Inversion of configuration Unit 4 - 4 4/11/2017 SN1 and SN2 Reactions SN1 SN2 Rate =k[RX] =k[RX][Nuc:-] Carbocation intermediate? Y N Stereochemistry mix Inversion of configuration Rearrangement ~H, ~ CH3 possible No rearrangements

Unimportant, but usually weak Better than nucleophile Unit 4 - 4 4/11/2017 SN1 and SN2 Reactions SN1 SN2 Substrate 3°>2°>”1°” CH3X>1°>2° Nucleophile Unimportant, but usually weak Strong and unhindered Leaving group Excellent Better than nucleophile Solvent Polar and ionizing Polar aprotic

SN1 and SN2 Reactions Do not occur with vinyl halides or aryl halides. Unit 4 - 4 4/11/2017 SN1 and SN2 Reactions Do not occur with vinyl halides or aryl halides. Consider the carbocation formed for SN1. Consider the backside attack for SN2.

Elimination Reactions The substitution reaction mechanisms you have learned are just part of the picture. In the SN1 and SN2 reactions, the species that acts as a nucleophile may also act as a base and abstract a proton. This causes the elimination of HX and the formation of an alkene. An elimination reaction can occur along with the substitution reaction.

Elimination B:- is a species acting as a base. Since HX is lost, this particular reaction is called a dehydrohalogenation.

E1 Reactions E1 = elimination, unimolecular Rate = k[substrate] (a first order process) The rate-limiting step is the formation of the carbocation, the same as for SN1 (that’s why E1 competes).

E1 Reaction Mechanism Step 1: The substrate forms a carbocation intermediate (rate-limiting step). Step 2: Methanol acts as a base and removes H+(fast step).

E1 Reaction Profile rate = k[(CH3)3Br] k = Ae -EA(step 1)/RT Unit 4 - 4 4/11/2017 E1 Reaction Profile rate = k[(CH3)3Br] -EA(step 1)/RT k = Ae

E1 Occurs with and Competes with SN1 When bromocyclohexane is heated with methanol, two products are possible. Can you draw the mechanism that leads to each product?

E1 Reactions E1 reactions are exothermic. E1 reactions occur in at least two steps and compete with SN1 reactions. The first step is slow. It is the formation of the carbocation intermediate. The second step is fast. It is the abstraction of H+ from the carbocation by the base.

Factors Affecting E1 Reactions Structure of the substrate Can a stable carbocation be formed? Strength of the base Nature of the leaving group The solvent in which the reaction is run. Must be able to stabilize the carbocation and the LG (which is usually an ion).

Factors Affecting E1 Reactions - Structure of the Substrate The most important factor influencing the rate of E1 reactions is the stability of the carbocation formed. Stability of carbocation: 3° > 2° >1° Relative rates for E1: 3°>2°≈1°(resonance)

Factors Affecting E1 Reactions - Strength of the Base The rate is not much affected by the strength of the base. Weak bases will work.

Factors Affecting E1 Reactions - the Leaving Group The LG should be good.

Factors Affecting E1 Reactions - Solvent Effects The solvent must be capable of dissolving both the carbocation and the leaving group. E1 reactions require highly polar solvents that strongly solvate ions. Typical solvents: water, an alcohol, acetone (to help the alkyl halide to dissolve), or a mix.

Rearrangements in E1 Reactions The carbocation can undergo a structural rearrangement to produce a more stable species. hydride shift (~H) methyl shift (~CH3) If ionization would lead to a 1° carbocation, look for a rearrangement to occur. Ionization rates can be increased by the addition of reagents such as AgNO3 (how?); however, Ag is not cheap.

A Hydride Shift Can Occur in Either SN1 or E1 Reactions CH3OH ~H -H+ -Br - SN1 What would the E1 products be?

A Methyl Shift Can Occur in Either SN1 or E1 Reactions CH3OH ~CH3 -H+ SN1 What would the E1 product be?

Zaitsev’s Rule When two or more elimination products are possible, the product with the more substituted double bond will predominate.

Zaitsev’s Rule When two or more elimination products are possible, the product with the more substituted double bond will predominate. Alkyl groups are electron-donating and contribute electron density to the π bond. Bulky groups can be more widely separated.

E1 Reactions - Summary The structure of the carbocation is the most important factor: Relative rates for E1: 3°>2°. The base is typically weak or moderate in strength. The LG should be good. The solvent should be polar and protic to stabilize the carbocation and LG. Products can exhibit rearrangements and will follow Zaitsev’s Rule.