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

6
Common Names
 Treat halogen as parent with alkyl side group

7
Learning Check:
 Give names for the following:

8
 Solution:
 Give names for the following:

Iodobutane
1-chloro-3-methylbutane
(butyl iodide)
(isopentyl chloride)
1,5-dibromo-2,2-dimethylpentane

1-chloro-3-ethyl-4-iodopentane
1,3-dichloro-3-methylbutane 2-bromo-5-chlorohexane

9
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

10
 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

11
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

12
 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

13
Relative Reactivity: Chlorination
 Based on quantitative analysis of reaction products,
relative reactivity is estimated
 Order parallels stability of radicals

14
 Relative Reactivity: Chlorination

1 3o H
9 1o H’s

So would expect 10:90 ratio

if # of H’s was sole factor
1 3o H 1x5=5
9 1o H’s 9x1=9

So would predict 5:9 ratio

Or 5/14 : 9/14 = 35.7: 64.3

15
Learning Check:
 Predict ratio of mono-chlorinated butanes

16
 Solution:
 Predict ratio of mono-chlorinated butanes

6 1o H’s
4 2o H’s
6 1o H’s 6x 1 =6
So would expect 60:40 ratio 4 2o H’s 4 x 3.5 = 14
if # of H’s was sole factor
So would predict 6:14 ratio
Or 6/20 : 14/20 = 30: 70

17
 Learning Check:
How many constitutional isomers will form in the
radical mono-chlorination of 2,3-dimethylpentane?

1. 3
2. 4
3. 5
4. 6
5. 7

18
 Solution:
How many constitutional isomers will form in the
radical mono-chlorination of 2,3-dimethylpentane?

1. 3
2. 4
3. 5
4. 6
5. 7

19
 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. 1/6
2. 1/5
3. 1/4
4. 1/3
5. 1/2

20
 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. 1/6
2. 1/5
3. 1/4
4. 1/3
5. 1/2

21
Relative Reactivity: Bromination
 Reaction distinction is more selective with bromine
than chlorine

22
 Relative Reactivity: Bromination

Formation of C radical more costly with Br. So Br more picky thus more selective.

23
 Learning Check:

Which of these radicals is expected to be

the least selective?
1. HO•
2. F•
3. Cl•
4. Br•
5. I•

24
 Solution:

Which of these radicals is expected to be

the least selective?
1. HO•
2. F•
3. Cl•
4. Br•
5. I•

25
10.4,5 Preparing Alkyl Halides from
Alkenes: Allylic Bromination
 Allylic position more reactive

 Allylic radical stabilized by resonance

26
 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

27
Allylic Bromination: NBS
 N-bromosuccinimide (NBS) selectively brominates
allylic positions
 Requires light for activation
 A source of dilute bromine atoms

28
Allylic Bromination: NBS

29
 Allylic Bromination: NBS
 Product mix favors more substituted C=C and less hindered Br

30
Examples:

NBS

Br Br

CH3 CH3 CH2 Br

Br
CH3 Br CH2

31
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

32
 Learning Check:
 Predict the products of allylic bromination w/ NBS

NBS

NBS

33
 Solution:
 Predict the products of allylic bromination w/ NBS

NBS

NBS CH3 CH3

CH3 C CH CH CH2 CH3 CH3 C CH CH CH CH3
CH3 CH3 Br H Br
Br
CH3 CH3
+ CH3 C CH CH CH2 CH3 CH3 C CH CH CH CH3
Br H Br

Br

34
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

35
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
CH3 OH
OH CH3
CH3 CH2 CH CH2 C CH3
OH CH3 CH CH2 CH CH3 CH3
CH3 C CH3
OH CH3
CH3 CH2 CH2 CH2 CH2 CH CH3

HCl PBr3
PBr3 HCl

39
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

40
 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

42
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

44
Palladium-catalyzed Tributyltin
chloride
 Works well with aryl or vinyl halides

45
 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

46
 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

47
 Oxidation Levels
 Functional groups are associated with specific levels

CH4

-4 -3 -2 0 +2 +4

48
Examples:

49
Examples:

50
 Learning Check:
Which of these is not a redox reaction?
HCl Cl
1. x
Br2 Br
2. x
Br

H2
3. x
Pd

NBS OH
4. x
H2O/DMSO Br

5. x 1. OsO4 HO OH

2. NaHSO3/H2O

51
 Solution:
Which of these is not a redox reaction?
HCl Cl
1. x
Br2 Br
2. x
Br

H2
3. x
Pd

NBS OH
4. x
H2O/DMSO Br

5. x 1. OsO4 HO OH

2. NaHSO3/H2O

52
Biological Halides

53
 Learning Check:
Radical chlorination of (2R)-fluorobutane yields 2-chloro-3-
fluorobutane as one of the products. Which is the best prediction
for the stereochemistry of this product?

