[wisconsinium]

I am trying to do a Pfitzinger reaction and can't isolate a product!
Here is the Wikipedia page link: http://en.wikipedia.org/wiki/Pfitzinger_reaction

More specifically I am trying to do the Halberkann variation, where I heat N-acetyl isatin with KOH and it should hydrolyze, rearrange, and condense into a 2-hydroxy-quinoline-4-carboxylic acid. I have tried different times, temps, concentrations, and have many procedure references that don't help with my problem. Upon careful acidification of the room temp solution, all I get back is about 20% of unsubstituted isatin, from the hydrolysis of the N-acetyl group. So where is my product? It is supposed to precipitate out when "neutral to Congo red" (which I think is pH4), but nothing happens until it is more acidic and isatin crashes out. I tried extracting and only got out a trace amount of isatin then too. Any help is appreciated!

[discodermolide]

I am trying to do a Pfitzinger reaction and can't isolate a product!
Here is the Wikipedia page link: http://en.wikipedia.org/wiki/Pfitzinger_reaction

More specifically I am trying to do the Halberkann variation, where I heat N-acetyl isatin with KOH and it should hydrolyze, rearrange, and condense into a 2-hydroxy-quinoline-4-carboxylic acid. I have tried different times, temps, concentrations, and have many procedure references that don't help with my problem. Upon careful acidification of the room temp solution, all I get back is about 20% of unsubstituted isatin, from the hydrolysis of the N-acetyl group. So where is my product? It is supposed to precipitate out when "neutral to Congo red" (which I think is pH4), but nothing happens until it is more acidic and isatin crashes out. I tried extracting and only got out a trace amount of isatin then too. Any help is appreciated!

How do you know that it is Isatin coming out of solution when you make it more acidic?
Did you run a TLC on this reaction?

[wisconsinium]

I do get new spots on the TLC so the starting material is reacting. The recovered isatin was identified by TLC and NMR.

[discodermolide]

I do get new spots on the TLC so the starting material is reacting. The recovered isatin was identified by TLC and NMR.

Did you isolate the new spots? Where are they after the second acidification, in the mother liquors?

[wisconsinium]

Yes it is in the mother liquor. It won't precipitate or come out with extraction.

[discodermolide]

Yes it is in the mother liquor. It won't precipitate or come out with extraction.

I would try and isolate the new products from the mother liquors.
Then you may be able to say better what is going on in the reaction.

[wisconsinium]

How can I get it out of the mother liquor if it won't precipitate or extract?

[discodermolide]

How can I get it out of the mother liquor if it won't precipitate or extract?

Evaporate it to dryness.

[wisconsinium]

Yeah, I can do that. I guess I was hoping that there was some trick to get it out of the water, because that can become a lot of water to evaporate on larger scales.

[discodermolide]

Yeah, I can do that. I guess I was hoping that there was some trick to get it out of the water, because that can become a lot of water to evaporate on larger scales.

Azeotrope it off with toluene or n-butanol.