21 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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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)
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
8
1. Catalysis: Introduction & Challenges
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!
3. Towards Biomimetic Catalysts
4. Save Reaction Steps
Outline
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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?
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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).
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
55% (1-Methylimidazole)
Br
66% (180°C)(1-Methylimidazole)
Br
CF3F3C
98% [-; 90] (1-Butylimidazole)
Br
CF3
83% (1-Butylimidazole)
NH2N
Br F
93% (1-Methylimidazole)
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
93% (1-Methylimidazole)
BrBr
78% (1-Butylimidazole)
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.
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
14
1. Catalysis: Introduction & Challenges
2. Development of More Environmentally BenignReagents
3. Towards Biomimetic Catalysts
Oxidations provide important challenges andinspiration for basic and applied research!
4. Save Reaction Steps
Outline
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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.
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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.
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
18
How to Control Homogeneous Catalysts
Ligands tune the catalyst!!!Ligands tune the catalyst!!!
N-Ligands
P-Ligands Others?
Car-benes
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
20Why Fe Catalysts ?Advantages
Feless toxic
abundant
biomimetic
cheap
hemoglobin
beside Al most frequent metal on earth
catalyses manyoxidation reactions in nature
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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%]
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
23
1. Catalysis: Introduction & Challenges
2. Development of More Environmentally BenignReagents
3. Towards Biomimetic Catalysts
4. Save Reaction Steps
The most efficient way to economical and environmentally improved processes is to reducethe necessary reaction steps.
Outline
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
24
Multicomponent Reactions (MCR)
MCR: ... at least three chemicalfunctionalities join throughcovalent bonds.
Classical synthesis:
123456789
101112131415161718192021222324252627282930
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
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
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Matthias Beller, 21 March 2007
28