Ch 25 - Amines Flashcards
3 ways to make an amine:
1) nuc substitution w/RX and nitrogen nucleophiles, steps?
1) NH3/amine attacks RX (Sn2)
2) NH3 deprotonates amine
• if SM is NH3 ➡ primary amine
• if SM is amine ➡ tetra alkyl ammonium salt (3 Sn2’s)
Amines that can hydrogen bond?
Yes: primary, secondary
No: tertiary (no H’s, ⬇ boiling pt)
3 ways to make an amine:
Gabriel synthesis of primary amines (variation on #1): alkyl halide ➡ primary amine. Steps?
1) SM = phthalimide, deprotonated by K+-OH ➡ (-) on N
2) nucleophile attacks RX (Sn2)
3) hydrolysis H2O/-OH ➡ primary amine + benzene ring w/2 COO-
3 ways to make an amine:
2) reduction of nitro compds, nitriles, amides. Reagents for each?
- Nitro compds NO2: H2/Pd-C ➡ primary amines
- nitriles: LiAlH4/H2O ➡ primary amines
- amides: LiAlH4/H2O ➡ all amines
3 ways to make amines:
3) Reductive amination of aldehydes /ketones ➡ all amines. Steps?
1) nuc addn of amine to carbonyl compd ➡ imine R2C=NH
2) reduction of imine w/NaBH3CN ➡ amine
Replaces C=O w/C-N & C-H
3 ways to make an amine:
3) 3 types of reductive amination?
- w/NH3 ➡ primary amine
- w/primary amine ➡ secondary amine
- w/secondary amine ➡ tertiary amine
Relative basicity of amines:
Generally, what ⬆ amine’s basicity? ⬇ basicity?
⬆ basicity: anything that ⬆ e- density on N
⬇ basicity: anything that ⬇ e- density on N
Basicity of NH3 vs amines?
Primary, secondary, tertiary amines all more basic than NH3 e- donating inductive effect of alkyl groups
Basicity of alkylamine vs arylamine?
Arylamine less basic than alkylamine b/c e- pair on N is delocalized on ring (via resonance)
Effect of e- donor groups on arylamines, compared to aniline?
- Add e- density to benzene ring ➡ more basic than aniline
* o,p activators
Effect of e- withdrawing groups on arylamines, compared to aniline?
- Remove e- density to benzene ring ➡ less basic than aniline
- deactivators
Basicity of alkylamine vs amide?
Amides less basic than amines b/c e- pair on N delocalized (via resonance)
Heterocyclic aromatic amines: basicity of pyrrole vs pyridine?
Pyrrole less basic than pyridine b/c e- pair on N is part of aromatic pi system
Hybridization effect: basicity of piperidine vs pyridine?
- Higher s character of orbital w/e- pair, more tightly it’s held ➡ weaker base
- pyridine N is sp2, 33% s (piperidine sp3, 25% s) ➡ pyridine less basic
2 ways amines act as nucleophiles?
- attack aldehydes & ketones ➡ nuc addn (imines & enamines)
* attack RCOZ ➡ nuc substitution (primary, secondary, tertiary amides)
