1. Dr. Wolf's CHM 201 & 202 4- 1 Chapter 4 Alcohols and Alkyl Halides

2. Dr. Wolf's CHM 201 & 202 4- 2 (1) alcohol + hydrogen halide ROH + HX  RX + H 2 O (2) alkane + halogen RH + X 2  RX + HX Both are substitution reactions Overview of Chapter This chapter introduces chemical reactions and their mechanisms by focusing on two reactions that yield alkyl halides.

3. Dr. Wolf's CHM 201 & 202 4- 3 Functional Groups

4. Dr. Wolf's CHM 201 & 202 4- 4 a structural unit in a molecule responsible for its characteristic behavior under a particular set of reaction conditions Functional Group

5. Dr. Wolf's CHM 201 & 202 4- 5 AlcoholROH Alkyl halideRX (X = F, Cl, Br, I) Amineprimary amine: RNH 2 secondary amine: R 2 NH secondary amine: R 2 NH tertiary amine: R 3 N tertiary amine: R 3 N Families of organic compounds and their functional groups

6. Dr. Wolf's CHM 201 & 202 4- 6 EtherROR' NitrileRCN NitroalkaneRNO 2 SulfideRSR' ThiolRSH Epoxide C C O Families of organic compounds and their functional groups

7. Dr. Wolf's CHM 201 & 202 4- 7 O C Carbonyl group O C Acyl group R Many classes of organic compounds contain a carbonyl group

8. Dr. Wolf's CHM 201 & 202 4- 8 O C Carbonyl group O C Aldehyde R H Many classes of organic compounds contain a carbonyl group

9. Dr. Wolf's CHM 201 & 202 4- 9 O C Carbonyl group O C Ketone R R' Many classes of organic compounds contain a carbonyl group

10. Dr. Wolf's CHM 201 & 202 4- 10 O C Carbonyl group O C Carboxylic acid R OH Many classes of organic compounds contain a carbonyl group

11. Dr. Wolf's CHM 201 & 202 4- 11 O C Carbonyl group O C Ester R OR' Many classes of organic compounds contain a carbonyl group

12. Dr. Wolf's CHM 201 & 202 4- 12 O C Carbonyl group O C Amide R NH 2 Many classes of organic compounds contain a carbonyl group

13. Dr. Wolf's CHM 201 & 202 4- 13 IUPAC Nomenclature of Alkyl Halides

14. Dr. Wolf's CHM 201 & 202 4- 14 The two that are most widely used are: functional class nomenclature substitutive nomenclature Both types can be applied to alcohols and alkyl halides. IUPAC Nomenclature There are several kinds of IUPAC nomenclature.

15. Dr. Wolf's CHM 201 & 202 4- 15 Name the alkyl group and the halogen as separate words (alkyl + halide) Functional Class Nomenclature of Alkyl Halides CH 3 F CH 3 CH 2 CH 2 CH 2 CH 2 Cl CH 3 CH 2 CHCH 2 CH 2 CH 3 Br H I

16. Dr. Wolf's CHM 201 & 202 4- 16 Name the alkyl group and the halogen as separate words (alkyl + halide) Functional Class Nomenclature of Alkyl Halides CH 3 F CH 3 CH 2 CH 2 CH 2 CH 2 Cl CH 3 CH 2 CHCH 2 CH 2 CH 3 Br Methyl fluoride Pentyl chloride 1-Ethylbutyl bromide Cyclohexyl iodide H I

17. Dr. Wolf's CHM 201 & 202 4- 17 Name as halo-substituted alkanes. Number the longest chain containing the halogen in the direction that gives the lowest number to the substituted carbon. Substitutive Nomenclature of Alkyl Halides CH 3 CH 2 CH 2 CH 2 CH 2 F CH 3 CHCH 2 CH 2 CH 3 Br CH 3 CH 2 CHCH 2 CH 3 I

18. Dr. Wolf's CHM 201 & 202 4- 18 Name as halo-substituted alkanes. Number the longest chain containing the halogen in the direction that gives the lowest number to the substituted carbon. Substitutive Nomenclature of Alkyl Halides CH 3 CH 2 CH 2 CH 2 CH 2 F CH 3 CHCH 2 CH 2 CH 3 Br 1-Fluoropentane 3-Iodopentane 2-Bromopentane CH 3 CH 2 CHCH 2 CH 3 I

19. Dr. Wolf's CHM 201 & 202 4- 19 Substitutive Nomenclature of Alkyl Halides Halogen and alkyl groups are of equal rank when it comes to numbering the chain. Number the chain in the direction that gives the lowest number to the group (halogen or alkyl) that appears first. CH 3 Cl Cl

20. Dr. Wolf's CHM 201 & 202 4- 20 Substitutive Nomenclature of Alkyl Halides 5-Chloro-2-methylheptane 2-Chloro-5-methylheptane CH 3 Cl Cl

