Haloalkanes and Haloarenes

Halogenated Compounds

• Halogenated compounds are resistant to breakdown by soil bacteria, causing them to persist in the environment.

Formation of Haloalkanes and Haloarenes

• Replacing hydrogen atoms in aliphatic or aromatic hydrocarbons with halogen atoms results in the formation of alkyl halides (haloalkanes) and aryl halides (haloarenes), respectively.
• Haloalkanes contain halogen atoms bonded to an sp³ hybridized carbon atom of an alkyl group.
• Haloarenes contain halogen atoms bonded to an sp² hybridized carbon atom of an aryl group.
• Many halogen-containing organic compounds occur naturally and some are clinically useful.
• These compounds are widely used in industry and everyday life as solvents for non-polar compounds and as starting materials for synthesizing various organic compounds.
• Chloramphenicol, a chlorine-containing antibiotic, is effective in treating typhoid fever.
• The human body produces thyroxine, an iodine-containing hormone; its deficiency causes goiter.
• Chloroquine, a synthetic halogen compound, treats malaria.
• Halothane is used as an anesthetic during surgery
• Fully fluorinated compounds are being explored as potential blood substitutes in surgery.

Classification of Haloalkanes and Haloarenes

• Haloalkanes and haloarenes are classified based on the number of halogen atoms: mono-, di-, or polyhalogen compounds.

Compounds Containing sp³ C-X Bond

• Alkyl halides (haloalkanes) have a halogen atom bonded to an alkyl group (R).
• They form a homologous series represented by CnH2n+1X.
• Alkyl halides are classified as primary (1°), secondary (2°), or tertiary (3°) based on the carbon atom to which the halogen is attached.
• Allylic halides involve a halogen atom bonded to an sp³-hybridized carbon atom adjacent to a carbon-carbon double bond (C=C).
• Benzylic halides have a halogen atom bonded to an sp³-hybridized carbon atom attached to an aromatic ring.

Compounds Containing sp² C-X Bond

• Vinylic halides contain a halogen atom bonded to an sp²-hybridized carbon atom of a carbon-carbon double bond (C=C).
• Aryl halides have a halogen atom directly bonded to an sp²-hybridized carbon atom of an aromatic ring.

Nomenclature of Haloalkanes and Haloarenes

• Common names of alkyl halides are derived by naming the alkyl group followed by the name of the halide.
• In the IUPAC system, alkyl halides are named as halo-substituted hydrocarbons.
• Common and IUPAC names are the same for mono-halogenated derivatives of benzene.
• Prefixes o-, m-, p- are used in the common system for dihalogen derivatives, while numerals 1,2; 1,3; and 1,4 are used in the IUPAC system.
• Dihaloalkanes with the same type of halogen atoms are named as alkylidene or alkylene dihalides.
• Dihalo-compounds are classified as geminal halides (gem-dihalides) when both halogen atoms are on the same carbon atom, and vicinal halides (vic-dihalides) when halogen atoms are on adjacent carbon atoms.
• Gem-dihalides are named alkylidene halides and vic-dihalides are named alkylene dihalides in the common name system.
• In the IUPAC system, they are named as dihaloalkanes.

Nature of C-X Bond

• Halogen atoms are more electronegative than carbon, resulting in a polar carbon-halogen bond in alkyl halides: the carbon atom has a partial positive charge, and the halogen atom has a partial negative charge.
• As you move down the periodic table group, the size of the halogen atom increases, which influences the carbon-halogen bond length, increasing from C-F to C-I.
• Alkyl halides are best prepared from alcohols, which are easily accessible.

Methods of Preparation of Haloalkanes

• Alcohols react with concentrated halogen acids, phosphorus halides, or thionyl chloride, replacing the hydroxyl group with a halogen
• Thionyl chloride is preferred because it forms alkyl halides and gaseous products (SO₂ and HCl) that escape, yielding pure alkyl halides.
• Primary and secondary alcohols require a ZnCl₂ catalyst, while tertiary alcohols react with HCl at room temperature without a catalyst.
• Heating alcohols with sodium or potassium iodide in 95% orthophosphoric acid yields good results of R-I
• The order of alcohol reactivity with haloacids is 3° > 2° > 1°.
• Phosphorus tribromide and triiodide are generated in situ by reacting red phosphorus with bromine and iodine, respectively.
• Alkyl chloride can be prepared by either passing dry hydrogen chloride gas through a solution of alcohol or by heating a mixture of alcohol and concentrated aqueous halogen acid.

Limitations of Methods

• The above methods are unsuitable for preparing aryl halides because the carbon-oxygen bond in phenols has partial double bond character, making it difficult to break.

