Katalyse – Eine Schlüsseltechnologie für die Nachhaltige ... · PDF file21 March 2007 Katalyse – Eine Schlüsseltechnologie für die Nachhaltige Chemie Matthias Beller

21 March 2007

Katalyse – Eine Schlüsseltechnologie für die Nachhaltige Chemie

Matthias Beller

Leibniz-Institut für Katalyse e.V. an der Universität Rostock

Matthias Beller, 21 March 2007

2

1. Catalysis: Introduction & Challenges

Catalysis is a key technology for providing a sustainable development in chemistry.

2. Development of More Environmentally BenignReagents

3. Towards Biomimetic Catalysts

4. Save Reaction Steps

Outline



3

ChemistryChemistry as Industry and as Science plays a key roleas Industry and as Science plays a key rolein meeting the demand for sustainable developmentin meeting the demand for sustainable development

Sustainable Development Sustainable Development -- ChemistryChemistry

Focus on precaution rather than aftertreatmentFocus on precaution rather than aftertreatment

Develop new technologies toDevelop new technologies to•• reduce consumption of raw materials and energy reduce consumption of raw materials and energy (selectivity)(selectivity)•• maximize the use of renewable resourcesmaximize the use of renewable resources•• minimize or eliminate the use of harmful chemicalsminimize or eliminate the use of harmful chemicals

Catalysis is the key technology to achieve these goalsCatalysis is the key technology to achieve these goals



4

CatalysisCatalysis

HomogeneousHomogeneouscatalysiscatalysis

BioBio--catalysiscatalysis

HeterogeneousHeterogeneouscatalysiscatalysis

ElectroElectro--catalysiscatalysis

PhotoPhoto--catalysiscatalysis

Fine Fine chemicalschemicals

HealthHealth

MolecularMolecularbiologybiology

FoodFood EnergyEnergy

EnvironmentalEnvironmentaltechnologiestechnologies

NewNewmaterialsmaterials

Basic Basic chemicalschemicals

Catalysis: A Key Technology

Oil Oil refineryrefinery

PolymerPolymersynthesissynthesis



5Catalysis - Challenges for the 21st Century

Allow for CO2-neutral raw materials for the chemical industry(use of renewable resources, carbon dioxide, …)

Allow for CO2-neutral raw materials for the chemical industry(use of renewable resources, carbon dioxide, …)

Contribute to the use of alternative energy supply(Hydrogen-technology, fuel cells, biomass to liquid, …)

Contribute to the use of alternative energy supply(Hydrogen-technology, fuel cells, biomass to liquid, …)

More sustainable processes for bulk and fine chemicals(aniline, phenol, caprolactam, propylene oxide, polyurethane, …)

More sustainable processes for bulk and fine chemicals(aniline, phenol, caprolactam, propylene oxide, polyurethane, …)

Enable new pharmaceuticals (Alzheimer, cancer, HIV, …), materials (polymers), and consumer electronics

Enable new pharmaceuticals (Alzheimer, cancer, HIV, …), materials (polymers), and consumer electronics



6Photokatalytische ‚Dream Reaction‘

Wasser + Energie Wasserstoff + Sauerstoff

2 H2O H2 + O2Thermolyse, Elektrolyse, chemische Reaktion

HomogenkatalyseMetalle:

Eisen, RutheniumTitan, Zirkonium …

LnM(OH2)H2

O2

H2O

LnM LnM(O)



7Towards A Sustainable Organic Synthesis

Most organic syntheses are fare away from being efficient.

New catalytic methods need to be developed and known methods must be improved!

EnvironmentEnvironment

EconomicsEconomics

EfficiencyEfficiency

SelectivitySelectivity

Produce a minimum of waste; use available feedstocks, no solvents or “green” solvents (e.g. water)

Perform reactions in standard equipment; minimize catalyst costs (“real catalytic processes); look for high space/time yields; use high concentrations

Obtain high selectivity (chemo-, regio-, stereoselective processes

Apply energy-efficient processes with 100% atom economy; safe steps and use domino processes and mcr´s



8


2. Development of More Environmentally Benign Reagents

>80% of all marketed drugs contain aromatic and/orheteroaromatic groups. To my knowledge there is no syntheticmethodology which has made in the last 10 years so manytransfers from mg- to >1000 kg-scale!