21. Dr. Wolf's CHM 201 & 202 4- 21 IUPAC Nomenclature of Alcohols

22. Dr. Wolf's CHM 201 & 202 4- 22 Name the alkyl group and add "alcohol" as a separate word. Functional Class Nomenclature of Alcohols CH 3 CH 2 OH CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 CCH 2 CH 2 CH 3 OH CH 3

23. Dr. Wolf's CHM 201 & 202 4- 23 Name the alkyl group and add "alcohol" as a separate word. Functional Class Nomenclature of Alcohols CH 3 CH 2 OH CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 CCH 2 CH 2 CH 3 OH CH 3 Ethyl alcohol 1-Methylpentyl alcohol 1,1-Dimethylbutyl alcohol

24. Dr. Wolf's CHM 201 & 202 4- 24 Name as "alkanols." Replace -e ending of alkane name by -ol. Number chain in direction that gives lowest number to the carbon that bears the —OH group. Substitutive Nomenclature of Alcohols CH 3 CH 2 OH CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 CCH 2 CH 2 CH 3 OH CH 3

25. Dr. Wolf's CHM 201 & 202 4- 25 Name as "alkanols." Replace -e ending of alkane name by -ol. Number chain in direction that gives lowest number to the carbon that bears the —OH group. Substitutive Nomenclature of Alcohols CH 3 CH 2 OH CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 CCH 2 CH 2 CH 3 OH CH 3 Ethanol 2-Hexanol 2-Methyl-2-pentanol

26. Dr. Wolf's CHM 201 & 202 4- 26 OH CH 3 Substitutive Nomenclature of Alcohols Hydroxyl groups outrank alkyl groups when it comes to numbering the chain. Number the chain in the direction that gives the lowest number to the carbon that bears the OH group CH 3 OH

27. Dr. Wolf's CHM 201 & 202 4- 27 Substitutive Nomenclature of Alcohols 6-Methyl-3-heptanol 5-Methyl-2-heptanol OH CH 3 OH

28. Dr. Wolf's CHM 201 & 202 4- 28 Classes of Alcohols and Alkyl Halides

29. Dr. Wolf's CHM 201 & 202 4- 29 Alcohols and alkyl halides are classified as primary, 1 o secondary, 2 o tertiary, 3 o according to their "degree of substitution." Degree of substitution is determined by counting the number of carbon atoms directly attached to the carbon that bears the halogen or hydroxyl group. ClassificationClassification

30. Dr. Wolf's CHM 201 & 202 4- 30 CH 3 CH 2 CH 2 CH 2 CH 2 F CH 3 CHCH 2 CH 2 CH 3 Br primary alkyl halide secondary alkyl halide ClassificationClassification CH 3 CCH 2 CH 2 CH 3 OH CH 3 tertiary alcohol H OH secondary alcohol

31. Dr. Wolf's CHM 201 & 202 4- 31 Bonding in Alcohols and Alkyl Halides

32. Dr. Wolf's CHM 201 & 202 4- 32 H H H alcohols and alkyl halides are polar  = 1.7 D  = 1.9 D H H C O H H C Cl ++++ –––– –––– ++++ ++++ Dipole Moments

33. Dr. Wolf's CHM 201 & 202 4- 33 alcohols and alkyl halides are polar  = 1.7 D  = 1.9 D Dipole Moments

34. Dr. Wolf's CHM 201 & 202 4- 34  +  –  –  +  +  – Dipole-Dipole Attractive Forces

35. Dr. Wolf's CHM 201 & 202 4- 35  +  –  –  +  +  – Dipole-Dipole Attractive Forces

36. Dr. Wolf's CHM 201 & 202 4- 36 Boiling point Solubility in water Density Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces

37. Dr. Wolf's CHM 201 & 202 4- 37 444846 -42-32+78 01.91.7 CH 3 CH 2 CH 3 CH 3 CH 2 F CH 3 CH 2 OH Molecular weight Boiling point, °C Dipole moment, D Effect of Structure on Boiling Point

38. Dr. Wolf's CHM 201 & 202 4- 38 44-420 CH 3 CH 2 CH 3 Molecular weight Boiling point, °C Dipole moment, D Intermolecular forces are weak. Only intermolecular forces are induced dipole-induced dipole attractions. Effect of Structure on Boiling Point

39. Dr. Wolf's CHM 201 & 202 4- 39 48-321.9 CH 3 CH 2 F Molecular weight Boiling point, °C Dipole moment, D A polar molecule; therefore dipole-dipole and dipole-induced dipole forces contribute to intermolecular attractions. Effect of Structure on Boiling Point

