CATALYSIS

Theory and Applications

Paul C.J. Kamer, Gadi Rothenberg,

Ron Wever

University of Amsterdam
 Definition of Catalysis and Catalyst

A catalyst is a substance that increases the

rate of a reaction remaining itself unchanged

A B

CAT
 Importance of Catalysis
• increasingly important in synthesis
• selectivity in production of fine chemicals
• clean processes, high atom economy (bulk processes)
• production of high-tech products / materials
• mild conditions (low energy consumption)
• environmentally friendly

Example: methyl metacrylate (MMA)

Old process: 2.5 kg waste / kg product

O HO CN 1. H2SO4
+ HCN + NH4SO4
2. CH3OH COOCH3

New catalytic process: 50 g waste / kg product

CO, Methanol
catalyst COOCH3
 Catalyst Activation and Regeneration
A + catalyst B + catalyst
a catalytic reaction wherein the catalyst is unchanged

active
By-product D Substrate A
catalyst

inactive
Reagent C Product B
catalyst
catalyst precursor

a catalytic reaction wherein the catalyst is deactivated and needs

to be regenerated (re-activated) or requires an incubation time
 How Does a Catalyst Work?

•Lowering activation energy

•Stabilization of a reactive transition state

•Bringing reactants together

•proximity effect
•orientation effect

•Enabling otherwise inaccessible reaction paths

Energy profile of a reaction
 Example: Lewis Acid Catalyzed Diels-Alder
Reaction

−
δ
AlCl3 AlCl3
O O

+
δ
−
δ
Frontier orbitals overlap

HOMO of butadiene (Ψ2)

LUMO of ethylene (π*)

LUMO of butadiene (Ψ3*)

HOMO of ethylene (π)

Secondary overlap stabilizes endo transition state

O
fast O
O

O O
O HOMO

O
O O LUMO
O
slow O
O
O O
O
 Frontier orbital interactions for DA reactions
energy
LUMO

LUMO
LUMO LUMO LUMO
LUMO

HOMO
HOMO HOMO HOMO
HOMO
HOMO

Z X

dienophile with a dienophile with neither dienophile with a

low energy LUMO a low energy LUMO nor high energy LUMO
a high energy HOMO
Influence Lewis Acids on endo-selectivity

+ H + CO2Me
CO2Me
CO2Me H

without AlCl3 at 0° 88% 12%

with AlCl3 at 0° 96% 4%
with AlCl3 at -80° 99% 1%

O AlCl3 H
O O
+ AlCl3
H H H
Frontier orbital energies and coefficients acrolein
O .51
LUMO 2.5
-.48
-.39 H H
.59 O .37
-.70
-.09
H -7
LUMO
.60
-.58
O
-.30
HOMO -14.5 .48 H
H
.58 O -.54
-.10
acrolein .65 H
-23.5 HOMO
.53

protonated
acrolein
Increased regioselectivity acid catalyzed DA

X H
O X O

-.39 H -.09 H
.59 .60

HOMO LUMO HOMO LUMO

without catalysis with catalysis
Increased endo selectivity acid catalyzed DA

-.48
-.7
O
HO
without catalysis with catalysis
 Catalysts

• general acid and base catalysis (ester hydrolysis),

• Lewis acids as catalysts (Diels-Alder reactions),
• organic catalysts (thiazolium ions in Cannizzarro
reactions),
• porphyrin complexes (epoxidations, hydroxylations),
• enzymatic processes,
• co-ordination complexes (polyester condensations),
• catalytic antibodies

world market for catalysts: 9 billion USD

 Catalysts affect both rate and selectivity
Reaction A+B P
uncatalyzed d[P]/dt = k1[A][B]
catalyzed d[P]/dt = k2[Cat][A][B]

number of atoms ended up in product

Atom economy
number of atoms from the reagents
mass units of waste
E factor
mass units of product

Diels Alder +

atom economy 100%

cat R
Hydroformylation R H2/CO +R
CHO CHO
atom economy 100%
 Examples atom economy
"Rh" H 2 /CO
100%
CO

H2
100%

R R
R R
"Ru" 100%
+

"Pd"
26/28
br
-HBR (69 mass percent)
 E factor

Industry Production ton/year waste/product

ratio

Oil 106-108 0.1

Bulk 104-106 <1-5
Finechemicals 102-104 5-50
Pharmaceuticals 10-103 25- >100
 Homogeneous catalysis

Definition: Catalyst components and substrates of the

reaction are in the same phase, most often the liquid phase
(some catalytic reactions in the gas phase are also known).

