Carbonyl chemistry- Esters and Amides

Question 1

Describe the properties of esters

Answer 1

1. Esters are electrophilic at C=O

2. acidic alpha-proton pKa is around 25

Question 2

Compare acid anhydride acidity to ester acidity

Answer 2

1. The -ve charge is delocalised across 2 ester so a more acidic proton
2. So acid anhydrides are more acidic

Question 3

What are the 2 methods of forming ester via carboxylic acid

Answer 3

1. Condensation

2. Steglich reaction

Question 4

Describe How to produce an ester from a carboxylic acid using condensation method

Answer 4

1. Add heat and alcohol

Question 5

Describe How to produce an ester from a carboxylic acid using condensation method

Answer 5

1. Add DCC, CH2Cl2

2. R-OH

Question 6

What problems come from the steglich reaction

Answer 6

1. Create stoichiometric waste- need to remove urea

Question 7

What are the two ways an ester can be hydrolysed

Answer 7

1. Acid hydrolysis

2. Base hydrolysis

Question 8

Which method of hydrolysing an ester is reversible

Answer 8

1. Acid hydrolysis

Question 9

Describe the acid hydrolysis of an ester

Answer 9

1. Add acid (H2SO4) and H2O
2. 60 degrees
3. It produces a carboxylic acid and alcohol

Question 10

Describe each step of acid hydrolysis of an ester

Answer 10

1. Ester is protonated to increase reactivity as it makes it more electrophilic so water can act as a nucleophile
2. Water attacks the ester, this is the rate determining step as H2O is not a great nucleophile- specific acid catalysis
3. A tetrahedral intermediate is formed and a proton transfer occurs
4. The carboxylic acid is formed

Question 11

What is specific acid/base catalysis

Answer 11

1. In ester hydrolysis it is specific acid/base hydrolysis- the pH of the system alone matters
2. Doesn’t occur at neutral pH and is a v shaped graph- occurs best at very high/low pH

Question 12

Why does ester hydrolysis work at a high pH

Answer 12

1. Water is a hydroxide - much better nucleophile attacking

Question 13

Describe base hydrolysis of a carboxylic acid

Answer 13

1. It is not reversible
2. There is excess base used
3. Produces a carboxylic acid and alcohol

Question 14

How does base hydrolysis rate vary

Answer 14

1. Bulkier esters have a slower rate of reaction

2. If two esters in compound- least hindered will react

Question 15

What are the two types of reduction reaction of esters

Answer 15

1. Hydrides produce primary alcohols

2. Carbon nucleophiles produce tertiary alcohols

Question 16

Why can’t you form an aldehyde by reduction from LiAlH4 of an ester

Answer 16

1. It is produced but is preferentially reduced by LiAlH4 as is more reactive than ester- so can’t just use less LiAlH4

Question 17

What reagent can you use to produce an aldehyde from an ester

Answer 17

1. Use diisobutyl aluminium hydride (DIBAL-H or DIBAL)

2. It is a lewis acid and reduces electron rich carbonyls most effectively

Question 18

What conditions do you need to produce an aldehyde from an ester using DIBAL

Answer 18

1. -78 degrees, then H+ (aq) produces an aldehyde

2. RT, then H+ (aq) - produces a primary alcohol

Question 19

Why does the temperature affect the product that forms

Answer 19

1. The intermediate that forms in the reaction is unstable at RT so breaks down before work up
2. At -78 it is stable so doesn’t break down until work up

Question 20

Describe the properties of amides

Answer 20

1. Least electrophilic at C=O
2. Acidic alpha proton pKa around 35
3. Acidic N-H pKa around 25- always deprotonates first as more acidic
4. Lewis basic- resonance

Question 21

Describe the Steglich reaction

Answer 21

1. Converts carboxylic acid to an amide using an amine

2. Uses DCC which forms a lot of bi-product

Question 22

Describe the hydrolysis of amides

Answer 22

1. Amides are very unreactive as electrophiles
2. Require much harsher conditions than esters- difficult
3. Acid or hydroxide promoted
4. Reversible reaction
5. 100 degrees
6. Forms an amine and carboxylic acid

Question 23

What are the 2 reagents that can reduce an amide

Answer 23

1. BH3.THF/ BH3.DMS

2. LiAlH4 (3eq)

Question 24

What is the difference in the reagents that can reduce an amide

Answer 24

1. BH3 reagents are more chemoselective so only reduce the amide if multiple carbonyl groups- form amine
2. LiAlH4 is very powerful so not selective and reduces other carbonyls as well like ketones

Question 25

How can you reduce an amide to only an aldehyde

Answer 25

1. Keep it cold-
2. Form a stable tetrahedral intermediate
3. LiAlH4- 0 degrees then add H+
4. DIBAL- -78 degrees then add H+
5. If warmed they form amines instead