Haloalkanes and Haloarenes

Haloalkanes and Haloarenes

Introduction

• Replacement of hydrogen in aliphatic or aromatic hydrocarbons by halogen(s) forms alkyl halides (haloalkanes) and aryl halides (haloarenes).
• Haloalkanes: Halogen(s) attached to sp^3 hybridized carbon of an alkyl group.
• Haloarenes: Halogen(s) attached to sp^2 hybridized carbon(s) of an aryl group.
• Many halogenated organic compounds occur naturally and are clinically useful.
• Applications:
  • Solvents for non-polar compounds.
  • Starting materials for organic synthesis.
  • Chloramphenicol (antibiotic for typhoid fever).
  • Thyroxine (iodine-containing hormone; deficiency causes goiter).
  • Chloroquine (treatment for malaria).
  • Halothane (anesthetic during surgery).
  • Fluorinated compounds (potential blood substitutes).
• Environmental Persistence: Halogenated compounds resist breakdown by soil bacteria.

Classification

Based on Number of Halogen Atoms

• Mono-, di-, or polyhalogen compounds based on the number of halogen atoms.

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

• (a) Alkyl Halides (Haloalkanes) (R—X):
  • Halogen bonded to an alkyl group (R).
  • Homologous series: CnH{2n+1}X
  • Classified as primary (1^o), secondary (2^o), or tertiary (3^o) based on the carbon to which the halogen is attached.
• (b) Allylic Halides:
  • Halogen bonded to an sp^3-hybridized carbon adjacent to a C=C double bond (allylic carbon).
• (c) Benzylic Halides:
  • Halogen bonded to an sp^3-hybridized carbon attached to an aromatic ring.

Compounds Containing sp^2 C—X Bond

• (a) Vinylic Halides:
  • Halogen bonded to an sp^2-hybridized carbon of a C=C double bond.
• (b) Aryl Halides:
  • Halogen directly bonded to an sp^2-hybridized carbon of an aromatic ring.

Dihaloalkanes

• Geminal (gem-) Dihalides: Both halogen atoms on the same carbon atom.
  • Common name: alkylidene halides.
  • IUPAC name: dihaloalkanes.
• Vicinal (vic-) Dihalides: Halogen atoms on adjacent carbon atoms.
  • Common name: alkylene dihalides.
  • IUPAC name: dihaloalkanes.

Nomenclature

• Common Names of Alkyl Halides: Alkyl group name + halide name (e.g., ethyl chloride).
• IUPAC System: Halo-substituted hydrocarbons (e.g., chloroethane).
• Benzene Derivatives: Use prefixes o-, m-, p- in common system, and numerals 1,2; 1,3; 1,4 in IUPAC system for dihalogen derivatives.

Table 6.1: Common and IUPAC Names of some Halides

Nature of C-X Bond

• Halogen atoms are more electronegative than carbon, making the C-X bond polar.
• Carbon has a partial positive charge (\delta+), and halogen has a partial negative charge (\delta--).
• Bond length increases from C-F to C-I due to increasing halogen size.

Table 6.2: Carbon-Halogen (C—X) Bond Lengths, Bond Enthalpies and Dipole Moments

Methods of Preparation of Haloalkanes

From Alcohols

• Reaction of alcohols with concentrated halogen acids, phosphorus halides, or thionyl chloride.
• Thionyl chloride (SOCl2) is preferred as it forms alkyl halide with gaseous SO_2 and HCl, which escape, yielding pure alkyl halides.
• R-OH + SOCl2 \rightarrow R-Cl + SO2 + HCl
• Primary and secondary alcohols require a catalyst (ZnCl2) with HCl.
• Tertiary alcohols react with concentrated HCl at room temperature.
• Alkyl bromides prepared by constant boiling with HBr (48%).
• Alkyl iodides prepared by heating alcohols with sodium or potassium iodide in 95% orthophosphoric acid.
• Reactivity order of alcohols with haloacids: 3° > 2° > 1°.
• Phosphorus tribromide (PBr3) and triiodide (PI3) are generated in situ by reacting red phosphorus with bromine and iodine, respectively.

From Hydrocarbons

• (I) From Alkanes by Free Radical Halogenation
  • Free radical chlorination or bromination yields a complex mixture of isomeric mono- and polyhaloalkanes.
  • Difficult to separate as pure compounds; low yield of any single compound.
• (II) From Alkenes
  • (i) Addition of Hydrogen Halides: Alkenes react with HCl, HBr, or HI to form alkyl halides.
    • Markovnikov’s rule applies (Unit 13, Class XI).
  • (ii) Addition of Halogens: Addition of bromine in CCl_4 to an alkene results in discharge of the reddish-brown color of bromine, indicating a double bond.
    • Forms vic-dibromides (colorless).

