Organic Halides Notes

and Haloarenes

Classification

• Based on the type of carbon to which the halogen is attached:

  • Alkyl halides (R-X)

  • Phenyl halides (Ph-X)

Types of Carbon

• Alkyl halides: Halogen is attached to an sp^3 hybridized carbon.

• Phenyl halides: Halogen is directly attached to a benzene ring.

Examples of Carbon Types

• Allylic: -CH=CH-CH_2-X

  • The carbon adjacent to a double bond.

• Vinylic: CH_2=CH-X

  • The carbon directly involved in a double bond (sp^2 hybridized).

• Benzylic: A phenyl group attached to a carbon that contains a halogen. (Ph-CH_2-X)

Examples

• Vinylic chloride: C=CH-CH_3

• Allylic halide: CH=CH-CH2-CH2-X

Reactions and Preparations of Haloalkanes

From Alcohols

• Alcohols react with PCl5, PCl3, or SOCl_2 to form alkyl chlorides.

  • R-OH + PCl5 \rightarrow R-Cl + HCl + POCl3

    • Not all PCl_5 molecules react due to steric hindrance.

    • Reactivity order of axial vs. equatorial chlorine.

  • R-OH + PCl3 \rightarrow R-Cl + H3PO_3

  • 3 R-OH + PBr3 \rightarrow 3 R-Br + H3PO_3

  • R-OH + SOCl2 \rightarrow R-Cl + SO2 + HCl (Darzen process)

    • This is a favorable reaction because the byproducts are gases and escape the system.

• Using Red P + Br2 or Red P + I2:

  • R-OH + Red P + Br2 \rightarrow R-Br + H3PO_3

  • R-OH + Red P + I2 \rightarrow R-I + H3PO_3

    • A reducing agent is needed to prevent iodine from leaving the group.

    • R-I + HI \rightarrow R-H + I_2

With Hydrohaloacids (HX)

• Alcohols react with hydrohaloacids to form alkyl halides.

  • R-OH + HCl \xrightarrow{\Delta, anhyd. ZnCl2} R-Cl + H2O

  • R-OH + HBr \xrightarrow{anhyd. ZnCl2} R-Br + H2O

  • R-OH + HI \rightarrow R-I + H_2O

  • R-I + HI \rightarrow R-H + I_2

Mechanism with HCl

• R-OH + HCl \xrightarrow{anhyd. ZnCl2} R-Cl + H2O

  • HCl \rightleftharpoons H^+ + Cl^- (electrophile and nucleophile)

  • R-OH + H^+ \rightarrow R-OH_2^+ (LA = Lewis Acid)

  • R^+ + H2O \rightarrow R-OH2^+

  • Function of anhyd. ZnCl2 to absorb H2O

Reactions That Don't Occur

• R-OH + NaCl \nrightarrow R-Cl + NaOH (No reaction)

  • NaCl \rightleftharpoons Na^+ + Cl^-

Borodine-Hunsdiecker Reaction

• Silver salts of monocarboxylic acids react with Br2 in the presence of CCl4 to form alkyl bromides with one carbon less.

  • R-COOAg + Br2 \xrightarrow{CCl4} R-Br + CO_2 + AgBr

Mechanism

• Br_2 \rightarrow 2Br (homolytic fission)

• R-COOAg + Br \rightarrow R-COO + AgBr

• R-COO \rightarrow R + CO_2

  • Minor products: ester (R-CO-O-R) and alkane (R-R)

  • Radical + Bromine = Alkyl Bromide (Main product)

• R + Br \rightarrow R-Br

Halide Exchange Reactions

Finkelstein Reaction

• Alkyl chlorides react with NaI in dry acetone to form alkyl iodides.

  • R-Cl + NaI \xrightarrow{dry acetone} R-I + NaCl

  • The function of dry acetone is to enhance the polarity and nucleophilicity of I^- by ion-dipole interaction.

Swartz Reaction

• Alkyl halides are heated with AgF, Hg2F2, or SbF_3 to form alkyl fluorides.

  • 2R-Cl + Hg2F2 \rightarrow 2R-F + Hg2Cl2

  • 3R-Cl + SbF3 \rightarrow 3R-F + SbCl3

From Alkenes

• Addition of HBr:

  • According to Markovnikov's rule:

    • CH3-CH=CH2 + HBr \rightarrow CH3-CHBr-CH3 (Electrophilic addition)

  • In the presence of R2O2:

    • CH3-CH=CH2 + HBr \xrightarrow{R2O2} CH3-CH2-CH_2-Br (Free radical, Anti-Markovnikov's rule)

• Bromination of alkanes using NBS (N-bromosuccinimide): This replaces allylic hydrogens with bromine.

