Polyurea Microencapsulated Palladium Catalysts. Pd EnCat TM

Transcription

1 Polyurea Microencapsulated Palladium Catalysts Pd EnCat TM

2 utline Introduction Catalyst synthesis Catalyst physical characteristics Catalyst activity optimisation Catalyst mechanism Chemistry examples Parallel synthesis examples Process Case Studies

3 Introduction

4 Pd catalysed C-C bond formations Heck, Suzuki, Stille, Carbonylation, Sonogashiras, etc Pd-Catalysed C-,C-,C-S bond formation. Pd reductions/oxidations

5 Common Process Issues with Homogeneous Pd Catalysis Pd contamination of product regulatory requirements Pd contamination of intermediate interferes with downstream chemistry Pd contamination of reactor vessels cleaning costs Pd contamination in waste streams treatment costs Pd loss from process = high cost Minimise Soluble Pd Downstream treatment Heterogeneous catalyst

6 Catalyst Synthesis

7 Microencapsulation of Palladium (II) Salts by in situ Interfacial Polymerisation Heating initiates polymerisation il-in-water emulsion Catalyst in organic solvent with crosslinking isocyanates C C C Filtered & dried EnCat TM µm water, stabilisers CH 2 CH 2 + Pd(II) salt n

8 Catalyst Physical Characteristics

9 SEM 0.4 mmol/g Pd EnCat TM 40

10 EDX Analysis 0.4 mmol/g Pd EnCat TM 40

11 Dry State Porosity of 0.4 mmol/g Pd EnCat TM 40 BET nitrogen adsorption surface area = 0.07m 2 /g - no meso or macro pores Mercury intrusion porosimetry = 0.06cc/g - no macro pores - some partial collapse of internal voids

12 Solvent Swelling f Pd EnCat TM 40 Solvent DMF DMA THF Acetone EtH IPA Toluene Swelling of EnCat TM %

13 Porosity of 0.4 mmol/g Pd EnCat TM 40 In THF swollen state Chromatographic Porosimetry investigation: Pd EnCat Pore Size Distribution 1.2 Volume-Avg PSD (norm) Pd EnCat 40 Low pore size - average pore diameter = 1.28nm Very low pore volume Mono dispersed pores Polystyrene molecules of MW >300 are excluded Pore diameter (nm)

14 Leaching of Pd from Pd EnCat TM 40 TM 40 Solvent Pd ppm % Pd extracted THF Acetone <1 <0.15 Ethanol <1 <0.15 Acetonitrile IPA <1 <0.15 Toluene <1 <0.15 Dioxane Ethyl acetate <1 <0.15 DMF DMA

15 Pd EnCat TM 40 Comparison with Pd(Ac) 2 in Simple Suzuki Coupling Br F + B(H) 2 Me F Me Conditions: 3 mol% Pd, K 2 C 3, 80 o C, EtH/Water 20/1 Reaction stopped after 5 hours Pd(Ac) 2 Pd (Ac)2 Pd EnCat % conversion Pd EnCat Time/ min

16 Pd EnCat TM Activity ptimisation

17 Enhancement of Pd EnCat TM Activity Achieved through increasing matrix porosity - improving access of substrates to metal species 1) Reducing polymer matrix content 2) Reducing cross-link density of PU matrix 3) Use of solvents capable of swelling matrix

18 Reducing Polymer Matrix Content % conversion to product Time/ hrs 40% 'wall' content 30% 'wall' content 20% 'wall' content Br B(H) 2 + F Me F Me

19 Porosity in Solvent Swollen State as a function of Matrix Content Chromatographic Porosimetry Investigation: Matrix Content (%) Swollen Bulk density (g/ml) Swollen Pore volume (ml/g) Average Pore Diameter (nm) PS MW Exclusion >300 >900 >300

20 Pore Size Distribution in Solvent Swollen State PSD (Volume) Pore Diameter (Å)

21 Leaching of Pd from Pd EnCat TM 30 TM 30 Solvent Pd ppm % Pd extracted THF Acetone Ethanol <1 <0.08 Acetonitrile <1 <0.08 IPA <1 <0.08 Toluene <1 <0.08 Dioxane <1 <0.08 Ethyl acetate <1 <0.08 DMF DMA

22 Post Addition f TPP to Pd EnCat TM 40 Suzuki Coupling Reaction Rate variation with PPh3 % conversion :1 PPh3 o PPh3 Initial induction period before reaction starts Low levels (<3 ppm) Pd detected in solution Time/ hours Br + B(H) 2 F Me TPP = 3 P F Me