Outline



9Aryl-X Activation

X

R

R

Angew. Chem. 2000, 112, 4315-4317; Chem. Commun.

2000, 2475-2476; Chem. Comm. 2004, 38-39.

CN

R

Tetrahedron Lett. 2001,6707-6710; Angew. Chem.

Int. Ed. 2003, 42, 1559-1661.

NR2

R

J. Mol. CatJ. Mol. Cat. 2002, . 2002, 182182--183183, 515;, 515;Chem. Chem. EurEur. J. J. 2004, . 2004, 1010,, 2983-2990..

R

R

Chem. E. J. 2001,7, 2908-2915; Synlett

2000, 1589-1592.

CO2R

R

Angew. Chem. 2001,113, 2940-2943; Chem.

Eur. J. 2004, 10, 746-757.

R

R

O

Adv. Synth. Catal. 2002,344, 209.

CH2R

R

Angew. Chem. Int. Ed. 2003, 41, 4056-4057.

Other groups active in catalyst developments: L. Ackermann, H. Alper, C. Amatore, R. Bedford, I. P. Beletskaya, S. L. Buchwald, H. Doucet, G. Fu, F. Glorius, A. Hallberg, J. F. Hartwig, W. A. Herrmann, A. Jutand, K. Köhler, G. Li, D. Milstein, S. P. Nolan, H. Plenio, M. Taillefer, J. G. de Vries, ....

CHO

RAngew. Chem. Int Ed. 2006, 45, 154-156.

Let´s have a closer look on thisreaction. Why is it so difficult?Let´s have a closer look on thisreaction. Why is it so difficult?



10

Price [€/1mol CN]

Prices based on Aldrich catalogue 2006 (lowest quality, biggest quantity).

Cyanide Sources for Coupling Reactions

• NaCN 1,5

• Acetoncyanhydrin 2,0

• K3Fe(CN)6 2,0

• K4Fe(CN)6x3H2O 2,4

• Zn(CN)2 4,9

• KCN 6,6

• CuCN 11,2

• TMSCN 384

LDLo (oral, rat): 1600mg/kg

LD50 (oral, rat): 3600mg/kg

LDLo (oral, human): 2.86mg/kg

LD50 (oral, rat): 18.6mg/kg

Toxicologicalvalues1

1 toxicological values from: Merck KGaA, Darmstadt (http://de.chemdat.info)

LDLo = Lethal Dose Low, lowest concentration for which lethality occurs;for comparison: NaCl LD50 (oral, rat): 3000mg/kg



11

0.01mol% Pd, 120°CYield = 87%TON = 8700

0.25 mol% Pd, 160°CYield = 75%TON = 300

0.1 mol% Pd, 120°CYield = 94%TON = 940

0.1mol% Pd, 120°CYield = 51%TON = 510

0.1 mol% Pd, 120°CYield = 99%TON = 990

0.1 mol% Pd, 140°CYield = 86%TON = 860

0.1 mol% Pd, 120°CYield = 95%TON = 950

0.1 mol% Pd, 140°CYield = 87%TON = 870

0.1 mol% Pd, 140°CYield = 78%TON = 780

T. Schareina, A. Zapf, M. Beller, Chem. Commun. 2004, 1388-1389.

Br

O

BrBr

O

Br

F3C

O

BrS Br

Br

FF

NBr

N

Cl

Pd-catalyzed Cyanations using K4[Fe(CN)6]

Pd(OAc)2, dppf,

K4[Fe(CN)6],NMP, Na2CO3

X

R

CN

R

1. Generation Catalysts1. Generation Catalysts In cooperation with Saltigo (Lanxess).



12A Novel Copper-catalyzed Cyanation

F3C CF3

Br

F3C CF3

CN

N

NR

Cu(I),

toluene, 160°C

98991-Butylimidazol

200%--CuI 10%1606

65661-MI 200%--CuI 10%1605

7571---CuI 10%1404

6177--Na2CO3 20%CuI 10%1403

1598DMEDA 100%KI 20%Na2CO3 20%CuI 10%1402

2192DMEDA 100%KI 20%Na2CO3 20%Cu(BF4)2 6H2O

10%1401

yield[%]

conv. [%]

ligand [mol%]

Additive [mol%]

base[mol%]

catalyst[mol%]

T [°C]No.

