Sn reaction


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Sn reaction

  1. 1. Reactions Ionic reactions: Radical reactions:Bond breaking and bond Bond breaking and bond makingmaking take place in a take place in aheterolytic fashion homolytic fashion -R X R+ + X R X R. + X.
  2. 2. Ionic Reactions :1) substitution : Y + R X R Y + X R = aliphatic as well as aromatic2) elimination : 3) addition : R1 R1 X H R1 XH X + Y R2 Y R2 Y R2 X = O , NH
  3. 3. Nucleophilic Substitution
  4. 4. Nucleophilic Substitution Y + R X R Y + X R = aliphatic as well as aromaticNucleophile + Substrate Product + Leaving group
  5. 5. Nucleophilic Substitution S N1 S N2 S: Substitution S: Substitution N: Nucleophilic N: Nucleophilic 1: unimolecular 2: Bimolecularleaving group goes first and nucleophile comes laterY + C X C+ C Y + X nucleophile attacks and leaving group goes simultaneously Y + C X C Y + X
  6. 6. SN2 reaction and mechanism kinetics stereochemistry substrate structure nucleophiles leaving groups solvents
  7. 7. SN2 reaction and mechanism
  8. 8. Synthetic Utility of the SN2 ReactionA variety of functional groups can be prepared employing a goodnucleophile and an electrophile with a good leaving group: 9
  9. 9. SN2 reaction : Kinetics
  10. 10. The Rate Law of an SN2 ReactionObtained experimentally: Rate law includes both the alkyl halide and the nucleophile, a second- order process 12
  11. 11. SN2 reaction : Stereochemistry
  12. 12. SN2 MECHANISM nucleophilic attack R (R)-config ..H O: .. .. C : Br : .. CH3 Rattacks Hback lobe .. H O: .. CINVERSION CH3 (S)-config H
  13. 13. Stereochemistry of SN2 Walden inversion =>
  14. 14. THE INVERSION sp2 R 2p HO C BPROCESS partial bonding HO C Br activated complex CH3 H is trigonal planar (sp2 ) configuration .. R sp3 is invertedH O: .. R sp3 C : Br Ea HO : C CH3 H CH3 (R)-configuration H (S)-configuration
  15. 15. SN2 reaction : substratestructure
  16. 16.  Less bulky Should stabilize the transition state
  17. 17. SN2 Reaction: substrate structureKI in Acetone at 25° krel CH3 Br 150 CH3 CH2 Br 1 CH3 CH Br 0.008 CH3 CH3 unreactive! CH3 C Br CH3
  18. 18. Relative rates of SN2 reactions of alkyl chlorides with the iodide ion The rates are given with respect to Alkyl chloride relative rate n-BuCl Me Cl 200 0.02 Cl Me 920 O Cl O Cl 1,00,000
  19. 19. O O Nu- only SN2, no SN1 Hal Nu R R R = alkyl, aryl, OR Relative rates of SN2 reactions with iodide ion O Cl 1:500 Me Cl C=O group stabilizes the T.S. by Overlap of its π* orbital with full P-orbital of the C-atom under attack σ * of of the C-Cl + +π* of the C=O Cl π* of Cl H the C=O H H H Nu Nu
  20. 20. SN2 reaction : Effect of Nucleophile
  21. 21.  The nucleophilicity may be correlated with the availability of the electron pairs and the ease with which it is donated
  22. 22. 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- > H2O, NH2- > NH3
  23. 23. Polarizability and nucleophilicity - increasedpolarizability makes for a better nucleophile I- > Br- > Cl- >F-
  24. 24. 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 CH3O + H3C I CH3OCH3 + I very CH3OH + H3C I CH3OCH3 + HI slow Nucleophilicity of CH3O > A negatively charged nucleophile is CH3OH always stronger than its conjugate acid. Stronger base weaker base better nucleophile poorer nucleophile HO > H2O CH3O > CH3OH H2N > NH3The direct relationship between basicity and nucleophilicityis maintained if the reaction occurs in the gas phase
