chemrox
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less common formylation
In page 521 PiKHAL, Shulgin reports formylating a tri-substituted benzene with dichloromethyl Me ether and SnCl4 as the catalyst. This seems a
departure from his usual Vilsmeir-Haack aldehyde preparations and I wonder if there's a structural or other reason such a method would have been
employed. The benzene was 2,5 dimethoxyfluorobenzene. As an aside, could TiCl4 be used as the Lewis acid in place of SnCl4?
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kristofvagyok
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It is called Rieche formylation and it is used sometimes.
The problem with this reaction is to obtain the pure dichloromethyl methyl ether what won't be you fav. substance. The preparation of it is not an
awesome reaction. First you have to mix methyl formate with PCl5, reflux it a bit and after that distill the dichlormethyl methyl ether separately
from the not reacted methyl formate and the reaction other product the POCl3.
And for you question: TiCl4 also works as a Lewis acid.
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ChemGradStudent
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Vilsmeir-Haack
The problem is the vilsmeir-haack reaction can be very temperamental when the electronics of the ring are not perfect. The two methoxy groups will
activate the ring, but also give the ring conflicting positions for the electrophillic attack. The halogen will help direct attack to the para
position but will also pull electron density from the ring, which will result in significantly lower reaction speed.
You said he had done vilsmeir-haack on other substrates; were their electronics more favorable and how hard did he have to hit them to get them to go
(and in what yield  )?
There might be other reasons as well, but that is my best guess as to why he went the less than traditional route.
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chemrox
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Yes I think the other ones were better nucleophiles. Another point I'm curious about is the substitution of N-methylformanilide for DMF in the 2CT
series as well as others from pihkal. 1) why? 2) does it work as well? better? Seems like DMF is cheaper....
@kristof.. thanks for that but please let me understand a little more: if I make the dichloromethyl methyl ether as outlined I get POCl3 as a
byproduct as well? which I can then use for the Vilsmeier-Haack formylation next?
[Edited on 28-7-2012 by chemrox]
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kristofvagyok
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Quote: Originally posted by chemrox  | | @kristof.. thanks for that but please let me understand a little more: if I make the dichloromethyl methyl ether as outlined I get POCl3 as a
byproduct as well? which I can then use for the Vilsmeier-Haack formylation next? |
You are a brave kid.
Dichloromethyl methyl ether (DCMME) is used as a reagent, seems easy, Sigma also sells it so i is not impossibe to work with that, BUT as I previously
wrote the preparation of it is not a girls dream.
The main problem of this is the separation of the products, as I remember DCMME is sensitive to moisture so the separation with water is impossible
(POCl3 + 3HOH = PO4H4 + 3 HCl), so the optimal would be a solvent extraction, to get a solvent what will dissolve the DCMME but not the POCl3.
I had a chlorination reaction with PCl5 recently where the solvent was benzene, and the POCl3 was soluble in it, so I assume that hydrocarbons and
also aromatics wouldn't be good an extraction... Maybe MeAc or DCE.
If you want to distill them... Forget it in time. To distill POCl3 you need a really good gas mask. And i would say that you should distill the DCMME
2,3 times to get a relative pure product.
The Vilsmeier-Haack is an awesome reaction, just needs some DMF and some POCl3, the only problem to obtain pure POCl3 from the previously described
reaction is not that easy. There are much easier ways to get pure POCl3, but to separate it from a chlorination with a similarry distilling voilate
liquid... Not easy.
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Scr0t
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| Quote: | | ...if I make the dichloromethyl methyl ether as outlined I get POCl3 as a byproduct as well? which I can then use for the Vilsmeier-Haack formylation
next? |
I did just that nearly 15yrs ago with rather simple equipment.
If I recall correctly I fractionally distilled the 1,1-Dichlorodimethyl ether/POCl3 mixture through a 200mm Vigreux column, 1st distillation over
narrow ranges to separate them and each were then fractionated once, I had no gas mask or fume hood at the time.
I don't remember there being any significant problems although I may have performed liquid transfers outside before setting up for distillation to
minimize atmospheric exposure in a confined space and used a NaOH trap to prevent moisture getting in and vapors getting out.
The Dichlorodimethyl ether so obtained worked fine for formylating 1,4-Dimethoxybenzene and the POCl3 worked fine for 1,3,5-Trimethoxybenzene.
[Edited on 29-7-2012 by Scr0t]
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