Determination of Reaction Mechanism

Question 1

Substituent effect

Answer 1

the manner in which the reactivity of the molecule changes when substituents are changed

Question 2

Resonance effects

Answer 2

reflect the ability of an atom or a group of atoms to withdraw or donate electrons through ⫪-bonds

Question 3

Inductive effects

Answer 3

reflect the ability of an atom or a group of atoms to withdraw or donate electrons through σ-bonds

Question 4

Examples of substituent effects

Answer 4

• resonance effects
• inductive effects
• field effects
• polarisability effects
• steric effects

Question 5

What are linear free energy relationships (LFERs) used for?

Answer 5

to quantify substituent effects

Question 6

What does a larger absolute value of σ mean (irrespective of sign)?

Answer 6

larger substituent effect

Question 7

What does the magnitude of the substituent effect depend on?

Answer 7

the combination of resonance and inductive effects

Question 8

What does a positive substituent effect indicate?

Answer 8

strong electron-withdrawing resonance effect

Question 9

What does a negative substituent effect indicate?

Answer 9

strong electron-donating resonance effect

Question 10

Reaction constant, 𝜌

Answer 10

the sensitivity of the reaction to the substituent change

Question 11

What is the reaction constant for the ionisation of substituted benzoic acids?

Answer 11

by definition 𝜌 = + 1.00
(for a plot of acidity constants of X-substituted benzoic acids against σ _x )

Question 12

What is σ _x ?

Answer 12

the Hammett substituent constants

Question 13

Signs of 𝜌 for rate - σ correlations:
𝜌 > 0 (positive 𝜌 value)

Answer 13

increase in electron density in the transition state near to or on the benzene ring (as for the ionisation of benzoic acid)

Question 14

Signs of 𝜌 for rate - σ correlations:
𝜌 < 0 (negative 𝜌 value)

Answer 14

decrease in electron density in the transition state near to or on the benzene ring

Question 15

Signs of 𝜌 for equilibrium - σ correlations:
𝜌 > 0 (positive 𝜌 value)

Answer 15

increase in electron density in the product near to or on the benzene ring

Question 16

Signs of 𝜌 for equilibrium - σ correlations:
𝜌 < 0 (negative 𝜌 value)

Answer 16

decrease in electron density in the product near to or on the benzene ring

Question 17

What does a large absolute value of 𝜌 suggest?

Answer 17

Larger absolute value of 𝜌 (irrespective of sign) = Larger sensitivity to substituent change

Question 18

Magnitude of 𝜌:
|𝜌| > 1

Answer 18

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

Question 19

Magnitude of 𝜌:
|𝜌| < 1

Answer 19

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

Question 20

How does the magnitude of the Hammett 𝜌- value change with position of the reaction centre?

Answer 20

the magnitude of 𝜌 decreases as the reaction centre moves further away from the substituted benzene ring

Question 21

Substituent scales: σ ^-

Answer 21

for groups that stabilise negative charge by direct resonance

Question 22

Substituent scales: σ ⁺

Answer 22

for groups that stabilise positive charge by direct resonance

Question 23

The σ ^- scale

Answer 23

this scale is based upon the ionisation of p-substituted phenols for which groups like nitro can stabilise the negative charge by direct resonance

Question 24

The σ ⁺ scale

Answer 24

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)

Question 25

Example of a reaction that shows better correlations with the σ ⁺ scale

Answer 25

electrophilic aromatic substitution

Question 26

What are the two types of non-linear Hammett Correlations?

Answer 26

1. a gradual curve (or concave downwards curve) in a Hammett plot indicates a change in rate-limiting step as the substituents change 2. an abrupt change in the slope of a Hammett plot indicates a change in mechanism as the substituents change

Question 27

Hammond's Postulate

Answer 27

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

Question 28

Thermodynamic control

Answer 28

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

Question 29

Kinetic control

Answer 29

product composition is controlled by the relative rates of formation of products (the relative stabilities of the products don't matter)

Question 30

Reaction conditions for equilibrium control (thermodynamic control)

Answer 30

- longer reaction times - increased reaction temperature - addition of a catalyst

Question 31

Conditions for sulfonation of aromatic rings: kinetic vs thermodynamic

Answer 31

Kinetic control: 120ºC, conc H ₂ SO ₄ / SO ₃ Thermodynamic control: 160ºC, conc H ₂ SO ₄ / SO ₃

Question 32

The Curtin-Hammett Principle

Answer 32

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

Question 33

Enthalpy controlled reaction

Answer 33

if ΔH ^‡ is the main contributor to ΔG ^‡

Question 34

What is the magnitude of ΔH ^‡ usually? (kJ mol ^-1 )

Answer 34

normally either positive (endothermic) or approximately zero

Question 35

Concerted reactions

Answer 35

(e.g. Diels-Alder and SΔH _N 2 reactions) Bond formation and bond cleavage occur at the same time in the reaction

Question 36

Magnitude of enthalpy of activation for concerted reactions

Answer 36

they can be very small and close to zero as long as bond cleavage is matched by bond formation in the transition state

Question 37

Magnitude of enthalpy of activation of reactions such as S _N 1 and E1

Answer 37

the rate-determining step involves bond dissociation only, which is why the enthalpy of activation is higher than for the S _N 2 reaction

Question 38

Why may the magnitude of activation of reactions such as S _N 1 and E1 be lower than expected?

