Comprehensive Study Guide on Haloalkanes and Haloarenes

Introduction and Biological Importance of Organohalogen Compounds

• Definition: The replacement of hydrogen atoms in aliphatic hydrocarbons results in alkyl halides (haloalkanes), while replacement in aromatic hydrocarbons results in aryl halides (haloarenes).

• Hybridisation: In haloalkanes, the halogen is attached to an $sp^3$ hybridised carbon. In haloarenes, the halogen is attached to an $sp^2$ hybridised carbon.

• Clinical and Industrial Applications:

  • Solvents: Used for relatively non-polar compounds and as starting materials for organic synthesis.

  • Chloramphenicol: A chlorine-containing antibiotic produced by microorganisms, used to treat typhoid fever.

  • Thyroxine: An iodine-containing hormone produced by the human body; its deficiency causes goiter.

  • Chloroquine: A synthetic halogen compound used for malaria treatment.

  • Halothane: Used as an anaesthetic during surgical procedures.

  • Fully Fluorinated Compounds: Studied as potential blood substitutes in surgery.

• Environmental Impact: Many halogenated compounds persist in the environment because they are resistant to breakdown by soil bacteria.

Classification of Halocompounds

• On the Basis of Number of Halogen Atoms:

  • Monohalocompounds: Contain one halogen atom.

  • Dihalocompounds: Contain two halogen atoms.

  • Polyhalocompounds: Contain three or more halogen atoms (tri-, tetra-, etc.).

• Compounds Containing $sp^3$ C—X Bond (X = F, Cl, Br, I):

  • Alkyl Halides or Haloalkanes (R—X): The halogen is bonded to an alkyl group. They form a homologous series with the formula $C_nH_{2n+1}X$. They are sub-classified as:

    • Primary (1°): Halogen attached to a primary carbon.

    • Secondary (2°): Halogen attached to a secondary carbon.

    • Tertiary (3°): Halogen attached to a tertiary carbon.

  • Allylic Halides: Halogen is bonded to an $sp^3$-hybridised carbon atom adjacent to a carbon-carbon double bond ($C=C$), known as the allylic carbon.

  • Benzylic Halides: Halogen is bonded to an $sp^3$-hybridised carbon atom attached to an aromatic ring.

• Compounds Containing $sp^2$ C—X Bond:

  • Vinylic Halides: Halogen is bonded to an $sp^2$-hybridised carbon of a carbon-carbon double bond ($C=C$).

  • Aryl Halides: Halogen is directly bonded to the $sp^2$-hybridised carbon of an aromatic ring.

Nomenclature and Isomerism

• Naming Conventions:

  • Common Names: Derived by naming the alkyl group followed by the halide (e.g., n-propyl fluoride).

  • IUPAC Names: Named as halo-substituted hydrocarbons (e.g., 1-fluoropropane).

  • Dihaloarenes: Common names use prefixes o-, m-, p-; IUPAC names use numerals 1,2; 1,3; or 1,4.

• Dihaloalkanes:

  • Geminal Halides (gem-dihalides): Both halogen atoms are on the same carbon atom of the chain. These are named as alkylidene halides.

  • Vicinal Halides (vic-dihalides): Halogen atoms are on adjacent carbon atoms. These are named as alkylene dihalides.

• Example Structures and Names:

  • $CH_3CH_2CH(Cl)CH_3$: sec-Butyl chloride (Common); 2-Chlorobutane (IUPAC).

  • $(CH_3)_3CCH_2Br$: neo-Pentyl bromide (Common); 1-Bromo-2,2-dimethylpropane (IUPAC).

  • $CH_2Cl_2$: Methylene chloride (Common); Dichloromethane (IUPAC).

  • $CHCl_3$: Chloroform (Common); Trichloromethane (IUPAC).

  • $CCl_4$: Carbon tetrachloride (Common); Tetrachloromethane (IUPAC).

• Structural Isomerism: For the molecular formula $C_5H_{11}Br$, eight isomers exist, ranging from primary (e.g., 1-bromopentane) to secondary (e.g., 2-bromopentane) and tertiary (e.g., 2-bromo-2-methylbutane).

Nature of the C—X Bond

• Polarity: Halogen atoms are more electronegative than carbon, leading to a polarised bond where carbon bears a partial positive charge ($\\delta+$) and the halogen bears a partial negative charge ($\\delta-$).

• Periodic Trends: As we move down the group from Fluorine to Iodine, the atomic size increases, bond length increases, and bond enthalpy decreases.

• Typical Bond Parameters ($CH_3-X$):

  • $CH_3-F$: Bond length $139\,pm$, Enthalpy $452\,kJ\,mol^{-1}$, Dipole moment $1.847\,D$.

  • $CH_3-Cl$: Bond length $178\,pm$, Enthalpy $351\,kJ\,mol^{-1}$, Dipole moment $1.860\,D$.

