10. Organohalides
Based on
McMurry’s Organic Chemistry, 7th edition
What Is an Organohalide?

An organic compound containing at least
one halogen attached to an sp3 hybridized
carbon

X (F, Cl, Br, I) replaces H
Can contain many C-X bonds
 Properties and some uses




Fire-resistant solvents
Refrigerants
Pharmaceuticals and precursors
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3
Epibatidine (200X more effective than
morphine!)
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Vancomycin (antibiotic from
amycolatopsis orientalis):
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10.1 Naming Alkyl Halides
 Name
chain
is based on longest carbon
 (Contains
double or triple bond if
present)
 Number from end nearest any
substituent (alkyl or halogen)
 Halogens have same priority as alkyl
groups
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Naming with Multiple Halides


If more than one of
the same kind of
halogen is present,
use prefix di, tri,
tetra
If there are several
different halogens,
number them and
list them in
alphabetical order
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Naming if Two Halides or Alkyl Are Equally
Distant from Ends of Chain

Begin at the end nearer the substituent
whose name comes first in the alphabet
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Many Alkyl Halides That Are Widely Used
Have Common Names
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10.2 Structure of Alkyl Halides
 C-X
bond is longer as you go
down periodic table
 C-X bond is weaker as you go
down periodic table
 C-X bond is polarized with slight
positive on carbon and slight
negative on halogen
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Properties of the Halomethanes
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10.3: Radical Halogenation

Alkane + Cl2 or Br2, initiated by heat or
light; replaces C-H with C-X




Hard to control for monosubstitution
Reacts via a free radical mechanism
See mechanism in Figure 10-1
It is usually not a good idea to plan a
synthesis that uses this method
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Multiple Substitution
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Radical Halogenation of Alkanes
If there is more than one type of hydrogen
in an alkane, the reaction favors replacing
the hydrogen at the most highly
substituted carbons: 3o>2o>1o
 The number of available hydrogens is a
factor
 Methyl hydrogens, for example, often
outnumber 2o or 3o hydrogens.

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Chlorination is unselective:
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Relative Reactivity
Based
on quantitative
analysis of reaction products,
relative reactivity is
estimated
Order parallels stability of
radicals (See Figure 10-2)
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Bromination is much more selective
than chlorination:
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10.4 Preparing Alkyl Halides


Alkyl halide is formed by the addition of HCl, HBr,
HI to alkenes to give the Markovnikov product
(see Alkenes chapter)
Alkyl geminal dihalide from anti addition of
bromine or chlorine
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10.5 Allylic Bromination of Alkenes


N-bromosuccinimide (NBS) selectively
brominates allylic positions
Requires light for activation: a source of
bromine atoms at very low concentrations
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Allylic Bromination of Alkenes
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Allylic Stabilization
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Allylic Stabilization



Allyl radical is delocalized
More stable than typical alkyl radical by 40
kJ/mol (9 kcal/mol
Allylic radical is more stable than tertiary alkyl
radical
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10.5 Stability of the Allyl Radical:
Resonance Revisited


Three electrons are delocalized over three
carbons
Spin density surface shows single electron is
dispersed
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Allylic Resonance:
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Allylic Radicals as Reaction
Intermediates:
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Use of Allylic Bromination


Allylic bromination with NBS creates an allylic
bromide
Reaction of an allylic bromide with base produces
a conjugated diene, useful in synthesis of
complex molecules
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Practice Problem 10.1: Products?
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Problem 10.5: Draw resonance forms
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Problem 10.5
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Problem 10.6: Explain?
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Problem 10.6: mechanism
CH2
CH2
Br2
CH2Br
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10.6 Preparing Alkyl Halides from
Alcohols


Reaction of tertiary C-OH with HX is fast and effective
 Add HCl or HBr gas into ether solution of tertiary alcohol
Primary and secondary alcohols react very slowly and often
rearrange, so alternative methods are used
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Reactivity of Alcohols with HX
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Preparation of Alkyl Halides from Primary and
Secondary Alcohols
 Specific
reagents avoid acid and
rearrangements of carbon skeleton
 Thionyl chloride converts alcohols
into alkyl chlorides (SOCl2 : ROH
to RCl)
 Phosphorus tribromide converts
alcohols into alkyl bromides (PBr3:
ROH to RBr)
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Problem 10.23: Products?
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Prob. 10.8: Synthesize from
alcohols?
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10.7 Reactions of Alkyl Halides:
Grignard Reagents


Reaction of RX with
Mg in ether or THF
Product is RMgX –
an organometallic
compound (alkylmetal bond)


R is alkyl 1°, 2°,
3°, aryl, alkenyl
X = Cl, Br, I
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François Auguste Victor Grignard
•Born in
Cherbourg, 1871
•PhD, University
of Lyon, 1901
•Nobel Prize in
Chemistry, 1912
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Grignard Carbon as Nucleophile:
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Reactions of Grignard Reagents
 Many
useful reactions
 RMgX
behaves as R- (adds to C=O)
 RMgX + H3O+ yields R-H
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10.8 Organometallic Coupling
Reactions
Alkyllithium (RLi)
forms from RBr
and Li metal
 RLi reacts with
copper iodide to
give lithium
dialkylcopper
(Gilman reagents)

Henry Gilman (1893-1986)
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Lithium dialkylcopper reagents react with
alkyl halides to give alkanes:
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Problem 10.23 (continued):
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Utility of Organometallic
Coupling in Synthesis
 Coupling
of two organometallic
molecules produces larger molecules
of defined structure
 Aryl and vinyl organometallics also
effective
 Coupling of lithium dialkylcopper
molecules proceeds through
trialkylcopper intermediate
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10.9 Oxidation and Reduction in
Organic Chemistry

In organic chemistry, oxidation occurs when
a carbon or hydrogen that is connected to a
carbon atom in a structure is replaced by
oxygen, nitrogen, or halogen


Not easily recognizable as loss of electrons by
an atom as in inorganic chemistry
Oxidation is a reaction that results in loss of
electron density at carbon (as more
electronegative atoms replace hydrogen or
carbon)
Oxidation: loss of H, and/or gain of O, N, X
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Reduction Reactions
 Organic
reduction is the opposite of
oxidation
 Results
in gain of electron density at
carbon
 (replacement of electronegative atoms
by hydrogen or carbon)
Reduction: gain of H and/or loss of O, N, X
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Oxidation Levels

Functional groups are associated with
specific oxidation levels
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Practice Problem 10.2: Rank in order of
increasing oxidation level
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Problem 10.13: oxidation or reduction?
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Problem 10.33: oxidation or reduction?
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Problem 10.39: Identify reagents
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Problem 10.39
a
= BH3/THF followed by
H2O2/OH-1
(hydroboration/oxidation)
 b = PBr3/ether
 c = (CH3)2CuLi/ether
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