40. Dr. Wolf's CHM 201 & 202 4- 40 46+781.7 CH 3 CH 2 OH Molecular weight Boiling point, °C Dipole moment, D Highest boiling point; strongest intermolecular attractive forces. Hydrogen bonding is stronger than other dipole-dipole attractions. Effect of Structure on Boiling Point

41. Dr. Wolf's CHM 201 & 202 4- 41 ++++ –––– –––– ++++ Figure 4.4 Hydrogen bonding in ethanol

42. Dr. Wolf's CHM 201 & 202 4- 42 Figure 4.4 Hydrogen bonding in ethanol

43. Dr. Wolf's CHM 201 & 202 4- 43 Boiling point increases with increasing number of halogens CH 3 Cl -24°C CH 2 Cl 2 40°C CHCl 3 61°C CCl 4 77°C CompoundBoiling Point Even though CCl 4 is the only compound in this list without a dipole moment, it has the highest boiling point. Induced dipole-induced dipole forces are greatest in CCl 4 because it has the greatest number of Cl atoms. Cl is more polarizable than H.

44. Dr. Wolf's CHM 201 & 202 4- 44 But trend is not followed when halogen is fluorine CH 3 CH 2 F -32°C CH 3 CHF 2 -25°C CH 3 CF 3 -47°C CF 3 CF 3 -78°C CompoundBoiling Point

45. Dr. Wolf's CHM 201 & 202 4- 45 But trend is not followed when halogen is fluorine CH 3 CH 2 F -32°C CH 3 CHF 2 -25°C CH 3 CF 3 -47°C CF 3 CF 3 -78°C CompoundBoiling Point Fluorine is not very polarizable and induced dipole- induced dipole forces decrease with increasing fluorine substitution.

46. Dr. Wolf's CHM 201 & 202 4- 46 Solubility in water Alkyl halides are insoluble in water. Methanol, ethanol, isopropyl alcohol are completely miscible with water. The solubility of an alcohol in water decreases with increasing number of carbons (compound becomes more hydrocarbon-like).

47. Dr. Wolf's CHM 201 & 202 4- 47 ++++ –––– –––– ++++ –––– ++++ Figure 4.5 Hydrogen Bonding Between Ethanol and Water

48. Dr. Wolf's CHM 201 & 202 4- 48 DensityDensity Alkyl fluorides and alkyl chlorides are less dense than water. Alkyl bromides and alkyl iodides are more dense than water. All liquid alcohols have densities of about 0.8 g/mL.

49. Dr. Wolf's CHM 201 & 202 4- 49 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides ROH + HX  RX + H 2 O

50. Dr. Wolf's CHM 201 & 202 4- 50 ROH + HX  RX + HOH Hydrogen halide reactivity HFHClHBrHI Reaction of Alcohols with Hydrogen Halides least reactive most reactive

51. Dr. Wolf's CHM 201 & 202 4- 51 Alcohol reactivity CH 3 OH RCH 2 OH R 2 CHOH R 3 COH MethanolPrimarySecondaryTertiary ROH + HX  RX + HOH Reaction of Alcohols with Hydrogen Halides least reactive most reactive

52. Dr. Wolf's CHM 201 & 202 4- 52 (CH 3 ) 3 COH + HCl (CH 3 ) 3 CCl + H 2 O 78-88% 25°C CH 3 (CH 2 ) 5 CH 2 OH + HBr CH 3 (CH 2 ) 5 CH 2 Br + H 2 O 87-90%120°C Preparation of Alkyl Halides 73% 80-100°C OH + HBr Br + H2OH2OH2OH2O

53. Dr. Wolf's CHM 201 & 202 4- 53 CH 3 CH 2 CH 2 CH 2 OH CH 3 CH 2 CH 2 CH 2 Br NaBr H 2 SO 4 70-83% heat A mixture of sodium bromide and sulfuric acid may be used in place of HBr. Preparation of Alkyl Halides

54. Dr. Wolf's CHM 201 & 202 4- 54 Mechanism of the Reaction of Alcohols with Hydrogen Halides

55. Dr. Wolf's CHM 201 & 202 4- 55 A mechanism describes how reactants are converted to products. Mechanisms are often written as a series of chemical equations showing the elementary steps. An elementary step is a reaction that proceeds by way of a single transition state. Mechanisms can be shown likely to be correct, but cannot be proven correct. About mechanisms

56. Dr. Wolf's CHM 201 & 202 4- 56 the generally accepted mechanism involves three elementary steps. Step 1 is a Brønsted acid-base reaction. About mechanisms (CH 3 ) 3 COH + HCl (CH 3 ) 3 CCl + H 2 O 25°C tert-Butyl alcohol tert-Butyl chloride For the reaction:

57. Dr. Wolf's CHM 201 & 202 4- 57 Step 1: Proton transfer.. H Cl :.. + fast, bimolecular.. H O : + (CH 3 ) 3 C H Cl :.. : – + tert-Butyloxonium ion H O :.. (CH 3 ) 3 C Like proton transfer from a strong acid to water, proton transfer from a strong acid to an alcohol is normally very fast.

