Substitution and Elimination Reaction of Alkyl Halides

Substitution and Elimination Reaction of Alkyl Halides

I. SN2 ⇒ Bimolecular Nucleophilic Substitution

A. SN2Mechanism ⇒ Concerted (one-step) backside attack and displacement of halide – penta-valent transition state

B. SN2Stereochemistry ⇒Stereospecific ⇒Inversion of configuration results due to backside attack

C. SN2Kinetics

1. Rate law ⇒ rate = k[alkyl halide][nucleophile]

2. SN2 Rate factors:

a. as concentration of the halide and/or nucleophile ↑ rate ↑

b. the weaker the base the better the leaving group ⇒ R-I > R-Br > R-Cl > R-F

(this is true for SN2, SN1, E2 and E1)

c. steric hindrance on the halide slows the reaction down ⇒ methyl > 1° > 2° (3° is too hindered and will not undergo an SN2 reaction)

d. stronger nucleophiles react faster

i. negative nucleophiles are stronger than neutral⇒ HO– > H2O

ii. smaller nucleophilic atoms are stronger in aprotic solvents⇒ CH3O–CH3S–

iii. larger nucleophilic atoms are stronger in protic solvents⇒ CH3O–CH3S–

iv. stronger bases are stronger nucleophiles if comparing nucleophilic atoms comparable in size (within the same period)⇒ CH3O–PhO–AcO–

v. bulky groups attached to the nucleophilic atom slow the reaction down⇒

HO–EtO– > t-BuO–

vi. aprotic solvents > protic solvents because protic solvents hinder the nucleophile with strong ion-dipole forces

II. SN1⇒Unimolecular Nucleophilic Substituion

A. SN1 Mechanism ⇒ two steps ⇒ Step 1: leaving group ionizes resulting in a carbocation intermediate – slowest or the rate determining step

watch out for possible rearrangement and/or resonance

Step 2: nucleophile associates with the carbocation

B. SN1 Stereochemistry ⇒ non-stereospecific ⇒ due to the planar geometry of the carbocation intermediate the nucleophile can approach from both sides of the plane resulting in a racemic or almost racemic mixture with a little bit more inversion (due to intimate ion pairing)

C. SN1 Kinetics

1. Rate Law ⇒ rate = k[alkylhalide]

2. SN1 Rate factors:

a. as the concentration of the halide ↑ the rate ↑

b. the weaker the base the better the leaving group ⇒ R-I > R-Br > R-Cl > R-F

(this is true for SN2, SN1, E2 and E1)

c. the more stable the carbocation the faster the rate ⇒ benzyl > allyl > 3°

(2° and 1° will not undergo SN1 reactions)

d. protic solvents stabilize the carbocation

note⇒ the strength and/or size of the nucleophile has no effect on the rate of an SN1 reaction

III. E2 ⇒ Bimolecular Elimination

A. E2 Mechanism ⇒ concerted ⇒ base removes a proton from the β-carbon (adjacent to carbon with the halide aka the α-carbon) forming a π bond and displacing the leaving group

1.

B. E2Stereochemistry ⇒ stereospecific anti-elimination ⇒ the proton on the β-carbon has to be 180° with respect to the leaving group – in cyclohexane the leaving group and the proton on the β-carbon must be in the axial positions in order to be 180°

When there’s more than one proton on the β-carbon that can undergo anti-elimination the reaction will select for the alkene with the bulkiest groups trans to one another

C. E2 Regiochemistry ⇒ E2 reactions are regioselective when there’sβ-carbon with a proton that can do anti-elimination

1. If the halide is Cl, Br or I and the base is unhindered ⇒

benzyl/allyl β-carbon > 3° β-carbon > 2° β-carbon > 1° β-carbon

2. If the halide is F and/or the base is hindered ⇒

benzyl/allyl β-carbon > 1° β-carbon > 2° β-carbon > 3° β-carbon

D. E2 Kinetics

1. E2 Rate law ⇒ rate = k[alkyl halide][base

2. E2 Rate factors:

a.a. as concentration of the halide and/or base ↑ rate ↑

b. the weaker the base the better the leaving group ⇒ R-I > R-Br > R-Cl > R-F

(this is true for SN2, SN1, E2 and E1)

c. the stronger the bas the faster the reaction

d. protic solvents

e. allyl/benzyl halides > 3° > 2° > 1°

IV. E1⇒Unimolecular Elimination

A. E1 Mechanism ⇒ 2 steps ⇒ Step 1:leaving group ionizes resulting in a carbocation intermediate – slowest or the rate determining step

watch out for possible rearrangement and/or resonance

Step 2: base removes proton from β-carbon forming a π bond

B. E1 Stereochemistry ⇒ because the reaction takes place in two steps anti-elimination is no longer an issue therefore resulting in alkenes with the bulkiest groups trans every time

C. E1 Regiochemistry ⇒ regioselective ⇒reactions are regioselective when there’s β-carbon with a proton that can be eliminated

benzyl/allyl β-carbon > 3° β-carbon > 2° β-carbon > 1° β-carbon

D. E1 Kinetics

1. E1 Rate law ⇒ rate = k[alkyl halide]

2. E1 Rate factors

a. as the concentration of the halide ↑ the rate ↑

b. the weaker the base the better the leaving group ⇒ R-I > R-Br > R-Cl > R-F

(this is true for SN2, SN1, E2 and E1)

c. the more stable the carbocation the faster the rate ⇒ benzyl > allyl > 3°

(2° and 1° will not undergo E1 reactions)

d. protic solvents stabilize the carbocation