MCAT Organic Chemistry · Lesson 9
Carboxylic Acid Derivatives
2 min read3 sectionsUpdated
3 sections
9.1 Amides, Esters, Anhydrides
Summary: Amides, esters, and anhydrides are all condensation derivatives of carboxylic acids. Their structures, naming, and physical properties are influenced by substituents, ring formation, and hydrogen bonding capabilities.
- Amides
- Formula: RCONR₂
- Alkyl substituents on N prefixed with
N- - Formed from COOH + ammonia or amine (primary/secondary)
- Cyclic amides = lactams; named according to carbon bonded to N
- Esters
- Dehydration synthesis of COOH + alcohol
- Named: esterifying group as prefix,
oatereplacesoic acid - Can form from COOH + alcohol under acidic conditions or from anhydrides
- Cyclic esters = lactones
- Usually lower BP than COOH (less H bonding)
- Triacylglycerols = esters of long-chain COOH
- Anhydrides
- Condensation dimers of 2 COOH
- Symmetrical:
anhydridereplacesacid - Can cyclize; formed by heating COOH
- Higher BP than related COOH (larger molecular weight)
9.2 Reactivity Principles
Reactivity of carboxylic acid derivatives is determined by electronic, steric, and structural factors, including substituents, induction, conjugation, and ring strain.
- Relative Reactivity of Derivatives
- General trend: Anhydrides > Esters > COOH > Amides
- Amides least reactive due to e⁻ donating amino group
- Steric Effects
- Bulky substituents hinder reactions (SN2 less favorable at tertiary carbons)
- Can be used to design protecting groups
- Electronic Effects
- Induction: distribution of charge across σ bonds
- Electronegative atoms attract e⁻ → dipole across bond → affects reactivity
- Anhydrides: two e⁻ withdrawing groups → higher reactivity
- Conjugation
- Alternating single/multiple bonds; sp² or sp hybridized
- Carbonyl contributes to conjugation → stabilizes intermediates
- Strain in Cyclic Derivatives
- Certain lactams resistant to hydrolysis if ring is strained
- 4-membered rings: torsional + angle strain
- Fusion to second ring → ↑ ring strain → ↑ hydrolysis susceptibility
- Pyramidal bond geometry can increase reactivity
9.3 Nucleophilic Acyl Substitution Reactions
Nucleophilic acyl substitution involves attack on the carbonyl carbon of COOH derivatives, forming tetrahedral intermediates and resulting in substitution. Reactions vary based on nucleophile and derivative type.
- Anhydride Cleavage
- All COOH derivatives can undergo nucleophilic substitution
- Ammonia → amides
- Alcohols → esters
- Water → reverts to COOH
- Transesterification
- Alcohol displaces esterifying group on ester
- Transfers ester group to new alcohol
- Hydrolysis of Amides
- Acidic conditions protonate carbonyl O
- Product: COOH + NH₃
- Reverse of condensation that forms amides
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