58. Dr. Wolf's CHM 201 & 202 4- 58.. H Cl :.. + fast, bimolecular.. H O : + (CH 3 ) 3 C H Cl :.. : – + tert-Butyloxonium ion H O :.. (CH 3 ) 3 C Two molecules react in this elementary step; therefore it is bimolecular. Step 1: Proton transfer

59. Dr. Wolf's CHM 201 & 202 4- 59.. H Cl :.. + fast, bimolecular.. H O : + (CH 3 ) 3 C H Cl :.. : – + tert-Butyloxonium ion H O :.. (CH 3 ) 3 C Species formed in this step (tert- butyloxonium ion) is an intermediate in the overall reaction. Step 1: Proton transfer

60. Dr. Wolf's CHM 201 & 202 4- 60 Potential energy Reaction coordinate Potential energy diagram for Step 1 HCl (CH 3 ) 3 CO H (CH 3 ) 3 COH + H—Cl + Cl – + (CH 3 ) 3 CO H H

61. Dr. Wolf's CHM 201 & 202 4- 61 (CH 3 ) 3 C O H :H+ + slow, unimolecular (CH 3 ) 3 C O H : H : tert-Butyl cation + Step 2: Carbocation formation Dissociation of the alkyloxonium ion involves bond-breaking, without any bond-making to compensate for it. It has a high activation energy and is slow.

62. Dr. Wolf's CHM 201 & 202 4- 62 (CH 3 ) 3 C O H :H+ + slow, unimolecular (CH 3 ) 3 C O H : H : tert-Butyl cation + A single molecule reacts in this step; therefore, it is unimolecular. Step 2: Carbocation formation

63. Dr. Wolf's CHM 201 & 202 4- 63 (CH 3 ) 3 C O H :H+ + slow, unimolecular (CH 3 ) 3 C O H : H : tert-Butyl cation + The product of this step is a carbocation. It is an intermediate in the overall process. Step 2: Carbocation formation

64. Dr. Wolf's CHM 201 & 202 4- 64 Potential energy Reaction coordinate Potential energy diagram for Step 2 + (CH 3 ) 3 CO H H (CH 3 ) 3 C + H 2 O +  (CH 3 ) 3 C OHH 

65. Dr. Wolf's CHM 201 & 202 4- 65 The key intermediate in reaction of secondary and tertiary alcohols with hydrogen halides is a carbocation. A carbocation is a cation in which carbon has 6 valence electrons and a positive charge. C R R R+CarbocationCarbocation

66. Dr. Wolf's CHM 201 & 202 4- 66 Figure 4.9 Structure of tert-Butyl Cation. Positively charged carbon is sp 2 hybridized. All four carbons lie in same plane. Unhybridized p orbital is perpendicular to plane of four carbons. C CH 3 H3CH3CH3CH3C +

67. Dr. Wolf's CHM 201 & 202 4- 67 fast, bimolecular + (CH 3 ) 3 C + tert-Butyl chloride.. (CH 3 ) 3 C Cl:.... Cl : :..– Step 3: Carbocation capture Bond formation between the positively charged carbocation and the negatively charged chloride ion is fast. Two species are involved in this step. Therefore, this step is bimolecular.

68. Dr. Wolf's CHM 201 & 202 4- 68 fast, bimolecular + (CH 3 ) 3 C + tert-Butyl chloride.. (CH 3 ) 3 C Cl:.... Cl : :..– The carbocation is an electrophile. Chloride ion is a nucleophile. This is a Lewis acid- Lewis base reaction. The carbocation is the Lewis acid; chloride ion is the Lewis base. Step 3: Carbocation capture

69. Dr. Wolf's CHM 201 & 202 4- 69 Step 3: Carbocation capture + (CH 3 ) 3 C + Cl– (CH 3 ) 3 CCl Lewis acid Lewis base ElectrophileNucleophile

70. Dr. Wolf's CHM 201 & 202 4- 70 Potential energy Reaction coordinate Potential energy diagram for Step 3 (CH 3 ) 3 C + Cl – +  (CH 3 ) 3 C Cl  (CH 3 ) 3 C—Cl

71. Dr. Wolf's CHM 201 & 202 4- 71 Potential Energy Diagrams for Multistep Reactions: The S N 1 Mechanism

72. Dr. Wolf's CHM 201 & 202 4- 72 The potential energy diagram for a multistep mechanism is simply a collection of the potential energy diagrams for the individual steps. Consider the three-step mechanism for the reaction of tert-butyl alcohol with HCl. Consider the three-step mechanism for the reaction of tert-butyl alcohol with HCl. Potential Energy Diagram-Overall (CH 3 ) 3 COH + HCl (CH 3 ) 3 CCl + H 2 O 25°C

