Homogeneous Catalysis HMC Dr. K.R.Krishnamurthy National Centre for Catalysis Research Indian Institute of Technology, Madras Chennai

Homogeneous Catalysis- 1 Basics Homogeneous Catalysis- General features Metal complex chemistry- Metals & Ligands –bonding & reactivity Reaction cycles Reaction types/ Elementary reaction steps Kinetics & Mechanism

Catalysis 1850 Berzelius 1895 Ostwald: A catalyst is a substance that changes the rate of a chemical reaction without itself appearing into the products Definition: a catalyst is a substance that increases the rate at which a chemical reaction approaches equilibrium without becoming itself permanently involved. Catalysis is a kinetic phenomenon. Obeys laws of thermodynamics Catalysis –Types Heterogeneous Homogeneous Enzymatic/Bio Photo/Electro/Photo-electro Phase transfer

Homogeneous Catalysis Reactions wherein the Catalyst components and substrates of the reaction are in the same phase, most often the liquid phase Mostly soluble organometallic complexes are used as catalysts Characterized by high TON & TOF Operate under milder process conditions Amenable to complete spectroscopic characterization Homogeneous processes without a heterogeneous counterpart: Pd-catalyzed oxidation of ethylene to acetaldehyde (Wacker process) Ni-catalyzed hydrocyanation of 1,3-butadiene to adiponitrile (DuPont) Rh- and Ru-catalyzed reductive coupling of CO to ethylene glycol Enantioselective hydrogenation, isomerization, and oxidation reactions.

Catalysis- Heterogeneous Vs Homogeneous AspectHeterogeneousHomogeneous Activity Reproducibility Comparable Difficulty in reproducibility Comparable Reproducible results SelectivityHeterogeneous sites. Difficult to control selectivity Relatively higher selectivity, easy to optimize, various types of selectivity Reaction conditionsHigher temp. & pressure, better thermal stability Lower temp. (<250ºC), Higher pressure, lower thermal stability Catalyst cost & recovery High volume –low cost. Easy catalyst recovery Low volume, high value. Recovery difficult. Major drawback Active sites, nature & accessibility Not well- defined, heterogeneous, but tunable, limited accessibility Molecular active sites, very well defined, uniform, tunable & accessible Diffusion limitationsSusceptible, to be eliminated with proper reaction conditions Can be overcome easily by optimization of stirring Catalyst lifeRelatively longer, regeneration feasibleRelatively shorter, regeneration may/may not be feasible Reaction kinetics mechanism & catalytic activity at molecular level Complex kinetics & mechanism, Difficult to establish & understand unequivocally l, but days are not far-off Reaction kinetics,mechanism & catalytic activity could be established & understood with relative ease Susceptibility to poisons Highly susceptibleRelatively less susceptible. Sensitive to water & oxygen Industrial Application Bulk/Commodity products manufacture ~ 85% Pharma, fine & specialty chemicals manufacture, ~15%

Homogeneous catalysis-Major industrial processes Processes/Products Terephthalic acid -PTA Acetic acid & acetyl chemicals Aldehydes and alcohols- Hydroformylation Adiponitrile- Hydrocyanation Detergent-range alkenes- SHOP- Oligomerization Alpha Olefins (C 4 - C 20 )- Dimerization & Oligomerization Total fine chemicals manufacture Olefins Polymerization (60% uses Ziegler-Natta) Production (Milln.MTA) < 1 60

Homogeneous catalysis-Features Cone Angle

Transition-metal catalysts- Features / Potential Activity & Selectivity can be controlled in several ways: Strength of metal-ligand bond can be varied Variety of ligands can be incorporated into the coordination sphere Specific ligand effects can be tuned- constituents Variable oxidations states are feasible Variation in coordination number can be possible Tailor made catalyst systems are possible

Effect of ligands and valance states on the selectivity in the nickel catalyzed reaction of butadiene Scheme: 1,3-butadiene reactions on “Ni”

Types of selectivity

12 Principles of green chemistry 1.Prevent waste 2.Increase atom economy 3.Use and generate no / less toxic chemicals 4.Minimize product toxicity during function 5.Use safe solvents and auxiliaries 6.Carry out processes with energy economy (ambient temperature and pressure) 7.Use renewable feedstocks 8.Reduce derivatives and steps 9.Use catalytic instead of stoichiometric processes 10.Keep in mind product life time (degradation vs. biodegradation processes) 11.Perform real-time analysis for pollution prevention 12.Use safe chemistry for accident prevention Amenable for adoption in homogeneous catalysis

