Lecture 5

Ionic reactions Q. What is called chemical reactions? Ans. In a chemical reaction, pre-existing bonds are broken and new bonds are formed. Q. What are ionic reactions? Ans. If bond breaking and bond making take place in a heterolytic fashion the reaction is called ionic reaction. On the other hand, if bond breaking and bond making take place in a homolytic fashion, the reaction is called a free radical reaction.

Ionic Reactions : 1) Nucleophilic substitution : 2) Eletrophilic substitution : 3) Nucleophilic addition : 4) Eletrophilic addition : 5) Rearrangements :

Nucleophilic Substitution at a saturated carbon : Two types of discrete mechanism : S N 1SN2SN2 Substitution Nucleophilic unimolecular Substitution Nucleophilic Bimolecular

S N 2 mechanism : 2 nd order kinetics Q. Are all SN 2 reactions follow 2 nd order kinetics? Ans. If Y - is in large excess as compared to R-X, ( eg. If solvent is the nucleophile) then Pseudo – first order reaction Effect of structure and solvent : Which mechanism will be operative will depend on structure and solvent polarity.

T.S. for S N 2 Inversion of configuration (Walden inversion) Why backside attack? To ensure maximum overlapping leading to stability of T.S.

Important Point to Remember : Inversion of configuration does not mean R going to S or vice versa. It means that bond formation takes place opposite to that of bond breaking….…..which leads to the inversion. it is like inversion of umbrella in a storm. Problem : Rate of racemization = 2 * rate of inversion or incorporations

For S N 1 : Racemization is expected Extent of inversion = extent of retention However, due to ion pair formation, more inversion then retention. Ion pair mechanism : More inversion then retention. Problem : Rate of solvolysis in EtOH : Explain?

Lecture - 6

Factors Affecting the Rates of S N 1 and S N 2 reactions : 1)The structure of the substrate 2)Concentration and Reactivity of Nucleophile (for bimolecular reactions only) 3) The effect of solvent. 4) The nature of leaving group Effect of substrate structure : For S N 2 methyl > primary > secondary >> tertiary (unreactive)

Solvent effect For S N 1 : Greater the ionizing ability of the solvent, faster will be the reaction. Dielectric constant reflects the ionizing ability. Rate of increase of [ Br - ] increases with increase in proportion of water. Dielectric constant Q. What will be the effect of solvent polarity on the following S N 1 reaction?

Effect of Nucleophile : Nucleophilicity of 1) A negatively charged nucleophile is always stronger than its conjugate acid. 2) In a group of nucleophiles in which nucleophilic atom is the same, nucleophilities parallel basicities. 3) In polar protic solvents, in a particular group, nucleophilicity increases as we go down the group. 4) In polar aprotic solvents, reverse trend follows :

Hammond’s postulate : In a particular step, the T.S. resembles the entity (substrate, product or intermediate) that is closer in energy. In S N 1, carbocation ( R + ) is the intermediate. T.S. should resemble more of the carbocation. T.S. stability will be reflected in the stability of the carbocation.

Reason : Steric effect Steric hindrance offered by R 1 / R 2 / R 3 to the approach of Nucleophile. If R 1 or R 2 or R 3 is bulky, this steric hindrance will slow down the reaction. For S N 1 : Stability of carbocation determines the rate.

S N 2 Inversion of configuaration S N 1 ideally Racemization Retention of configuaration : S N i ( substitution nucleophilic internal) However, it can’t be a simple S N 2. Problem :

Neighbouring Group Participation : “Retention” “Anchimeric asssitance” In presence of, carboxylate will be produced. Double Inversion = Retention Qn. Hydrolysis of EtS–CH 2 CH 2 – Cl is 10 4 times faster than that of EtO–CH 2 CH 2 –Cl. Explain?

Biological Nucleophilic Substitution :