Haloalkanes and Haloarenes

• Haloalkanes and haloarenes contain halogen atoms which affect their properties and reactivity
• These compounds are found in industry, medicine, and everyday life

Haloalkanes and Haloarenes

• Haloalkanes feature halogen atoms bonded to sp³ hybridized carbon atoms
• Haloarenes have halogen atoms bonded to sp² hybridized carbon atoms of an aryl group
• Halogenated substances persist in the environment
• They resist breakdown by soil bacteria
• Chlorine containing antibiotic, chloramphenicol is very effective for the treatment of typhoid fever
• The iodine containing hormone, thyroxine, prevents goiter
• Chloroquine is a treatment for malaria
• Halothane is an anaesthetic
• Fluorinated compounds are potential blood substitutes

Classifications

• Haloalkanes and haloarenes are classified by the number of halogen atoms
• Mono, di, or polyhalogen compounds contain one, two, or multiple halogen atoms, respectively

Compounds Containing sp³ C-X Bond

• This class includes alkyl halides or haloalkanes where the halogen atom bonds to an alkyl group

Alkyl Halides

• Alkyl halides form a homologous series, CnH2n+1X
• They are classified as primary (1°), secondary (2°), or tertiary (3°)
• This depends on the carbon atom the halogen is attached to

Allylic Halides

• Allylic halides feature a halogen atom bonded to an sp³ hybridized carbon atom
• This atom is adjacent to a carbon-carbon double bond (C=C)

Benzylic Halides

• Benzylic halides contain a halogen atom bonded to an sp³ hybridized carbon atom
• This atom is attached to an aromatic ring

Compounds Containing sp² C-X Bond

• This class includes vinylic halides

Vinylic Halides

• Vinylic halides feature a halogen atom bonded to an sp² hybridized carbon atom in a carbon-carbon double bond (C=C)

Aryl Halides

• Aryl halides feature a halogen atom directly bonded to an sp² hybridized carbon atom in an aromatic ring

Nomenclature

• Common names of alkyl halides derive from the alkyl group, followed by the halide name
• IUPAC names use "halo" as a prefix to the hydrocarbon name
• The prefixes o-, m-, and p- are for dihalogen derivatives in the common system
• Numerals 1,2; 1,3; and 1,4 are used in the IUPAC system
• Dihalocompounds with halogens on the same carbon are geminal (alkylidene halides)
• Dihalocompounds with halogens on adjacent carbons are vicinal (alkylene halides)
• In the IUPAC system, dihaloalkanes name both types of compounds

Nature of the C-X Bond

• Halogen atoms are more electronegative than carbon
• The carbon-halogen bond of alkyl halides is polarized
• The carbon atom has a partial positive charge
• The halogen atom has a partial negative charge
• As you go down the periodic table, halogen atom size increases
• The carbon-halogen bond length increases from C-F to C-I
• Alkyl halides are prepared best from alcohols

Methods of Preparation of Haloalkanes

• The hydroxyl group of an alcohol is replaced by halogen
• This is accomplished through reaction with halogen acids, phosphorus halides, or thionyl chloride
• Thionyl chloride is preferred
• Alkyl halide forms along with the gases sulfur dioxide(SO₂) and hydrochloric acid (HCl)
• The gases are easily removed and thus purifies the alkyl halide
• Primary and secondary alcohols need a zinc chloride (ZnCl₂) catalyst when using hydrogen chloride
• Tertiary alcohols react by shaking with concentrated hydrogen chloride at room temperature
• Heating alcohols with sodium or potassium iodide in orthophosphoric acid produces R-I
• Phosphorus tribromide and triiodide are produced in situ by reacting red phosphorus with bromine and iodine

Preparation from Hydrocarbons

• Free radical halogenation of alkanes produces a complex mixture of isomeric mono- and polyhaloalkanes

Methods of Preparation from Alkenes

• Alkenes convert to alkyl halides with hydrogen halides (hydrogen chloride, hydrogen bromide, or hydrogen iodide)

Addition of Hydrogen Halides

• Propene reacts with hydrogen halides following Markovnikov’s rule

Addition of Halogens

• The addition of bromine (Br₂) in carbon tetrachloride (CCl₄) to an alkene makes a reddish brown colour discharge
• This identifies double bonds in a molecule
• The product is a colorless vic-dibromide

Alkyl Iodides

• Alkyl iodides are prepared by the reaction of alkyl chlorides or bromides with sodium iodide(NaI) in dry acetone
• This is the Finkelstein reaction

Alkyl Fluorides

• Heating an alkyl chloride or bromide with a metallic fluoride (AgF, Hg₂F₂, CoF₃, or SbF₅) produces alkyl fluorides
• This is the Swarts reaction

Preparation of Haloarenes

• Haloarenes are prepared through electrophilic substitution of arenes with chlorine or bromine using Lewis acid catalysts (iron or iron(III) chloride)

Arenes Reacting Electrophilically

• Ortho- and para- isomers separate easily
• Reactions with iodine need an oxidizing agent (HNO₃, HIO₄) to oxidize the hydrogen iodide (HI) formed
• Fluoro compounds (F Compounds) are not prepared this way due to fluorine's high reactivity

