Organic Chemistry – Halogen Derivatives, Alcohols, Carbonyls & Amines

Halogen Derivatives

  • Introduction & General Reactions

    • Alkane halogenation: \text{R–H}+X_2 \rightarrow \text{R–X}+\text{HX}

    • Arene halogenation: \text{Ar–H}+X_2 \rightarrow \text{Ar–X}+\text{HX}

    • “Easy trick” (mnemonic) mentioned for quick recall.

  • Two–Way Classification

    • By hydrocarbon skeleton

    • Haloalkanes \text{R–X}

    • Haloalkenes (\text{CH}2{=}CH2\text{–Cl})

    • Haloalkynes (\text{–C}\equiv \text{C–X})

    • Haloarenes (Ar–X)

    • By number of halogens

    • Mono-, di-, tri-halogen compounds (formulas and skeletal examples shown).

  • Detailed Sub-Classification of Monohalides

    • Alkyl (haloalkane): X on sp^3 C of an alkyl chain.

    • Allylic: X on sp^3 C next to C=C: C{=}C–C–X

    • Benzylic: X on sp^3 C directly bonded to aromatic ring: \text{Ph–CH}_2\text{–X}

    • Vinylic: X on sp^2 C of a C=C: CH_2{=}CH–X

    • Halo-alkynes: X on sp C of C\equiv C chain.

    • Aryl: X directly on aromatic sp^2 C.

  • IUPAC Nomenclature Table

    • Exhaustive list of 14 common→IUPAC conversions given (CH$_3$Cl → chloromethane; vinyl chloride → 1-chloroethene; etc.).

    • Remember to number so halogen gets lowest locant; multiple halogens → di/tri prefixes.

  • Preparations of Alkyl Halides

    1. From alcohols

    • HX + anhy \text{ZnCl}2 (Lucas conditions) \text{R–OH}+HX \xrightarrow[\text{anhy ZnCl}2]{} \text{R–X}+H_2O

    • NaBr/H$2$SO$4$ or NaI/H$3$PO$4$ supply HBr/HI in situ.

    • Phosphorus halides: 3\text{R–OH}+PCl3 \rightarrow 3\text{R–Cl}+H3PO3 (similarly PCl5).

    • Thionyl chloride (best): \text{R–OH}+SOCl2 \rightarrow \text{R–Cl}+SO2\uparrow +HCl\uparrow

    1. From alkenes/alkynes

    • Markovnikov addition of HX; anti-Markovnikov in presence of peroxide (Kharasch effect).

    1. Halogen exchange

    • Finkelstein: \text{R–Cl}+NaI \rightarrow \text{R–I}+NaCl (acetone).

    • Swarts: \text{R–Cl}+AgF \rightarrow \text{R–F}+AgCl.

    1. Electrophilic substitution on aromatic ring (Fe / dark).

    2. Sandmeyer: diazonium salt + CuX → aryl-X.

  • Stereochemical Concepts

    • Chiral carbon = C with 4 different substituents.

    • Plane-polarised light, optical activity, dextro (+) vs laevo (–).

    • Enantiomers = non-superimposable mirror images; racemic mixture = 1:1 dl.

  • Substitution Mechanisms

    • \text{S}_\text{N}1 (unimolecular): carbocation intermediate; rate =k[\text{R–X}].

    • \text{S}_\text{N}2 (bimolecular, backside attack): single transition state; rate =k[\text{R–X}][Nu^-].

  • Characteristic Laboratory Test

    • \text{R–X}+OH^- \rightarrow \text{R–OH}+X^- followed by Ag^+ +X^- \rightarrow AgX \downarrow (white Cl, pale-yellow Br, yellow I).

  • Comprehensive Nucleophilic Substitutions

    • NaOH{(aq)} → alcohols; NaOR → ethers; RCOOAg → esters; alc NH3 → amines; alc KCN → nitriles; alc AgCN → isocyanides; KNO2 vs AgNO2 give alkyl nitrites vs nitroalkanes, etc.