Catalysts affect both rate & selectivity

Chemo selectivity

Regio selectivity

Diastereo & Enantio Selectivity

Basics - Reactivity of metal complexes A metal complex: The catalytic activity is influenced by the characteristics of the central metal ions and attached ligands. Metal The oxidation state and the electron count (EC) of the valence shell of the metal ion are the critical parameters for activity. A fully ionic model is implicit. Activity of a metal complex is governed by Rule of effective atomic number (EAN) or the 18 e - rule EC=18- Co-ordinative saturation Inactive EC < 18- Co-ordinative unsaturation Activity Easy displacement of weakly bound ligands; e.g., Zr Complex, THF can be easily replaced by the substrate and solvent molecules. Influenced of bulkier ligands; Steric constraints- Easy ligand dissociation NiL4 ↔NiL3 + L Many complexes have electron counts less that 16

Metal complexes-Electron counts for activity Oxidation stateElectron count

Homogeneous Catalysis- Reaction cycle The catalytically active species must have a vacant coordination site (total valence electrons = 16 or 14) to allow the substrate to coordinate. Noble metals (2nd and 3rd period of groups 8-10) are privileged catalysts (form 16 e species easily). In general, the total electron count alternates between 16 and 18. Ancillary ligands insure stability and a good stereoelectronic balance. One of the catalytic steps in the catalytic cycle is rate-determining.

Homogeneous Catalysis Role of ‘vacant site’ and Co-ordination of the substrate Catalyst provides sites for activation of reactant (s) Through surface/site activation the activation barrier for reaction is reduced. In homogeneous as well as heterogeneous catalysts such active sites are normally referred to as vacant site/ co-ordinatively unsaturated site (cus). Substrates on adsorption at cus get activated In a typical homogeneous catalyst the active site is a cus in a metal complex In heterogeneous catalysis, similar cus exist In homogeneous phase, metal complexes are fully saturated with ligand & solvent molecules There is a competition between the desired substrate and the other potential ligands present in the solution for co-ordination with metal ion. Nature of interaction/binding between Metal- ligand-substrate-solvent governs overall activity & selectivity These interactions/exchange takes place via different routes: Substitution Associative Dissociative

Homogeneous Vs Heterogeneous Functional similarities HomogeneousFunctionsHeterogeneous Dissociation Metal-ligand bond breakingDesorption Association Metal-ligand bond formationAdsorption Oxidative addition Fission of bond in substrateDissoc. Adsorption Reductive elimination Bond formation towards product Association

Wilkinson’s catalyst: Oxidative addition of H 2 H2 adds to the catalyst before the olefin. The last step of the catalytic cycle is irreversible. This is very useful because a kinetic product ratio can be obtained. S-Solvent

Metal complexes Metal complexes retain identity in solution Have characteristic properties- XRD,IR,UV,ESR Double salts exist as individual species

Co-ordination complex

Ligands-Types

Alkene additions

Wacker Oxidation- Catalyst & Chemical cycles Catalyst Chemical

Hydrogenation cycles

Ligand Effects P as donor element: Alkyl (aryl) phosphines (PR 3 ) and organo phosphites Alkyl phosphines are strong bases, good σ-donor ligands Organo phosphites are strong π-acceptors and form stable complexes with electron rich transition metals. Metal to P bonding resembles, metal to ethylene and metal to CO Which orbitals of P are responsible for π back donation? Antibonding σ * orbitals of P to carbon (phosphine) or to oxygen (phosphites) The σ-basicity and π-acidity can be studied by looking at the stretching frequency of the coordinated CO ligands in complexes, such as Ni L(CO) 3 or Cr L(CO) 5 in which L is the P ligand. 1)Strong σ donor ligands → High electron density on the metal and hence a substantial back donation to the CO ligands → Lower IR frequencies Strong back donation and low C – O stretch A. Electronic Effects P C O P C O Strong back donation-low C-O stretch Weak back donation-high C-O stretch

Trimethyl phosphite Triethyl phosphite Triphenyl phosphite

2) Strong π acceptor ligands will compete with CO for the electron back donation and C-O stretch frequency will remain high Weak back donation → High C – O stretch The IR frequencies represent a reliable yardstick for the electronic properties of a series of P ligands toward a particular metal, M. CrL(CO) 5 or NiL(CO) 3 as examples; L = P(t-Bu) 3 as reference The electronic parameter, χ (chi) for other ligands is simply defined as the difference in the IR frequencies of the symmetric stretch of the two complexes Ligand, PR 3, R= χ (chi)IR Freq (A 1 ) of NiL(CO) 3 in cm -1 T-Bu02056 N-Bu C 6 H 4 NMe Ph C 6 H 4 F CH 3 O PhO CF 3 CH 2 O Cl (CF 3 ) 2 CHO F CF