Halogen Exchange

• Finkelstein Reaction: Alkyl chlorides/bromides react with NaI in dry acetone to form alkyl iodides.
  • R-Cl/Br + NaI \rightarrow R-I + NaCl/NaBr
  • NaCl or NaBr precipitates in dry acetone, favoring the forward reaction (Le Chatelier’s Principle).
• Swarts Reaction: Alkyl fluorides prepared by heating alkyl chloride/bromide with a metallic fluoride (AgF, Hg2F2, CoF2, SbF3).
  • R-Cl/Br + AgF \rightarrow R-F + AgCl/Br

Preparation of Haloarenes

From Hydrocarbons by Electrophilic Substitution

• Aryl chlorides and bromides prepared by electrophilic substitution of arenes with chlorine and bromine, respectively.
• Lewis acid catalysts (Fe or FeCl_3) are required.
• Ortho- and para-isomers are easily separated due to differences in melting points.
• Iodination is reversible and requires an oxidizing agent (HNO3, HIO4) to oxidize HI formed during the reaction.
• Fluorine compounds are not prepared this way due to fluorine's high reactivity.

From Amines by Sandmeyer’s Reaction

• Primary aromatic amine in cold aqueous mineral acid reacts with sodium nitrite to form a diazonium salt.
• Mixing the diazonium salt with cuprous chloride or cuprous bromide replaces the diazonium group with –Cl or –Br.
• Replacement by iodine does not require cuprous halide; shake diazonium salt with potassium iodide.

Physical Properties

Color and Smell

• Alkyl halides are colorless when pure; bromides and iodides develop color upon exposure to light.
• Volatile halogen compounds often have a sweet smell.

Melting and Boiling Points

• Methyl chloride, methyl bromide, ethyl chloride, and some chlorofluoromethanes are gases at room temperature; higher members are liquids or solids.
• Organic halogen compounds are generally polar.
• Intermolecular forces (dipole-dipole and van der Waals) are stronger in halogen derivatives than in parent hydrocarbons.
  • Boiling points of chlorides, bromides, and iodides are higher than comparable hydrocarbons.
• Boiling points decrease with branching in isomeric haloalkanes.
• Boiling points of isomeric dihalobenzenes are similar; para-isomers have higher melting points due to symmetry.

Fig. 6.1: Comparison of boiling points of some alkyl halides

Solubility

• Haloalkanes are only slightly soluble in water.
  • Energy is needed to overcome haloalkane-haloalkane and water-water attractions.
  • New attractions between haloalkane and water are weaker than hydrogen bonds in water.
• Haloalkanes dissolve in organic solvents because new intermolecular attractions are similar in strength to those broken.

Table 6.3: Density of Some Haloalkanes

Density

• Bromo, iodo, and polychloro derivatives of hydrocarbons are heavier than water.
• Density increases with the number of carbon atoms, halogen atoms, and atomic mass of halogens.

Chemical Reactions of Haloalkanes

Nucleophilic Substitution Reactions

• Nucleophiles (electron-rich species) attack electron-deficient parts of substrate molecules.
• Nucleophilic substitution: A nucleophile replaces an existing nucleophile.
• Haloalkanes (substrate) have a partial positive charge on the carbon bonded to the halogen.
• Halogen atom (leaving group) departs as a halide ion.
• Halogen bonded to sp^3 hybridized carbon.

Table 6.4: Nucleophilic Substitution of Alkyl Halides (R–X)

Ambident Nucleophiles

• Groups like cyanides and nitrites have two nucleophilic centers.
• Cyanide (-C\equiv N) can link through carbon or nitrogen.
  • Carbon linkage forms alkyl cyanides.
  • Nitrogen linkage leads to isocyanides.
• Nitrite (–O—N=O) can link through oxygen or nitrogen.
  • Oxygen linkage forms alkyl nitrites.
  • Nitrogen linkage leads to nitroalkanes.

