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Alkyl Halides
Nucleophilic Substitution and
Elimination
State University of New York at Albany
Nomenclature of Alkyl Halides
Name halogen as substituent on alkane or
cylcoalkane.
 Learn common names for some of the simple
structures. e.g. chloroform, methylene chloride.
 Note degree of substitution - name as type of C
it is bonded to (i.e. 10, 20, 30).
 Geminal (gem-) dihalide has two halogen atoms
bonded to the same carbon.
 Vicinal (vic-) dihalide has two halogens bonded
to adjacent carbons.

Do problem 6-1, 6-2 and 6-3 of the text.
Example Problems:
CH3CH2CBr2CH2CH2CH3
CH3
(CH3)2CHCCH3
Br
Br
Cl
CH3
Cl H
CH(CH3)2
I
Cl CH3
Uses and General Chracteristics

BOND DIPOLE (): + at C, - at X
» all reactions based on this.
» The bond dipole moments increase in the order:
C—I < C—Br < C—F < C—Cl
 Physical properties
» generally, trends are similar to those seen in
alkanes.
» bp affected by London forces and dipole-dipole
attractions.

Common uses: solvents, anesthetics, freons
(refrigerants), pesticides.
Preparation of alkyl & allylic
halides

Free radical halogenation of alkanes (Chpt 4)
Br2
Br
h

You are expected to know the mechanism by
which this transformation takes place.
Preparation of Alkyl Halides

Free radical halogenation of alkenes at allylic
position
NBS
h
Br
OR
+
Br2
Br
h

need to know resonance structures for
intermediate & predict major/minor product
See pages 235-236 of the text. Do problems 6-8 and 6-9.
Nucleophilic Substitution (SN)
R—LG + Nuc:  R—Nuc + LG:
Substrate
 Reagent/Nucleophile (Nuc)
 Leaving Group (LG)
 Solvent/Reaction Conditions

Br
solvent
OH
+ HO
1. Identify electrophilic carbon in substrate
2. Identify nucleophilic electrons in nucleophile
3. Identify leaving group in substrate
Then draw product(s)
4. Draw substrate without LG but with bond
5. Add Nuc to bond where LG used to be
OH
Factors influencing what
products are formed
Substrate/steric effects
 Strength of nucleophile vs. basicity of
nucleophile
 Stability of leaving group
 Reaction conditions

» Polarity of solvent
» acidic/neutral/basic
Substitution Mechanisms

Continuum of possible mechanisms
Nuc

LG
Mechanism determined primarily by
substrate steric effects
SN2 - methyl, 1º & unhindered 2º
SN1 - 3º, hindered 2º
+ LG
Bimolecular (SN2) Nucleophilic
Substitution
concerted reaction; Nuc attacks, LG leaves
 pentacoordinate carbon in transition state
 rate depends on conc. of both reactants
 Me = methyl group; Et = ethyl group

Et
HO
H
Br
Me
(S)-2-bromobutane

HO
Et
H Me

Br
Reaction is “stereospecific”

100 % inversion of configuration

HO
Et
H Me

Br
Et
HO
H
Me
+ Br
(R)-2-butanol
You should know how to represent this
mechanism in an energy diagram!!
Factors that Affect SN2 Reaction
Rates




Strength of Nucleophile: species with negative charge
is a stronger nuc than an analogous neutral species
(e.g. -OH > H2O; -NH2 > NH3).
Nucleophilicity increases from left to right across the
periodic chart (e.g. -OH > -F).
Nucleophilicity increased down the periodic table
(I- > Br- > Cl- > F-) or (-SeH > -SH > -OH).
Solvent: Polar protic solvents (e.g. ethanol, ammonia
decrease nucleophilicity. Polar aprotic solvents e.g.
(acetonitrile, DMSO, acetone) increase nucleophilicity.
Factors that affect SN2 reaction rates


Steric Effects: When bulky groups interfere with a rxn.
because of their size, this is called steric hindrance.
Steric hindrance affects nucleophilicity, not basicity. (e.g.
ethoxide ion is a stronger base than t-butoxide ion).
Also, alkyl halide reactivity decreases from methyl to 10
to 20 to 30. In fact, 30 alkyl halides do not react by SN2.
Leaving group: The substrate should have a good
leaving group. A good leaving group should be electron
withdrawing, relatively stable, and polarizable. They are
weak bases. Examples are Cl-, Br-, I-, RSO3-, RSO4-,
RPO4-, and neutral molecules such as water, alcohols
and amines. Strong bases (OH-, RO-, H2N-) are not good
leaving groups!
Unimolecular (SN1)
Nucleophilic Substitution

