| Amines Chemical / Biological / Neurological Activity : Amines Chemical / Biological / Neurological Activity |
| Measures of Basicity : 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 |
| Basicity Constant (Kb) and pKb : Basicity Constant (Kb) and pKb Kb is the equilibrium constant for the reaction: + + Kb = [R3NH+][HO–] [R3N] pKb = - log Kb and |
| Ka and pKa of Conjugate Acid : Ka and pKa of Conjugate Acid Ka = [R3N][H+] [R3NH+] pKa = - log Ka and Ka is the equilibrium constant for the dissociation of the conjugate acid of the amine: |
| Relationships between acidity and basicity constants : Relationships between acidity and basicity constants pKa + pKb = 14 Ka Kb = 10-14 |
| A natural base from Erythroxylon spp. : 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? |
| The beverage reportedly produced using the extract of leaves of Erythroxylon coca: : 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…. |
| Acid -Base Chemistry (Physical Properties) : Acid -Base Chemistry (Physical Properties) m.p. 98 oC
b.p. (very volatile > 90 oC)
Solubility:
Water: 1.67 x 10-3 g/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? |
| “Regular” Cocaine Conjugate Acid of Cocaine (Physical Properties) : “Regular” Cocaine Conjugate Acid of 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? |
| Acid -Base Reactions : Acid -Base Reactions |
| Acid Base Reactions : Acid Base Reactions |
| Basicity of Amines in Aqueous Solution : Amine Conj. Acid pKa
NH3 NH4+ 9.3
CH3CH2NH2 CH3CH2NH3+ 10.8 Basicity of Amines in Aqueous Solution CH3CH2NH3+ is a weaker acid than NH4+; therefore, CH3CH2NH2 is a stronger base than NH3. |
| Effect of Structure on Basicity : Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than ammonia.
2. Alkylamines differ very little in basicity. |
| 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 Basicity of Amines in Aqueous Solution Notice that the difference separating a primary, secondary, and tertiary amine is only 0.3 pK units. |
| Effect of Structure on Basicity : 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. |
| 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 Basicity of Amines in Aqueous Solution |
| Decreased basicity of arylamines : + + + Aniline (reactant) is stabilized by conjugation of nitrogen lone pair with ring p system.
This stabilization is lost on protonation. Decreased basicity of arylamines |
| Decreased basicity of arylamines : Decreased basicity of arylamines C6H5NH2 (C6H5)2NH (C6H5)3N Kb 3.8 x 10-10 6 x 10-14 ~10-19 Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine. |
| Effect of Substituents on Basicity of Arylamines : 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. |
| 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 Basicity of Arylamines |
| p-Nitroaniline : p-Nitroaniline + Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization lost on protonation. |
| Effect is Cumulative : Effect is Cumulative Aniline is 3800 times more basic than p-nitroaniline.
Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline. |
| Heterocyclic Amines : Heterocyclic Amines piperidine pyridine is more basic than Kb = 1.6 x 10-3 Kb = 1.4 x 10-9 (an alkylamine) (resembles an arylamine in basicity) |
| Heterocyclic Amines : Heterocyclic Amines imidazole pyridine is more basic than Kb = 1 x 10-7 Kb = 1.4 x 10-9 |
| Imidazole : Imidazole Which nitrogen is protonated in imidazole? H+ H+ + |
| Imidazole : Imidazole Which nitrogen is protonated in imidazole? H+ |
| Imidazole : Imidazole Protonation in the direction shown gives a stabilized ion. H+ + • • |
| Slide31 : Alkaloids: Naturally Occuring Bases
Nitrogen Heterocycles |
| Preparation and Reactions of Amines : Preparation and Reactions of Amines |
| Slide33 : The Gabriel Synthesis of Primary Amines |
| Reductive Amination : Reductive Amination |
| Synthesis of Amines via Reductive Amination : The aldehyde or ketone equilibrates with the imine faster than hydrogenation occurs. Synthesis of Amines via Reductive Amination + NH3 fast + H2O In reductive amination, an aldehyde or ketone is subjected to catalytic hydrogenation in the presence of ammonia or an amine. |
| Synthesis of Amines via Reductive Amination : Synthesis of Amines via Reductive Amination H2, Ni + NH3 fast + H2O The imine undergoes hydrogenation faster than the aldehyde or ketone. An amine is the product. |
| Example: Ammonia gives a primary amine. : Example: Ammonia gives a primary amine. + NH3 H2, Ni ethanol (80%) via: |
| Example: Primary amines give secondary amines : Example: Primary amines give secondary amines H2, Ni ethanol (65%) |
| Example: Primary amines give secondary amines : Example: Primary amines give secondary amines H2, Ni ethanol (65%) via: |
| Example: Secondary amines give tertiary amines : Example: Secondary amines give tertiary amines H2, Ni, ethanol (93%) + |
| Slide42 : Amine Oxides Undergo a
Cope Elimination Reaction |
| Slide43 : Amines & Neurotransmitters |
| Slide44 : Barbiturates Can you draw the enolized form?
Is it aromatic?
Could it possibly be aromatic? |
| Slide45 : Mescaline |
| Slide46 : Tagamet: cimetidine
Histidine receptor antagonist (a precursor to histamine, a vasodilator)
Inhibits gastric secretions & pepsin output |
| Slide47 : Dopamine, Serotonin, Melatonin |
| Slide48 : Adrenalin |
| Slide49 : Cathecols: epinephrine & mdma
http://faculty.washington.edu/chudler/mdma.html
Principal sympathomimetic adrenal hormone
& a controlled substance |