Synthetic Pathways

Question 1

What is the industrial synthesis of phenol?

Answer 1

Aromatic halide(Cl) + NaOH, 340 degrees and high pressure = phenol

Question 2

What is the industrial synthesis of benzyne?

Answer 2

Aromatic Cl + NaOH+ base = phenyl ion= benzyne

Question 3

How do you form phenol from a benzyne ion?

Answer 3

Benzyne + NaOH = phenyl ion + water = phenol

Question 4

Describe the positive of the negative charge on a phenyl anion

Answer 4

The negative charge of the phenyl anion is held in an sp2 orbitals orthogonal to the pi system exactly the same as the phenyl cation

Question 5

What is the evidence for phenyl anion mechanism?

Eg synthesis of phenol

Answer 5

13c labelling experiment indicates that the reaction proceeds via a symmetrical intermediate in which both carbons to which the nucleophile can be attached at identical

Question 6

Describe the structure of benzyne

Answer 6

Benzyne is highly unstable and cannot be isolated
Although it is draw with a triple bond this is wrong as you cannot have a triple bond in a 6 membered ring
The actual structure is a combination of three resonance forms- a diradical and two zwitterions
Only one electrons moves in the resonance

Question 7

What do you need to consider when planning a synthetic strategy?

Answer 7

• try to use just electrophilic aromatic substitutions
• order is important- influences regiochemistry & reactivity
• take into occur whether R is activating or deactivating , where they direct to, reactivity of electrophile, conditions, byproducts and does it react further?

Question 8

Why can activating groups react with weaker electrophiles whereas deactivating require a strong electrophile?

Answer 8

Activating groups activate the ring and make it more reactive and so they can react with weak electrophiles
Deactivating groups deactivate the ring and make it less reactive and so require a strong nucleophile

Question 9

How do you decide a synthetic strategy?

Answer 9

1) determine number of groups that need to be introduced (how many steps)
2) determine mechanism ( Esub)
3) determine the nature of R
4) determine order R will need to be added
- introduce the most deactivating group last as they reduce reaction rate

Question 10

What is and can be used as a blocking group?

Answer 10

This blocks the position so other groups cannot attack
- reaction of SO3H is reversible and so it can temporarily block the position and then removed after to give a product that would be otherwise unavailable

Question 11

What other types of groups can be used as blocking groups?

Answer 11

The size of some activating groups are so large they can minimise the likelihood of attack at other positions that are undesirable

Question 12

How can temporarily increasing the size of a substituents be useful?

Answer 12

The ratio of para/ ortho depends on the siZe of the activating group
The larger the group the more para as this is the least hindered site
If you only have a small activating group but you need para, you can increase its size so para is favoured over ortho

Question 13

What can you do if neither substituents has the right directing influence to give the right product?

Answer 13

Consider it one the substituents can be made by functional group interconversion from a substituents with a different directing influence
Diazochemistry has many useful functional group transformations

Question 14

What do you do if you cannot make the product by electrophilic substitution?

Answer 14

Consider nucleophillic aromatic substitution or hezyne chemistry