral Hydrogenation Ru–121 Reduction of CO groups

s. chloroform

90614-07-6

s. dichloromethane, acetonitrile i. water v.s water s. acetone, alcohol sl.s ethyl acetate i. all known solvents

O, Xi CSNYFT

114615–82–6 ( –– )

Selective Oxidation

Ru–130

14898–67–0 * (2331675)

Catalyst precursor Available in solution

Oxidation

FibreCat® 3001 FibreCat® 3002

i. all known solvents

Oxidation

* CAS No. refers to a specific hydrate © 2008 Johnson Matthey Plc

85

7. Table: Smopex® Metal Scavenging Products
Trade name Product description Color Dry cont. Pharma % SMOPEX® Smopex-101 Styrene sulfonic acid grafted polyolefin fiber Acrylic acid grafted polyolefin fiber Styryl trimethylamine grafted polyolefin fiber Vinyl pyridine grafted polyolefin fiber Beige to brown White to beige White na. >20 >=2.5 0.3 Dry cont. Tech % Funct. Cap. (mmol/g) Std. Fibre Length (mm)

Smopex-102

>95

>20

>=5

0.3

Smopex-103

na.

>20

>=1.5

0.3

Smopex-105

White to beige to yellow White

>95

>20

>=3

0.3

Smopex-110

Styryl-based isothiouronium grafted polyolefin fiber Styryl thiol grafted polyolefin fiber

na.

>20

>=1.5

0.3

Smopex-111

White to beige to yellow Off-white to white White to beige White to beige to yellow

>95

>20

>=2

0.3

Smopex-112

Acrylate based “alpha“-hydroxyl thiol grafted polyoleifin fiber Mercaptoethylacrylate grafted polyolefin fiber Styryl diphenylphosphine grafted polyolefin fibre

na.

>20

>=2.5

0.3

Smopex-234

>95

>20

>=2

0.3

Smopex-301

na.

>95

>=0.9

0.3

Note: Pharmaceutical grade Smopex® can be used in API product streams and is supplied dry to conform with limits on residual solvents. Technical grade Smopex® is supplied with variable dry content.

86

© 2008 Johnson Matthey Plc

8. Glossary of Terms
API Asymmetric catalysis The Active Pharmaceutical Ingredient in a drug formulation. A catalytic reaction that produces a chiral molecule by controlling the reaction directly to give single enantiomer yields approaching 100%. Adsorption which involves the formation of a chemical bond between the adsorbed atom/molecule and the catalyst surface. A man-made material used for catalysis – often containing a PGM as the active component (see definition of PGM). A reaction is chemoselective when it converts exclusively or preferentially one functional group in the presence of other functional groups. A molecule is chiral if its image and mirror image are not superimposable. Chiral compounds such as solvents, additives, reactants which transform prochiral precursors to one of the two enantiomers preferentially. Molecules that are not superimposable with their mirror images (e.g. the right and left hand are mirror images which are not superimposable). Naturally occurring chiral molecules, such as carbohydrates, hydroxycarboxylic acids, amino acids, terpenes, alkaloids etc. A substance which adds its own activity (or deactivation) for the considered reaction to the catalyst itself and increases the overall rate of reaction by a synergetic contribution to the basic activity of the main catalyst. Structures with more than one chiral center and are not enantiomers. e.g. an R,R structure and an R, S structure. The R centers are identical while the R and S centers are enantiomers. The two forms of a chiral molecule. One enantiomer is the mirror image of the other. Distinguished as (R)- and (S)-isomers. A reaction or catalyst is called enantioselective if one of the product enantiomers is produced preferentially from a prochiral substrate. Also known as asymmetric. The selectivity of an enantioselective reaction is expressed as enantiomeric excess(ee), and is defined as: ee = [R] – [S] x 100% [R] + [S] Also known as optical yield (oy). Hüttig Temperature Hydrogenolysis Intermediates Ligand Temperature at which surface atoms become significantly mobile (= 0.3Tm in Kelvin). Cleavage of a bond by reaction with molecular hydrogen in the presence of a catalyst. Chemical substances isolated along the synthesis route to the API (see definition of API). In the context of this handbook, the ligand is a chiral molecule that is attached to the metal atom (which is responsible for the catalytic activity). The presence of the ligand, mainly through its shape and bulk close to the active metal, induces chirality in the product of the catalytic reaction. Molecules containing carbon-metal linkage; a compound containing an alkyl or aryl radical bonded to a metal, such as tetraethyllead, Pb(C2H5)4. However, the definition of organometallic is often broadened to include a variety of ligands such as phosphines, amines, and CO. The % substrate which is reacted to form reaction products. The quantity of desired product expressed as a percentage of the total reaction products. The % conversion x % selectivity, e.g. 90% conversion at 90% selectivity gives 81% yield. Pd, Pt, Rh, Ru, Ir, Os Pd, Pt, Rh, Ru, Ir, Os, Ag, Au A molecule is prochiral if it has one symmetry element (plane or inversion centre). Reactions that destroy this symmetry element lead to chiral molecules. Also known as achiral.

