Arenes, Phenol, Carboxylic Acids and Amides - Comprehensive Study Notes

Arenes and Benzene

  • Arenes: Organic hydrocarbons containing one or more benzene rings. General term for benzene-containing compounds: arenes or aromatic compounds; an example: chlorobenzene (a halogenoarene).
  • Simplest arene: benzene itself,
    extC<em>6extH</em>6ext{C}<em>6 ext{H}</em>6
  • Benzene structure:
    • Planar, perfectly symmetrical molecule.
    • Each carbon in the hexagonal ring is sp² hybridised, forming:
    • a σ bond with each of two neighbouring carbons,
    • a σ bond with a hydrogen atom,
    • plus one electron contributed to a π bond (delocalised).
    • All three bonds at each carbon are σ bonds; one electron is left over to participate in the π system.
    • The π bonding arises from the overlap of carbon p orbitals, creating a ring of delocalised electrons above and below the plane of the ring.
    • The π system is shown as overlapping p orbitals forming a continuous electron cloud above and below the ring.
    • Bond angles around each sp² carbon are 120°.
  • The phenyl group (C6H5) and aryl naming:
    • The phenyl group can be written as C6H5; e.g. phenylamine has formula C6H5NH2.
    • Table of aryl compounds (example names):
    • chlorobenzene (Cl substituted),
    • nitrobenzene (NO2 substituted),
    • phenol (OH substituted),
    • phenylamine (NH2 substituted).
    • 2,4,6-tribromophenol illustrates how positions on the ring are described when multiple substituents are present.

Electrophilic substitution on benzene (Cl & Br) and halogenation

  • Electrophilic substitution mechanism (Cl and Br):
    • A halogen molecule (Br2) forms a dative bond with a Lewis acid halogen carrier (e.g., FeCl3, AlCl3, FeBr3) to generate the electrophile Br+ (or Cl+).
    • Br+ (or Cl+) is attracted to the electron-rich π system of benzene.
    • The reaction typically runs at room temperature in the presence of the halogen carrier catalyst.
  • Substitution patterns:
    • Halogenation of arenes on alkylbenzenes tends to give substitution at ortho (2) and para (4) positions; in excess chlorine, multi-substitution can occur.
    • Example: halogenation of alkylbenzenes can yield 1-methyl-2,4,6-trichlorobenzene (positions 2 and 6 are equivalent).
  • Bond character:
    • The C–X bond in halogenoarenes is stronger than in halogenoalkanes because one lone pair on the halogen overlaps with the π-system of the benzene ring, giving the C–X bond partial double-bond character.
  • Free-radical substitution on the side-chain (Cl & Br):
    • In excess chlorine, the alkyl side-chain H atoms can be progressively replaced by Cl, eventually leading to complete chlorination of the side-chain.

Nitration of benzene

  • Nitration is an electrophilic substitution reaction:
    • Reagents: conc. HNO3 and conc. H2SO4 generate the nitronium ion NO2+ (electrophile).
    • Bath/temperature: benzene is nitrated around room temperature to form nitrobenzene (NO2 substituent).
    • Mechanism: Stage 1 NO2+ is attracted to the high electron density of the π system; Stage 2 C–H bond breaks heterolytically, giving H+ that leaves and restores the delocalised ring.
    • Further nitration yields polynitrated benzene, e.g. 1,3,5-trinitrobenzene.
    • The nitro group is introduced through electrophilic attack on the benzene ring.

Friedel–Crafts reactions (alkylation and acylation)

  • Friedel–Crafts reactions introduce a side-chain onto the benzene ring, either via alkylation or acylation.
  • These reactions create a substituted benzene with a new carbon-containing substituent attached to the ring.

Oxidation of side-chains on arenes (alkylbenzenes)

  • Alkylarenes’ side-chains can be oxidised to carboxylic acids.
  • Reagent conditions:
    • Reflux with alkaline potassium manganate(VII) followed by acidification with dilute H2SO4 (KMnO4 in basic conditions; decolourises the purple MnO4− solution).
    • Alternatively, reflux with potassium dichromate(VI) (K2Cr2O7) followed by dilution with dilute H2SO4.
  • Products: oxidation of the benzylic side-chain to a carboxylic acid group (–COOH).

