Lab 2: Three Step Synthesis

Question 1

What is the first step in three step synthesis? How does the mechanism work?

Answer 1

Nitric Acid:

• Really corrosive; strong oxidizing agent; make royal water (aqua regia) when combine with HCl.
• Oxidize alcohol in benzoin to benzil (ketone)

Question 2

What is the second step of the synthesis? Mechanism?

Answer 2

KOH take alpha proton from dibenzylketone to form an enolate, benzil and this enolate undergo aldol condensation to make a compound with conjugate pi bonds . This process repeats and forms tetraphenylcyclopentadienone.

Question 3

What is the third step? Mechanism?

Answer 3

1: Form Benzyne. Start with Anthranilic acid and isopentyl nitrite → diazonium salt → eliminate CO₂ and N₂ and form benzyne ( although benzyne is aromatic, this compound is unstable, but the equilibrium is still favored in making benzyne because it release two gases and all of them are really favorable)
2. In the same pot, benzyne (a dienophile) will react with tetraphenylcyclopentadienone (Diel- Alder) → a compound that is unstable due to ring strain → release CO → 1,2,3,4-Tetraphenylnaphthalene.

Question 4

When does Oiling out occur? Why is this bad?

Answer 4

Occurs when a compound is insoluble but too hot to freeze. Bad bc oil can trap impurities

Question 5

What is the main safety concern of the three-step synthesis?

Answer 5

Nitric acid is an oxidizer and can cause chemical burns.

Question 6

In the three-step synthesis lab, what was the point of using TLC during the reaction from benzoin to benzil?

Answer 6

You can monitor your reaction to see how complete it is based on how much benzil in the reaction.

Question 7

Will benzoin or benzil travel farther up the TLC plate?

Answer 7

Benzil will travel farther up the TLC plate since it is less polar.

Question 8

In the three-step synthesis lab, why does the reaction only need 0.5 equivalents of KOH even though two consecutive aldol condensations are occurring?

Answer 8

Since KOH is catalytic, once it is used to make the enolate, it is regenerated when the hydroxide is a leaving group.

Question 9

In the three-step synthesis lab, why does diphenylacetate not undergo an aldol reaction with itself?

Answer 9

Benzil is more electrophilic than diphenylacetate because of EWG nature of the benzene ring and neighboring carbonyl groups.

Question 10

In the three-step synthesis lab, why do we use isopentyl nitrite instead of sodium nitrite and phosphoric acid?

Answer 10

Sodium nitrite is not soluble in dimethoxyethane.

Question 11

To oxidize alcohols: OH to C=O

Answer 11

Kmno4, CrO3, PCC, TEMPO, HNO3