Homogeneous catalysis refers to reactions where the catalyst is in the same phase as the reactants. Common homogeneous catalysts include acids and bases in aqueous solutions. Homogeneous catalysts can provide selectivity in terms of chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity. Important reaction types for homogeneous catalysis include oxidative addition, reductive elimination, migratory insertion, and β-hydride elimination. Key reactions discussed are hydrogenation, hydroformylation, hydrocyanation, and applications of Ziegler-Natta catalysts and Wilkinson's catalyst. Chiral induction with chiral ligands is also discussed for producing chiral molecules in drug synthesis such as L-DOPA
2. Catalysis
- Catalysis is an action by a catalyst which takes part in a chemical reaction
process and can alter the rate of reactions, and yet itself will return to its
original form without being consumed or destroyed at the end of the reactions.
- A catalyst typically increases the rate of reaction by lowering the activation
energy by opening up pathways with lower Gibbs free energy of activation (G).
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6. Homogeneous Catalysts
- Homogeneous catalysis is a reaction in which the catalyst is in the same
phase as the reactants in the solution.
- Most often, homogeneous catalysis involves the introduction of aqueous
phase catalyst into an aqueous solution of reactants.
- In such cases, acids and bases are often very effective catalysts, as they
can speed up reactions by affecting bond polarization.
E.g. : Hydrolysis of sugar is catalysed by H+ ions furnished by sulfuric acid.
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8. Selectivity of Catalysts
1] Chemoselectivity
When two chemically different functionalities are present such as an alkene
and an aldehyde which both can be hydrogenated, the chemoselectivity tells us
whether the aldehyde or the alkene is being hydrogenated; or when more than
one reaction can take place for the same substrate.
E.g.: Hydrogenation
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9. Selectivity of Catalysts
2] Regioselectivity
The formyl group can be attached to either the primary, terminal carbon atom
or the secondary, internal carbon atom, which leads respectively to the linear
and branched product.
E.g.: Hydroformylation
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10. Selectivity of Catalysts
3] Diastereoselectivity
The substrate contains a stereogenic centre and this together with the
catalyst can direct the addition of dihydrogen in the example to give two
diastereomers, the selectivity for either one is called the diastereoselectivity.
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11. Selectivity of Catalysts
4] Enantioselectivity
The substrate is achiral in this instance, but the enantiopure or enantio-
enriched catalyst may give rise to the formation of one specific product
enantiomer.
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20. Hydrogenation
- It is a chemical reaction between molecular hydrogen (H2) with unsaturated
organic compound (alkene or aldehyde) in presence of a catalyst such as Rh
or Co.
- The process is commonly employed to reduce or saturate organic compounds
(alkane or alcohol).
E.g.:
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23. Applications of Hydrogenation Reaction
- Homogeneous catalysts are useful for selective hydrogenation of the C-C
double bond without hydrogenolysis of other susceptible groups.
E.g.: Benzyl cinnamate is converted into the dihydro compound without
hydrogenolysis of the benzyl group.
C6H5CH=CHCOOC6H5
E.g.: Allyl phenyl sulfide on reaction gives 93% phenyl propyl sulfide.
CH2=CHCH2SC6H5
H2, PPh3RhCl
C6H6
C6H5CH2CH2COOC6H5
H2, PPh3RhCl
C6H6
CH3CH2CH2SC6H5
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24. Hydroformylation
- Synthesis of aldehydes from terminal alkenes with cobalt and rhodium
catalysts.
- Hydroformylation, popularly known as ‘oxo’ process. The reaction is
catalyzed by organorhodium or organocobalt compounds and adds a hydrogen
atom to the C=C to form a C-C bond and a formyl group to the molecule,
creating an aldehyde.
- The metal hydride complexes namely the rhodium based HRh(CO)(PPh3)3 and
the cobalt based HCo(CO)4 complexes catalyzes the hydroformylation.
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25. Hydroformylation
- Hydroformylation is also used in specialty chemicals, relevant to the organic
synthesis of fragrances and natural products.
- Comparative study of three commercial homogeneous catalytic processes
for the hydroformylation reaction:
- Though most long-chain, branched chain and cyclic olefins can be
hydroformylated, the most common starting chemicals are ethylene and
propylene, which yield propionaldehyde, n-butaraldehyde and iso-
butaraldehyde. 25
26. Rhodium-catalysed Hydroformylation
- The high selectivity and mild
conditions make the rhodium
process more attractive than the
cobalt one for the manufacture
of n-butyraldehyde.
- In this process, rhodium was
recovered.
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28. Cobalt-catalysed Hydroformylation
- Cobalt catalysts operate at 1500C
and 250 atm pressure whereas
rhodium catalysts operate at
moderate temperature and 1 atm
pressure.