Two-step reaction
» LG leaves, then Nuc: attacks
Tricoordinate carbocation intermediate
 Solvolysis (when solvent is also the
nucleophile = SN1 reaction
 Rate depends on substrate conc. only

Mechanism of SN1 reaction
(CH3)3C-Br + CH3OH
step 1
(CH3)3C Br
step 2
(CH3)3C
(CH3)3C O CH3 + CH3OH
(CH3)3C
O-CH3
H
+ Br
(slow)
(CH3)3C O CH3 (fast)
step 3
(CH3)3C O CH3 + H O CH3
H
(CH3)3C O CH3
H
You must be able to represent this on an energy diagram!
+ H O CH3
H
Reaction Not Stereoselective
Unless Steric Factors Apply
Racemization - not always exactly 50/50.
Carbocation can be attacked from the top or
bottom face giving both enantiomers.
 Steric hindrance gives attack at one side
preferentially
 Longer-lived carbocations give more
racemization, shorter-lived give more inversion

Factors Influencing SN1
Reaction Rates

Stability of the carbocation*
Allylic 3° >> 3°  allylic 2° > 2°  allylic 1° >> 1° > Me
Carbocations are stabilized by alkyl groups (through
hyperconjugation and the inductive effect) and by
resonance.
Leaving group stability: the better the leaving
group, the faster the reaction.
 Solvent polarity: the reaction is favored in polar
protic solvents.

*
must have neutral to acidic conditions to form
carbocation
Rearrangement of Carbocations


Large difference in energy (stability) of 3° vs.
2° C+
H- (hydride) or R- will shift (migrate) to adjacent
position to form more stable carbocation. E.g.
when neopentyl bromide is boiled in methanol,
only rearranged product is formed.
H
CH3 C
C CH3
H CH3
secondary carbocation
H
CH3 C
C CH3
H CH3
tertiary carbocation
Elimination Reactions
May proceed by a unimolecular (E1) or
bimolecular (E2) mechanism.
 In an alkyl halide, when a halide ion leaves
with another atom or ion, the reaction is an
elimination.
 If the halide ion leaves with H+, the reaction
is called a dehydrohalogenation.

Elimination Mechanisms

Mechanism determined primarily by
substrate steric effects
LG
H
H
B:
o
LG
o
2 , hindered 1 , or
bulky strong base
E2
3o, -branched 2o
E1
step 1 - same as for SN1
Br
C H
H3C
CH CH3
H
E1 mechanism
H3C
H
C
CH CH3
H
step 2
H3C
H
C
CH3OH
C CH3
H
+
major
+
+ CH3OH2
E1 & SN1 Competition

Always
» by definition a nucleophile is Lewis Base
Br
NaOEt
+
OEt
EtOH
H
Elimination
Substitution
Carbocations generally
always give both products
 Relative
amounts not easily
predictable
 Always assume formed in
approximately equal amounts
E2 is Stereospecific

anti-coplanar elimination of H and LG
Br
H
B:
Br
H
B:
+ HBr
Product Distribution in E2

Seytzeff Product, most substituted
» major with small base, i.e., ethoxide, small LG
NaOEt
+
Br EtOH
major
minor
R2C=CR2 > R2C=CHR > RHC=CHR > R2C=CH2 > RHC=CH2
Decreasing alkene stability
E2 Mechanism
Concerted, anti-coplanar,  Stereospecific
 strong base & good LG

H
OEt
=
Br
Elimination is stereospecific
Ph
H
Me
Br
Me Ph
Me
=
Br
H
Ph
Br
Ph Me
Br
Ph
Me
Ph
H
Me
Ph
Me
OEt
Ph
Me
=
Ph
H
Me
Me
Ph =
Me
Ph
Ph
Me
stereospecific elimination
Comparison of SN1 and SN2
E1






Base strength unimportant
Substrates: reactivity order
is 3o > 2o > 1o
Solvent: good ionizing
solvent required
Rate: depends on substrate
conc. only
Stereochemistry: no
particular geometry
required for slow step;
Saytzeff rule followed
Rearrangements: very
common
E2






Strong bases required
Substrates: reactivity order
is 3o > 2o > 1o
Solvent polarity is not so
important
Rate: depends on conc. of
substrate and base.
Stereochemistry: coplanar
arrangement required in
transition state; Saytzeff rule
followed
Rearrangements: not
possible