B. Steric Effects 1) Cone angle (Tolman’s parameter, θ) (Monodentate ligands) From the metal center, located at a distance of 2.28 A from the phosphorus atom in the appropriate direction, a cone is constructed with embraces all the atoms of the substituents on the P atom, even though ligands never form a perfect cone. Sterically, more bulky ligands give less stable complexes Crystal structure determination, angles smaller than θ values would suggest. Thermochemistry: heat of formation of metal-phosphine adducts. When electronic effects are small, the heats measured are a measure of the steric hindrance in the complexes. Heats of formation decrease with increasing steric bulk of the ligand. Ligand, PR 3 ; R =H θ value =87 CH 3 O107 n-Bu132 PhO128 Ph145 i-Pr160 C 6 H t-Bu182

An ideal separation between Steric and electronic parameters is not possible. Changing the angle will also change the electronic properties of the phosphine ligand. Both the  - and θ- values should be used with some reservation Predicting the properties of metal complexes and catalysts: Quantitative use of steric and electronic parameters (QALE) The use of  - valaues in a quantitative manner in linear free energy relationships (LFER) Tolman’s equation: Property = a + b(  ) + cθ The property could be log of rate constant, equilibrium constant, etc. Refinements: Property = a + b (  ) + c(θ – θ th ) where,, the switching factor, reads 0 below the threshold and 1 above it. Refinement, the electronic parameter: Property = a(  d ) + b(θ – θth) + c(E ar ) + d(  p ) + e where  d is used for  -donicity and  p used for  -acceptor property; E ar is for “aryl effect”. For reactions having a simple rate equation, the evaluation of ligand effects with the use of methods such as QALE will augment our insight in ligand effects, a better comparison of related reactions, and a useful comparison between different metals.

Bite angle effects (bidentate ligands) Diphosphine ligands offer more control over regio- and stereoselectivity in many catalytic reactions The major dfiference between the mono- and bidentate ligands is the ligand backbone, a scaffold which keeps the two P donor atoms at a specific distance. This distance is ligand specific and it is an important characteristic, together with the flexibility of the backbone Many examples show that the ligand bite angle is related to catalytic performance in a number of reactions. Pt-diphosphine catalysed hydroformylation Pd catalyzed cross coupling reactions of Grignard reagents with organic halides Rh catalyzed hydroformylation Nickel catalyzed hydrocyanation and Diels-Alder reactions

Ligands - Types & properties 1. Ligands: CO, R 2 C=CR 1, PR 3 and H - (N 2, NO, etc.) All ligands behave as Lewis bases and the M acts as a Lewis acid Alkenes:  electrons Whereas H 2 O and NH 3 accept e - density from the metal, i.e., they act as Lewis Acids (  acid ligands) The donation of e - density by the metal atom to the ligand is referred to as back donation. H 2 acts as a Lewis acid. Also, Lewis acid-like behaviour of CO, C 2 H 4 and H 2 in terms of overlaps between empty orbitals of the ligand and the filled metal orbitals of compatible symmetry. Back donation is a bonding interaction between the metal atom and the ligands, because the signs of the donating metal ‘d’ orbitals and the ligand  * (  * for H 2 ) acceptor orbitals match. The  ligands play important roles in a large number of homogeneous catalytic reactions.

Acids & Bases Lewis acids A Lewis acid accepts a pair of electrons from other species Bronsted acids transfer protons while Lewis acids accept electrons A Lewis base transfers a pair of electrons to other species BF 3 - Lewis acid; Ammonia- Lewis base

2. Alkyl, Allyl and alkylidene ligands Alkyl ligands: Two reactions a)Addition of RX to unsaturated metal center Oxidation state: +n+n+2 valence electrons: p p-2 b) Insertion of alkene into a metal-H or an existing metal-C bond Reactivity of metal-alkyls: kinetic instability towards conversion by  -hydride elimination. Others:  -hydride elimination Agostic interaction Metallocycle formation M-Alkyl-Single bond- M-C M-Alkylidene-Double bond M=C M-Allyl group

Interaction between metal & α- H of alkyl group that weakens C-H bond but does not break

Homogeneous Catalysis –Key reaction steps 1.Ligand Coordination and Dissociation 2. Oxidative addition and Reductive elimination 3. Insertion and Elimination 4. Nucleophilic attack on coordinated ligands 5. Oxidation and Reduction

1. Ligand Coordination and Dissociation Basis Easy coordination of substrate to the metal center-activation Facile elimination of product from the metal coordination sphere- Desorption ? Requirement Co-ordinative unsaturation- active centre Highly labile metal complex- activity Substitution- addition-dissociation-migration Examples Many square-planar complexes with 16e EC are highly active. ML 4 complexes of Pd(II), Pt(II) and Rh(I) are commonly used as catalysts. E.g., Wilkinson’s catalyst

