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Adam Beneke

Alkylation problem

Bernard Peter Gore  Follow
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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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Deborah Denise Thomas  Follow
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.

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David Shanen  Follow

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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Carsten Junge  Follow
Would you not have the nitrogen acylated by chloroacetylchloride?

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Chris Pollard  Follow
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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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Cooking Secrets  Follow
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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Brian Dave  Follow
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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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Atilla  Follow
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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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