Structure of the Substrate
Rates of SN2 reactions depend on steric hindrance to
approach of nucleophile for “backside” attack
CH3—Br
methyl
reactive
(CH3)3CBr
3˚
unreactive
(CH3)3CCH2Br
1˚, neopentyl
unreactive
The Effect of the Nucleophile
SN2 reactions depend on the concentration
and nature of the nucleophile.
Factors Effecting Nucleophilicity
1. Charge: Charged nucleophiles are always
stronger than their conjugate acids.
HO–
RO–
RS–
> H2O
> ROH
> RSH
2. Basicity: For the same element,
nucleophilicity parallels basicity.
O
RO– > HO– > CH3CO–
3. Solvent Effects
> CH3OCH3 >
H2O
Solvent Effects
In SN2 reactions, the transition states are more polar
than the starting materials and products
SN2 reactions require polar solvents
Polar Protic
Solvents
Dielectric
Constants
H2O
HCO2H
CH3OH
CH3CH2OH
CH3CO2H
80
59
36
24
6
49
37
36
21
Polar Aprotic Solvents
DMSO
DMF
acetonitrile
acetone
DMF = dimethyl formamide DMSO = dimethylsulfoxide
O
O
S
C
CH3 CH3
H
NMe2
CH3C≡N is acetonitrile
The dielectric constant is a measure of solvent polarity.
Hexane, a non-polar aprotic solvent has a dielectric constant
of about 2
Solvent Effects on Nucleophilicity
In polar aprotic solvents, SN2 reactions are strongly
accelerated, and nucleophilicity follows basicity.
F– > Cl– > Br– > I–
S O
+
Na
O S
F–
DMSO solvates “Na+” but not F–, so F– is very reactive.
In polar protic solvents (H2O, CH3OH, etc.)
Larger, more polarizable elements are better nucleophiles
(reverse of basicity!).
I– > Br– > Cl– > F–
RS– > RO–
Smaller, more basic nucleophiles are more strongly Hbonded to solvent and must be desolvated to react.
Desolvation costs energy.
More polarizable elements can distort their electron clouds
to donate electron density more easily.