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Topic: hydroxymethyl imidazole synthesis  (Read 4274 times)

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Offline zarhym

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hydroxymethyl imidazole synthesis
« on: December 29, 2017, 12:29:07 AM »
I am trying to synthesis a hydroxymethyl imidazole following a literature procedure.

DOI: 10.1039/A701751K,
J. Chem. Soc., Perkin Trans. 1, 1997,0, 2203-2210.

My understanding of this imidazole formation mechanism is through loss of two water molecules to get a alkene intermediate. This intermediate further hydrolysis under acidic condition to for a hydroxymethyl imidazole.

Am I understand this mechanism correctly?

I tried reaction by mixing trifluoroacetamidine and butane-2,3-dione in water and stirred at R.T. overnight.
I am also trying neat reaction at 60 degree C.
Nothing happened so far. 

Is there any suggestions?

Thanks a lot.


Offline pgk

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Re: hydroxymethyl imidazole synthesis
« Reply #1 on: December 29, 2017, 10:33:55 AM »
Probably, fluorine atom forms H-bonds with the amidine group and the HCl that inhibit the reaction.
Try to work at temperatures higher than 70-80oC, in order to offer enough heat to break any fluorine H-bond. It might work.
Also, add a little amount of aqueous HCl.
« Last Edit: December 29, 2017, 11:18:45 AM by pgk »

Offline kriggy

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Re: hydroxymethyl imidazole synthesis
« Reply #2 on: December 29, 2017, 07:17:00 PM »
The CF3 group is strongly electron withdrawing so it reduces the reactivity of the nitrogen atoms, that might be why the reaction is not working for your. Maybe heat it more ? Also, the amine group is protonated which could also have some effect on reactivity, maybe try to add some base like TEA. It could increase the reactivity of the amine via neutralization while still being acidic enough to catalyze the reaction further...
trying more acid as suggested by pgk could work as well

Offline zarhym

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Re: hydroxymethyl imidazole synthesis
« Reply #3 on: January 05, 2018, 03:25:54 AM »
I guess I am finally getting something after several experiments. I'll update it soooooon.
Thanks for your suggestions.

Offline zarhym

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Re: hydroxymethyl imidazole synthesis
« Reply #4 on: February 01, 2018, 03:43:05 AM »
This synthesis approach does not work eventually. The reason is strongly electron withdrawing nature of the CF3 group. We tried replacing this CF3 group with a alkyl group, which gives clean reaction with high yield. However, with CF3 group, it never works and only gives messy reaction.



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