73. Dr. Wolf's CHM 201 & 202 4- 73 proton transferROH ROH 2 + carbocation formation R+R+R+R+ carbocation captureRX

74. Dr. Wolf's CHM 201 & 202 4- 74 proton transfer ROH ROH 2 + carbocation formation R+R+R+R+ carbocation capture RX (CH 3 ) 3 C O O H H H H Cl ++ ++ –– ––

75. Dr. Wolf's CHM 201 & 202 4- 75 proton transfer ROH ROH 2 + carbocation formation R+R+R+R+ carbocation capture RX (CH 3 ) 3 C ++ ++ O O H H H H ++ ++

76. Dr. Wolf's CHM 201 & 202 4- 76 proton transfer ROH ROH 2 + carbocation formation R+R+R+R+ carbocation capture RX (CH 3 ) 3 C ++ ++ Cl –– ––

77. Dr. Wolf's CHM 201 & 202 4- 77 The mechanism just described is an example of an S N 1 process. The mechanism just described is an example of an S N 1 process. S N 1 stands for substitution-nucleophilic- unimolecular. S N 1 stands for substitution-nucleophilic- unimolecular. The molecularity of the rate-determining step defines the molecularity of the overall reaction. Mechanistic notation

78. Dr. Wolf's CHM 201 & 202 4- 78 The molecularity of the rate-determining step defines the molecularity of the overall reaction. (CH 3 ) 3 C ++ ++ O O H H H H ++ ++ Rate-determining step is unimolecular dissociation of alkyloxonium ion. Mechanistic notation

79. Dr. Wolf's CHM 201 & 202 4- 79 Structure, Bonding, and Stability of Carbocations

80. Dr. Wolf's CHM 201 & 202 4- 80 Most carbocations are too unstable to be isolated, but occur as reactive intermediates in a number of reactions. When R is an alkyl group, the carbocation is stabilized compared to R = H. C R R R+CarbocationsCarbocations

81. Dr. Wolf's CHM 201 & 202 4- 81 C H H H+ Methyl cation least stable CarbocationsCarbocations

82. Dr. Wolf's CHM 201 & 202 4- 82 C H3CH3CH3CH3C H H + Ethyl cation (a primary carbocation) is more stable than CH 3 + CarbocationsCarbocations

83. Dr. Wolf's CHM 201 & 202 4- 83 C H3CH3CH3CH3C CH 3 H + Isopropyl cation (a secondary carbocation) is more stable than CH 3 CH 2 + CarbocationsCarbocations

84. Dr. Wolf's CHM 201 & 202 4- 84 C H3CH3CH3CH3C CH 3 + tert-Butyl cation (a tertiary carbocation) is more stable than (CH 3 ) 2 CH + CarbocationsCarbocations

85. Dr. Wolf's CHM 201 & 202 4- 85 positively charged carbon pulls electrons in  bonds closer to itself + Figure 4.15 Stabilization of carbocations via the inductive effect

86. Dr. Wolf's CHM 201 & 202 4- 86 positive charge is "dispersed ", i.e., shared by carbon and the three atoms attached to it   Figure 4.15 Stabilization of carbocations via the inductive effect

87. Dr. Wolf's CHM 201 & 202 4- 87 electrons in C—C bonds are more polarizable than those in C—H bonds; therefore, alkyl groups stabilize carbocations better than H.   Electronic effects transmitted through  bonds are called "inductive effects." Figure 4.15 Stabilization of carbocations via the inductive effect 

88. Dr. Wolf's CHM 201 & 202 4- 88 electrons in this  bond can be shared by positively charged carbon because the  orbital can overlap with the empty 2p orbital of positively charged carbon + Figure 4.16 Stabilization of carbocations via hyperconjugation

89. Dr. Wolf's CHM 201 & 202 4- 89 electrons in this  bond can be shared by positively charged carbon because the  orbital can overlap with the empty 2p orbital of positively charged carbon   Figure 4.16 Stabilization of carbocations via hyperconjugation

90. Dr. Wolf's CHM 201 & 202 4- 90 Notice that an occupied orbital of this type is available when sp 3 hybridized carbon is attached to C +, but is not available when H is attached to C +. Therefore,alkyl groups stabilize carbocations better than H does. Figure 4.16 Stabilization of carbocations via hyperconjugation  

91. Dr. Wolf's CHM 201 & 202 4- 91 Effect of Alcohol Structure on Reaction Rate

92. Dr. Wolf's CHM 201 & 202 4- 92 The more stable the carbocation, the faster it is formed. Tertiary carbocations are more stable than secondary, which are more stable than primary, which are more stable than methyl. Tertiary alcohols react faster than secondary, which react faster than primary, which react faster than methanol. Slow step is: R OHH + R + + OHH

