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 $(\text{CH}<em>2{=}CH</em>2\text{–Cl})$

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

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

  • Phosphorus halides: $3\text{R–OH}+PCl<em>3 \rightarrow 3\text{R–Cl}+H</em>3PO<em>3$ (similarly $PCl</em>5$).

  • Thionyl chloride (best): $\text{R–OH}+SOCl<em>2 \rightarrow \text{R–Cl}+SO</em>2\uparrow +HCl\uparrow$

  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

  • $NaOH<em>{(aq)}$ → alcohols; $NaOR$ → ethers; $RCOOAg$ → esters; alc $NH</em>3$ → amines; alc $KCN$ → nitriles; alc $AgCN$ → isocyanides; $KNO<em>2$ vs $AgNO</em>2$ 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, $\mathit{CHCl<em>3\xrightarrow{base}} :CCl</em>2$ 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 $LiAlH<em>4$ or $H</em>2/Pd$.

  • 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 + $FeCl<em>3$ → coloured complex; Lucas test (conc HCl + $ZnCl</em>2$): 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$2$, $PCl</em>3/PCl<em>5$, $SOCl</em>2$).

  • 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 $H<em>2O$ → $2,4,6$-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 $H<em>2SO</em>4$ 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 + $I<em>2/NaOH$ → $CHI</em>3\downarrow$.

  • 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, $NaHCO<em>3$ effervescence $(CO</em>2)$, esterification with alcohols (fruity odour).

  • Conversion to acyl chloride ($SOCl<em>2, PCl</em>3, PCl<em>5$); to amide (via ammonium salt or acyl chloride + NH$3$).

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

  • Decarboxylation of sodium salts with $NaOH/CaO$: $CH<em>3COONa \xrightarrow{\Delta} CH</em>4$.

  • $LiAlH_4$ reduction → primary alcohol.

Amines & Diazonium Salts

• Structural Types

  • Primary $1^\circ$ $\text{R–NH}<em>2$, secondary $2^\circ$ $\text{R}</em>2\text{NH}$, 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

  • $pK<em>b$ 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): $ArNH<em>2 + NaNO</em>2/HCl/273\,K \rightarrow ArN_2^+Cl^-$ (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: $RNH<em>2+CHCl</em>3+3KOH \rightarrow RNC +3KCl+3H_2O$ (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).

  • $H<em>3PO</em>2$ 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