Module Four – Chemistry of Functional Groups-I: Alkyl Halides (Preparation & Reactions)

Overview of Module Four

Focus: Chemistry of Functional Groups-I
• Halogen derivatives of hydrocarbons (alkyl & aryl halides)
• Alcohols
• Phenols
Current transcript: deals exclusively with halogen compounds, especially haloalkanes (alkyl halides).

Basic Definitions & Terminology

Halogen derivatives (halo-compounds): compounds obtained by replacing one or more $\text{H}$ atoms of hydrocarbons with halogen ( $\text{F} , \text{Cl} , \text{Br} , \text{I}$ ).
• Examples: alkyl halides (from alkanes), aryl halides (from arenes).
Hydroxy derivatives:
• Alcohols (aliphatic)
• Phenols (aromatic)
Alkyl halide notation: $\text{R-X}$ where $\text{R}$ is alkyl, $\text{X}$ is halogen.
Classification by nature of $\text{C–X}$ carbon:
• Primary $(1^\circ)$ – halogen on $1^\circ$ carbon
• Secondary $(2^\circ)$ – halogen on $2^\circ$ carbon
• Tertiary $(3^\circ)$ – halogen on $3^\circ$ carbon
Illustration with molecular formula $\text{C}4\text{H}9\text{Cl}:$
• $\text{CH}3\text{CH}2\text{CH}2\text{CH}2\text{Cl}$ → n-Butyl chloride (primary)
• $\text{CH}3\text{CH}(\text{CH}3)\text{CH}2\text{Cl}$ → Isobutyl chloride (primary) • $\text{CH}3\text{CH}2\text{CH}(\text{Cl})\text{CH}3$ → sec-Butyl chloride (secondary)
• $\text{(CH}3)3\text{CCl}$ → tert-Butyl chloride (tertiary)

Preparation of Alkyl Halides

A. From Alkanes – Radical Halogenation

Process: replace alkane $\text{H}$ atoms with halogen via a free-radical chain mechanism.
Conditions: UV light at ordinary temperature or thermal heating $250\text{–}400\,^\circ\text{C}$ .
Halogen reactivity order: \text{F}2 > \text{Cl}2 > \text{Br}2 > \text{I}2.
• $\text{F}2$ too explosive; $\text{I}2$ too slow & reversible → practical focus on $\text{Cl}2$ & $\text{Br}2$ .

(a) Chlorination Examples

Methane series (stepwise chlorination):
1. $\text{CH}4 + \text{Cl}2 \xrightarrow[\text{UV or } \Delta]{} \text{CH}_3\text{Cl} + \text{HCl}$
2. $\text{CH}3\text{Cl} + \text{Cl}2 \xrightarrow[\text{UV or } \Delta]{} \text{CH}2\text{Cl}2 + \text{HCl}$
3. $\text{CH}2\text{Cl}2 + \text{Cl}2 \xrightarrow[\text{UV or } \Delta]{} \text{CHCl}3 + \text{HCl}$
4. $\text{CHCl}3 + \text{Cl}2 \xrightarrow[\text{UV or } \Delta]{} \text{CCl}_4 + \text{HCl}$
 → Mixture of all four products obtained.
Chlorination of higher alkanes gives positional isomers; product distribution governed by radical stability & step energetics.
• Propane: $45\%$ 1-chloropropane vs $55\%$ 2-chloropropane.
• Butane: $72\%$ 1-chlorobutane vs $28\%$ 2-chlorobutane.

(b) Bromination Example

Similar mechanism, less reactive:
• $\text{CH}4 + \text{Br}2 \xrightarrow[\text{UV or } \Delta]{} \text{CH}_3\text{Br} + \text{HBr}$ .

B. From Alkenes – Electrophilic Addition of HX

General addition: $\text{RCH = CH}2 + \text{HX} \rightarrow \text{RCH}2\text{CH}_2\text{X}$ .
Reactivity order of acids toward a given alkene: \text{HCl} < \text{HBr} < \text{HI} (due to bond strength & polarizability).
Markovnikov’s Rule (1869): “In ionic addition of an unsymmetrical reagent to an unsymmetrical alkene, the positive part (H⁺) attaches to the carbon bearing more hydrogens.”
• Example: $\text{CH}3\text{CH} = \text{CH}2 + \text{HCl} \rightarrow \text{CH}3\text{CHCl}\text{CH}3$ (2-chloropropane).
Anti-Markovnikov (Peroxide/Kharasch Effect, 1933): In presence of peroxides, $\text{HBr}$ adds such that Br attaches to carbon with more hydrogens.
• Example: $\text{CH}3\text{CH} = \text{CH}2 \xrightarrow[\text{ROOR}]{\text{HBr}} \text{CH}3\text{CH}2\text{CH}_2\text{Br}$ (1-bromopropane).

Reactivity Concept: Nucleophilic Substitution (S N)

Driving force: Polar $\text{C–X}$ bond (halogen more electronegative → $\delta^+$ on carbon).
Stronger nucleophile (Nu⁻) replaces weaker leaving group (X⁻).
General schematic:
$\text{R–X} + \text{Nu}^- \rightarrow \text{R–Nu} + \text{X}^-$ .

