Haloalkanes and Haloarenes

When one or more hydrogen atoms of a hydrocarbon are replaced by halogen atoms (F, Cl, Br, I), the products are called halogen derivatives. If the halogen is attached to an sp³ hybridised carbon, the compound is a haloalkane (alkyl halide, general formula C_nH_2n+1X). If the halogen is attached directly to an sp² hybridised carbon of a benzene ring, the compound is a haloarene (aryl halide).

Halogen compounds are classified as mono-, di-, tri- or, generally, poly-halogen compounds based on the number of halogens present. Haloalkanes are further classified by the carbon bearing the halogen: primary (1°) — halogen on a carbon joined to only one other carbon, e.g. CH₃CH₂Cl; secondary (2°) — joined to two other carbons, e.g. (CH₃)₂CHCl; tertiary (3°) — joined to three other carbons, e.g. (CH₃)₃CCl.

Position relative to a double bond or ring gives further names: an allylic halide has X on an sp³ carbon next to a C=C, e.g. CH₂=CH–CH₂Cl (allyl chloride); a benzylic halide has X on an sp³ carbon attached directly to a ring, e.g. C₆H₅–CH₂Cl (benzyl chloride); a vinylic halide has X on a doubly-bonded sp² carbon, e.g. CH₂=CHCl (vinyl chloride); an aryl halide has X directly on the aromatic ring, e.g. C₆H₅Cl (chlorobenzene).

IUPAC nomenclature treats halogen as a substituent prefix (fluoro-, chloro-, bromo-, iodo-) on the parent hydrocarbon chain. Numbering of the chain first gives the lowest locant to the principal suffix feature (such as a C=C double bond, "-ene"), and only when there is still a choice does numbering fall back to giving the lowest locants to the substituent prefixes, with the group cited first alphabetically getting the lower number in a tie.

Worked example: Classify and name CH₂=CH–CH₂–Cl. The Cl sits on an sp³ carbon that is directly bonded to a carbon of the C=C bond, so it is an allylic halide. For IUPAC numbering, the carbon–carbon double bond (the principal suffix "-ene") is given priority over the halo- substituent prefix when the lowest locant is assigned, so the three-carbon chain is numbered starting from the =CH₂ end: the double bond falls between C1 and C2, and the Cl-bearing carbon is C3. The IUPAC name is therefore 3-chloroprop-1-ene (common name: allyl chloride).

Carbon is less electronegative than every halogen, so the C–X bond is polarised with a partial positive charge on carbon and partial negative charge on the halogen. As the halogen atom gets larger down the group (F → I), the C–X bond becomes longer (poorer orbital overlap) and its bond enthalpy decreases: C–F is the shortest and strongest, C–I the longest and weakest of the series.

From alcohols — the –OH group is replaced by halogen. With HX (X = Cl, Br, I) in the presence of a catalyst such as anhydrous ZnCl₂ (this mixture with conc. HCl is the Lucas reagent), 3° alcohols react almost instantly at room temperature, 2° alcohols react within a few minutes, and 1° alcohols show no visible reaction at room temperature (they need heating) — a difference used as a qualitative test to distinguish 1°, 2° and 3° alcohols. Cleaner routes avoid this variability: R–OH + SOCl₂ → R–Cl + SO₂↑ + HCl↑ (thionyl chloride method) is preferred because both by-products are gases, leaving a pure alkyl chloride; PCl₅ and PCl₃ (or red phosphorus with Br₂/I₂ generated in situ) are used similarly for chlorides, bromides and iodides.

From hydrocarbons — alkanes undergo free-radical halogenation with X₂ under heat or UV light, but this gives a mixture of products (poor for synthesis unless the molecule has only one type of hydrogen); alkenes add HX across the double bond following Markovnikov's rule (H adds to the carbon already bearing more hydrogens, X goes to the more substituted carbon, via the more stable carbocation), except that HBr specifically can add with the opposite (anti-Markovnikov) regiochemistry in the presence of peroxides (the peroxide/Kharasch effect), because the mechanism switches to a free-radical chain.