23 Initial Kinetics Following Post Addition f TPP to Pd EnCat TM 40 and 30 Pd EnCat TM 40 Pd EnCat TM % conversion :1 PPh3 1:2 PPh3 1:4 PPh3 o PPh Time/ hrs % conversion :0.5 PPh3 1:1 PPh3 1:2 PPh3 o PPh Time/ hrs Pd EnCat 30 shorter induction Induction period is sensitive to the amount of TPP Br B(H) 2 + F Me F Me

24 verall Kinetics Post Addition f TPP to Pd EnCat TM in Suzuki Coupling Reaction Pd EnCat TM 40 Pd EnCat TM % conversion to product :1 PPh3 1:2 PPh3 1:4 PPh3 o PPh Time/ hours % conversion Time/ hrs 1:0.5 PPh3 1:1 PPh3 1:2 PPh3 o PPh3 Br B(H) 2 + F Me F Me

25 Pd EnCat TM with Co-Encapsulated Phosphine Ligand C C CH 2 + Pd(II) salt + Ligand 3 P CH 2 n C Interfacial Polymerisation H H H H H H H H H H H H H H Pd (II) H H Pd (II) H Ligand H H Ligand H H H H PCy 2 3 P

26 Pd EnCat TM Activity with Co-Encapsulated Phosphine Ligands (Pd/P 1/0.5) Br F + B(H) 2 Me F Me Ar P Ar Ar Ar = Phenyl TPP Ar = o-tolyl TTP % Conversion to product Pd EnCat TPP Pd EnCat TTP Pd EnCat Standard With 1:0.5 PPh3 With 1:0.5 P(o-Tolyl)3 Crude Product <5ppm Pd <5ppm P Time/ hrs

27 BDPPB Pd EnCat TM Activity Ph Ph P BDPPB P Ph Ph Conditions: 3 mol% Pd, K 2 C 3, 80 o C, IPA/Water 20/1 100 % Crude Product 20ppm Pd 50ppm P 20 0 Pd EnCat 1:0.5 BDPPB Time/ hrs

28 Pd EnCat TM with Co-encapsulated Phosphine Ligand Fast reactions in quantitative yield Low palladium leach (<15ppm, <1% total)* Some phosphine ligand leach (<30ppm, <10% total)* Greatly simplified reaction work up Versatile tunable catalyst design * Solvent dependent

29 Customised Catalysts Pd EnCat TM catalysts - can be tailored to a specific process and chemistry by selection of: - Metal type and loading - Ligand type and loading - Matrix porosity and particle size P 3 3 P PCy 2 P(tBu) 2 PCy 2 PPh 2 PPh 2 Ph 2 P PPh 2 Ph 2 P PPh 2

30 Fluorescent Labelled Pd EnCat TM H 2 H 2 H2 H 2 Cl S H 2 H S

31 Microencapsulated Palladium Acetate Products Product Matrix Content % Pd content mmol/g (%) Coencapsulated ligand Average particle size micron Pd(II) EnCat TM (4) Pd(II) EnCat TM (4) Pd(II) EnCat TM TPP (4) P Pd(II) EnCat TM TTP (4) P

32 Microencapsulated Palladium Zero ano Particulate Products Product Matrix Content % Pd content mmol/g (%) Coencapsulated ligand Average particle size micron Pd(0) EnCat TM 40P (4) Pd(0) EnCat TM 30P (4)

33 TM Pd EnCat TM Mechanism

34 Catalyst Mechanism H RESI 1. B H Bu 4 Ac, CH 3 C, Pd catalyst. MW, 110 o C, 1h H Br 2. TFA/DCM/H 2 (23:75:2) Control reactions with Pd(Ph 3 ) 4 gave 4:1 product : Ar-Br Pd-EnCat TM - no detectable product. nly pure Ar-Br c.f. I. W. Davies et. al., J. Am. Chem. Soc., 2001, 123,

35 Catalyst Mechanism Reaction probably takes place within microcapsules: Suzuki substrates added to hot solvent extracts of Pd EnCat TM gave no reaction. Removal of Pd EnCat TM from Suzuki reaction mixture by hot filtration stopped reaction.