- Propylene coordination followed
by olefin insertion into the metal
hydrogen bond in a markovnikov
or anti-markovnikov fashion gives
the branched or the linear metal
alkyl complex.
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29. Hydrocyanation
- Hydrocyanation of olefins refers to the transition-metal-mediated or -
catalysed addition of hydrogen cyanide across a carbon-carbon 𝞹 bond.
- This reaction may be used to synthesize nitriles from olefins in a
Markovnikov or anti-markovnikov fashion.
- The common catalysts used to effect hydrocyanation are Ni(0) and Pd(0)
complexes. The industrial development of nickel-catalyzed hydrocyanation
was motivated by the need to mass produce adiponitrile (1,4-dicyanobutane)
for nylon synthesis.
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30. Hydrocyanation
- A key step in hydrocyanation is the oxidative addition of HCN 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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31. Ziegler-Natta Catalysts
- The German chemist “Karl Ziegler” discovered in 1953 that when TiCl4 and
Al(C2H5)3 are combined together, they produce an extremely active
heterogeneous catalyst for the polymerization of ethylene at atmospheric
pressure.
- “Giulio Natta”, an Italian chemist, extended the method to other olefins like
propylene and developed variations of the Ziegler catalyst based o his
findings on the mechanism of the polymerization reaction.
- The Ziegler-Natta catalysts family includes halides of titanium, chromium,
vanadium and zirconium, typically activated by alkyl aluminium compounds.
- Ziegler-Natta received the Nobel prize in chemistry for their work in 1963.
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32. Ziegler-Natta Catalysts
- The titanium chloride compound has a crystal structure in which each Ti
atom is coordinated to 6 chlorine atoms.
- On the crystal surface, a Ti atom is surrounded by 5 chlorine atoms with
one empty orbital to be filled.
- When ET3Al comes in, it donates an ethyl group to Ti atom and the Al atom
is coordinated to one of the chlorine atoms.
- Meanwhile, one Cl atom from titanium is kicked out during this process.
- Thus, the catalyst system has an empty orbital.
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34. Ziegler-Natta Catalysts
1] Regioselectivity
For propene polymerization, most ZN catalysts are highly regioselective,
favouring 1,2-primary insertion due to electronic and steric effects.
2] Stereoselectivity
The relative stereochemistry of adjacent chiral centers within a
macromolecule is defined as tacticity. Three kinds of stereochemistry are
possible: isotactic, syndiotactic and atactic.
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36. Wilkinson’s Catalysts
- Wilkinson’s catalyst is the common name for
chlorotris(triphenylphosphine)rhodium (I) [(C6H5)3P]3RhCl.
- It is red brown colored solid that is soluble in hydrocarbon solvents such as
benzene, and more so in THF or DCM.
- The compound is widely used as a catalyst for hydrogenation of alkenes.
- The catalyst is sensitive to the steric influence of the alkene substrate.
- Terminal alkynes are hydrogenated more rapidly than terminal alkenes.
- Conjugated dienes are reduced more slowly than isolated alkenes.
- For disubstituted alkenes, cis are more reactive than trans. Trisubstituted
alkenes are more reactive than tetra-substituted alkenes.
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37. Wilkinson’s Catalysts
● Preparation:
● Reaction:
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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39. Chiral Induction and Chiral Ligands
- Most chiral ligands combine with metals to form chiral catalyst engages in a
chemical reaction in which chirality is transferred to the reaction products.
- Chiral induction is also known as asymmetric induction.
- Substrate has to be prochiral.
- Catalyst has to be chiral.
- Homogeneous catalysts are also used for the manufacture of chiral
molecules.
- Depending on the number of asymmetric centres, chiral molecules have two
or more optical isomers.
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43. Chiral Induction and Chiral Ligands
- Chiral ligands are no different from the general categories of ligands that
we have already encountered.
- They, however, have one or more chiral or asymmetric centres and can be
broadly classified into two types:
1)The first type has ‘hard’ donor atoms such as nitrogen and/or oxygen and
can be monodentate or chelating depending upon the nature of reaction.
2)The second type is almost exclusively based on chelating phosphines.
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46. Homogeneous 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.
- Some of the important industrial processes include:
1) Oxidations of alkenes such as production of acetaldehyde, propylene oxide,
etc.
2)Polymerization such as production of polyethylene, polypropylene or
polyesters.
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47. A] Synthesis of l-DOPA
- The asymmetric hydrogenation of cinnamic acid derivatives involves the
synthesis of L-DOPA.
- The carbon atom bonded to the -NH2 group is the chiral centre.
- The enantiomer D-DOPA is inactive.
- The reaction is carried out in presence of rhodium complex having
asymmetric diphosphine ligand which induces enantio-selectivity.
- The main step in L-DOPA synthesis is the hydrogenation of prochiral alkene
to a specific optical isomer.
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