Chemical Principle

Kinetics give insight into mechanism (Unimolecular, Bimolecular,RDS etc)

First order kinetics unusual but not impossible

Rate law more complicated with late RDS

Higher order rate law => Implied late RDS

Identify product, intermediates and rate law to disprove mechanism

No mechanism will be completely proved by this process, only disproved

Change parts to test mechanism, e.g. radical introduction, base etc.

Isotopic labelling useful here (Change one or two based on desired effect)

Crossover experiments - Tests whether or not reaction intramolecular or intermolecular

Labels all over the place here to see where they mix (Inter = same molecule) 

Hammett uses pka of corresponding acids to investigate if rate correlated directly

Checked to see the effects of changing pka (Conformational change or steric)

Sigma x for any group x (Instead of pka for EDG or EWG)

Sigma x in relation to H (Overall polar effects by substituent x)

Sigma x = log(Kx/Kh) or Sigma x = pka(H)-pka(X)

Graphically, EWG = +ve Sigma x, EDG = -ve Sigma x

Log k vs Sigma x gives gradient of Rho

Sigma x combines inductive and mesomeric effects

If negative charge delocalises, Rho increases drastically

Not always linear due to through conjugation. Sigma x+ and Sigma x-

Meta = Sigma x, para EWG = Sigma x- and Sigma x, Para EDG = Sigma x+ and Sigma x

Both Sigma + and - are obtained as follows

• Plot log(kx/kh) against Sigma (Meta)x
• Obtain Rho from Gradient
• Use Log(Kx/Kh) = Rho Sigma(+ or -)

Yukawa-Tsuno equation: Log(Kx/Kh) = Rho(Sigma x +r(Sigma x+ - Sigma x)

r = New reaction parameter (Measure of through conjugation)

Rho Values

• Large - Rho: Positive charge on ring or deloalised around benzene ring
• Moderate - Rho : e- flow out of the transition state, + charge near ring, loss of conjugation
• Moderate + Rho: e- flow into transition state, - charge near ring, loss of conjugation
• Large + Rho: negative charge on ring or delocalised around benzene ring

Uses of Hammett plots:

• Calculate k or K for new substrates for a specific reaction of a specific compound.
• Uncover and compare mechanisms
• Better understanding of the transition state (e.g. 2 mechanistic probes)
• Indicate change in mechanism 

Two types of non-linear: Concave upwards and concave downwards

Essentially, 2 mechanisms exist dependant on sigma (EWG vs EDG)

Upwards indicates that reaction operates based on fastest mechanism for that group type (EWG vs EDG) - Mechanism change with substituent

Downwards indicates reaction rate is always limited by slowest step in the mechanism - Change in the RDS

Increase or decrease in entropy from SM to TS

• Positive delta s :Increase in entropy, decrease in order (e.g. 1 molecule to 2 molecules)
• Negative delta s :Decrease in entropy, increase in order (e.g. 2 molecules to 1 molecule) 

Large negative values are common (Bimolecular, pericyclic) 

Entropy indicates whether unimolecular or otherwise and can discount mechanisms.

Specific acid catalysis (SAC) : protonation with specific acid (Strong) followed by slow step. Protonated compound is much more reactive. e.g. ester hydrolysis

More acid = Faster rate, dependence of rate upon acid concentration/presence

SAC requires pH similar to or below pKa of substrates conjugate acid

SBC : Rapid deprotonation with a strong base in a fast pre-equilibrium 

Most base catalysed reactions are SBC

SBC rate depends on Ph equal to or higher than starting materials

Its common for SAC and SBC to occur in the same reaction e.g. ester hydrolysis (Depends on pH)

Removal of a proton on a heteroatom is always fast, on C can be RDS

These reactions experience an inverse solvent isotope effect where the reaction is faster in deuterated solvent

Only D2O is a good catalyst

Weak bases do not operate via SBC. 

e.g. ester formation from anhydrides. Base deprotonates nucleophile as nucleophile attacks anhydride.

Termolecular so very unfavourable. Huge -ve entropy = > Massive excess of reagent needed.

KIE= Kinetic isotope effect: Changes in rate when H is replaced by D

KIE = KH/KD , C-D bond is much stronger than C-H

Longer bond between C-D means stronger hydrogen bonding.

Assumptions are made:

• Isotopic substitution does not change the potential energy surface of the reaction or the energies of excited states
• Only mass dependent properties are affected namely vibrational frequencies

4 classifications of KIE: 1^o, 2^o, Normal and Inverse

Isopomers: Compounds having same number of each isotopic atom but differing in position (Isotopic isomers)

Isotopologues: Compounds differing only in thier isotopic composition

Deuterium prefers the bond with the higher force constant

Heavy atom isotopic effects are measurable but very small (1.07 for C12 vs C14)

Quantum tunnelling gives rise to massive KIE values. Tunnelling is where particles pass through an energy barrier as opposed to over it.

This happens with 4 hallmarks;

• Difference in Ea for H and D must be greater than the differences in thier ZPEs
• Temperature has little effect on rate with reactions proceeding even near to 0K
• large -ve entropy of activation implies TS structure is highly ordered
• The heavy atoms in TS move very little and only the hydrogen atoms are transferred

GBC : General base catalysis. Weak bases

Evidence: If rate of reaction changes with conc. of base at same pH, GBC

Normal KIE: I.e KH>KD

Catalyst is too weak a base to deprotonate target reagent

Catalyst removes a proton which is becoming more acidic in the RDS

GAC: General acid catalysis  (Termolecular again so massive -ve entropy)

GAC involves transfer of a proton from a weak acid during RDS

Termolecular problem can be overcome but the reaction being intramolecular

Effective at neutral pH even if above pKa of conjugate acid of substrate

Catalyst adds proton to a site which is becoming more basic in the RDS