Medchem 4

Nucleophilic Substitution Reactions

• Nucleophilic substitution involves a leading group disappearing during the reaction, leading to an inversion of configuration in the molecule.

Types of Reactions

Alkyl Halide Reactions

• Alkyl halides undergo nucleophilic substitution, categorized based on alpha and halide formation, transition states, rates of reaction, and energy profiles.

• Methane serves as a foundational example.

Identification of Longest Carbon Chain

• When analyzing alkanes, a straight chain should be prioritized without shortcuts in identification.

• For instance, identifying the longest chain in a given structure involves counting carbons:

  • Example: Six carbons in hexane.

• Substituents must receive the lowest possible numbers based on their positions along the carbon chain.

Example Compounds

• 3-bromohexane: A bromine substituent attached to the third carbon in a six-carbon chain.

• 2-iodo-2-methylpropane: An iodine and a methyl group on a propane backbone.

• 3,4-dichlorohexane: Two chlorine substituents at positions three and four on a six-carbon chain.

Classifying Alkyl Halides

• Alkyl halides are categorized as primary, secondary, or tertiary based on the number of neighboring carbons attached:

  • Primary (1°): One carbon attached to the carbon attached to the halogen.

  • Secondary (2°): Two carbons attached to the carbon with the halogen.

  • Tertiary (3°): Three carbons attached to the carbon with the halogen.

• The carbon bearing the halogen is referred to as the alpha carbon.

Polarity of Bond

• The carbon-halogen bond is polar due to differences in electronegativity:

  • The halogen (e.g., bromine) pulls electrons away from the carbon, generating a partial negative charge on the halogen and a partial positive charge on the carbon.

• This polarity allows for electrophilic behavior of the carbon, making it a target for nucleophiles.

Nucleophiles

• Nucleophiles are species that donate electron pairs:

  • Strong nucleophile example: Hydroxide ion (OH-) has an extra electron, making it a strong donor.

  • Neutral nucleophile example: Ammonia (NH3) with a lone pair of electrons; less reactive due to neutrality.

• The presence of a negative charge on the nucleophile indicates a higher reactivity.

Mechanism of Nucleophilic Substitution

• Two main types of nucleophilic substitution reactions:

  • SN1 Mechanism: Unimolecular nucleophilic substitution, involving a two-step process.

  • SN2 Mechanism: Bimolecular nucleophilic substitution, characterized by a direct one-step reaction where the nucleophile attacks from the backside, resulting in inversion of configuration.

• Transition States: States where bonds are breaking/forming, often represented by dotted lines to indicate partial bonds.

• Energy Profiles:

  • During a reaction, the energy of reactants is usually higher than the products, indicating that most nucleophilic reactions are exothermic.

Stereochemistry

• In nucleophilic substitution reactions:

  • If starting from an R configuration, an inversion will yield an S configuration, revealing the stereochemical outcome of the nucleophilic substitution.

Energy Profiles and Transition States

• Key points in the energy profile:

  • The reactants possess higher energy than the products.

  • The transition state is a critical point where bonds are not fully formed or broken.

• The number of transition states typically correlates with the type of nucleophilic substitution reaction and energy flow.

• Generally, one transition state is present in a straightforward SN2 reaction.