Generally homogeneous catalysis refers to the use of

organometallic complexes as the catalysts.
 Advantages / disadvantages

Advantages:
- understandable kinetics
- reproducibility
- relatively mild reaction conditions
- high selectivity
- easy modification of catalyst properties
- efficiency; all molecules are accessible
- mechanistic studies are relatively easy to perform (complex
identification by IR, NMR, UV etc.)

Disadvantages:
- water and oxygen sensitivity
- separation of catalyst and products often difficult
Development of Transition Metal Catalysts
Choice of metal

Use of ligands with proper donor atoms

Ligand effects on activity and selectivity

Steric effects
Electronic effects
Bite Angle

Secondary interactions

Substrate-metal
Substrate-ligand
Medium effects
level of sophistication
 Rational catalyst design
alkene metathesis
R1 R2 R1 R2
R
+ + catalyst: LnM
4 3 R'
R R 4 3
R R
alkyne metathesis
R1 R2
R1 R2 catalyst: Mo(CO)6 + HO
+ + rate: 2 mol / mol / h
R4 R3 Mortreux (1974) Cl
4 3
R R

O t-Bu
rate: 300,000 mol / mol / h
"designed catalyst": t-Bu W O t-Bu
Schrock (1984)
O t-Bu
Selectivity in nickel catalyzed butadiene reactions

n
n n

''Ni''

Selectivity to desired product

steered by choice of ligands
 Chemoselectivity

OH
H2, kat
O O

OH

H2
Regioselectivity

CHO

CO / H2

CHO
 Enantioselectivity

COOR' H2 COOR'
+ * + *
R NHCOR" [HRh L 2] R NHCOR"
99 % ee
 Diastereoselectivity

R OH
*
R OH
* H2
R OH
*
 Heterogeneous catalysis

Advantages:
- easy separation of catalyst and products
- low sensitivity to water and oxygen
- high temperature stability
- shape selectivity (zeolites)

Disadvantages:
- kinetics can be complex
- often high pressures and temperatures required
- catalyst poisoning by sulfur compounds
- sintering
- heat transfer
- surface chemistry; using a few atoms only
Immobilization of transition metal complexes
Supported Homogeneous Catalysts - Organic Polymers
- Dendrimers
- Inorganic Metal Oxides

Supported Aqueous Phase Catalysis

Two-phase catalysis - organic solvents (SHOP)

- fluorous phase
- aqueous phase

Sol-Gel catalysis disadvantages:

Extraction (acid / base) - degradation of polymer

- leaching of metal
Ultrafiltration - oxidation of anchored ligands
 Product shape-selectivity

