Chapter Notes

Introduction to Haloalkanes and Haloarenes

When one or more hydrogen atoms in an aliphatic or aromatic hydrocarbon are replaced by halogen atoms (Fluorine, Chlorine, Bromine, Iodine), the resulting compounds are called haloalkanes (or alkyl halides) and haloarenes (or aryl halides), respectively.

• Haloalkanes: The halogen atom is attached to an $sp^3$ hybridized carbon atom of an alkyl group.
• Haloarenes: The halogen atom is attached to an $sp^2$ hybridized carbon atom of an aryl group.

These compounds are found in nature and have many applications in industry and daily life.

• Medicine: The antibiotic chloramphenicol is effective for typhoid fever. Our body produces the hormone thyroxine, an iodine compound, deficiency of which causes goiter. Chloroquine is used to treat malaria, and halothane is used as an anesthetic.
• Industry: They are used as solvents for non-polar compounds and as starting materials for synthesizing other organic compounds.

Classification of Halogen Compounds

On the Basis of Number of Halogen Atoms

Based on how many halogen atoms are present, they can be classified as:

• Mono-halo compounds: Contain one halogen atom (e.g., Monohaloalkane, Monohaloarene).
• Di-halo compounds: Contain two halogen atoms (e.g., Dihaloalkane, Dihaloarene).
• Poly-halo compounds: Contain three or more halogen atoms (e.g., Trihaloalkane, Trihaloarene).

Compounds Containing $sp^3$ C-X Bond

This class includes compounds where the halogen (X) is bonded to an $sp^3$ hybridized carbon atom.

Alkyl Halides or Haloalkanes (R-X)

The halogen atom is bonded to an alkyl group (R). They have the general formula $C_nH_{2n+1}X$. They are further classified based on the type of carbon atom the halogen is attached to:

• Primary (1°): Halogen is attached to a primary carbon (a carbon bonded to only one other carbon).
• Secondary (2°): Halogen is attached to a secondary carbon (a carbon bonded to two other carbons).
• Tertiary (3°): Halogen is attached to a tertiary carbon (a carbon bonded to three other carbons).

Allylic Halides

The halogen atom is bonded to an $sp^3$-hybridized carbon atom that is adjacent to a carbon-carbon double bond (C=C). This $sp^3$ carbon is called an allylic carbon.

Benzylic Halides

The halogen atom is bonded to an $sp^3$-hybridized carbon atom that is directly attached to an aromatic ring.

Compounds Containing $sp^2$ C-X Bond

This class includes compounds where the halogen (X) is bonded to an $sp^2$ hybridized carbon atom.

Vinylic Halides

The halogen atom is bonded to an $sp^2$-hybridized carbon atom of a carbon-carbon double bond (C=C).

Aryl Halides

The halogen atom is directly bonded to the $sp^2$-hybridized carbon atom of an aromatic ring.

Nomenclature

Common Names

• Alkyl Halides: The name of the alkyl group is followed by the name of the halide (e.g., n-Propyl bromide).
• Dihaloarenes: Prefixes o- (ortho), m- (meta), and p- (para) are used to indicate the relative positions of the halogens.

IUPAC Names

• Alkyl Halides: Named as halo-substituted hydrocarbons (e.g., 1-Bromopropane). The position of the halogen is indicated by a number.
• Haloarenes: For monohalogen derivatives, the common and IUPAC names are the same (e.g., Bromobenzene). For dihalogen derivatives, numbers are used to indicate the positions (e.g., 1,3-Dibromobenzene).

Dihaloalkanes

• Geminal dihalides (gem-dihalides): Both halogen atoms are on the same carbon. In the common system, they are named alkylidene halides (e.g., Ethylidene chloride). In IUPAC, they are named as dihaloalkanes (e.g., 1,1-Dichloroethane).
• Vicinal dihalides (vic-dihalides): Halogen atoms are on adjacent carbon atoms. In the common system, they are named alkylene dihalides (e.g., Ethylene dichloride). In IUPAC, they are named as dihaloalkanes (e.g., 1,2-Dichloroethane).