  • $CH_3-Br$: Bond length $193\,pm$, Enthalpy $293\,kJ\,mol^{-1}$, Dipole moment $1.830\,D$.

  • $CH_3-I$: Bond length $214\,pm$, Enthalpy $234\,kJ\,mol^{-1}$, Dipole moment $1.636\,D$.

Methods of Preparation of Haloalkanes

• From Alcohols:

  • Reaction with halogen acids ($HX$): Secondary and primary alcohols require $ZnCl_2$ as a catalyst. Tertiary alcohols react by shaking with conc. $HCl$ at room temperature.

  • Reaction with Thionyl Chloride ($SOCl_2$): Preferred method because the by-products ($SO_2$ and $HCl$) are escapable gases, leaving pure alkyl halide.

  • Reaction with phosphorus halides ($PX_3$ or $PCl_5$). $PBr_3$ and $PI_3$ are generated in situ using red phosphorus and $Br_2$ or $I_2$.

  • Reactivity order of alcohols: 3^o > 2^o > 1^o.

• From Hydrocarbons:

  • Alkanes: Free radical halogenation gives a complex mixture of mono- and polyhaloalkanes, making isolation difficult.

  • Alkenes:

    • Addition of $HX$: Follows Markovnikov’s rule (e.g., propene reacting with $HI$ gives 2-iodopropane as major product).

    • Addition of halogens: Addition of $Br_2$ in $CCl_4$ is a test for unsaturation; the reddish-brown color of bromine disappears to form colorless vic-dibromides.

• Halogen Exchange:

  • Finkelstein Reaction: Preparation of alkyl iodides by reacting alkyl chlorides/bromides with $NaI$ in dry acetone. Precipitation of $NaCl$/$NaBr$ drives the reaction forward.

  • Swarts Reaction: Preparation of alkyl fluorides by heating alkyl chlorides/bromides with metallic fluorides like $AgF$, $Hg_2F_2$, $CoF_2$, or $SbF_3$.

Preparation of Haloarenes

• Electrophilic Substitution: Aryl chlorides/bromides are prepared by reacting arenes with chlorine/bromine in the presence of Lewis acids ($Fe$ or $FeCl_3$) in the dark. Ortho and para isomers are formed and separated by melting point differences. Reactions with $I_2$ are reversible and require oxidising agents ($HNO_3$, $HIO_4$).

• Sandmeyer’s Reaction: A primary aromatic amine is treated with sodium nitrite in cold aqueous mineral acid to form a diazonium salt. Mixing with cuprous chloride or bromide replaces the diazonium group with $-Cl$ or $-Br$. For iodine, simple shaking with $KI$ is sufficient.

Physical Properties

• State and Appearance: Pure alkyl halides are colourless. Bromides and iodides develop color in light. Many have a sweet smell.

• Boiling Points:

  • Higher than parent hydrocarbons due to stronger dipole-dipole and van der Waals forces.

  • For the same alkyl group, order is: RI > RBr > RCl > RF.

  • Isomeric haloalkanes: B.P. decreases with increased branching (smaller surface area).

  • Dihalobenzenes: Isomers have similar B.P., but para-isomers have much higher M.P. due to symmetry and better fit in the crystal lattice.

• Solubility: Slightly soluble in water (energy released by new attractions is less than energy needed to break water hydrogen bonds) but highly soluble in organic solvents.

• Density: Increases with civilian mass of halogen, number of halogens, and carbon chain length. $Bromo$, $iodo$, and $polychloro$ derivatives are heavier than water.

Nucleophilic Substitution Reactions ($S_N1$ and $S_N2$)

• General Mechanism: A nucleophile ($Nu^-$) attacks the electron-deficient carbon, and the halogen departs as a leaving group (halide ion).

• Ambident Nucleophiles: Groups with two nucleophilic centers (e.g., Cyanide and Nitrite).

  • KCN gives Alkyl Cyanide ($R-CN$) because it is ionic and bond through carbon.

  • AgCN gives Isonitrile ($R-NC$) because it is covalent and bond through nitrogen.

  • Nitrite ($NO_2^-$): Linkage through oxygen yields alkyl nitrite; linkage through nitrogen yields nitroalkane.

• $S_N2$ Mechanism (Substitution Nucleophilic Bimolecular):

  • Kinetics: Second order (rate depends on both substrate and nucleophile).

  • Process: One-step, simultaneous bond breaking and bond making. No intermediate.

  • Stereochemistry: Complete inversion of configuration ("umbrella turning inside out").

  • Reactivity: Primary > Secondary > Tertiary (due to steric hindrance).

• $S_N1$ Mechanism (Substitution Nucleophilic Unimolecular):

  • Kinetics: First order (rate depends only on the concentration of alkyl halide).

  • Process: Two-step. Step 1 (Slow) forms a carbocation. Step 2 (Fast) nucleophilic attack.

  • Solvent: Favored by polar protic solvents (water, alcohol).

  • Stereochemistry: Racemisation occurs because the flat carbocation intermediate can be attacked from either side.

