Ch 21 Aldehydes & Ketones - Nucleophilic Addn Flashcards
3 methods to synthesize aldehydes:
✳1) oxidation of primary alcohols. Reagent?
PCC
Reactivity as # of R groups around carbonyl C ⬆?
Reactivity ⬇(due to steric hindrance)
3 methods to synthesize aldehydes:
✳2) reduction of esters and acid chlorides. Reagent?
- DIBAL-H/H2O
* LiAlH(OR)3/H2O
3 methods to synthesize aldehydes:
3) Hydroboration-oxidation of alkynes. Reagent?
BH3/H2O2, OH-
4 methods to synthesize ketones:
✳1) oxidation of secondary alcohols. Reagent?
- PCC
* CrO3
4 methods to synthesize ketones:
✳2) nucleophilic substitution with acid chlorides. Reagent?
R2CuLi
4 methods to synthesize ketones:
3) Freidel-Crafts acylation of benzenes. Reagent?
Acid chlorides/AlCl3
4 methods to synthesize ketones:
4) Hydration (addn of H2O) of alkynes. Reagent?
H2O/H2SO4 or HgSO4
2 general types of rxns of aldehydes & ketones?
1) nucleophilic addn at carbonyl C
2) rxn at alpha C(➡enolate, rxt w/electrophile at alpha C)
Nucleophilic addn of aldehydes & ketones w/ (-) charged nucleophile, steps?
1) nucleophilic attack at carbonyl C
2) protonation of carbonyl O
Nucleophilic addn of aldehydes & ketones w/neutral nucleophile, steps?
1) protonate carbonyl O with HA
2) nucleophilic attack at carbonyl C
3) deprotonate nucleophile with A-
Nucleophilic addn of -CN to aldehyde or ketone➡cyanohydrin. Reagent? Cyanohydrin structure?
- NaCN/HCl
* CN & OH bonded to former carbonyl C
Two rxns that use cyanohydrins as SM?
- reconvert back to aldehyde or ketone (deprotonate, CN leaves)
- rxt with H2O/H+ or OH-, heat)➡alpha-hydroxy acid
Wittig rxn: aldehyde/ketone ➡ alkene. Steps?
Synthesize Wittig reagent:
1) Sn2 of Ph3P: with methyl alkyl halide or primary alkyl halide (some secondary halide)
2) acid-base rxn, BuLi extract H+, : on C ➡ Ph3P(+)C:(-)
Rxt w/C=O
3) ketone/aldehyde + Ph3P(+)C:(-) ➡ alkene
Formation of imines: aldehyde/ketone➡[carbinolamine]➡imine R2C=NR, 5 steps. Reagent?
1) primary amine RNH2/mild H+ (nucleophilic addn)
2) elimination of H2O
Formation of enamines: aldehyde/ketone➡[carbinolamine]➡enamine R2NC=C, 5 steps. Reagent?
1) secondary amine R2NH/mild H+
2) elimination of H2O
Main difference bet imine & enamine formation?
Step 4: H removed by H2O on N (imine) vs. on C (enamine)
Hydration: Aldehyde/ketone➡hydrate (gem-diol). Reagent?
H2O/H+ or OH-
H2O added across C=O
What do EW groups do to carbonyl group, and how is hydrate product affected?
Destabilize carbonyl group, ⬆hydrate product
What do ED groups do to carbonyl group, and how is hydrate product affected?
Stabilize carbonyl group, ⬇hydrate product
Aldehyde/ketone➡acetal R2(or H2)C(OR)2. Addn of what? Reagents?
- 2 alcohols
* catalyzed by TsOH
2 parts of aldehyde/ketone➡acetal mechanism (7 steps). Main rxns?
Part 1: addn of alcohol➡hemiacetal (steps 1-3)
Part 2: elimination of H2O, addn of alcohol➡acetal (steps 4-7)
Hydrolysis of acetal➡aldehyde/ketone + 2 alcohols. Reagents?
H2O/H2SO4
Steps to use acetals as PG to block aldehydes & ketones on a compd with other FGs?
1) protection (alcohol + TsOH)
2) red/rxn (LiAlH4, H2O)
3) deprotection (hydrolysis via
H3O+)
How to form a cyclic hemiacetal (5 or 6 membered rings, stable)?
Intramolecular cyclization of a hydroxy aldehyde
Stereochemistry of cyclic hemiacetal formation?
SM is achiral➡product gives equal amt of 2 enantiomers
Conversion of cyclic hemiacetal ➡acetal. Reagents? What happens when compd contains more than one OH?
- alcohol/H+
* only OH of hemiacetal portion of compd reacts (other OH left alone)
mechanisms to memorize?
- formation of imines
- formation of enamines
- acetal formation
Hydrolysis of imines & enamines➡aldehydes & ketones. Reagents?
H2O/H+