  • Elimination (dehydrohalogenation)

    • \text{R–CHX–CH}3\xrightarrow[\text{alc}]\text{KOH} \text{R–CH=}CH2 (Saytzeff orientation).

  • Metal Coupling

    • Grignard (R–Mg–X) formation; Wurtz 2\text{R–X}+2Na → \text{R–R}; Wurtz–Fittig, Fittig for aryl/alkyl couplings.

  • Special Reactivity of Haloarenes

    • Nucleophilic substitution facilitated by –NO_2 at o/p (elimination–addition, \text{Ar–Cl} \rightarrow \text{Ar–OH}).

    • Electrophilic substitution: halogenation, nitration, sulphonation, Friedel–Crafts on ring.

  • Important Polyhalogen Compounds – Uses & Hazards

    1. Dichloromethane – solvent/propellant; CNS depression, corneal damage.

    2. Chloroform – solvent, \mathit{CHCl3\xrightarrow{base}} :CCl2 source; hepatotoxic.

    3. Carbon tetrachloride – cleaning; liver toxin, greenhouse gas.

    4. Iodoform – antiseptic; skin/eye/respiratory irritant.

    5. Freons (CFCs) – refrigerants; ozone depletion, asphyxiant.

    6. DDT – insecticide; bio-persistent pollutant, tremors at high dose.

Alcohols, Phenols & Ethers

  • Definitions

    • Alcohols: \text{R–OH} on saturated C.

    • Phenols: \text{Ar–OH} on benzene ring.

    • Ethers: \text{R–O–R'},\;\text{Ar–O–Ar'},\;\text{R–O–Ar}.

  • Classification

    • Mono-, di-, tri-hydric (1, 2, 3 –OH).

    • sp^3 vs sp^2 C–O bonds: alkyl, allylic, benzylic, vinylic alcohols.

    • Ethers: symmetrical vs mixed.

  • Nomenclature Highlights

    • Alcohols: butan-2-ol, 2-methyl-propan-2-ol, glycerol (propane-1,2,3-triol), crotyl alcohol (but-2-en-1-ol).

    • Phenols: catechol (1,2-diol), resorcinol (1,3-diol), hydroquinone (1,4-diol), etc.

    • Ethers: methoxyethane, anisole (methoxybenzene), 1-propoxybenzene.

  • Preparations of Alcohols

    1. From alkyl halides (aq NaOH).

    2. Acid-catalysed hydration of alkenes (Markovnikov).

    3. Hydroboration–oxidation (anti-Markovnikov).

    4. Reduction of carbonyls

    • Aldehyde \rightarrow 1^\circ alcohol, ketone \rightarrow 2^\circ alcohol via LiAlH4 or H2/Pd.

    • Acids \xrightarrow{LiAlH_4} alcohols.

    1. Grignard on \mathrm{H_2CO}, aldehyde, ketone gives 1^\circ, 2^\circ, 3^\circ alcohols respectively.

  • Preparations of Phenol

    • Dow (chlorobenzene + NaOH_{(aq,150\,atm,623 K)}).

    • Cumene process (cumene → cumene hydroperoxide → phenol + acetone).

    • From benzene sulphonic acid, from aniline via diazonium salt.

  • Physical Properties

    • Extensive H-bonding → higher b.p.; low-MW alcohols/phenols water-soluble.

  • Chemical Tests

    • Neutral to litmus; phenols + FeCl3 → coloured complex; Lucas test (conc HCl + ZnCl2): 3^\circ>2^\circ>1^\circ cloudiness.

  • Reactivity via O–H Bond

    • Acidity order: phenol > water > alcohol.

    • Esterification with acids, anhydrides, acyl chlorides (pyridine).

    • Aspirin synthesis: salicylic acid + acetic anhydride.

  • Reactivity via C–O Bond (Alcohols)

    • ROH+HX \rightarrow RX (ZnCl$2$, PCl3/PCl5, SOCl2).

