Ch 06 - Haloalkanes and Haloarenes12th Chemistry

Structural Distinction:

• Allylic Halides: The halogen is bonded to an $sp^3$-hybridized carbon atom that is immediately adjacent to a carbon-carbon double bond (C=C).
• Vinylic Halides: The halogen is bonded directly to an $sp^2$-hybridized carbon atom of a carbon-carbon double bond (C=C).

Substrate Behavior:

• Allylic halides easily undergo nucleophilic substitution due to resonance stabilization of the intermediate carbocation.
• Vinylic halides are extremely unreactive towards nucleophilic substitution due to the partial double-bond character of the C-X bond (arising from resonance).

Definitions:

• Geminal Dihalides (Gem-dihalides): Both halogen atoms are attached to the same carbon atom.
• Vicinal Dihalides (Vic-dihalides): The two halogen atoms are attached to adjacent carbon atoms.

Naming Conventions:

• Gem-dihalides are commonly named as alkylidene halides (e.g., Ethylidene chloride).
• Vic-dihalides are commonly named as alkylene dihalides (e.g., Ethylene dichloride).

Dipole Moment Anomaly:
Dipole moment ($\mu$) is the product of charge magnitude ($q$) and internuclear distance ($d$).

• Electronegativity: Fluorine is more electronegative than Chlorine, creating a larger partial charge ($q$).
• Bond Length: However, the C-Cl bond is significantly longer than the C-F bond due to the larger atomic radius of Chlorine.
• Result: The increase in the internuclear distance ($d$) in C-Cl more than compensates for the smaller charge difference, making the overall dipole moment of $CH_3Cl$ ($1.860 \, D$) strictly greater than that of $CH_3F$ ($1.847 \, D$).

Variables & Reagents:

• R-OH = Alcohol
• SOCl₂ = Thionyl chloride
• R-Cl = Alkyl chloride

Conditions/Notes:

• Why Preferred? This is the most preferred method because the two byproducts ($SO_2$ and $HCl$) are escapable gases. This leaves behind pure alkyl chloride without the need for complex separation processes.

1. Effect of Halogen Size (Mass):

• For the same alkyl group, boiling points strictly increase in the order: R-F < R-Cl < R-Br < R-I.
• Reason: As halogen size and mass increase, the magnitude of van der Waals (London dispersion) forces increases.

2. Effect of Isomeric Branching:

• For isomeric haloalkanes, the boiling point decreases with an increase in branching.
• Reason: Branching makes the molecule more spherical, reducing the surface area of contact, which physically weakens the intermolecular van der Waals forces.

Variables & Byproducts:

• PCl₃ (Phosphorus trichloride): Yields $H_3PO_3$ (Phosphorous acid) as a byproduct. Requires 3 moles of alcohol.
• PCl₅ (Phosphorus pentachloride): Yields $POCl_3$ (Phosphorus oxychloride) and $HCl$ as byproducts.

Conditions/Notes:

• These reactions are standard laboratory methods for converting hydroxyl groups into chlorides.

Immiscibility Explanation:

• Energy Barrier: To dissolve haloalkanes in water, thermodynamic energy is required to overcome the attractions between the haloalkane molecules themselves and to break the strong hydrogen bonds between water molecules.
• Weak New Bonds: The new dipole-dipole attractions established between the haloalkane and water molecules are much weaker than the original hydrogen bonds in water.
• Thermodynamic Result: Less energy is released when new attractions form than is required to break the original ones, making them largely insoluble in water (but highly soluble in non-polar organic solvents).

Density Trends:
Bromo, iodo, and polychloro derivatives of hydrocarbons are generally heavier than water. Density strictly increases with:

1. An increase in the number of carbon atoms in the main chain.
2. An increase in the number of halogen atoms attached.
3. An increase in the atomic mass of the halogen atom (e.g., $R-I > R-Br > R-Cl$).

Variables & Conditions:

• Reactant: Propene (asymmetrical alkene)
• Reagent: Hydrogen halide (HBr)
• Product: 2-Bromopropane

Conditions/Notes:

• Markovnikov's Rule: The negative part of the addendum ($Br^-$) gets attached to that carbon atom of the double bond which possesses the lesser number of hydrogen atoms.
• If organic peroxides are present, Anti-Markovnikov addition occurs instead (yielding 1-Bromopropane).