93. Dr. Wolf's CHM 201 & 202 4- 93 High activation energy for formation of methyl cation. CH 3 OHH + CH 3 + + OHH E act CH 3 ++++ OHH ++++

94. Dr. Wolf's CHM 201 & 202 4- 94 RCH 2 OHH + RCH 2 + + OHH Smaller activation energy for formation of primary carbocation. RCH 2 ++++ OHH ++++ E act

95. Dr. Wolf's CHM 201 & 202 4- 95 R 2 CH OHH + R 2 CH + + OHH Activation energy for formation of secondary carbocation is less than that for formation of primary carbocation. R 2 CH ++++ OHH ++++ E act

96. Dr. Wolf's CHM 201 & 202 4- 96 E act R3CR3CR3CR3C OHH + R3CR3CR3CR3C + + OHH Activation energy for formation of tertiary carbocation is less than that for formation of secondary carbocation. R3CR3CR3CR3C ++++ OHH ++++

97. Dr. Wolf's CHM 201 & 202 4- 97 Reaction of Primary Alcohols with Hydrogen Halides. The S N 2 Mechanism

98. Dr. Wolf's CHM 201 & 202 4- 98 (CH 3 ) 3 COH + HCl (CH 3 ) 3 CCl + H 2 O 78-88% 73% CH 3 (CH 2 ) 5 CH 2 OH + HBr CH 3 (CH 2 ) 5 CH 2 Br + H 2 O 87-90% 25°C 80-100°C 120°C Preparation of Alkyl Halides OH + HBr Br + H2OH2OH2OH2O

99. Dr. Wolf's CHM 201 & 202 4- 99 CH 3 (CH 2 ) 5 CH 2 OH + HBr CH 3 (CH 2 ) 5 CH 2 Br + H 2 O 87-90% 120°C Primary carbocations are too high in energy to allow S N 1 mechanism. Yet, primary alcohols are converted to alkyl halides. Primary alcohols react by a mechanism called S N 2 (substitution-nucleophilic-bimolecular). Preparation of Alkyl Halides

100. Dr. Wolf's CHM 201 & 202 4- 100 Two-step mechanism for conversion of alcohols to alkyl halides: (1) proton transfer to alcohol to form alkyloxonium ion (2) bimolecular displacement of water from alkyloxonium ion by halide The S N 2 Mechanism

101. Dr. Wolf's CHM 201 & 202 4- 101 CH 3 (CH 2 ) 5 CH 2 OH + HBr CH 3 (CH 2 ) 5 CH 2 Br + H 2 O 120°C ExampleExample

102. Dr. Wolf's CHM 201 & 202 4- 102 Step 1: Proton transfer from HBr to 1-heptanol H.. :HBr :.... + O CH 3 (CH 2 ) 5 CH 2 H O : + H Br :.... : – + fast, bimolecular Heptyloxonium ion CH 3 (CH 2 ) 5 CH 2 MechanismMechanism

103. Dr. Wolf's CHM 201 & 202 4- 103 Step 2: Reaction of alkyloxonium ion with bromide ion. ion. Br : :....– + H O :H+ CH 3 (CH 2 ) 5 CH 2 1-Bromoheptane slow, bimolecular Br :.... CH 3 (CH 2 ) 5 CH 2 + O H : H : MechanismMechanism

104. Dr. Wolf's CHM 201 & 202 4- 104 CH 2 OH 2 ++ ++ Br –– –– CH 3 (CH 2 ) 4 CH 2 proton transfer ROH ROH 2 + RX

105. Dr. Wolf's CHM 201 & 202 4- 105 Other Methods for Converting Alcohols to Alkyl Halides

106. Dr. Wolf's CHM 201 & 202 4- 106 Thionyl chloride SOCl 2 + ROH  RCl + HCl + SO 2 Phosphorus tribromide PBr 3 + 3ROH  3RBr + H 3 PO 3 Reagents for ROH to RX

107. Dr. Wolf's CHM 201 & 202 4- 107 CH 3 CH(CH 2 ) 5 CH 3 OH SOCl 2 K 2 CO 3 CH 3 CH(CH 2 ) 5 CH 3 Cl (81%) (pyridine often used instead of K 2 CO 3 ) (CH 3 ) 2 CHCH 2 OH (55-60%) (CH 3 ) 2 CHCH 2 Br PBr 3 ExamplesExamples

108. Dr. Wolf's CHM 201 & 202 4- 108 Halogenation of Alkanes RH + X 2  RX + HX

109. Dr. Wolf's CHM 201 & 202 4- 109 RH + X 2  RX + HX explosive for F 2 exothermic for Cl 2 and Br 2 endothermic for I 2 EnergeticsEnergetics