Solution

• $CH_3CH_2CH_2CH_2CH_2Br$: 1-Bromopentane (1°)
• $CH_3CH_2CH_2CH(Br)CH_3$: 2-Bromopentane (2°)
• $CH_3CH_2CH(Br)CH_2CH_3$: 3-Bromopentane (2°)
• $(CH_3)_2CHCH_2CH_2Br$: 1-Bromo-3-methylbutane (1°)
• $(CH_3)_2CHCHBrCH_3$: 2-Bromo-3-methylbutane (2°)
• $(CH_3)_2CBrCH_2CH_3$: 2-Bromo-2-methylbutane (3°)
• $CH_3CH_2CH(CH_3)CH_2Br$: 1-Bromo-2-methylbutane (1°)
• $(CH_3)_3CCH_2Br$: 1-Bromo-2,2-dimethylpropane (1°)

(i) Structure with Br on C4 of pent-2-ene (ii) Structure with Br on C3 of 2-methylbut-1-ene (iii) Structure with Br on C4 of 3-methylpent-2-ene (iv) Structure with Br on C1 of 2-methylbut-2-ene (v) Structure with Br on C1 of but-2-ene (vi) Structure with Br on C3 of 2-methylpropene

Solution

(i) 4-Bromopent-2-ene (ii) 3-Bromo-2-methylbut-1-ene (iii) 4-Bromo-3-methylpent-2-ene (iv) 1-Bromo-2-methylbut-2-ene (v) 1-Bromobut-2-ene (vi) 3-Bromo-2-methylpropene

Nature of C-X Bond

Because halogen atoms are more electronegative than carbon, the carbon-halogen (C-X) bond is polarized. The carbon atom has a partial positive charge ($\delta^+$), and the halogen atom has a partial negative charge ($\delta^-$).

As we move down the halogen group in the periodic table (F, Cl, Br, I):

• The size of the halogen atom increases.
• The C-X bond length increases (C-F < C-Cl < C-Br < C-I).
• The C-X bond enthalpy (strength) decreases, meaning the C-I bond is the weakest and easiest to break.

Methods of Preparation of Haloalkanes

From Alcohols

The hydroxyl (-OH) group of an alcohol can be replaced by a halogen.

1. Using Halogen Acids (HX):
   • $R-OH + HCl \xrightarrow{ZnCl_2} R-Cl + H_2O$
   • Primary and secondary alcohols require a catalyst, anhydrous $ZnCl_2$.
   • Tertiary alcohols react readily with concentrated HCl at room temperature.
   • The order of reactivity of alcohols is 3° > 2° > 1°.
2. Using Phosphorus Halides:
   • $3R-OH + PX_3 \rightarrow 3R-X + H_3PO_3$ (where X = Cl, Br)
   • $R-OH + PCl_5 \rightarrow R-Cl + POCl_3 + HCl$
3. Using Thionyl Chloride ($SOCl_2$):
   • $R-OH + SOCl_2 \rightarrow R-Cl + SO_2 + HCl$
   • This is the preferred method for preparing alkyl chlorides because the byproducts ($SO_2$ and $HCl$) are gases and escape, leaving a pure product.

From Hydrocarbons

From Alkanes by Free Radical Halogenation

• Alkanes react with chlorine or bromine in the presence of UV light or heat.
• This method produces a complex mixture of isomeric mono- and polyhaloalkanes, which are difficult to separate. Therefore, the yield of any single product is low.
  • $CH_3CH_2CH_2CH_3 \xrightarrow{Cl_2/UV \text{ light}} CH_3CH_2CH_2CH_2Cl + CH_3CH_2CHClCH_3$

From Alkenes

1. Addition of Hydrogen Halides (HX):
   • An alkene reacts with HCl, HBr, or HI to form an alkyl halide.
   • The addition follows Markovnikov's rule, which states that the halogen atom adds to the carbon atom of the double bond that has fewer hydrogen atoms.
     • $CH_3CH=CH_2 + HI \rightarrow CH_3CH(I)CH_3$ (major product)
2. Addition of Halogens ($X_2$):
   • Alkenes react with bromine ($Br_2$) in an inert solvent like $CCl_4$ to form vic-dibromides (dihalides with halogens on adjacent carbons).
   • This reaction is used as a test for unsaturation, as the reddish-brown color of bromine disappears.