Halide exchange — the Finkelstein reaction converts R–Cl or R–Br to R–I by heating with NaI in dry acetone; NaCl/NaBr precipitates (insoluble in acetone) and drives the reaction forward. The Swarts reaction converts R–Cl/R–Br to R–F using AgF, Hg₂F₂, CoF₂ or SbF₃.

Worked example: Convert ethanol to bromoethane by two routes, and say which avoids carbocation rearrangement. Route 1: CH₃CH₂OH + HBr (conc., with conc. H₂SO₄ or NaBr/H₂SO₄, heat) → CH₃CH₂Br + H₂O. Route 2: 3CH₃CH₂OH + PBr₃ (from red P + Br₂) → 3CH₃CH₂Br + H₃PO₃. Route 2 (via PX₃) does not pass through a free carbocation, so it is the preferred method whenever the substrate is prone to rearrangement (e.g. secondary/allylic alcohols); the HX/acid route can rearrange such substrates.

Physical properties: for the same alkyl group, boiling point rises with the size (polarisability) of the halogen: R–I > R–Br > R–Cl > R–F. Among isomers, boiling point falls with branching (n- > iso- > tert-, since a more compact, spherical shape has less surface area for van der Waals contact). Density increases with the mass and number of halogens present — di- and tri-halomethanes are denser than water, and alkyl iodides are denser still. Haloalkanes and haloarenes are only sparingly soluble in water: although the halogen can form a weak hydrogen bond with water, the energy released is not enough to overcome the stronger hydrogen bonds that must be broken within the water itself, so these compounds dissolve much more readily in organic solvents.

Nucleophilic substitution is the characteristic reaction of haloalkanes: a nucleophile (Nu⁻ or Nu:) replaces the halide leaving group, Nu⁻ + R–X → R–Nu + X⁻. Two limiting mechanisms operate.

In the S_N2 (substitution, nucleophilic, bimolecular) pathway, the incoming nucleophile attacks the carbon from the side opposite the leaving group in a single concerted step, passing through a five-coordinate transition state; the leaving group departs as the new bond forms. This backside attack flips the carbon's configuration like an umbrella turning inside out — Walden inversion — so S_N2 is stereospecific. Because the transition state is crowded, reactivity falls sharply as substitution increases around the carbon: CH₃X > 1° > 2° > 3° (3° halides essentially do not react by S_N2). The rate law is second order overall: Rate = k[R–X][Nu⁻].

In the S_N1 (unimolecular) pathway, the C–X bond breaks first, in the slow, rate-determining step, to give a planar carbocation; the nucleophile then attacks this intermediate rapidly from either face. Because the rate depends only on how readily R–X ionises, Rate = k[R–X], independent of nucleophile concentration. Carbocation stability governs reactivity, so the order reverses: 3° > 2° > 1° (3° halides favour S_N1). Since the flat carbocation can be attacked from both faces, a chiral substrate gives a largely racemised product (a mixture of both configurations, not a single, clean inversion).

Worked example: Solvolysis of tert-butyl bromide, (CH₃)₃CBr, in aqueous acetone is first order. At [(CH₃)₃CBr] = 0.050 mol L⁻¹ the initial rate is 2.5 × 10⁻⁵ mol L⁻¹ s⁻¹. Find the rate constant, and the new rate if [(CH₃)₃CBr] is doubled to 0.100 mol L⁻¹ while [OH⁻] is independently doubled. Since this is S_N1, Rate = k[RX], so k = (2.5 × 10⁻⁵)/(0.050) = 5.0 × 10⁻⁴ s⁻¹. At 0.100 mol L⁻¹: new rate = (5.0 × 10⁻⁴)(0.100) = 5.0 × 10⁻⁵ mol L⁻¹ s⁻¹ — the rate exactly doubles when [RX] doubles, and changing [OH⁻] has no effect at all, since [OH⁻] does not appear in the S_N1 rate law.

