1. Revision Session
Organic Chemistry

2. Stereochemistry and mechanism
Starter
Past Paper Questions and Answers

6. Starter Past Paper Questions and Answers
Aromaticity
Starter
Past Paper Questions and Answers

7. Question 1
(a) Huckel’s Rule
Discuss
[100%]

8. Aromatics

10. Carbonyl Group Chemistry
Revision and Past Paper Questions and Answers
Carbonyl Group Chemistry

11. Basic Carbonyl Chemistry
Carbonyl acts as both an electrophile and a nucleophile
Carbonyl has resonance structure

12. Basic carbonyl chemistry
Electrophile:

13. Basic carbonyl chemistry
Formation of Enolates and Enols Removal of alpha-proton (most acidic)

14. Basic carbonyl chemistry
Enolate Alkylation Nucleophile

15. Basic carbonyl chemistry
Acidities of alpha and beta carbonyl protons

16. Basic carbonyl chemistry
1,3 – Dicarbonyl Compounds Why is central alpha proton more acidic? Conjugation and intramolecular H – bonding

17. Basic carbonyl chemisty
Alpha substitution reactions Reaction with an electrophile (acid catalysed)

18. Basic carbonyl chemistry
Alpha substitution reactions Reaction with an electrophile (base catalysed)

19. Basic carbonyl chemistry
Bases used for enolate formation Carbonyl compounds weakly acidic Strong base needed to ensure complete enolate formation LDA Lithium diisopropylamide

20. Basic carbonyl chemistry
Deuterium Substitution of alpha protons When enriched with D2O (acid or base), all alpha protons are in equilibria with deuterium Used as an isotopic label in molecules

22. Basic carbonyl chemistry
Racemization Stereochemistry at alpha carbon is lost during enolate formation Protonated unequally at two faces

23. Basic Carbonyl CHemistry
Halogenation of Carbonyls (acid catalysed)

24. Basic carbonyl chemistry
Halogenation of Carbonyls (lewis acid)

25. Basic carbonyl chemistry
Unsymmetrical Ketones Two different enols are formed Occurs preferentially at the more substituted position as more stable

26. Basic carbonyl chemistry
Enolates of Unsymetrical Ketones
Kinetic favoured due to unhindered alpha protons

27. Basic carbonyl chemistry
1,3 – Dicarbonyl Compounds Alkylate at different sites in different conditions

28. Basic carbonyl chemistry
Decarboxylation of beta-ketoesters

29. Basic carbonyl chemistry
Add a -CH2CO2H to an alkyl halide

30. Basic carbonyl chemistry
Add a -CH2COCH3 to an alkyl halide

31. Basic carbonyl chemistry
Add a -CH2CO2H then –COCH3 to an acyl halide

32. Aldol reaction
eset.jsp?tab_tab_group_id=_4_1&url=%2Fweba pps%2Fblackboard%2Fexecute%2Flauncher%3Ft ype%3DCourse%26id%3D_85894_1%26url%3D Click Vignettes – Level 1 – Aldol Reaction

33. Basic carbonyl chemistry
Aldol Reaction Mixed Aldol Reaction Use LDA (one equivalent) to convert all of aldehyde to enolate Same Ketone Aldol Reaction Use NaOEt/EtOH to convert a small proportion to enolate

34. Basic carbonyl chemistry
Aldol Dehydration Base Catalysed Acid Catalysed (more common)

35. Basic carbonyl chemistry
Intramolecular Aldol Reactions Dicarbonyl compounds treated with base Leads to cyclic product

36. Basic carbonyl chemistry
Intramolecular Aldol Reactions For Unsymmetrical Dicarbonyl Species more than one product is possible

37. Basic carbonyl chemistry
Claisen Condensation Esters react in same fashion as aldol reaction
Intramolecular Claisen Condensations aswell

38. Basic carbonyl chemistry
Knoevenagel Condensation

39. Basic carbonyl chemistry
Michael Reaction Enolates react with conjugated carbonyls through terminus double bonds rather than the carbonyl itself!

40. Robinson Annelation
Micheal reaction followed by intramolecular aldol Micheal Addition Intramolecular Aldol Aldol Condensation (Base catalysed)

41. Basic carbonyl chemistry
Condensation with Amine Derivatives Ketone  Imine

42. Basic carbonyl chemistry
Condensation with Amine Derivatives Imine  Enamine

43. Basic carbonyl chemistry
Enamine Reactivity React simular to enolates in neutral form. Forms iminium salt, hydrolysis leads to alkylated carbonyl

44. basic carbonyl chemistry
Enamine Reactivity

45. Basic carbonyl chemistry
Wittig Reaction Introduces alkenes from ketones using phosphorus ylids.

46. Wittig reaction
Stage 1 Preparation of a phosphonium salt from an alkyl halide

47. Wittig reaction
Stage 2 Deprotonation of the phosphonium salt to form a ylid

48. Wittig reaction
Stage 3 Reaction of the ylid with a carbonyl group

49. Wittig reaction
E or Z alkenes? Ylids that have a conjugating or anion- stablilizing substituent (such as a carbonyl) adjacent to negative charge give E – Alkenes Ylids without such groups are unstabilized ylids and tend to give Z – Alkenes

