Substitution and Elimination of Alkyl halides

1. Intro

Where x = Cl, Br, I

1. Halogen withdraws electron density via induction rendering C electrophilic
2. Halogen serves as LG
3. Alkyl halides classified into 1°, 2°, 3°
4. Solvent effect:
   1) Since SN2 Nuc is generally ionic, polar solvent is required.
   2) Polar solvent, solvates transition state.
   
   

2. SN2 Reactions

Summary
SN2 - Substitution nucleophilic bimolecular.

Concerted mechanism, change in configuration, due to back side attack.
Nuc attack and loss of LG
Rate = k[alkyl halide][nucleophile]
3° < 2° < 1° < CH3 at alpha position due to steric hindrance
Strong Nuc: I-,Br-,Cl-, HS-, RS-, OH-, RO-, NC-
Polar Aprotic Solvent: Acetone, DMF, DMSO, Acetonitrile, HMPA

Polar Aprotic Solvent is ideal for SN2 because it can only neutralize + charge, and as the result - charged Nuc are less stabilize/more reactive

3. E2 Reactions

E2 - Elimination bimolecular. Also known as beta elimination or 1,2 - elimination.

Summary
Concerted mechanism
Proton transfer and loss of LG
Rate = k[alkyl halide][base]
1° < 2° < 3°
Strong Base: NaH, DBN, DBU, OH-, MeO-, EtO-

Stability of alkenes:
1. trans < cis
2. mono < di < tri < tetra substitutions
3. 3 < 4 < 5 < 6 > 7 member rings

Z and E naming system
Sometimes it is hard to assign trans/cis configuration so the E/Z system is used instead:
1. Split the double bond in the middle with 1 carbon on each side.
2. Assign atom priorities based on Chan-Prelog-Ingold rules.
3. Z = same, E = opposite highest priorities.

- if β positions are not identical, double bond can form in two different regions of the molecule and the reaction is said to be regioselective and the products are regioisomers.


- if β has 2 protons both cis and trans sterisomers will be produced, but the trans will predominate.
substrate is not necessarily sterioisomeric, but it can produce two sterioisomeric products that will be major and minor.


- if β has 1 proton only 1 possible sterioisomer will be produced.
For the elimination to occur the halogen and proton must lie in coplanar plane (i.e dihedral angle must be 180°) OR periplanar plane (i.e dihedral angle must be close to 180°)

For stereospecific reaction, it would be wrong to say that the product will always be trans. The product obtained depends on the configuration of the starting alkyl halide:

Quick and Dirty Method:
1. Rotate 3 atoms on one of the carbons to place proton or halide into anti-periplanar position.
2. Redraw the carbon skeleton without halide, proton and geometry. 3. Draw a double bond.


When LG in occupies axial position it is in anti-periplanar conformation with neighboring proton and the reaction can proceed.



Example: