11. Nucleophilic Substitution

Question 1

What do nucleophilic substitution reactions involve?

Answer 1

A nucleophile attacks the carbon of an organic molecule and displaces a leaving group which carries away its bonding electrons

Question 2

What are the 2 mechanisms of nucleophilic substitution?

Answer 2

Sn1 = stepwise
Sn2 = concerted

Question 3

What factors influence the type of nucleophilic substitution reaction that a particular substrate undergoes?

Answer 3

• The nature of the alkyl group (variations at C site)
• The nature of the leaving group
• The nature of the nucleophile
• The solvent

Question 4

What is first order nucleophilic substitution?

Answer 4

• The rate of reaction depends only on the concentration of the substrate
• Rate = k x [R-K]

Question 5

What are the two distinct steps of the sn1 mechanism?

Answer 5

Step (a) is ionisation and is SLOW

Step (b) is nucleophilic attack and is FAST

Question 6

What is the rate determining step in the sn1 mechanism?

Answer 6

• Step (a) ionisation is the slower rate determining step

Step (b), nucleophilic attack is faster

Question 7

What does second order nucleophilic substitution involve?

Answer 7

• Sn2 mechanism
• The rate of reaction depends on both the concentration of the substrate and the nucleophile
• rate = k x [R-X][Nu}

Question 8

What is the mechanism of sn2?

Answer 8

The breaking and making of bonds is simultaneous or concerted.

Happens at the same time

Question 9

What is the intermediate like of an sn2 mechanism?

Answer 9

• The intermediate is very transient
• Carbon atom with 5 pairs of electrons that violates octet rule
• Trigonal bipyramid

Question 10

What is the Walden inversion?

Answer 10

• SN2 reaction occurs in a single step involving approach of incoming nucleophile from direction 180 degrees away from the leaving group
• This results in an umbrella like inversion of stereochemistry (Walden inversion)
• Thus an optically pure reactant will be converted to an optically pure product

Question 11

What does optically pure mean?

Answer 11

A sample that contains only one enantiomer is termed optically pure or homochiral. It will have a non-zero optical rotation

Question 12

What is the stereochemistry outcome of SN1 reaction?

Answer 12

• SN1 reaction occurs by spontaneous dissociation of the alkyl halide to give a planar carbocation intermediate
• This planar intermediate can be attacked from either face
• Thus a chirar substrate will give rise to a racemic mixture

Question 13

What is the order of carbocation stability?

Answer 13

Stability increases as it becomes more substituted

Question 14

How does the ease of the SN1 reaction relate to the order of carbocation stability?

Answer 14

The more stable, the faster the reaction because the hill of the transition state drops, increasing speed of reaction

Question 15

How are carbocations stabilised?

Answer 15

• Carbocations and alkenes are both sp2 hybridised

- The more substituted they are, the more stable

Question 16

What is the relative reactivity in SN2 reactions for substitutions at the carbon site?

Answer 16

Less substituted, faster the rate of reaction

This order of reactivity is ascribed to increasing steric hindrance in the transition state from the primary to the tertiary substrate

Question 17

Which level of substitution do SN1 reaction prefer?

Answer 17

• tertiary carbons because the tertiary carbon intermediate is very stable and because sn2 substitution is sterically hindered

Question 18

Which level of substitution do SN2 reactions prefer?

Answer 18

Methyl and primary carbons because they are sterically accessible, because the resulting carbocations are so unstable

Question 19

Which reaction mechanism do secondary substrates undergo?

Answer 19

Either sn1 or sn2

• Difficult to predict beforehand but can tell afterwards
• eg. Inversion of stereochemistry = sn2

Question 20

How do variations in the nucleophile affect reactivity?

Answer 20

• All nucleophiles are bases and generally stronger bases are better nucleophiles
• The affinity of a base for a proton parallels the affinity of the same species as a nucleophile for the electron deficient electrophile

Question 21

How do variations in the leaving group affect reactivity?

Answer 21

• All leaving groups are also bases and generally weaker bases are better leaving groups
• The better the ability of the base to stabilise negative charge, the better is is able to act as a leaving group