1. Chapter 6 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 SN2Reaction
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 SN2 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 SN2 Reactions
Nucleophiles approaches from the back side, that is directly opposite the leaving group.
Consider the cis-1-chloro-3-methylclyclopentane
When undergoes SN2, the product become trans

15. examples
Give the structure of the product that would be formed when trans-1-bromo-3-methylcyclobutane undergoes an SN2 reaction with NaI

16. A mechanism for SN1Reaction

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 SN1 reaction
2 step reaction
1st 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
The step is intrinsically slower than all other is called the rate-limiting step or rate determining step

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

22. Mechanism for SN1 Reaction
Show a complete mechanism with stereochemisty for the following reaction

23. Mechanism for SN1 Reaction
Show a complete mechanism with stereochemisty for the following reaction

24. Factors Affecting the Rates of SN1 and SN2 Reactions
The structure of the substrate,
The concentration and reactivity of the nucleophile
The effect of the solvent
The nature of the leaving group

25. The Effect of the Structure of the substrate
SN2 reaction shows the following general order of reactivity
Methyl > primary > secondary >> (tertiary – unreactive)
steric hindrance
SN1 reaction
Tertiary > secondary > methyl
Hyperconjugation between p orbitals

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

27. 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 H2O 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- >> RCO2- >> ROH > H2O
equilibrium favors the side with weaker acid

28. Solvent Effects on SN2 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

29. Solvent Effects on SN2 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 > N3- > Br- > CH3CO2- > Cl- > F- > H2O

30. Solvent Effects on SN2 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

31. Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solvent
They cannot form H-bond because their postive centers are well shielded by the steric effects from any interaction with anions
Rate of SN2 reaction generally increased when they are carried out in a polar protic solvent

32. Solvent Effects on SN1 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 SN1 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

33. Summary of SN1 and SN2 Reactions
Factor
SN1
SN2
Substrate
3o (requires formation of a relatively stable carbocation)
Methyl > 1o > 2o (requires unhindered substrate)
Nu:
Weak Lewis base, neutral molecule
Nu: may be the solvent
Strong Lewis Base, rate increased by high concentration of Nu:
Solvent
Polar Protic (e.g alcohol, water…)
Polar protic (e.g DMF, DMSO
Leaving Group: I > Br > Cl > F for both SN1 and SN2
( the weaker the base after the group departs
the better the leaving group)