  • Reactivity: Tertiary > Secondary > Primary (aligned with carbocation stability; allylic/benzylic also highly reactive due to resonance stabilization).

Stereochemical Principles and Notations

• Optical Activity: Certain compounds rotate the plane of plane-polarised light. Measured by a polarimeter.

  • Dextrorotatory ($d$ or +): Clockwise rotation.

  • Laevorotatory ($l$ or -): Anti-clockwise rotation.

• Chirality: Objects/molecules that are non-superimposable on their mirror images are chiral. A carbon bonded to four different groups is an asymmetric carbon or stereocentre.

• Enantiomers: Non-superimposable mirror image stereoisomers. They have identical physical properties except for the direction of optical rotation.

• Racemic Mixture: An equimolar mixture of enantiomers, showing zero optical rotation. Represented by $(\\pm)$ or $dl$.

• Definitions of Outcomes:

  • Retention: Preservation of spatial arrangement (no bond to stereocentre is broken).

  • Inversion: Arrangement is flipped.

  • Racemisation: Conversion into a racemic mixture.

Elimination and Metal Reactions

• $\\beta$-Elimination (Dehydrohalogenation): Haloalkane with a $\\beta$-hydrogen heated with alcoholic $KOH$ forms an alkene.

  • Zaitsev Rule: In dehydrohalogenation, the preferred product is the alkene with the greater number of alkyl groups attached to the doubly bonded carbons (more substituted alkene).

• Reaction with Metals:

  • Grignard Reagents ($RMgX$): Discovered by Victor Grignard (1912 Nobel Prize). Formed by reacting $RX$ with $Mg$ in dry ether. Carbon-Magnesium bond is covalent-polar; Magnesium-Halogen bond is ionic. They react with any proton source (water, alcohol) to give hydrocarbons.

  • Wurtz Reaction: Two molecules of alkyl halide react with sodium in dry ether to form a hydrocarbon with double the carbon atoms.

Reactions of Haloarenes

• Low Reactivity to Nucleophilic Substitution: Due to resonance (partial double bond character of C—X), difference in hybridisation ($sp^2$ carbon is more electronegative), and instability of phenyl cation.

  • Replacement by Hydroxyl: Chlorobenzene to phenol requires $623\,K$ and $300\,atm$.

  • Effect of Nitro Groups: Electron-withdrawing groups ($-NO_2$) at ortho and para positions facilitate nucleophilic attack. No effect is observed at the meta position.

• Electrophilic Substitution: Halogens are deactivating but ortho/para directing due to resonance.

  • Halogenation: Benzene reacting with $Cl_2$/anhy. $FeCl_3$ yields 1,4-dichlorobenzene (major).

  • Nitration: Conc. $HNO_3$ + Conc. $H_2SO_4$.

  • Sulphonation: Conc. $H_2SO_4$.

  • Friedel-Crafts: Alkylation/Acylation using anhydrous $AlCl_3$.

• Wurtz-Fittig Reaction: Reaction of an alkyl halide and aryl halide with sodium in dry ether to give an alkylarene.

• Fittig Reaction: Two aryl halides react with sodium to form biphenyl/diphenyl.

Polyhalogen Compounds

• Dichloromethane ($CH_2Cl_2$): Solvent for paint removal, aerosols, drug manufacture. Harms central nervous system.

• Trichloromethane ($CHCl_3$/Chloroform): Solvent and refrigerant production ($R-22$). Oxidises in air/light to Phosgene ($COCl_2$), a poisonous gas.

• Triiodomethane ($CHI_3$/Iodoform): Antiseptic (due to liberation of free iodine); has an objectionable smell.

• Tetrachloromethane ($CCl_4$): Refrigerant and propellant feedstock. Causes liver cancer and depletes the ozone layer.

• Freons (CFCs): Stable gases used in refrigeration. Freon 12 ($CCl_2F_2$) is common. Deplete stratospheric ozone via radical chain reactions.

• DDT ($p,p^\prime$-Dichlorodiphenyltrichloroethane): First chlorinated insecticide. Paul Muller won the Nobel Prize (1948) for its discovery. Highly toxic to fish, persistent in fat tissues; banned in the USA in 1973.

Questions & Discussion

• Q: Why is sulphuric acid not used with $KI$ to prepare alkyl iodides?

• A: $H_2SO_4$ is an oxidising agent; it converts $HI$ to $I_2$, preventing the reaction with alcohol.

• Q: Why is chlorine ortho/para directing if it's electron withdrawing?

• A: It withdraws electrons via the Inductive effect ($-I$), but releases them via Resonance ($+R$). Resonance increases density at o/p positions, making those sites more favorable for electrophiles despite the overall ring deactivation.

• Q: Why must Grignard reagents be anhydrous?

• A: They are highly reactive and react instantly with moisture to form hydrocarbons ($RMgX + H_2O \\rightarrow RH + Mg(OH)X$).