catalyddion aml-ochrog mewn hylyfoedd uwchradd martyn poliakoff [email protected]

73
Catalyddion Aml- Ochrog mewn Hylyfoedd Uwchradd Martyn Poliakoff [email protected]

Post on 21-Dec-2015

216 views

Category:

Documents


0 download

TRANSCRIPT

Catalyddion Aml-Ochrog mewn

Hylyfoedd Uwchradd

Martyn [email protected]

Supercritical Fluids

• Gases e.g. CO2, C2H4, H2O compressed until they are nearly as dense as liquids

• SCFs can dissolve solids solubility increases with density (applied pressure)

Critical Points

Pc

Tc

oC

HC3 8

H2O

35

65

95

360

390

CO2

CO2

C3H8

22

7.4

MPa

4.3H2O

Supercritical Catalysis

• Catalysis in scCO2:- Hydrogenation, Hydroformylation

• Supercritical Water• Biocatalysis

Miscibility of H2/scCO2

Howdle, S. M., Healy, M. A., Poliakoff, M. J. Am. Chem. Soc. 1990 112, 4804.

Jessop, Ph. G., Ikariya, T., Noyori, R. Nature 1994, 368, 231.

T > TcT < Tc

Liquid

H2

Higher Concentration of “Dissolved” H2 in scCO2

Continuous Supercritical Hydrogenation

scCO2

CO2Product

Substrate + H2

Catalyst

Other Hydrogenations successfullycarried out in scCO2 and scPropane

NR'

RR" C NR O

R

R'

R OH

Oximes, Imines

Schiff Bases Nitriles

Aldehydes and Ketones

EpoxidesAlcohols

O

HR

O

R'R

O

HR

O

R'R

• continuous• multipurpose• 1000 ton p.a.

scCO2

ChemicalPlant

opened July,2002

Thomas Swan & Co

Hydrogenation of IsophoroneO

Pd Deloxan®

100 bar, scCO240-170°C

+ H2

O

scCO2 - quantitative, no by-products

The product & by-products have similar boiling points

Conventional process requires an expensive downstream separation

scCO21-Octene

Aldehydesn : iso 50:1

ImmobilizedCatalyst

CO2

CO + H2

Rh COCO

PPh2

PPh2

ONSiO

O

O

H

scCO2 and Ionic Liquids

scCO2 very soluble in ILs (~ 0.6 mole fraction)

ILs are insoluble in scCO2

L.A. Blanchard, D. Hancu, E.J. Beckman and J.F. Brennecke, Nature, 1999, 399, 28

scCO2 can extract many organics from ILs L. A. Blanchard and J. F. Brennecke, Ind. Eng.

Chem. Res., 2001, 40, 287

Bi-phasic Catalysis: Cole-Hamilton

P. B. Webb, M. F. Sellin, et al. J. Am. Chem. Soc.,2003, 125, 15577

Green Chemistry 12 Principles- Prevent wastes- Renewable materials- Omit derivatization steps- Degradable chemical products- Use safe synthetic methods - Catalytic reagents- Temperature, Pressure ambient- In-Process Monitoring- Very few auxiliary substances- E-factor, maximize feed in product- Low toxicity of chemical products- Yes it’s safe

PRODUCTIVELY

- Prevent wastes- Renewable materials- Omit derivatization steps- Degradable chemical products- Use safe synthetic methods - Catalytic reagents- Temperature, Pressure ambient- In-Process Monitoring- Very few auxiliary substances- E-factor, maximize feed in product- Low toxicity of chemical products- Yes it’s safe

Gas-Expanded Liquids

Increasing Pressure

LiquidLiquid+CO2

Liquid+CO2

Hydrogenation of α-pinene

A. Serbanovic, V. Najdanovic-Visak,

A. Paiva, G. Brunner,

M. Nunes da Ponte

8th ISSF, Kyoto

Gas-Expanded liquids (GExLs)1. Autoxidation … by O2 in GExLs,

DH Busch, B Subramaniam & co-workers, Green Chem., 2004, 6, 387.

