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Transient methods in threeTransient methods in three--phase catalysisphase catalysis

E. Toukoniitty, J. Wärnå, D. Yu. Murzin and T. Salmi

ThreeThree--phase systems phase systems

Common in fine chemicals production: Common in fine chemicals production: •• ThreeThree--phase applications, phase applications,

HH2, 2, OO22(g) (g) -- reactant, solvent (l) reactant, solvent (l) -- catalyst (s)catalyst (s)

•• BatchBatch-- / Semi/ Semi--batch reactors utilized typicallybatch reactors utilized typically•• Complex reactions where Complex reactions where regioregio--, , diastereodiastereo-- and and

enantioselectivity can be involvedenantioselectivity can be involved•• High selectivity crucialHigh selectivity crucial

2

TypicalTypical rreaction eaction sschemecheme

O

O

O

OH

O

OH

O

HO

O

HO

OH

HO

(B)

(C)

(D)(E)

OH

HO

HO

OH

(I) (F)

(G)(H)

(A)

OH

HO

•Complex reaction scheme (parallel and consecutive)•Pt/Al2O3 catalyst•Toluene solvent•200C, 10 bar H2•Main product used for the synthesis of several pharmaceuticals e.g. ephedrine...

Hydrogenation of 1-phenylpropane-1,2-dione over a Pt/Al2O3 catalyst

Examples of threeExamples of three--phase reactions for phase reactions for fine chemicals productionfine chemicals production

Substrate Catalyst Reference

Citral Ni/SiO2(fibrous)

T. Salmi et al. Appl.Catal. A. Gen. 196

(2000) 193.Glucose Ru/C (pellets) P. Gallezot et al. J.

Catal. 180 (1998) 51Ethyl pyruvate Pt/Al2O3

(powder) + CDN. Kunzle et al. J.

Catal. 186 (1999) 239Ketopantolactone “ “

1-Phenyl-1,2-propanedione

Pt/ SiO2(fibrous)

E. Toukoniitty et al.216 (2000) 73

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Transient methodsTransient methods

• Well established tools in mechanistic studies of two-phase reactions (gas-solid)

• e.g. Temporal Analysis of Products (TAP), Steady State IsotopicTransient Kinetic Analysis (SSITKA)

TAP reactor set up(1%D2)/Ar→(1%H2)/Ar

Rahkamaa-Tolonen, J. Catal. 210 (2002) 17

Transient methodsTransient methods

• Transient methods are seldom used in three-phase reactions

⇒Experimentation and analysis is demanding

• Transients are introduced into a system by varying e.g. pressure, temperature, concentration etc.

• Typically step and pulse change

experiments

0

20

40

60

80

100

0 5 10 15 20 25 30Time-on-stream (min)

ee (%

)

4

Setup in transient experiments Setup in transient experiments --batch reactorbatch reactor

Required for transient Required for transient experimentsexperiments

H2, Ar or O2saturation

MS(gas phase)

GC(Liquid phase)

HPLC pump

Catalyst bed

6-way injection valve

H2 , Ar, O2or liquid

H2

di= 9 mm

Setup in transient experiments Setup in transient experiments ––fixed bed reactorfixed bed reactor

Pulse or Pulse or Step change Step change

H2

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Setup in transient experiments Setup in transient experiments --product analysisproduct analysis

• On-line methods (MS, IR, UV-VIS, etc.)

• In the presence of liquid-phase and complex product mixtures containing e.g. mixtures of enantiomers conventional on-line methods cannot be utilized

• Small liquid-phase samples are collected and analyzed off-line with e.g. GC, HPLC, etc.

• Analysis can be a bottle neck and a rate limiting factor in three-phase transient experiments

Practical solution

Transient experiments in a batch reactorTransient experiments in a batch reactor

•• Step change in modifier concentration/composition during reactiStep change in modifier concentration/composition during reactionon

•• Successfully applied in investigations of nonlinear behavior of Successfully applied in investigations of nonlinear behavior of binarybinarymodifier mixturesmodifier mixtures

•• Practical limitations due to slow transient responses and short Practical limitations due to slow transient responses and short reaction timesreaction times

•• VVLL changes, however, often changes, however, often ΔΔVVLLisis small and has insignificant small and has insignificant influence on the resultsinfluence on the results

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Transient experiments in a fixed bed reactorTransient experiments in a fixed bed reactor