Answer 38

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.

Question 39

Entropy controlled reaction

Answer 39

if ΔS ^‡ is the main contributor to ΔG ^‡

Question 40

What is the magnitude of ΔS ^‡ usually? (JK ^-1 mol ^-1 )

Answer 40

can be either positive or negative

Question 41

How do you calculate total entropy of a molecule or activated complex?

Answer 41

the sum of the translational, rotational and internal entropies of the molecule or activated complex

Question 42

Values of ΔS ^‡ for favourable and unfavourable reactions

Answer 42

> -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

Question 43

Entropy of activation for a reaction of two molecules to form one in the rate-determining step

Answer 43

usually leads to very high entropies of activation due to the highly ordered activated complex that is required

Question 44

Kinetic effects resulting from an isotope change

Answer 44

- at the bond being broken (1º isotope effect) - elsewhere in the reacting molecule (2º isotope effect) - in the solvent (solvent isotope effects)

Question 45

Primary kinetic isotope effects: How does vibrational frequencies vary with isotope?

Answer 45

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

Question 46

Primary kinetic isotope effects: considerations to be taken for the isotope effect

Answer 46

- 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

Question 47

Primary kinetic isotope effects: when are maximum isotope effects observed?

Answer 47

- Maximum isotope effect observed when H is half-transferred in the transition state.

Question 48

Primary kinetic isotope effects: when are no isotope effects observed?

Answer 48

- No isotope effect is observed when the H atom is still strongly bonded to the reactant site (k _x >> k _y ) or almost completely transferred to the product site (k _x << k _y )

Question 49

Primary kinetic isotope effects: when are partial isotope effects observed?

Answer 49

- Partial isotope effect is observed when the bond is less or more than half broken in the transition state

Question 50

What are examples of primary isotope effect reactions?

Answer 50

- Acetate ion catalysed enolisation of acetone - Nitroethane ionisation - Elimination reactions - Electrophilic aromatic sulfonation

Question 51

When are 2º kinetic isotope effects observed?

Answer 51

when isotopic changes are made elsewhere in the molecule (i.e. the reacting atoms are not changed)

Question 52

What are the two main 2º kinetic isotope effects?

Answer 52

- ɑ- Secondary isotope effect - β-Secondary isotope effect

Question 53

What is ɑ-Secondary hydrogen kinetic isotope effects?

Answer 53

When a hydrogen atom attached to one of the reacting atoms is changed for deuterium, a small kinetic isotope effect may be observed.

Question 54

What is β-Secondary hydrogen kinetic isotope effect?

Answer 54

These small kinetic isotope effect changes are observed mainly for carbocation forming reactions. When a β-hydrogen atom to the developing cationic carbon is changed for deuterium, a small kinetic isotope effect may be observed.

Question 55

Why do ɑ-Secondary hydrogen kinetic isotope effects occur?

Answer 55

due to a change in hybridisation that occurs upon forming the transition state from the reactants

Question 56

Why do β-Secondary hydrogen kinetic isotope effects occur?

Answer 56

due to hyperconjugation

Question 57

Example reactions for secondary isotope effects

Answer 57

- Ionisation of diphenylmethanol in concentrated sulfuric acid - Diels-Alder cycloaddition of butadiene and ethene - Elimination reactions

Question 58

What is the origin of solvent kinetic isotope effects?

Answer 58

- D ₂ O is more viscous than H ₂ O - H ₂ O is more acidic than D ₂ O H ₂ O reactions are faster

Question 59

What are the two different types of acid-base catalysis?

Answer 59

- General catalysis ~ rate-determining proton transfer - Specific catalysis - non rate-determining proton transfer

Question 60

Acidic buffers

Answer 60

A solution that contains comparable concentrations of the weak acid and its conjugate base (much less susceptible to pH changes) - Dissociation of a weak acid in solution is small

Question 61

Example of specific acid catalysis

Answer 61

- Ester hydrolysis

Question 62

Example of general acid catalysis

Answer 62

- Acid-catalysed hydrolysis of enol ethers

Question 63

Specific base catalysis

Answer 63

Only dependent on the concentration of OH- (hydroxide ion) in solution

Question 64

General base catalysis

Answer 64

Reaction rate is dependent on any base, not just OH-

Question 65

Example of general and specific base catalysis

Answer 65

The aldol condensation is specific base catalysed at low concentrations of carbonyl substrates, but general base catalysed at higher concentrations of carbonyl substrates

Question 66

What are two kinetically equivalent mechanisms?

Answer 66

General base catalysis and nucleophilic catalysis (when the catalyst could act as a nucleophile or as a base)

Question 67

How can you distinguish between nucleophilic and general base catalysis?

Answer 67

- Solvent isotope effects (nucleophilic catalysis doesn't expect solvent isotope effects) - Isolation/ identification of intermediate if nucleophilic catalysis - Measurement of a Brønsted Coefficient, β (if 0<β<1: general base catalysis, if β>1 or β<0: nucleophilic catalysis)