Mastery of Alkene Preparation: Dehydration Coupling with Transformations

1. CHEM 494 - Lecture 7 Prof. Duncan Wardrop October 22, 2012

2. Preparation of Alkenes Elimination Chapter 19

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. Rate of Alcohol DehydrationMirrors Ease of Carbocation Formation Reactivity Stability rate of dehydration = 3º > 2º > 1º alcohol tertiary cation (3º) tertiary alcohol (3º) secondary cation (2°) secondary alcohol (2º) primary alcohol (1º) primary cation (1°)

5. Self Test Question Predict the product for the following reaction scheme. A. B. C. D. E. no reaction

6. Self Test Question Predict the product for the following reaction scheme. A. B. C. D. E. no reaction

7. Regioselectivity & Stereoselectivity of Dehydration Chapter 19

8. Self Test Question What is the product(s) of the following reaction? A. B. C. D. E.

9. Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider . . . . • Chemoselectivity: whichfunctional group will react • Regioselectivity: where it will react • Stereoselectivity: howit will react with regards to stereochemical outcome . . . for each transformation, always question which of these are factors are at play.

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. 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. 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. Regioselectivity of EliminationZaitsev Rule 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 3 Hs on this β carbon 1 Hs on this β carbon 2 Hs on this β carbon

14. Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) major product trisubstituted trisubstituted disubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other

15. Self Test Question What is the major product expected for the reaction scheme below? A. B. C. D. E.

16. E1 & E2 Mechanisms of Alcohol Dehydration Chapter 19

17. Organic Mechanisms (SN1)

18. Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms atoms electrons resonance:electrons in a covalent bond moving out to an atom bond making: lone pair of electrons forming a new bond to another atom resonance: lone pair of electrons moving in between two atoms to form a new covalent bond bond breaking:electrons in a bond leaving to most electronegative atom

19. Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) pKa = -3.0

20. Mechanism of Dehydration (E1) Step Two Dissociation

21. Mechanism of Dehydration (E1) Step Three Carbocation Capture β-Deprotonation!

22. Hughes-Ingold Nomenclature E1 elimination unimolecular overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order

23. Each Step of E1 Mechanism is Reversible If all steps in E1 are reversible, what drives the reaction forward?

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 remain

25. Why Can’t Hydrogen Halides Be Used for Elimination Reactions? Nucleophilic addition of chloride (Cl–) to a carbocation is not reversible

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. Bimolecular Substitution - SN2 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 = SN2 • fewer steps does not mean faster reaction

28. Dehydration of Primary AlcoholsProceeds 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 = SN2 • fewer steps does not mean faster reaction

29. Regioselectivity & Stereoselectivity of Dehydration

30. Self Test Question What is the product(s) of the following reaction? A. B. C. D. E.

31. Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider . . . . • Chemoselectivity: whichfunctional group will react • Regioselectivity: where it will react • Stereoselectivity: howit will react with regards to stereochemical outcome . . . for each transformation, always question which of these are factors are at play.

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. 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. 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. Regioselectivity of EliminationZaitsev Rule 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 3 Hs on this β carbon 1 Hs on this β carbon 2 Hs on this β carbon

36. Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) major product trisubstituted trisubstituted disubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other

37. Self Test Question What is the major product expected for the reaction scheme below? A. B. C. D. E.

38. E1 & E2 Mechanisms of Alcohol Dehydration Section: 5.12

39. Organic Mechanisms (SN1)

40. Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms atoms electrons resonance:electrons in a covalent bond moving out to an atom bond making: lone pair of electrons forming a new bond to another atom resonance: lone pair of electrons moving in between two atoms to form a new covalent bond bond breaking:electrons in a bond leaving to most electronegative atom

41. Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) pKa = -3.0

42. Mechanism of Dehydration (E1) Step Two Dissociation

43. Mechanism of Dehydration (E1) Step Three Carbocation Capture β-Deprotonation!

44. Hughes-Ingold Nomenclature E1 elimination unimolecular overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order

45. Each Step of E1 Mechanism is Reversible If all steps in E1 are reversible, what drives the reaction forward?

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 remain

47. Why Can’t Hydrogen Halides Be Used for Elimination Reactions? Nucleophilic addition of chloride (Cl–) to a carbocation is not reversible

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. Bimolecular Substitution - SN2 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 = SN2 • fewer steps does not mean faster reaction

50. Dehydration of Primary AlcoholsProceeds 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 = SN2 • fewer steps does not mean faster reaction