Intergalactic_Captain
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Incompatibilities in organometallics?
All right, what I'm looking for is a listing of functional groups that are incompatible with organometallic reagents, whether they are on the
organometallic molecule or the substrate.
I'm in need of a carbon-carbon bond forming reaction to place an alkyl chain on the carboxyl group of 3,5-dinitrobenzoic acid (or a derivative thereof
more likely). Those of you who know what I'm doing know the logic behind the desire to use 3,5-dinitrobenzoic acid...End goal of this particular step
is 3,5-dintiro-n-pentyl-benzene, or the corresponding butyl ketone or alcohol.
As far as I'm aware, the nitro groups will screw with a grignard or organolithium reaction...What I'm wondering about in particular is a gilman
reagent - I've seen nothing regarding compatibilities regarding them.
Oh, and before anyone suggests exotic reagents - I am unable to order anything from any chemical supplier (the near future may change things, but for
the moment...), so try to keep that in mind.
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not_important
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Why not do a crossed Claisen condensation?
Organo-lithium are still fairly reactive, Gilman is a bit lower but aromatic nitros are fairly reactive - I can't find anything that says it would be
a go. Some suggestive conjugate addition reactions, but nothing like what you're trying to do. Low temperatures might help, but I've no evidence for
anything similar to your case.
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Intergalactic_Captain
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Hmm... Claisen looks interesting, that may be an option. Need to do a little more looking into it though.
What about an alkyl zinc halide, such as (for this application) n-butyl zinc bromide (or iodide)? I've been reading up a bit on organozinc reagents,
and it appears that the reagents and conditions may be within my reach. Unfortunately, none of my books provide any practical details, only
theoretical.
On a side note, how good is Vogel's for providing practical details regarding the limitations of a given reaction? I've got an old (think it came
from here) pdf and am quite impressed with the details it provides, though I'd like something a bit newer. I've been considering picking it up (5th
edition), but the only prices I've found are $20, which is probably a scam, and around $100 everywhere else. If it provides what I'm looking for,
I'll probably pick up a copy, but if not, are there any other recommendations?
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vulture
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Vogel's is very good for practical details. Another option to consider might be Organikum (the book), if there's an english version or if you
understand German.
Organozinc reagents are mild, but they are not that easy to prepare. You either need highly reactive rieke zinc or perform metathesis of a more
reactive organometallic and ZnCl2 (which is a pain to get anhydrous).
One shouldn't accept or resort to the mutilation of science to appease the mentally impaired.
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matei
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A very useful book would also be "Organometallics in Synthesis - A Manual" edited by Manfred Schlosser" (Wiley, 2002).
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chemrox
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Possible workaround
There might be a workaround. I haven't read in detail to find out but the attached ref might lead to an idea or two.
Attachment: Grignard nitroarene mech.pdf (804kB)
This file has been downloaded 5037 times
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Intergalactic_Captain
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Not particularly useful for my purposes, but it is an interesting one-pot method for substituted aryl-hydroxylamines from the nitoarene.
Good thing that they go over the mechanism of attack with a grignard agent and a nitro compound - All I've been able to gather is that they're
incompatible, this paper explains why and the product distributions.
It's interesting though that there are two achievable pathways, neither of which would give the product I'm after. With a normal grignard, you get a
hydroxylamine intermediate that cyclizes/breaks to give the grignard "R" ortho to the nitro. However, if R-O-MgBr is used, you get the hydroxylamine.
That's one hell of an interesting paper. I'm sure I missed something in my interpretation, but I'll probably be pouring over every line of it for
the next couple of days...Hopefully come up with something useful, as I can already see a couple of applications unrelated to this project where it
would be extremely useful.
EDIT
It would appear that the above interpretation is almost entirely wrong. I was looking at the intermediates and reading the wrong numbers...It would
appear that this method gives ortho and para addition of the grignard R to the nitrobenzene through a resonance-stabilized intermediate. I've got to
track this down and see if anyone has done any more mechanistic work on the matter - This paper is pretty good, but they did their work with
naphthalenes, not nitrobenzenes (what I'm looking to work with).
[Edited on 3-1-08 by Intergalactic_Captain]
damn editing....fix one error and find another...
[Edited on 3-1-08 by Intergalactic_Captain]
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Nicodem
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The addition of nucleophiles (in this case RMgX) on nitroaromatics (as well as other electron poor aromatics with substituents able to stabilize
carboanions) proceeds by the formation of the so called Meisenheimer complex. Maybe this can help you finding more information about it, however you
can not use this reaction for preparing 3,5-dinitropentylbenzene.
Have you considered a mixed decarboxylative ketonization of 3,5-dimethoxybenzoic acid with valeric acid? This should give at least some
3,5-dimethoxyvalerophenone which should be easily hydrogenated to 3,5-dimethoxypentylbenzene with 5% Pd-C and 1-3 bar pressure H2 (or else reduced
with Clemensen or Wolf-Kishner reduction system). Since you do not have any delicate functional groups you can then demethylate the MeO groups with
conc. HCl in an autoclave at 150°C or whatever much is required (or just reflux in aq. HBr). This way you can use only simple chemistry without any
delicate step using organometalics.
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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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