AMINA

1. AMINA Senyawa yang mengandung gugus NH2 Strukrur : RNH2 Jenis : Amina primer (1o) Amina sekunder (2o) Amina tersier (3o)

2. Tata Nama • Amina alifatik sederhana dinamakan dengan gugus alkil yang terikat pada atom N dan diberi akhiran amin.

3. Sistem IUPAC, gugus NH2 dinamakan gugus amino

4. Tata Nama : • Jika atom N mengikat 4 gugus hidrokarbon akan bermuatan positif dam dikenal sebagai ion ammonium kuartener

5. Tata Nama : • Senyawa yang mengandung gugus –NH2 pada cincin benzena dinamakan sebagai derivat anilin.

6. Tata Nama : • Senyawa siklis dimana satu atom C atau lebih diganti dengan atom nitrogen, diberi nama khusus sebagai heterosiklik amin.

7. Beberapa Contoh Senyawa Heterosiklis Amin • Alkaloid : senyawa yang mengandung nitrogen yang bersifat basa dari tumbuhan dan hewan. Senyawa ini mempunyai struktur yang rumit dan sifat farmakologis (faali) yang nyata • Nikotin dari tembakau • Porfirin : senyawa heterosiklis yang mengandung 4 cicin pirol yang saling berikatan. Porfirin membentuk kompleks dengan ion logam. Apabila membentuk kompleks dengan Fe membentuk besi-porfirin yang menyebabkan warna darah merah pada darah arteri  Hemoglobin

8. Contoh Senyawa Heterosiklis • Klorofil berwarna hijau adalah kompleks Mg dengan porfirin yang termodifikasi.

9. Sifat-Sifat Fisik Amina : • Amina 1 dan 2 bersifat polar karena mampu membentuk ikatan hydrogen intermolekuler. • Larut dalam air karena mampu membentuk ikatan hidrogen dengan air. • Ikatan hidrogen

10. Measures of Basicity • The basicity of amines may be measured by: • 1) Kb • 2) pKb • 3) Ka of conjugate acid • 4) pKa of conjugate acid

11. + – •• •• R3N H OH OH R3N H •• •• •• •• Basicity Constant (Kb) and pKb • Kb is the equilibrium constant for the reaction: + + [R3NH+][HO–] Kb = [R3N] and pKb = - log Kb

12. + R3N + R3N H H+ •• Ka and pKa of Conjugate Acid • Ka is the equilibrium constant for the dissociation of the conjugate acid of the amine: [R3N][H+] Ka = [R3NH+] and pKa = - log Ka

13. Relationships between acidity and basicity constants Ka Kb = 10-14 pKa + pKb = 14

14. The beverage reportedly produced using the extract of leaves of Erythroxylon coca: The compound: cocaine, it is an organic base:Merck Index, #2450, 11th ed.: Caution: May be habit forming….

15. Acid -Base Chemistry(Physical Properties) • m.p. 98 oC • b.p. (very volatile > 90 oC) Solubility: • Water: 1.67 x 10-3g/mL • CHCl3: 1.43 g/mL • Ether: 0.29 g/mL What structural feature makes cocaine a base? What simple compound can you relate it to?

16. “Regular” Cocaine Conjugate Acidof Cocaine(Physical Properties) • m.p. >195 oC Solubility: • Water: 2.5 g/mL • CHCl3: 0.08 g/mL • Ether: insoluble What accounts for the differences in solubilities of the base and conjugate acid?

17. Acid -Base Reactions

18. Acid Base Reactions

19. Basicity of Amines in Aqueous Solution • Amine Conj. Acid pKa • NH3 NH4+ 9.3 • CH3CH2NH2 CH3CH2NH3+ 10.8 CH3CH2NH3+ is a weaker acid than NH4+;therefore, CH3CH2NH2 is a stronger base than NH3.

20. Effect of Structure on Basicity • 1. Alkylamines are slightly stronger bases than ammonia. • 2. Alkylamines differ very little in basicity.

21. Basicity of Amines in Aqueous Solution • Amine Conj. Acid pKa • NH3 NH4+ 9.3 • CH3CH2NH2 CH3CH2NH3+ 10.8 • (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 • (CH3CH2)3N (CH3CH2)3NH+ 10.8 Notice that the difference separating a primary,secondary, and tertiary amine is only 0.3 pK units.