Halogen Exchange

1. Finkelstein Reaction:
   • Used to prepare alkyl iodides.
   • An alkyl chloride or bromide is treated with sodium iodide (NaI) in dry acetone.
     • $R-X + NaI \xrightarrow{\text{dry acetone}} R-I + NaX$ (where X = Cl, Br)
   • The NaCl or NaBr formed precipitates in acetone, driving the reaction forward according to Le Chatelier's Principle.
2. Swarts Reaction:
   • Used to prepare alkyl fluorides.
   • An alkyl chloride or bromide is heated with a metallic fluoride like $AgF$, $Hg_2F_2$, $CoF_2$, or $SbF_3$.
     • $CH_3-Br + AgF \rightarrow CH_3-F + AgBr$

Preparation of Haloarenes

From Hydrocarbons by Electrophilic Substitution

• Aryl chlorides and bromides are prepared by reacting arenes with chlorine or bromine in the dark, in the presence of a Lewis acid catalyst like iron or iron(III) chloride.
• This reaction produces a mixture of ortho and para isomers, which can be separated due to a large difference in their melting points.
• Iodination is a reversible reaction and requires an oxidizing agent (like $HNO_3$ or $HIO_4$) to oxidize the HI formed.
• Fluorination is not done by this method due to the high reactivity of fluorine.

From Amines by Sandmeyer's Reaction

1. A primary aromatic amine is dissolved in a cold aqueous mineral acid and treated with sodium nitrite ($NaNO_2$) to form a diazonium salt.
2. The solution of the freshly prepared diazonium salt is mixed with cuprous chloride ($Cu_2Cl_2$) or cuprous bromide ($Cu_2Br_2$) to replace the diazonium group with -Cl or -Br.
3. To prepare iodobenzene, the diazonium salt solution is simply shaken with potassium iodide (KI).

Physical Properties

Melting and Boiling Points

• Haloalkanes have considerably higher boiling points than hydrocarbons of comparable molecular mass. This is due to their polarity and higher molecular mass, leading to stronger intermolecular forces (dipole-dipole and van der Waals attractions).
• For the same alkyl group, the boiling point order is: RI > RBr > RCl > RF. This is because van der Waals forces increase with the size and mass of the halogen atom.
• For isomeric haloalkanes, boiling points decrease with increased branching. A more branched isomer has a smaller surface area, leading to weaker van der Waals forces.
• For isomeric dihalobenzenes, boiling points are nearly the same. However, para-isomers have much higher melting points than their ortho and meta isomers. This is because the symmetrical structure of para-isomers allows them to fit better into the crystal lattice.

Density

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

Solubility

• Haloalkanes are very slightly soluble in water. Energy is required to break the hydrogen bonds between water molecules, and the new attractions formed between haloalkane and water molecules are not strong enough to compensate for this.
• They are soluble in organic solvents because the new intermolecular forces formed are of similar strength to those broken in the separate solute and solvent.

Chemical Reactions

Reactions of Haloalkanes

Haloalkanes undergo three main types of reactions:

1. Nucleophilic Substitution
2. Elimination Reactions
3. Reaction with Metals

Nucleophilic Substitution Reactions

A nucleophile is an electron-rich species that attacks an electron-deficient part of a molecule. In haloalkanes, the carbon of the C-X bond is electron-deficient. In a nucleophilic substitution reaction, a stronger nucleophile replaces the weaker nucleophile (the halide ion, which is the leaving group).

