[texascarbon]

Hi all,
I have a question regarding the gabriel amine synthesis.

At the start you have a phthalimide molecule, which is a secondary amine. It has one hydrogen.

If treated with an acid or a proton donor such as HCl, or HI, can the phtalimide can protonated?

This was an exam question scenario. I was jut wondering, since all the gabriiel amine syntheses I have  seen have involved the nitrogen being deprotonated via a base. However, in this problem, HI/HCl is an acid.

thanks for any input!

[billnotgatez]

Starting off by formatting your post the way you did - especially the title all in caps (shouting) makes me think you did not read forum rules

Click on the link near the top center of the forum page (dark red).
Forum Rules: Read This Before Posting.

[texascarbon]

hey sorry about that im a newb

do you mind answering my question if you have a clue while you're at it? I'm really curious. I'm pretty certain my question didn't violate anymore of your rules

[orgopete]

At the start you have a phthalimide molecule, which is a secondary amine. It has one hydrogen.

If treated with an acid or a proton donor such as HCl, or HI, can the phtalimide can protonated?

This was an exam question scenario. I was jut wondering, since all the gabriiel amine syntheses I have  seen have involved the nitrogen being deprotonated via a base. However, in this problem, HI/HCl is an acid.

thanks for any input!

An amine + HCl  amine•HCl salt

That doesn't look like the question being asked, but I'm just guessing. If one wanted to make a hydrohalide salt of an amine, one would not use HCl/HI together. I'm also presuming this is not intended to be a trick question. A phthalimide can be hydrolyzed with boiling HCL to give phthalic acid and the HCL salt of the amine. In that case, phthalimide must have been protonated to a small degree, but normally a phthalimide plus HCL will not give a salt. I am inclined to think there was additional functionality present that might also react or since HCL is not very effective in hydrolyzing phthalimide, then an HCL/HI mixture might be used. This is just conjecture about what may have been given in a class I didn't attend.

[texascarbon]

thanks for your response pete.

to make things clear, the question was a multistep synthesis that required me to put a structure in a blank box:

firstly, phthalimide is treated with HCl/HI (one of the two i dont remember). There's a blank box for the resulting structure, and I put down a protonated structure ( R-NH2+).

secondly, there's an incoming alkyl bromide. There's a blank box for that resulting structure. I assumed the alkyl bromide would displace a proton via substitution to make HBr and the amine would attack the alkyl group, resulting in R-NH+-R.

The rest of the problem is pretty straight forward, completing the gabriel synthesis.

I was just wondering if I had answered the first part of the question correctly. Is HCl/HI expected to deprotonate the amine?

Does protonation of the amine or aka the pthalimide acting as a BASE also work for the Gabriel amine synthesis?

Hope this makes things more clear. Thanks again!

[orgopete]

This sounds like an error.

Phthalimide + HCl  A

A + alkyl bromide  B

B  etc.

If this is what you are describing, then I think this was an error. This sequence needed a base to make the anion of phthalimide.

[texascarbon]

yeah thats the issue here. Since HCl/HI both are both acids, I didn't think an anion would form. Formation of a cation seemed more likely.

Is forming an anion necessary in the gabriel amine synthesis? From what I see, the imide would eventually be protonated two to threefold anyway, so a cationic pthlalimide species would've resulted in our final liberated primary amine anyway.

[orgopete]

An anion is necessary for an alkylation in the next step. Phthalimide is resistant to protonation and therefore requires harsh conditions to hydrolyze under acidic conditions. Although this is not reported very often, they can be hydrolyzed more easily if first treated with base to cleave the imide into a carboxlic acid-amide. Now that only a single carbonyl group is pulling electrons away from the nitrogen, the amide can be hydrolyzed more easily under acidic conditions.

This should convince you that phthalimide + HCl is probably an error, assuming nothing else can be taking place and that is exactly the sequence being described. I too made errors. I made it a rule to offer points to any student that was the first to discover an error.