When a haloalkane is heated with alcoholic (not aqueous) KOH, instead of substitution it can undergo dehydrohalogenation: a proton is removed from a carbon adjacent to the one bearing the halogen, and the halide ion leaves, forming a carbon–carbon double bond (an alkene). When more than one type of β-hydrogen is available, Saytzeff's rule predicts that the major product is the more highly substituted (more stable) alkene.

Substitution and elimination are always in competition: aqueous KOH (a good nucleophile, weaker base) favours substitution, while alcoholic KOH (a strong, bulky base) favours elimination; 3° halides, which cannot easily undergo SN2, tend to eliminate especially readily with strong bases.

Reactions with metals: in the Wurtz reaction, two molecules of an alkyl halide react with sodium metal in dry ether to couple into a longer, symmetrical alkane: 2R–X + 2Na → R–R + 2NaX. This method only cleanly gives a single product when both halide molecules are identical (an unsymmetrical mixture of two different halides gives a mixture of three coupling products), so it is mainly used to prepare symmetrical alkanes with an even number of carbon atoms.

Alkyl (or aryl) halides react with magnesium turnings in dry ether to form Grignard reagents, R–Mg–X, powerful carbon nucleophiles used throughout organic synthesis. Grignard reagents must be kept completely free of moisture, since even traces of water destroy them: R–MgX + H₂O → R–H + Mg(OH)X.

Worked example: A primary alkyl halide of formula C₄H₉Br (A) is heated with alcoholic KOH to give alkene (B); (B) is treated with HBr to give (C), an isomer of (A); and (A) treated with sodium metal gives octane (D), C₈H₁₈, different from the n-octane obtained by treating n-butyl bromide with sodium. Identify (A). Since the Wurtz product from n-butyl bromide would be n-octane, and (D) is a different octane isomer, (A) must be isobutyl bromide, (CH₃)₂CH–CH₂–Br (a primary halide). Dehydrohalogenation removes a β-H from the tertiary carbon to give (B) = (CH₃)₂C=CH₂ (2-methylpropene). Markovnikov addition of HBr to (B) puts Br on the more substituted carbon, giving (C) = (CH₃)₂CBr–CH₃ (tert-butyl bromide), which is indeed a C₄H₉Br isomer of (A). The Wurtz coupling of two molecules of (A) gives (D) = (CH₃)₂CH–CH₂–CH₂–CH(CH₃)₂, i.e. 2,5-dimethylhexane, which is indeed different from n-octane.

Preparation: chlorobenzene and bromobenzene are made by direct electrophilic halogenation of benzene, C₆H₆ + X₂ in the presence of a Lewis-acid catalyst such as FeCl₃ or FeBr₃, giving mainly the ortho and para products. Direct fluorination is too violent to control, and direct iodination is reversible (the HI formed reduces the product back to benzene), so iodoarenes are instead made via a diazonium-salt route.

Aryl diazonium salts, formed from primary aromatic amines with NaNO₂/HCl at 0–5 °C, are versatile intermediates for making every haloarene under mild conditions: the Sandmeyer reaction uses Cu₂Cl₂/Cu₂Br₂ (cuprous halides) to give ArCl or ArBr; the closely related Gattermann reaction uses copper powder with the corresponding halogen acid; the Balz–Schiemann reaction heats the diazonium tetrafluoroborate salt to give ArF; and treating the diazonium salt directly with KI gives ArI, with no catalyst needed.

