myristicinaldehyde
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Another mechanism question
Chem player posted a very good video a while back about making a precursor to indole (Reissert reaction). It used a very powerful base and 2-nitro
toluene.
If I understand correctly, the base deprotonates the toluene, and the carbanion is stabilized by resonance and the electron withdrawilingness of the
NO2 group.
This carbanion reacts with the б+ of the oxalic ester, which is due to the 2 carbonyls.
1- would any EWG work in place of the nitro? Like for example dimethyltoluidine. It could resonate to make the amine to an imin(ium?) with 2 methyl- a
quaternary amine of sorts. But this looks strange.
2- If a condensation was to be done with a malonate ester, would a bond be formed between the carbanion and the а-carbon?
Casual source hunting didn't conclusively answer my questions, and my org Chem is shakey. I would like to set up an experiment to test my theories,
but I have no reagent! (Unless someone is willing to donate    )
Edit: Ænglish
[Edited on 2016-6-29 by myristicinaldehyde]
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aga
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Cool. somebody doing at least a little research.
Makes a very nice change.
WHICH casually sourced references were inadequate ?
Perhaps they were not, and maybe you missed something.
Post the references you found/read and we will avidly read them for answers.
[Edited on 29-6-2016 by aga]
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myristicinaldehyde
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The inadequacy was my own- the papers I could read in the entirety were highly technical, and "easier" too vague! Since I obsessively horde very paper
aimcome across, I will post them once the labtop boots up- I am using my phone right now.
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myristicinaldehyde
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OK, iminium IS the name, and they do exist. Whether they could play a role is in doubt.
Wiki for the lazy: https://en.m.wikipedia.org/wiki/Iminium
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aga
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'lazy' describes it quite well.
We're just looking for Chemistry here.
Perhaps this is the wrong website ?
Maybe not.
If you're looking for Help, switch to U2U and i'll try.
Can't guarantee results, but i'm willing to give it a go.
You can always go back to Behaviour #1 if it does not work out.
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myristicinaldehyde
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OK, here are the ones I chose to keep for a "second reading", and some backgrounds
The reaction: http://www.orgsyn.org/demo.aspx?prep=cv5p0567
the wiki gives some that I looked at, so just look at the ref part: https://en.wikipedia.org/wiki/Reissert_indole_synthesis
Obligatory hive thread, but mostly about the cyclization, not the intermediate formation: https://the-hive.archive.erowid.org/forum/showflat/Cat-/Numb...
Helpful Ochem page: http://www.masterorganicchemistry.com/2012/02/27/7-factors-t...
Paper (link): http://onlinelibrary.wiley.com/doi/10.1002/1522-2675(20010613)84:6%3C1441::AID-HLCA1441%3E3.0.CO;2-W/abstract
Casual reading left me confused, but it did give me the name of the resonance! It's aci-nitro tautomerization! aci-nitro tautomerization confuses me,
I need to do more reading.
Another paper: http://www.nrcresearchpress.com/doi/pdf/10.1139/v86-321 It helped me with the theory
So, a better question would be
"do other functional groups undergo aci-(group) tautomerization?" and
"does the carbanion intermediate undergo the Claisen (pretty sure it counts as a claisen) Condensation with other esters of similar structure?"
Edit: Didn't see your post! There is more, but I am also working on a literature review for school, so my browser and desktop is a mess of PDFs and
tabs right now.
[Edited on 2016-6-29 by myristicinaldehyde]
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aga
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Test: Failed.
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myristicinaldehyde
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Interestingly, the Hive's Nicodem says
>>When I said that the deprotonation of o-nitrotoluene is a much slower process than the usual acid-base reaction, I meant that it is not in the
microseconds range of speed but maybe up to 8 magnitudes slower (in the 10 sec range – not days!). From my own experience I can tell you that p- and
o-nitrotoluene deprotonate completely in few minutes when stirred in NaOH/EtOH. This can bee nicely followed by the slow change of color from the
nitrotoluenes’ yellow to the dark brown-reddish color of the quinone-like structure of the anion counterpart (the nitronate form).
This is curious- the OrgSyn calls upon KOEt, and Chemplayer got NaOEt to work, (however it didn't make indole, so maybe it did not...). Unless I am
missing something, why would a plebeian base work here?
And something interesting here (Name Reactions in Heterocyclic Chemistry, Li)- alkyl groups, which are electron donating, prevent the carbanion from
forming. So it is stabilized by electron withdrawal.
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myristicinaldehyde
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Oh, I'm retarded! No wonder why I failed the test!
It's a ducking ACID BASE REACTION! (The deprotonation, anyway)
The pKa's are:
p-nitrotoluene -11.35
o-toluidine 4.44
p-toluidine 5.07
o-dimethyltoluidine 5.15
p-dimethyltoluidine 4.64
So, a dimethylamine would react, but it would need one hell of a base! Unfortunately I failed to find pKa explicitly for those methyl hydrogens, and
any at all for o-nitrotoluene so these numbers might be wrong.
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chemplayer...
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We subsequently did a re-try of the experiment. One thing you have to do (which we didn't the first time round) is that if you want to make the
indole-2-carboxylic acid as a follow-up, do it IMMEDIATELY. The intermediate seems to decompose if left.
We found that the freshly prepared intermediate dissolves easily in acetic acid (no brown insoluble stuff left over) and on reduction using the zinc
metal the colour of the solution becomes much lighter (yellow). On work-up and adding water, you get a fine white precipitate forming which is the
indole compound. You can also smell a little bit of funky indole in the reduction mixture as a result of the acid decarboxylating slightly.
The yields though using sodium are not good (as all the references say). We got below 10% yield of the carboxylic acid from the sodium intermediate
salt.
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myristicinaldehyde
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Very interesting! I wasn't looking to make the indole originally, but it certainly is the path less beaten. OrgSyn says to use K metal, and they ask
for an inert atmosphere while making the potassium ethoxide. Is it to prevent the apparatus from exploding? It certainly isn't necessary for sodium
ethoxide
Thanks for the tip on decomposition. I'll keep that in mind!
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