selective diffusion of para-xylene out of the pores of silicalite

 Product shape-selectivity

computer simulation of para-xylene in a silicalite pore

 Dendrimers as support

Dendrimer particle that serves as a catalyst support

 Catalyst immobilisation on dendrimers

Si
Si Ph2P Ph2P
Si Ph2P Ph2P
Si Me Si PPh2
Ph2P 2 Me2Si
SiMe2 Me2Si SiMe PPh2
Si Si Si Ph2P SiMe2 2PPh PPh2
Si Si Si 2
Si SiMe2 Me Si
Si Ph2P Si Si Si 2
SiMe2 PPh2
Si Me2
Si Si Si
Si Ph2P Me2 SiMe2 PPh2
Si Si
Si Si Si Ph2P Si Si Me 2SiMe
SiMe2 2 PPh
Si 2
SiMe2 Si
Si Si Ph2P Si
Si Me2Si SiMe2
Ph2P Si Si Si PPh
Si P Me2Si Si SiMe2 2
Si Fe Si Si PPh2
Si Me2Si
Si P Ph2P Me2 Me 2 Si
Si Si SiMe2 Si Si PPh2
Si Ph2P Me2Si Me2PPh2
Me2 Si Si
Si Si Si
Si Si Ph2P Me2Si Si Si
Si SiMe2 Si PPh2
Ph2P Ph2PMe2Si Me 2Si Me2 PPh2
Si Si Si PPh2 SiMe
Si SiMe2SiMeSiMe 2 PPh2
Si Si Ph2P 2 2
Si Si PPh2
Si PPh2 PPh2
Si PPh2
Si Si Si Si Si Si
Si

G.E. Oosterom et al. Chem. Commun.1999, 1119 D. de Groot et al. Chem. Commun.2000, 711
Dendritic transition metal catalysts: covalent approach
Core functionalization Periphery functionalization
CAT CAT CAT CAT
CAT CAT
CAT CAT
CAT CAT
CAT CAT
CAT
CAT
CAT
CAT
CAT CAT
CAT CAT
CAT CAT

CAT CAT CAT

CAT
CAT CAT
CAT
CAT
CAT CAT CAT

• site isolation • multiple active sites

• micro-environment • potential cooperativity
• easy accessibility
 Direct comparison core and periphery
functionalized dendrimers
Ph2P PPh2

Ph2P Me2N
OAc [Pd] Fe PPh2
Ph2P Me2N
Fe PPh2
N N N N Me2N SiMe2
Fe
SiMe2 SiMe2
Ph2P NMe2 PPh2

Fe
Ph2P Si Fe PPh2
SiMe2 SiMe2
Me2N
Ph2P NMe2
90 linear, trans linear, cis branched Fe
Me2
Si Si Si Si
PPh2
Si
Me2 Fe
80
Ph2P
Me2N PPh2

Me2Si NMe2
70
Ph2P Me2Si
Fe Si PPh2
Fe

60 Ph2P Me N
conversion / %

2
PPh2
Me2Si Me2Si

50 Fe
Me2Si
Fe
NMe2

Ph2P PPh2

40 Ph2P
NMe2 Fe
NMe2 PPh2

Ph2P PPh2

30 Me3Si
SiMe3 SiMe3
SiMe3

20 Me3Si
Me3Si
Me3Si SiMe3
Si Si
SiMe3

SiMe3 SiMe3
Me3Si
10 Me3Si
Si
Si
Si
Si
SiMe3

0
SiMe3
Me3Si
Si
Si P

0 2 4 6 8 10 Me3Si
Me3Si P
Fe SiMe3

Si SiMe3

reactor volumes Me3Si Si Si

Si
SiMe3
Si

Me3Si Si SiMe3
Si

Room temperature, solvent: CH2Cl2, P/Pd=2. Me3Si Si

SiMe3 SiMe3
SiMe3
Me3Si
Me3Si Me3Si SiMeSiMe
3
3 Me3SiMe3Si
Me3Si
Biocatalysis: the use of enzymes or cells

Enzyme optimization:
• protein “engineering”
• molecular evolution
• enzyme “engineering”
Enzymes can be applied in:
• Water
• Organic solvents
• Supercritical CO2
• Ionic liquids
Energy profile of an enzyme catalyzed reaction
 Enzymes give great rate enhancements

Michaelis-Menten parameters for selected enzymes

Enzyme specificity
Examples of classes of enzymes
 Coenzymes, vitamins and metals

Some important coenzymes and related vitamins

Active site of carboxypeptidase A
 Ideal catalyst characteristics

• High activity (mild reaction conditions)

• High selectivity (chemo, regio, enantio)
• Stable catalyst
• Easy separation and reuse of catalyst
 New “green” processes:

• Atom economic
• No or as little as possible waste
• decrease in solvent use
• Mild reaction conditions
• Catalytic use of reagents instead of stochiometrisch
• Non-toxic reagents,
• New sustainable starting materials