50. Wittig reaction
Example of Z – Alkene formation Example of E – Alkene formation

53. Revision and Past Paper Questions and Answers
Pericyclic Reactions
Revision and Past Paper Questions and Answers

54. Pericyclic Reactions
Pericyclic Reaction: A concerted reaction that takes place as a result of a cyclic rearrangement of electron density Concerted: Bond making and bond breaking takes place at the same time No intermediates are formed, proceeds through a single transition state

55. Cycloaddition
Cycloadditions
Diels-Alder Reaction [4+2] cycloaddition (4π + 2π = 6π electrons) Reversible reaction but driven to product due to loss of 2 pi bonds and formation of 2 sigma bonds Diene must be Z (cis)

56. Stereochemistry of Diels Alder
Cycloaddition
Stereochemistry of Diels Alder

57. Stereochemistry of Diels Alder
Cycloaddition
Stereochemistry of Diels Alder

58. Hetero Diels-Alder Reactions
Cycloaddition
Hetero Diels-Alder Reactions
Examples

59. Cycloaddition
Other Cycloadditions
Example: [8 + 2] Thermal Conditions

60. Cycloaddition
Other Cycloadditions

61. Cycloaddition
Other Cycloadditions
How to tell if a cycloaddition under thermal conditions work? If Aromatic Intermediate (4n+2) then yes If Antiaromatic Intermediate (4n) then no [2+2] Antiaromatic No [4+2] Aromatic Yes [4+4] Antiaromatic No [6+4] Aromatic Yes [8+2] Aromatic Yes Etc…

62. Cycloaddition
Photochemical [2+2]
By exciting the HOMO to a higher energy state (HOMO*) the phases are changed to allow orbital overlap

63. Thermal [2+2] Cycloaddition
Special Case where photochemical activation is not needed, use Ketene. Why? Central carbon atom is sp hybridised and overlaps antiarafacial

64. Antarafacial Overlap for Ketene [2+2]
Cycloaddition
Antarafacial Overlap for Ketene [2+2]

65. Sigmatropic Rearrangements
Sigmatropic Rarrangement
Sigmatropic Rearrangements
Example [3,3]-sigmatropic rearrangement
Driving Force
Enol – Keto tautomerisation – C=O stronger than C=C

66. Claisen Rearrangement
Sigmatropic Rarrangement
Claisen Rearrangement
First sigmatropic rearrangement
Phenyl allyl ether is heated to give ortho-substituted phenol

67. Sigmatropic Rearrangement
Sigmatropic Rarrangement
Sigmatropic Rearrangement
Proceed via a chair-like transition state For Substituted Allyl Ethers (on sp3 next to oxygen) the resulting alkene is always E (trans)!

68. Sigmatropic Rarrangement
Cope Rearrangement
Use Carbon instead of oxygen. Note with no substituents; no overall reaction.
Again only E (trans) alkenes formed

69. [2,3]-Sigmatropic Rearrangements
Sigmatropic Rarrangement
[2,3]-Sigmatropic Rearrangements
Proceeds via a 5 membered transition state Requires negative charge for 6 electron movement

70. [2,3]-Sigmatropic Rearrangements
Sigmatropic Rarrangement
[2,3]-Sigmatropic Rearrangements
Again E (Trans) favoured due to nature of transition state (not going to cover here)

71. [1,5]-Sigmatropic Hydrogen Shifts
Sigmatropic Rarrangement
[1,5]-Sigmatropic Hydrogen Shifts

72. Electrocyclic Reactions
Only one sigma bond formed across conjugated system, loss of one pi bond.

73. Electrocyclic Reactions
Exceptions
Expect Anti-Aromatic transition state so this should not happen?

74. Electrocyclic Reactions
Nazarov Cyclisation

75. Carbocation Rearrangements
More Alkyl Substituents = More Stable
Carbocation will rearrange to give an alternative more thermodynamic cation by adding substituents wherever possible

76. Carbocation Rearrangements
Driven by thermodynamics

77. Wagner-Meerwein Rearrangements
Carbocation Rearrangements

78. Pinacol Rearrangement
Carbocation Rearrangements
Pinacol Rearrangement

79. Choice of Migrating Group
Carbocation Rearrangements
Choice of Migrating Group

80. Carbocation Rearrangements
Unsymmetrical Diols

81. Dienone-Phenol Rearrangement
Carbocation Rearrangements
Dienone-Phenol Rearrangement
Again, phenyl has right of way against methyl.

82. Beckmann Rearrangement
Carbocation Rearrangements
Beckmann Rearrangement

83. Beckmann Rearrangement
Carbocation Rearrangements
Beckmann Rearrangement

84. Beckmann Rearrangement
Carbocation Rearrangements
Beckmann Rearrangement

85. Benzillic Acid Rearrangement
Anionic Rearrangements
Benzillic Acid Rearrangement
Related to Pinacol Rearrangement

86. Favorskii Rearrangement
Anionic Rearrangements
Favorskii Rearrangement
Similar to Benzillic Acid Rearrangement

87. Favorskii Rearrangement
Anionic Rearrangements
Favorskii Rearrangement
Ring Contraction method

88. Baeyer-Villiger Reaction
Anionic Rearrangements
Baeyer-Villiger Reaction
Very Important Migration to Oxygen

89. Baeyer-Villiger Reaction
Anionic Rearrangements
Baeyer-Villiger Reaction
Preference of Migrating Group The group that is more able to stabilise a positive charge has right of way. Phenyl has right of way due to cyclopropane intermediate Stereochemistry is retained during reaction