•• Step change and pulse experimentsStep change and pulse experiments

•• More versatile compared to batch reactor: More versatile compared to batch reactor: –– Reaction time does not limit the experiments in case of slow resReaction time does not limit the experiments in case of slow responsesponses–– Change of solvent, reactant, concentration, etc. possibleChange of solvent, reactant, concentration, etc. possible

•• More demanding experimentation More demanding experimentation compared to batch reactor (kinetic compared to batch reactor (kinetic regime, flow conditions)regime, flow conditions)

(R)-enantiomer (S)-enantiomer

O

OHH

O

OHH

Mirror plane

•Non-superimposible mirror image structures

e.g. left and right hands

EnantiomersEnantiomers

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•Enantiopure chemicals play a central role in the areas of

•Pharmaceuticals

•Agrochemicals

•Fragrances

(R)- and (S)- enantiomers behave differently in the human body (chiral environment)

Living organisms

EnantiomersEnantiomers

• Chirally modified metals (Ni, Pt, Pd…)•• easy catalyst separation and handlingeasy catalyst separation and handling•• continuous operationcontinuous operation•• inexpensiveinexpensive

• Research aims to increased mechanistic understanding

Asymmetric heterogeneous catalysisAsymmetric heterogeneous catalysis

The demand for enantiopure chemicals is increasing and technically simple and inexpensive production

methods are needed.

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• Cinchona alkaloid modified Pt catalyst were discovered by Orito et al. 1979 for hydrogenation of α-keto esters

• Trace amounts of modifier (monolayer) can induce high enantioselectivity (ee=98%) and up to 100-fold rate acceleration

• Extensively studied in batch reactors

Asymmetric heterogeneous catalysis over Asymmetric heterogeneous catalysis over cinchona alkaloid modified Pt catalystscinchona alkaloid modified Pt catalysts

N

N

OHH

Cinchonidine (CD)

Catalyst modifierCatalyst modifier

N

N

OHH

• anchoring part

• quinuclidine N atom

• chirality

Cinchonidine (CD)

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Principle of a Principle of a chirallychirally modified catalystmodified catalyst

Unmodified catalyst:

50% (R) and 50% (S)

ReactantReactantpropro--SS

Pt particlePt particle

(R)-enantiomerproduct

(S)-enantiomerproduct

ReactantReactantpropro--RR

[ ] [ ][ ] [ ] %0%100 =×

+−

=SRSRee

+ H2 + H2

Principle of a Principle of a chirallychirally modified catalystmodified catalyst

Modified catalyst:

90% (R) and 10% (S)(R)-enantiomer product

(S)-enantiomer product

Pt particlePt particle ReactantReactantReactantReactant

ModifierModifierModifierModifier

11--toto--1 reactant1 reactant--modifier interactionmodifier interaction

[ ] [ ][ ] [ ] %80%100 =×

+−

=SRSRee

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CatalystsCatalysts

4 nm

TEM image of the 5 wt.% Pt/Al2O3(Strem Chemicals) catalyst

SEM image of the 5 wt.% Pt/SiO2fiber catalyst

1 mm

125-90 μm particles

D = 27% dPt= 4 nm

D = 40% dPt= 2.5 nm

• Structure sensitive reactions• Relatively large metal particles are needed for optimum selectivity and reaction rate (~ 4 nm)

Mechanistic questions Mechanistic questions

•• Is there any deactivation?Is there any deactivation?•• Catalyst regeneration and prevention of deactivation?Catalyst regeneration and prevention of deactivation?•• Mechanism of nonlinear behavior of binary modifier mixtures?Mechanism of nonlinear behavior of binary modifier mixtures?•• Mechanism of ligand acceleration?Mechanism of ligand acceleration?•• Can one increase selectivity under transient conditions?Can one increase selectivity under transient conditions?

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Catalyst deactivationCatalyst deactivation

Typical batch reactor kinetics.