110. Dr. Wolf's CHM 201 & 202 4- 110 Chlorination of Methane

111. Dr. Wolf's CHM 201 & 202 4- 111 carried out at high temperature (400 °C) CH 4 + Cl 2  CH 3 Cl + HCl CH 3 Cl + Cl 2  CH 2 Cl 2 + HCl CH 2 Cl 2 + Cl 2  CHCl 3 + HCl CHCl 3 + Cl 2  CCl 4 + HCl Chlorination of Methane

112. Dr. Wolf's CHM 201 & 202 4- 112 Structure and Stability of Free Radicals

113. Dr. Wolf's CHM 201 & 202 4- 113 contain unpaired electrons...... O O:O:O:O: : Examples: O 2 NO N O :..:. ClCl... :.. Free Radicals

114. Dr. Wolf's CHM 201 & 202 4- 114 Most free radicals in which carbon bears the unpaired electron are too unstable to be isolated. Alkyl radicals are classified as primary, secondary, or tertiary in the same way that carbocations are. C R R R. Alkyl Radicals

115. Dr. Wolf's CHM 201 & 202 4- 115 Figure 4.19 Structure of methyl radical. Methyl radical is planar, which suggests that carbon is sp 2 hybridized and that the unpaired electron is in a p orbital.

116. Dr. Wolf's CHM 201 & 202 4- 116 C R R R. The order of stability of free radicals is the same as for carbocations. Alkyl Radicals

117. Dr. Wolf's CHM 201 & 202 4- 117 C H H H. Methyl radical less stable than C H3CH3CH3CH3C H H. Ethyl radical (primary) C H3CH3CH3CH3C CH 3 H. Isopropyl radical (secondary) less stable than C H3CH3CH3CH3C CH 3. tert-Butyl radical (tertiary) Alkyl Radicals

118. Dr. Wolf's CHM 201 & 202 4- 118 The order of stability of free radicals can be determined by measuring bond strengths. By "bond strength" we mean the energy required to break a covalent bond. A chemical bond can be broken in two different ways—heterolytically or homolytically. Alkyl Radicals

119. Dr. Wolf's CHM 201 & 202 4- 119 In a homolytic bond cleavage, the two electrons in the bond are divided equally between the two atoms. One electron goes with one atom, the second with the other atom. In a heterolytic cleavage, one atom retains both electrons. In a heterolytic cleavage, one atom retains both electrons. – + Homolytic Heterolytic

120. Dr. Wolf's CHM 201 & 202 4- 120 The species formed by a homolytic bond cleavage of a neutral molecule are free radicals. Therefore, measure energy cost of homolytic bond cleavage to gain information about stability of free radicals. The more stable the free-radical products, the weaker the bond, and the lower the bond-dissociation energy. Homolytic

121. Dr. Wolf's CHM 201 & 202 4- 121 Bond-dissociation energy measurements tell us that isopropyl radical is 13 kJ/mol more stable than propyl. 410397 CH 3 CH 2 CH 3 CH 3 CH 2 CH 2 +H.. CH 3 CHCH 3 +H.. Measures of Free Radical Stability

122. Dr. Wolf's CHM 201 & 202 4- 122 Bond-dissociation energy measurements tell us that tert-butyl radical is 30 kJ/mol more stable than isobutyl. 410 (CH 3 ) 3 CH (CH 3 ) 2 CHCH 2 +H.. (CH 3 ) 3 C + H.. 380 Measures of Free Radical Stability

123. Dr. Wolf's CHM 201 & 202 4- 123 Mechanism of Chlorination of Methane

124. Dr. Wolf's CHM 201 & 202 4- 124 The initiation step "gets the reaction going" by producing free radicals—chlorine atoms from chlorine molecules in this case. Initiation step is followed by propagation steps. Each propagation step consumes one free radical but generates another one. :.. Cl.. : Cl..:.... Cl..:. : Cl..... + Free-radical chain mechanism. Initiation step: Mechanism of Chlorination of Methane

125. Dr. Wolf's CHM 201 & 202 4- 125 Cl:..... H 3 C : H H : Cl:.... H3CH3CH3CH3C.+ + First propagation step: Second propagation step: + + Cl:..... H3CH3CH3CH3C. :.. Cl.. : Cl.. :.. H3CH3CH3CH3C.... : Cl : Mechanism of Chlorination of Methane

126. Dr. Wolf's CHM 201 & 202 4- 126 Cl:..... H 3 C : H H : Cl:.... H3CH3CH3CH3C.+ + Second propagation step: + + ++ First propagation step: Cl:..... H3CH3CH3CH3C. :.. Cl.. : Cl..:.. H 3 C : H H : Cl:.... :.. Cl.. : Cl..:.. H3CH3CH3CH3C.... : Cl : H3CH3CH3CH3C.... : Cl : Mechanism of Chlorination of Methane