  • NBS + CH3-CH=CH2 \rightarrow Br-CH2-CH=CH2

    • NBS facilitates free radical substitution in the allylic position.

Halogenation of Alkanes

• Free radical substitution reaction:

  • CH4 + Cl2 \xrightarrow{h\nu} CH_3-Cl + HCl (E-R = Electrophilic Reagent)

  • CH3-CH2-CH3 + Cl2 \xrightarrow{h\nu} CH3-CHCl-CH3

Preparation of Haloarenes

Halogenation of Benzene

• Electrophilic substitution reaction:

  • Benzene + Cl2 \xrightarrow{FeCl3} Chlorobenzene + HCl

  • Benzene + Br_2 \xrightarrow{Fe} Bromobenzene + HBr

Sandmeyer's Reaction

• Conversion of benzenediazonium chloride to halobenzene using suitable reagents.

• Aniline \xrightarrow{NaNO2 + HX, 0-5^\circ C} Benzenediazonium Chloride \xrightarrow{CuX} Halobenzene + N2

  • From HCl: Benzenediazonium Chloride \xrightarrow{Cu2Cl2} Chlorobenzene + N_2

Gattermann Reaction

• Similar to Sandmeyer's, but uses Cu + HX instead of Cu2X2.

  • Benzenediazonium Chloride \xrightarrow{Cu + HCl} Chlorobenzene + N_2

Balz-Schiemann Reaction

• Preparation of aryl fluorides:

• Benzenediazonium Chloride \xrightarrow{HBF4} Aryl-N2^+BF4^- \xrightarrow{\Delta} Aryl-F + N2 +BF_3

Properties of Haloalkanes and Haloarenes

Reactivity

• Factors affecting reactivity:

  • Hybridization:

    • Bond energy is higher for sp^2 hybridized carbon (as in aryl halides) compared to sp^3 hybridized carbon (as in alkyl halides).

  • Resonance:

    • Due to resonance in aryl halides, a partial double bond character is formed between the carbon and halogen, increasing the bond energy and decreasing reactivity.

  • Dipole Moment:

    • Polarity and reactivity increase with dipole moment (\mu = e \times l).

    • Since the C-X bond length is greater in alkyl halides, they are more polar and reactive than aryl halides.

Comparing Hydrolysis Rates

• Cyclohexyl chloride hydrolyzes faster than chlorobenzene.

• Resonance forms of chlorobenzene stabilize the C-Cl bond.

Physical Properties

• As surface area increases, the magnitude of van der Waals forces increases, and so do boiling point and osmotic pressure; volatility decreases.

Reactions with KCN and AgCN

• Ambident Nucleophiles: CN can form both cyanide and isocyanide.

  • KCN (ionic) vs. AgCN (covalent):

    • R-X + KCN \rightarrow R-CN + KX (Alkyl cyanide)

    • R-X + AgCN \rightarrow R-NC + AgX (Alkyl isocyanide)

• Explanation:

  • KCN dissociates into K^+ and CN^-.

    • The alkyl group combines with the carbon end.

  • AgCN is covalent and the alkyl group combines with the nitrogen end to produce isocyanide.

Reactions with KNO2 and AgNO2

• R-X + KNO_2 \rightarrow R-O-N=O (Alkyl nitrite)

• R-X + AgNO2 \rightarrow R-NO2 (Nitroalkane)

Reactions with Aqueous and Alcoholic KOH

• Aqueous KOH (KOH + H2O): Nucleophilic substitution (SN).

• Alcoholic KOH (KOH + EtOH): Elimination reaction.

• Aqueous KOH is more nucleophilic and less basic than alcoholic KOH.

Condition A (SN)

• Nu attack occurs more.

Nucleophilic Substitution (S_N) Reactions

Conditions

• The nucleophilicity of the attacking group should be greater than the leaving group.

Mechanisms

• S_N2 (Bimolecular):

  • Rate = k[CH_3-X][OH^-]

  • Molecularity = 2

  • Inversion of configuration (Walden inversion).

• S_N1 (Unimolecular):

  • Rate = k[alkyl halide]

Types of S_N Reactions

• S_N1: Forms a carbocation intermediate.

  • Favored in polar protic solvents.

• S_N2: Occurs via a transition state.

  • Favored in polar aprotic solvents.

  • Backside attack.

• S_Ni: Intramolecular nucleophilic substitution (e.g., Darzen process).

Factors Affecting S_N1 Reactions

• Stability of carbocation (3° > 2° > 1°).

• Leaving group ability.

Examples

• Alkaline hydrolysis of tert-butyl bromide occurs via S_N1.

• Alkaline hydrolysis of ethyl bromide occurs via S_N2.

