Haloalkanes and Haloarenes

• Haloalkanes and Haloarenes contain halogen atoms that cause resistance to breakdown by soil bacteria, thus persisting in the environment.
• This unit explores preparation methods, physical/chemical properties, and uses of organohalogen compounds.

Alkyl Halides (Haloalkanes)

• Result from replacing hydrogen in aliphatic hydrocarbons with halogen atoms.
• Halogen atoms attach to sp3 hybridized carbon atoms of an alkyl group.
• Classified as primary (1°), secondary (2°), or tertiary (3°) based on the carbon bonded to the halogen.

Aryl Halides (Haloarenes)

• Result from replacing hydrogen in aromatic hydrocarbons with halogen atoms
• Halogen atoms are directly attached to sp2 hybridized carbon atoms of an aryl group.

Applications of Halogen-containing Compounds

• Solvents for non-polar substances, and starting materials for synthesizing organic compounds.
• Chloramphenicol: A chlorine-containing antibiotic used to treat typhoid fever.
• Thyroxine: An iodine-containing hormone produced by the body; its deficiency causes goiter.
• Chloroquine: A synthetic halogen compound for malaria treatment.
• Halothane: Used as an anaesthetic during surgery.
• Fully fluorinated compounds: Considered as potential blood substitutes in surgery.

Classification of Haloalkanes and Haloarenes

• Classified as mono-, di-, or polyhalogen compounds based on the number of halogen atoms in their structure.

Compounds Containing sp3 C-X Bond

• Alkyl halides or haloalkanes (R-X): Halogan atoms bond to an alkyl group (R), represented by CnH2n+1X, and are classified as primary, secondary or tertiary.
• Allylic halides: Halogen atoms bond to an sp3-hybridised carbon atom adjacent to a carbon-carbon double bond (C=C).
• Benzylic halides: Halogen atoms bond to an sp3-hybridised carbon atom attached to an aromatic ring.

Compounds Containing sp2 C-X Bond

• Vinylic halides: Halogen atoms bond to a sp2-hybridised carbon atom of a carbon-carbon double bond (C=C).
• Aryl halides: Halogen atoms directly bond to a sp2-hybridised carbon atom of an aromatic ring.

Nomenclature of Haloalkanes and Haloarenes

• Common names of alkyl halides: Named by identifying the alkyl group followed by the halide name, e.g., n-Propyl bromide.
• IUPAC nomenclature: Alkyl halides are named as halosubstituted hydrocarbons
• Benzene derivatives: The prefixes o-, m-, p- are used for dihalogen derivatives in the common system, while numerals like 1,2-; 1,3-; and 1,4- are used in the IUPAC system.
• Dihaloalkanes: Dihaloalkanes with the same type of halogen atoms are named as alkylidene or alkylene dihalides.
• gem-dihalides: Compounds with both halogen atoms on the same carbon atom.
• vic-dihalides: Halogen atoms are present on adjacent carbon atoms
• Dihaloalkanes: In the IUPAC system are named as dihaloalkanes

Nature of C-X Bond

• Halogen atoms are more electronegative than carbon, resulting in a polar carbon-halogen bond
• Carbon carries a partial positive charge, and the halogen a partial negative charge
• The size of the halogen atom increases down the periodic table, increasing the C-X bond length from C-F to C-I.
• Alkyl halides are synthesized from readily available alcohols

Preparation of Haloalkanes and Haloarenes

• From alcohols: The hydroxyl group of an alcohol is replaced by a halogen through reactions with concentrated halogen acids, phosphorus halides, or thionyl chloride (best for pure alkyl halides).
• Reactivity order: 3°>2°>1° for alcohols reacting with haloacids.
• From alkenes: Alkenes convert to alkyl halides via addition of hydrogen halides (follows Markovnikov's rule) or halogens, which detects double bonds.
• Halogen exchange: Alkyl iodides are produced from alkyl chlorides/bromides reacting with NaI in dry acetone (Finkelstein reaction). Alkyl fluorides are synthesized by heating alkyl chlorides/bromides with metallic fluorides like AgF (Swarts reaction).
• From hydrocarbons(Electrophilic substitution): Arenes react with chlorine or bromine in presence of Lewis acid catalysts.
• From amines (Sandmeyer's reaction): Primary aromatic amines react with sodium nitrite and then cuprous chloride/bromide to replace the diazonium group with -Cl or -Br.
• Diazonium salt can be reacted with potassium iodide to replace diazonium group with iodine

Physical Properties of Alkyl Halides

• Colorless when pure, but bromides and iodides develop color on light exposure.
• Volatile halogen compounds have a sweet smell.
• VDW forces increase: Boiling points of chlorides, bromides, and iodides are higher than comparable hydrocarbons, with the boiling point increasing with size and number of electrons.
• Boiling points: RI > RBr > RCl > RF due to increased size and mass of the halogen atom.
• Branching decreases boiling points in isomeric haloalkanes.
• Density: Bromo, iodo, and polychloro derivatives are heavier than water, and density increases with carbon/halogen count and atomic mass.
• Solubility: Slightly soluble in water because energy to disrupt haloalkane and water attractions isn't fully offset by new attractions; more soluble in organic solvents where intermolecular forces are similar.

