Chapter 10: Alkyl Halides
X
X
R C X
C C
Alkyl halide
Aryl halide
X = F, Cl, Br, I
Vinyl halide
10.1 Naming alkyl halides- Read
10.2 Structure of alkyl halides
Table 10.1
Halomethane
H3C-F
H3C-Cl
H3C-Br
H3C-I
X
C
R C C
Bond
Bond strength
length (pm)
(KJ/mol)
139
452
178
351
193
293
214
234
The significant dipole moment of alkyl
halides make then good electrophiles
for substitution reactions
dd+
R
_
+
Na +
Dipole
Moment
1.85
1.87
1.81
1.62
H
R
THF
C X
R C C C
H
H
+
NaX
H
Preparation of Alkyl Halides:
Electrophilic addition of HX and X2 to alkenes (Chapter 6)
HBr
Br2
H
Br
Br
CH3
Br
CH3
CH3
1
Free radical halogenation
Mechanism of free radical halogenation (Chapter 5)
• three distinct steps
1. Initiation
2. Propagation
3. Termination
Free radical chlorination is not very useful for making alkyl chlorides
polychlorination
non-specific chlorination
H H H H
H H H H
Cl2, hn
H H Cl H
H C C C C H
H C C C C Cl
H H H H
H H H H
H H H H
(30%)
(70%)
four 2° hydrogens
six 1° hydrogens
H
H C H
H
H
Cl2, hn
+
H C C C C H
H
H
H C H
H
H
H C H
H
H
+
H C C C H
H C C C Cl
H H H
H C C C H
H H H
H Cl H
one 3° hydrogens
nine 1° hydrogens
(35%)
(65%)
Relative reactivity of hydrogens toward free radical chlorination
H
H
R
R C H
R C H
R C H
H
Primary (1°)
hydrogens
R
<
Secondary (2°)
hydrogens
R
<
3.5
1.0
Tertiary (3°)
hydrogens
5.0
Reactivity is reflective of radical stability
H
H
R C•
H
Primary (1°)
R
R C•
R C•
R
<
Secondary (2°)
R
<
Tertiary (3°)
H
H
R
R C H
R C H
R C H
H
DH° = 420 KJ/mol
R
R
401 KJ/mol
390 KJ/mol
2
Free radical bromination is much more selective for the most stable
radical intermediate.
H
H
H C H
H
H
H
H C H
H
H
H C H
H
H
X2, hn
H C C C H
H H H
+
H C C C X
H C C C H
H H H
H X H
X = Cl
X = Br
65 : 35
1 : 99
The propagation step for free radical bromination is endergonic,
as opposed to chlorination which is exergonic. According to the
Hammond postulate the transition state for bromination should
resemble the product radical, and therefore be more selective for the
product going through the more stable radical intermediate
R3C-H
+
X•
X = Cl
X = Br
R3C•
+
HX
DH° = -50 KJ/mol
DH° = +12 KJ/mol
3
Allylic Bromination of Alkenes
allylic position is the next to a double bond
allylic hydrogen
C
C
C
H
allylic carbon
Br
NBS, hn
CCl4
Allylic bromination of an alkene takes place through a
free radical mechanism.
Radical Stability
H
C
C•
H
H C•
H
Vinylic
<
<
Primary (1°)
R
<
C
R C•
R C•
H
Methyl
•
R
R C•
R
<
Secondary (2°)
Tertiary (3°)
<
Benzylic
~
_
C
C•
Allylic
Increasing stability
C
C
DH° (KJ/mol) = 444
H
H
H
H
R
H C H
R C H
R C H
R C H
H
H
R
R
438
420
401
390
C
C
361
C
H
H
368
Radicals are also stablized by hyperconjugation
4
Allylic radical is resonance stabilized
Recall (and please review) from Chapter 2:
resonance forms- atoms remain fixed in all resonance forms.
Resonance forms differ only by the placement of electrons
No one resonance form is entirely accurate. The actual structure
is a hybrid of all the resonance forms. Resonance forms do not
necessarily contribute equally to the resonance hybrid.
The greater the number of resonance structures the more stable
the resonance hybrid.