Low reactivity towards nucleophilic substitution: unlike haloalkanes, haloarenes resist nucleophilic substitution under ordinary conditions, for several reinforcing reasons. First, a lone pair on the halogen conjugates (delocalises) into the aromatic π-system by resonance, giving the C–X bond partial double-bond character; this makes the bond shorter and stronger than a normal single C–X bond, so it resists being broken. Second, the ring carbon is sp² hybridised, which holds the bonding electron pair of C–X more tightly than an sp³ carbon would (sp² carbon has greater effective electronegativity), reinforcing the bond strength. Third, an S_N1 pathway is blocked because the resulting phenyl cation would not be resonance-stabilised (its empty orbital lies in the plane of the ring, perpendicular to the π-system) and is therefore very unstable. Fourth, the electron-rich aromatic ring tends to repel an approaching electron-rich nucleophile. Only under forcing conditions — high temperature and pressure, or with strong electron-withdrawing groups (like –NO₂) positioned ortho/para to the halogen — does nucleophilic substitution proceed, e.g. the industrial Dow process, C₆H₅Cl + NaOH at 623 K/300 atm → C₆H₅OH + NaCl.

Electrophilic substitution still occurs readily on the ring itself (halogenation, nitration, sulfonation, Friedel–Crafts). Here halogen shows its dual character: it is an ortho, para-director because the same lone-pair resonance donation that strengthens the C–X bond also selectively stabilises the arenium-ion (Wheland) intermediate formed when the electrophile attacks the ortho or para position (not meta). Yet, taken over the whole ring, the strong electron-withdrawing inductive (−I) effect of the electronegative halogen outweighs this resonance donation, so the ring as a whole is deactivated — haloarenes undergo electrophilic substitution more slowly than benzene itself, even though the new substituent still goes mainly to the ortho/para positions.

Worked example: Chlorobenzene undergoes nitration (HNO₃/H₂SO₄) more slowly than benzene, giving mainly a mixture of ortho- and para-nitrochlorobenzene with only a trace of the meta isomer. This is explained exactly as above: the −I effect of Cl slows the overall reaction (deactivation), while resonance donation from the Cl lone pair stabilises the intermediate carbocation specifically for ortho/para attack (o,p-direction), and the bulkier para product usually predominates over the sterically hindered ortho product.

Compounds bearing more than one halogen atom find everyday and industrial use, though a few require careful handling.

Dichloromethane (CH₂Cl₂) is a widely used industrial solvent and paint remover. Trichloromethane (chloroform, CHCl₃) is an excellent solvent and was historically used as a surgical anaesthetic; however, it is slowly oxidised by air and light into the extremely poisonous gas phosgene (COCl₂). For this reason chloroform is stored in dark-coloured bottles that are completely filled (to exclude air) and to which about 1% ethanol is added — the ethanol converts any phosgene formed into harmless diethyl carbonate. Triiodomethane (iodoform, CHI₃) was once used as an antiseptic on wounds, its action really coming from the free iodine it slowly liberates rather than from the compound itself.

Tetrachloromethane (carbon tetrachloride, CCl₄) is a non-flammable solvent that was formerly used in fire extinguishers (known by the trade name pyrene) and dry cleaning; its use has now been curtailed because of its toxicity and its role, like other chlorinated compounds, in ozone depletion.

Freons (chlorofluorocarbons, CFCs, e.g. Freon-12, CCl₂F₂) are inert, non-toxic, non-flammable, easily liquefiable gases historically used as refrigerants and aerosol propellants. Their very inertness lets them survive long enough to drift up into the stratosphere, where intense UV radiation photolyses the C–Cl bond to release chlorine free radicals: CF₂Cl₂ + UV → •CF₂Cl + Cl•. Each Cl• then destroys ozone catalytically: Cl• + O₃ → ClO• + O₂, followed by ClO• + O → Cl• + O₂, regenerating the chlorine radical so that a single Cl atom can destroy many thousands of ozone molecules in a chain reaction — this is the chief cause of stratospheric ozone-layer depletion.

DDT (para,para′-dichlorodiphenyltrichloroethane, C₁₄H₉Cl₅) was, for decades, the most widely used synthetic insecticide because it is cheap and highly effective. Unfortunately it is chemically very stable and non-biodegradable: it persists in soil and water and accumulates in the fatty tissue of animals, becoming increasingly concentrated (biomagnified) as it passes up the food chain. Because of this environmental persistence and toxicity to wildlife, DDT is now banned or heavily restricted in many countries.