4.2 Substitution Reactions in Octahedral Complexes

Substitution reactions in octahedral complexes are key to understanding coordination compound behavior. These reactions involve the replacement of one ligand with another, following either dissociative or associative mechanisms, which impact reaction rates and product stereochemistry.

The mechanism depends on factors like metal center properties, ligand characteristics, and reaction conditions. Understanding these factors helps predict and control reaction outcomes, crucial for designing catalysts and synthesizing specific complex structures.

Dissociative vs Associative Substitution

Dissociative Mechanism (D)

• Leaving ligand dissociates from the metal center first, forming a five-coordinate intermediate before the incoming ligand binds to the vacant coordination site
• Rate-determining step is the dissociation of the leaving ligand
  • Reaction rate is independent of the concentration and nature of the incoming ligand
• Favored for metal centers with high electron density and ligands that are good leaving groups (weak bases, poorly donating ligands)
• Can lead to scrambling of stereochemistry in the product due to pseudorotation of the five-coordinate intermediate
  • Pseudorotation is a low-energy rearrangement process that interconverts different trigonal bipyramidal geometries (e.g., Berry pseudorotation)
  • Degree of stereochemical change depends on the relative rates of pseudorotation and the binding of the incoming ligand

Associative Mechanism (A)

• Incoming ligand binds to the metal center first, forming a seven-coordinate intermediate before the leaving ligand dissociates
• Rate-determining step is the formation of the seven-coordinate intermediate
  • Reaction rate depends on the concentration and nature of both the incoming and leaving ligands
• Favored for metal centers with low electron density and ligands that are poor leaving groups (strong bases, strongly donating ligands)
• Stereochemistry of the product is determined by the approach of the incoming ligand to the seven-coordinate intermediate
  • Retention of stereochemistry occurs when the incoming ligand approaches along the axis of the leaving ligand
  • Inversion of stereochemistry occurs when the incoming ligand approaches perpendicular to the axis of the leaving ligand

Interchange Mechanism (I)

• Combination of dissociative and associative pathways may occur
• Further classified as dissociative interchange (Id) or associative interchange (Ia), depending on the relative importance of bond breaking and bond formation in the transition state
  • Id mechanism has a dissociative-like transition state with significant bond breaking (e.g., [Co(NH3)5Cl]2+)
  • Ia mechanism has an associative-like transition state with significant bond formation (e.g., [Pt(NH3)4]2+)

Factors Affecting Substitution Rates

Metal Center Properties

• Electronic configuration and oxidation state of the metal center play a crucial role in determining the preferred substitution mechanism
  • High electron density (low oxidation states, d6 configuration) favors dissociative mechanism
    • Electron-rich metal can stabilize the five-coordinate intermediate (e.g., [Co(NH3)5Cl]2+)
  • Low electron density (high oxidation states, d3 configuration) favors associative mechanism
    • Electron-poor metal benefits from the additional electron density provided by the incoming ligand (e.g., [Cr(H2O)6]3+)

Ligand Properties

• Size, charge, and donor/acceptor properties of the ligands influence the substitution mechanism
  • Bulky ligands sterically hinder the formation of the seven-coordinate intermediate, favoring dissociative mechanism (e.g., [Co(en)3]3+)
  • Strongly donating ligands increase electron density on the metal center, favoring dissociative mechanism (e.g., [Co(NH3)6]3+)
  • Strongly accepting ligands (π-acceptors) decrease electron density on the metal center, favoring associative mechanism (e.g., [Ru(NH3)5(py)]2+)
• Leaving group ability of the ligands affects the rate of substitution
  • Good leaving groups (weak bases, poorly donating ligands) facilitate dissociative mechanism and increase reaction rate (e.g., Cl-, H2O)
  • Poor leaving groups (strong bases, strongly donating ligands) slow down dissociative mechanism and decrease reaction rate (e.g., CN-, NH3)

Reaction Conditions

• Temperature and solvent can influence the substitution mechanism and rate
  • Higher temperatures generally increase reaction rate and may favor dissociative mechanism by providing energy to break metal-ligand bond
  • Polar solvents can stabilize charged intermediates and transition states, potentially favoring associative mechanism (e.g., water, dimethylformamide)

Stereochemical Change in Substitution Reactions

Dissociative Mechanism and Stereochemistry

• Dissociative mechanism can result in stereochemical changes due to pseudorotation of the five-coordinate intermediate
  • Pseudorotation leads to a scrambling of stereochemistry in the product
  • Non-stereospecific reactions with scrambling of stereochemistry are indicative of a dissociative mechanism (e.g., racemization of [Co(en)2Cl2]+ via dissociative mechanism)

Associative Mechanism and Stereochemistry

• Stereochemistry of the product in associative mechanism is determined by the approach of the incoming ligand to the seven-coordinate intermediate
  • Retention of stereochemistry occurs when incoming ligand approaches along the axis of the leaving ligand, resulting in a stereospecific reaction (e.g., [Pt(NH3)4]2+ + Py → [Pt(NH3)4(Py)]2+ with retention)
  • Inversion of stereochemistry occurs when incoming ligand approaches perpendicular to the axis of the leaving ligand, resulting in a stereospecific reaction with inversion of configuration (e.g., [Co(NH3)5Cl]2+ + OH- → [Co(NH3)5(OH)]2+ with inversion)

Chiral Complexes and Stereochemistry

• Substitution reactions in complexes with chiral ligands or a chiral metal center can lead to the formation of diastereomers or enantiomers
  • Diastereomers have different configurations at chiral centers and different physical properties (e.g., [Co(en)2(NO2)Cl]+ and [Co(en)2(ONO)Cl]+)
  • Enantiomers are non-superimposable mirror images with identical physical properties but opposite optical activity (e.g., Δ-[Co(en)3]3+ and Λ-[Co(en)3]3+)

Stereochemical Probes and Synthesis

• Stereochemical outcome of substitution reactions can be used to probe the mechanism and to synthesize complexes with desired stereochemistry
  • Stereospecific reactions with retention or inversion of configuration are indicative of an associative mechanism
  • Non-stereospecific reactions with scrambling of stereochemistry are indicative of a dissociative mechanism
  • Stereochemical control can be achieved by selecting appropriate ligands, metal centers, and reaction conditions to favor the desired mechanism and stereochemical outcome (e.g., using a chiral auxiliary ligand to induce enantioselectivity)