Nucleophilic Substitution Reaction 1

Flashcards covering key concepts related to Nucleophilic Substitution Reactions, including SN1 and SN2 mechanisms, factors affecting reactivity, and stereochemistry.

What is a nucleophilic Substitution reaction?

It is a reaction in which one nucleophile displaces another (leaving group) at a tetravalent carbon

What are nucleophiles?

“nucleus loving” molecules that can donate a pair of electrons to form a covalent bond

In alkyl halides, why is the carbon atom susceptible to nucleophilic attack?

Because the halogen is more electronegative than the carbon, drawing electrons towards it and creating a partial positive charge on the carbon.

What are alkyl halides?

Organic molecules where a halogen atom (like chlorine, bromine, or iodine) is bonded to a carbon atom.

What are nitrogen mustards used for, in the context of nucleophilic reactions?

Nitrogen mustards act as anti-cancer agents through nucleophilic reactions.

Why is the partial positive charge on the carbon atom important in nucleophilic substitution?

It makes the carbon atom vulnerable or susceptible to attack by a nucleophile.

What is a nucleophilic attack?

When an electron-rich nucleophile approaches the carbon atom and donates a pair of electrons to form a new bond.

What happens to the bond between the carbon and halogen during a nucleophilic attack?

The bond between the carbon and the halogen breaks, leading to the displacement of the halogen by the nucleophile.

What are the two main types of SN reactions?

SN1 and SN2 reactions

In SN1 reactions, when does bond forming begin with the nucleophile?

After the bond breaking step between carbon and the leaving group is completed.

How many species are present in the rate determining step of an SN1 reaction?

Only one species (substrate)

In SN2 reactions, when do bond-breaking and bond-forming steps take place?

Simultaneously

How many species are involved in the rate determining step of an SN2 reaction?

Both species (nucleophile and substrate)

What is the key difference between SN1 and SN2 reactions in terms of timing?

The timing of bond-breaking and bond-forming steps

Why are SN1 reactions termed unimolecular?

Because their rate depends solely on the concentration of the substrate molecule undergoing substitution.

What is the rate-determining step in SN1 reactions?

The formation of a carbocation intermediate.

Why are SN2 reactions termed bimolecular?

Because their rate depends on the concentrations of both the substrate and the nucleophile.

What is the rate-determining step in SN2 reactions?

The collision of both the substrate molecule and the nucleophile, leading to the formation of the product.

In SN1 reactions, which occurs first: departure of the leaving group or nucleophilic attack?

Departure of the leaving group

What intermediate do SN1 reactions proceed through?

A carbocation intermediate

In SN2 reactions, what type of step is involved?

A single, concerted step where the nucleophile attacks the substrate while the leaving group departs.

Is there formation of an intermediate in SN2 reactions?

No

In SN1 reactions, are bond-breaking and bond-forming steps sequential or simultaneous?

Sequential

In SN2 reactions, are bond-breaking and bond-forming steps sequential or simultaneous?

Simultaneous

In an SN2 reaction, where does the nucleophile attack the carbon atom of the substrate?

Opposite to the leaving group

What is the transition state in an SN2 reaction?

A state where the substrate is partially bonded to both the nucleophile and the leaving group.

What happens to the bond between the substrate and the leaving group as the nucleophile attacks in SN2?

The bond between the substrate and the leaving group starts breaking.

What is a key characteristic of SN2 reactions regarding stereochemistry?

They often lead to inversion of stereochemistry at the carbon center where substitution occurs.

Why does inversion of configuration happen in SN2 reactions?

Because the nucleophile approaches the carbon atom from the side opposite to the leaving group.

What is formed once the transition state is passed in an SN2 reaction?

The product with the nucleophile substituted for the leaving group is formed.

What does the initial state in an SN2 reaction energy profile consist of?

The reactants, which typically consist of the substrate molecule (with the leaving group) and the nucleophile.

What is the transition state in the SN2 reaction energy profile?

The highest energy point along the reaction pathway.

What is the activation energy (Ea)?

The energy required to reach the transition state; it represents the energy barrier that must be overcome for the reaction to proceed.

Is there a stable intermediate formed in SN2 reactions?

No, there is typically no stable intermediate formed.

What happens to energy after passing through the transition state in SN2?

The system proceeds downhill in energy towards the formation of products.

What is the product of an SN2 reaction?

The substrate with the nucleophile substituted for the leaving group.

What is the typical relationship between the energy of reactants and products in SN2 reactions?

The energy of the products is typically lower than that of the reactants.

What does a negative overall energy change (ΔE) indicate about a reaction?

That the reaction is exergonic (releases energy).

What determines the rate at which a reaction proceeds?

The height of the energy barrier (activation energy).

In an SN2 reaction, how many steps does the reaction occur in?

One step

What molecules are involved in the reaction leading to the transition state in SN2?

The substrate (haloalkane) and the nucleophile

What is the order of an SN2 reaction?

It is a second-order reaction; first order in the substrate (haloalkane) and first order in nucleophile.

Briefly describe the reaction mechanism of SN2.

The nucleophile attacks the substrate while the leaving group departs, leading to simultaneous bond formation and bond breaking in the transition state.

What does it mean for SN2 reactions to be second-order?

