Benzene, Phenols & Amines – Comprehensive Notes

9.1 Structure of Benzene

  • Benzene (C6H6) was isolated by Faraday (1825); molecular formula shows a high degree of unsaturation when compared to C6H{14} (hexane) or C6H{12} (cyclohexane).
  • Despite 3 implied "double bonds", benzene does NOT undergo alkene-type additions (e.g. Br_2, HCl, peracids) but reacts mainly by substitution.
  • Terminology
    • Aromatic compound: historically odor-based; now means "exceptionally stable, highly unsaturated compound that resists alkene reagents".
    • Arene = aromatic hydrocarbon.
    • Aryl group (Ar–): group formed by removing an H from an arene. Analogy: R– for alkyl.
  • Kekulé’s model (1872)
    • Six-membered ring with alternating single/double bonds; bonds "oscillate" rapidly; explains single monosubstitution product and 3 dibromobenzenes.
    • Could not explain lack of alkene-type reactivity.
  • Orbital overlap (Pauling, 1930s)
    • Each C is sp^2-hybridized; sigma framework is a regular hexagon (120^\circ bond angles).
    • Six unhybridized 2p orbitals overlap to produce a continuous \pi cloud (torus above & below ring).
    • All C–C bonds identical in length: 1.39\,\text{Å} (between typical single (1.54 Å) & double (1.33 Å)).
  • Resonance description
    • Actual benzene = hybrid of two equivalent Kekulé structures; bonds are "not single/not double".
  • Resonance energy
    • Estimate via heats of hydrogenation.
    • Cyclohexene \Delta H^0_{hyd} = -120\,\text{kJ mol}^{-1}; a hypothetical "triene" benzene would predict 3\times(-120)=-359\,\text{kJ mol}^{-1}.
    • Experimental benzene: -209\,\text{kJ mol}^{-1} → Resonance energy =150\,\text{kJ mol}^{-1} (35.8 kcal mol^{-1}).
    • High RE explains unusual stability/chemistry.

9.2 Aromaticity (Hückel rules)

  • To be aromatic a ring must:
    1. Possess one 2p orbital on each atom of the ring.
    2. Be planar (continuous overlap).
    3. Contain 4n+2 \pi electrons (2, 6, 10, 14 …).
  • Examples
    • Pyridine, pyrimidine: six \pi electrons; heteroatom lone pairs NOT in the ring system if already part of an sp^2 lone pair perpendicular to ring.
    • Furan, pyrrole, imidazole: 5-membered rings; one heteroatom lone pair enters the \pi system to provide the aromatic sextet.
  • Key heteroaromatic biomotifs: indole (tryptophan, serotonin), purine (adenine, NAD^+).
  • How-To 9.1: Lone pair participation
    • If the atom is already in a double bond → its lone pair is not in \pi system.
    • If not in a double bond, hybridise atom sp^2; include lone pair in ring; check 4n+2 count.

9.3 Naming & Physical Properties of Benzenes

  • Monosubstituted: retain common names (toluene, styrene, phenol, aniline, anisole, benzaldehyde, benzoic acid).
  • Phenyl (Ph–) = C6H5–; Benzyl (Bn–) = C6H5CH_2–.
  • Disubstituted: use numbering or prefixes
    • ortho (o-) = 1,2-; meta (m-) = 1,3-; para (p-) = 1,4-.
  • Polysubstituted: choose parent that confers special name; otherwise lowest locant set & alphabetical order.
  • Polynuclear aromatics (PAHs): naphthalene, anthracene, phenanthrene, benzo[a]pyrene (carcinogenic; Chemical Connection 9A: metabolic diol-epoxide binds to DNA).

9.4 Benzylic Position Chemistry

  • Benzylic carbon = sp^3 C directly attached to aromatic ring.
  • Strong oxidants (H2CrO4, KMnO_4) oxidise any benzylic carbon bearing ≥1 H to \ce{-COOH}.
    • Toluene → benzoic acid.
    • Side chains without benzylic H (e.g. t-butylbenzene) are inert.
    • Multiple side chains each oxidised (e.g. m-xylene → isophthalic acid).

