Haloalkanes and Haloarenes

• The replacement of hydrogen atom(s) in aliphatic or aromatic hydrocarbons by halogen atom(s) results in the formation of alkyl halide (haloalkane) and aryl halide (haloarene) respectively
• Haloalkanes contain halogen atom(s) attached to the sp3 hybridised carbon atom of an alkyl group
• Haloarenes contain halogen atom(s) attached to sp2 hybridised carbon atom(s) of an aryl group
• Halogen-containing organic compounds occur in nature and have various applications in industry and daily life
• Chlorine-containing antibiotic chloramphenicol is effective for treating typhoid fever
• Iodine-containing hormone thyroxine is produced by the body and its deficiency causes goiter
• Synthetic halogen compounds like chloroquine are used for malaria treatment, and halothane is used as an anesthetic during surgery
• Fully fluorinated compounds are being considered as potential blood substitutes in surgery
• Haloalkanes and haloarenes may be classified as mono, di, or polyhalogen compounds based on the number of halogen atoms in their structures
• Alkyl halides or haloalkanes are classified as primary, secondary, or tertiary based on the nature of the carbon to which the halogen is attached
• Allylic halides have the halogen atom bonded to an sp3-hybridised carbon atom adjacent to a carbon-carbon double bond
• Benzylic halides have the halogen atom bonded to an sp3-hybridised carbon atom attached to an aromatic ring
• Vinylic halides have the halogen atom bonded to an sp2-hybridised carbon atom of a carbon-carbon double bond
• Aryl halides have the halogen atom directly bonded to the sp2-hybridised carbon atom of an aromatic ring
• Alkyl halides are named as halosubstituted hydrocarbons in the IUPAC system of nomenclature
• Dihaloalkanes with the same type of halogen atoms are named as alkylidene or alkylene dihalides
• Geminal halides have both halogen atoms present on the same carbon atom, while vicinal halides have halogen atoms on adjacent carbon atoms
• The carbon-halogen bond in alkyl halides is polarized, with the carbon atom bearing a partial positive charge and the halogen atom a partial negative charge
• As we go down the group in the periodic table, the size of the halogen atom increases, affecting the carbon-halogen bond length and properties
• Alkyl halides are best prepared from alcohols, which are easily accessible
• Methods of preparing aryl halides:

  • Not applicable methods: heating a mixture of alcohol and concentrated aqueous halogen acid, or by heating a mixture of alcohol and concentrated aqueous halogen acid
  • Reason: the carbon-oxygen bond in phenols has a partial double bond character, making it difficult to break as it is stronger than a single bond
• From alkanes by free radical halogenation:

  • Gives a complex mixture of isomeric mono- and polyhaloalkanes
  • Difficult to separate as pure compounds
• From alcohols:

  • The hydroxyl group of an alcohol is replaced by halogen on reaction with concentrated halogen acids, phosphorus halides, or thionyl chloride
  • Thionyl chloride preferred as it gives pure alkyl halides along with gases SO2 and HCl
• From alkenes:

  • Addition of hydrogen halides: alkene reacts with hydrogen chloride, hydrogen bromide, or hydrogen iodide to form corresponding alkyl halide
  • Addition of halogens: addition of bromine in CCl4 to an alkene results in vic-dibromides
• From hydrocarbons by electrophilic substitution:

  • Aryl chlorides and bromides prepared by electrophilic substitution of arenes with chlorine and bromine in the presence of Lewis acid catalysts like iron or iron(III) chloride
  • Ortho and para isomers easily separated due to large difference in melting points
• Factors affecting boiling points:

  • Boiling points increase with molecular size and mass
  • Boiling points increase with stronger intermolecular forces
  • Boiling points increase with increased branching in molecules
• Boiling points of the given compounds:

  (i) Bromomethane < Dibromomethane < Bromoform < Chloromethane

  (ii) 1-Chloropropane < 1-Chlorobutane < Isopropyl chloride
• Nucleophilic substitution reactions involve a nucleophile reacting with a haloalkane

  • Haloalkanes are substrates in these reactions
  • The nucleophile attacks the carbon atom bonded to the halogen, causing a substitution reaction
• Common nucleophiles and their products in nucleophilic substitution reactions:

  • NaOH (KOH): Alcohol
  • H2O: Alcohol
  • NaOR¢: Ether
  • NaI: Alkyl iodide
  • NH3: Primary amine
  • RCN: Nitrile (cyanide)
  • AgCN: Isonitrile (isocyanide)
  • KNO2: Alkyl nitrite
  • R¢COOAg: Ester
  • LiAlH4: Hydrocarbon
• SN2 Reaction Mechanism:

  • Bimolecular nucleophilic substitution
  • Involves the attack of a nucleophile on an alkyl halide
  • Carbon-halide bond breaks, forming a new bond with the nucleophile
  • Configuration of the carbon atom under attack inverts during the reaction
• For single-celled organisms, substances can easily enter the cell due to a short distance
• In multicellular organisms, the distance for substances to enter the cell is larger due to a higher surface area to volume ratio
• Multicellular organisms require specialised exchange surfaces for efficient gas exchange of carbon dioxide and oxygen
• For a reaction at an asymmetric carbon atom, when a bond directly linked to an asymmetric carbon atom is broken:

  • If compound (A) is the only product obtained, the process is called retention of configuration, even though the configuration has been rotated in A.
  • If compound (B) is the only product obtained, the process is called inversion of configuration, where the configuration has been inverted in B.
  • If a 50:50 mixture of A and B is obtained, the process is called racemisation, resulting in an optically inactive product where one isomer rotates plane-polarised light in the opposite direction to another
• In SN2 reactions of optically active alkyl halides, the product formed has an inverted configuration compared to the reactant, as the nucleophile attaches itself on the side opposite to where the halogen atom is present
• In SN1 reactions of optically active alkyl halides, racemisation occurs due to the planar nature of the carbocation formed in the slow step, allowing the attack of the nucleophile from either side of the plane of the carbocation, resulting in a mixture of products with the same or opposite configurations
• Elimination reactions:

  • When a haloalkane with a β-hydrogen atom is heated with an alcoholic solution of potassium hydroxide, elimination of a hydrogen atom from the β-carbon and a halogen atom from the α-carbon occurs, forming an alkene as a product
  • This process, involving the removal of a β-hydrogen atom, is often referred to as β-elimination
  • The Zaitsev rule states that in dehydrohalogenation reactions, the preferred product is the alkene with the greater number of alkyl groups attached to the doubly bonded carbon atoms
• Reaction with metals:

  • Organic chlorides, bromides, and iodides react with certain metals to form compounds containing carbon-metal bonds, known as organo-metallic compounds
  • Grignard reagents, discovered by Victor Grignard, are alkyl magnesium halides obtained by the reaction of haloalkanes with magnesium metal in dry ether
  • Grignard reagents are highly reactive and react with any source of a proton to give hydrocarbons
• Wurtz reaction:

  • Alkyl halides react with sodium in dry ether to produce hydrocarbons containing double the number of carbon atoms present in the halide
• Nucleophilic substitution:

  • Aryl halides are less reactive towards nucleophilic substitution reactions due to factors like resonance effects, difference in hybridization of carbon atoms, and instability of phenyl cation