sciencebob
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Need help with synthetic route
Hello fellow chemists! 
I'm working with the attached reaction but have issues synthesizing to the third step - yield is only 10%. Any advice? I can give more details as
needed!
Thanks as ever!
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smuv
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Could you post a reference for that DBU claisen? I might be able to provide some help if you post your procedures and also what the side products
were.
I assume aldol reactions are your side-products? Might help to run the reaction very dilute to keep the intramolecular claisen (or would it be
Dieckmann even though its an ester and ketone?) favored over intermoleculer aldols. But I don't think the yields will ever be high because the ketone
is a good bit more acidic than the amide.
Of course you can get around this problem by changing the steps of your synthesis, taking the mannich product, and adding it to a huge excess ethyl
acetate enolate followed by cyclization of this product by an intramolecular transesterification.
[Edited on 1-5-2011 by smuv]
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sciencebob
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Thanks so much for the quick reply! I'm going to look into your suggestions and will get back to you.
Thanks again!
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chemrox
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How did you select DBU as the catalyst? Is this a procedure you got from a paper or from a patent? If the former, which one? Please post the
article If the latter, patents often leave out critical information. (@SMUV) I'm assuming the acylation goes in almost quantitative yield so maybe
a different catalyst is in order. Or maybe some CuI in the mix?
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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smuv
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I dunno chemrox. The problem is I don't see any way of selectively deprotonating the C-H amide vs the C-H ketone. There is no way to rely on sterics
because there are no steric differences between a methyl ketone and an acetate, and i believe the deprotonated ketone is both the kinetic and
thermodynamic product. While it is true, the cyclicized final product is thermodynamically more stable, I can't see a great way of favoring its
production. Maybe prolonged reaction times and hoping the reversibility of aldols will allow for more of the desired cyclicized product.
I will admit though, I know less about this type of chemistry than I wish I did. I very well may be overlooking something.
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Nicodem
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Quote: Originally posted by sciencebob  | | I'm working with the attached reaction but have issues synthesizing to the third step - yield is only 10%. Any advice? I can give more details as
needed! |
You want an advice, yet you don't bother posting the pertaining references? How very nice of you!
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