The rate of the reaction is directly proportional to the concentrations of both the substrate (haloalkane) and the nucleophile.

Write the rate equation for an SN2 reaction.

Rate = k [Substrate] [Nucleophile]

What is 'k' in the rate equation for an SN2 reaction?

The rate constant, which represents the rate of reaction at a given temperature and is specific to the particular reaction.

Where does the second-order kinetics of SN2 reactions arise from?

The bimolecular nature of the reaction mechanism.

What happens to the rate of an SN2 reaction as the concentrations of the substrate and nucleophile increase?

The rate of the reaction increases.

Name four factors that affect SN2 reactions.

Nature of the nucleophile, nature of the substrate, nature of the leaving group, solvent

What properties do all nucleophiles and bases have in common?

Both contain a lone pair of electrons.

What is nucleophilicity a measure of?

A kinetic property measured by the rate at which a Nu causes a nucleophilic substitution at atoms other than H (typically C).

What is basicity a measure of?

An equilibrium property measured by the position of equilibrium in an acid-base reaction (reactivity towards H).

Explain nucleophilicity in simple terms.

The eagerness of a molecule to donate electrons to another molecule.

Explain basicity in simple terms.

A measure of how good a molecule is at grabbing a proton (H^+).

Are negatively charged molecules generally more or less nucleophilic and basic than neutral ones?

More nucleophilic and basic

Why are negatively charged molecules more nucleophilic and basic?

Because they have extra electrons to donate.

How does nucleophilicity change as you go down the periodic table?

Generally increases

Why does nucleophilicity generally increase as you go down the periodic table?

Because larger atoms are better at donating electrons.

How do stronger nucleophiles affect SN2 reactions?

Lead to faster SN2 reactions.

What is the primary focus of nucleophilicity versus basicity?

Nucleophilicity is focused on the reaction's speed, while basicity is more about the equilibrium in an acid-base reaction.

Are anionic groups generally more or less nucleophilic than neutral groups?

More nucleophilic

Why are anionic groups more nucleophilic?

Because anionic groups have extra electrons available for donation.

How does polarizability affect nucleophilicity going down the periodic table?

Nucleophilicity increases going down the periodic table as polarizability increases.

How does nucleophilicity change as you move from left to right across a period in the periodic table?

Nucleophilicity generally decreases

Why does nucleophilicity decrease across a period from left to right?

Atoms to the right of the periodic table are more electronegative and less willing to donate electrons.

How does an increase in atomic size affect polarizability and nucleophilicity in the same column of the periodic table?

Increases polarizability and nucleophilicity

How does an increase in atomic size affect basicity in the same column of the periodic table?

Decreases basicity

What is the relationship between basicity and nucleophilicity in many cases?

Molecules that are good at accepting protons (strong bases) are also good at donating electrons (strong nucleophiles).

What is more likely to increase with basicity?

Nucleophilicity

What are some exceptions and considerations when considering basicity and nucleophilicity?

Bulky molecules might be strong bases but poor nucleophiles due to steric hindrance. The solvent and reaction conditions can also affect nucleophilicity independently of basicity.

What is the steric factor in SN2 reactions?

Refers to the physical size of the substituents attached to the electrophilic carbon in the substrate molecule.

How does the steric factor affect the rate of SN2 reactions?

Bulky substituents on the electrophilic carbon can hinder the approach of the nucleophile, slowing down the reaction.

How do substituents affect the rate of SN2?

If the electrophilic carbon is surrounded by small or no substituents, the nucleophile can approach it more easily, leading to a faster reaction. Conversely, if the electrophilic carbon is hindered by bulky substituents, the nucleophile will have difficulty approaching, resulting in a slower reaction rate.

What defines protic solvents?

Protic solvents are hydrogen bond donors.

What defines aprotic solvents?

Aprotic solvents cannot act as a hydrogen bond donor.

Are protic solvents usually polar or nonpolar?

Usually polar

Can aprotic solvents be polar?

Aprotic solvents can be either polar or non-polar

What is the dielectric constant a measure of?

Solvent polarity

What does the dielectric constant determine?

Solvent’s ability to insulate opposite charges from one another

What range is considered a polar solvent?

dielectric constant > 15

What range is considered a nonpolar solvent?

dielectric constant < 15

How do polar protic solvents affect the nucleophile?

Forms hydrogen bonds with the nucleophile thus putting it in a cage and making it sterically hindered

How does solvent-nucleophile compare in polar aprotic solvents versus polar protic solvents?

A weaker solvent-nucleophile interaction means a weaker solvent cage for the nucleophile to break through, so the solvent effect is much less important

In polar protic solvents, are nucleophiles more or less reactive?

Less reactive: the strong "cage" formed around the nucleophile restricts its movement and makes it less reactive.

What type of attack do all SN2 reactions proceed with?

Backside attacks (opposite to the leaving group)

What does a backside attack result in when talking about stereochemistry?

Inversion of stereochemistry at a stereogenic centre

Why does backside attack occur regarding leaving groups?

This backside attack occurs because it allows the nucleophile to avoid repulsion from the leaving group and proceed with the substitution smoothly.

What happens as a result of the backside attack?

The arrangement of groups around the carbon atom undergoing substitution changes.