36 Mechanism Mechanism PRDUCTS REAGETS H H H H H H H H H H H H H H H H H H H H H Ligand Pd (II) Pd (II) Ligand H H

37 Chemistry Examples with Pd EnCat TM

38 Chemistry Examples Suzuki: R 1 B(H) 2 + Br R 2 R 1 R 2 Pd EnCat TM Heck: 2 Br + Pd EnCat TM 2 Carbonylation M e I + C + n-buh Pd EnCat TM Me C 2 n-bu Transfer Hydrogenation Pd EnCat TM 2 H 2

39 Suzuki Couplings Catalysed by Pd EnCat TM 40 TM 40 R1 + R2 R1 p-me R2 p-me Yield % 87 B(H) 2 Br p-me p-f 89 p-me p mol% Pd EnCat 40 Tol/W/EtH 4/2/1 K 2 C 3 80 o C, 8-12h o-me p-ac p-ac o-me p-me p-f p-ac p R1 R2 H H p-me p-f H p- 2 97

40 Pd EnCat TM Development Product Pd EnCat TM Binap30 PPh 2 PPh 2

41 Electron Rich Suzuki Couplings Pd EnCat TM Binap30 Catalysed Aryl Halide + Product Encap Ligand (% Yield) one TPP TTP Binap Me B(H) 2 P 3 P 3 PPh 2 PPh 2 Br Me >99 Br H Me H Br Me >99 Br Me

42 Pd EnCat TM Binap30 Catalysed Electron Rich Suzuki Couplings Aryl Halide + Product % conv *Pd ppm *P ppm Me B(H) 2 Br Me > Br H Me H Br Me > Br Me * In crude product following solvent evaporation

43 Pd EnCat TM 40 Catalysed Heck Reactions Substrate Product Yield (%) Br C 2 nbu Br Ph Br C 2 nbu 25 Me I Me C 2 nbu 98 Conditions: 2.5mol% Pd EnCat TM 40, IPA, nbu 4 Ac,90 o C, olefin

44 Pd EnCat TM 40 Catalysed Carbonylations Substrate Product Yield (%) I C 2 nb u 89 I C 2 nbu 99 M e I M e C 2 nb u 95 Me C I M e C C 2 nbu 93 S I S C 2 nbu 98 Conditions: 3mol% Pd EnCat TM 40, nbuh, C, TEA, 90 o C

45 Pd EnCat TM 40 Catalysed Stille Reactions Br Ph 99% 2 Br 2 Ph 88% Me Br Me Ph 82% F Br F Ph 74% Me Me I Ph 91% Conditions: 2.5mol% Pd EnCat TM 40, IPA/Tol 1/1, nbu 4 Ac, 90 o C, Me 3 SnPh

46 Influence of Thiol Substrates In Pd EnCat TM Suzuki Couplings B(H) 2 Br + 3 mol% PdEnCat K 2 C 3, IPA/H 2 (20:1) Br S S Br Me SH 80 o C,24h B(H) 2 Br + 3 mol% PdEnCat K 2 C 3, IPA/H 2 (20:1) Me Me 80 o C,24h 77%

47 Pd EnCat TM 40 Suzuki Coupling of Sulfides B(H) 2 Br + 6 mol% PdEnCat K 2 C 3, IPA Me SMe Me SMe 95 o C, 36h 65%

48 Pd EnCat TM 40 & Suzuki Coupling In the Presence of Thiol Contaminant B(H) 2 Br HS + 3 mol% PdEnCat K 2 C 3, IPA/H 2 (20:1) Me 2 Me 2 80 o C,4.5h 4-THICRESL 45min 2.5h 3h 4h Crude 0% 66% 82% 82% 82% >90% (5h) 0.1% 37% 73% 79% 81% >90% (5h) 1% 1% 1% - 3% 3% (24h) 3% 1% 2% - 4% 4% (24h)

49 Hydrogenation and Transfer Hydrogenation with Pd(0) EnCat TM and Pd(0) EnCat TM P Pre activation of catalyst required: Reduction of Pd with hydrogen or Reduction of Pd with formic acid

50 Characteristics Pd(0) EnCat TM Pd EnCat TM H 2 50 bar Pd 0 EnCat Low activity catalyst Pd Particles > 5nm, single domain and well ordered Selective reductions possible

51 Pd(0) EnCat TM 40 Hydrogenations Pd(Ac) 2 En Cats in Hydrogenation Ph Pd(Ac) 2 En Cat EtH, H 2, 4h RT Ph Ph H Ph Pd(Ac) 2 En Cat EtH, H 2, 18h RT Ph H Ph Ph C Pd(Ac) 2 En Cat EtH, H 2, 5h, 60 o Pd(Ac) 2 En Cat EtH, H 2, 18h, RT, 50bar Ph C All Quantitative Ph Pd(Ac) 2 En Cat EtH, H 2, 18h, RT, 50bar Ph Pd(Ac) 2 En Cat Br EtH, H 2, 18h, RT, 50bar Br