Conditions: c0(EP) 0.025 mol L-1, c0(CD)= 0 mol L-1, 50 mg 5 wt.% Pt/Al2O catalyst, toluene, 15oC, 10 bar H2

Possible catalyst deactivation difficult to distinguish

O

O

O

Ethyl pyruvate

OH

O

O

+ H2

(R)-Ethyl lactate

0.000

0.005

0.010

0.015

0.020

0.025

0.030

0 10 20 30 40 50 60

Time (min)

c (m

ol/L

)

0

20

40

60

80

100

ee(%

)EP

(R )-EL

(S )-EL

ee

0.025 M (racemic)

Catalyst deactivationCatalyst deactivation

Identical conditions as in batch reactor =>Relatively rapid catalyst deactivation noticeable

0

20

40

60

80

100

0 10 20 30 40Time-on-stream (min)

ee o

r con

vers

ion

(%) Conversion

Enantiomeric excess (ee)

Conditions: c0(EP) 0.025 mol L-1, c0(CD)= 0 mol L-1, 25 mg 5 wt.% Pt/Al2O3 catalyst, toluene, 15oC, 10 bar H2 , VL 3.0 ml min-1, VH2 50 3.0 ml min-1

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Step change: Step change: c(modifierc(modifier))

• No rate acceleration

• Slow decrease of ee

5%Pt/SiO2 fiber, T=25oC, Toluene, cDIONE=0.025M

0

0.2

0.4

0.6

0.8

1

0 20 40 60 80 100 120 140 160 180Time-on-stream (min)

ee

0.0E+00

5.0E-03

1.0E-02

1.5E-02

2.0E-02

2.5E-02

Hyd

roge

n up

take

(mol

dm

-3)

CD stopCD on

Appl. Catal. 235 (2002) 125

Pulse of OPulse of O22

Pulse of O2 at 40 and 80 min

Increase of ee and rate

CO(Ads)+½O2 -> CO2

Catal. Lett. 93 (2004) 171

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0

20

40

60

80

100

0 20 40 60 80 100 120Time-on-stream (min)

Enan

tiom

eric

exc

ess

(%) Change of

solvent during reaction

Acetic acid

Toluene

Toluene

Acetic acid

Change of solventChange of solvent

∝ c(modifier inlet)

∝ liquid flow rate

Instantaneous drop of ee(R)-1

toluene -> acetic acid

acetic acid -> toluene

Increased selectivity under transient operationIncreased selectivity under transient operation

•• ee increased under ee increased under transient operation transient operation

•• conversion decreasedconversion decreased

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Origin ligand acceleration (LA)Origin ligand acceleration (LA)

– 50-500 fold higher TOF over modified site due to reactant-modifier interactions

=> ligand acceleration – Over 100 articles state that

LA is an intrinsic kinetic feature

– The LA concept is included in all previous kinetic models

Batch reactor, 10 bar HBatch reactor, 10 bar H22 1515°°CC

Journal of Catalysis 241 (2006) 96

0.00

0.05

0.10

0.15

0.20

0.25

0 0.5 1 1.5 2

c(EP) / mol L-1

rate

(mol

L-1

min

-1g-1

)

0

20

40

60

80

100

ee (%

)

LALA

O

O

O

Journal of Catalysis 241 (2006) 96

OriginOrigin of ligand of ligand accelerationacceleration

LA requires a 50LA requires a 50––500 500 times higher TOF times higher TOF which is induced by which is induced by reactantreactant--modifiermodifier--interactions interactions

Increased activity Reduced deactivation

Modifier prevents Modifier prevents deactivation and deactivation and maintains high initial maintains high initial activityactivity

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Journal of Catalysis 241 (2006) 96

OriginOrigin of ligand of ligand accelerationacceleration

LA requires a 50LA requires a 50––500 500 times higher TOF times higher TOF which is induced by which is induced by reactantreactant--modifiermodifier--interactions interactions

Increased activity Reduced deactivation

Modifier prevents Modifier prevents deactivation and deactivation and maintains initial maintains initial activityactivity

0.0

0.2

0.4

0.6

0.8

1.0

0 10 20 30 40Time-on-stream (min)

Con

vers

ion

of E

P

Racemic Enantioselective

0.01 M

0.05 M

0.025 M

SteadySteady--state and transient experiments state and transient experiments revealed that revealed that ””ligand accelerationligand acceleration””originates from reduced catalyst originates from reduced catalyst deactivation !!!deactivation !!! Journal of Catalysis 241 (2006) 96

Fixed bed reactor, 10 bar HFixed bed reactor, 10 bar H22 1515°°CC

O

O

OTransient experimentTransient experiment

•• The deactivation rate The deactivation rate proportional to reactant proportional to reactant inlet concentrationinlet concentration

•• Modifier restores Modifier restores initial activity and initial activity and prevents deactivationprevents deactivation

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Kinetic modelingKinetic modeling

• Non-steady state and steady state kinetic models were tested

• Parallel and tilted adsorption modes for modifier

• Different number of adsorption sites for reactant (two adsorption modes) and modifier (two adsorption modes).