$R-X + Nu^- \rightarrow R-Nu + X^-$

• Ambident Nucleophiles: These are nucleophiles that have two nucleophilic centers.
  • Cyanide ion ($CN^-$): Can attack through carbon to form alkyl cyanides (R-CN) or through nitrogen to form isocyanides (R-NC).
  • Nitrite ion ($NO_2^-$): Can attack through oxygen to form alkyl nitrites (R-O-N=O) or through nitrogen to form nitroalkanes ($R-NO_2$).

Solution

KCN is predominantly ionic and provides cyanide ions ($CN^-$) in solution. Attack occurs mainly through the carbon atom because the C-C bond formed is more stable than the C-N bond. However, AgCN is mainly covalent. In this case, the nitrogen atom is free to donate its electron pair, so the attack occurs through nitrogen, forming isocyanide as the main product.

Mechanism of Nucleophilic Substitution

1. Substitution Nucleophilic Bimolecular ($S_N2$)

• Kinetics: The reaction rate depends on the concentration of both the alkyl halide and the nucleophile (second-order kinetics).
• Mechanism: It is a single-step process. The nucleophile attacks the carbon atom from the side opposite to the leaving group (backside attack). A temporary, unstable transition state is formed where the carbon is simultaneously bonded to both the incoming nucleophile and the outgoing leaving group.
• Stereochemistry: This mechanism results in an inversion of configuration, similar to an umbrella turning inside out in the wind. This is also known as Walden inversion.
• Reactivity Order: The reaction is sensitive to steric hindrance (crowding). Bulky groups on or near the carbon atom slow down the reaction. The order of reactivity is: Methyl halide > Primary halide (1°) > Secondary halide (2°) > Tertiary halide (3°)

2. Substitution Nucleophilic Unimolecular ($S_N1$)

• Kinetics: The reaction rate depends only on the concentration of the alkyl halide (first-order kinetics).
• Mechanism: It is a two-step process.
  • Step 1 (Slow): The C-X bond breaks to form a planar carbocation intermediate. This is the rate-determining step.
  • Step 2 (Fast): The nucleophile attacks the carbocation to form the product.
• Stereochemistry: The planar carbocation can be attacked by the nucleophile from either side with equal probability. This results in a 50:50 mixture of both inverted and retained products. The final mixture is optically inactive and is called a racemic mixture. The process is called racemisation.
• Reactivity Order: The rate depends on the stability of the carbocation intermediate. More stable carbocations form faster. The order of reactivity is: Tertiary halide (3°) > Secondary halide (2°) > Primary halide (1°)
• Allylic and benzylic halides show high reactivity in $S_N1$ reactions because their carbocations are stabilized by resonance.

For a given alkyl group, the reactivity of the halide is R-I > R-Br > R-Cl >> R-F for both $S_N1$ and $S_N2$ reactions, because the C-I bond is the weakest and iodine is the best leaving group.

Stereochemical Aspects of Nucleophilic Substitution

• Optical Activity: The ability of certain compounds to rotate the plane of plane-polarized light.
  • Dextrorotatory (d or +): Rotates light to the right (clockwise).
  • Laevorotatory (l or -): Rotates light to the left (anticlockwise).
• Chirality: An object or molecule that is non-superimposable on its mirror image is called chiral. A carbon atom bonded to four different groups is a chiral center or stereocentre. Chiral molecules are optically active.
• Enantiomers: Stereoisomers that are non-superimposable mirror images of each other. They have identical physical properties but rotate plane-polarized light in opposite directions.
• Racemic Mixture: An equimolar mixture of two enantiomers. It has zero optical rotation.
• Retention of Configuration: The preservation of the spatial arrangement of bonds to a stereocentre during a reaction.
• Inversion of Configuration: The spatial arrangement of bonds is inverted during a reaction.
• Racemisation: The conversion of an enantiomer into a racemic mixture.

Summary of Stereochemistry in Substitution Reactions:

• $S_N2$ reactions of optically active halides proceed with inversion of configuration.
• $S_N1$ reactions of optically active halides proceed with racemisation.

Elimination Reactions

When a haloalkane with a hydrogen atom on the adjacent carbon ($\beta$-hydrogen) is heated with an alcoholic solution of potassium hydroxide (KOH), a molecule of HX is eliminated to form an alkene. This is called $\beta$-elimination or dehydrohalogenation.