52 Preparation of ano Particulate Pd(0) EnCat TM P Pd EnCat TM HCH/ether 1/1 Ligand exchange H H Pd reduction P Pd 0 EnCat Pd particles <2nm (approx 10 atoms) ano structure stabilised by polyurea matrix Highly active and recyclable H 2 transfer catalyst High chemoselectivity on pyrophoric

53 ano Particulate Pd(0) EnCat TM P

54 Transfer Hydrogenation with Pd(0) EnCat TM 40P P Pd (0) EnCat (10mol%), HC 2 H, Et 3, H EtAc, rt, 21hr 99% Ley, S.V.; Ramarao, C.; Yu, J-Q.; Wu, H-C.; Spencer, J., Chem Commun., 2003, Smith S. C., Speciality Chemicals, in press, Sep C2 Et P Pd (0) EnCat (5mol%), C 2 Et HC 2 H, Et 3, H EtAc, rt, 3hr 92% Ley, S.V.; Mitchell, C.; Pears, D.; Ramarao, C.; Yu, J.-Q.; Zhou, W., rg. Lett., 2003, 5(24),

55 Kinetics Pd(0) EnCat TM 40P vs Pd(0) EnCat TM 30P P Pd(0) EnCat 30 5 mol% catalyst HC 2 H (4 eq) Et 3 (4 eq) EtAc % Conversion P Pd(0) EnCat 40 EnCat 30 1st recycle H EnCat 30 2nd recycle <1ppm Pd in reaction solution Time (hours) EnCat 30 3rd recycle

56 Transfer Hydrogenation of Aryl Ketones Catalyst Loading Study P Pd (0) EnCat, HC 2 H (5 eq), Et 3 (5 eq), EtAc, rt, 40 hr % Conversion P Pd(0) EnCat 30 P Pd(0) EnCat 40 2 eq HC 2 H & Et 3 H Catalyst Loading (Mol %)

57 Recycle - Transfer Hydrogenation of Aryl Ketones with Pd(0) EnCat TM 40P H b Run Yield (%) Time (h) b Reagents and conditions: 10 mol% P Pd 0 EnCat, 200 L EtAc, 0.8 mmol HCH, 0.8 mmol Et 3, 0.16 mmol acetophenone, 24 ºC.

58 Recycle - Transfer Hydrogenation of Benzylic Epoxides with Pd(0) EnCat TM 40P Ph Ph Ph H Ph 99% Conditions: 5 mol% P Pd 0 EnCat TM, Et 3, HCH, EtAc, 5 hours Catalyst recycled 10 times without loss of activity or yield

59 Transfer Hydrogenation of Aryl Ketones with Pd(0) EnCat TM 40P Substrate Product Time (hr) Yield (%) H H Cl Cl H F 3 C F 3 C H H 21 99

60 Transfer Hydrogenations Aryl Ketones with Pd(0) EnCat TM 40P Substrate Product Time (hr) Yield (%) H H CF 3 CF 3 H H 18 99

61 Chemo-selective Transfer Hydrogenation f itro Groups with Pd(0) EnCat TM 40P 2 H 2 99% Conditions: 10 mol% P Pd 0 EnCat TM, EtAc, HCH, Et 3, Ketone, RT

62 Transfer Hydrogenation of Benzylic Epoxides by Pd(0) EnCat TM 40P H 90% H 81% Conditions: 5 mol% Pd EnCat TM, Et 3, HCH, EtAc, 3 hours

63 Transfer Hydrogenation f Benzylic Epoxides with Pd(0) EnCat TM 40P Substrate Product Time (h) Yield (%) H Ph Ph H H 5 72 CH 2 H CH 2 H H H

64 Transfer Hydrogenation f Benzylic Epoxides with Pd(0) EnCat TM 40P Ph Ph Ph H Ph 99% Conditions: 5 mol% P Pd 0 EnCat TM, Et 3, HCH, EtAc, 5 hours Catalyst recycled 10 times without loss of activity or yield

65 Transfer Hydrogenation - Comparison of Pd(0) EnCat TM 40P with Pd/C Pd(0) catalyst HCH, Et 3, EtAc H 10% Pd/C (5 mol%) - 48% Pd EnCat TM (5mol%) - 90% Ph Pd(0) catalyst Ph HCH, Et 3, EtAc H 10% Pd/C (5 mol%) - 80% Pd EnCat TM (5mol%) - 97%

