Nucleophiles

Question 1

What is a Nucleophile?

Answer 1

Something that attacks electron poor molecules such as carbon or atoms with a partially polarised bond

Question 2

What is a Nucleophilic anion?

Answer 2

Has a negative charge or can be a molecule with a lone pair

Question 3

What is basicity a measure of?

Answer 3

A measure of the stability of an anion

The more stable an anion, the less reactive it is

Question 4

Examples of electronegative leaving groups

Answer 4

Cl, Br or I

Question 5

What does a negative charge on an electronegative atom indicate?

Answer 5

The molecule is less basic

Question 6

Compare nucleophiles

Answer 6

E.g. MeOH and CF3OH

2 alcohols = same type of atom

CF3OH has electron withdrawing fluorines —> 3 negative inductive effects and thus is the more stable anion

MeOH is more reactive than CF3OH

Question 7

Stable vs unstable anions

Answer 7

A stable anion is a weaker base and thus a weaker Nucleophile

An unstable anion is a strong base and thus a good Nucleophile

Question 8

Contributing factors to nucleophilicity

Answer 8

1. Charge —> a negative charge makes the group more Nucleophilic so it is more potent, makes it a stronger base
2. Delocalisation —> the ability to have resonance means there is inductive effects which can delocalise the charge and make the molecule less stable and a better Nucleophile/base
3. Hybridisation —> sp2 is less Nucleophilic whereas sp3 is more likely to get protonated so will be the better Nucleophile
4. Electronegativity —> increase of electronegativity increases the availability of the lone pair so the lower the electronegativity of the atom, the better the nucleophilicity
5. Size/polarity —> nucleophilicity increases as the molecule gets bigger as the greater the atomic radius, the more available electrons
6. Steric hinderance —> the most reactive nucleophile will be a primary carbocation as steric crowding in the a tertiary one will hinder its properties

Question 9

Stability vs reactivity in nucleophiles

Answer 9

Must be balanced or else the molecule will react with water in the biological system (will get destroyed by the large excess of water)

Question 10

pKa of water

Answer 10

14 at 25 degrees Celsius

Question 11

Common Nucleophilic groups

Answer 11

Must not be too reactive or will react with water as a base
E.g.

Question 12

Nucleophilic side chains of amino acids

Answer 12