Untitled Quiz

Haloalkanes (Structure and Reactivity)

• Haloalkanes, also known as alkyl halides, are organic compounds containing a halogen atom (F, Cl, Br, or I) covalently bonded to an sp³ hybridized carbon. The general formula is R-X, where R represents the organic framework and X represents the halogen.

Structure

• Haloalkanes are named as substituents, akin to alkyl sidechains.
• Halogen substituents are named as fluoro-, chloro-, bromo-, or iodo-.
• The numbering system should prioritize the lowest possible number for the first substituent.
• Named in alphabetical order with other substituents.
• Reactivity is driven by the nature of the C-X bond.

Nomenclature

• Halogen groups are named as substituents, similar to alkyl sidechains.
• Examples of substituent names include fluoro-, chloro-, bromo-, and iodo-.
• Numbering should give the first substituent the lowest possible number.
• Listing in alphabetical order with other substituents.

Common Haloalkanes

• Many polyhaloalkanes are used as solvents.
• They are often referred to by their common/trivial names within the brackets.
  • Examples include dichloromethane (methylene chloride), trichloromethane (chloroform), 1,1,1-trichloroethane (methyl chloroform), and trichloroethylene (trichlor).

Freons and Alternatives

• Freons are chlorofluorocarbons (CFCs) that were widely used.
• Less ozone-depleting alternative compounds are available such as hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs).

Reactivity: Substitution & Elimination

• Two key reaction types are nucleophilic substitution (replacing a halogen with a nucleophile) and β-elimination (losing a halogen and an adjacent hydrogen to form a C-C π-bond).

Nucleophilic Substitutions

• Substitution happens on the sp³ hybridized carbon atom.
• The halogen atom acts as the leaving group.
• Halides are good leaving groups forming stable anions .
• The carbon atom is electrophilic due to the polarity of the C-X bond.
• Nucleophiles, often anions, will attack this carbon.
• Many types of functional groups can be produced from different nucleophiles.

SN2 Mechanism

• At one extreme, C-X and C-Nu bond breaking and forming are simultaneous in one step.
• Designated SN2 (substitution, nucleophilic, bimolecular).
• Rate is directly proportional to the concentration of both haloalkane and nucleophile ([R-X][Nu:]).
• Inversion will occur in stereochemistry.

SN1 Mechanism

• Two-step mechanism:
  • Step 1 (rate-determining): C-X bond breaks forming a carbocation intermediate plus a halide ion.
  • Step 2: Nucleophile reacts with the carbocation to form a new C-Nu bond.
• Designated SN1 (substitution, nucleophilic, unimolecular).
• Rate depends only on the concentration of haloalkane ([R-X]).
• Racemization will occur in stereochemistry.
• Carbocation rearrangements are possible.

SN1 Carbocation Rearrangements

• Carbocation rearrangements are possible, often to more stable 3° carbocations before attack by nucleophile.

Stereochemistry

• SN1 reactions at stereocenters lead to racemic mixtures.
• SN2 reactions at stereocenters lead to inverted stereochemistry.

SN1 vs. SN2 Mechanisms

• Factors that affect the rate of the reaction including the structure of the nucleophile, the haloalkane, the leaving group, and the solvent.

Nucleophilicity

• A kinetic property related to how nucleophiles influence the rate of an SN2 reaction with a reference haloalkane in standard conditions .
• Size, charge, and electronegativity of the nucleophilic atom influence nucleophilicity.

Structure of the Haloalkane

• The substitution of the carbon atom attached to the halogen has a big impact on the reaction rate via SN1 or SN2.
• SN1 reactions are determined by electronic factors (3° > 2° > 1° > methyl).
• SN2 reactions are determined by steric factors (methyl > 1° > 2° > 3°).

Structure of the Leaving Group

• The best leaving groups form stable species (I-, Br-, Cl-, and H₂O).

The Solvent: Protic Solvents

• Protic solvents are hydrogen bond donors containing -OH groups (e.g., water, methanol, ethanol).
• They favor SN1 reactions because they greatly stabilize both carbocations and leaving groups via solvation.

The Solvent: Aprotic Solvents

• Aprotic solvents are not hydrogen bond donors.
• They usually favor SN2 reactions (e.g., DMSO, acetone, acetonitrile).
• Formation of carbocations is considerably more difficult in aprotic solvents relative to protic solvents.

SN1 vs. SN2 in Haloalkanes

• Methyl/primary haloalkanes proceed best via SN2.
• Secondary haloalkanes react by various reactions, often mixture of SN2 and SN1 depending on the bases/nucleophiles present and solvent/conditions.
• Tertiary haloalkanes are more apt to follow SN1 mechanisms, but E1 mechanism is just as likely

β -Elimination (Formation of Alkenes)

• Beta-elimination is a reaction where atoms/groups are removed from adjacent carbons.
  • A common reaction type involves dehydrohalogenation (loss of H-X).
  • Losing a halogen atom and a hydrogen adjacent to it form a π-bond which creates an alkene.

β-Elimination Selectivity

• Zaitsev's rule indicates formation of the more stable alkene (more substituted) as the major product. Trans alkenes are favored in cis-trans situations.

Beta-Elimination Mechanisms

• Two mechanisms for β-elimination:
  • E1 mechanism is a two-step process: first, a carbocation forms; then, a hydrogen is removed
  • E2 mechanism is a concerted one-step process in which both the leaving group and a hydrogen are removed simultaneously.

Elimination Reactions

• Strong bases favor E2, while weak bases favor E1.
• E1 is easier with 3° or 2° alkyl halides.
• E2 is possible with 3° alkyl halides, but easier with 1°, 2°

Substitution versus Elimination

• SN and E reactions are competing pathways. Ratio dependent on product relative rates.

SN1 versus E1

• Reactions of 2°, 3° haloalkanes in polar protic solvents yield mixtures of substitution and elimination products.
• Poor base/nucleophile, and presence of the solvent, favour carbocation formation. Product ratios are hard to predict.

SN2 versus E2

• Predicting the ratio of SN2 to E2 is easier, the base/nucleophile is a key factor.
• Large strong bases favor E2 reactions due to steric reasons.
• Small good nucleophiles favor SN2

SN versus E for Methyl and 1° Haloalkanes

SN versus E for 2°,3° Haloalkanes