Carbonyl chemistry- Esters and Amides Flashcards
Describe the properties of esters
- Esters are electrophilic at C=O
2. acidic alpha-proton pKa is around 25
Compare acid anhydride acidity to ester acidity
- The -ve charge is delocalised across 2 ester so a more acidic proton
- So acid anhydrides are more acidic
What are the 2 methods of forming ester via carboxylic acid
- Condensation
2. Steglich reaction
Describe How to produce an ester from a carboxylic acid using condensation method
- Add heat and alcohol
Describe How to produce an ester from a carboxylic acid using condensation method
- Add DCC, CH2Cl2
2. R-OH
What problems come from the steglich reaction
- Create stoichiometric waste- need to remove urea
What are the two ways an ester can be hydrolysed
- Acid hydrolysis
2. Base hydrolysis
Which method of hydrolysing an ester is reversible
- Acid hydrolysis
Describe the acid hydrolysis of an ester
- Add acid (H2SO4) and H2O
- 60 degrees
- It produces a carboxylic acid and alcohol
Describe each step of acid hydrolysis of an ester
- Ester is protonated to increase reactivity as it makes it more electrophilic so water can act as a nucleophile
- Water attacks the ester, this is the rate determining step as H2O is not a great nucleophile- specific acid catalysis
- A tetrahedral intermediate is formed and a proton transfer occurs
- The carboxylic acid is formed
What is specific acid/base catalysis
- In ester hydrolysis it is specific acid/base hydrolysis- the pH of the system alone matters
- Doesn’t occur at neutral pH and is a v shaped graph- occurs best at very high/low pH
Why does ester hydrolysis work at a high pH
- Water is a hydroxide - much better nucleophile attacking
Describe base hydrolysis of a carboxylic acid
- It is not reversible
- There is excess base used
- Produces a carboxylic acid and alcohol
How does base hydrolysis rate vary
- Bulkier esters have a slower rate of reaction
2. If two esters in compound- least hindered will react
What are the two types of reduction reaction of esters
- Hydrides produce primary alcohols
2. Carbon nucleophiles produce tertiary alcohols
Why can’t you form an aldehyde by reduction from LiAlH4 of an ester
- It is produced but is preferentially reduced by LiAlH4 as is more reactive than ester- so can’t just use less LiAlH4
What reagent can you use to produce an aldehyde from an ester
- Use diisobutyl aluminium hydride (DIBAL-H or DIBAL)
2. It is a lewis acid and reduces electron rich carbonyls most effectively
What conditions do you need to produce an aldehyde from an ester using DIBAL
- -78 degrees, then H+ (aq) produces an aldehyde
2. RT, then H+ (aq) - produces a primary alcohol
Why does the temperature affect the product that forms
- The intermediate that forms in the reaction is unstable at RT so breaks down before work up
- At -78 it is stable so doesn’t break down until work up
Describe the properties of amides
- Least electrophilic at C=O
- Acidic alpha proton pKa around 35
- Acidic N-H pKa around 25- always deprotonates first as more acidic
- Lewis basic- resonance
Describe the Steglich reaction
- Converts carboxylic acid to an amide using an amine
2. Uses DCC which forms a lot of bi-product
Describe the hydrolysis of amides
- Amides are very unreactive as electrophiles
- Require much harsher conditions than esters- difficult
- Acid or hydroxide promoted
- Reversible reaction
- 100 degrees
- Forms an amine and carboxylic acid
What are the 2 reagents that can reduce an amide
- BH3.THF/ BH3.DMS
2. LiAlH4 (3eq)
What is the difference in the reagents that can reduce an amide
- BH3 reagents are more chemoselective so only reduce the amide if multiple carbonyl groups- form amine
- LiAlH4 is very powerful so not selective and reduces other carbonyls as well like ketones
How can you reduce an amide to only an aldehyde
- Keep it cold-
- Form a stable tetrahedral intermediate
- LiAlH4- 0 degrees then add H+
- DIBAL- -78 degrees then add H+
- If warmed they form amines instead