  25. 25. SN2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic. =>
  26. 26. SN2 reaction : Effect of leaving group
  27. 27. •A good leaving group needs to be aStable anions that are weak baseswhich can delocalize charge 31
  28. 28. The Leaving Group
  29. 29. Sulfonate Leaving Groups O R O S CH3 R OTs O para-Toluenesulfonate Tosylate O R O S Br R OBs O para-Bromobenzenesulfonate Brosylate
  30. 30. SN2 reaction : Effect of Solvent
  31. 31.  Solvent Polar Solvent nonpolar Solvent Polar protic Solvent Polar aprotic SolventSN2 reaction prefers polar aproticsolvent
  32. 32. 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. =>
  33. 33. Solvent Effects (2) Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile Examples: OCH3 C N O C CH3 acetonitrile H N C CH3 H3C CH3 => dimethylformamide acetone (DMF)
  34. 34. Marked effect on the rate of S N 2 reaction, when that transferred frompolar protic solvent to polar aprotic solvent. solvent Me I + N3-Na+ Me N3 + NaI Rate in MeOH (ε = 33) 1 DMF (ε = 37) 4.5X104 DMF: HCONMe2 DMSO (ε = 46) 1X109 DMSO: Me2SO • 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
  35. 35. SN1 reaction and mechanism kinetics stereochemistry substrate structure nucleophiles leaving groups solvents
  36. 36. SN1: reaction and mechanism
  37. 37. Solvolysis of tert-Butyl Bromide CH3 CH3 acetoneCH3 C CH3 + H2O CH3 C CH3 + H Br Br OH + other products
  38. 38. SN1: Mechanism carbocation 1935: Hughes & Ingold
  39. 39. SN1 reaction : Kinetics
  40. 40. SN1 Reaction: kinetics Thereactions follows first order (unimolecular) kinetics Rate = k [R-Br]1
  41. 41. Reaction profile for SN1 reaction slow fastR LG LG + R R Nu Nu Rate = K[R-LG]
  42. 42. SN1 reaction : Stereochemistry
  43. 43. S N 1: Hydrolysis of t -butyl chloride by base proceed according to Rate = k 1 [ t -BuCl] or independent of [OH - ] Me HO Me fast Me Me Me - slow OH Me Cl + fast Me Me - Me Me OH 3 2 Me OH sp sp Me1. Halide undergoes slow ionization to yield the ion pair R + and Cl - followed by first attack by – OH or solvent or nuleophile.2. The energy necessary to effect the initial ionization is largely recovered from the energy evolved through solvation of the resultant ion-pair.
  44. 44. SN1 reaction : substratestructure
  45. 45.  Stability of carbocation
  46. 46. CH3 CH3 C Br > CH3 CH Br > CH3-CH2-Br > CH3-Br CH3 CH3 tertiary secondary primary CH3 + + + CH3 CH CH3 CH 2 CH3 CH3 C+ CH3 CH3 tertiary secondary primary very unstable carbocation carbocation carboc carbocation carbocation (very stable) (unstable)three methyl two methyl one methyl no methyl groups groups group groups
  47. 47. SN1 Reaction: substrate structure krelCH3 Br no reactionCH3 CH2 Br 1.00CH3 CH Br 11.6 CH3 CH3 6CH3 C Br 1.2 x 10 CH3 Solvolysis in water at 50°C
  48. 48. SN1 reaction : Effect of Nucleophile
  49. 49. Nucleophiles in SN1 Since nucleophilic addition occurs after formation of carbocation, reaction rate is not normally affected by nature or concentration of nucleophile (weak nucleophile)
  50. 50. A protic solvent acts as both asolvent and nucleophile in S N 1 reactions - solvolysis: Water O H H abbreviations O HOMe Methanol H CH3 Ethanol O CH3 HOEt H CH2 Acetic acid O HOAc H C CH3 O Formic acid O H C H O
