Medchem 4

Nucleophilic Substitution Reactions

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

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.

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.

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.

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.

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 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.

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.

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.

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.