Ch 21 Aldehydes & Ketones - Nucleophilic Addn

Question 0

3 methods to synthesize aldehydes:

✳1) oxidation of primary alcohols. Reagent?

Answer 0

PCC

Question 1

Reactivity as # of R groups around carbonyl C ⬆?

Answer 1

Reactivity ⬇(due to steric hindrance)

Question 2

3 methods to synthesize aldehydes:

✳2) reduction of esters and acid chlorides. Reagent?

Answer 2

• DIBAL-H/H2O

* LiAlH(OR)3/H2O

Question 3

3 methods to synthesize aldehydes:

3) Hydroboration-oxidation of alkynes. Reagent?

Answer 3

BH3/H2O2, OH-

Question 4

4 methods to synthesize ketones:

✳1) oxidation of secondary alcohols. Reagent?

Answer 4

• PCC

* CrO3

Question 5

4 methods to synthesize ketones:

✳2) nucleophilic substitution with acid chlorides. Reagent?

Answer 5

R2CuLi

Question 6

4 methods to synthesize ketones:

3) Freidel-Crafts acylation of benzenes. Reagent?

Answer 6

Acid chlorides/AlCl3

Question 7

4 methods to synthesize ketones:

4) Hydration (addn of H2O) of alkynes. Reagent?

Answer 7

H2O/H2SO4 or HgSO4

Question 8

2 general types of rxns of aldehydes & ketones?

Answer 8

1) nucleophilic addn at carbonyl C

2) rxn at alpha C(➡enolate, rxt w/electrophile at alpha C)

Question 9

Nucleophilic addn of aldehydes & ketones w/ (-) charged nucleophile, steps?

Answer 9

1) nucleophilic attack at carbonyl C

2) protonation of carbonyl O

Question 10

Nucleophilic addn of aldehydes & ketones w/neutral nucleophile, steps?

Answer 10

1) protonate carbonyl O with HA
2) nucleophilic attack at carbonyl C
3) deprotonate nucleophile with A-

Question 11

Nucleophilic addn of -CN to aldehyde or ketone➡cyanohydrin. Reagent? Cyanohydrin structure?

Answer 11

• NaCN/HCl

* CN & OH bonded to former carbonyl C

Question 12

Two rxns that use cyanohydrins as SM?

Answer 12

• reconvert back to aldehyde or ketone (deprotonate, CN leaves)
• rxt with H2O/H+ or OH-, heat)➡alpha-hydroxy acid

Question 13

Wittig rxn: aldehyde/ketone ➡ alkene. Steps?

Answer 13

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

Question 14

Formation of imines: aldehyde/ketone➡[carbinolamine]➡imine R2C=NR, 5 steps. Reagent?

Answer 14

1) primary amine RNH2/mild H+ (nucleophilic addn)

2) elimination of H2O

Question 15

Formation of enamines: aldehyde/ketone➡[carbinolamine]➡enamine R2NC=C, 5 steps. Reagent?

Answer 15

1) secondary amine R2NH/mild H+

2) elimination of H2O

Question 17

Main difference bet imine & enamine formation?

Answer 17

Step 4: H removed by H2O on N (imine) vs. on C (enamine)

Question 18

Hydration: Aldehyde/ketone➡hydrate (gem-diol). Reagent?

Answer 18

H2O/H+ or OH-

H2O added across C=O

Question 19

What do EW groups do to carbonyl group, and how is hydrate product affected?

Answer 19

Destabilize carbonyl group, ⬆hydrate product

Question 20

What do ED groups do to carbonyl group, and how is hydrate product affected?

Answer 20

Stabilize carbonyl group, ⬇hydrate product

Question 21

Aldehyde/ketone➡acetal R2(or H2)C(OR)2. Addn of what? Reagents?

Answer 21

• 2 alcohols

* catalyzed by TsOH

Question 22

2 parts of aldehyde/ketone➡acetal mechanism (7 steps). Main rxns?

Answer 22

Part 1: addn of alcohol➡hemiacetal (steps 1-3)

Part 2: elimination of H2O, addn of alcohol➡acetal (steps 4-7)

Question 23

Hydrolysis of acetal➡aldehyde/ketone + 2 alcohols. Reagents?

Answer 23

H2O/H2SO4

Question 24

Steps to use acetals as PG to block aldehydes & ketones on a compd with other FGs?

Answer 24

1) protection (alcohol + TsOH)
2) red/rxn (LiAlH4, H2O)
3) deprotection (hydrolysis via
H3O+)

Question 25

How to form a cyclic hemiacetal (5 or 6 membered rings, stable)?

Answer 25

Intramolecular cyclization of a hydroxy aldehyde

Question 26

Stereochemistry of cyclic hemiacetal formation?

Answer 26

SM is achiral➡product gives equal amt of 2 enantiomers

Question 27

Conversion of cyclic hemiacetal ➡acetal. Reagents? What happens when compd contains more than one OH?

Answer 27

• alcohol/H+

* only OH of hemiacetal portion of compd reacts (other OH left alone)

Question 28

mechanisms to memorize?

Answer 28

• formation of imines
• formation of enamines
• acetal formation

Question 31

Hydrolysis of imines & enamines➡aldehydes & ketones. Reagents?

Answer 31

H2O/H+