Transcript 10. Alkyl Halides - faculty at Chemeketa

10. Organohalides
Why this Chapter?
 Reactions involving organohalides are less
frequently encountered than other organic
compounds, but reactions such as
nucleophilic substitutions/eliminations that
they undergo will be encountered
 Alkyl halide chemistry is model for
mechanistically similar but more complex
2
What Is an Alkyl Halide
 An organic compound containing at least one carbon-
halogen bond (C-X)
 X (F, Cl, Br, I) replaces H
 Can contain many C-X bonds
 Properties and some uses
 Fire-resistant solvents
 Refrigerants
 Pharmaceuticals and precursors
3
10.1 Naming Alkyl Halides
 Find longest chain, name it as parent chain


(Contains double or triple bond if present)
Number from end nearest any substituent (alkyl or
halogen)
4
 Number all halogens and list different in
alphabetical order.
5
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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Common Names
 Treat halogen as parent with alkyl side group
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Learning Check:
 Give names for the following:
8
Solution:
 Give names for the following:
Iodobutane
(butyl iodide)
1-chloro-3-methylbutane
(isopentyl chloride)
1,5-dibromo-2,2-dimethylpentane
1-chloro-3-ethyl-4-iodopentane
1,3-dichloro-3-methylbutane
2-bromo-5-chlorohexane
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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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10.3 Preparing Alkyl Halides from
Alkenes:
 Alkyl halide from addition of HCl, HBr, HI to alkenes
to give Markovnikov product (see Alkenes chapter)
 Alkyl dihalide from anti addition of bromine or chlorine
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10.3 Preparing Alkyl Halides from
Alkanes: Radical Halogenation
 Alkane + Cl2 or Br2, heat or light replaces C-H with C-
X but gives mixtures
 Hard to control
 Via free radical mechanism
 It is usually not a good idea to plan a synthesis that
uses this method
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Radical Halogenation of Alkanes
 If there is more than one type of hydrogen in an
alkane, reactions favor replacing the hydrogen at the
most highly substituted carbons (not absolute)
9 1o H’s
1 3o H
So would expect 10:90 ratio
if # of H’s was sole factor
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Relative Reactivity: Chlorination
 Based on quantitative analysis of reaction products,
relative reactivity is estimated
 Order parallels stability of radicals
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Relative Reactivity: Chlorination
1
9
3o H
1o H’s
So would expect 10:90 ratio
if # of H’s was sole factor
1
9
3o H
1o H’s
1x5=5
9x1=9
So would predict 5:9 ratio
Or 5/14 : 9/14 = 35.7: 64.3
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Learning Check:
 Predict ratio of mono-chlorinated butanes
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Solution:
 Predict ratio of mono-chlorinated butanes
6
4
1o H’s
2o H’s
So would expect 60:40 ratio
if # of H’s was sole factor
6
4
1o H’s
2o H’s
6x 1 =6
4 x 3.5 = 14
So would predict 6:14 ratio
Or 6/20 : 14/20 = 30: 70
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Learning Check:
How many constitutional isomers will form in the
radical mono-chlorination of 2,3-dimethylpentane?
1.
2.
3.
4.
5.
3
4
5
6
7
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Solution:
How many constitutional isomers will form in the
radical mono-chlorination of 2,3-dimethylpentane?
1.
2.
3.
4.
5.
3
4
5
6
7
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Learning Check:
The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3°
hydrogens, respectively. If only monochlorides were to form in the
radical chlorination of 1,3-dimethylcyclobutane, what is the expected
yield of the tertiary chloride?
1.
2.
3.
4.
5.
1/6
1/5
1/4
1/3
1/2
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Solution:
The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3°
hydrogens, respectively. If only monochlorides were to form in the
radical chlorination of 1,3-dimethylcyclobutane, what is the expected
yield of the tertiary chloride?
1.
2.
3.
4.
5.
1/6
1/5
1/4
1/3
1/2
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Relative Reactivity: Bromination
 Reaction distinction is more selective with bromine
than chlorine
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Relative Reactivity: Bromination
Formation of C radical more costly with Br. So Br more picky thus more selective.
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Learning Check:
Which of these radicals is expected to be
the least selective?
1.
2.
3.
4.
5.
HO•
F•
Cl•
Br•
I•
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Solution:
Which of these radicals is expected to be
the least selective?
1.
2.
3.
4.
5.