Chemisorption

Chemo-catalyst

Chemoselectivity

Chiral Chiral auxiliary

Chiral molecule

Chiral pool

Co-catalyst

Diastereomers

Enantiomer

Enantioselective

Enantioselectivity (ee)

Organometellic compound

% Conversion % Selectivity % Yield

Platinum Group Metals (PGM) Precious Metals (PM) Prochiral

© 2008 Johnson Matthey Plc

87

Glossary of Terms – continued
Promoter Racemate Regioselectivity Dopants added to catalysts to improve their action – activity, selectivity or stability. A 1:1 mixture of enantiomers. A reaction is regioselective when it takes place at only one of two or more possible functional groups to form just one of two possible isomers. Starting material (or reactant or feedstock) for the catalytic reaction. Unique scavenging system where metal binding functionality is grafted onto fibres allowing the effective recovery of a range of precious metals. Temperature at which lattices begin to be appreciably mobile (=0.5Tm in Kelvin). Melting point in Kelvin. The number of molecular reactions or reaction cycles occurring at the reactive centre up to the decay of activity. Specifies the maximum use that can be made of a catalyst for a particular reaction under defined reaction conditions. Volatile Organic Compound.

Substrate Smopex®

Tammann temperature Tm Turnover number (TON)

VOC

9. Other publications from Johnson Matthey
Platinum
Platinum is an annual review of world supply and demand for the PGMs, published each year in May. It is updated after 6 months by an Interim Review. The review contains a market summary and outlook, information on supplies, mining and exploration, discussions of the markets for platinum, palladium and other PGMs, information on prices and futures and a breakdown of supply and demand.

Platinum should be read by anyone involved in sourcing decisions involving PGMs. Copies are available free and can be obtained by contacting your local Johnson Matthey office (see section 10).

Platinum Metals Review
Platinum Metals Review is a quarterly journal of scientific research on PGMs, published by Johnson Matthey. It covers all areas in which PGMs find application, and not just catalysis. It is freely available on the internet at: http://www.platinum.matthey.com

Those wishing to subscribe to Platinum Metals Review or to submit papers for publication should contact Johnson Matthey offices or the Editor, 40-42 Hatton Garden, London EC1N 8EE; E-mail: jmpmr@matthey.com

Catalytic Reaction Guide
The Catalytic Reaction Guide, available free from Johnson Matthey, is a pocket-sized slide chart setting out over 100 reaction types and giving, for each, recommendations covering catalyst type, catalytic metal and reaction conditions. It is very useful as a first point of reference.

New Catalyst Development for Cross-Coupling Reactions
Includes examples of catalysts for application in C-C, C-N, C-O, C-S coupling reactions.

88

© 2008 Johnson Matthey Plc

10. Addresses of Local Offices
UNITED KINGDOM Johnson Matthey Plc Orchard Road Royston Hertfordshire SG8 5HE Tel: (44) 176 325 3000 Fax: (44) 176 325 3419 e-mail: chemicals@matthey.com Johnson Matthey Plc 33 Jeffreys Road Brimsdown Enfield Middlesex EN3 7PW Tel: (44) 208 804 8111 Fax: (44) 208 804 1918 Johnson Matthey Plc Technology Centre Blounts Court Sonning Common Reading Berkshire RG4 9NH Tel: (44) 118 924 2000 Fax: (44) 118 944 2254 Johnson Matthey Plc PO Box 88 Haverton Hill Road Billingham Cleveland TS23 1XN Tel: (44) 1642 525 343 Fax: (44) 1642 522 542 Johnson Matthey Plc 28 Cambridge Science Park Milton Road Cambridge CB4 0FP Tel: (44) 1223 226160 Fax: (44) 1223 438037 AUSTRALIA Johnson Matthey (Aust) Ltd 339 Settlement Road Thomastown Victoria 3074 Tel: (61) 3 9465 2111 Fax: (61) 3 9466 4932 AUSTRIA Johnson Matthey & Co GmbH Steckhovengasse 12 A 1132 Vienna Tel: (43) 187 79890 Fax: (43) 187 798903 BELGIUM S.A. Johnson Matthey N.V. Avenue de Bâle 8 – Bazellaan 8 B – 1140 Brussels Tel: (32) 2 729 07 43 Fax: (32) 2 726 90 61 BRAZIL Johnson Matthey Brazil Rua Dr. Jesuino Maciel, 919 Campo Belo 04615-002 São Paulo – SP Tel: (55) 11 5561 3805 Fax: (55) 11 5561 3098 CHINA Johnson Matthey (Shanghai) Catalyst Co., Ltd. 88 Dong Xing Road Songjiang Industrial Zone Shanghai P 201613 .C. Tel: (86) 21 33528282-6210 Fax: (86) 21 33528728 email: catalystenquiries@mattheyasia.com CHINA – HONG KONG Johnson Matthey Hong Kong Ltd Suites 2101 CMG Asia Tower The Gateway 15 Canton Road Tsimshatsui Kowloon Tel: (852) 27380327 Fax: (852) 27362345 CZECH and SLOVAC REPUBLICS Johnson Matthey V sadech 4 – Bubenec 160 00 Prague 6 Tel: (420-2) 24321549 (420-2) 24320367 (420-2) 33332384 Fax: (420-2) 24320433 DENMARK Johnson Matthey A/S Frederikssundvej 274D Bronshoj 2700 Copenhagen Tel: (45) 3889 6200 Fax: (45) 3889 6201
89

