1. Amines

2. Nitrogen-Based Functional Groups

3. Amines as Pharmaceutical Agents

4. 22.1 Amine Nomenclature

5. The Naming of Parts Alkylamines Nitrogen atom is attached to alkyl group: Arylamines Nitrogen atom is attached to aryl group:

6. Nomenclature of Primary Alkylamines (RNH 2 ) Two IUPAC styles 1) analogous to alcohols: replace -e ending by -anamine 2) name alkyl group and attach -amine as a suffix

7. Nomenclature of Primary Alkylamines n-propylamine or propanamine cyclopropylamine or cyclopetanamine 2-bromo-3-chlorobutylamine

8. Nomenclature of Arylamines (ArNH 2 ) aniline 2,4-dibromoaniline 4-bromo-2-ethylaniline These compounds are named as derivatives of aniline

9. Amino Groups have Lower Priority than Alcohols aminoethanol p-aminobenzoic acid With regards to nomenclature, amines rank lower than alcohols and are named as substituents:

10. Secondary and Tertiary Amines N,N-diisopropylethylamine (a.k.a. Hünig’s base) 4-bromo-N,N-dimethyl-2-methylaniline Name as N-substituted derivatives of parent primary amine. The longest chain takes the root name.

11. Ammonium Salts (R 4-n H n N + X - ) Nitrogen atoms are positively charged when bonded to four substituents. The root name in this case is the ammonium ion (NH 4 + ). Remember to name as a salt - two words. methylammonium acetate N-ethyl-N-methylbenzylammonium chloride

12. Quaternary Ammonium Salts (R 4 N + X - ) Nitrogen atoms are positively charged when bonded to four substituents: when all of these substituents are carbon, the molecule is referred to as a quaternary ammonium ion. tetrabutylammonium fluoride (TBAF) benzyltrimethylammonium hydroxide Quaternary ammonium salts are relatively soluble in organic solvents and consequently are used as phase transfer catalysts

13. 22.2 Structure and Bonding of Amines

14. 147 pm 106° 112° Structure of Alkylamines

15. Note the high electron density on the nitrogen atom. The chemistry of amines is dominated by reactivity of the lone pair on this atom. Amines behave as nucleophiles and Bronsted bases. Alkylamines - Distribution of Electron Density

16. The hybridization adopted by nitrogen depends upon the nature of the N-substituents. Compare methylamine and formamide: Alkylamines - Hydridization at Nitrogen

17. the hybridization adopted by nitrogen depends upon the nature of the N-substituents - compare methylamine and formamide. Amines & Amides - Geometry at Nitrogen

18. Angle that the C—N bond makes with bisector of H—N—H angle is a measure of the pyramidalization at nitrogen. sp 3 sp 2 ~125° 180° 142.5° Amines - Geometry at Nitrogen

19. Angle that the C—N bond makes with bisector of H—N—H angle is a measure of the pyramidalization at nitrogen. 142.5° Amines - Geometry at Nitrogen Geometry at the nitrogen atom in aniline is pyramidal; closer to methylamine than to formamide.

20. 142.5° The hybridization of the nitrogen atom in aniline lies between sp 2 and sp 3 1)Delocalization of the nitrogen lone pair into the aromatic ring is most effective if the nitrogen atom is sp 2 -hybridized and planar. 2) A planar nitrogen atom increases repulsion between filled lone pair orbital and  -system of aromatic ring - sp 3 hybridization reduces this “bad” interaction. Geometry of Aniline

21. Aniline - Distribution of Electron Density Enforce a non-planar geometry (sp 3 -like) at the nitrogen center - highest negative potential is on nitrogen. Enforce a planar geometry (sp 2 -like) at the nitrogen center - negative potential is shared by both nitrogen and ring.

22. 22.3 Physical Properties of Amines

23. Amines - Physical Properties Amines are more polar and have higher boiling points than alkanes; but are less polar and have lower boiling points than alcohols. CH 3 CH 2 CH 3 CH 3 CH 2 NH 2 CH 3 CH 2 OH dipole moment (  ): boiling point: 0 D 1.2 D1.7 D -42°C17°C78°C

24. Amines - Physical Properties Boiling points of isomeric amines decrease in going from primary to secondary to tertiary amines. Primary amines have two hydrogens on nitrogen capable of being involved in intermolecular hydrogen bonding. Secondary amines have one. Tertiary amines cannot be involved in intermolecular hydrogen bonds. CH 3 CH 2 NHCH 3 CH 3 CH 2 CH 2 NH 2 (CH 3 ) 3 N boiling point: 50°C 34°C 3°C

