1. Chapter 10
Alkyl Halides

2. Introduction
Alkyl halides – are compounds containing halogen bonded to a saturated, sp3-hybridized carbon atom
– are haloalkanes

3. Properties and some uses

4. It is a pain reliever
It is more potent than morphine

5. A. Naming Alkyl Halides
Alkyl halides are named according to the system of nomenclature devised by the International Union of Pure and Applied Chemistry (IUPAC):

6. Steps to naming alkyl halides1
Find the parent hydrocarbon
Include the double or triple bond if present
Number the atoms in the main chain
The correct sequence is when the substituents have the lowest possible number
Use multiplicity prefixes di-, tri-, tetra-, …
Put the substituents in alphabetical order (Do not consider multiplier prefixes)

7. Steps to naming alkyl halides2
If the parent chain can be properly numbered from either end by step 2, begin at the end nearer the substituent that has alphabetical precedence

8. 2,4,5
3,4,6
2,4,5
3,4,6

9. 2,3,4
3,4,5
2,3,5
1,3,4

11. Practice Problem: Give IUPAC names for the following alkyl halides:

12. Practice Problem: Draw structures corresponding to the
Practice Problem: Draw structures corresponding to the following IUPAC names:
2-Chloro-3,3-dimethylhexane
3,3-Dichloro-2-methylhexane
3-Bromo-3-ethylpentane
1,1-Dibromo-4-isopropylcyclohexane
4-sec-Butyl-2-chlorononane
1,1-Dibromo-4-tert-butylcyclohexane

13. B. Structure of Alkyl Halides
As you go down the periodic table,
C-X bond is longer
C-X bond is weaker

14. Due to DEN, C-X bond is polarized with:
slight positive on carbon and
slight negative on halogen
The C-X carbon atom can behave as an electrophile

15. C. Preparing Alkyl Halides
Alkyl halide - is synthesized from addition of HCl, HBr, HI to alkenes to give Markovnikov product
Alkyl dihalide - is synthesized from anti addition of Br2 or Cl2

16. Reaction of Alkanes with Halogens
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

17. Mechanism of the radical chlorination of methane

18. D. Radical Halogenation of Alkanes
Radical halogenation of alkanes is not a good method of alkyl halide synthesis because mixtures of products usually result.

19. If there is more than one type of hydrogen in an alkane, reactions favor replacing the hydrogen at the most highly substituted carbons
30% / 6 = 5%
70% / 4 = 17.5%
Primary H’s
Secondary H’s

20. 35% / 1 = 35%
65% / 9 = 7.2%
Tertiary H’s
Primary H’s

21. Relative Reactivity
Based on quantitative analysis of reaction products, relative reactivity is estimated
Order parallels stability of radicals

22. Increasing alkyl substitution stabilizes the transition state and radical intermediate
The more stable radical forms faster

23. Reaction distinction is more selective with bromine than chlorine

24. Reaction distinction is more selective with bromine than chlorine
Reaction with Br. is much less exergonic
T.Sbromination resembles the alkyl radical more closely than does T.Schlorination

25. Practice Problem: Draw and name all monochloro products you
Practice Problem: Draw and name all monochloro products you would expect to obtain from radical chlorination of 2-methylpentane. Which, if any, are chiral?

26. Practice Problem: Taking the relative reactivities of 1o, 2o, and 3o
Practice Problem: Taking the relative reactivities of 1o, 2o, and 3o hydrogen atoms into account, what product(s) would you expect to obtain from monochlorination of 2-methylbutane? What would the approximate percentage of each product be? (Don’t forget to take into account the number of each type of hydrogen)

27. E. Allylic Bromination of Alkenes
N-bromosuccinimide (NBS) selectively brominates allylic positions
It requires light for activation
It is a source of dilute bromine atoms

28. NBS allylic bromination
Br. radical abstracts an allylic hydrogen
Allylic radical forms as an intermediate and reacts with Br2

29. Bromination with NBS occurs exclusively at an allylic position because:
an allylic radical is more stable than a typical alkyl radical by about 40 kJ/mol

30. Stability Order
Allylic radical is more stable than tertiary alkyl radical

31. F. Stability of the Allyl Radical
Allyl radical is resonance-stabilized
Allyl radical has two resonance forms
Alkyl radical has only one structure

32. The greater the number of resonance forms, the greater the stability

33. Allyl radical is delocalized
The unpaired electron is spread out over an extended p orbital network
The unpaired electron is equally shared between the two terminal carbons

34. Allylic bromination of an unsymmetrical alkene often leads to a mixture of products
less hindered

35. Allylic bromination can be used to convert alkenes into dienes by dehydrohalogenation with base.

36. Practice Problem: Draw three resonance forms for the
Practice Problem: Draw three resonance forms for the cyclohexadienyl radical

37. Practice Problem: The major product of the reaction of
Practice Problem: The major product of the reaction of methylenecyclohexane with N-bromo succinimide is 1-(bromomethyl)cyclohexene Explain.

