[Chantel]

hi,
I have a compound, which is has three ethylphthalimide attached to each N atoms on TACN(1,4,7-triazacyclononane) respectively. I have been trying to deprotect the pthalimide groups to form primary amines. I tried with hydrazine monohydrate in ethanol and refluxed for 3 nights. However, i could not get the complete deprotected compound. I am not sure what goes wrong. Probably the work up part. Any suggestion?
I found a thesis which showed 1,2-diaminoethane could deprotect pthalimide as well,however I do not have it in my lab,do you think that 1,2-diaminopropane can work the same way?

[MissPhosgene]

 With the longer alkyl chain on the diaminopropane, reaction rates regarding displacement of the amine being deprotected may be longer. You will be making a 7-membered ring instad of 6, so that could also take some time or not work so well. Worth a shot so you can know unless looking it up is easier.

Have you tried reducing with sodium borohydride followed by treatment with acetic acid at 80 celsius or so?

[Chantel]

nope.I couldn't find any other methods except hydrazine and 1,2-diaminoethane. How much sodium borohydride should I use and in which solvent?

[MissPhosgene]

Tetrahedron Lett., 1984, 25, 2093-2096

Transformation: Pthalimide to hydroxy-amide:

NaBH4, 5 eq. i-PrOH:H20 6:1, RT 24 hrs

Transformation: hydroxy-amide to free amine

AcOH, 18 eq. 80 deg Celsius, 2 hours or so.

[Chantel]

Thanks a lot for your information. However, what is dowex column?is it different with those normal column chromatography?

[MissPhosgene]

Dowex is probably a type of ion exchange resin. Are there specifications which come after the word Dowex, such as a number and/or some letters?

[Chantel]

ya,it said is Dowex 50 (H+) column..i have no any idea about it >.<

[orgopete]

I suggest simply hydrolyzing the imide with base to the acid amide. With examples I have tried, this is a virtual titration reaction. Then, you can treat the amide to standard acid catalyzed hydrolysis if you compound is stable to such conditions. This is milder than hydrolysis with strong base or beating it with a mineral acid. Phthalimides are rather acid stable, but the acid amide derived from it will be rather more easily hydrolyzed.

[AC Prabakar]

I just want to add some points regarding Phthalimeide deprotection.

hi,
I have a compound, which is has three ethylphthalimide attached to each N atoms on TACN(1,4,7-triazacyclononane) respectively. I have been trying to deprotect the pthalimide groups to form primary amines. I tried with hydrazine monohydrate in ethanol and refluxed for 3 nights. However, i could not get the complete deprotected compound. I am not sure what goes wrong. Probably the work up part. Any suggestion?
I found a thesis which showed 1,2-diaminoethane could deprotect pthalimide as well,however I do not have it in my lab,do you think that 1,2-diaminopropane can work the same way?

Have you tried any time with other organic bases like methylamine(40% in water or 25% in methanol)?
The following are the some of the commonly used organic bases.
1.Ethanolamine
2.Methylamine
The advantage of these bases are relatively milder condition when compare to Inorganic bases.

Tetrahedron Lett., 1984, 25, 2093-2096

Transformation: Pthalimide to hydroxy-amide:

NaBH4, 5 eq. i-PrOH:H20 6:1, RT 24 hrs

Transformation: hydroxy-amide to free amine

AcOH, 18 eq. 80 deg Celsius, 2 hours or so.

This is a very elegant method for the phthalimide deprotection.thanks "MissPhosgene" for your timely given literature.
Although the above method requires milder condition reaction rate will be slower  when compare to usage or organic bases.

The advantages of this method are as follows:-
1.Relatively milder reaction condition with wide variety of functional group tolerablility
2.As a by product we will be getting phthalide which is having same commercial value.

What ever reagent you use it is better to understand what exactly going in your reaction.

Try to define your reaction under any one of the following cases:-
(i)Reaction is proceeding not going for completion
(ii)Reaction is completing only isolation of product is problem
(i)Reaction is not proceeding due to
    (a)Reactant/compound degradation
    (b)Side reaction of Reactant/compound

Best of luck!!!