25. 22.4 Basicity of Amines

26. Amines are Brønstead Bases and Nucleophiles

27. Brønstead Basicity of Amines

28. Basicity of Amines in Aqueous Solution

29. The Relationship between pK a and Basicity

30. The Relationship Between Basicity and Structure

31. Basicity of Amines in Aqueous Solution

32. The Relationship Between Basicity and Structure

33. Basicity of Amines in Aqueous Solution

34. Arylamines are Relatively Weak Brønstead Bases Anilinium Ion

35. Arylamines are Relatively Weak Brønstead Bases Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine.

36. Arylamines - Effect of Substituents on Basicity 1. Alkyl groups on the ring increase basicity by only one 1 pK unit.

37. 2. Electron withdrawing groups, especially ortho and/or para to amine group, decrease basicity and can have a large effect. Arylamines - Effect of Substituents on Basicity

38. Basicity of Arylamines - p-Nitroaniline Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. This delocalization is lost upon protonation.

39. Electron Withdrawing Effects are Cumulative

41. piperidinepyridine pK a of conjugate acid: 11.2 pK a of conjugate acid: 5.2 (an alkylamine) (resembles an arylamine in basicity) Heterocyclic Amines

42. imidazolepyridine pK a of conjugate acid: 7.0 pK a of conjugate acid: 5.2 Heterocyclic Amines

43. q. Which nitrogen is protonated in imidazole? Protonation of Imidazole

44. Protonation in the direction shown gives a stabilized ion. Protonation of Imidazole - Resonance Picture

45. The Term ‘Alkaloid’

48. Amines as Natural Products - Alkaloids Conium maculatum Hemlock contains the alkaloid coniine, among other compounds

49. The Toxic Alkaloids of Conium maculatum

50. Reduction of Nitroarenes - Example Aromatic nitro compounds are easy to prepare and are readily reduced to the corresponding anilines under a wide range of conditions.

51. Reduction of Nitroarenes - Example

52. 18.9 The Aldol Condensation

53. Aldol Condensation

54. Aldol Condensation of Butanal

55. dehydration of  -hydroxy aldehyde can be catalyzed by either acids or bases Dehydration of Aldol Addition Product C O C C OH H C O C C

56. in base, the enolate is formed Dehydration of Aldol Addition Product OH H C O C C NaOH OH C O C C –

57. the enolate loses hydroxide to form the ,  -unsaturated aldehyde Dehydration of Aldol Addition Product OH H C O C C NaOH OH C O C C –

58. Aldol reactions of ketones the equilibrium constant for aldol addition reactions of ketones is usually unfavorable

59. Termite Self-Defense!

60. Diethyl Zinc and Deacidification of Brittle Books

61. 14.13 Carbenes and Carbenoids

62. Carbene name to give to species that contains a divalent carbon (carbon with two bonds and six electrons) CBrBr dibromocarbene Carbenes are very reactive; normally cannot be isolated and stored. Are intermediates in certain reactions.

63. Generation of Dibromocarbene C Br Br Br H + OC(CH 3 ) 3 – H + C Br Br Br –

64. Generation of Dibromocarbene + C Br BrBr– C BrBr Br –

65. Carbenes react with alkenes to give cyclopropanes + CHBr 3 Br Br (75%) CBr 2 is a highly reactive (shortlived) intermediate KOC(CH 3 ) 3 (CH 3 ) 3 COH

66. Why the synthesis of cyclopropanes is important? Chrysanthemum cinerariaefolium

67. Why the synthesis of cyclopropanes is important?

68. 20.7 Sources of Esters

69. 3-methylbutyl acetate also called "isopentyl acetate" and "isoamyl acetate" contributes to characteristic odor of bananas Esters are Commonly Found in Natural Products

70. R, R', and R" can be the same or different called "triacylglycerols," "glyceryl triesters," or "triglycerides" fats and oils are mixtures of glyceryl triesters Esters of Glycerol

71. Tristearin: found in many animal and vegetable fats Fat & Oil are Mixtures of Glyceryl Triesters

72. (Z)-5-Tetradecen-4-olide (sex pheromone of female Japanese beetle) OO H H CH 2 (CH 2 ) 6 CH 3 Lactones are Cyclic Esters