Mechanisms

• (a) Substitution Nucleophilic Bimolecular (S_N2)

  • Second-order kinetics: Rate depends on the concentration of both reactants.
  • Incoming nucleophile interacts with alkyl halide, breaking the carbon-halide bond and forming a new bond with the nucleophile.
  • Processes occur simultaneously in a single step; no intermediate is formed.
  • Inversion of configuration occurs (like an umbrella turning inside out).
  • Bulky substituents near the carbon atom inhibit the reaction.
  • Reactivity order: Primary halide > Secondary halide > Tertiary halide.

• (b) Substitution Nucleophilic Unimolecular (S_N1)

  • First-order kinetics: Rate depends on the concentration of only one reactant (alkyl halide).
  • Generally carried out in polar protic solvents (water, alcohol, acetic acid).
  • Two steps:
    • Step I: Slow cleavage of the C—Br bond to form a carbocation and a bromide ion.
    • Step II: Attack of the nucleophile on the carbocation.
  • Greater stability of carbocation leads to faster reaction.
  • Reactivity order: 3° alkyl halides > 2° alkyl halides > 1° alkyl halides.
  • Allylic and benzylic halides also show high reactivity due to resonance stabilization of the carbocation.

Stereochemical Aspects of Nucleophilic Substitution Reactions

• (i) Optical Activity: Certain compounds rotate the plane of plane-polarized light.

  • Measured using a polarimeter.
  • Dextrorotatory (d-form): Rotates light clockwise (+).
  • Laevorotatory (l-form): Rotates light counterclockwise (–).
  • (+) and (–) isomers are optical isomers; the phenomenon is optical isomerism.

• (ii) Molecular Asymmetry, Chirality, and Enantiomers:

  • Asymmetric carbon (stereocenter): A carbon atom with four different substituents.
  • Asymmetric molecules lack symmetry and are responsible for optical activity; non-superimposable mirror images.
  • Chiral molecules: Non-superimposable mirror images (like hands).
  • Achiral molecules: Superimposable mirror images.
  • Enantiomers: Stereoisomers that are non-superimposable mirror images.
    • Identical physical properties except for rotation of plane-polarized light.
    • If one enantiomer is dextrorotatory, the other is laevorotatory.
  • Racemic mixture: Equal proportions of two enantiomers; zero optical rotation (denoted by dl or (±)).
  • Racemization: Conversion of an enantiomer into a racemic mixture.

• (iii) Retention: Preservation of the spatial arrangement of bonds to an asymmetric center during a chemical reaction.
  * No bond to the stereocenter is broken, the product will have the same general configuration.

• (iv) Inversion, Retention, and Racemization: Three outcomes when a bond directly linked to an asymmetric carbon atom is broken.

  • Retention: Only compound (A) is obtained.
  • Inversion: Only compound (B) is obtained.
  • Racemization: 50:50 mixture of A and B is obtained.

• SN1 and SN2 mechanisms from stereochemical perspective

  • S_N2 changes stereochemistry to the inverted configuration
  • S_N1 causes racemization

Elimination Reactions

• Haloalkane with β-hydrogen atom heated with alcoholic KOH.
• Elimination of hydrogen from β-carbon and halogen from α-carbon, forming an alkene.
• β-elimination (dehydrohalogenation).
• Zaitsev’s rule: The preferred product is the alkene with more alkyl groups attached to the doubly bonded carbon atoms.

Reaction with Metals

• Organic chlorides, bromides, and iodides react with metals to form organometallic compounds.
• Grignard Reagents (RMgX): Alkyl magnesium halides formed by reacting haloalkanes with magnesium metal in dry ether.
  • R-X + Mg \rightarrow R-Mg-X
  • Carbon-magnesium bond is covalent but highly polar. Magnesium halogen bond is essentially ionic.
  • Highly reactive; react with any source of proton (even water, alcohols, amines) to give hydrocarbons.
• Wurtz Reaction: Alkyl halides react with sodium in dry ether to form hydrocarbons with double the number of carbon atoms.
  • 2R-X + 2Na \rightarrow R-R + 2NaX

Elimination versus substitution

• A chemical reaction is the result of competition; it is a race that is won by the fastest runner. A collection of molecules tend to do, by and large, what is easiest for them.
• An alkyl halide with α-hydrogen atoms when reacted with a base or a nucleophile has two competing routes: substitution (SN1 and SN2) and elimination.
• Which route will be taken up depends upon the nature of alkyl halide, strength and size of base/nucleophile and reaction conditions.
• Thus, a bulkier nucleophile will prefer to act as a base and abstracts a proton rather than approach a tetravalent carbon atom (steric reasons) and vice versa.
• Similarly, a primary alkyl halide will prefer a SN2 reaction, a secondary halide- SN2 or elimination depending upon the strength of base/nucleophile and a tertiary halide- S_N1 or elimination depending upon the stability of carbocation or the more substituted alkene.

