1. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Prof. Duncan Wardrop October 22, 2012 CHEM 494 - Lecture 7

2. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Chapter 19 Preparation of Alkenes Elimination

3. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 3 Dehydration can be “Coupled” with Other Chemical Transformation Two-step, one-pot transformation involves a Friedel-Crafts reaction (see, Chapter 12) and dehydration of the resulting 3° alcohol

4. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 4 Rate of Alcohol Dehydration Mirrors Ease of Carbocation Formation rate of dehydration = 3º > 2º > 1º alcohol tertiary alcohol (3º) secondary alcohol (2º) primary alcohol (1º) tertiary cation (3º) secondary cation (2°) primary cation (1°) ReactivityStability

5. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 5 Predict the product for the following reaction scheme. Self Test Question A.B. C.D. E. no reaction

6. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 6 Predict the product for the following reaction scheme. Self Test Question A.B. C.D. E. no reaction

7. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Chapter 19 Regioselectivity & Stereoselectivity of Dehydration

8. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 8 A. B. C. D. E. What is the product(s) of the following reaction? Self Test Question

9. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 9 Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider.... Chemoselectivity: which functional group will react Regioselectivity: where it will react Stereoselectivity: how it will react with regards to stereochemical outcome... for each transformation, always question which of these are factors are at play.

10. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 10 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009

11. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 11 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009

12. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 12 Greek Lettering & Elimination Reactions Nomenclature The α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at α- carbon

13. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 13 Regioselectivity of Elimination Zaitsev Rule 1 Hs on this β carbon 2 Hs on this β carbon 3 Hs on this β carbon Zaitsev Rule When elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens

14. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 14 Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) trisubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other major product

15. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 15 What is the major product expected for the reaction scheme below? Self Test Question A. B. C. D. E.

16. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Chapter 19 E1 & E2 Mechanisms of Alcohol Dehydration

17. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 17 Organic Mechanisms (S N 1)

18. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 18 Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms electrons atoms resonance: electrons in a covalent bond moving out to an atom resonance: lone pair of electrons moving in between two atoms to form a new covalent bond bond making: lone pair of electrons forming a new bond to another atom bond breaking: electrons in a bond leaving to most electronegative atom

19. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 19 Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) pK a = -3.0

20. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 20 Mechanism of Dehydration (E1) Step Two Dissociation

21. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 21 Mechanism of Dehydration (E1) Step Three Carbocation Capture β- Deprotonation!

22. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 22 Hughes-Ingold Nomenclature E1 overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order elimination unimolecular

23. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 23 Each Step of E1 Mechanism is Reversible If all steps in E1 are reversible, what drives the reaction forward?

24. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 24 Alkenes Isolated from Dehydration Reactions by Distillation alkenes have much lower boiling points than alcohols alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogen- bonding by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remainLeChatlier Principle

25. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 Why Can’t Hydrogen Halides Be Used for Elimination Reactions? Nucleophilic addition of chloride (Cl – ) to a carbocation is not reversible

26. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 26 Reactivity Explained 3º carbocations are more stable than 2º = 3º lower in energy smaller activation energy leading to 3º carbocation results in faster reaction

27. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 27 Bimolecular Substitution - S N 2 Mechanism (from Lecture 8) C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond RDS is nucleophilic attack; bimolecular, therefore Ingold notation = S N 2 fewer steps does not mean faster reaction

28. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 28 Dehydration of Primary Alcohols Proceeds via E2 Mechanism C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond RDS is nucleophilic attack; bimolecular, therefore Ingold notation = S N 2 fewer steps does not mean faster reaction

29. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Regioselectivity & Stereoselectivity of Dehydration

30. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 30 A. B. C. D. E. What is the product(s) of the following reaction? Self Test Question

31. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 31 Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider.... Chemoselectivity: which functional group will react Regioselectivity: where it will react Stereoselectivity: how it will react with regards to stereochemical outcome... for each transformation, always question which of these are factors are at play.

32. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 32 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009

33. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 33 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009

34. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 34 Greek Lettering & Elimination Reactions Nomenclature The α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at α- carbon

35. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 35 Regioselectivity of Elimination Zaitsev Rule 1 Hs on this β carbon 2 Hs on this β carbon 3 Hs on this β carbon Zaitsev Rule When elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens

36. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 36 Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) trisubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other major product

37. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 37 What is the major product expected for the reaction scheme below? Self Test Question A. B. C. D. E.

38. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Section: 5.12 E1 & E2 Mechanisms of Alcohol Dehydration

39. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 39 Organic Mechanisms (S N 1)

40. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 40 Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms electrons atoms resonance: electrons in a covalent bond moving out to an atom resonance: lone pair of electrons moving in between two atoms to form a new covalent bond bond making: lone pair of electrons forming a new bond to another atom bond breaking: electrons in a bond leaving to most electronegative atom

41. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 41 Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) pK a = -3.0

42. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 42 Mechanism of Dehydration (E1) Step Two Dissociation

43. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 43 Mechanism of Dehydration (E1) Step Three Carbocation Capture β- Deprotonation!

44. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 44 Hughes-Ingold Nomenclature E1 overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order elimination unimolecular

45. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 45 Each Step of E1 Mechanism is Reversible If all steps in E1 are reversible, what drives the reaction forward?

46. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 46 Alkenes Isolated from Dehydration Reactions by Distillation alkenes have much lower boiling points than alcohols alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogen- bonding by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remainLeChatlier Principle

47. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 Why Can’t Hydrogen Halides Be Used for Elimination Reactions? Nucleophilic addition of chloride (Cl – ) to a carbocation is not reversible

48. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 48 Reactivity Explained 3º carbocations are more stable than 2º = 3º lower in energy smaller activation energy leading to 3º carbocation results in faster reaction

49. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 49 Bimolecular Substitution - S N 2 Mechanism (from Lecture 8) C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond RDS is nucleophilic attack; bimolecular, therefore Ingold notation = S N 2 fewer steps does not mean faster reaction

50. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 50 Dehydration of Primary Alcohols Proceeds via E2 Mechanism C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond RDS is nucleophilic attack; bimolecular, therefore Ingold notation = S N 2 fewer steps does not mean faster reaction

51. University of Illinois at Chicago UIC CHEM 494 Special Topics in Chemistry Addition Reactions of Alkenes

52. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 52 Addition Reactions of Alkenes

53. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 53 Hydrogenation Pd/C, CH 3 CH 2 OH exothermic reaction (-∆Hº), but high E act - catalyst required catalysts are heterogeneous transition metals (Pd, Rsolvent is typically an alcohol (e.g. ethanol, CH 3 CH 2 OH)metals are insoluble (heterogeneous mixture)heat of hydrogenation = -∆Hº

54. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 54 Heat of Hydrogenation (-∆Hº)

55. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 55 Heat of Hydrogenation (-∆Hº) Alkene-∆Hº (kJ/mol)example ethylene136 monosubstituted126 cis-disubstituted119 terminally disubstituted117 trisubstituted112 tetrasubstituted110 Since only the double bond is undergoing the reaction, heat of hydrogenation is independent of the number of carbon atoms in the molecule

56. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 56 General Mechanism for Heterogenious Hydrogenation reaction takes places at the surface of the catalyst (many metal atoms combined)

57. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 57 Step 1: Oxidative Addition hydrogen (H 2 ) is added to metal metal is oxidized from M 0 to M II

58. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 58 Step 2: Coordination metal is a Lewis acid (electron acceptor) π-bond is a lewis base (electron donor) coordination = Lewis acid/base complex

59. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 59 Step 3: Insertion two carbon atoms inserted between Pd-H formation of a weak metal-carbon σ-bond formation of a strong C-H σ-bond break a weak metal-H σ-bond

60. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 60 Step 4: Reductive Elimination metal is reduced from M II to M 0 last σ C-H -bond is formed from the same face of alkene as previous metal is a catalyst; it is regenerated

61. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 61 Complete Mechanism

62. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 62 Syn Addition of Hydrogen as a consequence of mechanism, both hydrogens are added to the same face of the π-bond: syn additionno anti-addition products are formed (addition of hydrogen to opposite faces)

63. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 63 Hydrogenation is Stereoselective This methyl group sterically hinders hydrogen from approaching the π-bond from the top face both products are arise from syn additions of hydrogen to alkenestereoselective: preference for one stereoisomer when two or more are possible

64. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 64 Example of Syn Addition

65. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 65 A. B. C. D. What is the major product of the following hydrogenation reaction? Self Test Question

66. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 66 Addition of Electrophiles to Alkene

67. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 67 Electrophilic Addition of HX δ+δ+ δ–δ– electrophile nucleophile

68. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 68 Reaction Conditions hydrogen halide: HXcommon solvents: chloroform (CHCl 3 ),dichloromethane (CH 2 Cl 2 ), pentane, acetic acidgenerally performed at low temperature (below 0 °C)generally a fast reaction

69. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 69 Electrophilic Addition (Ad E ) Mechanism electrophilic addition: AdERDS = protonation of carbonrate = k[alkene][hydrogen halide]unlike oxygen and nitrogen, protonation of carbon is slowproceeds through carbocation intermediate

70. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 70 HX Addition is Regioselective Regioselectivity Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2010

71. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 71 Markovnikov’s Rule 3º 2º addition of HX to an unsymmetrically substituted alkene proceeds so that hydrogen (H) adds to the least substituted carbon and the halide (X) adds to the most substituted carbon atom

72. UIC University of Illinois at Chicago CHEM 494, Fall 2012 Slide Lecture 8: November 5 72 A. 3-chloro-2,4-dimethylpentane B. 2-chloroohexane C. 2,3-dichloro-2,4- dimethylpentane D. 2-chloro-2,4-dimethylpentane E. 1-chloro-2,4-dimethylpentane Predict the product when 2,4-dimethyl-2-pentene is treated with HCl? Self Test Question

73. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 73 Mechanistic Basis for Markovnikov’s Rule curved arrows do not indicate which carbon is protonated fastest protonation leads to more stable (more substituted) carbocation more substituted carbocation = more substituted alkyl halide

74. UIC University of Illinois at Chicago CHEM 494, Spring 2010 Slide Lecture 8: November 5 74 Mechanistic Basis for Markovnikov’s Rule Hammond Postulate: transition state structure resembles closest energy intermediate transition state resembles carbocation for endothermic RDS (late transition state) what stabilizes carbocation also stabilizes transition state lowest energy transition state leads to more substituted carbocation more substituted carbocation provides more substituted alkyl halide