Pharmaceutical Organic Chemistry I - Lecture 7

Pharmaceutical Organic Chemistry I (POC101) - Lecture 7: Aromaticity

• Aromatic hydrocarbons are compounds like benzene and its related compounds, which exhibit similar chemical behavior to benzene.
• Unlike aliphatic hydrocarbons which undergo addition reactions to multiple bonds (C=C, C≡C) and free radical substitution, aromatic hydrocarbons primarily undergo substitution reactions.

Aromaticity

• Benzene is a key member of a broad group of aromatic compounds.
• Aromaticity is a property of compounds that are stabilized by delocalization of π electrons.
• Resonance energy quantifies the stability gain in aromatic compounds. (e.g., benzene = 36 kcal/mol, naphthalene = 61 kcal/mol)

Benzene and Aromatic Compounds

• Benzene (C₆H₆) is the simplest aromatic hydrocarbon.
• Benzene structure is a resonance hybrid of two equivalent Lewis structures, with alternating double and single bonds.
• The π electrons are delocalized around the ring.
• Benzene has 6 π electrons.

Benzene Bond Length

• Actual C-C bond length in benzene (1.39 Å) is intermediate between single (1.53 Å) and double (1.34 Å) bonds.
• This indicates that all C-C bonds in benzene are equivalent and intermediate in length.

Stability of Benzene

• Benzene's heat of hydrogenation is lower than expected, implying unusually high stability compared to cyclohexene or cyclohexadiene.
• Benzene does not undergo addition reactions. Reaction with Br₂ results in substitution not addition.

Nomenclature of Benzene Derivatives

• Naming benzene derivatives involves identifying the substituent and adding the word "benzene."
• Common names exist for some monosubstituted benzenes (e.g., toluene, phenol, aniline).
• For disubstituted benzenes, prefixes ortho (o), meta (m), and para (p) are used to specify the relative positions of the two substituents.
• Alphabetizing substituent names is needed if more than one substituent is present.

Hückel's Rule for Aromaticity

• Cyclic: The molecule must form a closed ring.
• Planar: The molecule must be flat.
• Completely conjugated: All atoms involved in the delocalized π system must have p orbitals.
• 4n + 2 π electrons: The number of π electrons must follow this rule where 'n' is an integer (0, 1, 2…)

Examples of Aromatic and Non-Aromatic Compounds

• Cyclobutadiene (4 π electrons) is non-aromatic.
• Benzene (6 π electrons) is aromatic.
• Cycloheptatrienyl cation (6 π electrons) is aromatic cation.
• Cyclopentadienyl anion (6 π electrons) is aromatic.
• Cycloheptatriene (6 π electrons) is not fully delocalized because the CH₂ group lacks a p orbital in the π system.

Annulenes

• Completely conjugated rings larger than benzene can also be aromatic if they are planar and abide by Hückel's rule.
• Hydrocarbons with alternating double and single bonds in a single ring are called annulenes.
• The number of atoms in the ring is indicated in brackets to name an annulene.