Phenol: Properties and chemistry

  • Phenol, C6H5OH, is a crystalline solid that melts at ~43°C; hydrogen bonding contributes to its physical properties.
  • Solubility: phenol is only slightly soluble in water due to its non-polar benzene ring.
  • Acidity: phenol is weakly acidic (more acidic than water or alcohols), with its conjugate base (phenoxide, C6H5O−) resonance-stabilised across the ring.
    • Phenoxide ion: negative charge is delocalised across the whole ion via overlap of the oxygen lone pair with the π-system, reducing charge density on O− compared with OH− or EtO−.
    • Equilibrium lies further to the right for phenol compared with many other alcohols, reflecting stronger acidity.
  • Solubility and reactivity with bases:
    • Phenol slightly dissolves in water but dissolves well in alkaline solutions; sodium phenoxide is water-soluble.
    • Reaction with sodium metal liberates H2 and forms sodium phenoxide.
  • Electrophilic substitution in phenol:
    • Phenol is more activated toward electrophiles than benzene because the lone pair on the O atom donates electron density into the ring.
    • Halogenation (Cl2, Br2) at room temperature gives substitution with a white precipitate.
  • Additional reactions:
    • Nitration with dilute nitric acid at room temperature is possible (phenol behaves as a more activated ring).

Carboxylic acids: acidity, dissociation, and reactivity

  • Neutralisation (alkali):
    • extCH<em>3extCOOH+extNaOHightarrowextCH</em>3extCOONa+extH2extOext{CH}<em>3 ext{COOH} + ext{NaOH} ightarrow ext{CH}</em>3 ext{COONa} + ext{H}_2 ext{O}
  • Dissociation: carboxylic acids are weak acids; equilibrium:
    • extCH<em>3extCOOHightleftharpoonsextCH</em>3extCOO−+extH+ext{CH}<em>3 ext{COOH} ightleftharpoons ext{CH}</em>3 ext{COO}^- + ext{H}^+
  • Acidity trends and substituent effects:
    • Electron-withdrawing groups adjacent to the –COOH group increase acidity by stabilising the carboxylate anion and weakening the O–H bond.
    • Electron-donating groups decrease acidity.
    • Examples:
    • Trifluoromethyl carboxylic acid: …CCl3COOH is stronger due to three strongly electron-withdrawing Cl atoms.
    • Acetic acid, CH3COOH, is weaker because the methyl group is electron-donating.
  • Special oxidations:
    • Oxidation of formic acid (HCOOH): strong oxidising agents (e.g., KMnO4 or dichromate) can further oxidise it; observed by decolourisation of MnO4− solution and other colour changes.
    • Oxidation of ethanedioic acid (oxalic acid, HOOC–COOH) with strong oxidants occurs as a standard method to standardise KMnO4 solutions.
    • A solution of oxalic acid is titrated with KMnO4 until a pale pink endpoint persists; a form of autocatalysis occurs via Mn2+ catalysis.
  • Nucleophilic substitution: formation of acyl chlorides from carboxylic acids
    • Reagents: PCl5, PCl3, SOCl2 (thionyl chloride) can convert –OH to –Cl, giving acyl chlorides, R–COCl.
  • Acyl chlorides: properties and reactivity
    • Acyl chlorides are more reactive than carboxylic acids and are widely used in synthesis.
    • Hydrolysis tendency: acyl chlorides hydrolyse readily in water to give carboxylic acids and HCl.
    • Hydrolysis comparison: hydrolysis rate order is acyl chloride > chloroalkane > aryl chloride.
  • Esterification with acyl chlorides
    • Acyl chlorides react with alcohols or phenols to form esters (and HCl) and do so more rapidly and to completion than carboxylic acid + alcohols.
    • For phenyl esters (phenyl esters) to form, acyl chlorides are used under heating with a base (to form the phenoxide as nucleophile) and the reaction proceeds to form the ester.
  • Nucleophilic substitution with amines and amide formation
    • Amines (primary, secondary, tertiary) have lone pairs on nitrogen that act as nucleophiles and attack the carbonyl carbon of acyl chlorides, producing amides.
    • Ammonia and amines act as bases (lone-pair donation to H+).
    • Reactions with dilute acids give ammonium salts.
    • Amide naming: the N-substituent naming uses an 'N' to denote the substituent attached to the nitrogen (e.g., N-ethylbutanamide: C3H7CONHC2H5). If more than one N-substituent, two Ns are used (e.g., N,N-diethylbutanamide).
  • Basicity of amines vs ammonia and phenylamines
    • Relative basicity in aqueous solution: Ethylamine > ammonia > phenylamine.
    • Reason: electron-donating alkyl group on the amine increases electron density on N (more basic); the benzene ring in aniline (phenylamine) withdraws electron density via delocalisation of the lone pair into the ring, reducing basicity.
  • Preparation of amines (two general methods):
    • Ethylamine synthesis:
    • Ammonia (NH3) in ethanol, excess, heated with bromoethane (to promote SN2 and avoid multiple substitutions) → ethylamine salt forms; subsequent steps are used to isolate the free amine (not fully detailed in the transcript).
    • Alternatively: Bromomethane + KCN yields ethanenitrile, which can be reduced (e.g., H2 over Ni catalyst) to give ethylamine; LiAlH4 in dry ether is mentioned for reduction.
    • Phenylamine synthesis:
    • Reduction of nitrobenzene with tin (Sn) and concentrated HCl, followed by separation of phenylamine by steam distillation.
  • Electrophilic substitution on phenylamine and diazotisation
    • Electrophilic substitution of Br into phenylamine (Br into Br(aq) on phenylamine) yields a white precipitate; the –NH2 group donates electrons into the ring, increasing activation toward electrophiles.
    • Diazotisation (formation of diazonium salts):
    • Step 1: Aniline (phenylamine) + nitrous acid (NO2H produced in situ from sodium nitrite, NaNO2, and dilute HCl) → diazonium salt (C6H5N2+). This step must be kept below 10°C due to instability of the diazonium salt at higher temperatures.
    • Step 2: the diazonium ion undergoes coupling with an alkaline solution of phenol, producing an azo dye (an orange, very stable dye) via electrophilic substitution onto phenol at the para position; the diazonium ion acts as an electrophile in the coupling reaction.
    • The structure contains a delocalised π-bonding system extending between the two benzene rings across the NN linkage (diazonium group).
  • A note on aryl compounds and amino acids as alternatives
    • Alternative aryl compounds to phenol include amino acids:
    • General structure: R–CH(NH2)–COOH.
    • Examples: glycine (R = H), alanine (R = –CH3).
    • The R group can be acidic, basic or neutral.
    • Amino acids exist as zwitterions in solution (NH3+ and COO−) and are crystalline and soluble in water.
    • Solutions of amino acids are amphoteric and act as buffers (amphoteric behavior).
  • Peptide formation and amino acids
    • Two amino acids react via a condensation reaction to form a dipeptide with a peptide (amide) bond, releasing a molecule of water.
    • This step can continue to form polypeptides and ultimately proteins.

