Acid derivatives, phenols, polycyclic and heterocyclic aromatics
Acid derivatives (anhydrides, amides, esters)
Acid derivatives such as anhydrides, amides, and esters come from carboxylic acids by replacing the -OH group with a different substituent. They all contain a carbonyl group (C=O). Because the carbonyl carbon is electrophilic, these compounds commonly react with nucleophiles and serve as useful intermediates in organic synthesis.
Even though they share the same carbonyl “core,” their properties and reactivity differ mainly because:
- different derivatives have different leaving groups, and
- resonance effects can stabilize (or destabilize) the carbonyl, changing how reactive it is.
Nomenclature
Acid chlorides: Suffix “-oyl chloride” (e.g., ethanoyl chloride).
Anhydrides: Suffix “-oic anhydride” (e.g., ethanoic anhydride).
Amides: Suffix “-amide” (e.g., N-methyl ethanamide).
Esters: Suffix “-oate” (e.g., methyl ethanoate).
Physical properties
- The C=O bond is polar, so these molecules experience dipole-dipole interactions. This typically raises boiling points compared with nonpolar alkanes of similar size.
- Amides can hydrogen-bond through their N-H group, which usually gives them even higher boiling points. This same hydrogen bonding is important in protein secondary structure.
- Esters, anhydrides, and acid chlorides generally don’t donate hydrogen bonds, but they still show dipole-dipole interactions.
- IR spectra show characteristic C=O absorptions:
- Acid chloride: Near 1800 cm⁻¹
- Anhydride: Two bands between 1700-1800 cm⁻¹
- Amide: N-H stretch ~3300 cm⁻¹, C=O ~1700 cm⁻¹
- Ester: C=O ~1700 cm⁻¹ and a C-O stretch ~1200 cm⁻¹
Important reactions
- Preparation:
- Acid chloride from carboxylic acid +
- Anhydride from two carboxylic acids (with heat) or from acid chloride + carboxylate
- Ester from acid chloride + alcohol, or from carboxylic acid + alcohol under acidic conditions
- Amide from acid chloride + amine
- Nucleophilic substitution: A nucleophile attacks the electrophilic carbonyl carbon, and the original substituent leaves (for example, chloride leaves from an acid chloride).
- Hofmann rearrangement (amide to amine): The amide’s C=O is removed by alkyl or aryl migration to nitrogen.
- Transesterification: An ester reacts with an alcohol to form a different ester.
- Hydrolysis:
- Esters hydrolyze (saponification in base) to yield carboxylates and alcohols.
- Amides hydrolyze to yield a carboxylic acid and amine (though more vigorous conditions are often required).
Phenols
Phenols are aromatic rings bearing a hydroxyl (-OH) substituent. They’re more acidic than typical alcohols because the conjugate base (the phenolate ion) is stabilized by resonance. Phenols appear in many natural products and synthetic compounds, and they’re used as antiseptics and as intermediates in industrial chemistry.
Oxidation and reduction (e.g., hydroquinones, ubiquinones)
Some phenols - especially those with two hydroxyl groups on the ring - can act as 2e⁻ redox centers.
In biological systems, they can cycle between reduced hydroquinones and oxidized quinones (as in ubiquinones). This reversible redox chemistry supports electron transport in respiratory and photosynthetic pathways. The aromatic ring’s ability to accommodate these oxidation-state changes is what makes these molecules effective redox carriers.
Polycyclic and heterocyclic aromatic compounds
Polycyclic aromatics contain fused benzene rings (for example, naphthalene and anthracene). They retain strong aromatic stabilization and often undergo familiar aromatic reactions such as electrophilic substitution.
Heterocyclic aromatics contain at least one heteroatom (nitrogen, oxygen, or sulfur) in the ring, producing molecules such as pyridine and pyrrole. Replacing a carbon with a heteroatom changes how electrons are distributed in the ring, which can strongly affect acidity, basicity, and other electronic properties.
Biological aromatic heterocycles
Many essential biomolecules contain heterocyclic aromatic rings. The nucleobases in DNA and RNA (purines and pyrimidines), for example, have conjugated ring systems that are central to base-pairing and genetic information storage.
Heterocycles also appear in vitamins, cofactors, and pigments. In these molecules, resonance and functional groups help enable binding, catalysis, and light absorption in key biochemical reactions.