22. Effect of Structure on Basicity • 1. Alkylamines are slightly stronger bases than ammonia. • 2. Alkylamines differ very little in basicity. • 3. Arylamines are much weaker bases than ammonia.

23. Basicity of Amines in Aqueous Solution • Amine Conj. Acid pKa • NH3 NH4+ 9.3 • CH3CH2NH2 CH3CH2NH3+ 10.8 • (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 • (CH3CH2)3N (CH3CH2)3NH+ 10.8 • C6H5NH2 C6H5NH3+ 4.6

24. •• •• H OH NH2 •• – •• OH NH3 •• •• Decreased basicity of arylamines • Aniline (reactant) is stabilized by conjugation of nitrogen lone pair with ring p system. • This stabilization is lost on protonation. + + +

25. Decreased basicity of arylamines • Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine. C6H5NH2 (C6H5)2NH (C6H5)3N 3.8 x 10-10 6 x 10-14 ~10-19 Kb

26. Effect of Substituents on Basicity of Arylamines • 1. Alkyl groups on the ring increase basicity, but only slightly (less than 1 pK unit). • 2. Electron withdrawing groups, especially ortho and/or para to amine group, decrease basicity and can have a large effect.

27. X NH2 X NH3+ Basicity of Arylamines • X pKb pKa • H 9.4 4.6 • CH3 8.7 5.3 • CF3 11.5 2.5 • O2N 13.0 1.0

28. – •• •• O O •• •• •• + + •• N NH2 N NH2 O O •• •• •• •• – – •• •• p-Nitroaniline • Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization lost on protonation. +

29. Effect is Cumulative • Aniline is 3800 times more basic thanp-nitroaniline. • Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.

30. •• N N •• H Heterocyclic Amines is more basic than piperidine pyridine Kb = 1.6 x 10-3 Kb = 1.4 x 10-9 (an alkylamine) (resembles anarylamine inbasicity)

31. Preparation and Reactions of Amines

32. The Gabriel Synthesis of Primary Amines

33. Reductive Amination

34. R R O NH C C R' R' Synthesis of Amines via Reductive Amination In reductive amination, an aldehyde or ketoneis subjected to catalytic hydrogenation in thepresence of ammonia or an amine. • The aldehyde or ketone equilibrates with theimine faster than hydrogenation occurs. fast + + NH3 H2O

35. R R O NH C C R' R' R R' NH2 C H Synthesis of Amines via Reductive Amination The imine undergoes hydrogenation fasterthan the aldehyde or ketone. An amine is the product. fast + + NH3 H2O H2, Ni

36. H O NH2 NH Example: Ammonia gives a primary amine. H2, Ni + NH3 ethanol (80%) via:

37. O + CH3(CH2)5CH H2N CH3(CH2)5CH2NH Example: Primary amines give secondary amines H2, Ni ethanol (65%)

38. O + CH3(CH2)5CH H2N CH3(CH2)5CH2NH CH3(CH2)5CH N Example: Primary amines give secondary amines H2, Ni ethanol (65%) via:

39. O CH3CH2CH2CH N H N CH2CH2CH2CH3 Example: Secondary amines give tertiary amines + H2, Ni, ethanol (93%)

40. Reductive Amination Is Versatile • Ammonia, primary amines, and secondary amines yield primary, secondary, and tertiary amines, respectively

41. Mechanism of Reductive Amination • Imine is intermediate

42. Hofmann and Curtius Rearrangements • Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement and the Curtius rearrangement

43. Hofmann Rearrangement • RCONH2 reacts with Br2 and base • Gives high yields of arylamines and alkylamines

44. Curtius Rearrangement • Heating an acyl azide prepared from substitution an acid chloride • Migration of R from C=O to the neighboring nitrogen with simultaneous loss of a leaving group

45. COPE REACTION N-OXIDE LESS HINDERED BETA HYDROGEN SYN ELIMINATION

46. Amine Oxides Undergo a Cope Elimination Reaction

47. COPE EXAMPLE Mild conditions

48. Reactions of Amines • Alkylation and acylation have already been presented

49. Arylamines Are Not Useful for Friedel-Crafts Reactions • The amino group forms a Lewis acid–base complex with the AlCl3 catalyst, preventing further reaction • Therefore we use the corresponding amide

50. Diazonium Salts: The Sandmeyer Reaction • Primary arylamines react with HNO2, yielding stable arenediazonium salts NaNO2 + HCl HONO