Sn2 reaction

Complete Sn2 reaction

1. S N 2 Reaction Present by- Akash Dubey

2. Nucleophilic Substitution R = aliphatic as well as aromatic Nucleophile + Substrate Product + Leaving group

3. Nucleophilic Substitution S N 2 S N 1 S: Substitution N: Nucleophilic 1: unimolecular S: Substitution N: Nucleophilic 2: Bimolecular Y C X C Y + X + C + leaving group goes first and nucleophile comes later Y C X C Y X + + nucleophile attacks and leaving group goes simultaneously

4. S N 2  R ea c t i on and mechanism K inetics S tereochemistry of SN2 reaction Factors affecting SN2 reaction- The structure of substrat e Effect of n ucleophiles Effect of l eaving groups Effect of s olvents Phase transfer catalysis –Role of crown ether

5. S N 2 reaction and mechanism Transition state

6. Mechanism of SN2 reaction activation energy:  G 1 activation energy:  G 2 (R)-2-bromobutane (S)-2-butanol E n ergy reaction coordinate reaction coordinate Inversion of configuration Steric effect

7. Synthetic Utility of the S N 2 Reaction A variety of functional groups can be prepared employing a good nucleophile and an electrophile with a good leaving group:

8. Obtained experimentally: Rate law includes both the alkyl halide and the nucleophile, a second- order process S N 2 reaction : Kinetics

9. S N 2 reaction : Stereochemistry

10. S N 2 MECHANISM R C C H 3 H A ttacks back lobe nucleophilic attack (R)-config .. H O .. : (S)-config C R H B . . r .. : : H .. O . . : C H 3 INVERSION

11. Stereochemistry of S N 2 Walden inversion

12. n R H C H 3 C : Br R H C H 3 H O : C C CH 3 H Br H O H O . . : . . activated complex is trigonal planar (sp 2 ) (R)-configuration (S)-configuration C onfiguration is inverted Ea HO C B partial bonding R 2 p THE INVERSION PROCESS sp 3 s p 3 sp 2

13. S N 2 r e a c ti o n : s ubs t ra t e structure  Less bulky  Should stabilize the transition state

14. S N 2 Reaction: substrate structure KI in Acetone at 25° k r el 1 5 1 0.008 unreactive! CH 3 Br CH 3 CH 2 Br CH 3 C H B r CH 3 CH 3 C B r CH 3 CH 3

15. Relative rates of S N 2 reactions of alkyl chlorides with the iodide ion relative rate Alkyl chloride Me Cl 2 C l . 2 M e O C l 9 2 C l O 1,00,000 The rates are given with respect to n-BuCl

16. H al O R N u - N u O R Me C l C l H C l  * of the C=O  * of of the C-Cl H N u only S N 2, no S N 1 R = alkyl, aryl, OR' Relative rates of S N 2 reactions with iodide ion O 1 : 5 N u C l H H +  * of the C=O C=O group stabilizes the T.S. by Overlap of its  * orbital with full P-orbital of the C-atom under attack

17. S N 2 reaction : Effect of Nucleophile  The nucleophilicity may be correlated with the availability of the electron pairs and the ease with which it is donated

18. Trends in Nuc. Strength Increases down Periodic Table, as size and polarizability increase: I - > Br - > Cl - >F - Of a conjugate acid-base pair, the base is stronger: OH - > H 2 O, NH - > NH 2 2 3

19. Polarizability and nucleophilicity - increased polarizability makes for a better nucleophile I- > Br- > Cl- >F-

20. CH 3 O H 3 C I CH 3 OH H 3 C I CH 3 OCH 3 C H 3 O C H 3 H I I + + Effect of Nucleophile : The nucleophilicity may be correlated to its basicity as both involve the availability of the electron pairs and the ease with which it is donated rapid v e r y slow + + N u cle op hi lic it y of 3 CH O 3 CH OH > A negatively charged nucleophile is always stronger than its conjugate acid. Stronger base better nucleophile weaker base poorer nucleophile H O CH 3 O H 2 N > > > H 2 O CH 3 O H NH 3 The direct relationship between basicity and nucleophilicity is maintained if the reaction occurs in the gas phase