    • Dehydration to alkenes (acid, heat).

    • Oxidation: 1^\circ → aldehyde / acid; 2^\circ → ketone; 3^\circ – no oxidation, dehydrated by Cu/573 K.

  • Reactions of Phenol

    • Halogenation: in H2O → 2,4,6-tribromophenol; in CS$2$ (low T) → o/p-bromophenol.

    • Nitration: dilute HNO_3 gives o/p; conc → picric acid.

    • Sulphonation (temperature-controlled ortho ↔ para).

    • Reimer–Tiemann (CHO at ortho).

    • Kolbe (Salicylic acid).

    • Catalytic hydrogenation → cyclohexanol; Zn dust → benzene.

  • Ethers

    • Dehydration of alcohols (413 K) → symmetrical ether; 443 K → alkene.

    • Williamson synthesis R–X+R'O^-Na^+ \rightarrow R–O–R' (works except hindered 3^\circ halide).

    • Lab test: reacts with cold conc H2SO4 to give oxonium salt.

    • Slow auto-oxidation → peroxides.

    • Cleavage by hot HI: R–O–R' + HI \rightarrow R–I + R'–OH (anisole yields phenol + MeI).

    • Aromatic ether electrophilic substitutions: anisole directs o/p.

  • Uses

    • Methanol – solvent, fuel.

    • Ethanol – beverages, antifreeze.

    • Phenol – Bakelite resin, antiseptic.

    • Diethyl ether – historical anaesthetic, solvent for Grignard.

Aldehydes, Ketones & Carboxylic Acids

  • Key Functional Groups

    • Aldehyde: –CHO, at least one H on carbonyl C.

    • Ketone: >C{=}O with two C groups.

    • Acid: –COOH (carbonyl + hydroxyl).

  • Classifications

    • Aliphatic vs aromatic for each family; ketones further into symmetrical / unsym.

  • Nomenclature Essentials

    • Comprehensive tables provided (formaldehyde = methanal; acetone = propanone; phthalaldehyde = benzene-1,2-dicarbaldehyde; etc.).

  • Preparations (General)

    • Oxidation of alcohols: PCC (mild) or Cu/573 K.

    • Ozonolysis of alkenes, hydration of alkynes (Hg$^{2+}$/H$2$SO$4$).

    • Rosenmund (acid chloride → aldehyde, Pd/BaSO_4).

    • Acyl chloride + dialkylcadmium → ketone.

    • Stephen reduction (nitrile → imine → aldehyde).

    • Grignard on nitrile → ketone.

    • Etard oxidation, benzylic side-chain oxidation / chlorination for benzaldehyde.

    • Friedel–Craft acylation → aromatic ketone.

    • Esters + \text{DIBAL-H} → aldehyde (only).

    • Carboxylic acids from nitriles, acyl chlorides, anhydrides, esters, alkyl-benzene oxidation, KMnO$4$ of alkenes, Grignard + CO$2$.

  • Qualitative Tests

    • Aldehydes: Schiff (magenta), Tollens (Ag mirror), Fehling (red Cu$_2$O).

    • Ketones: sodium-nitroprusside → red colour.

  • Important Nucleophilic Additions

    • HCN → cyanohydrin; NaHSO_3 → bisulfite adduct; alcohols (dry HCl) → hemi-/acetals, ketals; Grignard → alcohols.

    • Addition–elimination with NH_2Y reagents gives imines/oximes, hydrazones, phenylhydrazones, semicarbazones, 2,4-DNPH derivative (bright orange ppt).

    • Haloform: methyl ketone + I2/NaOH → CHI3\downarrow.

    • Aldol (self & cross) requires \alpha-H aldehydes/ketones → \beta-hydroxy carbonyl, dehydration to \alpha,\beta-unsat carbonyl.

    • Cannizzaro: aldehydes without \alpha-H under conc alkali → one reduced (alcohol) + one oxidised (acid).

