Functional Groups 2: Nucleophilic substitution

Question 1

How do alkyl halides generally react with nucleophiles?

Answer 1

Alkyl halides will undergo nucleophilic attack at the carbon atom
This would result in a pentavalent carbon atom, therefore the C-X bond must break
Releasing X as a leaving group

Question 2

Describe nitrile synthesis from alkyl halides.

Answer 2

Alkyl halides will react with the cyanide ion in a nucleophilic substitution reaction, releasing the halide as the leaving group and forming a nitrile

Question 3

How can nitriles be converted into amines?

Answer 3

Using a reducing agent such as LiAlH4

Question 4

What is retrosynthesis?

Answer 4

Working backwards from a target molecule to work out the starting components

Question 5

What is retrosynthetic analysis?

Answer 5

The reverse of synthesis and is used for planning a synthesis

Question 6

What does a double forward arrow represent?

Answer 6

A retrosynthetic step
Often associated with functional group interconversion

Question 7

How do you generate a new C-C bond?

Answer 7

Using a carbon-based nucleophile
To generate the nucleophile, first deprotonate an alkyne using NH2- (made by carefully adding sodium metal to liquid ammonia at low temperature)

Question 8

Why is NH2- used in nucleophilic substitution reactions to form new C-C bonds?

Answer 8

Because sodium amide is a very strong base and alkynic protons are weakly acidic

Question 9

How does the anion formed from an alkyne react with alkyl halides?

Answer 9

The anion can act as a nucleophile
So carries out a nucleophilic substitution reaction
Produces an alkyne which can undergo further useful reactions
Also forms a new C-C bond

Question 10

How do you form primary alkyl amines from alkyl halides?

Answer 10

By reacting alkyl halides with azides (i.e. sodium azide)
Then reduce this with LiAlH4

Question 11

How do you form alcohols from alkyl halides?

Answer 11

React the alkyl halide with sodium hydroxide
Not often carried out on small molecules as the alcohol is usually cheaper and more easily available than the halide

Question 12

What is Williamson ether synthesis?

Answer 12

A useful reaction with oxygen-based nucleophiles to form ethers

Question 13

Describe how Williamson ether synthesis is carried out.

Answer 13

React an alcohol with sodium to deprotonate the alcohol and form nucleophile
Then react the nucleophile with the alkyl halide to form the ether

Question 14

What starting material would you use in Willamson ether synthesis to form thioethers?

Answer 14

R-SH instead of an alcohol

Question 15

How can carboxylic acids be used to make esters?

Answer 15

Carboxylic acids can be used as nucleophiles
Although esters are mostly made by reaction of carboxylic acids and alcohols

Question 16

What is the Finkelstein reaction?

Answer 16

Alkyl halide + metal halide
e.g. using an iodide salt such as potassium iodide
The reaction is driven forward by KCl and KBr which are insolbule in organic solvents such as methanol
This reaction is useful for preparing alkyl iodides

Question 17

Why are alkyl iodides a useful product of the Finkelstein reaction?

Answer 17

because I- is an excellent leaving group
Alkyl iodides give better yields with other nucleophiles

Question 18

What are the two different cases of nucleophilic substitution?

Answer 18

1) The leaving group can leave as an anion to give a carbocation which is attacked by a nucleophile
2) The nucleophilic attack and loss of leaving group occur at the same time

Question 19

What is an SN1 reaction?

Answer 19

Two step reaction
1) The halide is removed from R-X to produce an anion and the leaving group
2) The nucleophile then attacks the anion, forming the product
S = substitution
N = nucleophilic
1 = unimolecular
The slow step of the reaction involves RX only (Rate = k[RX])