Chemistry Forums for Students > Organic Chemistry Forum

Sildenafil Synthesis - Ring Formation

(1/2) > >>

daylightbabii:
Hello, I was just wondering how the mechanism would occur in the final steps of synthesizing Sildenafil. I know that the tert butoxide would deprotonate the primary amide so it can attack the carbonyl group. I’m just not sure about the mechanism in removing the resulting alkoxide and forming the enamine in an acidic condition (HCl/H2O). I don’t know how to start the proton transfers because I’m confused on what goes first. An advice could really help me, thank you. :)

rolnor:
Question is how the intermediate after the first step looks like but the last step is perhaps the same as when imines form?
https://www.researchgate.net/publication/296906421_Synthesis_of_novel_2-amino-5-arylazothiazol_derivatives_and_their_biological_impacts_Assessment_of_toxicity_and_antioxidant_enzyme_activities/figures?lo=1

daylightbabii:

--- Quote from: rolnor on July 20, 2021, 04:05:50 PM ---Question is how the intermediate after the first step looks like but the last step is perhaps the same as when imines form?
https://www.researchgate.net/publication/296906421_Synthesis_of_novel_2-amino-5-arylazothiazol_derivatives_and_their_biological_impacts_Assessment_of_toxicity_and_antioxidant_enzyme_activities/figures?lo=1

--- End quote ---

First of all thank you for replying, the link you sent me is what I thought at first and then I tried to draw it but I got confused on which would be deprotonated first, the HCl or the NH because it still has a hydrogen that can undergo proton transfer. I tried to do it with HCl first but then if I protonated the OH with H2O won't the OH in water be a poor leaving group?

rolnor:
The OH gets protonated and becomes  a better leavinggroup and there is a electron pair on the nitrogen that can attack the carbon even if you dont pick the proton on the nitrogen. This way you get a positive charge on the nitrogen  and then finaly the proton leaves the nitrogen.

daylightbabii:

--- Quote from: rolnor on July 20, 2021, 11:56:35 PM ---The OH gets protonated and becomes  a better leavinggroup and there is a electron pair on the nitrogen that can attack the carbon even if you dont pick the proton on the nitrogen. This way you get a positive charge on the nitrogen  and then finaly the proton leaves the nitrogen.

--- End quote ---

I just need to ask, will the OH be protonated by another HCl or is it going to deprotonate H2O so that it becomes a good leaving group? I'm just really confused on what is used up and what by products where left at the end of the reaction, thank you for helping me.

Navigation

[0] Message Index

[#] Next page

Go to full version