HO•
F•
Cl•
Br•
I•
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10.4,5 Preparing Alkyl Halides from
Alkenes: Allylic Bromination
 Allylic position more reactive
 Allylic radical stabilized by resonance
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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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Allylic Bromination: NBS
 N-bromosuccinimide (NBS) selectively brominates
allylic positions
 Requires light for activation
 A source of dilute bromine atoms
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Allylic Bromination: NBS
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Allylic Bromination: NBS
 Product mix favors more substituted C=C and less hindered Br
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Examples:
NBS
Br
Br
CH3
CH3
CH2 Br
Br
CH3
Br
CH2
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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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Learning Check:
 Predict the products of allylic bromination w/ NBS
NBS
NBS
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Solution:
 Predict the products of allylic bromination w/ NBS
NBS
NBS
CH3
Br
CH3
CH3
CH3
CH3
+
CH3
C CH CH CH2
CH3
CH3
C CH CH CH
Br
H
CH3
CH3
C CH CH CH2
Br
CH3
CH3
CH3
Br
C CH CH CH
CH3
H Br
Br
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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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Example:
36
Alkyl Halides from Alcohols
 Alternative methods for slow primary and secondary
alcohols to avoid rearrangements.
37
Learning Check:
 Prepare the following from alcohols
38
Solution:
 Prepare the following from alcohols
OH
OH
CH3
CH3
CH3
CH3
CH CH2 CH
CH3
CH3
C CH3
OH
CH3
CH2
HCl
PBr3
CH2
OH
CH CH2 C
CH3
CH3
CH3
CH2
CH2 CH2 CH
PBr3
CH3
HCl
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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 (alkyl-metal
bond)
 R is alkyl 1°, 2°, 3°, aryl, alkenyl
 X = Cl, Br, I
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Grignard Reagents
 Forms a basic/nucleophilic Carbon
Example:
41
10.8 Organometallic Coupling
Reactions
 Alkyllithium (RLi) forms from RBr and Li metal
 RLi reacts with copper iodide to give lithium dialkylcopper (Gilman
reagents)
 Lithium dialkylcopper reagents react with alkyl halides to give alkanes
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Examples:
43
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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Palladium-catalyzed Tributyltin
chloride
 Works well with aryl or vinyl halides
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10.9 Oxidation and Reduction in
Organic Chemistry
 In organic chemistry, we say that oxidation occurs when a
carbon or hydrogen that is connected to a carbon atom in a
structure is replaced by oxygen, nitrogen, or halogen
 Oxidation is a reaction that results in loss of electron density at
carbon (as more electronegative atoms replace hydrogen or
carbon)
 Oxidation =
LEO
 Gaining an Oxygen
 Or Losing a Hydrogen

Oxidation: break C-H (or C-C) and form C-O, C-N, C-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 =
GER
 Losing an Oxygen
 Or Gaining a Hydrogen

Reduction: form C-H (or C-C) and break C-O, C-N, C-X
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Oxidation Levels
 Functional groups are associated with specific levels
CH4
-4
-3
-2
0
+2
+4
48
Examples:
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Examples:
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Learning Check:
Which of these is not a redox reaction?
1.
2.
x
HCl
Cl
x
Br2
Br
Br
3.
x
H2
Pd
4.
x
H2O/DMSO
5.
x
OH
NBS
1. OsO4
Br
HO
OH
2. NaHSO3/H2O
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Solution:
Which of these is not a redox reaction?
1.
2.
x
HCl
Cl
x
Br2
Br
Br
3.
x
H2
Pd
4.
x
H2O/DMSO
5.
x
OH
NBS
1. OsO4
Br
HO
OH
2. NaHSO3/H2O
52
Biological Halides
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Learning Check:
Radical chlorination of (2R)-fluorobutane yields 2-chloro-3fluorobutane as one of the products. Which is the best prediction
for the stereochemistry of this product?
1.
2.
3.
4.
5.
two enantiomers in equal amounts
two diastereomers in different amounts
two diastereomers in equal amounts
four stereoisomers, in different amount each
four stereoisomers, with enantiomeric pairs
in equal amounts, but diastereomeric pairs
in non-equal amounts
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Solution:
Radical chlorination of (2R)-fluorobutane yields 2-chloro-3fluorobutane as one of the products. Which is the best prediction
for the stereochemistry of this product?
1.
2.
3.
4.
5.
two enantiomers in equal amounts
two diastereomers in different amounts
two diastereomers in equal amounts
four stereoisomers, in different amount each
four stereoisomers, with enantiomeric pairs
in equal amounts, but diastereomeric pairs
in non-equal amounts
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Learning Check:
Which mechanistic step determines the regiochemistry
of the radical-chain chlorination of 2-methylpropane?
1.
2.
3.
4.
5.
protonation step
hydrogen abstraction step
chlorine abstraction step
chloride addition step
initiation step
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Solution:
Which mechanistic step determines the regiochemistry
of the radical-chain chlorination of 2-methylpropane?
1.
2.
3.
4.
5.
protonation step
hydrogen abstraction step
chlorine abstraction step
chloride addition step
initiation step
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Learning Check:
Dipole moments of CH3–X are 1.85, 1.87, 1.81, and 1.62 D for F,
Cl, Br, and I, respectively. What is the best explanation of the
small differences in dipole moments?
1.
2.
3.
4.
5.
The electronegativity of halogens in alkyl halides is nearly
constant.
The inductive effects are counterbalanced by hyperconjugation.
The electronegativity effects are counterbalanced by bond
strengths.