9.5 Electrophilic Aromatic Substitution (EAS) – Overview

  • Characteristic benzene reaction: E^+ replaces ring H; aromaticity preserved.
  • Directly install: halogen (Cl, Br), nitro (–NO2), sulfonic acid (–SO3H), alkyl (–R), acyl (RCO–).
  • General mechanism (3 steps)
    1. Generate electrophile E^+.
    2. \pi attack → resonance-stabilised sigma complex (arenium ion).
    3. Base removes proton → restores aromaticity.

9.6 Mechanistic Details

  • Halogenation (Cl, Br)
    • \ce{Cl2/FeCl3} or \ce{AlCl3} → \ce{Cl+} (chloronium) + \ce{FeCl4-}.
  • Nitration: \ce{HNO3 + H2SO4} → \ce{NO2+} (nitronium).
  • Sulfonation: hot conc. \ce{H2SO4} or \ce{SO3} → \ce{HSO3+}/\ce{SO3}.
  • Friedel–Crafts Alkylation
    • \ce{R–Cl/AlCl3} → R^+; limitations: rearrangements, polyalkylation, failure with strongly E-withdrawing substituents.
  • Friedel–Crafts Acylation
    • \ce{RCOCl/AlCl3} → acylium RCO^+ (resonance-stabilised); no rearrangements; product ketone can be further reduced (Clemmensen, Wolff–Kishner) to achieve "clean" alkylation.
  • Alternative alkylations
    • Alkenes or alcohols + strong acid (H2SO4, H3PO4) generate carbocations in situ.
  • Comparison with alkene addition: both start with electrophilic attack; alkene path ends with nucleophile adding to carbocation (addition) whereas EAS ends with deprotonation (substitution, aromaticity regained).

9.7 Substituent Effects in EAS

  • Directing effects
    • Ortho/Para directors: alkyl, phenyl, groups with lone pair directly attached (–OH, –OR, –NH2, –NHR, –NR2, halogens).
    • Meta directors: groups with atom bearing partial/full positive charge (–NO2, –C\equivN, –SO3H, –C(=O)R, –NR3^+, –CF3, –CCl_3).
  • Activating vs deactivating
    • Activators speed up ring vs benzene; all ortho/para except halogens. Strong > moderate > weak.
    • Deactivators slow ring; all meta plus halogens (weak deactivators).
  • Rationale
    • Lone-pair donors give extra resonance stabilisation of sigma complex → o/p.
    • Electron-withdrawing groups destabilise sigma complex at o/p via positive charge adjacency; meta avoids this.
    • Alkyl groups stabilise via hyperconjugation → o/p.
  • How-To 9.2: determine if a substituent is electron-withdrawing → check atom directly bonded to ring for \delta^+ or + charge.
  • Synthetic planning: order of steps critical (e.g. nitration before bromination with nitro meta director vs opposite order leads to o/p product).

9.8 Phenols

  • Phenol = benzene ring bearing –OH.
  • Nomenclature: phenol, cresols (o-, m-, p-), catechol/resorcinol/hydroquinone (benzenediols).
  • Natural examples: thymol (thyme), vanillin (vanilla), eugenol (cloves), urushiol (poison ivy).
  • Acidity
    • Phenol pKa = 9.95 vs ethanol pKa = 15.9 (phenol 10^6 times stronger).
    • Resonance delocalisation in phenoxide ion: charge over O plus ortho & para carbons (4 atoms).
    • E-withdrawing substituents (Cl, NO2) further stabilise anion → lower pKa.
  • Reactions
    • Deprotonation with strong bases (NaOH) → water-soluble phenoxide; basis for extraction separation from alcohols.
    • Weak bases (NaHCO_3) generally do not deprotonate phenols (contrast carboxylic acids).
  • Phenols as antioxidants
    • Autoxidation: radical chain converting allylic R–H → R–OOH (hydroperoxide) via ROO^•; causes rancidity, LDL oxidation, aging effects.
    • Phenolic antioxidants (vitamin E, BHT, BHA) donate H^• to terminate chain (stable phenoxyl radical).
    • Chemical Connection 9B: Capsaicin as medicinal phenol; lace with extraction question.

