[Albert]

Hello guys, today I saw a possible synthesis of a quite common molecule: Naproxen.

My professor highlighted a step of this pathway, where it's carried out a process, called Wilgerodt reaction.

Can you show me its detailed mechanism?

[HP]

   
Hi Albert,
thats what i found your problem. This reacton seems to be like multicomponent reactions.
Heres a link this subject: http://www.organic-chemistry.org/frames.htm?http://www.organic-chemistry.org/topics/multicomponent-reactions.shtm
Ts-OH is useful catalist this thioamide synthesis
Willgerodt-Kindler Reaction

C. Willgerodt, Ber. 20, 2467 (1887); 21, 534 (1888); K. Kindler, Ann. 431, 193 (1923).

Conversion of aryl alkyl ketones to amides and/or the ammonium salts of the corresponding acids by aqueous ammonium polysulfide or by sulfur and a primary or secondary amine.
Reviews: M. Carmack, M. A. Spielman, Org. React. 3, 83 (1946); R. Wegler et al., Newer Methods of Preparative Organic Chemistry vol. 3 (Academic Press, New York, 1964) pp 1-51; E. E. Campaigne in The Chemistry of the Carbonyl Group, S. Patai, Ed. (Wiley, New York, 1966) p 954; A. L. J. Beckwith, The Chemistry of Amides, J. Zabicky, Ed. (Interscience, London, 1970) pp 145-147; S. W. Schneller, Int. J. Sulfur Chem. 8, 591 (1976).

[Mitch]

This is the intermediate before you begin reacting S8 with it. If you ever finish the mechanism, post it here and I'll add it to the Name Reactions section of the forum.

[Albert]

Ok, first of all, I'd like to thank both of you, guys.

Here is the detailed mechanism. Mitch: I think I should improve the quality of the image, but, unfortunately, I don't know how. Or do you think it's good enough?

[Albert]

Before you add the mechanism to the Name Reactions section: I realized that the correct name of the reaction is Willgerodt and not Wilgerodt as I first wrote.

[HP]

And what do you think about the Tos-OH role in this reaction(as catalist may be?)

[Albert]

My prof didn't say anything about catalysis for what concerns this step. Being an industrial process, I daresay temperature plays a key role.

[Mitch]

I think he is referring to the role S8 plays. The S8 has to be modified before the reaction can take place.

[HP]

I also tought about this possible reaction something like ring opening S8 but then Tos-OH + S8-->
Tos-OS7SH - i think this hypothetic intermediat is much reactive than the sulfur itself. Its hard to think NH2 or NH or CHO may open the S8 ring.

[Albert]

Well guys, to be frank with you, I wasn't looking for such a detailed mechanism: the one I posted is sufficient for my purpose.