C
C
•
C
•
C
1/2 •
C
C
C
C 1/2 •
C
1 1/2 bonds
Map of the electron density
due to the unpaired electron
(the “spin”)
5
NBS, hn
R
R
R
•
•
R
R
+
Br
Br
+
Br
(17 %)
R
(83 %)
Br
KOH
NBS, hn
1,3-cyclohexadiene
(conjugate diene)
Alkyl halides from alcohols
the most general method of preparing alkyl halides
1. Substitution reaction of alcohols with HX
R-OH + HX
R-X
+ H2O
Works better with more substituted alcohols
H
H C OH
H
>
R C OH
H
H
Methyl
Primary (1°)
H
>
R C OH
R
R
>
R C OH
R
Secondary (2°) Tertiary (3°)
increasing reactivity
Polar mechanism with a carbocation intermediate. Reactivity
reflects the stability of the carbocation intermediate (Chapter 11).
One drawback to this method is that carbocations can rearrange.
6
2. Prepartion of alkyl chlorides by the treatment of alcohols
with thionyl chloride (SOCl2)
R-OH + SOCl2
R-Cl
+ SO2
+ HCl
3. Prepartion of alkyl bromides by the treatment of alcohols
with Phosphorous tribromide (PBr3)
R-OH +
PBr3
R-Br
+ P(OH)3
These methods work best on primary and secondary alcohols.
They do not work at all for tertiary alcohols
. . . more reactions of alkyl halides: Grignard reagents
Alkyl halides will react with some metals (M0) in ether or THF to
form organometallic reagents
Grignard reagent- organomagnesium
R-X
+
ether
or THF
Mg(0)
R-Mg(II)-X
X= Cl, Br, I
R can be a variety of organic groups: 1°-, 2°-, 3°-alkyl, aryl or vinyl
d- d+
C MgX
_
C
carbon nuccleophile
(recall acetylide anion)
Carbanions: nucleophile
react with electrophile
7
R-X
H2O
R-MgX
R-H
Grignard reagents are most commonly used in reactions with
carbonyl compounds (Chapter 19).
Lab:
_
MgBr
Br
Mg(0)
ether
_
O
O
O
O
_
H3O
C
OH
+
O
Organometallic coupling reactions:
organolithium reagents
R-X
Li(0)
R-Li +
pentane
d- d+
_
C
C Li
LiX
very strong bases
very strong nucleophiles
organolithium reagents are most commonly used as very strong
bases and in reactions with carbonyl compounds
Cuprates (Gilman’s reagent)
ether
2 CH3Li
+
H3C
CuI
_
Cu Li+
+ LiI
H3C
Gilman's reagent
(dimethylcuprate, dimethylcopper lithium)
8
-
R2CuLi = R
strong nucleophiles
Nucleophilic substitution reaction with alkyl halides (alkylation)
CH3(CH2)8CH2-I + (CH3)2CuLi
ether
CH3(CH2)8CH2-CH3
+ CH3Cu + LiI
Reaction with vinyl and aryl halides
H
H
(CH3)2CuLi
I
CH3
H
H
double bond geometry
is preserved
Br
(CH3)2CuLi
CH3
Oxidation [O]: the loss of electrons.
Decrease in electron density on carbon by forming a
C-O, C-N, C-X bonds or by breaking C-H bonds
Increase in O, N, X content or decrease in H content
Reduction [H]: the gain of electrons
Increase in electron density on carbin by forming C-H
bonds or breaking C-O, C-N, C-X bonds
increase on H content or decrease in O, N, X content
9
CH4 + Cl2
H3C-Cl
H
Mg
H3O+
oxidation
CH4
reduction
+ Br2
H
H
H
H
H
H
H
H
H
C C
H
H
H
H
C C
C C
H
H
H
C C
H
H
H
C C
H
H
H
H
H
OH
H
+ H2O
Reduction
H
Br
H
+ HBr
Oxidation
H
H
H
Pd
+ H2
C C
Br
Br
H
C C
H
1)
2)
H3C-Cl
C C
H
H
H
Neither [O] or [H]
Neither [O] or [H]
(hydration)
Table 10.5: Increasing oxidation state
C C
C C
C C
O
C OH
C NH2
C O
C NH
C
CO2
OR
C N
10