Hybridization Difference:

• Chlorobenzene: The carbon atom attached to Chlorine is $sp^2$ hybridized. $sp^2$ carbons have more s-character, making them more electronegative. This physically decreases the electronegativity difference between Carbon and Chlorine, resulting in a lower dipole moment.
• Cyclohexyl chloride: The carbon attached to Chlorine is $sp^3$ hybridized (less s-character, less electronegative), creating a more polar C-Cl bond and a higher dipole moment.

Note: Resonance in chlorobenzene also imparts partial double bond character, shortening the bond length ($d$) and further reducing the dipole moment ($\mu = q \times d$).

Variables & Units:

• R-X = Alkyl chloride or Alkyl bromide (X = Cl, Br)
• NaI = Sodium Iodide
• R-I = Alkyl Iodide

Conditions/Notes:

• Solvent: Must be dry acetone.
• Le Chatelier's Principle: $NaCl$ and $NaBr$ are less soluble in dry acetone compared to $NaI$. They precipitate out, driving the forward reaction.

Variables:

• R-X = Alkyl chloride or bromide (X = Cl, Br)
• AgF = Silver Fluoride (Metallic fluoride)

Conditions/Notes:

• It is the best method to synthesize alkyl fluorides.
• Instead of $AgF$, other metallic fluorides like $Hg_2F_2$, $CoF_2$, or $SbF_3$ can also be used.

Variables:

• $Ar-N_2^+ X^-$ = Aryl diazonium salt (prepared by reacting aniline with $NaNO_2$ and $HX$ at 273-278 K).
• $Cu_2X_2$ = Cuprous halide catalyst (where X = Cl, Br).

Conditions/Notes:

• Nitrogen gas escapes, pushing the reaction forward.
• For synthesizing Aryl Iodides, cuprous halide is not required; simply shaking the diazonium salt with Potassium Iodide (KI) is sufficient.

The Oxidizing Problem:

• The reaction of KI with an acid initially produces Hydrogen Iodide ($HI$), which is meant to substitute the alcohol.
• $H_2SO_4$ is a strong oxidizing agent. It prematurely oxidizes the generated $HI$ into elemental iodine gas ($I_2$) before it can ever react with the alcohol.
• The Fix: A non-oxidizing acid like 95% Phosphoric Acid ($H_3PO_4$) must be used instead to ensure $HI$ successfully substitutes the hydroxyl group.

The Problem with Free Radical Halogenation:

• Complex Mixtures: Free radical halogenation lacks selectivity and produces a complex statistical mixture of isomeric mono- and polyhaloalkanes.
• Separation Difficulty: These isomers typically have very similar boiling points, making them extremely difficult to separate into pure individual compounds via fractional distillation.
• Low Yield: Consequently, the practical yield of any single specific halogenated compound is very low.

Definition:
Nucleophiles that possess two distinct nucleophilic centers through which they can attack a substrate are called ambident nucleophiles.

Example: Cyanide / Isocyanide

• The cyanide group is a resonance hybrid: $[:C \equiv N:]^- \leftrightarrow [:C=N:]^-$.
• Attack through Carbon: Yields alkyl cyanides (nitriles). Occurs with $KCN$ because it is predominantly ionic, leaving the carbon lone pair free to attack.
• Attack through Nitrogen: Yields isocyanides. Occurs with $AgCN$ because the Ag-C bond is predominantly covalent, leaving only the Nitrogen lone pair free to attack.

(Another classic example is the nitrite ion $NO_2^-$, which can attack via N to form nitroalkanes or via O to form alkyl nitrites).

Variables & Conditions:

• Reagent: Alcoholic KOH (Base, heated)
• Reaction Type: $\beta$-elimination (Dehydrohalogenation)

Saytzeff's Rule:

• "In dehydrohalogenation reactions, the preferred product is that alkene which has the greater number of alkyl groups attached to the doubly bonded carbon atoms."
• For example, 2-bromobutane yields But-2-ene (81%) over But-1-ene (19%).

Kinetics:

• Bimolecular: The rate depends strictly on the concentration of BOTH the alkyl halide substrate and the incoming nucleophile. (Rate = $k[R-X][Nu^-]$).
• Concerted Step: Bond breaking (C-X) and bond forming (C-Nu) occur exactly simultaneously in a single, concerted step.

Transition State:

• Forms an unstable, non-isolable, high-energy transition state where the central Carbon is simultaneously partially bonded to 5 atoms/groups.

