seton2007
TRANSCRIPT
Selective heterogeneous catalytic Selective heterogeneous catalytic hydrogenations for the fine hydrogenations for the fine
chemical industrychemical industryTechnical University of BudapestTechnical University of Budapest
Department of Organic Chemical TechnologyDepartment of Organic Chemical Technology
Antal TunglerAntal Tungler
Most important properties of Most important properties of catalysts:catalysts:
activityactivity
stabilitystability
selectivityselectivity
Types of selectivity:Types of selectivity:
RegioselectivityRegioselectivity ChemoselectivityChemoselectivity
NO2
Cl
NH2
ClNH
2
3H2Ni
Pd4H2
OH
OH
OH2H2
Pd, OH-
Pd, H+
Regioselectivity in the hydrogenation of Regioselectivity in the hydrogenation of polychlorinated benzenespolychlorinated benzenes
180oCCatalyst Pd/C Temp.
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl Cl
ClCl
Cl
ClCl
Cl
Cl
Cl
Cl
StereoselectivityStereoselectivity
H2
menthol
neomenthol
isomenthone
menthoneOH-
Pd
+HPd
2H2
Pd
OH
OH
O
O
OH
EnantioselectivityEnantioselectivity
In the presence of chiral auxiliaries or modifiers
O
O OCH3
O
OHO
CH3*
H2/Ni
NaBr+tartaric acid
methanol
/ PdH2
*
OO
* OEt
H
O
HOO
Et
O
OPt catalysts H2
solventcinchona alkaloids
How can be influenced How can be influenced chemoselectivity?chemoselectivity?
–Changing the solventChanging the solvent
methanol
selectivity >90%ethyl acetate
+ HCl
4H2
Pd
3H2 NH2
NH2
Cl
NO2
Cl
How can be influenced How can be influenced chemoselectivity?chemoselectivity?
Changing the catalystChanging the catalyst
COOH
NO2
Cl
COOH
NH2
Cl
COOH
NH2
Ni v. Pt3H2
Pd 4H2
+ HCl
Modifying of the catalystModifying of the catalyst
Alloying of the active metalAlloying of the active metal
Ar CO
Cl
Pd
H2
Pd-Cu
Ar CH3
Ar CO
H
The alloying can be carried out together withthe preparation of the palladium catalyst onactive carbon or with controlled metaladsorption on the Pd catalyst.
Poisoning of the catalysts with strong Poisoning of the catalysts with strong basesbases
CH CH CHO Pd/C, H2
EtOAc, pyridineCH2 CH2 CHO
selectivity ~ 65%
CH3
O2N NH2
strong base
Pd/C, H2
CH3
NO2O2N
Poisoning of the catalystPoisoning of the catalyst
NH3C CH
3
NO
NH3C CH
3
NH2
2 H2
Pd-Fe2+
water /NH3
N CH3
N CH3
H H
H2
Pd/C Cl-
water / H2SO4
Pd/C methanol
N CH3
H
Anions and cations both can increaseselectivity (and deteriorate activity).
Hydrogenation of heteroaromatic compoundsHydrogenation of heteroaromatic compounds(potencial catalyst poisons)(potencial catalyst poisons)
N OH
CH3
N OH
CH3
H2 Pd/C
HN
O
NH
Pd/C H2H
N
O
N
X-N OH
CH3
Pd/C H2+N OH
CH3
non miscible solvents
water
water and methanol
Optimizing reaction conditionsOptimizing reaction conditions
hydrogenolysis
water
Pd / C
6 H2
O
OO
O
O
OO
O
O
OO
O
Determining the optimal temperature, pressure,catalyst and substrate concentration selectivitycould be improved from 40 to 65%.
How can be influenced regioselectivity?How can be influenced regioselectivity?
Optimization of catalyst preparationOptimization of catalyst preparation
(PdCl4)
2
+CH2
CH3
CH3
CH3
NH2(PdCl4)
With tetraalkyl ammonium palladate precursorthe dispersion of the reduced metal is above 0.5
and the catalyst contains tertiary amine.The high dispersion and amine containing Pd/C
SELCAT Q-type catalyst has both higherselectivity and activity in the hydrogenation of
naphtol to aromatic tetralol.
Improvement of regioselectivity with the Improvement of regioselectivity with the use of the proper catalystuse of the proper catalyst
Pd/C, H+
Pd, OH-
2H2
OH
OH
OH Ni,
aromatic tetralol
with SELCAT Q selectivity is above 80% with respect
aliphatic tetralol
SQ
to the aromatic tetralol
The role of pH in the stereochemistry of The role of pH in the stereochemistry of hydrogenationshydrogenations
(known examples in the reduction of ketones)(known examples in the reduction of ketones)
OH
NHCOCH3
NHCOCH3
HO3 H2
SELCAT Pd
OH- water
trans-acetamino cyclohexanol
80 % stereoselectivity
The intermediate of the hydrogenation is thecyclohexanone derivative: among basicconditions equatorial alcohol is formed in
excess.