127. Dr. Wolf's CHM 201 & 202 4- 127 Almost all of the product is formed by repetitive cycles of the two propagation steps. Cl:..... H 3 C : H H : Cl:.... H3CH3CH3CH3C.+ + Second propagation step: + + ++ First propagation step: Cl:..... H3CH3CH3CH3C. :.. Cl.. : Cl..:.. H 3 C : H H : Cl:.... :.. Cl.. : Cl..:.. H3CH3CH3CH3C.... : Cl : H3CH3CH3CH3C.... : Cl :

128. Dr. Wolf's CHM 201 & 202 4- 128 stop chain reaction by consuming free radicals hardly any product is formed by termination step because concentration of free radicals at any instant is extremely low hardly any product is formed by termination step because concentration of free radicals at any instant is extremely low + H3CH3CH3CH3C. Cl:..... H3CH3CH3CH3C.... : Cl : Termination Steps

129. Dr. Wolf's CHM 201 & 202 4- 129 Halogenation of Higher Alkanes

130. Dr. Wolf's CHM 201 & 202 4- 130 CH 3 CH 3 + Cl 2 CH 3 CH 2 Cl + HCl 420°C (78%) Cl + Cl 2 + Cl 2 + HCl + HCl h (73%) can be used to prepare alkyl chlorides from alkanes in which all of the hydrogens are equivalent to one another Chlorination of Alkanes

131. Dr. Wolf's CHM 201 & 202 4- 131 Major limitation: Chlorination gives every possible monochloride derived from original carbon skeleton. Not much difference in reactivity of different hydrogens in molecule. Chlorination of Alkanes

132. Dr. Wolf's CHM 201 & 202 4- 132 CH 3 CH 2 CH 2 CH 3 Cl 2 h Chlorination of butane gives a mixture of 1-chlorobutane and 2-chlorobutane. CH 3 CH 2 CH 2 CH 2 Cl CH 3 CHCH 2 CH 3 Cl (28%) (72%) ExampleExample

133. Dr. Wolf's CHM 201 & 202 4- 133 Percentage of product that results from substitution of indicated hydrogen if every collision with chlorine atoms is productive 10% 10% 10% 10% 10% 10% 10% 10% 10% 10%10%

134. Dr. Wolf's CHM 201 & 202 4- 134 Percentage of product that actually results from replacement of indicated hydrogen 4.6% 4.6% 4.6% 18% 18% 18% 10% 4.6% 4.6% 4.6% 18%

135. Dr. Wolf's CHM 201 & 202 4- 135 divide by 4.6 4.64.6 = 1 184.6 = 3.9 A secondary hydrogen is abstracted 3.9 times faster than a primary hydrogen by a chlorine atom. 4.6% 18% Relative rates of hydrogen atom abstraction

136. Dr. Wolf's CHM 201 & 202 4- 136 Similarly, chlorination of 2-methylproane gives a mixture of isobutyl chloride and tert-butyl chloride H CH 3 CCH 3 CH 3 CH 3 CCH 2 Cl CH 3 H Cl CH 3 CCH 3 CH 3 h Cl 2 (63%)(37%)

137. Dr. Wolf's CHM 201 & 202 4- 137 Percentage of product that results from replacement of indicated hydrogen 7.0% 37%

138. Dr. Wolf's CHM 201 & 202 4- 138 37 7.0 divide by 7 7 = 1 7 = 5.3 A tertiary hydrogen is abstracted 5.3 times faster than a primary hydrogen by a chlorine atom. Relative rates of hydrogen atom abstraction

139. Dr. Wolf's CHM 201 & 202 4- 139 R 3 CH>R 2 CH 2 >RCH 3 chlorination: 5 41 bromination:1640821 Chlorination of an alkane gives a mixture of every possible isomer having the same skeleton as the starting alkane. Useful for synthesis only when all hydrogens in a molecule are equivalent. Bromination is highly regioselective for substitution of tertiary hydrogens. Major synthetic application is in synthesis of tertiary alkyl bromides. Selectivity of free-radical halogenation

140. Dr. Wolf's CHM 201 & 202 4- 140 Chlorination is useful for synthesis only when all of the hydrogens in a molecule are equivalent. (64%) Cl 2 h Synthetic application of chlorination of an alkane Cl

141. Dr. Wolf's CHM 201 & 202 4- 141 Bromination is highly selective for substitution of tertiary hydrogens. Major synthetic application is in synthesis of tertiary alkyl bromides. Major synthetic application is in synthesis of tertiary alkyl bromides. (76%) Br 2 hH CH 3 CCH 2 CH 2 CH 3 CH 3 Br CH 3 CCH 2 CH 2 CH 3 CH 3 Synthetic application of bromination of an alkane

142. Dr. Wolf's CHM 201 & 202 4- 142 End of Chapter 4