Chemical Reactions of Haloalkanes

• Divided into nucleophilic substitution, elimination reactions, and reactions with metals.
• Nucleophilic substitution: A nucleophile replaces an existing nucleophile on a haloalkane.

SN1 and SN2 Reactions

• Haloalkanes undergo nucleophilic substitution via SN1 or SN2 mechanisms.
• SN2 reactions: Incoming nucleophile interacts with alkyl halide - the carbon-halide bond breaks and a new bond is formed.
• Configuration Inversion: In transition state, carbon bonds to both nucleophile and leaving group, inverting the stereochemistry.
• Steric Hindrance: Bulky substituents near the carbon atom slowdown reaction.
• SN1 reactions: Carbocation intermediate is formed, high reactivity towards SN1 reactions.

Stereochemical Aspects of Nucleophilic Substitution Reactions

• Understanding optical activity, chirality, retention, inversion, racemisation, etc is needed.
• Optical activity: Plane-polarized light rotates through certain types of compounds and is measured by polarimeter. Compound is dextrorotatory if light is rotated clockwise direction, laevo-rotatory if rotates left. Optical isomers creates phenomenon is known as optical isomerism.
• Molecular asymmetry, chirality and enantiomers: The observation of Louis Pasteur (1848) that crystals shown optical rotation created stereochemistry and is associated with molecules (configurations) of two types of crystals. All four groups had to be different to show tetrahedal shapes of molecules. molecule lacking symmetry and cannot be superimposed the molecules is called asymmetric molecule

Spacial arrangment of molecules with functional groups, creates chirality. Molecules has no asymmetry that is optically inactive. stereoisomers, or enantiomers related to one another are called non-superimposable of mirror images. Enantiomers have identical physical properties, one enantiomer shows dextrorotatory, other will be laevo rotatory (absolute configuration). optical isomers

Reactions of Haloarenes

• Less reactive toward nucleophilic substitutions due to resonance, carbon hybridisation, instability of phenyl cation, and possible repulsions

Methods of Altering Haloarenes

• By hydroxyl group: Chlorobenzene can be converted into phenol by heating in aqueous sodium hydroxide solution with a temp of 623K and 300 atmospheres of pressure.
• By adding electron withrawing groups: Presence of an electron at orthon and para- postions increase reactivity of haloarenes

Polyhalogen Compounds

• Carbon compounds containing multiple halogen atoms.

Dichloromethane (Methylene Chloride)

• Common uses: Solvent, paint remover, aerosol propellant, and metal cleaner/finisher.
• Hazardous effects: Damages the central nervous system, impairing hearing and vision, and causing skin/eye burns.

Trichloromethane (Chloroform)

• Common uses: Solvent (fats, alkaloids, iodine), once as a general anaesthetic.
• Hazardous effects: Depresses the central nervous system and can damage the liver/kidneys, as well as forming the poisonous gas phosgene when exposed to air and light.

Triiodomethane (Iodoform)

• Note: its antiseptic properties derived from free iodine liberation, not iodoform itself
• Now: replaced due to smell.

Tetrachloromethane (Carbon Tetrachloride)

• Common uses: refrigerant, aerosol propellant, feedstock in the synthesis and use of chlorofluorocarbons, pharmaceutical manufacture, and general solvent.
• Hazardous effects: Liver cancer and causes dizziness, affects nerves leading to stupor, coma, or death, also can affect heartbeat and irritation
• Ozone Layer Depletion: Released in the air causing ozone depletion.

Freons

• Extremely stable, unreactive, non-toxic, non-corrosive, and liquefiable used as aerosol refrigerants
• Total freons: ~2 billion pounds annually.
• Atmosphere: Initiates a radical chain reactions upsetting in the nature balance.

DDT (p,p'-Dichlorodiphenyltrichloroethane)

• It increased enormously after WW11 because of its effectiveness against the mosquito that spreads malaria
• By 1940's insects developed resistance
• Toxicity is high towards fish which builds up over time
• Banned in the States around 1973.