Amides: structure, formation, hydrolysis, and naming

  • Amide structure: CONH2 (primary amide example: ethanamide, CH3CONH2).
  • Amides are neutral compounds (unlike amines) because the amide nitrogen’s lone pair is conjugated with the carbonyl, decreasing basicity and reducing availability for donation.
  • Formation of amides
    • Ethanoyl chloride (CH3COCl) reacts with concentrated NH3(aq) to give ethanamide (CH3CONH2) and HCl (at room temperature).
    • A primary amide reacting with an acyl chloride yields a substituted amide.
    • Excess amine reacts with HCl to form ammonium halide salts (e.g., C2H5NH3+Cl−).
    • Reactions described occur readily at room temperature; the amide product retains the –NH2 group at the terminal of the molecule.
  • Nomenclature of amides with N-substitution
    • The N-substituent is indicated in the name using an 'N' prefix, e.g. N-ethylbutanamide: C3H7CO-NH-C2H5.
    • If more than one N-substituent is present, two 'N' positions are indicated, e.g. N,N-diethylbutanamide: C3H7CON(C2H5)2.
  • Hydrolysis of amides
    • Substituted amides (-CONH−):
    • Acidic hydrolysis: yields a carboxylic acid (R1COOH) and a primary amine (R2NH2); excess acid converts the amine to its ammonium salt (R2NH3+Cl−).
    • Basic hydrolysis: yields sodium carboxylate (R1COO−Na+) and the primary amine (R2NH2).
    • Unsubstituted amide (RCONH2):
    • Hydrolysis under acidic or basic conditions yields ammonia and the corresponding carboxylic acid or its salt, depending on the conditions.
  • Summary of key themes
    • Amides are prepared from carboxylic acid derivatives (e.g., acyl chlorides) and amines or ammonia.
    • The amide linkage (–CONH–) is a defining feature of peptides and proteins, linking amino acids in biological systems.

Connections and practical implications

  • Aromatic chemistry (arenes) underpins many industrial syntheses (halogenation, nitration, Friedel–Crafts) and natural products.
  • Activation of the benzene ring by substituents (e.g., OH in phenol or –NH2 in aniline) dramatically affects reactivity toward electrophiles and subsequent substitution patterns.
  • The chemistry of carboxylic acids (acidity, oxidation, and conversion to acyl chlorides) provides a versatile toolbox for forming esters, amides, and other derivatives used in polymers, pharmaceuticals, and organic synthesis.
  • Azo dyes formed via diazonium chemistry illustrate how aromatic amines can be transformed into colored compounds with extended conjugation across linked aromatic rings.
  • The interplay between structure and reactivity (e.g., electron-donating vs electron-withdrawing substituents) governs acid strength, nucleophilicity, and basicity—crucial for predicting or rationalizing mechanisms in organic reactions.