Alkyl Halides: Nucleophilic Substitution and Elimination Reactions

Substitution

leaving group replaced by a nucleophile

Elimination

leaving group and beta hydrogen removed to forma double bond

Basicity

How well a compound shares its lone pair with a proton. Strong bases donate readily

Base Strength Trends

More negative charge
Less electronegative
Smaller atom
Less resonance

Nucleophilicity

How readily a compound can attack an electron-deficient atom. Donates to form a covalent bond

Nucleophilicity Trend

Base strength
Less electronegative

Smaller atoms in polar aprotic solvents
Larger atoms in polar protic solvents
Less steric interference

Polar aprotic (non-ionizing)

solvents don’t contain hydrogen bond donors
smaller atoms are stronger nucleophiles

DMSO, DMF, HMPA, THF, CH3CN, toluene

Polar protic (ionizing)

solvents that contain hydrogen bond donors (H attached to N, O, or S)

H2O, CH3OH, NH3, CH3NH2
Larger atoms are stronger nucleophile (solvation shell)

Strong Nucleophile/Strong Base (SN/SB)

negatively charged carbon, oxygen and nitrogen

bound to spectator

OH-, -OCH3, -NHCH3

Weak Nucleophile/Strong Base (WN/SB)

sterically hindered bases → can’t attack substrate

NaH, N with bulk

Strong Nucelophile/Weak Base

charged compounds not in SB/SN. coupled with spectator
CN-, N3-, -S-R

Weak Nucleophile/Weak Base

neutral oxygen containing compounds
H2O, R-OH

Nucleophible/Base Trends with Substitution and Elimination

Eliminations favor SB/WN bc remove b-H and base accepts P+
Substitution favor SN/WB bc less comp for WB

Leaving Groups

atom/group of atoms displaced by nucleophile
the weaker the base the better the leaving group

Substitution Reaction Concerted vs. Multistep

Concerted is one step (SN2)
Multistep is two steps (SN1/Carbocation)

Substitution Rate Laws

SN2: rate=k[alkyl halide][nucleophile]

SN1: rate=k[alkyl halide]

SN2 Reaction

Primary>Secondary Alkyl Halides

Strong Nucleophile

Polar Aprotic

Inversion of Stereochemistry

Rxn Rate ↓ when ↑ steric interference

SN/WB favors SN2>E2

SN1 Reactions

Tert Alkyl Halides

Weaker Nucleophiles > Stronger (doesn’t affect rate)
Polar Protic

Equal amounts of R/S isomers (more inversion)

Lower temps favor SN1>E1 & E2

Elimination Reactions Concerted vs. Multistep

Concerted is 1 step (E2)
Multistep is 2 step (E1 & Carbocation)

Elimination Reaction Rate Laws

E2: rate = k[alkyl halide][base]

E1: rate = k[alkyl halide]

Zaitsev’s Rules

When multiple beta hydrogens in Elimination, favors more substituted beta hydrogen

Exceptions to Zaitsev’s Rule (Hoffman’s Rule)

Fluorine is leaving group

Base is too bulky

Anti-Periplanar Conformation

When leaving group is present with B-hydrogen (E2), molecule must be in anti-periplanar conformation for E to occur.

Anti & Planar

E2 Reaction

Tert>secondary>primary alkyl halide

Strong Base = faster

Polar aprotic

Zaitsev regiochemistry

Anti-periplanar Stereochemistry

Competes with all pathways
SB favors E2>SN1 & E1
WN discourages SN2

E1 Reaction

Tert>Secondary + Heat

More stable carbocation = Faster rxn

Weaker bases

Polar protic

Zaitsev alkene

Largest groups on opposing sides (E)

Competes with SN1 & E2

Heat favors E1>Sn1

Weak Base favors E1>E2

Predicting Major Reaction Pathway

SN/WB = Substitution
Sn1 = 3>2>1
Sn2 = 1>2>3

WN/SB = Elimination
E2 = 3>2>1 

Heat = E1