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Topic: Is theophylline a good nucleophile?  (Read 2840 times)

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Offline Lintaro

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Is theophylline a good nucleophile?
« on: February 22, 2017, 11:59:59 PM »
Hello there!

My research team and I are trying to synthesise a new compound, and one of the steps involves an SN2 reaction with theophylline as our nucleophile:



Our hypothesis is that since Br is a good leaving group, it will be displaced by the N-H from the imidazole ring of theophylline. However, we're still not sure if theophylline is a good nucleophile.

I wanted to ask if this reaction is feasible, and if it is, what sort of catalysts and conditions do we need to prepare to carry out this reaction? Any papers. journals and references that I could read would also be appreciated.

Thank you in advance.  :)
« Last Edit: February 23, 2017, 12:10:55 AM by Lintaro »

Offline sjb

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Re: Is theophylline a good nucleophile?
« Reply #1 on: February 23, 2017, 05:31:17 AM »
Imidazole is certainly a good leaving group (look into CDI chemistry) so I'd be wary about that. Also, be careful of regioselectivity, I'm not sure that the reaction will go as shown.

Offline rolnor

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Re: Is theophylline a good nucleophile?
« Reply #2 on: February 23, 2017, 06:23:11 AM »
One problem with the bromide, if you want to use any base as catalyst, is that it easily will eliminate. Perhaps the so formed unsaturated amid can react with the theophyline anyway?

Offline hypervalent_iodine

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Re: Is theophylline a good nucleophile?
« Reply #3 on: February 23, 2017, 04:46:50 PM »
Your problem might be the other nitrogen, which has a lone pair available for reaction and doesn't need to be deprotonated to react.

Offline hypervalent_iodine

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Re: Is theophylline a good nucleophile?
« Reply #4 on: February 23, 2017, 04:52:14 PM »
You could build up the theophylline with the amide pre-installed as another option, but that depends on your synthetic capabilities. This might be of use:

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200300377/abstract

Offline Optimist

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Re: Is theophylline a good nucleophile?
« Reply #5 on: February 27, 2017, 09:38:32 PM »
I have done this kind of reaction before, It will go fine with more than 80% yield.
But don't forgot to add base like K2CO3 anhydrous. I use to do these kind of reaction in dry DMF and stirred reaction mixture under inert atmosphere overnight.

Cheers!!!!!!

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