38. Practice Problem: What products would you expect from the
Practice Problem: What products would you expect from the reaction of the following alkenes with NBS? If more than one product is formed, show the structures of all.

39. G. Preparing Alkyl halides from Alcohols
Alcohols react with HX to form alkyl halides, but the reaction works well for tertiary alcohols, R3COH

40. 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

41. Preparation of Alkyl Halides from Primary and Secondary Alcohols
Primary and secondary alkyl halides are normally prepared from alcohols using either
thionyl chloride (SOCl2)
SOCl2 : ROH  RCl
phosphorus tribromide (PBr3)
PBr3 : ROH  RBr
These reactions use mild conditions – less acidic and less likely to cause rearrangements

43. Practice Problem: How would you prepare the following alkyl
Practice Problem: How would you prepare the following alkyl halides from the corresponding alcohols?

44. H. Reaction of Organohalides: Grignard Reagents
Alkyl halides react with magnesium in ether solution to form organomagnesium halides, Grignard reagents (RMgX)

45. 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

46. The carbon-magnesium bond is polarized
The carbon atom is thus both nucleophilic and basic

47. Reactions of Grignard Reagents
Many useful reactions
RMgX behaves as R-
R- (carbon anions) are very strong bases
RMgX react with such weak acids as H2O, ROH, RCO2H and RNH2 to abstract H+
RMgX + H3O+  R-H

48. Practice Problem: Just how strong a base would you expect a
Practice Problem: Just how strong a base would you expect a Grignard reagent be? Look at Table 8.1, and then predict whether the following reactions will occur as written. (The pKa of NH3 is 35)
CH3MgBr H-CΞC-H  CH H-CΞC-MgBr
CH3MgBr NH3  CH H2N-MgBr

49. Practice Problem: How might you replace a halogen substituent
Practice Problem: How might you replace a halogen substituent by a deuterium atom if you wanted to prepare a deuterated compound?

50. I. 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

51. Alkyllithium (RLi) forms from RBr and Li metal
Alkyllithiums are both nucleophiles and bases

52. RLi reacts with copper iodide to give lithium dialkylcopper (Gilman reagents)

53. Lithium dialkylcopper reagents react with alkyl halides to give alkanes
Gilman reagents undergo organometallic coupling reactions
with chlorides, bromides and iodides (but not fluorides)

54. Utility of Organometallic Coupling in Synthesis
Coupling of two organometallic molecules produces larger molecules of defined structure
Aryl and vinyl organometallics are also effective

55. Coupling of lithium dialkylcopper molecules proceeds through trialkylcopper intermediate

56. Practice Problem: How would you carry out the following
Practice Problem: How would you carry out the following transformations using an organocopper coupling reaction? More than one step is required in each case.

57. J. Oxidation and Reduction in Organic Chemistry
Oxidation is a reaction that results in loss of electron density at carbon either by
bond formation between carbon and a more electronegative atom (oxygen, nitrogen, or halogen)
bond breaking between carbon and a less electronegative atom (usually hydrogen)
Not necessarily defined as loss of electrons by an atom as in inorganic chemistry
Oxidation: break C-H (or C-C) and
: form C-O, C-N, C-X

58. Organic Reduction is the opposite of oxidation
Organic Reduction is the opposite of oxidation. It results in increase of electron density at carbon either by
bond breaking between carbon and a more electronegative atom (oxygen, nitrogen, or halogen)
bond formation between carbon and a less electronegative atom (usually hydrogen)
Reduction: form C-H (or C-C) and
break C-O, C-N, C-X

59. Halogenation
Conversion of alkyl halide to alkane

61. Functional groups are associated with specific levels
Maximum number of C-H
Maximum number of C-X

62. Practice Problem: Rank each of the following series of
Practice Problem: Rank each of the following series of compounds in order of increasing oxidation level:

63. Practice Problem: Tell whether each of the following reactions is
Practice Problem: Tell whether each of the following reactions is an oxidation, a reduction, or neither. Explain your answers.

64. Chapter 10
The End