  • Redox Conversions

    • Strong oxidants convert aldehydes → acids; ketones resistant but severed by hot KMnO$_4$.

    • Clemmensen (Zn–Hg/HCl) & Wolff–Kishner (NH$2$NH$2$/base/heat) reduce C=O → CH$_2$.

  • Electrophilic Substitution on Aromatic Carbonyls

    • –CHO is meta-directing: nitration gives m-nitrobenzaldehyde.

  • Carboxylic Acid Chemistry

    • Litmus red, NaHCO3 effervescence (CO2), esterification with alcohols (fruity odour).

    • Conversion to acyl chloride (SOCl2, PCl3, PCl5); to amide (via ammonium salt or acyl chloride + NH$3$).

    • P$2$O$5$ dehydration of two acids → anhydride.

    • Decarboxylation of sodium salts with NaOH/CaO: CH3COONa \xrightarrow{\Delta} CH4.

    • LiAlH_4 reduction → primary alcohol.

Amines & Diazonium Salts

  • Structural Types

    • Primary 1^\circ \text{R–NH}2, secondary 2^\circ \text{R}2\text{NH}, tertiary 3^\circ \text{R}_3\text{N}.

    • Further: symmetrical vs mixed; aliphatic vs aromatic.

  • IUPAC / Common Naming

    • Detailed table (methylamine = methanamine, aniline = benzenamine, p-toluidine = 4-methylbenzenamine, trimethylamine = N,N-dimethyl-methanamine, etc.).

  • Preparations

    1. Ammonolysis of alkyl halide (excess NH$_3$ for 1^\circ).

    2. Reduction of nitro compounds (Sn/HCl or H_2/Pd).

    3. Mendius: nitrile +4[H] \rightarrow amine (Na/EtOH or LiAlH_4).

    4. Reduction of amides → amines.

    5. Gabriel (phthalimide + alkyl halide, followed by hydrolysis) ⇒ pure 1^\circ.

    6. Hofmann degradation: amide + Br$_2$/KOH ⇒ 1^\circ amine with one C less.

  • Basicity Trends

    • pKb order: R2NH > RNH2 > R3N > NH_3 in gas phase; in water, hydration changes order but 2^\circ often strongest.

    • Aromatic amines less basic due to resonance.

  • Key Reactions & Tests

    • Acid-base: turns red litmus blue.

    • Diazotisation (primary aromatic): ArNH2 + NaNO2/HCl/273\,K \rightarrow ArN_2^+Cl^- (gives orange azo dye with \beta-naphthol).

    • Alkylation (exhaustive) → quaternary ammonium iodide → Hofmann elimination \rightarrow least substituted alkene.

    • Acylation (Schotten–Baumann): RNH_2+R'COCl \rightarrow RNHCOR'.

    • Carbylamine: RNH2+CHCl3+3KOH \rightarrow RNC +3KCl+3H_2O (foul odour, lab test for 1^\circ amine).

    • HNO_2:

      • 1^\circ aliphatic → alcohol, N_2.

      • 2^\circ → nitrosoamine (yellow oil).

      • 3^\circ → no diazonium, but forms nitrite salt.

  • Aryl Diazonium Reactions

    • Sandmeyer: ArN_2^+Cl^- + CuCl \rightarrow ArCl (CuBr, CuCN analogues).

    • Gattermann: same but Cu powder + HX.

    • KI → ArI; HBF_4/heat → ArF (Schiemann).

    • H3PO2 reduces to Ar–H.

    • Water (warm) → phenol.

    • Coupling with phenol/aniline → azo dyes (p-hydroxy/p-amino-azobenzene).

    • Hinsberg test: 1^\circ/2^\circ/3^\circ amines discrimination via benzenesulphonyl chloride.

  • Electrophilic Substitution on Aniline

    • Direct bromination in water → 2,4,6-tribromoaniline.

    • Controlled bromination/nitration possible via acetanilide protection.

    • Sulphonation gives p-sulphonamide.

End of Notes