10 Amines: Introduction

10.1 Definition & Classification

  • Amines = derivatives of ammonia where H replaced by alkyl/aryl.
  • Degrees
    • 1^\circ: RNH_2
    • 2^\circ: R_2NH
    • 3^\circ: R_3N
  • Aliphatic vs Aromatic (nitrogen attached to only alkyl vs at least one aryl).
  • Heterocyclic amine: N is part of ring; aromatic variants e.g. pyridine, indole.
  • Examples: coniine (hemlock), nicotine, cocaine (Example 10.1).

10.2 Nomenclature of Amines

  • Systematic (IUPAC) alkanamines: replace “-e” of parent alkane by “-amine”; number chain from end nearest N.
    • \ce{CH3CH2CH2NH2} → 1-propanamine (propylamine).
    • Diamines: 1,6-hexanediamine.
  • Aniline retained as parent for aromatic amines (toluidine, anisidine derivatives).
  • Secondary/tertiary: named as N-substituted primary amines; prefix N- (or N,N-).
  • Salts (four substituents on N): change suffix to “-ammonium”, “-anilinium”, etc., plus anion name.
    • e.g. \ce{(CH3)4N+ Cl-} tetramethylammonium chloride.
  • Common names: list alkyls alphabetically + “amine” (e.g. diethylamine).

10.3 Physical Properties of Amines

  • Geometry: trigonal pyramidal at N (lone pair occupies one vertex).
  • Intermolecular forces
    • 1^\circ & 2^\circ amines: N–H……N hydrogen bonding (weaker than O-based H-bond; \Delta\chi N–H = 0.9 vs O–H = 1.4).
    • 3^\circ amines: no N–H bonds → no H-bond donors → lower b.p.
  • Boiling points
    • Methylamine bp -6.3^{\circ}!\text{C} vs methanol 65^{\circ}\text{C} (stronger H-bond in alcohol).
    • Isomeric effects: bulky t-butylamine (bp 46^{\circ}\text{C}) < n-butylamine (bp 78^{\circ}\text{C}) due to steric hindrance in H-bonding (Example 10.4).
  • Solubility
    • All classes form H-bonds with water; low-MW amines very soluble; solubility decreases with size/bulk.
    • Table 10.1 summarises mp, bp, solubilities.

Chemical Connections & How-Tos Included

  • 9A Carcinogenic PAHs: benzo[a]pyrene metabolism → diol epoxide that alkylates DNA.
  • 9B Capsaicin: dual role as irritant & analgesic; applied in creams (Mioton, Zostrix) for neuropathic pain.
  • 10A Morphine analog design: codeine, heroin, meperidine, levo/dextromethorphan; structural simplifications & stereochemistry.
  • 10B Poison dart frogs: batrachotoxin, action on Na^+ channels; illustrates natural product discovery.

Key Equations & Values

  • Resonance energy of benzene = 150\,\text{kJ mol}^{-1}.
  • Hückel 4n+2 rule.
  • Oxidation of side chain: \ce{Ar–CH3 ->[H2CrO4] Ar–COOH}.
  • General EAS mechanism (three steps) – see above.
  • Phenol acidity: pKa(PhOH)=9.95 vs pKa(EtOH)=15.9.
  • Autoxidation chain propagation illustrated (Steps 2a + 2b).

Ethical, Biological & Practical Notes

  • Environmental/health impact of benzo[a]pyrene from combustion, cigarette smoke.
  • Industrial importance of terephthalic acid (from p-xylene) in PET/polyester.
  • Phenolic antioxidants extend shelf-life of fats, protect polymers.
  • Amines in drugs (antihistamine chlorphenamine, CNS stimulants such as amphetamine) highlight structure–activity relationships.