Determination of Reaction Mechanism Flashcards
Substituent effect
the manner in which the reactivity of the molecule changes when substituents are changed
Resonance effects
reflect the ability of an atom or a group of atoms to withdraw or donate electrons through ⫪-bonds
Inductive effects
reflect the ability of an atom or a group of atoms to withdraw or donate electrons through σ-bonds
Examples of substituent effects
- resonance effects
- inductive effects
- field effects
- polarisability effects
- steric effects
What are linear free energy relationships (LFERs) used for?
to quantify substituent effects
What does a larger absolute value of σ mean (irrespective of sign)?
larger substituent effect
What does the magnitude of the substituent effect depend on?
the combination of resonance and inductive effects
What does a positive substituent effect indicate?
strong electron-withdrawing resonance effect
What does a negative substituent effect indicate?
strong electron-donating resonance effect
Reaction constant, 𝜌
the sensitivity of the reaction to the substituent change
What is the reaction constant for the ionisation of substituted benzoic acids?
by definition 𝜌 = + 1.00
(for a plot of acidity constants of X-substituted benzoic acids against σ x )
What is σ x ?
the Hammett substituent constants
Signs of 𝜌 for rate - σ correlations:
𝜌 > 0 (positive 𝜌 value)
increase in electron density in the transition state near to or on the benzene ring (as for the ionisation of benzoic acid)
Signs of 𝜌 for rate - σ correlations:
𝜌 < 0 (negative 𝜌 value)
decrease in electron density in the transition state near to or on the benzene ring
Signs of 𝜌 for equilibrium - σ correlations:
𝜌 > 0 (positive 𝜌 value)
increase in electron density in the product near to or on the benzene ring
Signs of 𝜌 for equilibrium - σ correlations:
𝜌 < 0 (negative 𝜌 value)
decrease in electron density in the product near to or on the benzene ring
What does a large absolute value of 𝜌 suggest?
Larger absolute value of 𝜌 (irrespective of sign) = Larger sensitivity to substituent change
Magnitude of 𝜌:
|𝜌| > 1
the reaction rate or equilibrium constant is more sensitive to a change of the substituent X than in the case of the ionisation of benzoic acid
Magnitude of 𝜌:
|𝜌| < 1
the reaction rate or equilibrium constant is less sensitive to a change of the substituent X than in the case of the ionisation of benzoic acid
How does the magnitude of the Hammett 𝜌- value change with position of the reaction centre?
the magnitude of 𝜌 decreases as the reaction centre moves further away from the substituted benzene ring
Substituent scales: σ -
for groups that stabilise negative charge by direct resonance
Substituent scales: σ +
for groups that stabilise positive charge by direct resonance
The σ - scale
this scale is based upon the ionisation of p-substituted phenols for which groups like nitro can stabilise the negative charge by direct resonance
The σ + scale
this scale is based upon the S N 1 reaction of p-substituted phenyldimethyl chloromethanes for which groups like amino can stabilise the positive charge by direct resonance
(carbocation forming reactions)
Example of a reaction that shows better correlations with the σ + scale
electrophilic aromatic substitution
What are the two types of non-linear Hammett Correlations?
- a gradual curve (or concave downwards curve) in a Hammett plot indicates a change in rate-limiting step as the substituents change
- an abrupt change in the slope of a Hammett plot indicates a change in mechanism as the substituents change
Hammond’s Postulate
if two states, as for example, a transition state and an unstable intermediate, occur consecutively during a reaction process and have nearly the same energy content, their interconversion will involve only a small reorganisation of the molecular structures
Thermodynamic control
product formation is governed by the equilibrium thermodynamics of the system (i.e. the relative thermodynamic stabilities of the products)
- gives the equilibrium mixture of products
Kinetic control
product composition is controlled by the relative rates of formation of products (the relative stabilities of the products don’t matter)
Reaction conditions for equilibrium control (thermodynamic control)
- longer reaction times
- increased reaction temperature
- addition of a catalyst
Conditions for sulfonation of aromatic rings: kinetic vs thermodynamic
Kinetic control:
120ºC, conc H 2 SO 4 / SO 3
Thermodynamic control:
160ºC, conc H 2 SO 4 / SO 3
The Curtin-Hammett Principle
In a chemical reaction that yields one product (P A ) from one conformational isomer (A) and a different product (P B ) from another conformational isomer (B), the product composition is not in direct proportion to the relative concentrations of the conformational isomers in the substrate; it is controlled only by the different in standard free energies of the respective transition states
Enthalpy controlled reaction
if ΔH ‡ is the main contributor to ΔG ‡
What is the magnitude of ΔH ‡ usually?
(kJ mol -1 )
normally either positive (endothermic) or approximately zero
Concerted reactions
(e.g. Diels-Alder and SΔH N 2 reactions)
Bond formation and bond cleavage occur at the same time in the reaction
Magnitude of enthalpy of activation for concerted reactions
they can be very small and close to zero as long as bond cleavage is matched by bond formation in the transition state
Magnitude of enthalpy of activation of reactions such as S N 1 and E1
the rate-determining step involves bond dissociation only, which is why the enthalpy of activation is higher than for the S N 2 reaction
Why may the magnitude of activation of reactions such as S N 1 and E1 be lower than expected?
SOLVATION EFFECTS
The carbocation transition state is better solvated than the neutral reactant in a polar solvent.
If the S N 1/ E1 reaction had been carried out in less polar solvent (e.g. diethyl ether), the enthalpy of activation would be much higher and closer to that for a bond dissociation reaction.
Entropy controlled reaction
if ΔS ‡ is the main contributor to ΔG ‡
What is the magnitude of ΔS ‡ usually?
(JK -1 mol -1 )
can be either positive or negative
How do you calculate total entropy of a molecule or activated complex?
the sum of the translational, rotational and internal entropies of the molecule or activated complex
Values of ΔS ‡ for favourable and unfavourable reactions
> -20 JK -1 mol -1 = favourable
-20 to -40 JK -1 mol -1 = grey area (can be favourable or unfavourable)
< -40 JK -1 mol -1 = unfavourable
Entropy of activation for a reaction of two molecules to form one in the rate-determining step
usually leads to very high entropies of activation due to the highly ordered activated complex that is required
Kinetic effects resulting from an isotope change
- at the bond being broken (1º isotope effect)
- elsewhere in the reacting molecule (2º isotope effect)
- in the solvent (solvent isotope effects)
Primary kinetic isotope effects:
How does vibrational frequencies vary with isotope?
there’s a difference in vibrational frequencies of bonds
- force constant, k, isn’t altered by a change in isotope however the reduced mass, 𝜇, is altered by a change in isotope
Primary kinetic isotope effects: considerations to be taken for the isotope effect
- usually hydrogen is transferred to another molecule
- isotope effect is dependent on the nature of the transition state
- three types of vibrations need to be considered at the transition state: bending, antisymmetric stretch and symmetric stretch
Primary kinetic isotope effects: when are maximum isotope effects, no isotope effects and partial isotope effects observed?
- Maximum isotope effect observed when H is half-transferred in the transition state.
- No isotope effect is observed when the H atom is still strongly bonded to the reactant site (k x »_space; k y ) or almost completely transferred to the product site (k x «_space;k y )
- Partial isotope effect is observed when the bond is less or more than half broken in the transition state