  51. 51. SN1 reaction : Effect of leaving group
  52. 52. Leaving groups Leaving groups are the same as in S N2 reactions:
  53. 53. SN1 reaction : Effect of Solvent
  54. 54. Solvent effect Increase in dielectric constant and/or ion-solvating ability result in a marked increase in reaction rateDielectric constant (ε, at 25 C): H2O 79 EtOH 25
  55. 55.  Polar protic solvents favoring the SN1 reaction since it stabilizes carbocation of the transition state Protic solvents disfavor the SN2 reaction by stabilizing the ground stateTransfer from polar, protic to polar, aprotic solventscan change the reaction mode from SN1  SN2
  56. 56. Things to remember
  57. 57. SN2 or SN1? Primary or methyl  Tertiary Strong nucleophile  Weak nucleophile Polar aprotic (may also be solvent) solvent  Polar protic solvent, Rate = k [halide] silver salts [Nuc]  Rate = k [halide] Inversion  Racemization No rearrangements  Rearranged products =>
  58. 58.  Competition reaction in SN1
  59. 59. Rearrangements Carbocations can rearrange to form a more stable carbocation. Hydride shift: H- on adjacent carbon bonds with C+. Methyl shift: CH3- moves from adjacent carbon if no H’s are available. =>
  60. 60. Hydride Shift Br H HCH3 C C CH3 CH3 C C CH3 H CH3 H CH3 H HCH3 C C CH3 CH3 C C CH3 H CH3 H CH3 H H Nuc CH3 C C CH3 Nuc CH3 C C CH3 => H CH3 H CH3
  61. 61. Methyl Shift Br CH3 CH3CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 CH3 CH3CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 CH3 CH3 Nuc NucCH3 C C CH3 CH3 C C CH3 => H CH3 H CH3
  62. 62. Important substrates……..
  63. 63. Allylic and Benzylic compounds
  64. 64. Allylic and Benzylic compoundsAllylic and benzylic compounds are especially reactive inSN1 reactions.Even though they are primary substrates, they are morereactive most other halides! They form resonancestabilized carbocations. CH2-Br CH2=CH-CH2-Br benzyl bromide allyl bromide
  65. 65. ++CH2 CH2 etc ++CH2 CH2 etc
  66. 66. Allylic and Benzylic compounds Allylic and benzylic compounds are especially reactive in SN2 reactions. They are more reactive than typical primary compounds! CH2-Br CH2=CH-CH2-Br benzyl bromide allyl bromide
  67. 67. For S N 2: stabilisation of TS by conjugation with allylic π-bond + δ(-) + + δ(-) + Br Nu Nu H H Br H H Nu Br δ(-) Nu δ(-) T.S. T.S.
  68. 68. BENZYL ( GOOD FOR SN1 )IS ALSO A GOOD SN2 SUBSTRATE primary, but faster than other primary CH2 Br + NaI CH2 I + NaBr I overlap in the activated H complex lowers the activation energy H Br critical overlap
  69. 69. Vinyl and aryl halides
  70. 70. Vinyl and aryl halides do not undergo SN1 because: 76
  71. 71. Vinyl and aryl halides do not undergo SN2 because: 77
  72. 72. Cyclic systems
  73. 73. rigid bicyclic molecule.You can’t have p orbitals on a -- You cannot form abridgehead position carbocation at a bridgehead position. X Br + cannot become + planar “steric rigidity” +
  74. 74. Problems : 1) S N 2 reaction by EtO - in EtOH: CH3CH2 Br CH3CH2CH2 Br Me2HCCH2 Br Me3CCH2 Br Explain ?relative rate 1 2.8X10-1 3.0X10-2 24.2X10-6 2) Rate of solvolysis in EtOH : Br Br Explain? A) Br cc at bridge head, less stable, difficult to attain planarity due to rigidity 1 10-6 10-14 Br Br B) Explain ? A) Rigid structure, cation empty p-orbitals are at right angles to π orbitals of Ph 1 10-23 1-bromotriptycene