Stereochemistry of S_N Reactions

• Optical isomers: Rotate plane polarized light.

  • Dextrorotatory (d-form): (+)

  • Levorotatory (l-form): (-)

  • Racemic mixture: 50:50 mixture of enantiomers (optically inactive).

• S_N2: Inversion of configuration.

  • S_N1: Racemization.

Meso Compounds

• Have chiral centers but are optically inactive due to an internal plane of symmetry.

  • Total number of optical isomers = 2^n (where n is the number of chiral carbons).

Fischer Projections

• Two-dimensional representation of a 3D molecule.

• Horizontal lines: Substituents above the plane.

• Vertical lines: Substituents below the plane.

R/S Nomenclature

• Cahn-Ingold-Prelog (CIP) rules:

  • Assign priority based on atomic mass.

  • If the 4th priority group (lowest priority) is on the vertical line, the configuration is as determined.

  • If the 4th priority group is on the horizontal line, the determined configuration must be reversed.

Elimination Reactions

Reaction with Alc. KOH

• CH3-CH2-Cl + alc. KOH \rightarrow CH2=CH2

  • More basic but less nucleophilic.

  • Forms alkene.

Types of Elimination Reactions

• E1 (Unimolecular elimination).

• E2 (Bimolecular elimination):

• E1cB (Unimolecular elimination via conjugate base).

Reaction with Dry Ag_2O

• Forms ether.

Reactions with Other Reagents

• R-X + NaSH \rightarrow R-SH (Thioalcohol).

• R-X + Na_2S \rightarrow R-S-R (Thioether).

• R-X + NaN3 \rightarrow R-N3 (Alkyl azide).

• R-X + R'ONa \rightarrow R-O-R' (Williamson synthesis, ether).

• Reaction with Ammonia (Hoffmann ammonolysis):
  R-X + NH3 -> R-NH2

• Reaction with Sodium Acetylide:
  H-C≡CNa + R-X -> H-C≡C-R

Wurtz Reaction

• R-X + Na \xrightarrow{dry ether} R-R

Grignard Reagent

• R-X + Mg \xrightarrow{dry ether} R-Mg-X

Fittig Reaction

• Ar-X + Na \xrightarrow{dry ether} Ar-Ar

Wurtz-Fittig

• \text{Wurtz reaction} > \text{Wurtz-Fittig} > \text{Fittig}

Ullmann Reaction

• Ar-X + Cu \rightarrow Ar-Ar

Di-haloalkanes

• Geminal: 2 halogens on the same carbon.

Preparation of Chloroform ($(CHCl_3)$)

• From Ethyl Alcohol and Acetone using Bleaching Powder:

• Chloroform is a colourless, volatile liquid.

Haloform Reaction

• From Ketomethyl Groups (CH3-C=O) or Potential Ketomethyl Groups in the Presence of Base Reacts with Halogen to form CHX3.

Mechanism

• Base-Catalyzed Alpha-Halogenation: Enolates are intermediates in the halogenation, deuterium exchange, and racemization of ketones and are formed more readily when base is used rather than acid. Once a monohalogenated product forms, it forms a similar enolate to get to the dihalogenated product through essentially the same mechanism and so on and so forth until a trihalogenated product is formed.

Properties of chloroform

Acidity

• Chloroform is acidic due to the -I effect of three chlorine atoms.

Oxidation & how to store chloroform in laboratory

• Oxidation in the presence of air and sunlight converts chloroform into phosgene (carbonyl dichloride). Is placed into a brown bottle while adding 1%-2% ethanol.

• CHCl3 + \frac{1}{2} O2 \rightarrow COCl_2 + HCl

  • To detect phosgene add silver nitrate (AgNO3). A white precipitate, insoluble in HNO3 but soluble in NH_4OH, indicates phosgene.

Reaction with Ag/Cu metal with nitric acid

• Reaction with Silver Metal: Reduces halo to alkyne chain.
  [1 marks]

• Reaction with Nitric Acid: Produces chloropicrin, a potent insecticide.

Reduction of Chloroform

• Reduction forms dichloromethane and methyl chloride
  CHCl+232 + dilHel\rightarrow CH C

• H { 2 }+HClZn + dil Hill\rightarrow CHCl+ 4
  +2HClZn+H2OPCH4+ 3H _ a

Properties of Haloarenes

Reaction with Chloral

• 2 Ph-Cl + Cl3C-CHO \rightarrow (ClC6H4)2CHCCl_3$$ (DDT)

Electrophilic Substitution

• Halobenzenes are ortho-para directing due to resonance but are deactivating.
  Reactions and directing effects are related with the location for the upcoming addition.

Chlorination