Nucleophilic Substitution Reactions in Organic Chemistry

A reaction where a nucleophile replaces a leaving group on an alkyl halide.

A leaving group that can easily depart from a molecule, taking an electron pair with it.

The transition state in an SN2 reaction where the nucleophile and the leaving group are simultaneously bonded to the carbon atom.

The rate of reaction depends on the concentrations of both the alkyl halide and the nucleophile.

The arrangement of atoms in a molecule when a stereocenter undergoes an SN2 reaction.

The study of the factors that affect the rate of a reaction.

An equation that describes the relationship between the rate of a reaction and the concentrations of the reactants.

A compound with an electron-withdrawing group attached to an sp3 carbon.

Solvents with a hydrogen atom directly bonded to an oxygen atom (like water or alcohols).

Solvents that lack a hydrogen atom directly bonded to an oxygen atom.

The strongest base will be the best nucleophile, unless the reaction happens in a protic polar solvent and there's a difference in size.

Protic polar solvents can form strong interactions with anions (negatively charged species), hindering their ability to act as nucleophiles.

Aprotic polar solvents can better solvate cations (positively charged species) than anions.

Larger nucleophiles are often poorer nucleophiles due to difficulty in getting close to the reaction site.

SN2 reactions (bimolecular nucleophilic substitution) are irreversible because a weaker base cannot displace a stronger base.

SN1 reactions (unimolecular nucleophilic substitution) only involve the alkyl halide in the rate-determining step, making the rate independent of the nucleophile concentration.

The rate of SN2 reactions is affected by the structure of the alkyl halide. Primary alkyl halides react fastest, followed by secondary, and tertiary alkyl halides react the slowest. This is due to steric hindrance, which makes it harder for the nucleophile to approach the carbon atom in tertiary halides.

The SN2 reaction proceeds through a backside attack of the nucleophile on the carbon atom bearing the leaving group. This results in an inversion of configuration at the stereocenter.

The SN2 reaction is bimolecular because the rate depends on the concentration of both the alkyl halide and the nucleophile. This means that the rate law is second order.

The SN2 reaction is a one-step process where the nucleophile attacks the carbon atom and the leaving group departs simultaneously. This is why the reaction is called concerted.

In an SN2 reaction, the leaving group is the atom or group that departs from the alkyl halide. The weaker the base, the better the leaving group.

The rate of SN2 reactions is affected by the leaving group. Better leaving groups lead to faster reactions. Good examples of leaving groups are halides like bromide and chloride.

Polarizability refers to the ability of an atom to distort its electron cloud in response to an electric field. Larger atoms are more polarizable, which makes them better nucleophiles in protic solvents.

In aprotic solvents, the larger the atom, the weaker the nucleophile. However, in protic solvents, the larger the atom, the stronger the nucleophile. This is because in protic solvents, smaller atoms like fluorine are more strongly solvated, making them less reactive.

In an elimination reaction, a halogen is removed from one carbon and a hydrogen is removed from an adjacent carbon. A double bond forms between the two carbons where the atoms were removed.

The alkyl halide and the base are in the transition state of the rate-limiting step of the reaction. This means they both contribute to the reaction speed and are involved in an unstable intermediate state.

The halogen is removed from a carbon called the 'alpha carbon' while the hydrogen is removed from a carbon adjacent to it, known as the 'beta carbon'.

The major product formed is the most stable alkene due to the removal of a hydrogen from the beta carbon that is bonded to the fewest hydrogens. This is because less substituted alkenes (fewer carbons attached to the double bond) are generally more stable.

The transition state leading to a more stable alkene is also more stable. This means that the reaction path leading to the most stable alkene is more likely to be followed.

Zaitsev's rule suggests that the more substituted alkene is the most stable product. However, this rule doesn't always hold true, especially if conjugation (alternating double and single bonds) is present. This is because conjugated systems can have unexpected stability.

If the alkyl halide and the base are very bulky (large), the base will preferentially remove a hydrogen that is easily accessible, which could lead to the formation of a less stable product. This is due to steric hindrance, where the size of the groups makes the reaction less likely to occur at a more substituted carbon.

The major product of the E2 reaction of an alkyl fluoride is the less stable alkene. This is because fluoride is a poor leaving group. This makes the transition state look more like a carbanion, which is less stable when more substituted.

The type of leaving group significantly influences the products of a reaction. Better leaving groups, like halides, are more likely to leave, leading to a wider range of possible products.

The stability of the alkene formed determines which product is favored in an elimination reaction. Alkenes with more alkyl groups attached to the double bond are more stable.

In an E1 reaction, the rate-determining step involves the formation of a carbocation from the alkyl halide. The base only plays a role in the second step, removing a proton.

An E2 reaction requires the base and the leaving group to be positioned on opposite sides of the molecule. This alignment ensures maximum overlap of orbitals in the transition state.

The presence of a positive charge on a carbon atom significantly weakens the C-H bond, making it easier for a base to remove a proton.

Strong bases favor the E2 reaction pathway, while weak bases promote the E1 reaction pathway.

E1 reactions are regioselective, meaning they favor the formation of the more stable alkene. The more stable alkene is obtained by removing a hydrogen from the beta carbon with fewer attached hydrogens.

The transition state for the formation of the more stable alkene is more stable itself, making that product formation more favorable.

Tertiary alkyl halides undergo only elimination (E2) reactions when reacted with a strong base.

Tertiary alkyl halides undergo both substitution (SN1) and elimination (E1) reactions when reacted with a weak base. Substitution is generally favored.

Benzylic and allylic halides readily undergo SN2 reactions because the transition state is stabilized by resonance.

Benzylic and allylic halides undergo SN1 reactions due to the formation of stable carbocations, stabilized by resonance.

Vinylic and aryl halides cannot undergo SN2 reactions due to steric hindrance and the electron-withdrawing nature of the double bond/aromatic ring.

Vinylic and aryl halides cannot undergo SN1 or E1 reactions because the resulting carbocations are too unstable.

Vinylic halides can undergo E2 reactions when treated with a strong base, leading to the formation of an alkene.

Polar solvents stabilize charges, leading to a decrease in the rate of reactions involving charged reactants.