21. S N 2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic.

22. A good leaving group needs to be a Stable anions that are weak bases which can delocalize charge S N 2 reaction : E ffect of leaving group

23. The Leaving Group

24. Sulfonate Leaving Groups O R O S C H 3 O B r O para -Toluenesulfonate O R O S Tosylate para -Bromobenzenesulfonate Brosylate R OT s R O B s

25. S N 2 reaction : Effect of Solvent

26. Solvent Polar Solvent nonpolar Solvent Polar protic Solvent Polar aprotic Solvent SN2 reaction prefers polar aprotic solvent

27. Solvent Effects (1) Polar protic solvents (O-H or N-H) reduce the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon.

28. Solvent Effects (2) Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile Examples: CH 3 C N acetonitrile O C H 3 C C H 3 acetone di m e t hy l f o r m a m ide (DMF) O C H N C H 3 CH 3

29. M e I + Me N 3 N 3 - N a + + N a I s ol v en t Rat e i n Me O H (   33 ) 1 D M F (   3 7 ) 4.5X10 4 DMF: HCONMe 2 Marked effect on the rate of S N 2 reaction, when that t ransferred from polar protic solvent to polar aprotic solvent. In MeOH both Na + and N 3 - are solvated. In DMF only Na + is solvated, but not N 3 -. So, unsolvated N 3 - is a much more powerful nucleophile DMSO (   46) 1 X 10 9 DMSO: Me 2 SO

30. S N 2 o r S N 1? Primary or methyl Strong nucleophile Polar aprotic solvent  Rate = k [halide] [Nuc]  Inversion Tertiary Weak nucleophile (may also be solvent) Polar protic solvent, silver salts Rate = k [halide]  Racemization  No rearrangements  Rearranged products =>

31. Important substrates……..

32. Allylic and Benzylic compounds Allylic and benzylic compounds are especially reactive in S N 1 reactions. Even though they are primary substrates, they are more reactive most other halides! They form resonance stabilized carbocations. CH 2 -Br CH 2 =CH-CH 2 -Br benzyl bromide allyl bromide

33. C H 2 C H 2 e t c + + + + e t c C H 2 C H 2

34. Allylic and Benzylic compounds Allylic and benzylic compounds are especially reactive in S N 2 reactions. They are more reactive than typical primary compounds! CH 2 -Br CH 2 =CH-CH 2 -Br benzyl bromide allyl bromide

35. For S N 2: stabilisation of TS by conjugation with allylic  - bond B r N u H N u H Br  (-)  (- ) N u + T . S. B r + T .S.  ( -) H H N u  ( -)

36. BENZYL ( GOOD FOR S N 1 ) IS A L S O A GOOD S N 2 SU B S T R ATE C H 2 B r + N a I + C H 2 I N aB r primary, but faster than other primary overlap in the activated complex lowers the activation energy I Br critical o v e rl ap

37. Vinyl and aryl halides

38. Vinyl and aryl halides do not undergo S N 1 because:

39. Vinyl and aryl halides do not undergo S N 2 because:

40. Cyclic systems

41. -- You cannot form a carbocation at a bridgehead position. You can’t have p orbitals on a bridgehead position rigid bicyclic molecule. + X + “steric rigidity” B r +

42. Problems : Br Br Br 1 1 - 6 1 - 1 4 2) Rate of solvolysis in EtOH : relative rate C H 3 C H 2 B r 1 C H 3 C H 2 C H 2 B r 2.8X10 -1 M e 2 H C C H 2 B r 3.0X10 -2 M e 3 C C H 2 B r 24.2X10 -6 1) S N 2 reaction by Et O - in Et OH: Expl ain ? Br B r 1 10 -23 1-bromotriptycene Expl ain ? Rigid structure, cation empty p-orbitals are at right angles to  orbitals of Ph Explain? cc at bridge head, less stable, difficult to attain planarity due to rigidity A) B)