1. Nucleophilic substitution and elimination reactions
Alkyl halides
Nucleophilic substitution and elimination reactions

2. Alkyl halides - industrial sources

3. Alkyl halides - industrial sources

4. Preparation from alcohols
SOCl2 - thionyl chloride

5. Halogenation of hydrocarbons

6. Addition of HX to alkenes

7. Addition of halogens to alkenes and alkynes

8. Finkelstein reaction

9. Nucleophilic substitution reactions
The halide ion is the conjugate base of a strong acid. It is therefore a very weak base and little disposed to share its electrons.
When bonded to a carbon, the halogen is easily displaced as a halide ion by stronger nucleophiles - it is a good leaving group.
The typical reaction of alkyl halides is a nucleophilic substitution:

10. Nucleophiles reagents that seek electron deficient centres
negative ions or neutral molecules having at least one unshared pair of electrons

11. Leaving groups
a substituent that can leave as a weakly basic molecule or ion

12. Nucleophilic substitution
A knowledge of how reaction rates depend on reactant concentrations provides invaluable information about reaction mechanisms. What is known about this reaction?

13. Nucleophilic substitution
[CH3Br]I [OH-]I initial rate
0.001 M 1.0 M 3 x 10-7 molL-1s-1
0.002 M 1.0 M 6 x 10-7 molL-1s-1
0.002 M 2.0 M 1.2 x 10-6 molL-1s-1
rate a [CH3Br]
[OH-]
rate = k[CH3Br][OH-]

14. Order - a summary
The order of a reaction is equal to the sum of the exponents in the rate equation.
Thus for the rate equation rate = k[A]m[B]n, the overall order is m + n.
The order with respect to A is m and the order with respect to B is n.

15. Nucleophilic substitution
[(CH3)3CBr]I [OH-]I initial rate
0.001 M M 4 x 10-7 molL-1s-1
0.002 M 1.0 M 8 x 10-7 molL-1s-1
0.002 M 2.0 M 8 x 10-7 molL-1s-1
rate a [(CH3)3CBr]
[OH-]0
rate = k[(CH3)3CBr]

16. The SN2 mechanism rate = k[CH3Br][OH-] References of interest:
E.D. Hughes, C.K. Ingold, and C.S. Patel, J. Chem. Soc., 526 (1933)
J.L. Gleave, E.D. Hughes and C.K. Ingold, J. Chem. Soc., 236 (1935)

17. Stereochemistry of the SN2 reaction

18. Stereochemistry of the SN2 reaction
A Walden inversion.
P. Walden, Uber die vermeintliche optische Activät der Chlorumarsäure und über optisch active Halogen-bernsteinsäre, Ber., 26, 210 (1893)

19. The SN1 mechanism

20. Carbocations
G.A. Olah, J. Amer. Chem. Soc., 94, 808 (1972)

21. Carbocation stability
Hyperconjugation stabilizes the positive charge.

22. Stereochemical consequences of a carbocation

23. Stereochemical consequences of a carbocation
Why?

24. Stereochemical consequences of a carbocation
retention
inversion predominates

25. Carbocation rearrangements
Williamson ether synthesis
a rearrangement and elimination

26. Carbocation rearrangements
1,2 hydride and alkyl shifts

27. Carbocation rearrangements

28. Steric effects in the SN2 reaction
Look at the transition state to see how substituents might affect this reaction.

29. Steric effects in the SN2 reaction
The order of reactivity of RX in these SN2 reactions is
CH3X > 1o > 2o > 3o

30. Steric effects in the SN2 reaction

31. Structural effects in SN1 reactions
3o > 2o > 1o > CH3X

32. RO- > HO- >> RCO2- > ROH >H2O
Nucleophilicity
Rates of SN2 reactions depend on concentration and nucleophilicity of the nucleophile.
A base is more nucleophilic than its conjugate acid:
CH3Cl + H2O  CH3OH2+ slow
CH3Cl + HO-  CH3OH fast
The nucleophilicity of nucleophiles having the same nucleophilic atom parallels basicity:
RO- > HO- >> RCO2- > ROH >H2O

33. I- > Br- > Cl- > F-
Nucleophilicity
When the nucleophilic atoms are different, their relative strengths do not always parallel their basicity.
In protic solvents, the larger the nucleophilic atom, the better:
I- > Br- > Cl- > F-
In protic solvents, the smaller the anion, the greater its solvation due to hydrogen bonding. This shell of solvent molecules reduces its ability to attack.

34. Nucleophilicity
Aprotic solvents tend to solvate cations rather than anions. Thus the unsolvated anion has a greater nucleophilicity in an aprotic solvent.

35. Polar aprotic solvents
These solvents dissolve ionic compounds.

36. Solvent polarity more polar
transition state less solvated than reagents
A protic solvent will decrease the rate of this reaction and
the reaction is 1,200,000 faster in DMF than in methanol.

37. Solvent polarity less polar more polar
greater stabilization by polar solvent
The transition state is more polarized.
Therefore the rate of this reaction increases with increase in solvent polarity.
A protic solvent is particularly effective as it stabilizes the transition state by forming hydrogen bonds with the leaving group.

38. Solvent polarity
Explain the solvent effects for each of the following second order reactions:
a) 131I- + CH3I  CH3131I + I-
Relative rates: in water, 1; in methanol, 16; in ethanol, 44
b) (n-C3H7)3N + CH3I  (n-C3H7)3N+CH3 I-
Relative rates: in n-hexane, 1; in chloroform,

39. I- > Br- > Cl- > H2O > F- > OH-
Leaving group ability
Weak bases are good leaving groups.
They are better able to accommodate a negative charge and therefore stabilize the transition state.
Thus I- is a better leaving group than Br-.
I- > Br- > Cl- > H2O > F- > OH-

40. SN1 v SN2 SN1 SN2 kinetics: 1st order second order
reactivity: 3o > 2o > 1o > CH3X CH3X > 1o > 2o > 3o
rearrangements no rearrangements
partial inversion inversion of configuration
eliminations possible

41. Problems
Try problems 6.6 – 6.11 and 6.14 – 6.16 in chapter 6 of Solomons and Fryhle.

42. Functional group transformations using SN2 reactions
R = Me, 1o, or 2o

43. Problems
Try problems 6.12 and 6.17 in chapter 6 of Solomons and Fryhle.

44. ROH + HX - an SN reaction

45. Experimental facts 1. The reaction is acid catalyzed
2. Rearrangements are possible
3. Alcohol reactivity is 3o > 2o > 1o < CH3OH

46. The mechanism

47. Reaction of primary alcohols with HX
SN2