Stereochemistry:

• Because the nucleophile attacks from the backside (180° opposite to the leaving group to avoid electron repulsion), it results in a 100% inversion of configuration (Walden Inversion), structurally analogous to an umbrella flipping inside out in strong wind.

Variables:

• R-X = Alkyl halide
• Mg = Magnesium metal
• R-Mg-X = Grignard Reagent (Organometallic compound)

Boundary Conditions / Exceptions:

• Must be strictly prepared under anhydrous conditions (dry ether).
• Why? Grignard reagents are highly reactive. If even a trace of water is present, it acts as a proton donor, reacting rapidly to form an alkane: $R-Mg-X + H_2O \rightarrow R-H + Mg(OH)X$.

Reactivity Order:

• Methyl > Primary (1°) > Secondary (2°) > Tertiary (3°)
• Order: $CH_3X > 1^\circ > 2^\circ > 3^\circ$

Primary Factor: Steric Hindrance

• In an $S_N2$ reaction, the incoming nucleophile must physically approach the central carbon from the backside.
• Bulky alkyl groups structurally block this approach.
• Tertiary halides possess three bulky alkyl groups causing massive steric hindrance, rendering them practically inert towards $S_N2$ reactions.

Variables:

• R-X = Alkyl Halide
• Na = Sodium metal
• R-R = Alkane with double the number of carbon atoms.

Conditions/Notes:

• The reaction is carried out in dry ether.
• It is an excellent method for preparing symmetrical alkanes (even number of carbon atoms).

Kinetics & Steps:

• Unimolecular: Rate depends ONLY on the concentration of the substrate. (Rate = $k[R-X]$).
• Two-Step Process:
  1. Slow, rate-determining heterolytic cleavage of the C-X bond to form a carbocation.
  2. Fast, rapid attack by the nucleophile on the carbocation.

Intermediate:

• Forms a distinct, planar carbocation intermediate ($sp^2$ hybridized).

Stereochemistry:

• Because the carbocation is entirely planar, the nucleophile has an equal probability of attacking from either face (front or back).
• This results in a 50:50 mixture of retention and inversion, leading to Racemization (yielding an optically inactive racemic mixture if the starting material was chiral).

Reactivity Order:

• Tertiary (3°) > Secondary (2°) > Primary (1°) > Methyl

Primary Factor: Carbocation Stability

• The rate-determining (slowest) step is the formation of the carbocation intermediate.
• Tertiary carbocations are highly stabilized by the +I (inductive) effect of three surrounding alkyl groups and extensive hyperconjugation.
• Note: Allylic and Benzylic halides show exceptionally high reactivity towards $S_N1$ because their resulting carbocations are highly stabilized by resonance.

Variables:

• Ar-X = Aryl Halide
• R-X = Alkyl Halide
• Ar-R = Alkylarene (Wurtz-Fittig Product)
• Ar-Ar = Diaryl / Biphenyl (Fittig Product)

Distinctions:

• Wurtz-Fittig: Couples one Aryl ring with one Alkyl chain.
• Fittig: Couples two Aryl rings together to form diphenyls.

Chirality:

• An object or molecule that is strictly non-superimposable on its mirror image is called chiral (e.g., left and right hands).
• In organic chemistry, a carbon atom bonded to four entirely different groups forms a stereocenter (asymmetric carbon), rendering the entire molecule chiral.

Enantiomers:

• Stereoisomers that are non-superimposable mirror images of each other are called enantiomers.
• They possess identical physical properties (boiling point, refractive index) but strictly rotate plane-polarized light in opposite directions (one dextrorotatory, one laevorotatory).

If an optically active starting material undergoes substitution:

• Retention: The spatial arrangement of bonds to the asymmetric center is completely preserved. The nucleophile occupies the exact same relative position as the departing leaving group.
• Inversion: The nucleophile attaches from the direct opposite side of the leaving group (backside attack). The entire 3D configuration turns 'inside out' (Walden Inversion).
• Racemization: A 50:50 equimolar mixture of two enantiomers (both retention and inversion products) is formed. The resulting mixture has zero net optical rotation because the optical rotation of one isomer perfectly cancels the other.

Variables & Reagents:

• $C_6H_6$ = Benzene
• $FeBr_3$ (or Fe shavings): A Lewis acid catalyst required to generate the active electrophile ($Br^+$).

Boundary Conditions:

• The reaction must be carried out in the dark (or absence of UV light).
• Why? If light is present, a free-radical chain reaction occurs, which would lead to substitution on alkyl side-chains (if present) rather than the aromatic ring.

