Benzene, Phenols & Amines – Comprehensive Notes

9.1 Structure of Benzene

• Benzene (C$<em>6$H$</em>6$) was isolated by Faraday (1825); molecular formula shows a high degree of unsaturation when compared to $C<em>6H</em>{14}$ (hexane) or $C<em>6H</em>{12}$ (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–) = $C<em>6H</em>5–$; Benzyl (Bn–) = $C<em>6H</em>5CH_2–$.
• 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 (H$<em>2$CrO$</em>4$, 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 (–NO$<em>2$), sulfonic acid (–SO$</em>3$H), 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 (H$<em>2$SO$</em>4$, H$<em>3$PO$</em>4$) 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, –NH$<em>2$, –NHR, –NR$</em>2$, halogens).
  • Meta directors: groups with atom bearing partial/full positive charge (–NO$<em>2$, –C$\equiv$N, –SO$</em>3$H, –C(=O)R, –NR$<em>3^+$, –CF$</em>3$, –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 $pK<em>a = 9.95$ vs ethanol $pK</em>a = 15.9$ (phenol 10$^6$ times stronger).
  • Resonance delocalisation in phenoxide ion: charge over O plus ortho & para carbons (4 atoms).
  • E-withdrawing substituents (Cl, NO$<em>2$) further stabilise anion → lower $pK</em>a$.
• 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: $pK<em>a(PhOH)=9.95$ vs $pK</em>a(EtOH)=15.9$.
• 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.