Reactions of Haloarenes

Nucleophilic Substitution

• Aryl halides are much less reactive towards nucleophilic substitution reactions.

Reasons:

• (i) Resonance Effect: Electron pairs on the halogen atom are conjugated with π-electrons of the ring, giving the C—Cl bond a partial double bond character.

• (ii) Hybridization: Carbon atom attached to halogen is sp2-hybridized in haloarenes, while it is sp3-hybridized in haloalkanes. Sp2 carbon is more electronegative and holds the electron pair of the C—X bond more tightly.

• (iii) Instability of Phenyl Cation: Phenyl cation is not stabilized by resonance.

• (iv) Repulsion: Less likely for electron-rich nucleophiles to approach electron-rich arenes.

Replacement by Hydroxyl Group

• Chlorobenzene can be converted into phenol by heating with aqueous sodium hydroxide at 623K and 300 atm.
• Electron-withdrawing groups (-NO2) at ortho- and para-positions increase the reactivity of haloarenes.
• The presence of nitro group at ortho- and para-positions withdraws the electron density from the benzene ring and thus facilitates the attack of the nucleophile on haloarene. The carbanion thus formed is stabilised through resonance.
• The negative charge appeared at ortho- and para- positions with respect to the halogen substituent is stabilised by –NO2 group while in case of meta-nitrobenzene, none of the resonating structures bear the negative charge on carbon atom bearing the –NO2 group.
• Therefore, the presence of nitro group at meta- position does not stabilise the negative charge and no effect on reactivity is observed by the presence of –NO_2 group at meta-position.

Electrophilic Substitution Reactions

• Haloarenes undergo halogenation, nitration, sulfonation, and Friedel-Crafts reactions.

• Halogen atom is slightly deactivating but o, p-directing.

• Due to resonance, the electron density increases more at ortho- and para-positions than at meta-positions.

• The halogen atom because of its –I effect has some tendency to withdraw electrons from the benzene ring. As a result, the ring gets somewhat deactivated as compared to benzene and hence the electrophilic substitution reactions in haloarenes occur slowly and require more drastic conditions as compared to those in benzene.

• (i) Halogenation

• (ii) Nitration

• (iii) Sulphonation

• (iv) Friedel-Crafts reaction

Reaction with Metals

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

• Fittig Reaction: Aryl halides react with sodium in dry ether to join two aryl groups.

Polyhalogen Compounds

Dichloromethane (Methylene Chloride)

• Used as a solvent, paint remover, aerosol propellant, and metal cleaning solvent.
• Harms the central nervous system; can cause impaired hearing and vision, dizziness, nausea, and skin burns.

Trichloromethane (Chloroform)

• Used as a solvent for fats, alkaloids, and iodine; also used in the production of freon refrigerant R-22.
• Formerly used as a general anesthetic but replaced by safer anesthetics.
• Depresses the central nervous system; chronic exposure may damage the liver and kidneys.
• Slowly oxidized by air and light to phosgene (carbonyl chloride), an extremely poisonous gas.

Triiodomethane (Iodoform)

• Antiseptic properties due to the liberation of free iodine.
• Replaced by other iodine-containing formulations due to its objectionable smell.

Tetrachloromethane (Carbon Tetrachloride)

• Used in the manufacture of refrigerants and aerosol propellants; also used as a solvent and cleaning fluid.
• Causes liver cancer in humans; can cause permanent damage to nerve cells and heart irregularities.
• Depletes the ozone layer when released into the atmosphere.

Freons

• Chlorofluorocarbon compounds of methane and ethane; extremely stable, unreactive, non-toxic, and easily liquefiable gases.
• Freon 12 (CCl2F2) is commonly used in industrial applications and aerosol propellants, refrigeration and air conditioning.
• Freons diffuse unchanged into the stratosphere, where they can initiate radical chain reactions that upset the natural ozone balance.

p,p’-Dichlorodiphenyltrichloroethane (DDT)

• Chlorinated organic insecticide discovered by Paul Muller in 1939.
• Effective against mosquitoes that spread malaria and lice that carry typhus.
• Use was banned in the United States in 1973 due to insect resistance, high toxicity to fish, and chemical stability (builds up in fatty tissues of animals).