1. Nucleophilic Substitution and Elimination
Alkyl Halides
Nucleophilic Substitution and Elimination

2. Nomenclature of Alkyl Halides
Name halogen as substituent on alkane or cylcoalkane.
Learn common names for some of the simple structures. e.g. chloroform, methylene chloride.
Note degree of substitution - name as type of C it is bonded to (i.e. 10, 20, 30).
Geminal (gem-) dihalide has two halogen atoms bonded to the same carbon.
Vicinal (vic-) dihalide has two halogens bonded to adjacent carbons.
Do problem 6-1, 6-2 and 6-3 of the text.

3. Example Problems:

4. Uses and General Chracteristics
BOND DIPOLE (): + at C, - at X
all reactions based on this.
The bond dipole moments increase in the order: C—I < C—Br < C—F < C—Cl
Physical properties
generally, trends are similar to those seen in alkanes.
bp affected by London forces and dipole-dipole attractions.
Common uses: solvents, anesthetics, freons (refrigerants), pesticides.

5. Preparation of alkyl & allylic halides
Free radical halogenation of alkanes (Chpt 4)
You are expected to know the mechanism by which this transformation takes place.

6. Free radical halogenation of alkenes at allylic position
Preparation of Alkyl Halides
Free radical halogenation of alkenes at allylic position
need to know resonance structures for intermediate & predict major/minor product
See pages of the text. Do problems 6-8 and 6-9.

7. Nucleophilic Substitution (SN)
R—LG + Nuc:  R—Nuc + LG:
Substrate
Reagent/Nucleophile (Nuc)
Leaving Group (LG)
Solvent/Reaction Conditions

8. 1. Identify electrophilic carbon in substrate
2. Identify nucleophilic electrons in nucleophile
3. Identify leaving group in substrate

9. Then draw product(s) 4. Draw substrate without LG but with bond
5. Add Nuc to bond where LG used to be

10. Factors influencing what products are formed
Substrate/steric effects
Strength of nucleophile vs. basicity of nucleophile
Stability of leaving group
Reaction conditions
Polarity of solvent
acidic/neutral/basic

11. Substitution Mechanisms
Continuum of possible mechanisms
Mechanism determined primarily by substrate steric effects
SN2 - methyl, 1º & unhindered 2º
SN º, hindered 2º

12. Bimolecular (SN2) Nucleophilic Substitution
concerted reaction; Nuc attacks, LG leaves
pentacoordinate carbon in transition state
rate depends on conc. of both reactants
Me = methyl group; Et = ethyl group

13. Reaction is “stereospecific”
100 % inversion of configuration
You should know how to represent this
mechanism in an energy diagram!!

14. Factors that Affect SN2 Reaction Rates
Strength of Nucleophile: species with negative charge is a stronger nuc than an analogous neutral species (e.g. -OH > H2O; -NH2 > NH3).
Nucleophilicity increases from left to right across the periodic chart (e.g. -OH > -F).
Nucleophilicity increased down the periodic table (I- > Br- > Cl- > F-) or (-SeH > -SH > -OH).
Solvent: Polar protic solvents (e.g. ethanol, ammonia decrease nucleophilicity. Polar aprotic solvents e.g. (acetonitrile, DMSO, acetone) increase nucleophilicity.

15. Factors that affect SN2 reaction rates
Steric Effects: When bulky groups interfere with a rxn. because of their size, this is called steric hindrance. Steric hindrance affects nucleophilicity, not basicity. (e.g. ethoxide ion is a stronger base than t-butoxide ion). Also, alkyl halide reactivity decreases from methyl to 10 to 20 to 30. In fact, 30 alkyl halides do not react by SN2.
Leaving group: The substrate should have a good leaving group. A good leaving group should be electron withdrawing, relatively stable, and polarizable. They are weak bases. Examples are Cl-, Br-, I-, RSO3-, RSO4-, RPO4-, and neutral molecules such as water, alcohols and amines. Strong bases (OH-, RO-, H2N-) are not good leaving groups!

16. Unimolecular (SN1) Nucleophilic Substitution
Two-step reaction
LG leaves, then Nuc: attacks
Tricoordinate carbocation intermediate
Solvolysis (when solvent is also the nucleophile = SN1 reaction
Rate depends on substrate conc. only

17. Mechanism of SN1 reaction
You must be able to represent this on an energy diagram!

18. Reaction Not Stereoselective Unless Steric Factors Apply
Racemization - not always exactly 50/50. Carbocation can be attacked from the top or bottom face giving both enantiomers.
Steric hindrance gives attack at one side preferentially
Longer-lived carbocations give more racemization, shorter-lived give more inversion

19. Factors Influencing SN1 Reaction Rates
Stability of the carbocation*
Allylic 3° >> 3°  allylic 2° > 2°  allylic 1° >> 1° > Me Carbocations are stabilized by alkyl groups (through hyperconjugation and the inductive effect) and by resonance.
Leaving group stability: the better the leaving group, the faster the reaction.
Solvent polarity: the reaction is favored in polar protic solvents.
* must have neutral to acidic conditions to form carbocation

20. Rearrangement of Carbocations
Large difference in energy (stability) of 3° vs. 2° C+
H- (hydride) or R- will shift (migrate) to adjacent position to form more stable carbocation. E.g. when neopentyl bromide is boiled in methanol, only rearranged product is formed.

21. Elimination Reactions
May proceed by a unimolecular (E1) or bimolecular (E2) mechanism.
In an alkyl halide, when a halide ion leaves with another atom or ion, the reaction is an elimination.
If the halide ion leaves with H+, the reaction is called a dehydrohalogenation.

22. Elimination Mechanisms
Mechanism determined primarily by substrate steric effects

23. E1 mechanism

24. E1 & SN1 Competition
Always
by definition a nucleophile is Lewis Base

25. Carbocations generally always give both products
Relative amounts not easily predictable
Always assume formed in approximately equal amounts

26. E2 is Stereospecific
anti-coplanar elimination of H and LG

27. Product Distribution in E2
Seytzeff Product, most substituted
major with small base, i.e., ethoxide, small LG +
major
minor
R2C=CR2 > R2C=CHR > RHC=CHR > R2C=CH2 > RHC=CH2
Decreasing alkene stability

28. E2 Mechanism Concerted, anti-coplanar,  Stereospecific
strong base & good LG

29. Elimination is stereospecific

30. E1 E2 Comparison of SN1 and SN2 Base strength unimportant
Substrates: reactivity order is 3o > 2o > 1o
Solvent: good ionizing solvent required
Rate: depends on substrate conc. only
Stereochemistry: no particular geometry required for slow step; Saytzeff rule followed
Rearrangements: very common
Strong bases required
Substrates: reactivity order is 3o > 2o > 1o
Solvent polarity is not so important
Rate: depends on conc. of substrate and base.
Stereochemistry: coplanar arrangement required in transition state; Saytzeff rule followed
Rearrangements: not possible