How can be influenced How can be influenced diastereoselectivity?diastereoselectivity?
Most important factors:Most important factors: -the properties of the molecule to be -the properties of the molecule to be
hydrogenated-the substituents of the hydrogenated-the substituents of the unsaturated atomsunsaturated atoms
-catalitically active metal, support, dispersion -catalitically active metal, support, dispersion of the metalof the metal
-solvent (protic-aprotic, polar-apolar)-solvent (protic-aprotic, polar-apolar) -preliminary reduction of the catalyst surface -preliminary reduction of the catalyst surface
and its saturation with hydrogenand its saturation with hydrogen pH of the reaction mixturepH of the reaction mixture
(S)-proline as chiral auxiliary(S)-proline as chiral auxiliary
H2
*
OO
enantiomeric excess 80%
CH3
O
CH
OH
CH3*
H2
enantiomeric excess 25%
Pd, stoichiometric (S)-proline, methanol assolvent
Pd, stoichiometric (S)-proline, methanol assolvent
(S)-proline is a chiral auxiliary which reacts withthe substrate giving an adduct and this adduct
is hydrogenated diastereoselectively.
Pd/C catalyst
2
*O+H2
*
+O
N COOH
*
*
*N COOH
H2
H2
chemo- and diastereoselective
diastereoselective
-H2O
oxazolidinones
2R,4S és 2S,4S
iminium salts
EZenamine
++N C
O
CO
NCOO
-
NCOO
-
N COOH
C
carbinol amine
N COOH
CHO
O
+N COOH
Enantioselective hydrogenationsEnantioselective hydrogenations
Pd black catalystmethanol as solvent
O O
*
H2
NN
H
EtOOC
(-)-dihydro vinpocetine as chiral modifier
methanol as solvent
H2Pt catalystsO
Et
O
O
OEt
H
O
HO*
ee 45%
ee 30%
Scheme of processes ofenantiodifferentiation
Similar processes can take place in Pt-cinchonaand Ni-tartaric acid mediated reactions.
Enantiomeric excess depends on equilibriumconstants and rates.
The formation of modifier-substrate adduct was verifiedby circular-dichroism spect-roscopy
*optically active
racemicO
H2/Pd
H2/Pd
+
In adsorbed state
In solution
catalyst surface
O
O
O
O
catalyst surfacecatalyst surface
NN
H
EtOOC
NN
H
EtOOC
NN
H
EtOOC
NN
H
EtOOC
Possibilities of producing enantiomerically pure Possibilities of producing enantiomerically pure products with heterogeneous catalytic products with heterogeneous catalytic
hydrogenations:hydrogenations:
Methods Chiralmodification of the
catalysts
Use of chiralauxiliaries in thereaction mixture
Forming newchiral compound
with a chiralreactant and carry
outdiastereoselective
hydrogenationExamples Pt/Al2O3
cinchonidineethyl
pyruvate
Pd/C(S)-prolineisophorone
Schiff-basesfrom a chiralamine and aprochiralketone
Optical purity good-excellent
good poor-excellent
Scope narrow narrow broad
Industrialapplicationpossibility
limited no hopeful
AcknowledgementAcknowledgement T. Máthé, K. Fodor, G. Farkas, L. Hegedüs, G. Tóth, J. Kajtár, T. Máthé, K. Fodor, G. Farkas, L. Hegedüs, G. Tóth, J. Kajtár, I. Kolossváry, I. Kolossváry, B. Herényi, R. A. Sheldon, P. Gallezot B. Herényi, R. A. Sheldon, P. Gallezot
Department of Chemical Technology, Technical University of Budapest, H-1521. b Department of Chemical Technology, Technical University of Budapest, H-1521. b Organic Chemical Technology Research Group of the Hungarian Academy of SciencesOrganic Chemical Technology Research Group of the Hungarian Academy of Sciences
Technical Analytical Research Group of HASTechnical Analytical Research Group of HAS Department of Organic Chemistry, Eötvös University, BudapestDepartment of Organic Chemistry, Eötvös University, Budapest Department of Chemical Information Technology, Technical University of Budapest Department of Chemical Information Technology, Technical University of Budapest Gedeon Richter Co., BudapestGedeon Richter Co., Budapest Laboratory of Organic Chemistry and Catalysis, Delft University of TechnologyLaboratory of Organic Chemistry and Catalysis, Delft University of Technology Institut de Recherces sur la Catalyse-CNRS, 2, Av. Albert Einstein, 69626 Institut de Recherces sur la Catalyse-CNRS, 2, Av. Albert Einstein, 69626
Villeurbanne, FranceVilleurbanne, France