Nucleophiles, Electrophiles and Leaving Groups

Almost all organic reactions can be divided into two groups. What are they?

Oxidation-reduction

Nucleophile-electrophile

Nucleophiles and electrophiles are particularly important to reactions involving which two functional groups?

Alcohols and Carbonyl containing compounds

Nucleophile

Lone pair or pi bonds

which can form new bonds with electrophiles

Nucleophiles as they relate to bases

Good nucleophiles tend to be good bases

How are nucleophiles and bases different?

How they are measured

Nucleophiles strength is based on relative rates of reaction with a common electrophile

Base strength is measured by equilibrium position of a reaction

What are some common nucleophiles?

Anions: Br-, OH -, CN-

Pi bonds: Alkene, Alkyne, Benzene

Atoms w/ Lone Pairs: water, NH3, Acetone

What four factors determine nucleophilicity ?

Charge: more charge = stronger

Electronegative: less electronegative = stronger

Steric hindrance = smaller = stronger

Solvent = aprotic = stronger

Why is aprotic better for nucleophile strength?

Because no hydrogen bonds means no protonation of nucleophile or intermolecular forces with nucleophile to decrease it's strength

Why are less electronegative atoms better for nucleophile strength?

Because they are less likely to hold onto the electron density meaning that they are more likely to give it up, thus react with electrophilic.

What's the trend for nucleophilicity for POLAR protic vs POLAR aprotic solvents?

Nucleophilicity increases down the table for protic solvent

Nucleophilicity increases up the table for aprotic solvents

Common protic solvents

Carboxylic acids

Ammonia/amines

Water

Alcohols

Common aprotic solvents

Dimethyformamide (DMF)

Dimethylsulfoxide (DMSO)

Acetone

Dimethylsulfoxide (DMSO) structure

Dimethyformamide (DMF) structure

Amine structure

Can be 1, 2, OR 3

Acetone (structure)

most basic ketone = acetone

If solvent isn't given on test day, what do should you assume?

It is polar solvent

polar solvents, whether protic or aprotic can assist in movement of electrons (WHICH IS WHAT OCHEM is all about)

I>Br >Cl > F

Nucleophilicity for which type of polar solvent? Why?

Polar protic solvent

HF = weak acid = unstable CB

thus F- is more likely to form bonds with protons than a strong acids CB which is more stable

HI = strong acid = stable CB

protons less likely to form bonds because the stable CB is less likely to be affected by the protons in solution. This allows it to act on the electrophile

F> Cl> Br > I>

Nucleophilicity for which type of polar solvent?

Polar aprotic

No protons in the solution means that they can't get in the way of the nucleophile

Thus aprotic solvents, nucleophilicity relates directly to basicity.

Examples of strong nucleophiles

OH-, RO-, CN-, N3-

Examples of Medium nucleophiles

Nh3 and RCO2- (ester ion)

Examples of Weak nucleophiles

H20, RCOOH, ROH

Electrophiles

positive charge or partially positive

accepts electron pair to form bonds with nucleophile

Difference between electrophilicity and lewis acid ?

Both are electron acceptors but they are measured differently

Electrophiles = kinetic property

Lewis Acid = thermodynamic property

Electrophilicity increases with ?

Positive charge

Why Carbocation is more electrophilic than Carbonyl atom

What can affect the electrophilicity of a species that has no empty orbitals?

The strength of leaving group

better leaving group makes reaction more likely to happen

If empty orbitals are present on the electrophile, what does this mean for the leaving group?

The nucleophile can form bond with the electrophile without kicking off leaving group

Electrophilicity and acidity are effectively identical properties when it comes to reactivity

Examples of good electrophiles

Alcohols, ketones, carboxylic acids, aldehydes and carboxylic acids derivatives

Why can't you use nonpolar solvent in a electrophile-nucleophile reaction?

Because the reactants are polar and need to be dissolved into solution

Nonpolar solvents wouldn't dissolve them

What's the order of best electrophilicity of the carboxylic acid derivatives

Anhydrides

Carboxylic acids

Esters

Amides

Leaving Groups

leaves and take the electrons with them

Heterolytic group = opposite of coordinate covalent formation

What's a characteristic of good leaving groups

able to stabilize the extra electrons after leaving with them

How are good leaving groups related to strong acids?

Strong acids are strong because the CB is stable and doesn't mind leaving

Good leaving groups are stable and don't mind leaving

What are some good leaving groups?

I-

Br-

Cl-

What can increase the strength of leaving group to leave?

Resonance

Inductive effect by electron withdrawing groups

Helps delocalize negative charge and stabilizes it.

What are two of the worst leaving groups, ones that will almost never act as leaving groups?

Alkanes and hydrogen ions

form very reactive, strongly basic anions

can think of leaving group and nucleophiles as serving opposite functions, how?

In substitution reactions weaker base acts as leaving group and is replaced by stronger base which is nucleophile