Russianwannabe76
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Questions About the Hofmann Elimination
I am enrolled in a supervised study at my community college and the subject I chose is the Hofmann Elimination. Specifically, I wanted to see if it
would be possible to carry it out on amino acid esters/amides. There was a crucial mistake in my research: The Hoffmann Elimination is usually carried
out in water using the hydroxide ion as a source of base. This would lead to the hydrolysis of any ester/amide group on the molecule. Please don't
chew me out for choosing this topic for my supervised study. I am already well aware of the fact that I bit off more than I can chew.
Fortunately, a paper on OrgSyn demonstrated that it is possible to use trimethylamine as a base instead of hydroxide:
http://www.orgsyn.org/demo.aspx?prep=CV7P0491
Would it be possible to use magnesium methoxide in methanol to carry out the Hofmann Elimination on hypaphorine methyl ester iodide? Could another methoxide salt work?
I've also thought about using a 2,6-dimethylphenylamide group in place of the methyl ester because it appears to be less susceptible to hydrolysis
than other amides, due to it co-existing with a quaternary ammonium hydroxide in NileRed's video about denatonium benzoate. Would that work?
Please, by all means, let me know of possible solutions to my problem.
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j_sum1
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My first question is, are you committed to this topic? If it is possible to change then you probably should do so. Otherwise your project will be an
uphill battle one way or another.
I would be talking with my supervisor, outlining the details of the hurdle encountered and the possible solutions and asking for advice. Such an
approach gives you the maximum number of options and demonstrates that you have acquired a good understanding of the chemistry involved. Neither of
these two things are bad.
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Texium
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Well, the orgsyn link you sent is not a Hofmann elimination (Hofmann elimination ONLY encompasses the elimination of a quaternary ammonium), so that
isn’t doing you any favors, since elimination of a halide is much easier and doesn’t require as strong of a base.
You’re in luck though! It so happens that my research is focused on Hofmann eliminations, so I’m well read on the subject, and have in fact
contributed to the recent literature.
Sodium methoxide in methanol may work for the substrate that you ask about. Potassium t-butoxide would work better because it’s an even stronger
base, but you would likely see some substitution of the ester.
Typically, we run our eliminations in refluxing THF with potassium t-butoxide as a base. In a case containing a methyl ester, we saw partial
conversion to the t-butyl ester, so we ran it again with the t-butyl ester from the start, and it worked beautifully.
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DraconicAcid
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I'll also add that amides are far less easily hydrolyzed than esters.
Please remember: "Filtrate" is not a verb.
Write up your lab reports the way your instructor wants them, not the way your ex-instructor wants them.
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Russianwannabe76
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Thank you so much, Texium! Hopefully this will solve my problem.
By the way, may I have the link to the research you are referring to? It could really help me with my project.
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