Aromaticity 1 (Rahime Şimşek)
Organic Chemistry Cell Sciences I
Professor: Rahime Simsek, PhD
Email: rsimsek@hacettepe.edu.tr
Department: Pharmaceutical Chemistry
Faculty: Pharmacy
Phone: 305-1872
Aromaticity and Benzene
Course Objectives
To enable students to gain knowledge and skills on the topic of aromaticity and benzene.
Learning Goals
Knowledge to be Gained:
Nomenclature of aromatic compounds
Structure of benzene:
Kekulé’s proposal
Representations of benzene
Resonance approach
Meaning of aromaticity and the Huckel 4n + 2 rule
Chemistry of benzene:
Electrophilic aromatic substitution reactions:
Nitration
Sulfonation
Halogenation
Friedel-Crafts alkylation
Friedel-Crafts acylation
Directing effects of substituents in monosubstituted benzene derivatives:
Activating and deactivating groups
Synthesis of disubstituted benzene derivatives
Course Content
Nomenclature of aromatic compounds
Structure of benzene: Kekulé’s proposal, representations, resonance
Meaning of aromaticity and the Huckel 4n + 2 rule
Chemistry of benzene, electrophilic aromatic substitutions
Textbooks:
Organik Chemistry by John McMurry 13th Ed.
Organik Kimya by Hart H., Craine L.E., Hart D.J
Organic Chemistry by Graham Solomons
Advanced Organic Chemistry by Jerry March
Organik Kimya by Robert C. Atkins, Francis A Carey(Translation: G Okay, Yilmaz Yıldırır)
Historical Background of Benzene
Michael Faraday (1825): Discovered hydrocarbon called “bicarburet of hydrogen” (now benzene).
Eilhardt Mitscherlich (1834): Synthesized benzene via heating benzoic acid with CaO; determined molecular formula C6H6.
Classifications of Organic Compounds
Aliphatic Compounds: Characterized as "fatlike"; includes alkanes, alkenes, alkynes and derivatives.
Aromatic Compounds: Characterized by low hydrogen-carbon ratio and fragrance.
Nomenclature of Benzene Derivatives
Naming Systems
Benzene is the parent name; substituent indicated by a prefix.
Substituent and benzene can form a new parent name.
Examples of Substitutes
Common Substituted Benzene:
Fluorobenzene, Chlorobenzene, Bromobenzene, Nitrobenzene
Toluene, Phenol, Aniline, Benzenesulfonic acid, Benzoic acid
Anisole
Position of Substituents
Two substituents' positions indicated by:
Ortho (o-), Meta (m-), Para (p-); or by using numbers.
Dimethylbenzenes (Xylenes)
1,2-Dimethylbenzene (o-xylene), 1,3-Dimethylbenzene (m-xylene), 1,4-Dimethylbenzene (p-xylene).
Multiple Substitution Indications
The benzene ring is numbered to give the lowest possible numbers.
Different substituents are listed in alphabetical order.
The C6H5 group is termed a phenyl group when named as a substituent.
Reactions of Benzene
Expected Reactions (Mid-19th Century)
Expected to behave like alkenes (e.g., react with bromine, oxidized by potassium permanganate).
Actual Behavior
Does not undergo addition; rather, it undergoes substitution to form bromobenzene without addition of hydrogen.
Kekule Structure for Benzene
Proposed by August Kekule in 1865; suggests alternating single and double bonds in a carbon ring, with hydrogens attached to carbons.
Stability of Benzene
Benzene undergoes substitution reactions rather than addition, indicating higher stability than suggested by its structure.
More stable than theoretical predictions (e.g. hydrogenation of 1,3,5-cyclohexatriene).
Huckel Rule
Compounds with a planar ring and 4n + 2 π electrons (n=0,1,2...) are aromatic.
Indicates stability arises from
Planar conjugated systems.
Aromaticity Criteria
4n + 2 rule indicates stability and aromatic character.
Annulenes
Monocyclic compounds represented by alternating single and double bonds; e.g., benzene is [6] annulene.
Huckel’s rule applies to annulenes predicting aromatic properties based on electron count.
Heterocyclic Aromatic Compounds
Cyclic compounds containing elements other than carbon (e.g., nitrogen, oxygen, sulfur).