66 Reductive Cyclisation to Indole by Pd(0) EnCat TM 40P Step 1 Step Me2 H Step 1 Leimgruber-Batcho microwave, DMF, Lewis acid Step 2 6 mol% P Pd 0 EnCat TM, EtAc, 5 equiv HCH/Et 3, 24 o C, 24 hours or microwave, 120 o C, 2 hours

67 Influence of Thiol Substrates in Pd(0) EnCat TM 40P Transfer Hydrogenation f itro Groups 2 10 mol% PdEnCat H 2 Et 3 /HC 2 H, EtAc 2.5h 99% 2 10 mol% PdEnCat H 2 HS Et 3 /HC 2 H, EtAc 24h HS

68 Advantages of Pd(0) EnCat TM 30P Easy and safe to handle vs Pd/C Hydrogenations without the need for hydrogen gas Simple recovery of catalyst Very low metal contamination Versatile matrix Can be recycled

69 Pd EnCat TM TM in Parallel Synthesis

70 Automated Library Synthesis with Pd(0) EnCat TM 40P -capped biaryl carbinols of interest as herbicides X R Y Can we use Pd 0 EnCat to prepare a range of alcohol intermediates in a library synthesis? Building blocks would be of general use in other chemistries

71 Parallel Substrate Screening Experiment Use of 2 x 48 Bohdan Miniblocks for scale and ease of filtration Evaporated filtrate + DCM + water filtered through phase separation plate 96 products analysed by LC-MS, GC-MS and MR Ar X X = alkyl, aryl, CR, CH 2 X P Pd (0) EnCat (10 mol%), HC 2 H (5 eq), Et 3 (5 eq), EtAc, rt, 40hr H Ar X

72 Examples of Successful Reactions Ar X P Pd (0)-EnCat (10 mol%), HC 2 H (5 eq), Et 3 (5 eq), EtAc, rt, 40hr Ar H X Reduction of a range of aryl ketones proceeded cleanly: Cl H H Cl H 100% H 94% H 83% Et H Et 100% 79% Et H CH H Et H H 100% 100% 100%

73 Examples of Low Yield Transfer Reductions with Pd(0) EnCat TM 40P Ar X P Pd (0)-EnCat (10 mol%), HC 2 H (5 eq), Et 3 (5 eq), EtAc, rt, 40hr Ar H X Aryl electronics and sterics have the greatest influence on reactivity: F Me F H Me 0% H 0% H H 10% 15% + 10% CH 2 Me Me H 0% 0%

74 Influence of Switching to Pd(0) EnCat TM 30P with Difficult Substrates P Pd (0)-EnCat (10 mol%), HC 2 H (5 eq), E t 3 (5 eq), H Ar X EtAc, rt, 40hr Ar X P Pd 0 EnCat 40 P Pd 0 EnCat 30 H Me Me H H 4 13 Me H 0 2 H 55 93

75 Influence of Switching to Pd(0) EnCat TM 30P with Difficult Substrates P Pd (0)-EnCat (10 mol%), HC 2 H (5 eq), E t 3 (5 eq), H Ar X EtAc, rt, 40hr Ar X Me H P Pd 0 EnCat 40 P Pd 0 EnCat 30 <5 20 H H H 10 29

76 Unusual Products Ar X P Pd (0)-EnCat (10 mol%), HC 2 H (5 eq), Et 3 (5 eq), EtAc, rt, 40hr Ar H X Alternative reduction products: C 2 Me C 2 H C 2 Me + Cl 27% 73% 21% + H 59% Cl H 79% H + Cl 63% 37%

77 Intramolecular Heck Library: Pd EnCat TM 30 vs 40 Br Pd Catalyst (5 mol%) Solvent, Et 3 (2 eq) Use of Zinsser Sophas for top filtration of catalyst % Conversion CH 3 C 80 o C Pd EnCat 40 Pd EnCat 30 Pd(PPh3)4 % Conversion DMF 120 o C Pd EnCat 40 Pd EnCat Time (hours) Time (hours)

78 Process Case Studies with Pd EnCat TM

79 Suzuki Coupling Process Example Pd EnCat TM 30 vs 5% Pd/C R1 B(H) 2 + R2 Br R2 5% Pd/C R1 R1 R1 R1 a 2 C 3 80 o C, 8-12h + + A B C 5% Pd/C 2.5mol% 30min min EnCat mol% 30min 97 <1 <1 1.25mol% 30min >99 <1 <1 0.5mol% 30min >99 <1 <1 0.05mol% 30min >99 <1 <1