• Zaitsev's Rule (or Saytzeff's Rule): If more than one alkene can be formed, the preferred product is the alkene that has a greater number of alkyl groups attached to the doubly bonded carbon atoms (i.e., the more substituted alkene is the major product).

Elimination versus Substitution

Substitution and elimination reactions often compete with each other. The outcome depends on:

• Nature of the alkyl halide: 1° halides prefer $S_N2$, 3° halides prefer $S_N1$ or elimination, and 2° halides can do either.
• Strength and size of the base/nucleophile: A bulky nucleophile will prefer to act as a base and cause elimination.
• Reaction conditions: Higher temperatures favor elimination.

Reaction with Metals

1. Grignard Reagents:
   • Alkyl halides react with magnesium metal in dry ether to form alkyl magnesium halides (RMgX), known as Grignard reagents.
     • $CH_3CH_2Br + Mg \xrightarrow{\text{dry ether}} CH_3CH_2MgBr$
   • Grignard reagents are highly reactive. They react with any source of protons (like water, alcohol, amines) to give hydrocarbons.
     • $RMgX + H_2O \rightarrow RH + Mg(OH)X$
   • Therefore, they must be prepared under anhydrous (dry) conditions.
2. Wurtz Reaction:
   • Alkyl halides react with sodium in dry ether to form hydrocarbons containing double the number of carbon atoms.
     • $2RX + 2Na \xrightarrow{\text{dry ether}} R-R + 2NaX$

Reactions of Haloarenes

Nucleophilic Substitution

Aryl halides are extremely less reactive towards nucleophilic substitution reactions than alkyl halides. This is due to:

1. Resonance Effect: The C-X bond acquires a partial double bond character due to resonance, making it stronger and harder to break.
2. Difference in Hybridisation: The carbon in the C-X bond of a haloarene is $sp^2$ hybridized. This carbon is more electronegative than the $sp^3$ carbon in a haloalkane, so it holds the C-X bond more tightly, making the bond shorter and stronger.
3. Instability of Phenyl Cation: The phenyl cation that would form in an $S_N1$ reaction is highly unstable and not stabilized by resonance.
4. Repulsion: The electron-rich nucleophile is repelled by the electron-rich benzene ring.

• Substitution can occur under drastic conditions (e.g., high temperature and pressure).
• The presence of an electron-withdrawing group (like $-NO_2$) at the ortho and para positions increases the reactivity of haloarenes. This group stabilizes the intermediate carbanion formed during the attack of the nucleophile.

Electrophilic Substitution Reactions

Haloarenes undergo typical electrophilic substitution reactions like halogenation, nitration, sulphonation, and Friedel-Crafts reactions.

• The halogen atom is deactivating towards electrophilic substitution because of its strong electron-withdrawing inductive effect (-I effect). This makes haloarenes less reactive than benzene.
• However, the halogen atom is ortho, para-directing. This is because the resonance effect (+R effect) increases the electron density at the ortho and para positions, directing the incoming electrophile to these positions.
• Reactivity is controlled by the stronger inductive effect, while orientation is controlled by the resonance effect.

Examples:

• Halogenation: Chlorobenzene reacts with $Cl_2$ in the presence of anhydrous $FeCl_3$ to give 1,2-Dichlorobenzene (minor) and 1,4-Dichlorobenzene (major).
• Nitration: Chlorobenzene reacts with conc. $HNO_3$ and conc. $H_2SO_4$ to give 1-Chloro-2-nitrobenzene (minor) and 1-Chloro-4-nitrobenzene (major).
• Sulphonation: Chlorobenzene reacts with conc. $H_2SO_4$ to give 2-Chlorobenzenesulphonic acid (minor) and 4-Chlorobenzenesulphonic acid (major).
• Friedel-Crafts Reaction: Chlorobenzene reacts with $CH_3Cl$ in the presence of anhydrous $AlCl_3$ to give 1-Chloro-2-methylbenzene (minor) and 1-Chloro-4-methylbenzene (major).

