1. Ionic Reactions Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

2. Organic Halides Alkyl Halides: alkane molecule in which a halogen has replaced a hydrogen

3. Physical Properties Of Organic Halides Low solubilities in water Miscible with each other and other relatively nonpolar solvent E.g CH2Cl2 CHCl3 CCl4

4. Reaction Intermediates 3 major types Carbocation (C+) Carbanion (C-) Free radical (C· )

5. Reaction Sites Nucleophiles: (nucleus-loving) any species containing electron pairs Electrons are (-), so Nu: are attracted to (+) site Charge Nu: are better than neutral one E.g

6. Reaction Sites Electrophiles (electron-loving): any species or site in molecule that’s deficient in electron density because it’s near a electronegative atom or lacking of e- altogether

7. Multiple bonds The electrons are available to be donated to another species

8. Nucleophilic Substitution Reactions General Reaction

9. Reaction Schemes

10. Leaving Groups Relatively stable, weakly basic molecule or anion Halogen atom of an alkyl halide is a good leaving group because once departed it is a weak base and table anion

11. A mechanism for S N 2Reaction The nucleophile approaches the carbon bearing the leaving group from the back side Directly opposite the leaving group As the reaction progresses, the bond between nucleophile and the carbon strengthens, and the bond between the carbon atom and the leaving group weakens Carbon atom has its configuration turned inside out  inversion

12. Transition State Arrangement of the atoms in which nucleophile and the leaving group are both partially bonded to the carbon atom undegoing substitution Bond breaking and forming and occurred simultaneouly Concerted reaction

13. Kinetics of a Nucleophilic substitution: an S N 2 reaction 1 step reaction Second order Rate of reaction depends an alkyl halides and Nu: Rate Rxn = k [alkyl halide] x [Nu:]

14. Stereochemistry of S N 2 Reactions Nucleophiles approaches from the back side, that is directly opposite the leaving group. Consider the cis-1-chloro-3-methylclyclopentane When undergoes S N 2, the product become trans

15. examples Give the structure of the product that would be formed when trans-1-bromo-3-methylcyclobutane undergoes an S N 2 reaction with NaI

16. A mechanism for S N 1Reaction

17. The Relative stabilities of Carbocations The order of stability of carbocations can be explained on the basic of hyperconjugation. Involves electrons delocalization from a filled bonding orbital to an adjacent unfilled orbital Any time a charge can be disperred or delocalized, a system will be stabilized

18. The Relative stabilities of Carbocations

19. Kinetics of a Nucleophilic substitution: an S N1 reaction 2 step reaction 1 st order rate determination Rate of reaction depends the slowest step Heterocleavage of halide Rate Rxn = k [alkyl halide]

20. Multistep Reactions and The Rate-Determining Step

21. The step is intrinsically slower than all other is called the rate-limiting step or rate determining step

22. Transition State Stabilization of leaving group I - > Br - > Cl - > F - Weaker conjugated base  stronger leaving group

23. Mechanism for S N 1 Reaction Show a complete mechanism with stereochemisty for the following reaction

24. Mechanism for S N 1 Reaction Show a complete mechanism with stereochemisty for the following reaction

25. Factors Affecting the Rates of S N 1 and S N 2 Reactions The structure of the substrate, The concentration and reactivity of the nucleophile The effect of the solvent The nature of the leaving group

26. The Effect of the Structure of the substrate S N 2 reaction shows the following general order of reactivity Methyl > primary > secondary >> (tertiary – unreactive) steric hindrance S N 1 reaction Tertiary > secondary > methyl Hyperconjugation between p orbitals

27. Hammond-Leffler Postulate The structure of a transition state resembles the stable species that is nearest it in free energy

28. The effect of the Concentration and Strength of the Nucleophile A negatively-charged nucleophile is always a more reactive nucleophile than its conjugated acid HO - is a better Nu: then H 2 O and RO- is better than ROH In a group of nucleophiles in which the nucleophilic atom is the same, nucleophilicities parallel to basicities RO - > HO - >> RCO 2 - >> ROH > H 2 O equilibrium favors the side with weaker acid

29. Solvent Effects on S N 2 Reactions: Polar Protic and Aprotic solvent The effect of hydrogen bonding with the nucleophile is to encumber the Nu: and hinder its reactivity in a substitution reaction

30. Solvent Effects on S N 2 Reactions: Polar Protic and Aprotic solvent Hydrogen bonds to a small nucleophile atom are more stronger than those to larger nucleophilic atoms Halide Nucleophilic in Protic Solvent I - > Br - > Cl - > F - Larger atoms have greater polarizability  larger nucleophile atom can donate a greater degree of electron density to substrate SH - > CN - > I - > - OH > N 3 - > Br - > CH 3 CO 2 - > Cl - > F - > H 2 O

31. Solvent Effects on S N 2 Reactions: Polar Protic and Aprotic solvent Aprotic solvents are those solvents whose molecules do not have a hydrogen that is attached to an atom of an electronegative element They do the same way as protic solvents solvate cations; by orienting their negative ends around cation and by donating unshared electron pairs to vacant orbitals of the cation

32. Solvent Effects on S N 2 Reactions: Polar Protic and Aprotic solvent They cannot form H-bond because their positive centers are well shielded by the steric effects from any interaction with anions Rate of S N 2 reaction generally increased when they are carried out in a polar protic solvent

33. Solvent Effects on S N 1 Reactions: The Ionizing Ability of the solvent The use of polar protic solvent will greatly increase the rate of ionization of an alkyl halide in S N 1 reaction Able to solvate cations and anions more affectively Stabilize transition state leading to the intermediate carbocation and halide ion more than it does the reactant Lower activation energy

34. Summary of S N 1 and S N 2 Reactions FactorSN1SN1SN2SN2 Substrate3 o (requires formation of a relatively stable carbocation) Methyl > 1 o > 2 o (requires unhindered substrate) Nu:Weak Lewis base, neutral molecule Nu: may be the solvent Strong Lewis Base, rate increased by high concentration of Nu: SolventPolar Protic (e.g alcohol, water…)Polar protic (e.g DMF, DMSO Leaving Group: I > Br > Cl > F for both S N 1 and S N 2 ( the weaker the base after the group departs the better the leaving group)

35. Elmination Reactions of Alkyl Halides General Reaction If carbon next to alkyl halide has a halogen, Elimination is possible Require a strong base

36. Dehydrohalogenation General Reaction Elements of hydrogen halide are eliminated from a haloalkane

37. 1,2 Elimination Alpha (α) carbon atom: carbon that bears the substituent Beta (β) hydrogen atom: hydrogen that attached to the carbon adjacent to α carbon

38. Bases used in Dehydrohalogenation

40. Mechanism for E2 Reaction

41. Example Show a complete mechanism for E2 reaction

42. Mechanism for E1 Reaction Unimolcular reaction

43. Example Show a complete mechanism for E1 reaction

44. Substitution Versus Elmination As a rule: If your subsitution mechanism is S N 1, E1 is the elimination mechanism If your substitution mechanism is S N 2, E2 is the elmination mechanism 2 o alkyl halides: if 2 o ; weak Nu: E1 if 2 o ; strong Nu: E2

45. Substitution Versus Elmination

46. Examples Prove the possible mechanisms (S N 1, S N 2, E1 and/or E2) and possible products for the reaction below