2. Enhanced Solubility of gases in GExLs,

JF Brennecke & coworkers, Ind. Eng. Chem. Res., 2006, 45, 5351.

3. CO2-Protected Amine Formation in GExLs

X. Xie, C. L. Liotta & C. A. Eckert, Ind. Eng. Chem. Res., 2004, 43, 7907.

Hydrogenation of Isophorone

O

Pd Deloxan®

100 bar, scCO240-170°C

+ H2

O

Reaction has a high space-time yield

How is this influenced by the phase behaviour of the system?

Isophorone /CO2/H2 phase boundaries

O OH2

Two phase Operational

window

50

100

150

200

250

300

350

40 90 140Temp/°C

Pre

ssu

re/B

ar

5%

13%

17%

22%

Two phase Operational

window

M. SokolovaKe Jie

CO2- expansion & Hydrogenation• Increases solubility of H2

(B. Subramaniam, J. Brennecke)

• Increases diffusion faster transport across phase boundary (EJ Beckman)

• Reduces viscosity

All of these accelerate reaction

Hydrogenation of sertraline imine in CO2–expanded THF

Commercial Route to Zoloft®

N

ClCl

HN

ClCl

15 psi, 25oCH2/EtOH

Pd / CaCO3

(4S -) sertraline imine

cis- (1S-, 4S-) sertraline

HCl/ EtOH

HN

ClCl

Sertraline hydrochloride

.HClHH

OH

Cl

Cl

(i) AlCl3+

O

ClCl

H(ii) Continuous Chromatography

(4S -) tetralone

MeNH2 / EtOH

HH

H

Batch Process

Continuous hydrogenation of rac-sertraline in scCO2/THF

• Investigate both chemoselectivity & diastereoselectivity

• Aims: (1) < 1.5 % dechlorination (2) > 92:8 de

N

ClCl

HN

ClCl

rac-sertraline imine (1S, 4S), cis

H

H

scCO2H2/ cat.

Co-solvent

HN

ClCl

(1R, 4R), cis

H

H

HN

ClCl

(1R, 4S), trans

H

H

HN

ClCl

(1S, 4R), trans

H

H+ ++

P. Clark

Hydrogenation of rac-sertraline imine in scCO2/THF

Catalyst de (%) from NMR

cis- trans-

5% Pt/ C 56 44

2% Pd/ C 87 13

5% Pd/ CaCO3 97 3

• System pressure (125-175 bar) has little effect on selectivity

(Conditions: 175 bar; 3x excess H2; 0.4 ml/ min org flow; 0.1 M soln in THF; 0.5 g catalyst; 1.0 ml/ min CO2 flow)

Summary

• Switch from Batch to Continuous

• Dechlorination is reduced in scCO2 –why?

• One of the first examples of diastereoselective hydrogenation in scCO2

• First example of hydrogenation of final stage pharmaceutical in scCO2

Supercritical Catalysis

• Catalysis in scCO2

• Supercritical Water:- Selective Oxidation,

Formation of Caprolactam• Biocatalysis

Total Oxidation in scH2O

• Tc 374 oC; pc 218 atm.

• At 300 oC, H2O is similar to acetone

• O2 is miscible with H2O above Tc

• Already in commercial use

Johnson Matthey +ChematurAquaCat

Process for Catalyst

Recoveryopened

Oct 10th 2003

Before After

Heterogeneous Catalyst Recovery

Partial oxidation in scH2O?Nottingham: P.A. Hamley, E.G. Verdugo,

J. Fraga-Dubreuil, C. Yan, E. Venardou, R. Auerbach, R.J. Pulham,T. Ilkenhans, M.J. Clarke, J.M. Webster, M. Thomas, A. Johal.