Solution

Chlorine influences the benzene ring in two ways:

1. Inductive Effect (-I): Being electronegative, chlorine withdraws electrons from the ring, which deactivates it and destabilizes the intermediate carbocation formed during substitution. This effect is strong.
2. Resonance Effect (+R): Through its lone pairs, chlorine can donate electron density to the ring, which tends to stabilize the carbocation. This effect is more pronounced when the attack is at the ortho and para positions.

The inductive effect is stronger than resonance, causing net deactivation of the ring (making the reaction slower than with benzene). However, the resonance effect opposes the inductive effect for attack at the ortho and para positions, making these positions less deactivated than the meta position. Therefore, reactivity is controlled by the stronger inductive effect, but the orientation of the incoming group is controlled by the resonance effect, making halogens ortho-, para- directing.

Reaction with Metals

1. Wurtz-Fittig Reaction:
   • A mixture of an alkyl halide and an aryl halide reacts with sodium in dry ether to form an alkylarene.
2. Fittig Reaction:
   • Two molecules of an aryl halide react with sodium in dry ether to form a biaryl compound (e.g., biphenyl).

Polyhalogen Compounds

These are carbon compounds containing more than one halogen atom.

Dichloromethane (Methylene chloride, $CH_2Cl_2$)

• Uses: Solvent, paint remover, propellant in aerosols, drug manufacturing.
• Harmful Effects: Harms the central nervous system, can impair hearing and vision, cause dizziness and nausea. Direct contact can burn skin and eyes.

Trichloromethane (Chloroform, $CHCl_3$)

• Uses: Solvent for fats and alkaloids, production of the refrigerant Freon R-22.
• Harmful Effects: Depresses the central nervous system. Was used as an anesthetic but is now replaced by safer alternatives. Chronic exposure can damage the liver and kidneys.
• Important Reaction: Chloroform is slowly oxidized by air in the presence of light to form an extremely poisonous gas, phosgene ($COCl_2$).
  • $2CHCl_3 + O_2 \xrightarrow{\text{light}} 2COCl_2 + 2HCl$
  • To prevent this, chloroform is stored in dark, completely filled bottles to keep out air and light.

Triiodomethane (Iodoform, $CHI_3$)

• Uses: Was used as an antiseptic. Its antiseptic properties are due to the liberation of free iodine, not iodoform itself.
• It has been replaced by other formulations due to its objectionable smell.

Tetrachloromethane (Carbon tetrachloride, $CCl_4$)

• Uses: Manufacturing refrigerants and propellants, solvent use. Was used as a cleaning fluid and in fire extinguishers.
• Harmful Effects: Causes liver cancer in humans. Exposure can lead to dizziness, nausea, and permanent nerve damage. It can cause irregular heartbeat.
• Environmental Effect: When released into the air, it rises to the stratosphere and contributes to the depletion of the ozone layer.

Freons

• Definition: Chlorofluorocarbon (CFC) compounds of methane and ethane.
• Properties: Extremely stable, unreactive, non-toxic, non-corrosive, and easily liquefiable gases. Freon 12 ($CCl_2F_2$) is very common.
• Uses: Aerosol propellants, refrigeration, and air conditioning.
• Environmental Effect: Freons diffuse into the stratosphere where they initiate radical chain reactions that deplete the natural ozone layer.

p,p'-Dichlorodiphenyltrichloroethane (DDT)

• History: The first chlorinated organic insecticide, its effectiveness was discovered by Paul Muller in 1939.
• Uses: Was used extensively after WWII to combat malaria-spreading mosquitoes and typhus-carrying lice.
• Problems:
  • Many insect species developed resistance.
  • It is highly toxic to fish.
  • DDT is chemically stable and fat-soluble, so it is not easily metabolized by animals. It gets deposited in fatty tissues and builds up in the food chain (bioaccumulation).
• Its use was banned in the United States in 1973 but continues in some parts of the world.