2. Oxidative Addition & Reductive Elimination Oxidative Addition Addition of a molecule AX to a complex Steps Dissociation of the A—X bond Coordination of the two fragments to the metal center Reductive Elimination Reverse of oxidative addition: Steps Formation of a A—X bond Dissociation of the AX molecule from the coordination sphere

Examples of Oxidative addition

Examples of reductive elimination

3. Insertion and Elimination Insertion : Migration of alkyl (R) or hydride (H) ligands from the metal center to an unsaturated ligand Elimination: Migration of alkyl (R) or hydride (H) ligands from a ligand to the metal center e.g., β-hydride elimination

3. Insertion reactions : Migratory insertion - Examples Migratory insertion of R in M-CO

Insertion reactions are ‘cis’ in character

4. Nucleophilic Attack on Coordinated Ligands A (+)ve charge on a metal-ligand complex tends to activate the coordinated C atom toward attack by a nucleophile.

Nucleophilic attack on a coordinated ligand Upon coordination to a metal center, the electronic environment of the ligand undergoes a change. The ligand may become susceptible to electrophilic or nucleophilic attack. The extent of the reactivity of the ligand is reflected in the rate constants

5. Oxidation and Reduction During a catalytic cycle, metal atoms frequently alternate between two oxidation states: Cu 2+ /Cu + Co 3+ /Co 2+ Mn 3+ /Mn 2+ Pd 2+ /Pd Catalytic Oxidation: generating alcohols and carboxylic acids The metal atom 1) initiates the formation of the radical R 2) contributes to the formation of R-O-O radical

The Catalytic Cycle –Elementary steps ML n+1 ⇋ ML n + L ML n+ + H 2 ⇋ H 2 ML n H 2 ML n + alkene ⇋ H 2 ML n (alkene) H 2 ML n (alkene) ⇋ HML n (alkyl) HML n (alkyl)→ML n + alkane Example: A metal complex catalyzed hydrogenation of an alkene Alkene + H 2 →Alkane

Kinetic studies Reaction rates Dependent on the concentration of reactants and the products in some cases Useful in understanding the mechanism of the reaction Empirically derived rate expressions Ligand dissociation Leads to generation of catalytic active intermediate. Addition of ligand in such a catalytic system, the rate of the reaction decreases. Examples CO dissociation in Co-catalyzed hydroformylation Phosphine dissociation in RhCl(PPh 3 ) catalyzed hydrogenation Cl - dissociation in the Wacker process

Michaelis-Menten Kinetics (Enzyme catalysed reactions - Saturation kinetics A complex is formed between the substrate and the catalyst by a rapid equilibrium reaction. K -The equilibrium constant of this reaction k- rate constant for rate-determining step Increasing the substrate concentration will increase the rate initially, followed by more or less constant rate At high substrate concentration, when K[substrate] ~ 1 + K[substrate] At constant catalyst concentration, plot of (1/rate) vs. (1/(substrate) will give a straight line. Rate = k.K[substrate][catalyst]/1 + K[substrate]

Homogeneous Catalysis- Kinetics & Mechanism a.Kinetic studies and mechanistic insight i) Macroscopic rate law ii) Isotope labelling and its effect on the rate or stoichiometry iii) Rate determining step iv) Variation of ligand structure and its influence on ‘k’ b. Spectroscopic investigations ‘in-situ’ IR, NMR, ESR c. Studies on model compounds d. Theoretical calculations

Limitations: - Kinetic studies are informative about the slowest step only, not other steps. - Spectroscopic investigations of a complex requires a minimum concentration. - It is possible that the catalytically active intermediates never attain such concentrations and therefore, not observed. -The species that are seen by spectroscopy may not be involved in the catalytic cycle! However, a combination of kinetic and spectroscopic methods can resolve such uncertainties to a large extent.

Reference Books 1.Homogeneous Catalysis: The Applications and Chemistry of Catalysis by soluble Transition Metal Complexes, G.W. Parshall and S.D. Ittel, Wiley, New York, Applied Homogeneous Catalysis with Organometallic Compounds, Vols 1 & 2, edited by B. Cornils and W.A. Herrmann, VCH, Weinheim,New York, Homogeneous Catalysis: Mechanisms and Industrial Applications, S. Bhaduri and D. Mukesh, Wiley, New York, Homogeneous catalysis: Understanding the Art, Piet W.N.M. van Leeuwen, Kluwer Academic Publishers, Catalysis-An integrated approach- R.A.van Santen, Piet W.N.M. van Leeuwen, J.A.Moulijn &B.A.Averill