a123x
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Methods of adding OH/CH3O
In making things like 5-hydroxyvanillin, 3,4,5-trimethoxybenzaldehyde, and other compounds, it's necessary to add OH groups to an aromatic
aldehyde. This often involves halogenating and then substituting OH or CH3O for the halogen which requires a long refluxing under an inert atmosphere.
I'm trying to think of alternative method that doesn't require reflux under an inert atmosphere. Two thoughts came to mind.
My first idea is for small scale use(mainly what I'm interested in). Instead of refluxing a reaction mixture under an inert atmosphere, it would
involve heating the reaction in a sealed vessel. I was thinking of using a length of narrow copper tubing(probably 1/4" filled with the mixture and sealed at both ends(crimped somehow I think). This would
then be placed in a boiling water bath and allowed to react. I'm pretty sure the copper tubing would hold up to the pressure created at 100C
using water, ethanol, and methanol as solvents. I can't really think of any reason why this won't work as a substitute for the inert
atmosphere since any oxygen trapped in the tube when it's sealed will get consumed rapidly and thus only minorly harm the yields.
The second idea was to try a completely different route. I was thinking of nitration, reduction of the nitro group, and then diazotization in water to
give an OH group. In addition, I think doing the same thing in the corresponding alcohol can actually give the methoxy or ethoxy group although I only
have come across one reference to such being used. My main concern here is that the nitration won't go well. I'm thinking it might oxidize
the aldehyde group even in the case of vanillin which shouldn't require terrible severe conditions to nitrate since the OH is strongly activating
to the ring.
Any thoughts or comments would be greatly appreciated.
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The_Davster
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| Quote: | Originally posted by a123x
The second idea was to try a completely different route. I was thinking of nitration, reduction of the nitro group, and then diazotization in water to
give an OH group. In addition, I think doing the same thing in the corresponding alcohol can actually give the methoxy or ethoxy group although I only
have come across one reference to such being used. My main concern here is that the nitration won't go well. I'm thinking it might oxidize
the aldehyde group even in the case of vanillin which shouldn't require terrible severe conditions to nitrate since the OH is strongly activating
to the ring.
Any thoughts or comments would be greatly appreciated. |
To introduce OH groups perhaps use the diazotized product to produce the halo-derivitave then react that with base to get the OH derivitave. I am not
100% sure that an OH can be attached directly to a diazo compound, Ill take a look in a few books at the uni library for info. Reaction of diazo
compounds with alcohols gives a huge mess of products including alkyl, H, and if your referance is correct, the alkoxy. Reaction of the halo
derivative with alkoxide is likely better.
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a123x
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I'm sure that a Sandmeyer reaction in water will convert quite readily to the hydroxy compound upon simply allowing the solution of the diazonium
salt to warm. Such a reaction also readily produces the iodo or thioether compound if I- or RSH are the nucleophiles present. I've provided a
quick reference. My o-chem textbook says the same. I thought that perhaps such a reaction in methanol or ethanol would also work but I only was able
to find one reference either way and it wasn't very in depth. So long as the nitration can proceed without trouble though(something I'm nt
too sure on), it might be a useful way to add OH's to benzaldehydes. I'll probably work on it this december when I'm home for break.
http://www.organic-chemistry.org/namedreactions/sandmeyer-re...
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The_Davster
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Thanks for clarifing on the OH addition, I forgot about that reaction. Well if you are wanting something like trimethoxybenzaldehyde, I bet you would
have to go through TNT , and the tridiazonium salt you would have as
intermediates, salts of those would be rather fun.
I'll try to look up alkoxy compounds from diazo in a book on diazotizations within the next few days.
EDIT: I looked up addition of alkoxy, and it is very dependant on the alcohol being used, the substrate and reaction conditions. Under pressure you
get the purest product (20% max) but under no excess pressure higher yields(around 30%) are had, but more contaminants.
EDIT2: And OH groups are actually rather easy to add using the method you mentioned.
[Edited on 22-11-2005 by rogue chemist]
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