Medicinal and Pharmaceutical Chemistry – MEDCHEM MEDCHEM.5: Alkylhalides II

These flashcards cover key concepts related to nucleophilic substitution reactions of alkyl halides, focusing on the differences between SN1 and SN2 mechanisms, the properties of different alkyl halides, and factors affecting reactivity.

What are the three types of alkyl halides?

Primary, secondary, and tertiary alkyl halides.

Why do tertiary alkyl halides generally not undergo SN2 reactions?

Because they are sterically hindered for nucleophilic attack.

What characterizes an SN1 reaction mechanism?

It involves the formation of a carbocation and occurs in two steps.

What is the rate determining step in an SN1 reaction?

The formation of the carbocation.

How does the pKa of a leaving group relate to its reactivity?

Weaker bases with lower pKa values make better leaving groups.

Which alkyl halide type is most reactive in SN2 reactions?

Primary alkyl halides.

What is a nucleophile?

Any species with a lone pair of electrons, which can donate it to form a bond.

In SN2 reactions, how does the nucleophile approach the substrate?

From the opposite side of the leaving group.

What happens to the configuration during an SN2 reaction?

There is inversion of configuration.

What can affect the rate of SN2 reactions?

The concentration of both the nucleophile and the substrate.

What is the maximum reactivity order for SN2 in terms of substrate types?

Primary > Secondary > Tertiary (not reactive).

What is the key feature of the transition state in an SN2 mechanism?

It involves both the nucleophile and substrate.

How do negatively charged nucleophiles compare to neutral ones in reactivity?

Negatively charged nucleophiles are usually more reactive.

What is indicated by a second order reaction in the context of SN2?

The rate depends on the concentrations of two reactants.

What characterizes an SN1 reaction in terms of steps?

It involves more than one step with a carbocation as an intermediate.

Why are tertiary alkyl halides not suitable for SN2 reactions?

They are sterically hindered.

What determines the reactivity of secondary alkyl halides?

They can undergo either SN1 or SN2 mechanisms depending on conditions.

What is the relationship between nucleophilicity and basicity?

Stronger bases are generally stronger nucleophiles.

What occurs in the transition state of an SN2 reaction?

The bond forming and bond breaking processes occur simultaneously.

What type of leaving group enhances SN2 reactions?

Good leaving groups with low pKa values.

How does the structure of a leaving group influence its ability?

Better leaving groups can stabilize the negative charge they carry.

Describe the mechanism of SN1 reactions.

SN1 involves the formation of a carbocation followed by a fast attack by the nucleophile.

What is the effect of steric hindrance on SN2 reactions?

Steric hindrance increases the transition state's energy, slowing the reaction.

What type of substrate does the SN1 mechanism favor?

Tertiary substrates, especially if they can stabilize a carbocation.

Which alkyl halide structures are less reactive in SN2 reactions?

Tertiary alkyl halides.

What type of nucleophile is typically more reactive?

Negatively charged nucleophiles.

What determines whether a secondary alkyl halide undergoes SN1 or SN2?

The presence of steric hindrance or stabilizing groups like benzene.

Describe the difference in reactivity between different leaving groups.

Weaker bases with lower pKa are generally better leaving groups.

What reaction type is preferred if a secondary alkyl halide has a benzene ring?

SN1 mechanism becomes more favorable.

What is the rate determining step for an SN1 reaction?

Formation of the carbocation.

How does the presence of steric bulk around a carbocation affect its stability?

Increased substituents stabilize the carbocation.

What is the consequence of SN1 reactions on chiral centers?

They yield racemic mixtures due to loss of stereochemistry.

What generally happens when H2O acts as a nucleophile in SN1 reactions?

It can react with tertiary substrates, following the usual SN1 mechanism.

What is the relationship between nucleophile strength and rate of the reaction?

Stronger nucleophiles typically react faster.

What are the implications of the reaction mechanism for tertiary alkyl halides?

They cannot undergo SN2 reactions but can still react by SN1.

What is indicated by the activation energy in an SN2 reaction?

It is the energy difference between the ground state and the transition state.

How do reactivities of alkyl halides compare between SN1 and SN2 mechanisms?

SN1 is favored by tertiary alkyl halides, while SN2 favors primary.

What is the expected product of a nucleophilic substitution reaction when alcohol and tertiary halide react?

Formation of an ether or alcohol.

How does the rate of an SN1 reaction depend on the alkyl halide structure?

Rate depends primarily on the alkyl halide concentration alone.

What type of intermediate exists in an SN1 reaction mechanism?

Carbocation.

Why is the inversion of configuration important in SN2 reactions?

It affects the stereochemistry of the resulting product.

How does the presence of bulky groups affect nucleophilic substitution reactions?

They hinder the nucleophile's approach, especially in SN2.

In what scenario would a nucleophile be neutral?

If the nucleophile is water (H2O), it can still participate in the reaction.

What should be noted about SN1 mechanisms across different nucleophiles?

They're generally similar regardless of the nucleophile.

What is the summary characterization of SN1 and SN2 mechanisms?

SN1 is unimolecular with carbocations; SN2 is bimolecular with simultaneous bond formation.