Preparation from Hydrocarbons

• From Alkanes:*
• Free radical chlorination or bromination of alkanes yields a complex mixture of isomeric mono- and polyhaloalkanes
• From Alkenes:*
• Alkenes react with hydrogen halides (HCl, HBr, HI) to form corresponding alkyl halides, following Markovnikov's rule
• Adding bromine in CCl₄ to an alkene discharges the reddish-brown color, indicating the presence of a double bond and synthesizing vic-dibromides

Halogen Exchange

• Alkyl iodides are prepared by reacting alkyl chlorides/bromides with NaI in dry acetone through the Finkelstein reaction
• Forming NaCl or NaBr precipitates in dry acetone, facilitates the forward reaction according to Le Chatelier's Principle.
• Alkyl fluorides are synthesized by heating an alkyl chloride/bromide with a metallic fluoride, like AgF, via the Swarts reaction.

Preparation of Haloarenes

• From Hydrocarbons:*
• Electrophilic substitution of arenes with chlorine or bromine, using Lewis acid catalysts (iron or iron(III) chloride), produces aryl chlorides and bromides.
• Ortho and para isomers are easily separated due to the large difference in melting point
• From Amines via Sandmeyer's Reaction:*
• Primary aromatic amines dissolved or suspended in cold aqueous mineral acid react with sodium nitrite to form diazonium salts.
• Mixing the diazonium salt solution with cuprous chloride or cuprous bromide replaces the diazonium group with -Cl or -Br.
• Replacing the diazonium group with iodine doesn't need cuprous halide; instead, shaking the diazonium salt with potassium iodide.

Physical Properties of Haloalkanes

• Alkyl halides with 1-2 carbon atoms or haloalkanes that contain fluorides are colorless gasses, alkyl halides of moderate size are colorless liquids, and higher alkyl halides are colorless solids.
• Alkyl halides are colorless when pure, but develop colors upon exposure to light, and volatile halogen compounds usually have sweet odors.
• Density increases with the number of carbon and halogen atoms.

Boiling and melting point

• The boiling points of halogenated compounds are higher than hydrocarbons of comparable molecular masses, due to dipole-dipole and Van der Waals forces.
• Among isomeric haloalkanes, branching decreases boiling point.

Solubility

• Haloalkanes are slightly soluble in water.
• They tend to dissolve in organic solvents.

Chemical Reactions of Haloalkanes

1. Nucleophilic Substitution: Involves replacing a nucleophile with another.
2. Elimination Reactions: Involves the removal of atoms or groups of atoms from adjacent carbon atoms, forming a double bond
3. Reaction with Metals: Forms organometallic compounds like Grignard reagents.

Nucleophilic Substitution Reactions

• You have learnt previously that nucleophiles are rich in electrons, they will attack the electron defficient parts of the substrate
• The reaction, in which the substance is replaced by a nucleophile is called a substitution reaction.

SN1 vs SN2 reactions

• SN2 reactions are known as substitution nucleophilic bimolecular.
• SN1 reactions are known as substitution nucleophilic unimolecular.

Reactions of Haloarenes

• Haloarenes are far less reactive to nucleophilic substitution reactions
• Haloarenes can undergo electrophilic substitution
• Haloarenes can be metalated.

Electrophilic substitution reactions:

• Haloarenes undergo the haloarenes undergo halogenation, nitration and sulphonation and Friedel-crafts reactions.

Friedel-Crafts reaction

• Aromatic compounds reacts with an alkyl or acyl halide in the presence of a strong Lewis acid catalyst

Polyhalogen Compounds

• Polyhalogen compounds are carbon compounds comprising of multiple halogen atoms.

Uses of Polyhalogen Compounds

• These are useful in medicine, agriculture, and Industry.

Specific Examples of Polyhalogen Compounds

• Dichloromethane (Methylene chloride) is used as a process solvent and in a lot of industrial applications. This can lead to some slight hearing loss, as well as liver damage if precautions are not taken.
• Trichloromethane (Chloroform) can be employed as a solvent in industrial applications; it's a central nervious system depressor, can cause dizziness, fatigue, or headaches.
• Triiodomethane (Iodoform) was used earlier as an antiseptic. However, the antiseptic properties are due to the liberation of free iodine and not due to Iodoform itself.
• Tetrachloromethane (Carbon tetrachloride) used for refrigerants and propellants. Until the mid 1960's, it was also widely used as a cleaning fluid; now, there is evidence that exposure to terachloromethane can cause liver cancer damage.
• Freons (chlorofluorocarbon compounds) are used now for aersol, by the year 1974, around 2 billion pounds was created for use. However, Freon is able to initiate radical chain reactions, which can ultimately upset the natural ozone balance.
• p,p'-Dichlorodiphenyltrichloroethane(DDT) is used as an insecticide commonly after World War II, however; problems with this use was discover around the 1940's, where it was seen it increased many species resistance and had a high toxicity towards fish.