1. two enantiomers in equal amounts

2. two diastereomers in different amounts
3. two diastereomers in equal amounts
4. four stereoisomers, in different amount each
5. four stereoisomers, with enantiomeric pairs
in equal amounts, but diastereomeric pairs
in non-equal amounts

54
 Solution:
Radical chlorination of (2R)-fluorobutane yields 2-chloro-3-
fluorobutane as one of the products. Which is the best prediction
for the stereochemistry of this product?

1. two enantiomers in equal amounts

2. two diastereomers in different amounts
3. two diastereomers in equal amounts
4. four stereoisomers, in different amount each
5. four stereoisomers, with enantiomeric pairs
in equal amounts, but diastereomeric pairs
in non-equal amounts

55
 Learning Check:
Which mechanistic step determines the regiochemistry
of the radical-chain chlorination of 2-methylpropane?

1. protonation step
2. hydrogen abstraction step
3. chlorine abstraction step
4. chloride addition step
5. initiation step

56
 Solution:
Which mechanistic step determines the regiochemistry
of the radical-chain chlorination of 2-methylpropane?

1. protonation step
2. hydrogen abstraction step
3. chlorine abstraction step
4. chloride addition step
5. initiation step

57
 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. The electronegativity of halogens in alkyl halides is nearly

constant.
2. The inductive effects are counterbalanced by hyperconjugation.
3. The electronegativity effects are counterbalanced by bond
strengths.
4. Lone-electron pairs are more delocalized on smaller halogens.
5. The charge-separation and bond-lengths trends have opposite
effects.

58
 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. The electronegativity of halogens in alkyl halides is nearly

constant.
2. The inductive effects are counterbalanced by hyperconjugation.
3. The electronegativity effects are counterbalanced by bond
strengths.
4. Lone-electron pairs are more delocalized on smaller halogens.
5. The charge-separation and bond-lengths trends have opposite
effects.

59
 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. PBr3
2. HBr
3. NBS/hv/CCl4
4. Br2/hv
5. NBS/H2O/DMSO

62
 Solution:
What is the best reagent to carry out the following
transformation?

Br

1. PBr3
2. HBr
3. NBS/hv/CCl4
4. Br2/hv
5. NBS/H2O/DMSO

63
 Learning Check:
What is the best reagent to carry out the following
transformation?

OH Br
1. PBr3
2. HBr/ether
3. NBS/hv/CCl4
4. Br2/hv
5. NBS/H2O/DMSO

64
 Solution:
What is the best reagent to carry out the following
transformation?

OH Br
1. PBr3
2. HBr/ether
3. NBS/hv/CCl4
4. Br2/hv
5. NBS/H2O/DMSO

65
 Learning Check:
Which sequence of reagents is best to accomplish the
following transformation?

Br D

1. KOH followed by BD3/THF

2. KOH followed by NaBH4
3. Mg/ether followed by D2O
4. Li/pentane followed by D2/CuI
5. NaNH2 followed by D2/Pd

66
 Solution:
Which sequence of reagents is best to accomplish the
following transformation?

Br D

1. KOH followed by BD3/THF

2. KOH followed by NaBH4
3. Mg/ether followed by D2O
4. Li/pentane followed by D2/CuI
5. NaNH2 followed by D2/Pd

67
 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. 1/6
2. 1/4
3. 1/2
4. 3/5
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. 1/6
2. 1/4
3. 1/2
4. 3/5
5. 5/6

69
 Learning Check:
The reaction shown produces 5 different bromides. Which of the
compounds listed is one of the expected products?
NBS

CCl4

1. 2. 3.

4. 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. 3.

4. 5.

71
 Learning Check:

Which of the following molecules would not yield an

organolithium reagent when treated with Li in pentane?

1. iododecane
2. 4-bromo-1-pentanol
3. phenyl bromide
4. 4-bromobutyl methyl ether
5. cyclohexylbromide

72
 Solution:

Which of the following molecules would not yield an

organolithium reagent when treated with Li in pentane?

1. iododecane
2. 4-bromo-1-pentanol
3. phenyl bromide
4. 4-bromobutyl methyl ether
5. cyclohexylbromide

73
 Learning Check:
What is the IUPAC name of the following molecule?
Cl

1. 2,4-dimethylheptyl-6-chloride
2. 2,4,6-trimethyl-6-chlorohexane
3. 2-chloro-4,6-dimethylheptane
4. 1-chloro-1,3,5-trimethylhexane
5. 2-chloro-4-methyl-isoheptane

74
 Solution:
What is the IUPAC name of the following molecule?
Cl

1. 2,4-dimethylheptyl-6-chloride
2. 2,4,6-trimethyl-6-chlorohexane
3. 2-chloro-4,6-dimethylheptane
4. 1-chloro-1,3,5-trimethylhexane
5. 2-chloro-4-methyl-isoheptane

75
 Learning Check:
What is the product of the following sequence of reactions?
I
2Li CuI
I
pentane ether ether

1. 2. 3.

4. 5.

76
 Solution:
What is the product of the following sequence of reactions?
I
2Li CuI
I
pentane ether ether

1. 2. 3.

4. 5.

77