Sciencemadness Discussion Board

Ester enolate

nelsonB - 25-7-2016 at 15:17

so i was looking about some reaction
i saw this
Ester Enolates

i was wondering what is the typical yield for this kind of reaction
and if the X could a chlorine molecule


such as this reaction

stoichiometric_steve - 25-7-2016 at 18:18

maybe

AvBaeyer - 25-7-2016 at 19:15

As written, this will likely be a poor yielding reaction overall as you are proposing to alkylate a secondary (and not all that reactive) anion with a secondary alkyl chloride. This first step will really poorly impact your overall yield. Switching to an iodide from the chloride will probably help a fair amount but the alkylation yield will still not be anywhere near quantitative. It would also help to use a fair excess (>50%) of the iodide to help things along. Finally, the alkylation reaction as posted is VERY concentrated. This will probably result in a hard-to-manage slurry at some point during the process. All that being said, you will no doubt be able to obtain your desired ketone if you can isolate the intermediate alkylated keto ester. Those last steps are a relative piece of cake.

AvB

Pasrules - 26-7-2016 at 15:12

Sec-butyl ethyl ether will be produced and your base will attack the ethyl acetoacetate.
To improve the scheme use 2-iodobutane as suggested by AvB and reduce your quantities down adding base gradually.

Metacelsus - 26-7-2016 at 16:10

I've never done any acetoacetic ester syntheses, but I have done a malonic ester synthesis (using a primary alkyl bromide, and anhydrous potassium carbonate as a base). One cause of lower yield was formation of dialkylated product. However, this might be less likely to happen with a relatively unreactive secondary alkyl chloride.

CuReUS - 26-7-2016 at 17:28

using Cl ,there can be both O and C alkylation -http://pubs.acs.org/doi/abs/10.1021/jo01258a101
better to use Br or I

DraconicAcid - 26-7-2016 at 18:00

Quote: Originally posted by Metacelsus  
I've never done any acetoacetic ester syntheses, but I have done a malonic ester synthesis (using a primary alkyl bromide, and anhydrous potassium carbonate as a base). One cause of lower yield was formation of dialkylated product. However, this might be less likely to happen with a relatively unreactive secondary alkyl chloride.


If you can deprotonate your acetoacetate with carbonate, do so. Carbonate won't compete for the alkyl bromide. It may be slower, but that's better than getting nothing.

Dr.Bob - 26-7-2016 at 18:31

Also, try using the 2-chlorobutene or 2-bromobutene instead, it will be a much hotter alkylating agent. You could then reduce it back to the saturated group later. I have done almost that exact alkylation before that way. The alkyl was very hard to get any reaction, but the haloalkene was much more reactive. Adds a step, but works well. Just a suggestion.

AvBaeyer - 26-7-2016 at 18:54

Dr.Bob,
I assume you are referring to 2-halo-3-butene (the allylic derivative) and not the vinylic halide.

AvB

Dr.Bob - 28-7-2016 at 07:26

Yes, I was low on coffee at the time. I think I used the 2-chloro-3-methyl-3-butene, which is symetrical, thus giving only one major product, whereas the 2-halo-3-butene can give both isomers, due to allylic reactivity. It's been a long time since I tried that, so I barely remember the details now, unfortunately. But halo allyl groups are much hotter akylating agents.