nucleophilic substitution and elimination reactions (copy)

2 most common reactions in ochem

substitution: nucleophile attacks an α carbon to trade place with a halogen

elimination: a base attacks a β proton to form a double bond

what do nucleophiles and bases have in common?

they both have at least one pair of electrons

2 reasons why alkyl halides undergo substitution and elimination reactions

1. the halogen creates a partial positive on the alpha carbon, making it susceptible to a nuc. attack

2. the halogen is a good leaving group

what makes a halogen a good leaving group

pK_a< 0

conjugate bases of strong acids

α vs β carbon

α carbon: the carbon connected to the halogen/substituent

β carbon: the carbon connected to the α carbon

primary, secondary, and tertiary alkyl halides

primary 1^o: 1 β carbon attached to an α carbon

secondary 2^o: 2 β carbons attached to an α carbon

tertiary 3^o: 3 β carbons attached to an α carbon

S reactions

S_N1: S: substitution, N: nucleophilic, 1: unimolecular (1st order)

• stepwise: (1) loss of a leaving group, (2) nucleophilic attack at α carbon

• Rate = k[substrate]

• does not require backside attack resulting in racemization

S_N2: S: substitution, N: nucleophilic, 2: bimolecular (2nd order)

• concerted: loss of the leaving group and nucleophilic attack happen at the same time

• Rate = k[substrate][nucleophile]

• aprotic solvent preferred

• requires backside attack resulting in inversion of configuration

why do nucleophiles attack from the back in S_N2 reactions?

steric hinderance: electron density repels the nuc from the front side

S_N2 prefers 1^o because a lack of steric hinderance from β carbons

what factors make a strong nucleophile

polarizability, charge, and solvent

anions are strong nucleophiles

E reactions

E₁: E: elimination, 1: 1st order

• Rate = k[base]

• stepwise: (1) loss of a leaving group, (2) nucleophilic attack at β proton

• does not require backside attack

E₂: E: elimination, 2: 2nd order

• Rate = k[alkyl halide][base]

• concerted: loss of the leaving group and nucleophilic attack happen at the same time

• protic solvent preferred

• requires backside attack

how E and Z are related to cis and trans structures

(Z) cis

(E) trans

how do alkyl groups stabilize pi carbon bonds

via hyperconjugation

mono-substituted (least stable): a pi bond with 1 substituent

di-substituted: a pi bond with 2 substituents

tri-substituted: a pi bond with 3 substituents

tetra-substituted (most stable): a pi bond with 4 substituents

weak base

weak nucleophile

3^o: S_N1 and E1

weak base

strong nucleophile

1^o: Sn2

2^o: Sn2

3^o: Sn1

strong base

strong nucleophile

1^o: Sn2 (E2 minor)

2^o: E2 (Sn2 minor)
3^o: E2

strong base

weak nucleophile

1^o: E2

2^o: E2
3^o: E2

NaH, DBN, DBU, t-BuO^-

strong base

non nucleophilic

HO^-, MeO^-, EtO^-

strong base

strong nucleophile

I^-, Br^-, Cl^-, RS^-, HS^-, RSH, H₂S

weak base

strong nucleophile

H₂O, MeOH, EtOH

weak base

weak nucleophile