karlos³
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7-bromo-2-heptanone preparation
Hi!
I want to prepare the title compound, from 6-bromo hexanoic acid and acetic acid anhydride. My main concern, does the bromine atom interfere in this
reaction?
What would bee the best catalyst, i thought about carrying out the whole reaction in pyridine, or is it better to use an anhydrous acetate salt?
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Nicodem
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Please provide more details and references. You can't really expect anybody to give a reliable opinion without knowing what procedure you are
following. Since you mention base catalysis I would expect you talk about some sort of a Dakin–West reaction, but then your substrate is an
aliphatic carboxylic acid that has none of the features required for the mechanism of this reaction to apply. As a conclusion, I truly have no idea
what you are talking about and without the pertaining references I think nobody else ever will.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
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Nicodem
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Thread Moved
4-8-2012 at 10:17 |
karlos³
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So
Tran, K.; Bickar, D. J. Org. Chem. 2006, 71, 6640–6643. (doi:10.1021/jo0607966)
my general question is if this reaction could be applied to aliphatic carboacids, yes thats right.
So the answer is, if my acid is not enolizable its not fitted for the modified dakin west for production of methylketones from carboxylic acids?
Is there another more convenient method to produce methylketones from carboacids beside methyllithium?
[Edited on 4-8-2012 by karlos³]
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Nicodem
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Quote: Originally posted by karlos³  | So
Tran, K.; Bickar, D. J. Org. Chem. 2006, 71, 6640–6643. (doi:10.1021/jo0607966)
my general question is if this reaction could be applied to aliphatic carboacids, yes thats right.
So the answer is, if my acid is not enolizable its not fitted for the modified dakin west for production of methylketones from carboxylic acids?
Is there another more convenient method to produce methylketones from carboacids beside methyllithium? |
The classical Dakin-West reaction involves the C-acylation of the intermediate azlactone and is thus limited to alpha-aminoacids. That article
describes the application of a modified Dakin-West reaction on arylacetic acids. This is nothing new, there are older articles describing the same.
Arylacetic acids are easily enolizable in the form of their mixed anhydrides, but your substrate does not apply. What is new is the application of
1-alkylimidazole catalysts and the authors claim:
| Quote: | | Hydrocinnamic acid, a compound previously reported to be unreactive under Dakin−West conditions, forms 4-phenyl-2-butanone when the reaction is
catalyzed by 1-methylimidazole. |
Now, hydrocinnamic acid is certainly not that easily enolizable and this efficiency demonstrated by the catalysis with 1-methylimidazole is thus
something promising and is potentially an indication that other difficult substrates could work as well. Unfortunately, the authors do not report
trials on any other such difficult substrate. So it is not possible to say it could apply in your case. The 6-bromo substituent is another problem of
its own. The compound can potentially succumb to nucleophilic substitutions or cyclization to a lactone. I do not believe it could work, but try and
see.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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karlos³
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Hm this sucks, is there any other option to make the title compound out of 6-bromohexanoic acid? Methyllithium is no option because of the bromine
atom, and i dont know any other method to do this.
A grignard is no option either out of the same reason.
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Nicodem
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The Mg-Br exchange is not even remotely so rapid as the Li-Br exchange, and thus the alkyl bromides are compatible with grignards (except for allyl,
benzyl and tertiary bromides) when the actual grignard addition is rapid enough and the product does not react further (e.g., cyclize).
In this specific case, you would first have to prepare the 4-bromohexanoyl chloride and react it with MeMgCl (which is commercially available) in the
presence of NMP or DMF using the method described in DOI: 10.1039/C1OB05780D. With some luck you might be able to obtain the desired product.
Or, to cite my self from another thread (where a quite suitable reference is given):
| Quote: Originally posted by Nicodem | | Also, keep in mind that the ketones can be obtained from grignards and acyl chlorides directly if certain conditions are met. Not always do the
ketones react further. Additionally, certain reaction conditions (solvents and additives) highly increase the selectivity (for such an example, see DOI: 10.1039/SP533). |
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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karlos³
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Thank you for the input Nicodem.
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