Variables:

• R-X = Alkyl halide (Substrate)
• $R'-O^-Na^+$ = Sodium alkoxide (Nucleophile)
• R-O-R' = Ether

Conditions/Notes:

• This reaction proceeds via the $S_N2$ mechanism.
• To achieve high yields, the alkyl halide (R-X) must be primary (1°). If a secondary or tertiary halide is used, elimination dominates over substitution, yielding alkenes instead of ethers.

Variables & Mechanism:

• $KNO_2$ (Potassium Nitrite): The bond is predominantly ionic. The oxygen atom is free to attack, yielding Alkyl Nitrites ($R-O-N=O$).
• $AgNO_2$ (Silver Nitrite): The bond is predominantly covalent. The lone pair on the nitrogen atom acts as the attacking center, yielding Nitroalkanes ($R-NO_2$).

(This mirrors the exact ambident logic of KCN forming cyanides vs AgCN forming isocyanides.)

Variables & Reagents:

• $R-NH_2$ = Primary amine (Aliphatic or Aromatic, e.g., Aniline $C_6H_5NH_2$)
• $CHCl_3$ = Chloroform
• R-NC = Alkyl/Aryl Isocyanide (Carbylamine)

Conditions/Notes:

• The reaction requires heating ($\Delta$) with alcoholic KOH.
• The product, Isocyanide, has an extremely foul, pungent smell.
• This is a definitive chemical test to detect the presence of 1° amines.

Four Main Reasons:

1. Resonance Effect: Lone pairs on the halogen delocalize into the benzene ring. This gives the C-X bond a partial double bond character, making it significantly shorter and harder to break.
2. Difference in Hybridization: The carbon attached to the halogen in haloarenes is $sp^2$ hybridized (more electronegative, holds electron pairs tighter) versus $sp^3$ in haloalkanes.
3. Instability of Phenyl Cation: An $S_N1$ mechanism is entirely ruled out because the resulting phenyl cation is highly unstable.
4. Electronic Repulsion: The electron-rich nucleophile is electrostatically repelled by the high electron density of the arene $\pi$-cloud.

Dichloromethane (Methylene Chloride, $CH_2Cl_2$):

• Uses: Highly effective solvent, paint remover, and aerosol propellant.
• Hazards: Harms the human central nervous system. Low levels impair vision/hearing; high levels cause dizziness and numbness. Burns the cornea upon direct contact.

Carbon Tetrachloride ($CCl_4$):

• Uses: Manufacture of refrigerants (Freons) and aerosols; used as a pharmaceutical solvent.
• Hazards: Major contributor to Ozone Depletion in the stratosphere. In humans, it causes liver cancer, dizziness, and permanent nerve cell damage.

The Dual Nature of Halogens:

1. Deactivation (-I Effect): Halogens are more electronegative than carbon, so they physically withdraw electron density from the benzene ring via the strong Inductive Effect (-I). This makes the ring less reactive than pure benzene.
2. Directive Influence (+R Effect): Simultaneously, halogens possess lone pairs that they donate back into the ring via the Resonance Effect (+R). This resonance specifically localizes negative charge density at the ortho and para positions, directing incoming electrophiles there.

Conclusion: The -I effect controls the overall rate (deactivation), while the +R effect strictly controls the orientation (o/p directing).

Reagents & Mechanism:

1. First Dehydrohalogenation: Alcoholic KOH (heated) removes one equivalent of $HBr$ to form a vinyl halide ($CH_2=CHBr$).
2. Second Dehydrohalogenation: Vinyl halides are unreactive. A much stronger base, Sodamide ($NaNH_2$) in liquid $NH_3$, is required to rip off the second $HBr$ equivalent and form the alkyne triple bond.

1. Dichloromethane ($CH_2Cl_2$): Harms the human central nervous system. Low levels impair vision/hearing; high levels cause dizziness and numbness.
2. Carbon Tetrachloride ($CCl_4$): Causes liver cancer and permanent nerve cell damage in humans. Released into the air, it is a major contributor to Ozone Depletion.
3. Freons (CFCs, e.g., $CF_2Cl_2$): Once widely used as refrigerants. They are unreactive until they reach the stratosphere, where UV radiation triggers radical reactions that severely deplete the Ozone Layer.
4. DDT: A chlorinated insecticide that is highly toxic to fish and extremely fat-soluble. It undergoes biomagnification (accumulating in the fatty tissues of top predators) because it is not rapidly metabolized.