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Measures of Basicity in Amines: Kb, pKb, Ka, and pKa

Learn about the different measures of basicity in amines, including Kb, pKb, Ka, and pKa. Explore the relationships between acidity and basicity constants and understand the effects of structure and substituents on basicity. Discover the basicity of various amines in aqueous solution and the differences between arylamines and alkylamines.

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Measures of Basicity in Amines: Kb, pKb, Ka, and pKa

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  1. Amines Chemical / Biological / Neurological Activity

  2. 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

  3. + – •• •• 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

  4. + 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

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

  6. A natural base from Erythroxylon spp. • It is very valuable. The leaves are chewed by indigenous tribes in the Andes to boost their energy. • It has been used as a psycho-therapeutic, an opthalmic anesthetic and was purportedly used in a popular beverage that is at the heart of a $20 billion corporation. • However, both its base and conjugate acid are currently controlled substances under U.S. Federal Regulations: Title 21 secs. 329.1 & 1308.12 (1987). • Can you name the beverage and the base?

  7. 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….

  8. 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?

  9. “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?

  10. Acid -Base Reactions

  11. Acid Base Reactions

  12. 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.

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

  14. 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.

  15. 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.

  16. 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

  17. •• •• 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. + + +

  18. 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

  19. 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.

  20. 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

  21. •• •• 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. +

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

  23. •• 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)

  24. N H •• N •• N •• Heterocyclic Amines is more basic than imidazole pyridine Kb = 1 x 10-7 Kb = 1.4 x 10-9

  25. N H •• N •• + H H N H N •• N N •• H Imidazole • Which nitrogen is protonated in imidazole? H+ H+ +

  26. N H •• N •• + H N H •• N Imidazole • Which nitrogen is protonated in imidazole? H+

  27. N H •• N •• + H H N H N H N N •• Imidazole • Protonation in the direction shown gives a stabilized ion. H+ + ••

  28. Alkaloids: Naturally Occuring Bases Nitrogen Heterocycles

  29. Preparation and Reactions of Amines

  30. The Gabriel Synthesis of Primary Amines

  31. Reductive Amination

  32. 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

  33. 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

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

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

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

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

  38. Amine Oxides Undergo a Cope Elimination Reaction

  39. Amines & Neurotransmitters

  40. Barbiturates • Can you draw the enolized form? • Is it aromatic? • Could it possibly be aromatic?

  41. Mescaline

  42. Tagamet: cimetidine Histidine receptor antagonist (a precursor to histamine, a vasodilator) Inhibits gastric secretions & pepsin output

  43. Dopamine, Serotonin, Melatonin

  44. Adrenalin

  45. Cathecols: epinephrine & mdma http://faculty.washington.edu/chudler/mdma.html Principal sympathomimetic adrenal hormone & a controlled substance

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