Preparation from Amines by Sandmeyer's Reaction

• Aromatic amines react with sodium nitrite (NaNO₂) and mineral acid
• Forms a diazonium salt
• Reacting a diazonium salt with cuprous chloride or cuprous bromide replaces the diazonium group with -Cl or -Br
• Replacement using iodine needs potassium iodide instead of cuprous halide

Reactions to Know

• The products of two reactions
• The halogenated compound and HBr
• The alkene compound plus HCL in the presence for peroxide
• Which structure from the set of structures would produce products with each given reagent

Physical Properties

• Pure alkyl halides are colorless, but bromides and iodides develop color when exposed to light
• Volatile halogen compounds have a sweet smell

Melting and Boiling Points

• Methyl chloride (CH₃Cl), methyl bromide (CH₃Br), ethyl chloride (C₂H₅Cl), and chlorofluoromethanes are gases at room temperature
• Higher members are liquids or solids
• Halogen compounds are generally polar
• Stronger dipole-dipole and van der Waals interactions lead to boiling points higher than hydrocarbons
• The magnitude of van der Waals forces increases across alkyl halides
• Size and mass of a halogen atom contributes to stronger the van der Waal force

Isomers

• As branching increases, boiling points of isomeric haloalkanes decrease

Dihalobenzenes

• Para-isomers have melting points due to symmetry
• This symmetry results in a better fit in crystal lattices

Density

• Bromo, iodo, and polychloro derivatives of hydrocarbons are heavier than water
• Density increases with more carbons, halogens, and a higher atomic mass of the halogens

Solubility

• Haloalkanes are slightly soluble in water
• The energy required to break haloalkane intermolecular forces and water hydrogen bonds impacts solubility
• Haloalkanes dissolve in safe organic solvents

Chemical Reactions

• Nucleophilic substitution
• Elimination reactions
• Reaction with metals

Nucleophilic Substitution Reactions

• A nucleophile replaces an existing nucleophile in a molecule
• Haloalkanes are the substrate
• A nucleophile with haloalkane substitutes halogen
• Halogen departs as a halide ion
• The substitution is initiated by a nucleophile The table lists the different products depending on the Nucleophile

Ambident Nucleophiles

• Cyanides and nitrites have two nucleophilic centers
• The cyanide group links through C or N
• Nitrite ions link through O or N

Reaction Kinetics

• KCN forms alkyl cyanides
• AgCN forms isocyanides

Stereochemical Aspects of Nucleophilic Substitution Reactions

• Stereochemical principles and notations needed
  • Optical activity
  • Chirality
  • Retention
  • Inversion
  • Racemization
• Optical Activity
  • Plane of polarized light rotates when passing through solutions
  • Measured with polarimeter for the degree
  • Rotation to the right gives a (+), dextrorotatory compound
  • Rotation to the left gives a (-), laevorotatory compound
• Enantiomers have equal but opposite rotation

Spacial Orientation

• Arrangement is called configuration
• Mirror images are enantiomers

SN1 Reaction

• The carbocation formed gets stabilised through resonance

Elimination Reactions

• A beta-hydrogen atom is removed with alcoholic potassium hydroxide
• B-elimination is followed
• Alexander Zaitsev summarized the elimination
• In dehydrohalogenation reactions, the preferred product is that alkene which has the greater number of alkyl groups attached to the doubly bonded carbon atoms

Reaction with Metals

• Most organic halides reacted to form carbon-metal bonds
• Organometallic compounds of particular note
  • Victor Grignard is credited discovering many metallic catalysts

Organometallics

• Most notable reagents
  • Alkyl Magnesium halide is often referred to as Grignard Reagents

Reactions of Haloarenes

• Haloarenes are less reactive due to resonance, bond length, instability and repulsion

Electrophilic Substitution Reaction

• Halogen atom is deactivating
• Directing to para-positions

Polyhalogen Compounds

• Polyhalogen compounds contain multiple halogens
• They are useful in industry and can be environmentally hazardous

Dichloromethane (Methylene Chloride)

• Dichloromethane is used as a solvent and paint remover
• It harms the central nervous system and skin
• Its low exposure leads to impairment
• High exposure leads to drowsiness

Trichloro-Methane (Chloroform)

• Used to dissolve fats, alkaloids
• It was replaced in the medical industry for anesthetics due to the central nervous system being affected
• Breathing 900 parts of it per million to parts of air causes dizziness
• Chronic exposer damages the liver and kidneys
• Chloroform is oxidized by air in the presence of light, creating an extremely dangerous gas "phosgene"
• Is kept in a dark color bottles that are closed tightly and completely filled

Triidomethane (iodoform)

• Used as antiseptic to some degree
• Contains free iodine but has an annoying smell
• It can be a replacement to existing medicine with idodine

Tetrachloromethane (Carbon Tetrachloride)

• Used as a refrigerant, and in synthesizers
• Causes cancer in humans
• Exposure can damage nerve cells which may lead to death
• Irregular heart-rate or a complete stopage may occur due to exposer
• Causes irritation and depletes the ozone layer

Freons

• Chlorofluorocarbon (CFC) are a mixture of methane and ethane
• Very unreactive an non toxic
• Freon 12 is very common
• Is believed to increase cancer due to UV rays

p,p'-Dichlorodiphenyltrichloroethane(DDT)

• Very harmful pesticides
• Paul Muller discovered its effectivness in 1939
• Use increased after world war 2 due to its properties to combat mosquitos and lice
• Insects and fish have problems from it and the US gave it a hard ban