Tilted Parallel

θT θP

Journal of Catalysis. 213 (2003) 7

MechanismMechanism

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steps 1 and 2 : adsorption of the reactant (A)

A1m and A2n : the adsorption modes of 1- and 2-carbonyls

n, m—the number of sites required for adsorptionof them

MechanismMechanism

CH3

O

O

steps 3 and 4: adsorption of the steps 3 and 4: adsorption of the modifiermodifier

•• Mp : the parallel adsorption mode of the Mp : the parallel adsorption mode of the cinchonidinecinchonidine, interacts with An or Am ., interacts with An or Am .

•• MqMq : the tilted adsorption mode; a : the tilted adsorption mode; a spectator.spectator.

MechanismMechanism

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•• RacemicRacemic hydrogenation on unmodified siteshydrogenation on unmodified sites

MechanismMechanism

Enantioselective hydrogenation to (R)

Some hydrogenation to (S) may take place on the modified sites

cA(mK1(1+ k7/k8)c0 (m-1)Θm + nK2(1+ k9/k8)c0

(n-1)Θn) +

cM(pK3c0 (p-1)Θp + qK4c0

(q-1)Θq) +

(m+p+f)K1K3K5(1+k11/k12)cAcMc0(m+p+f-1) +

(n+p+l)K2K3K6(1+ k13/k14)cAcMc0 (n+p+l-1) + Θ = 1

Impossible to obtain explicit rate expressions,

but fractional coverages are solved numerically by Newton’s method

Kinetic modelKinetic model

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RatesRates

Mass balancesMass balances

0.000

0.005

0.010

0.015

0.020

0.025

0 10 20 30 40 50 60time

mod_10.txt.001

Response simulation (Dump file)

c (m

ol d

m-3

)

Time (min)

D + EC

BA

Kinetic modelling :slurryKinetic modelling :slurry

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E.Toukoniitty, B. Sevcikova, P. Mäki-Arvela, J. Wärnå, T.Salmi, D.Yu. Murzin, Journal of Catalysis, 2003, 213, 7

Kinetic modelling: parameters

Kinetic modelling: parameters

•• Dynamic axial dispersion model for Dynamic axial dispersion model for continuous fixed bed reactorcontinuous fixed bed reactor

•• PecletPeclet number from impulse experiments number from impulse experiments with an inert tracerwith an inert tracer

Reactor modelingReactor modeling

H2O

response

Injection 200 μl (H

2O + NaCl)

H2

( ) ( )dz

dcdz

cdPer

dtdc Li

LLLi

LLLBiLi 1

2

21 −− −+= τετερ

21

•kinetic parameters from batch

•non-steady adsorption (dynamics)

0 10 20 30 40 50 60 70 80 0

0.00

0.0

0.01

time

B

C

Transient modelling :dioneTransient modelling :dione

0.000

0.002

0.004

0.006

0.008

0.010

0.012

0.014

0 10 20 30 40 50 60 70 80

time

B

C

Catalysis Today 79-80 (2003) 383Problems with by- porducts description

0 5 10 15 20 25 300

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5x 10

-3 20 C

time (min)

c (m

ol/l)

0 5 10 15 20 25 300

0.01

0.02

0.03

0.04

0.05

0.0620 C

time (min)

c (m

ol/l)

More recent modellingMore recent modelling

0 5 10 15 20 25 300

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5x 10

-3 20 C

time (min)

c (m

ol/l)

0 5 10 15 20 25 300

0.01

0.02

0.03

0.04

0.05

0.0630 C

time (min)

c (m

ol/l)

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ConclusionsConclusions

•Three-phase pulse and step change experiments are technically possible and give reproducible results

• Continuous operation and transient experiments give valuable mechanistic information about catalyst regeneration and deactivation mechanisms

• Suitable for investigation of solvent effects

• Ideal for studying competitive adsorption

• Transient operation can also increase selectivity

ConclusionsConclusions

• Transient three-phase experiments give valuable information about reaction mechanisms and catalyst deactivation, which cannot be obtained from steady state experiments