SUBSTITUTION AND ELIMINATION HANDOUT

SUBSTRATE

Remember that SN2 reactions are under steric control. The more sterically hindered the halogen
bearing carbon of an alkyl halide is, the slower the rate of reaction.

(fastest) CH 3-X > 1˚ R-X > 2˚ R-X > Neopentyl R-X > 3˚ R-X (slowest)

Remember that SN1 reactions are controlled by the stability of the carbocation intermediate
formed. The greater the stability of the carbocation intermediate, the faster the rate of reaction.
Remember that primary allylic and primary benzylic carbocations are between 3° and 2°
carbocations in terms of stability. This is due to resonance stabilization of the carbocation
intermediate.
Stability of carbocation intermediates
R R R H
> CH2 ≈ > > >
R R R H H H H H

3˚ Benzylic Allylic 2˚ 1˚ methyl

CH3-X (Methyl halides):

May only react by SN2. This type of alkyl halide lacks beta hydrogens, and therefore are
incapable of undergoing elimination reactions.

1˚ R-X (Primary alkyl halides):

May react by either SN2 or E2.

SN2:
Favors SN2 reactions under most conditions
E2:
High reaction temperatures and the use of a very large (sterically hindered) strong bases
favors E2.

1° Allylic or Benzylic Alkyl Halides:

May only react by either SN1 or SN2. This type of alkyl halide lacks beta hydrogens, and
therefore are incapable of undergoing elimination reactions. Note E1 may be possible for
the resonance structure!

Solvent will determine whether the reaction mechanism will be unimolecular (SN1) or
bimolecular (SN2). Polar aprotic solvents favor SN2 while SN1 requires polar aprotic
solvents.

2˚ R-X (All secondary alkyl halides):

May react by either SN2,SN1, E1, or E2.
 Solvent will determine whether the reaction mechanism will be unimolecular (SN1 or E1)
Or bimolecular (SN2 or E2). Polar protic solvents favor SN1 and E1 while polar aprotic
solvents require SN2 or E2. Note: a strong base will always favor E2!!!!

SN2:
Weakly basic nucleophiles favor SN2.
Reactions at room temperature (R.T.) favor SN2.

E2:
Strong bases favor E2.
Sterically hindered bases favor E2.
High reaction temperatures favor E2.

SN1:
Polar protic solvents favor SN1.
Reactions at room temperature (R.T.) favor SN1.
Will always be favored over E1.

E1:
Polar protic solvents favor E1.
E1 will always compete with SN1.

3˚ R-X (All tertiary alkyl halides):

May react by SN1, E1, or E2.
Note: E1 and SN1 always compete with one another.

SN1:
Polar protic solvents favor SN1.
Reactions at room temperature (R.T.) favor SN1.
SN1 will always be favored over E1.

E1:
Polar protic solvents favor E1.

E2:
Strong bases always favor E2.
Sterically hindered bases favor E2.
High reaction temperatures favor E2.

SOLVENT:

There are three types of solvents: polar protic solvents, polar aprotic solvents, and non-polar
solvents.

Non-polar solvents:

Non-polar solvents cannot solvate (dissolve) cations or anions. As a result, they are usually
incapable of dissolving the ionic compounds (or other nucleophiles) typically used in either
nucleophilic substitution or elimination reactions. Thus, this class of solvents is unfavorable for
substitution and elimination reactions.
Examples of these solvents are hexane and benzene (Any hydrocarbon is non-polar).

Polar aprotic solvents:

This class of solvents can solvate cations AND NOT ANIONS. This is primarily due to the fact
that these solvents contain oxygen atoms which can act as a Lewis base towards metal ions;
however, they do not have hydrogen atoms bonded to highly electronegative elements (such as
oxygen). Accordingly, these solvents may not form hydrogen bonds around the anions, and thus
solvate them. Anions dissolved in this class of solvents are referred to as being “naked,” or free
of the inhibitory solvent cage which retards their reactivity in substitution reactions. This class of
solvents requires SN2 and E2 reactions.

Examples of this class of solvents are DMSO, DMF, HMPA, acetonitrile, acetone, etc. These
solvents have dipole moments, but are not capable of forming hydrogen bonds.
Polar protic solvents:

This class of solvents can solvate both cations and anions. They differ from polar aprotic
solvents in that they have hydrogen atoms which are bonded to strongly electronegative atoms.
Thus, these solvents may form hydrogen bonds around the anion, forming a solvent cage.

This class of solvents favors SN1 and E1 reactions. It is important to note that SN2 and E2
reactions may occur in this type of solvent. E2 will usually be favored when you have a very
strong base. SN2 will usually be favored when your substrate is a methyl or 1° alkyl halide
(excluding allylic or benzylic, which would prefer to react via SN1 under these conditions).

Examples of this class of solvents are EtOH, any alcohol, any carboxylic acid, and H2O.

NUCLEOPHILES:

Remember that all nucleophiles are bases and all bases are nucleophiles.

Note: Nucleophiles which are neutral (uncharged molecules, exe. H2O) are weaker than
nucleophiles which are negatively charged (anions, exe. H-O-). Anions have an abundance of
electrons and want to become neutral, while neutral nucleophiles become ionic intermediates
upon substitution.
+
Exe: H2 O + CH3-I → H2O-CH3 +I- Weaker nucleophile
neutral charged
vs.
F- + CH3-I → F-CH3 +I- Stronger nucleophile
charged neutral

As a general rule, the larger the nucleophilic atom, the greater it’s reactivity in substitution
reactions. This comparison is only valid when comparing ions in the same group of the Periodic
Table. Remember that this effect may be dependent upon solvent (especially the halogens).
Exe:
PH3 is a better nucleophile than NH3
H-S- is a better nucleophile than H-O-
I- is a better nucleophile than F-
When comparing Nuc with the same Nuc atom, the stronger base will be the better nucleophile.

Exe:
(Strong Nuc) R-O- > H-O- > RCO2- > R-O-H > H2O (Weak Nuc)
pKa of conj. acid: ~16 15.7 ~4-5 ~ -1 ~ -2

Remember that SN1 reactions are insensitive to nucleophile strength.

LEAVING GROUP

For all intensive purposes, there are only three types of leaving groups you need to concern
yourself with: halogens, sulfonates and small neutral molecules. In general, the more stable the
anion, the better the leaving group. Leaving group ability is opposite the basicity of the
ions/molecules in question.

Halogens:

(Best L.G.) I- > Br- > Cl- > F- (Worst L.G.)

(Strongest acid) (Weakest acid)
(Weakest base) (Strongest base)

Sulfonates:

The tosylate ion is a slightly better leaving group than iodide and it is a much better leaving
group than bromide. Also note that other sulfonates exist and they are also excellent leaving
groups (Methane sulfonate = MsO- = CH3SO3- ; trifluoromethane sulfonate = TfO- = CF3SO3-;
benzene sulfonate = PhSO3- = C6H5SO3-)

O
S O-
O
Tosylate ion
TsO-

Small neutral molecules:

Water molecules (and occasionally alcohols, ROH) are excellent leaving groups in reactions that
are performed under highly acidic conditions. Water is an excellent leaving group because it is
neutral.

Thus, the overall leaving group ability follows this trend.

(Best L.G.) TfO- > TsO- > I- > Br - > Cl- > H2O (Worst L.G.)