Author Topic: propyl iodide vs propyl bromide for n-alkylations  (Read 124 times)

antibody2

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propyl iodide vs propyl bromide for n-alkylations
« on: December 13, 2012, 02:17:38 PM »
Is there any reason to think that propyl bromide would be less effective for n-alkylations than propyl iodide. It would certainly be less hassle to make and acquire the reagents for.

Thanks in advance for any thoughts/experience on the matter.
Ab2

Conrad

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Re: propyl iodide vs propyl bromide for n-alkylations
« Reply #1 on: December 15, 2012, 06:02:37 PM »
Iodide is the better leaving group, but the tendency for quaternization (when n-alkylating sec. amines) is higher for iodides. Off course, this also has steric reasons.
HI is easily prepared from KI and phosphoric acid. I just did it two days ago. Use 85% Phosphoric and you can watch the HI formation when the solution turns brown. This way you can easily halogenate your propylalcohol via SN2.
Can u be more specific what substance you want to alkylate?
Speaking of the n-alkylation of 4-piperidone, according to a paper I recently read, they obtained the best results with alkyl chloride, with bromides and iodides giving lesser yields, as well as quaternisation issues. But this might be specific for piperidone chemistry...

atara

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Re: propyl iodide vs propyl bromide for n-alkylations
« Reply #2 on: December 16, 2012, 06:47:36 AM »
Simply put, no. The alkylation will proceed just fine with propyl bromide. It will go faster with the iodide, but a little patience is all you need.

There is one caveat: alkylating an amide must use the alkyl iodide. Some atypical amines will also go too slowly with the bromide. But for 90% of cases you're likely to encounter, bromide is fine.
« Last Edit: December 16, 2012, 06:50:34 AM by atara »

antibody2

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Re: propyl iodide vs propyl bromide for n-alkylations
« Reply #3 on: December 17, 2012, 04:06:43 PM »
Thanks for the feedback wasps.

It was intended as a general question, but the most obvious application would be the n-di-alkylation of tryptamine, for which Shulgin used propyl iodide.

I was not aware that an amide could be successfully alkylated, assumed them to be insufficiently reactive, requiring reduction before subsequent alkylation. Thanks for the tip Atara. This could give rise to some interesting asymmetrical alkylations   8)

atara

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Re: propyl iodide vs propyl bromide for n-alkylations
« Reply #4 on: December 17, 2012, 07:46:10 PM »
Thanks for the feedback wasps.

It was intended as a general question, but the most obvious application would be the n-di-alkylation of tryptamine, for which Shulgin used propyl iodide.

I was not aware that an amide could be successfully alkylated, assumed them to be insufficiently reactive, requiring reduction before subsequent alkylation. Thanks for the tip Atara. This could give rise to some interesting asymmetrical alkylations   8)

The reaction relies on the exceptional basicity of the hydroxide ion in DMSO. KOH in DMSO can deprotonate not only amides but toluene.

http://www.sciencedirect.com/science/article/pii/0040402079870350

akcom

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Re: propyl iodide vs propyl bromide for n-alkylations
« Reply #5 on: January 12, 2013, 06:29:05 AM »
If the amide can be deprotonated, then one would think the alkyl bromide would work just fine?