Teaching of substitution reaction iitbhu.pptx

Sn reaction notes

1. Aliphatic Nucleophilic substitution reactions

2. Nucleophilic substitution reactions A reaction in which a nucleophile displaces a leaving group and takes its position is called a  nucleophilic substitution reaction. In this reaction nucleophile selectively attacks the electrophile to make a new bond.

3. Major Factors Involved in the NS Reaction Substrate Nucleophile Leaving group Solvent

4. Substrates for Nucleophilic Substitution Reactions In general Alkyl halides are the best substrates for NS reactions A positively charged (+) species usually attached with a leaving group

5. Nucleophiles : A  nucleophile  is a chemical species that donates an electron pair to an  electrophile .  Nucleophiles can be negatively charged molecules or neutral molecules

6. A molecular fragment that leaves with a pair of electrons in heterolytic bond cleavage Leaving groups Leaving groups are also nucleophiles and consider to be weak Lewis bases Leaving groups can be negatively charged molecules or neutral molecules Halogen leaving groups S ulfonate Leaving groups Neutral leaving groups

7. Solvents: A medium used for dissolving the reactants Non-polar solvents are not suitable of NS reaction e.g. Hexane

8. Types of Nucleophilic substitution reactions Nucleophilic substitution can occur under different mechanistic pathways (Majority of them are one of the following…) SN1 (Substitution nucleophilic unimolecular   reaction) SN2 (Substitution nucleophilic bimolecular  reaction) SNi (Substitution nucleophilic internal  reaction)

9. Types of nucleophilic substitution 1) S N 1 (Substitution nucleophilic unimolecular   reaction) This implies that the rate determining step of the mechanism depends on the decomposition of a single molecular species. Best Example for SN1 reaction: Solvolysis of tert -alkyl halides

10. S N 1 Mechanism : Multi-steps reaction (at least two steps) It is a unimolecular reaction because, Reaction rate only depends on a formation of carbocation which is a slow process. Rate (R)= k(Substrate) Rate (R)= k[(CH 3 ) 3 CCl] For the particular reaction

11. Energy profile Diagram Multi-step reactions have intermediates and a several transition states (TS).  In an SN1 there is loss of the leaving group generates an intermediate carbocation which is then undergoes a rapid reaction with the nucleophile .. 

12. Energy profile Diagram

13. Examples for SN1 reaction

14. Stereochemistry Ideally SN1 reaction provides Racemic Mixture

15. 2) S N 2 (Substitution nucleophilic bimolecular  reaction) Rate of the reaction depends on two substrates. Types of nucleophilic substitution Example: Kinetic data show that the rate of reaction depends on the concentration of both reactants, which suggests a bimolecular reaction with a one-step mechanism. This is an example of an S N 2 (substitution nucleophilic bimolecular) mechanism.

16. S N 2 Mechanism : Single step reaction One step reaction: nucleophilic attack and dismiss of a leaving group takes place simultaneously .   Examples of SN2 reactions

17. Energy profile diagram

18. All S N 2 reactions proceed with backside attack of the nucleophile , resulting in inversion of configuration at a stereogenic center. Stereochemistry of the S N 2 reaction

19. examples of S N 2 inversion of configuration: The Walden Inversion .

20. Factors affecting SN1 and SN2 Nucleophilic reactions are mainly defended on the following factors Substrate (Primary Vs Secondary Vs Tertiery carbon ) Nucleophile ( charged Vs neutral) Leaving group Solvent (polar protic Vs polar aprotic )

21. Substrates Play Important Role in Deciding Mechanism of the NS reaction More Stable carbocation : More number of hyperconjugation and Inductive effect Less steric hindrance for the back side attack

22. SN 1 Reaction Rate

23. SN2 Rate of the reaction

24. Nucleophile Prefers SN2 Mechanism Prefers SN1 Mechanism Negatively charged nucleophiles like HO ¯ and HS¯ are used as salts with Li + , Na + , or K + counterions to balance the charge. Since the identity of the counterion is usually inconsequential, it is often omitted from the chemical equation.