Common heterocyclic compounds: pyridine, pyrrole, furan, thiophene.
Biochemistry and Aromatic Compounds
Aromatic rings are significant in biochemical reactions; amino acids like phenylalanine and tyrosine contain benzene rings.
Heterocyclic compounds like purines and pyrimidines are integral to DNA and RNA structure.
Summary of Benzene Chemistry
Benzene is more stable than alkenes; predominantly undergoes substitution reactions.
Molecular structure is planar with identical C-C bond lengths, leading to aromatic stabilization.
Electrophilic Aromatic Substitution (EArS)
Key reactions include nitration, sulfonation, halogenation, and Friedel-Crafts reactions.
Mechanism involves formation of carbocations by substituting hydrogen atoms in benzene.
Orientation Effects in EArS
Activating groups (e.g., -OH, -CH3) direct electrophiles to ortho and para positions; deactivating groups (e.g., -NO2) direct to meta positions.
Summary of Substituent Effects
Activating vs. Deactivating Groups; resonance and inductive effects influence reactivity and orientation in substitution reactions.
Halogens are unique as they deactivate inductively but direct ortho- and para- due to resonance.
Further Reactions of Aryl Side-Chains
Include reactions of alkyl benzenes, nucleophilic substitutions, and oxidations that modify the benzene ring.
Aromaticity and Benzene
Course Objectives
To enable students to gain knowledge and skills on the topic of aromaticity and benzene.
Learning Goals
Knowledge to be Gained:
Nomenclature of Aromatic Compounds: Understanding the naming conventions and how substituents affect compound names.
Structure of Benzene:
Kekulé’s Proposal: Proposed structure showing alternating single and double bonds in a hexagonal ring.
Representations of Benzene: Including Kekulé structure and resonance contributors.
Planar Configuration: Benzene is a flat molecule with bond angles of 120° and equal C-C bond lengths (1.39 Å).
Dimensional Geometry: The benzene molecule is represented as a hexagonal shape with a circle in the center, indicating delocalized electrons.
Meaning of Aromaticity and the Huckel 4n + 2 Rule: Learn how this rule identifies aromatic compounds based on their electron counts.
Chemistry of Benzene:
Electrophilic Aromatic Substitution Reactions:
Nitration: Introduction of a nitro group (NO2) into the benzene ring.
Sulfonation: Introduction of a sulfonic acid group (SO3H).
Halogenation: Reaction with halogens (e.g., Cl2 or Br2).
Friedel-Crafts Alkylation: Formation of alkyl-substituted benzene.
Friedel-Crafts Acylation: Formation of acyl-substituted benzene.
Directing Effects of Substituents in Monosubstituted Benzene Derivatives:
Activating Groups: Such as -OH, -NH2 (ortho/para directors).
Deactivating Groups: Such as -NO2 (meta directors).
Synthesis of Disubstituted Benzene Derivatives: Understanding how to synthesize and name benzene derivatives with multiple substituents.
Summary of Key Concepts:
Kekulé’s Structure: Depicts benzene as having alternating double and single bonds.
Stability of Benzene: High stability due to resonance, preventing addition reactions typical of alkenes.
Huckel Rule: Reclining the allowances for aromaticity, reinforcing concepts of electron delocalization.
Annulenes: Hexagonal configurations with alternating bonds; interchanging between aromatic and non-aromatic states depending on electron count.
Nomenclature of Benzene Derivatives
Naming Systems: Benzene as the parent name, with substituents indicated as prefixes or new parent names.
Examples of Substitutes:
Common Substituted Benzene: Fluorobenzene, Chlorobenzene, Bromobenzene, Nitrobenzene, Toluene, Phenol, Aniline.
Position of Substituents: Ortho (o-), Meta (m-), Para (p-), applied in naming compounds with two substituents.
Multiple Substitution Indications: Numbering benzene to provide the lowest possible numbers and listing different substituents alphabetically.
C6H5 Group: Referred to as the phenyl group when named as a substituent.
Summary of Benzene Chemistry
Benzene displays enhanced stability and primarily undergoes substitution reactions over addition. Its planar structure and identical C-C bond lengths contribute to its lower reactivity compared to alkenes, indicated by varied substitution patterns influenced by the groups attached to the ring.