© 2008 Johnson Matthey Plc

FINLAND Johnson Matthey Virnatie 5B FIN-01300 Vantaa Tel: (358) 9 857 4800 Fax: (358) 9 857 4807

FRANCE Johnson Matthey SA 13 Rue de la Perdrix ZI Paris Nord II BP 50240 95956 Roissy CDG Cedex Tel: (33) 1 48 17 21 72 Fax: (33) 1 48 17 21 55 GERMANY Johnson Matthey GmbH Otto-Volger-Str. 9B 65843 Sulzbach Tel: (49) 6196 703885 Fax: (49) 6196 73944 HUNGARY Mr. Peter Hajdu Royston Kft H-1121 Budapest Normafa ut 17A Tel: (36) 1 275 41 35 Fax: (36) 1 275 41 34 INDIA Johnson Matthey Chemicals India Pvt. Ltd Plot No. 6, MIDC Industrial Estate Taloja, District Raigad Maharashtra 410 208 Tel: +91 22 27 401710 Fax: +91 22 27 401711 email: catalystenquiries@mattheyasia.com ISRAEL N. Intrater & Associates 5 Lurie Street P O Box 21016 Tel Aviv 61210 Tel: (972) 3629 2965 Fax: (972) 3528 8008 ITALY Please contact our Royston, UK facility for all inquiries

JAPAN Johnson Matthey Japan Inc The Imperial Tower 14th Floor 1-1-1 Uchisaiwai-cho Chiyoda-ku Tokyo 100-0011 Tel: (81) 3 5511 8551 Fax: (81) 3 5511 8561 email: jmj-catalog@mattheyasia.com KOREA Johnson Matthey Korea Ltd 6th Floor, Woonam Building 294 Chamsil-dong Songpa-ku Seoul Tel: (82) 2 3431 3816 Fax: (82) 2 3431 3819 PORTUGAL Lusomelt – Fornecimento de bens e Serviços, Lda Rua de Belém, 48 – 2˚ P-1300-085 Lisbon Tel: (351) 21 361 62 10 Fax: (351) 21 363 49 95 RUSSIA Johnson Matthey Moscow Ilyinka 3/8 Building 5, Office 301 Moscow 109012 Russia Tel: 7095 101 2100 Fax: 7095 101 2113 SOUTH AFRICA Johnson Matthey (Pty) Limited Henderson Road South Gerniston Ext 7 Gauteng 1401 Republic of South Africa Tel: (27) 1134 58 500 SPAIN C.J. Chambers Hispania S.L. Apartado 92 08840 Viladecans Barcelona Tel: (34) 607 811 550 Fax: (34) 936 376 913

90

© 2008 Johnson Matthey Plc

SWEDEN Please contact our Royston, UK facility for all inquiries SWITZERLAND Johnson Matthey & Brandenberger AG Glattalstrasse 18 CH-8052 Zurich Tel: (41) 1 307 19 19 Fax: (41) 1 307 19 20

USA Johnson Matthey Inc 2001 Nolte Drive West Deptford New Jersey 08066 1727 Tel: (1) 856 384 7000 Fax: (1) 856 384 7282 e-mail: inquiries@jmusa.com

TAIWAN Johnson Matthey Pacific Ltd Taiwan Branch 9F-3, 51 Keelung Road Section 2 Taipei Tel: (886) 2 23786818 Fax: (886) 2 27366558

Information contained in this publication is given in good faith, but Johnson Matthey will accept no liability for any claims made against a customer for any infringement of patent rights, registered or unregistered trademarks (including any copyright therein) or of registered designs or copyright involved in the use, resale or offering for resale of the compound either as sold by Johnson Matthey or otherwise. While Johnson Matthey has taken all reasonable care to ensure the accuracy of the contents of this brochure, it is incumbent on the user to exercise due care and diligence when handling these materials. Johnson Matthey can therefore accept no liability for loss or damage arising from their use. Ref 01.04 / UK © 2008 Johnson Matthey Plc
91

92

© 2008 Johnson Matthey Plc

Sign up to vote on this title
UsefulNot useful

Master Your Semester with Scribd & The New York Times

Special offer for students: Only $4.99/month.

Master Your Semester with a Special Offer from Scribd & The New York Times

Cancel anytime.