WILKINSON CATALYST ZIGER NILLA TYPES SYNTHESI OF DRUG USING HOMOGENOUS CATALYST APPLICATION

1. HOMOGENOUS
CATALYSIS
PRESENTED BY
Mr. Darshan N U
M Pharmacy II Semester
Dept. of Pharmaceutical Chemistry
Sri Adichunchanagiri College of Pharmacy
PRESENTED TO
Dr. Shankar Mani
Associate Professor
Dept. of Pharmaceutical Chemistry
Sri Adichunchanagiri College of Pharmacy
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2. Homogenouscatalysis
 In homogeneous catalysis the catalysts are present in the same phase as the
substances which are going into the reaction phase.
 The homogeneous forms of catalysts are nothing but chemical compound which
remains in same phase as the reactants and help in accelerating the process of
chemical change.
 Hydrogenation: is a chemical reaction between molecular hydrogen (H2) and
another compound or element, usually in the presence of a catalyst such as Ni, Pd or
Pt. The process is commonly employed to reduce or saturate organic compounds.
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3. Application: In food industry for large scale production of vegetable oils.
Hydrogenation converts liquid vegetable oils into solid or semi-solid fats.
In petrochemical processes, hydrogenation is used to convert alkenes and
aromatics into saturated alkanes (paraffins) and cycloalkanes (naphthenes),
which are less toxic and less reactive.
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4. Hydroformylation: Hydroformylation, popularly known as the "oxo" process,
is a Co or Rh catalyzed reaction of olefins with CO and H2 to produce the value-
added aldehydes. The metal hydride complexes namely, the Rhodium based
HRh(CO)(PPh3)3 and the cobalt based HCo(CO)4 complexes, catalyzed the
hydroformylation reaction.
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5. • Hydrocyanation: It is most fundamentally, the process whereby H+ and –CN
ions are added to a molecular substrate. Usually the substrate is an alkene and the
product is a nitrile.
A key step in Hydrocyanation is the oxidative addition of hydrogen cyanide to
low–valent metal complexes.
In Hydrocyanation of unsaturated carbonyls addition over the alkene
competes with addition over the carbonyl group.
It is basically used in steroids synthesis.
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(3E)-pent-3-enenitrile
2-ethylbut-3-
enenitrile
Hexan enitrile

7. •Wilkinsoncatalysts
Wilkinson's catalyst, is the common name for chloride-
tris(triphenylphosphane)rhodium(I), a coordination complex of rhodium with the
formula RhCl(PPh3)3 (Ph = phenyl). It is a red-brown colored solid that is soluble
in hydrocarbon solvents such as benzene, and more so in tetrahydrofuran or
chlorinated solvents such as dichloromethane. The compound is widely used as a
catalyst for hydrogenation of alkenes. It is named after chemist and Nobel
Laureate, Sir Geoffrey Wilkinson, who first popularized its use.
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8. Wilkinson's catalyst is usually obtained by treating rhodium(III) chloride hydrate
with an excess of triphenylphosphine in refluxing ethanol.
RhCl3(H2O)3 + 4 PPh3 → RhCl(PPh3)3 + OPPh3 + 2 HCl + 2 H2O
Uses: It is used in the selective hydrogenation of alkenes and alkynes without
affecting the functional groups like: C=O, CN, NO2, Aryl, CO2R etc.
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9. • ChiralLigands& Chiral Induction
Most chiral ligands combine with metals to form chiral catalyst engages in a chemical
reaction in which chirality is transfer to the reaction product. Chiral induction are also
known as asymmetric induction.
If we want to create a new chiral center in a molecule, our starting material must have
prochirality (the ability to become chiral in one simple transformation).
The most common prochiral units that give rise to new chiral centers are the trigonal
carbon atom of alkenes and carbonyl groups, which become tetrahedral by addition
reaction.
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10. One of the simplest transformations you could imagine of a prochiral unit into a chiral
one is the reduction of a ketone.
The left hand structure has a C2-rotational axis whereas the right hand structure is
asymmetric. Arrows indicate the proposed trajectories for attack by substrates,
identical colors lead to identical transition states (and hence products) with red arrows
being disfavored due to steric repulsion.
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11. Ziegler-Nattacatalyst
A Ziegler–Natta catalyst, named after Karl Ziegler and Giulio Natta, is a catalyst used in the
synthesis of polymers of 1-alkenes (alpha-olefins). 2 broad classes of Ziegler-Natta catalysts
are employed:
Heterogeneous supported catalysts based on titanium compounds are used in polymerization
reactions in combination with co-catalysts, organoaluminum compounds such as
triethylaluminium, Al(C2H5)3. This class of catalyst dominates the industry.
Homogeneous catalysts usually based on complexes of Ti, Zr or Hf. They are usually used in
combination with a different organoaluminum co-catalyst, methylaluminoxane (or
methylalumoxane, MAO). These catalysts traditionally contains metallocenes but also feature
multidentate oxygen- and nitrogen-based ligands.
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12. Commercial Application: In synthesis of variety of polymers like:
Polyethylene, Polypropylene, Polymethylpentene, Polybutadiene,
Polyisoprene, Polyacetylene etc.
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13. Homogenous catalysis in drug synthesis
Contribution of homogeneous catalytic process in chemical industry is
significantly smaller compared to heterogeneous catalytic process, it is only
about 17-20 %. But importance of homogeneous catalysis is increasing
significantly. The significance of homogeneous catalysis is growing rapidly
particularly in the area of pharmaceutical and polymer industry. Some of the
important industrial processes include:
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14. Oxidations of alkenes such as production of acetaldehyde, propylene oxide etc.
Polymerization such as production of polyethylene, polypropylene or polyesters.
Examples: Acid catalyzed condensation of phenol and acetone to bisphenol which is an
important intermediate in the manufacture of epoxy resin and polycarbonates.
Synthesis of L-dopa:
The asymmetric hydrogenation of cinnamic acid derivatives involves synthesis of L-
Dopa. L-Dopa is a drug for treating Parkinson’s disease. It is one of the recently
developed industrial processe. The C atom bonded to the NH2 group is the chiral
center. The enantiomer D-Dopa is ineffective form.
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15. The reaction is carried out in the presence of rhodium complex having asymmetric
diphosphine ligand which induces enantio- selectivity. The hydrogenation reaction is carried
out with a substituted cinnamic acid. The main step in L-Dopa synthesis, the hydrogenation of
prochiral alkene to a specific optical isomer.
Catalyst is prepared by reacting Rh salt with an alkene chloride, such as hexadiene chloride or
cyclooctadiene chloride producing a cationic Rh species
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16. Reference
1)“Green Chemistry and Catalysis”, Roger A. Sheldon, Isabel Arends, Ulf Hanefold, WILEY-VCH
Verlag GmbH& Co. KGaA, Weinhein, Germany; Pg. no. 106, 223-244, 250, 304, 310, 314.
2) “Multistep Continuous-flow Synthesis of (R)- and (S)-Rolipram using Heterogeneous Catalyst”,
Tetsu Tsubogo, Hidekazu Oyamada & Shu Kobayashin. (DOI: 10.1038/nature14343)
3) https://nptel.ac.in/courses/103103026/44
4) “General and efficient Copper-Catalyzed Three-Component Coupling Reaction towards
Imidazoheterocycles: One-Pot synthesis of Alpidem & Zolpidem”, Natalia Chernyak and Vladimir
Gevorgyan; AngewandteChemie. (DOI: 10.1002/anie.200907291)
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