[weiweishen]

Has anyone used 4-nitrophthaloyl protection group to protect amine? Is it easy to be removed. I used phthaloyl protection group to protect amine group of my compound that also has a acylal linkage. When I used hydrazinolysis to remove the phthaloyl group, the acylal linkage was also destroyed. Some literature said the 4-nitrophthaloyl group is much easier to be removed by using methylhydrazine at -50 degree for half hour. Does anyone have some experiences on that.

Thank you

[sjb]

Is there anything in Greene and Wuts or similar? What else do you need your protecting group to be stable towards? Do you have to use the 4-nitrophthaloyl group? Deprotection with a hydrazine doesn't really seem my idea of fun, but if that's what it takes...

[kiwi]

Is there anything in Greene and Wuts or similar? What else do you need your protecting group to be stable towards? Do you have to use the 4-nitrophthaloyl group? Deprotection with a hydrazine doesn't really seem my idea of fun, but if that's what it takes...

Actually knocking phthaloyl groups off with hydrazine is much more fun than quite a few of the alternatives. Tetrachlorophthaloyl has also been used to protect sensitive (b-lactam) substrates according to Green and Wutts, and you can cleave it under similar conditions. Have you tried heating your phthalate with MeNH2?

[weiweishen]

The reason why I have to use phthaloyl or nitro-phthaloyl as protection group for amino acid is that I have to protected the both H of amine in order to make acyl bromide of amino acid. Fmoc is good for makine acyl chloride of amino acid but the Fmoc protected amino acid bromide is not stable. But the final product has an acylal group (also called gem-diester of aldehyde), it is very easily to be broken by hydrazine. When I used phthaloyl as protection group, only 10 to 20% product was obtained from hydrazinolysis. This is the reason why I decided to choose 4-nitrophthaloyl as protection group because 4-nitrophthaloyl has an electron-withdrawing nitro that may make the hydrazinolysis much milder. I still did not start the test. I wanted to know whether anyone had similiar experiences that may help my experiment design

[orgopete]

If you lack selectivity with phthaloyl deprotection, then I would expect the nitro to be better. If you lack reactivity in the deprotection, then methyl hydrazine is probably more reactive. I would expect the second part of the hydrolysis to be selective as it is intramolecular, however, since you have a derivative of an amino acid, I don't know whether you have done anything to block an intramolecular reaction on it.

If you gave the structures, we might be able to agree with your premise or even suggest suitable alternate routes. If you do not have an amide or ester that you are trying to protect, then an acid catalyzed amide hydrolysis can be done if you hydrolyze the phthalimide first.