Catalogue of Alkyl Halide Substitution Reactions

#	Nucleophile / Reagent	Product	Typical Conditions / Notes
1	$\text{OH}^-$ (aq. $\text{KOH}$ / $\text{NaOH}$ ) or moist $\text{Ag}_2\text{O}$	Alcohol $\text{R–OH}$	Hydrolysis, boiling.
2	$\text{OR}'^-$ (alkoxide) – Williamson synthesis OR dry $\text{Ag}_2\text{O}$	Ether $\text{R–O–R}'$	Heat; versatile route to symmetrical/unsymmetrical ethers.
3	$\text{CN}^-$ (alc. $\text{KCN}$ )	Nitrile (alkyl cyanide) $\text{R–C≡N}$	Increases carbon chain by one.
4	$\text{AgCN}$ (alc.)	Isocyanide (carbylamine) $\text{R–N≡C}$	Small amount of nitrile forms concurrently.
5	$\text{NO}<em>2^-$ from alc. $\text{KNO}</em>2$	Alkyl nitrite $\text{R–O–NO}$	Nitrito-O product.
6	$\text{AgNO}_2$ (alc.)	Nitroalkane $\text{R–NO}_2$	Mixture with some nitrite; $\text{N}$ -bound nitro dominates.
7	$\text{R}'\text{COO}^-$ (silver salt of fatty acid)	Ester $\text{R}'\text{COO–R}$	Alcoholic medium; e.g., silver acetate → ethyl acetate.
8	Sodium alkynide \text{^-C≡C–R}'	Higher alkyne $\text{R–C≡C–R}'$	Chain elongation at terminal alkyne.
9	Excess $\text{NH}_3$ (alc., pressure)	Amines: 1°, 2°, 3°, and quaternary ammonium salt	Primary predominates initially; over-alkylation occurs with further halide.
10	$\text{KI}$ (methanolic)	Iodide $\text{R–I}$	Finkelstein exchange; only for $\text{R–Cl}$ or $\text{R–Br}$ .

Representative Equations (LaTeX Form)

Hydrolysis: $\text{CH}3\text{I} + \text{KOH}{(aq)} \xrightarrow[\Delta]{} \text{CH}_3\text{OH} + \text{KI}$ .
Williamson: $\text{CH}3\text{Br} + \text{NaOCH}3 \xrightarrow[\Delta]{} \text{CH}3\text{OCH}3 + \text{NaBr}$ .
Nitrile synthesis: $\text{CH}3\text{CH}2\text{Br} + \text{KCN} \xrightarrow[\text{alc.}]{} \text{CH}3\text{CH}2\text{C≡N} + \text{KBr}$ .
Carbylamine: $\text{CH}3\text{I} + \text{AgCN} \rightarrow \text{CH}3\text{NC} + \text{AgI}$ .
Alkyl nitrite: $\text{C}2\text{H}5\text{Br} + \text{KNO}2 \xrightarrow[\text{alc.}]{} \text{C}2\text{H}_5\text{ONO} + \text{KBr}$ .
Nitroalkane: $\text{CH}3\text{I} + \text{AgNO}2 \rightarrow \text{CH}3\text{NO}2 + \text{AgI}$ .
Esterification: $\text{CH}3\text{COOAg} + \text{C}2\text{H}5\text{Br} \rightarrow \text{CH}3\text{COOCH}2\text{CH}3 + \text{AgBr}$ .
Alkyne extension: \text{CH}3\text{I} + \text{Na}^+\text{^-C≡CH} \rightarrow \text{CH}3\text{C≡CH} + \text{NaI}.
Amination:
$\text{R–Br} + 2\text{NH}3 \xrightarrow[\text{alc.},\, P]{\Delta} \text{R–NH}2 + \text{NH}_4\text{Br}$ (simplified primary step).
Finkelstein: $\text{C}2\text{H}5\text{Cl} + \text{KI}{(MeOH)} \rightarrow \text{C}2\text{H}_5\text{I} + \text{KCl}$ .

Conceptual & Practical Significance

Radical halogenation introduces functional handles for further elaboration (e.g., synthesis of solvents, anesthetics, and polymers).
Stepwise chlorination of methane provides industrially vital chemicals: methylene chloride (paint remover), chloroform (past anesthetic), carbon tetrachloride (cleaning solvent).
Alkyl halide additions to alkenes underpin hydrohalogenation in petrochemical feedstock processing.
Anti-Markovnikov peroxide effect is foundational for free-radical polymer chemistry and synthetic planning.
Nucleophilic substitution versatility: creates alcohols, ethers, nitriles, amines → critical for pharmaceuticals, agrochemicals, fragrances.
Chain-extension via $\text{CN}^-$ or alkynide boosts molecular complexity (homologation strategies).
Williamson ether synthesis is strategy of choice for lab-scale preparation of symmetrical/unsymmetrical ethers.
Over-alkylation caveat in amine synthesis illustrates need for controlled stoichiometry or protective groups.
Finkelstein reaction exemplifies halogen exchange & relative leaving-group abilities: $\text{I}^-$ > $\text{Br}^-$ > $\text{Cl}^-$ .

Key Numerics & Trends Recap

Halogen reactivity in radical halogenation: \text{F}2 (\text{explosive}) > \text{Cl}2 > \text{Br}2 > \text{I}2 (reversible).
HX addition reactivity toward a fixed alkene: \text{HCl} < \text{HBr} < \text{HI}.
Positional selectivity examples:
• Propane chlorination → $45\%$ 1-Cl vs $55\%$ 2-Cl.
• Butane chlorination → $72\%$ 1-Cl vs $28\%$ 2-Cl.

Practical & Safety Notes (Implicit Ethical/Operational Aspects)

$\text{F}_2$ reactions avoided in lab due to explosiveness & toxicity.
Chloroform formation in radical halogenation historically led to anesthetic use but later restricted (liver toxicity, phosgene risk).
Carbon tetrachloride is an ozone-depleting substance; industrial use regulated (Montreal Protocol).
Radical halogenations require UV lamps or high-temp furnaces; proper shielding & ventilation essential.
Alkyl isocyanides possess extremely pungent odors → handle under fume hood.
Nitrile & nitro compounds may be toxic; avoid inhalation/skin contact.