With SaltigoWith Saltigo

Biomimetic: Inspired by naturefor example: plant catechol oxidase

Klabunde, T.; Eicken, C.; Sacchettini, J. C.; Krebs, B.; Nat. Struct. Biol., 1998, 5, 1084 - 1090.

N

HN

(S) COOH

NH2histidine

nature uses histidineabundantly as ligand

for metals



13A Solution for Difficult Substrates

O Br

49% (1-Butylimidazole)

Br

O2N

80% [0%; 8%] (1-Butylimidazole)

N

Br

H2N

55% (1-Methylimidazole)

NH

Br


Br

66% (180°C)(1-Methylimidazole)

Br

CF3F3C

98% [-; 90] (1-Butylimidazole)

Br

CF3


NH2N

Br F


N N

Br

95% [0%; 0%] (1-Butylimidazole)

S

N

Br

99% [0%; 0%] (1-Methylimidazole)

N Br

100% [0%; 30%](1-Methylimidazole)

CuI, N-alkylimidazole,

K4[Fe(CN)6], toluene

X

R

CN

R[Buchwald-Cu; Pd]

N

Br

NH253% (1-Butylimidazole)

BrNO2

92%(1-Butylimidazole)

N

NH2

F

Br


BrBr


Br

NHCOCH361%

(1-Butylimidazole)

N

O SiBr

95%; (1-Butylimidazole)

T. Schareina, A. Zapf, W. Mägerlein, N. Müller,M. Beller, Chem. Eur. J.

2007 in press.



14




Oxidations provide important challenges andinspiration for basic and applied research!


Outline



15Oxidation Catalysis

Catalytic oxidations are among the most applied reactions in industry in terms of scale. They make mainly use of structurallymore simple feedstocks.

The oxidant determines primarily the applicability of the process. Air/O2 or H2O2 are among the most environmentally friendlyoxidants and should be used.

Catalyst productivity and selectivity are often difficult to control.

Challenging goals: efficient catalysis with functionalizedsubstrates; selective C1-C4 functionalizations; selective areneoxidation; …..

General comments



16Environmental Impact of the Oxidant

Oxidant Active oxidant content [wt.%]

Waste Product

O2/Reductor 50 H2OH2O2 47 H2O

O3 33,3 O2

NaOCl 21,6 NaClCH3CO3H 21,1 CH3COOHt -BuOOH 17,8 t -BuOH

N -Methylmorpholine-N -oxide 13,6 N -MethylmorpholineNaOBr 13,4 NaBrKHSO5 10,5 KHSO4

NaIO4 7,5 NaIO3 (NaI)PhIO 7,3 PhI

The oxidant determines primarily the applicability of the process.



17

R R

HO OH OsO

O

OO

OsOO

O

O

R

R

R

R

L

Os OO

OHO

OHO

Os OHOH

OHO

OHO

2 22 OH2 OH

2 H2O

organic

aqueos

+ L

+ L

VI VIII

VIII

VI

0.5 O2 H2O

Sharpless Dihydroxylation with O2

C. C. DDööblerbler, G. , G. MehltretterMehltretter, U. , U. SundermeierSundermeier, M. Beller, , M. Beller, J. Am. Chem.J. Am. Chem. SocSoc. 2000, . 2000,

122122, 10289., 10289.



18

How to Control Homogeneous Catalysts

Ligands tune the catalyst!!!Ligands tune the catalyst!!!

N-Ligands

P-Ligands Others?

