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Author Topic: Alkylation problem  (Read 409 times)

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GinaTageldin

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Alkylation problem
« on: May 19, 2017, 03:25:00 AM »

I have a problem if i use chloro acetylchloide to react with this compound, which is likely to be done O-alkylation or N-alkylation at room temperature and is N-alkylation is preferred since OH is tautomerized with N1 of pyrimidine.
and if i need only N-alkylation to proceed how to prevent alkylation of OH and preserve it free.
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rolnor

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Re: Alkylation problem
« Reply #1 on: May 19, 2017, 06:33:43 AM »

Would you not have the nitrogen acylated by chloroacetylchloride?
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wildfyr

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Re: Alkylation problem
« Reply #2 on: May 19, 2017, 06:46:57 AM »

The N-acetylation is vastly preferred. I would not be surprised if simply mixing them together with a proton scavenger gives nearly pure N-acetylated product in less than an hour.
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GinaTageldin

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Re: Alkylation problem
« Reply #3 on: May 19, 2017, 09:58:05 AM »

Would you not have the nitrogen acylated by chloroacetylchloride?
No, i did not perform the reaction but i am worrying about the activity of OH group
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GinaTageldin

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Re: Alkylation problem
« Reply #4 on: May 19, 2017, 09:59:57 AM »

The N-acetylation is vastly preferred. I would not be surprised if simply mixing them together with a proton scavenger gives nearly pure N-acetylated product in less than an hour.
Could you please specify the reaction condition?
Did you mean to use a base as TEA or what??
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wildfyr

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Re: Alkylation problem
« Reply #5 on: May 21, 2017, 03:27:06 PM »

Yes, a base such as TEA would be fine usually. Though actually in this particular case, since you have a pyridine, perhaps K2CO3 would be better since you can't acid wash out the TEA, but water will get the carbonate salt. Run it in dry DMF, MeCN, or THF at RT.

PS. I just reread your first post. if you use chloroacetylchloride, little alkylation will occur at the amine, since the amine will react with the acid chloride side to give an amide. During that reaction, it is possible to for williamson ether to occur with the hydroxy and alkyl halide and up with dimers. In my experience Williamson ether is usually a crappy reaction with low yields.
« Last Edit: May 21, 2017, 04:28:27 PM by wildfyr »
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GinaTageldin

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Re: Alkylation problem
« Reply #6 on: May 22, 2017, 09:40:19 AM »

Yes, a base such as TEA would be fine usually. Though actually in this particular case, since you have a pyridine, perhaps K2CO3 would be better since you can't acid wash out the TEA, but water will get the carbonate salt. Run it in dry DMF, MeCN, or THF at RT.

PS. I just reread your first post. if you use chloroacetylchloride, little alkylation will occur at the amine, since the amine will react with the acid chloride side to give an amide. During that reaction, it is possible to for williamson ether to occur with the hydroxy and alkyl halide and up with dimers. In my experience Williamson ether is usually a crappy reaction with low yields.
Thank you sir, really appreciate your help
As i understand, chloro acetylchloride would react with the amino group with high yield but it would be contaminated with a little amide at N1 of pyimidine or alkylation at OH. But i could obtain pure product by simple crystallization. Am i true? or need column chromatography.
Thanks again
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wildfyr

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Re: Alkylation problem
« Reply #7 on: May 22, 2017, 10:15:22 AM »


I would expect to see 90+% this if you added those two compounds together in the presence of a proton scavenger.
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GinaTageldin

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Re: Alkylation problem
« Reply #8 on: May 22, 2017, 01:00:39 PM »


I would expect to see 90+% this if you added those two compounds together in the presence of a proton scavenger.
Thank you Sir, appreciate your help.
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