Substitution Reactions

SN2

S - Substitution

N - Nucleophile

2 - RDS involves 2 species (2nd order)

Concerted reaction that happens in 1 step

• transition state formed

• Bond breaking/forming happens in same step

backside attack

Substitution Reaction

Leaving group is replaced by a nucleophile.

Halogens are electronegative, drawing electrons to them therefore creating a polar compound. This makes the carbon positive, thereby attracting a nucleophile(LP)

Nucleophile

have a lone pair, and are a lewis Base.

inversion of configurations

Configurations are inverted upon an SN2 reaction

Steric Hindrance

SN2

1. nature of substrate for SN2

Since SN2 reactions result in a backside attack, the carbon should not be bulky. Therefore, methyl groups > 1 > 2 > 3 are preferred substrates

Tertiary carbons do not result in SN2 reactions because of how much _______ there is.

Weak Base

SN2

2. Strength of leaving group

Sn2 reactions can be thought of as an acid base reaction. Acid base reactions occur in the order of strongest A/B to weakest A/B. Therefore, you want the leaving group to be a _______.

*TsO-, Ts and TsOCH3 are great leaving groups

Strength of nucleophile

A negative charge on a nucleophile is typically stronger than the neutral counter part (faster)

• will give a neutral product

• A neutral nucleophile will give a positive product

Typically a stronger base is a better nucleophile. Go across period, basicity decreases, therefore strongest nucleophile for neutral compounds are to the left.

Nucleophiles are subject to solvation (formation of intermolecular bonds between solvent and nucleophile). The smaller the nucleophiles, the stronger solvation forces. The stronger the solvation forces, the weaker the nucleophile.

• therefore for ions, a larger anion is more preferable since it experience less solvation than a smaller anion.

• Ex: While F- is a stronger base than Cl-, it is significantly smaller, therefore Cl- is a better nucleophile.

• Going down a group = stronger nucleophile

left

SN2

3.1. Strength of nucleophile

For a neutral nucleophile, it is better if it is to the ____ of the periodic table.

*ions of the each is gonna be noticeable stronger than the neutral counterpart

down

SN2

3.2. Strength of nucleophile

For an ion, it is better if it is ___ a group

Weaker

SN2

3.3. Strength of nucleophile

Bulky groups on a nucleophile will increase steric effect, therefore making it a ____ nucleophile.

Protic solvent

A solvent which has a hydrogen attached to an electronegative element. Will form HB with nucleophile

aprotic solvent

Solvent which does not have hydrogen bonds attached to electronegative elements

• DMF

• DMA

• HMPA

• ACE

• DMSO

Nature of solvent

SN2

4. Nature of solvent

   • protic solvents solvates the anion, thereby decreasing reactivity since energy is needed to strip the anion of the intermolecular bonds

   • Aprotic solvents solvate the cation, thereby making the anion readily available to be used in the reaction/leaving it naked

*in an aprotic solvent, cations are solvated therefore anions are extremely active. HOWEVER, this changes nucleophiles of ions. Since solvation is no longer of concern, ions are not ranked based on size, but rather based on basicity (therefore F- > Cl- > Br- > I- >)

Intramolecular substitution

When the molecule has both the leaving group and the nucleophile.

• can result in a circular product

• Typically more preferred, so long the internal angles are sufficient

protonated, heat

Poor leaving groups can be converted into good leaving groups: ex: OH-

CH3CH2-OH can be ____ into CH3CH2-O(+)H2

this step is called _____

water is a better leaving group than OH-. _____ may be needed to overcome the difference in Ka

SN1 Reaction

S - Substitution

N - Nucleophile

1 - number of species involved in RDS

***REACTION RATE DOES NOT CONCERN the nucleophile, only the subtrate

Occurs only in bulky substrates (tertiary), where the steric effect does not allow the nucleophile to easily access the positively charged carbon

• Solvolysis occurs

• 2 step reaction

• Results in a racemic mixture

Solvolysis

Attack of a substrate by solvent molecules

SN1 mechanism

Two steps:

1. the slow RDS step, whereby heterolytic cleavage occurs and a positive charge on substrate(carbon specifically) is formed. Carbocation is formed as an intermediate. Largest Ea needed

2. Attack on the carbocation by the solvent.

   1. Nucleophile sticks onto carbocation

   2. Deprotonation may be necessary to form a neutral compound

   3. ** A third transition state may be visible due to this deprotonation

Racemic mixture

These are TERTIARY CARBONS

When a carbocation is formed, either p-orbital could be vacated. Therefore, there is an equal chance of the nucleophile attacking one, as it has the other (no steric factor is considered)

• ____ is formed due to this

Stable substrate

SN1

1. Nature of substrate:

• Based on stability of carbocation. The more stable the carbocation, the more favourable the cleavage reaction(RDS). Therefore, a tertiary carbon is preferable.

• *Aromatics may stabilize a lot more

Hyperconjugation

carbocations from tertiary carbons experience ____. This is when the delocalized electrons from the adjacent bonding orbitals contribute their electrons to the vacated p-orbital, thereby stabilizing the carbocation(TS)

weak

SN1

2. Nature of nucleophile

Nucleophile does not participate in the rate RDS (purely based on the cleavage step)

Therefore it is not effected, and ___ nucleophiles can be just as effective as strong nucleophiles

Strong nucleophiles may result in an elimination reaction

Nature of leaving groups

SN1

3. Nature of leaving groups

• solvolysis still applies

• Larger = more solvolysis, therefore it is more stable

• Larger the halogen, the more stable it is when it is cleaved(more favourable the reaction)

polar protic

SN1

4. Nature of solvent

   • Since RDS is the cleavage, we want to stablizing the TS and the halogen

   • halogen stablized due to more solvolysis

   • Formation of TS in step 1 has a partial positive and negative charge. More protic the carbocation, the more stabilized the TS is.

   • Thus, a ___ solvent is preferred

Polar

____ aprotic/protic solvents are necessary for SN1/2 reactions, since ions are typically involved either as a substrate, nucleophile, or the leaving group.

therefore to prevent clumping and to make it soluble, a ____ solvent is preferred.