Catalysts in Organic Synthesis Dr. Christoph, Phayao University Feb. 2012

Commercial Applications

.... and many more industrial applications !

Top 20 synthetic chemicals produced in the US in 2004

Why catalysis ? In the chemical production there is a lot of waste produced in each synthesis. The amount of waste in kg per kg product is about: 1-5 kg waste for bulk chemicals 5 – 50 kg wastefor fine chemicals 25 – 100 kg waste for pharmaceuticals

Why Catalysts ? – an example:

Types of catalyzed reactions Hydrogenation = Reduction Oxidation Hydroformylation Addition of HX to Olefins (esp. Hydration) C-C bond formation

Catalyst = active site + support Most often transition metals, finely distributed on a support. “Inert” porous materials which carry the metal atoms or ions. Most often used are Aluminumoxide Titaniumoxide Active Charcoal

Catalytic Cycles

How to make a catalyst ? A common way is to use a transition metal salt (like AuCl 3 -) in solution and make a slow precipitation in aqueous solution (see demo video)see demo video If there is some support material in the reaction also, the metal “nanoparticles” could precipitate on the support like Al 2 O 3 or TiO 2.

Catalytic Steps (Homogenous Catalysis)

(a) Ligand coordination and dissociation Catalytic steps often require easy coordination of reactants to metal ions and equally easy loss of products. For this task, square-planar 16-el. Complexes are ideal because they are coordinatively unsaturated Especially Pd(II), Pt(II) and Rh(I) complexes are suitable For example the catalyst for the Wilkinson reaction (industrial hydrogenation of alkenes at mild conditions)

Exceptions to the 18-electron rule:

Oxidative addition, reductive elimination17 Basic reaction: The new M-X and M-Y bonds are formed using: the electron pair of the X-Y bond one metal-centered lone pair The metal goes up in oxidation state (+2) X-Y formally gets reduced to X -, Y - Common for transition metals, rare for main-group metals (b) Oxidative Addition

Oxidative addition, reductive elimination18 One reaction, multiple mechanisms Concerted addition, mostly with non-polar X-Y bonds – H 2, silanes, alkanes, O 2,... – Arene C-H bonds more reactive than alkane C-H bonds (!) Intermediate A is a  -complex. Reaction may stop here if metal-centered lone pairs are not readily available. Final product expected to have cis X,Y groups.

Oxidative addition, reductive elimination19 Concerted addition, "arrested" Cr(CO) 5 : coordinatively unsaturated, but metal-centered lone pairs not very available:  -complex Cr(PMe 3 ) 5 : phosphines are better donors, weaker acceptors: full oxidative addition

Which of the following can undergo oxidative addition of MeI? (Check ox.number of metal before and after reaction)

Which of the following will be MORE ACTIVE towards ox. addition of H 2 ? The most electron-rich complex will be easiest to oxidize.

(c) Reductive Elimination Favoured by electron-poor metal centers !

Example:

How does it work ? Pd and Pt atoms have a high affinity for Hydrogen to form M-H bonds. The hydrogen molecule can accept electron density from a d-orbital into the σ* antibonding MO !  the H-H bond becomes weaker and can easily split up. (this works also for C-H bonds ! )

Unusual HIGH ox.number for Pt !

(d) Insertion / Migration Research showed that the X-group migrates to the unsaturated ligand U The reverse reaction is called beta-Hydrid-Elimination

“CO Insertion” – actually the Methylgroup migrates to the CO ! Note that the ox.number of Mn does NOT change !

Mindmap: “All in One” – made by

Part 2: Overview Basic industrial important reactions

(1) From crude oil to Olefins => CRACKING The ethene and propene are important materials for making plastics or producing other organic chemicals. The octane is one of the molecules found in petrol (gasoline).

Catalytic Cracking – Zeolites as “Superacids” Mixed structure of Al 2 O 3 and SiO 2. Each Al(3+) needs an additional cation (like Na+ or H+) so that the charges are balanced ! Cation exchange is exploited in water softening, where alkali metals such as Na + or K + in zeolite framework are replaced by Ca 2+ and Mg 2+ ions from water.

Zeolites can protonate an alkane to give a carbocation or carbenium ion. (Haag-Dessau Mechanism, 1984) The carbonium ion then decomposes and forms smaller parts including double-bonds.

Base-catalyzed Production of Bio-Diesel Follow this link to watch the movie This is an example of a homogenous catalysis, where the catalyst (NaOH) is in the same phase as the product (vegetable oil). The byproducts and the catalyst have to be separated from this phase later.

Hydration of Alkenes => Alcohols The catalyst is an acid, so that a hydronium ion is formed that act as electrophil. To save material, in industrial scale we can use zeolites as acid catalyst instead of for example sulfuric acid. (2) From olefins to alcohols => Hydration

(3) From alcohols to aldehydes=> Oxidation In industry, formaldehyde is produced on a large scale by oxidation of methanol (“Formox” process) over a catalyst of molybdenum and iron oxide. A mixture of air and methanol is vaporised and passed into catalyst-packed reactor tubes. The reaction which takes place at 350oC is highly exothermic and generates heat to provide steam for turbines and process heating. Another oxidation route significant in industry is the Wacker process, whereby ethylene is oxidized to acetaldehyde in the presence of copper and palladium catalysts. (see next)Wacker process In the lab we can use dichromate as oxidation agent - to prevent formation of the carboxylic acid, we have to take the aldehyde product out by distilliation !

Hydroformylation At the end, it is a hydrogenation and CO insertion H2H2

(4) From aldehydes to carboxylic acids => Oxidation Compare the conventional way of oxidation with strong oxidizing agent to the reaction with molecular oxygen from air

Especially the metals Pd and Pt are suitable for this kind of reaction ! Example: intermediate for Ibuprofen (5) From ketones to alcohols => Reduction

Hydrogenation The exact mechanism of heterogeneous processes is often not fully understood ! In a simplified way, a multiple bond can be hydrogenated by Pd or Pt atoms on a support:

Oxidative addition, reductive elimination44 Catalytic olefin hydrogenation (1) Homogenous catalysis Usually with platinum metals. – e.g. Wilkinson's catalyst Many chiral variations available. – Enantioselectivity Rarely possible with early transition metals

Oxidative addition, reductive elimination45 Catalytic olefin hydrogenation (2) Alternative mechanism for metals not forming a "stable" hydride. Requires oxidative addition, not observed for early transition metals.

How does it work ? Pd and Pt atoms have a high affinity for Hydrogen to form M-H bonds. The hydrogen molecule can accept electron density from a d-orbital into the σ* antibonding MO !  the H-H bond becomes weaker and can easily split up. (this works also for C-H bonds ! )

In addition, transition metals can make covalent bonds to π-bonds of ligands: The π-MO of ethylene acts as electron donor, the antibonding π*-MO can accept electron density from a metal d-orbital (“backbonding”).

Thank you for your attention ! Please visit our class again and good luck for your exams !