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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: syunchow on September 18, 2010, 05:48:44 AM

Title: Pthalimide deprotection.
Post by: syunchow on September 18, 2010, 05:48:44 AM
I'm trying to deprotect a pthalimide-protected amine. The standard protocol involves methylhydrazine  in ethanol, unfortunately I can't get the reagent until 2 weeks later. Is it possible to use dimethylhydrazine instead?
Title: Re: Pthalimide deprotection.
Post by: orgopete on September 18, 2010, 08:43:30 AM
As long as it isn't 1,1-dimethylhydrazine. The rational for the effectiveness is to formation of the diketopiperazine. That is, tethering a second nitrogen enhances the amide cleavage by intramolecular ring formation.

There was some discussion on nitrile hydrolyses, here: http://www.chemicalforums.com/index.php?topic=42921.0
Movies suggested using lithium hydroxide, including conditions. I agree with this as a possible receipe for use under basic conditions as movies explained the chemistry. If your amine can tolerate acidic conditions, the alternate method I would suggest is to first treat your phthalimide with base to open the phthalimide. They are very base sensitive and this reaction occurs very readily, as a virtual titration. Then, add a mineral acid and hydrolyze the remaining amide bond.

Two carbonyl groups greatly reduce the basicity of the nitrogen. An amide is far more basic and can be protonated readily. Formation of a tetrahedral intermediate will protonate your amine making it the weakest base and therefore the best leaving group. You can filter off the phthalic acid, neutralize and isolate your amine.
Title: Re: Pthalimide deprotection.
Post by: discodermolide on September 19, 2010, 02:42:00 AM
I'm trying to deprotect a pthalimide-protected amine. The standard protocol involves methylhydrazine  in ethanol, unfortunately I can't get the reagent until 2 weeks later. Is it possible to use dimethylhydrazine instead?

If your molecule can stand it, you can reflux it in a solution of conc HCl.
Title: Re: Pthalimide deprotection.
Post by: syunchow on September 20, 2010, 03:08:49 AM
I have decided to go with hydrazine monohydrate in MeOH, in the presence of an olefin scavenger (4-pentenol) as my compound has an acetylene group. Reaction is running and seems like the reaction is working (checked using MS).