25. Nucleophile in predicting SN1 vs SN2 mechanisms: The strong nucleophile favors an S N 2 mechanism. The weak nucleophile favors an S N 1 mechanism. H 2 O

26. Nucleophilicity does not parallel basicity when steric hindrance becomes important. Steric hindrance is a decrease in reactivity resulting from the presence of bulky groups at the site of a reaction. Steric hindrance decreases nucleophilicity but not basicity . Sterically hindered bases that are poor nucleophiles are called non nucleophilic bases . The Nucleophile : Size effect

27. The leaving group is the third factor. A better leaving group increases the rate of both S N 1 and S N 2 reactions. Leaving Group in predicting SN1 vs SN2 mechanisms:

28. Polar protic solvent has a hydrogen atom attached to a strongly electronegative element (e.g. oxygen) that forms hydrogen bonds. - Polar protic solvent solvate cations and anions effectively while aprotic solvents do not solvate anions to any appreciable extend. - Polar protic solvents are more suitable for S N 1 reactions, while aprotic solvents are used for S N 2 reactions Example of polar protic solvents Solvent effect: Polar protic solvent

29. Polar Protic solvent in SN1 reaction Polarization Stabilization

30. Polar Protic solvent in SN2 reaction For SN2 reaction: We need Strong Nucleophile e.g. NaOMe

31. Solvent effect: Polar Aprotic solvents Polar aprotic solvents are those solvents whose molecules do not have a hydrogen atom that's attached to an atom of an electronegative element. Polar aprotic solvents also exhibit dipole—dipole interactions, but they have no O—H or N—H bonds. Thus, they are incapable of hydrogen bonding. Examples of polar aprotic solvents

32. Polar aprotic solvent in SN2 reaction Strong “free” Nu Polar aprotic solvent increases the reactivity of SN2 reaction

33. In polar aprotic solvents, nucleophilicity parallels basicity , and the stronger base is the stronger nucleophile . Because basicity decreases as size increases down a column, nucleophilicity decreases as well. F highest nucleophilicity and I lowest If we consider NaBr as nucleophile in SN2 Rxn

34. Solvent Vs halogen Nucleophile

35. Rearrangements in SN1 reactions

36. examples

37. H vs alkyl Shift

38. S N i ( S ubstitution N ucleophilic I nternal) I nternal Transfer of nucleophile SNi reaction is a reaction in which substitution of a nucleophile takes place internally

39. S N i : stereochemistry We get Retention of configuration

40. SNi reaction

41. Sni with pridine

42. Nucleophilic substitution at allylic Carbon What is allylic Carbon? An allylic carbon is a carbon that attached immediate next to the double bond

43. Allyl halides such as chlorides, bromides and iodides are good substrates for substitution reactions. A variety of nucleophiles can be used to generate a range of new functional groups.

44. Reactivity of Allylic carbon in NS rxn Solvolysis of allyl halides are >100 Times Faster than simple alkyl halides Allyl carbocations are stabilized by resonance

45. SN1 or SN2 reactions in Allyl substrate Allylic Substrates can undergo either SN1 or SN2 depends on substrate, nucleophile

46. Simple example Products cannot be distinguished

47. SN 1 vs SN 1 Prime (SN' 1 ) Reactions --------SN 1 ------- SN' 1 Prime Reaction Allylic rearrangement

48. SN 1 vs SN 1 Prime (SN' 1 ) Reactions --------SN 1 ------- SN' 1 Prime Reaction Allylic rearrangement

49. SN2 Vs SN2 prime (SN' 2 ) Reactions

50. SN2 Vs SN2 prime (SN' 2 ) Reactions

51. Neighbouring group participation The role of the nucleophilic atom in the substrate in the overall reaction is known as neighbouring group participation or anchimeric assistance. 1. Slow reaction 2. Fast reaction The second reaction is very fast, Because sulfur participate in the reaction as shown in the mechanism No Neighbouring group effect. Slow Rxn Neighbouring group effect. Fast Rxn

52. Some examples…

53. Over all mechanism Two SN2 reactions taking place.

54. Stereochemistry in NGP Silver ion here act as electrophilic catalyst & ease the removal of bromine More Imporatant : low concentrated nucleophile will be used to occur N.G.P Retention of configuration

55. Simple SN 2 When nucleophile concentration will be higher in reaction medium then normal SN2 reaction will undergo & product will be with inversion of configuration

56. Other Examples Participates in SN2 Back attack Not Participates in SN2 Back attack

57. Thank you