Lone-electron pairs are more delocalized on smaller halogens.
The charge-separation and bond-lengths trends have opposite
effects.
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Solution:
Dipole moments of CH3–X are 1.85, 1.87, 1.81, and 1.62 D for F,
Cl, Br, and I, respectively. What is the best explanation of the
small differences in dipole moments?
1.
2.
3.
4.
5.
The electronegativity of halogens in alkyl halides is nearly
constant.
The inductive effects are counterbalanced by hyperconjugation.
The electronegativity effects are counterbalanced by bond
strengths.
Lone-electron pairs are more delocalized on smaller halogens.
The charge-separation and bond-lengths trends have opposite
effects.
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Learning Check:
Which of the following is not the product of the radical
chain-reaction of 2-pentene with NBS?
1.
2.
3.
4.
60
Solution:
Which of the following is not a product of the radical
chain-reaction of 2-pentene with NBS?
1.
2.
3.
4.
61
Learning Check:
What is the best reagent to carry out the following
transformation?
Br
1.
2.
3.
4.
5.
PBr3
HBr
NBS/hv/CCl4
Br2/hv
NBS/H2O/DMSO
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Solution:
What is the best reagent to carry out the following
transformation?
Br
1.
2.
3.
4.
5.
PBr3
HBr
NBS/hv/CCl4
Br2/hv
NBS/H2O/DMSO
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Learning Check:
What is the best reagent to carry out the following
transformation?
OH
1.
2.
3.
4.
5.
Br
PBr3
HBr/ether
NBS/hv/CCl4
Br2/hv
NBS/H2O/DMSO
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Solution:
What is the best reagent to carry out the following
transformation?
OH
1.
2.
3.
4.
5.
Br
PBr3
HBr/ether
NBS/hv/CCl4
Br2/hv
NBS/H2O/DMSO
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Learning Check:
Which sequence of reagents is best to accomplish the
following transformation?
Br
1.
2.
3.
4.
5.
D
KOH followed by BD3/THF
KOH followed by NaBH4
Mg/ether followed by D2O
Li/pentane followed by D2/CuI
NaNH2 followed by D2/Pd
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Solution:
Which sequence of reagents is best to accomplish the
following transformation?
Br
1.
2.
3.
4.
5.
D
KOH followed by BD3/THF
KOH followed by NaBH4
Mg/ether followed by D2O
Li/pentane followed by D2/CuI
NaNH2 followed by D2/Pd
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Learning Check:
The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3° hydrogens,
respectively. Assuming that only monochlorides are produced in the radical
chain chlorination of 2,3-dimethybutane, what would be the expected ratio of
the two isomeric alkyl chlorides formed in the reaction?
1.
2.
3.
4.
5.
1/6
1/4
1/2
3/5
5/6
68
Solution:
The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3° hydrogens,
respectively. Assuming that only monochlorides are produced in the radical
chain chlorination of 2,3-dimethybutane, what would be the expected ratio of
the two isomeric alkyl chlorides formed in the reaction?
1.
2.
3.
4.
5.
1/6
1/4
1/2
3/5
5/6
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Learning Check:
The reaction shown produces 5 different bromides. Which of the
compounds listed is one of the expected products?
NBS
CCl4
1.
2.
4.
3.
5.
70
Solution:
The reaction shown produces 5 different bromides. Which of the
compounds listed is one of the expected products?
NBS
CCl4
1.
2.
4.
3.
5.
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Learning Check:
Which of the following molecules would not yield an
organolithium reagent when treated with Li in pentane?
1.
2.
3.
4.
5.
iododecane
4-bromo-1-pentanol
phenyl bromide
4-bromobutyl methyl ether
cyclohexylbromide
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Solution:
Which of the following molecules would not yield an
organolithium reagent when treated with Li in pentane?
1.
2.
3.
4.
5.
iododecane
4-bromo-1-pentanol
phenyl bromide
4-bromobutyl methyl ether
cyclohexylbromide
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Learning Check:
What is the IUPAC name of the following molecule?
Cl
1.
2.
3.
4.
5.
2,4-dimethylheptyl-6-chloride
2,4,6-trimethyl-6-chlorohexane
2-chloro-4,6-dimethylheptane
1-chloro-1,3,5-trimethylhexane
2-chloro-4-methyl-isoheptane
74
Solution:
What is the IUPAC name of the following molecule?
Cl
1.
2.
3.
4.
5.
2,4-dimethylheptyl-6-chloride
2,4,6-trimethyl-6-chlorohexane
2-chloro-4,6-dimethylheptane
1-chloro-1,3,5-trimethylhexane
2-chloro-4-methyl-isoheptane
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Learning Check:
What is the product of the following sequence of reactions?
I
I
1.
2Li
CuI
pentane
ether
ether
3.
2.
4.
5.
76
Solution:
What is the product of the following sequence of reactions?
I
I
1.
2Li
CuI
pentane
ether
ether
3.
2.
4.
5.
77