Carboxylic acids Flashcards
(19 cards)
Key ester reactions?
- Fischer esterification (classic ester formation)
- Nucleophilic acyl substitution (alt. ester formation)
- Transesterification (swap over ester parts)
- Ester hydrolysis (base or acid cat)
Four key derivatives of carboxylic acids?
- Acid halide
- Acid anhydride
- Ester
- Amide
Why are carboxylic acids more acidic than alcohols?
Carboxylic acids are more acidic than alcohols because of
- Resonance stabilisation
- Electrostatic stabilisation
Hi Ruby,
Electrostatic stabilisation is probably not the best term to be using to describe this.
The concept relates to understanding how the electronic effects of susbtituents influence the acidity of carboxylic acids. In class, I suggested that it was instructive to consider the conjugate base (RCO2–) and consider whether the substituent in question would increase/decrease the capacity of the conjugate base to stablise the negative charge.
Using this approach, we observe that electron-withdrawing susbtituents can help to better stabilise this negative charge, increasing the stability of the conjugate base, and thus increasing the acidity. While electron-donating susbtituents are less able to stabilise this negative charge, decreasing the stability of the conjugate base, and thus decreasing the acidity.
I hope that this answers your question/ clears things up?
Regards,
Alex
How does substitution at the alpha carbon affect acidity?
- If you sub with an EWG it weakens the OH bond leading to inc. acidity and stabilises conjugate base
- If you sub with an EDG it strengthens OH bond leading to dec. acidity and weakens conjugate base.
This affect dec. with distance.
How can carboxylic acids be basic?
Carboxylic acids can be basic because of the O on the (C=O) group which forms a resonance stabilised conjugate acid. This is due to the fact that it has an e- lone pair.
What are the chief ways to synthesise carboxylic acids?
Carboxylic acids can be synthesised through…
- Oxidation of 1° alcohol with strong oxidant or of aldehydes with tollens.
- Grignard addition to CO2 and protonation
- Hydrolysis product of a nitrile
What are some of the key behaviours in carboxylic acid reactions?
+ Nuc. sub can occur at (C=O) carbon
—> O acts as nuc. and C acts as electrophile.
+ (-OH) only works as a leaving group if acidified.
What is the basis of carboxylic acid reactivity?
Carboxylic acid reactivity is based off…
- Stability of derivative
- Stability of leaving group
Key acid chloride reactions?
- With Grignard reagents
- Synthesis from carboxylic acid and (S=O-Cl) group
- Reactions with water or alcohols
- With LiAlH4
Key amide reactions?
- Synthesis from amines
- With water
Key anhydride reactions?
Synthesis from acid chloride and salt.
Ester hydrolysis with acid cat vs with base cat?
- Acid cat: reverse of fischer esterification
- –> Forms alcohol and carb acid
- Base cat: saponification
- –> Forms carb acid
Nuc. acyl substitution vs fischer esterification? Mechanisms
Nuc. acyl: e.g. anhydride and hydroxybenzoic acid.
1) Protonation of the carbonyl group to generate an activiated electrophile and (O-H+)
2) Attack by the nuc. occurs at carbonyl carbon, donating pair of electrons from (O-H) bond to the pos. (OH) group, stabilising it, these from (O-H) bond hence deprotonating at new ester linkage. Atom is neutral. Forms tetrahedral diester in this case.
3) Elim of leaving group by donating e- from (OH), formation of double bond to (OH) leaving +ve charge
4) Deprotonation by base to form clean (C=O) bond and remove +ve charge.
Fischer esterification:
1) Protonation into activated electrophile
2) Activated electrophile and alchohol react, forms tetrahedral diol with a +ve ester with H bonded to it. (Like an internal +ve OH group)
3) Proton shift to generate H2O leaving group and clean neutral ester.
4) Elimination of water and reformation of (C=O) double bond, leaves H and +ve charge attached to C=O
5) deprotonation provides clean C=O and regenerates acid catalyst.
Nuc. acyl substitution vs fischer esterification? Situations
- Nuc. ac. sub: in aldehydes and ketones because they lack a stable leaving group (e.g. carboxylic acid + anhydride) where carboxylic acid provides the leaving group.
- Fischer: in alcohols because they already have a potential leaving group: create (OH+-H) water leaving group from (OH)
- Reversible, generally leaves large amounts of carb. acid and alcohol behind.
- Acid cat.
Mechanism for acid chloride + grignard reagents?
- Forms ketone/aldehyde then 3° alcohol
Takes 2 units of Grignard reagants
1) Convert acid chloride to regular ketone/aldehyde in the first round
2) Second unit of grignard then acidification forms regular alchohol
EXPANDED:
1) MgX attracts to O while simultaneously the acyl fragment/carbanion R attacks the alpha carbon. This generates a tetrahedral intermediate.
2) Cl takes electrons and is eliminated, leaving ketone
3) Attack by second grignard unit
4) Acidification into 3° alcohol
Mechanism for acid chloride + LiAlH4?
- Forms 1° alcohol
1) Addition of hydride ion generates intermediate with -ve oxygen
2) Elimination of Cl-: this leaves a neutral aldehyde/ketone
3) Addition of another hydride ion generates tetrahedral structure again with -ve oxygen
4) Acidification forms 1° alcohol
Mechanism for synthesis of anhydride?
- From acid chloride and carboxylic acid salt
1) Nuc attack by -ve O of carb acid salt generates tetrahedral intermediate with -ve oxygen
2) Elimination of Cl to reform carbonyl = bond.
You now have an anhydride, voila.
Mechanism for synthesis of amide? (Acid chloride and two units of amines).
1) NH2 attacks alpha carbon forming tetrahedral intermediate with -ve O and +ve NH-H group
2) Elimination of Cl- to form = bond
3) Deprotonation to restore neutrality.
Mechanism for synthesis of amide? (Acid chloride and two units of amines).
1) NH2 attacks alpha carbon forming tetrahedral intermediate with -ve O and +ve NH-H group
2) Elimination of Cl- to form = bond
3) Deprotonation to restore neutrality.