80 Suzuki Coupling Process Example Pd EnCat TM 30 vs 5% Pd/C R1 B(H) 2 + R2 Br R2 5% Pd/C R1 R1 R1 R1 a 2 C 3 80 o C, 8-12h + + A B C % Yield A Pd (ppm) in crude product 5% Pd/C 2.5mol% 60min EnCat mol% 30min > mol% 30min > mol% 30min >99 9

81 Hindered Suzuki Process E.g. Problem Residual Pd with Homogeneous Catalyst PdCl 2 (PPh 3 ) 2 Tf R + R' B(H) 2 R' 1.5 equiv Pd EnCat 3 equiv Cs 2 C 3, PPh 3 85o C, DME R' R' R Conversion Time (h) <50ppm Pd in crude product

82 Hindered Suzuki Process E.g. Problem Residual Pd with Homogeneous Catalyst PdCl 2 (PPh 3 ) 2 Br R + R' B(H) 2 R' 1.5 equiv Pd EnCat 3 equiv Cs 2 C 3, PPh 3 85 o C, DME R' R' R Conversion PPh3 P(o-Tolyl)3 PCy3 Ligand Comparison with bromo compound TPP TTP <15ppm Pd in crude product 20 PCy Time (h)

83 Case Study - Pd EnCat TM 40 TM 40 Suzuki Coupling Route to 4-Pyridin-4-yl-benzoic acid: H

84 Existing Homogeneous Route Br HCl + H B H H 80-90% H Conditions: EtH/Water, K 2 C 3, Ligand, mole% Pd (PPh 3 ) 4 Issues: 600ppm Pd in crude product Pd in waste stream Cost - no catalyst reuse Target to achieve <100ppm Pd in crude

85 Pd EnCat TM 40 Case Study

86 Pd EnCat TM 40 Case Study Changed to much cheaper chloro pyridine: Cl HCl + H B H H H o product under previous conditions Pd EnCat TM 40 / TPP Extensive ligand screen monitoring yields and impurity profiles: H minor H H major H

87 Pd EnCat TM 40 Case Study Biphenyl phosphines best ligands: Cy P Cy Highly active catalyst, optimisation reduced both Pd and ligand charge versus bromopyridine reaction: Ligand: 0.3 mole% biphenyl vs 2.5 mole% for TPP Pd EnCat TM : 0.13 mole% Pd vs 0.75 mole% Rate x3 faster than bromopyridine

88 Pd EnCat TM ptimised Process 85% product yield Successful scale up - easy to charge & filter catalyst with low cake resistance - good mixing with retreat curve impellers Rate acceleration for Pd EnCat TM x30 that of Pd(Ac) 2 * Catalyst recycle 90 ppm Pd in crude product achieving 100ppm customer target. Remove catalyst & reaction stops, implies reaction occurs within EnCat TM matrix * Reaction in beads provides an area of localised high catalyst/reagent concentration?

89 Pd EnCat TM - Reported Benefits at Process Scale no plating out of palladium metal on vessel walls reduced cleaning issues; reducing solvent use and cycle time ability to access a wider range of process technology e.g. fixed bed, fluidised, trickle bed and microwave reactors safer to handle vs palladium on carbon reduced metal loss integrates into standard chemical plant

90 Acknowledgments Avecia Cambridge Syngenta AstraZeneca D Pears Prof S V Ley S Smith I McConvey M isar Prof A Holmes I Shirley A Wells I Houson Dr C Ramarao D Beirne J Blacker R Gordon Dealmeida R Fieldhouse Dr Jin Yu J Hebblethwaite K Treacher C Mitchell Millenium D Tapolczay

91 Microencapsulated Palladium(II) Products - Pd EnCat TM Product Matrix Content % Pd content mmol/g (%) Coencapsulated ligand Average particle size micron Pd(II) EnCat TM (4) Pd(II) EnCat TM (4) Pd(II) EnCat TM TPP (4) 3 P Pd(II) EnCat TM TTP (4) 3 P

92 Microencapsulated Palladium Zero ano Particulate Products Product Matrix Content % Pd content mmol/g (%) Coencapsulated ligand Average particle size micron Pd(0) EnCat TM 40P (4) Pd(0) EnCat TM 30P (4)