synthesis of dulcin

[Leroy]

I'm doing an experiment where i make acetaminophen from p-aminophenol. I then make phenacetin from acetaminophen and in the final stage i synthesise dulcin.

 

The problem i have is i can't figure out the reaction mechanism of the last step and i've looked all over.

See the picture for the reaction.

 

Can anyone explain to me how the NH2 group is built in and replaces the CH3 group.

 

Thanx

[chemistry]

I'm no expert on this, however I do have a suggestion for you to consider. With the first set of reagents the phenacetin undergoes a base-catalyzed haloform reaction which cleaves off the methyl group. Now with the second set it may be that the acetic acid is used to oxidate the carbonyl carbon and subsequently undergoes a nucleophilic addition (and elimination?) reaction with the urea. Especially this second aspect is a bit fuzzy and I'll get back to you later on it.

[chemistry]

Try this http://www.fau.edu/~mogul/dulcin.pdf

[chemistry]

although it does not seem to have the correct structure for phenacetin it describes, in one of its paragraphs, the mechanism. Hydrolysis followed by nucleophilic addition for the second part. The bicarbonate got me a bit confused, it seems that, rather than being used as a base it is used to moderate the pH of the reaction.

[Leroy]

but how should i picture the hydrolysis of the phenacetin into the p-phenetidine salt.

How does the acetyl group get cleaved off. Should i imagine that a +(C=O)CH3 gets cleaved because i don't understand how that would happen.

[chemistry]

Here's how you can picture it; it is essentially a hydrolysis of an amide. Catalyzed by the acid, water can act as a nucleophile, that is the acid turns the oxygen carbonyl to an oxonium ion. This causes the carbonyl carbon to become more electrophilic. Water adds through as a nucleophile and elimination results in a amine salt...NH4+ Cl-. I am assuming that you know the rest.

[Leroy]

yeah thanx.

i figured it out with the pdf before you posted the last post, but thanx for confirming my own ideas.

[Guest budfoxxx]

i still do not understand the mechanism of the nh2 group adding to the carbonyl carbon?

[Leroy]

the nitrogen atom is a pretty strong nucleofile. And the carbonyl carbon is partially positive. the nitrogen can therefore attack the carbonyl carbon.