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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: zuriel on December 04, 2012, 05:47:19 AM

Title: Acylation of 7-azaindole at the C-3 position.
Post by: zuriel on December 04, 2012, 05:47:19 AM

Hi folks,

I recently managed to acylate 7-azaindole following this paper here:

http://www.ncbi.nlm.nih.gov/pubmed/12182666

My only issue now is the next synthetic step which is under basic conditions. My fear here is that the free NH will be deprotonated. I've tried a benzenesulfonyl protecting group to no avail but I'm wondering are there any other good protecting groups for the NH that won't affect so much the reactivity of the 7-aza?

Thanks!

Title: Re: Acylation of 7-azaindole at the C-3 position.
Post by: OC pro on December 04, 2012, 09:58:49 AM

Boc?

Title: Re: Acylation of 7-azaindole at the C-3 position.
Post by: Dan on December 04, 2012, 10:55:33 AM

I'd probably try the reaction without a protecting group on a test scale to see if it is really necessary to protect it. How basic are the conditions going to be? It would help if you can give more info on the next step, but I realise you may not be in a position to do so.

Quote from: zuriel on December 04, 2012, 05:47:19 AM

I've tried a benzenesulfonyl protecting group to no avail

Does this mean the protection step failed, or that the following step failed as a result of the protecting group?

Quote

but I'm wondering are there any other good protecting groups for the NH that won't affect so much the reactivity of the 7-aza?

Electron withdrawing PGs (like sulfonamides, carbamates etc.) will probably significantly alter the electronics of the system due to their conjugation with the indole N lone pair. While this may not translate to a problem (depending on the next step), perhaps an alkyl group (e.g. Bn) would behave more similarly to the unprotected compound?

Title: Re: Acylation of 7-azaindole at the C-3 position.
Post by: zuriel on December 05, 2012, 06:11:22 PM

Quote from: Dan on December 04, 2012, 10:55:33 AM

I'd probably try the reaction without a protecting group on a test scale to see if it is really necessary to protect it. How basic are the conditions going to be? It would help if you can give more info on the next step, but I realise you may not be in a position to do so.

Quote from: zuriel on December 04, 2012, 05:47:19 AM

I've tried a benzenesulfonyl protecting group to no avail

Does this mean the protection step failed, or that the following step failed as a result of the protecting group?

Quote

but I'm wondering are there any other good protecting groups for the NH that won't affect so much the reactivity of the 7-aza?

Electron withdrawing PGs (like sulfonamides, carbamates etc.) will probably significantly alter the electronics of the system due to their conjugation with the indole N lone pair. While this may not translate to a problem (depending on the next step), perhaps an alkyl group (e.g. Bn) would behave more similarly to the unprotected compound?

Hi Dan,

Thank you for your response. I will give more details on the conditions soon! My main goal is to make the potassium oxalate salt of 7-azaindole and combine this with an acetic acid (for example indole-3-acetic acid) under base conditions to make a maleic anhydride.

This procedure is well documented in the case of indole but not so much 7-azaindole.

The main reason I want to protect the -NH is of course to keep good yields and to have the possibility of functionalizing the NH with other groups.

I tried acylating 7-azaindole with a benzenesulfonyl group 'on the NH' but that failed.

 :)