Exam 2 Reaction Mechanisms

What are good leaving groups?

• Halogens

  • I- > Br- > Cl- > > > > > > F-

• Sulfonates

  • -OMs

  • -OTs

  • -OTf

What are bad leaving groups?

• -OH

• -OR

• -R (C or H)

What makes a good nucleophile for Sn2?

1. Charge: Nuc with - charge generally better than neutral

2. Basicity: decrease across a row

   1. H₂N- > -OH/-OR > NH3/NR3 > H2O

3. Solvent Effects:

   1. Polar Protic solvents: MeOH, ROH, R=O-OH, H2O

      1. I- > Br- > Cl- > F-

   2. Polar Aprotic solvents: =O, acetonitrile, DMF, DMSO, THF, dimethyl ether

      1. F- > Cl- > Br- > I-

4. Polarizability: bigger size = more ability to shift e- cloud = more nucleophilic

5. Steric Hinderance: bigger size/bulkier = less reactivity

   1. Common bulky: LDA

What are good Sn2 nucs?

• H2N-

• -OH/-OR

• R-SH

• R-S^-

• R=O-O^-

• -CN

• Benzene attached to O-

• -C triple bonded to C-R

• Azide N3-

What is the general pKa rule for good leaving groups?

conj pKa less than/equal to 0

What is general pKa rule for good nucleophile for Sn2?

conj acid pKa less than or equal to 10

What is pKa of protic solvents?

less than 20

What is pKa of aprotic solvents?

greater than or equal to 20

Does Sn2 favor aprotic or protic solvents?

Aprotic

For Sn1, what is involved in rate equation?

Just the concentration of the electrophile

What is important about the steps of Sn1?

All steps are reversible

When is Sn1 possible?

1. Good LG on 2 or 3 alpha C OR resonance-stabilized 1C⁺

2. Weak nucleophiles

   1. Alcohols (R-OH)

   2. Thiols (R-SH)

   3. Water

3. Polar protic solvent

When is it possible to convert a bad LG to a good LG in Sn1?

If you have a strong acid or sulfonate

Why are carbocations unstable?

Due to empty p-orbital

What is hyperconjugation? What does it have to do with carbocations?

Interaction between p-orbital and sigma bond of new adjacent atom

• Sigma bond is source of e- density to stabilize p orb

• 3C⁺ has more hyperconjugative interactions and therefore is the most stable C⁺

What is the inductive effect? What does it have to do with carbocations?

Stabilizes empty p-orbital

• Alkyl group (CH3) donates e- density from sigma bond directly attached to C⁺

Why can resonance-stabilized 1C⁺ do Sn1?

Beta atom with lone pairs leads to stabilizing lone pair effect

Why are oxocarbocation's especially good for resonance?

Fufills octet rule

Why does Sn1 lead to scrambling of any chiral aC?

Because the empty p-orbital allows nucleophile to attack from top and bottom

Why is Sn1 faster in polar protic solvents?

The partial negative on the protic solvent stabilizes the high energy C⁺

What are the 2 requirements for nucleophile for Sn1?

• Nuc has to be able to form a new sigma bond

• Nuc should have a conj pKa < 5

What are nucleophiles just for Sn2?

• NH2

• Benzene connected to O-

• -C

• -CN

• S-

• O-

• RCOO-

What are nucleophiles for both Sn1 and Sn2?

• Cl-

• Azide (N3-)

• Thiol

• Br-

• I-

What are nucleophiles just for Sn1?

• Alcohols

• Water