INVISTA Performance Technologies, UK: W.B. Thomas, G.R. Aird, I. Pearson,

S.D. Housley, A.S. Coote, K. Whiston, L.M. Dudd, J. Fraga-Dubreuil (ICI D.A. Graham, P. Saxton)

Nottingham: P.A. Hamley, E.G. Verdugo, J. Fraga-Dubreuil, C. Yan, E. Venardou, R. Auerbach, R.J. Pulham,T. Ilkenhans, M.J. Clarke, J.M. Webster, M. Thomas, A. Johal.

INVISTA Performance Technologies, UK: W.B. Thomas, G.R. Aird, I. Pearson,

S.D. Housley, A.S. Coote, K. Whiston, L.M. Dudd, J. Fraga-Dubreuil (ICI D.A. Graham, P. Saxton)

0.7 Mton p.a. per plant

• TA insoluble in CH3COOH

• 18% of world production of CH3COOH lost in the process

Oxidation of p-XyleneCH3

CH3

COOH

COOH

190oC CH3COOH solvent

Mn2+/Co2+, CH3COO- /Br-

catalysts

CH3

CH3

COOH

COOH

+ 3 O2 + 2 H2O

TA

Oxidation of p-Xylene / scH2O

p-Xyl

Products

MnBr2 catalyst in cold H2O

scH2O + O2

PA Hamley, et al. Green Chem. (2002) 4, 235; (2005) 7, 294

Oxidation of p-Xylene in scH2O• > 80% yield of TA• > 90% selectivity for TA

Selective Oxidation in scH2O

If our results are scalable,

• total elimination of CH3COOH • increased energy recovery

compared to existing process• significant reduction in cost of

manufacturing TA

EXAFS & Molecular Dynamics Results with 0.4 m MnBr2

W. Partenheimer, Y. Chen, J. L. FultonJ. Am. Chem. Soc. 127, 14086, (2005)

IR spectroscopy in scH2O

• First achieved 1967 (Franck + Roth)

• Much work by T. B. Brill et al. J. Phys. Chem. (1996) 100, 7455

• Recent work by Y. Ikushima et al., Achema, (2003)

4000.0 3600 3200 2800 2400 2000 1800 1600 1400 1200.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.62

cm-1

A

FTIR of Water

25 µm pathlength

High T & P IR Cell; Yu. E. GorbatyChanges pathlength

Windows

Cell body

Driving Mechanism

500 oC1000 bar

Inlet

Hydrolysis of MeCN

4000.0 3600 3200 2800 24000.01

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.13

cm-1

A

CN

N-H

O-H

500bar300ºC

H2ON

O

NH2

O

OH

High pressure Sample Loop

CO2Product

Reactants

Catalyst

CO 2

GC Analysi

s

H2

Raman Spectroscopy

Eleni Venardou; Appl. Spectrosc., (2003) 57

Raman Spectra of CH3CN in ncH2O

1000 1500 2000 2500

2268938866

Time

0

30 min

CN

Raman shift / cm -1

no added acid 300 °C, 300 bar

CH3COOH in water

CH3CONH2 in water

500 1000 1500 2000 2500 3000Raman shift / cm -1

16801140

2268938866

Time

0

30 min

CN

Raman Spectra of CH3CN in ncH2O

autocatalysis

Hydrolysis of MeCN Effect of Concentration

Caprolactam

• Industrial synthetic route

• Problem

5 kg (NH4)2SO4 are made per kg CPL

O O

HN

(NH2OH)2SO4Oleum

AmmoximationBeckmann

rearrangement

NHO

Alternative Synthesis

• Cheaper feedstock, • No cyclohexane oxidation • No ammonium sulphate Yan Chong

O

HN

N

N NH2N

H2O

H. Vogel et al. Chem. Eng. Technol. (1999) 22, 494

70% conv. ACN but only 45% yield CPL 400 oC, 4 min. residence time

Strategy• Study effects of T and p

• Concentration of feedstock

O

HN

NH2N

H2O

ACN CPL

Caprolactam Summary

• Single-step green process

NH2N

O

NH2

H2N O

HN

Hydrolysis, SCW Cyclization, SCW

6-Aminocapronitrile, ACN 6-Aminocaproic acid amide, ACACPL

>60% yield of CPL within <2 min No organic solvent No additional catalysts

C. Yan et al. WO2006078403

Supercritical Catalysis

• Catalysis in scCO2

• Supercritical Water • Multiphasic Biocatalysis

Helen Hobbs, Neil Thomas

Enzymes in Fluorous Biphase

Hexane+

substrate

PFMC + Enzyme

25 ºC

SubstrateHexane

+Product

PFMC +

Enzyme

0 ºC

Product

Enzyme +

substrate

40 ºC

EnzymeRecycle

PFMCPerfluoro-

MethylCyclohexane

How can one dissolve an enzyme in a fluorous solvent

(or even scCO2)?

Hydrophobic Ion Pairing

+

+

+

+

+

+ +

+

Protein- -

--

--- -

Fluorinated Anionic Surfactant

CF CF2 O

CF3

CF

CF3

F CO2 NH4

n

Krytox NH4+ n ~ 14/2500

KDP NH4+ n ~ 7/1400

Soluble in Fluorous phase and scCO2

Cytochrome c inaqueous buffer

Fluorous Phase added

Fluorous + Krytox

HIP extraction

into theFluorous

Phase

Butis the enzyme

really dissolved?

+

+

+ +

+

+

+

+

Expected Diameter: 6.8 nm

Dynamic Light ScatteringCandida rugosa lipase

KDP surfactantmw~1400

Expected length: 1.4 nm

+

+

+ +

+

+

+

+

CRL

- -

-

-

-

-

-

-

Expected diameter: 9.6 nm (CRL-KDP)

Native CRL: 10.1 nm

CRL-KDP: 6.5 nm CRL-Krytox: 10.1 nm

Diameter (nm)

Volu

me (

%)

0

5

10

15

20

0.1 1 10 100 1000 10000

CRL Size Distribution By Volume

Biocatalysis in Fluorous Biphase

Ph

HNAc

O

O

OH

Ph

HNAc

O

O

OH

APEE

n-propanol

APPE

ethanol

CMT-KDP (FBS)

0

1

2

3

4

5

6

7

8

9

1 2 3 4

Cycle

AP

PE

Yie

ld %

CMT-KDP native CMT

CMT-KDP Recycling (FBS)

Dissolving BiomoleculesPrecipitation from aqueous buffer

Dissolve in scCO2

Biological Molecules in scCO2

it works!!!!

Cytochrome C

Supercritical Catalysis

• Continuous Reactions: Key aspect of supercritical fluids

• New Developments: “Green” technologies are not in competition

• Partnership between Chemists & Chemical Engineers

DICE: Driving Innovation in Chemistry & Chemical Engineering

EPSRC initiative led by Nottingham to stimulate research at the interface of Chemistry/Chem.Eng

6 new faculty posts in Chem. & Chem. Eng. including 3 joint posts

Big opportunities for collaboration particularly with POC at Cardiff

P. ClarkE VenardouEG Verdugo

J Fraga DubreuilChong YanHR Hobbs

P. Fields, R. Wilson, M. GuylerINVISTA, Thomas Swan & Co, GSK, ICIEPRSC, Royal Society, EU Marie Curie

All our Students,Postdocs and Collaborators

P Licence NR Thomas PA Hamley

Impact Factor

3.26 www.rsc.org/Greenchem

[email protected]

GSC-33rd International Conference on Green & Sustainable Chemistry

1-5 July 2007, Delft, The Netherlands

GSC-33rd International Conference on Green & Sustainable Chemistry

1-5 July 2007, Delft, The Netherlands

Professor Graham Hutchings

RSC

Green Chemistry Lecturer