Car-benes



19

The Importance of Ligands …

Ligand Conv. [%] Sel. [%] Ligand Conv. [%] Sel. [%]

none

NHOOC COOH

NHOOC COOH (without FeCl3)

pyridine/acetic acidNCH3 CH3

34 0

100 99

0 0

20 0 0 0

HOOC COOH

NO O

N COOH

29 0

26 0

5 0

PhPh

PhPhO

5 mol% RuCl3.6H2O, ligand

3 equiv. H2O2, t-AmylOH, R.T., 1h Addition



20Why Fe Catalysts ?Advantages

Feless toxic

abundant

biomimetic

cheap

hemoglobin

beside Al most frequent metal on earth

catalyses manyoxidation reactions in nature



21

N

N

OO

N

R RRu

NO

O

O

O

N

N

OO

N

R R

NO

OH

O

OH

Fe??

Pybox

Pydic

Cartoon Chemistry: From Ru to Fe ?Goal: Fe catalysts for epoxidation with hydrogen peroxide

??

Is it possible to mimic nature with easily available catalyst systems?

Problems: Fenton reactions and hydrogen peroxide decomposition



22

Fe-catalyzed Epoxidations - Initial Scope

OH OH

Cl

(73%, 53%)

MeO

OMe

(83%, 62%)*(91%, 68%) (100%, 84%)

(87%, 85%)(48%, 36%)

(100%, 69%) (40%, 21%)

(78%, 60%) (85%, 66%) (94%, 26%)(100%, 75%)[100%, 67%]

R1R2

5 mol% FeCl3.6H2O, pydic acid, Pyrrolidine

2equiv. H2O2, t-AmylOH, R.T., 1h addition*R1

R2O

* Results from a 5 min addition are given in sq. parenthesis

(94%, 93%) *[88%, 69%]

Cl(100%, 77%)[100%, 79%]

(100%, 97%)[88%, 87%]



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The most efficient way to economical and environmentally improved processes is to reducethe necessary reaction steps.

Outline



24

Multicomponent Reactions (MCR)

MCR: ... at least three chemicalfunctionalities join throughcovalent bonds.

Classical synthesis:

123456789

101112131415161718192021222324252627282930



25

A Different View on MCR´s

steamcrackerlow severity

A. Seayad, M. Ahmed, H. Klein, R. Jackstell, T. Gross, M. Beller, Science, 2002, 297, 1676-1678.

2

Alkynes2

Alkynes2

4

3220

7

7

R2NH2C

Rh(I)/Iphos

NH3, CO/H2

26



26

NHHNR2 =

Catalyst:0.1 mol% [Rh(cod)2]BF4,

0.4 mol% L, p(CO+H2) = 5+33 bar, MeOH:Toluene = 1:1,

T: 125°C, t: 16 h

O

tBu tBu

P P

OO

NR2

CO/H2HNR2

Cat.

3-4 %

47-48 %

29 %

16 %

HNHNR2 =

Conv. 90 %Selec. 90 %Yield 81 %l:b 85:15

Conv. 90 %Selec. 94 %Yield 85 %l:b 88:12

M. Ahmed, R. Jackstell, H. Klein, M. Beller, R. Bronger, P. van Leeuwen, 2006, in press.

SelectiveSelective HydroaminomethylationHydroaminomethylation of of MixturesMixtures

7 isomers



27Acknowledgements

Previous funding: Mecklenburg-Vorpommern, BMBF, DFG, AIF, EU, Degussa, Lanxess, Esteve, BASF, Merck, Grünenthal, DSM, Clariant, Umicore, Solvias, Altana, …

Academic cooperations:

Profs. K. Köhler,N. Stoll, K. Thurow,K. Cavell, S. Nolan,

U. Kragl, U. Bornscheuer, P. van

Leeuwen, W. Thiel, G. Frenking.

Industrial partners:

Drs. T. Riermeier, W. Mägerlein, K. Wiese, C.

Weckbecker, D. Decker, J. Holenz, H.-U. Blaser, O. Briel, R.

Parton, W. Melder



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Katalyse – Eine Schlüsseltechnologie für die Nachhaltige ... · PDF file21 March 2007 Katalyse – Eine Schlüsseltechnologie für die Nachhaltige Chemie Matthias Beller