Last Sunday I decided to test the Magnesium methoxide formylation. It has been reported high yield with this method. And the trial-up is easier than
reimer-tiemann.
The 4-MeO-phenol (assay = 98%) is crushed and placed in a dessicator.
Tha Magnesium turnings (assay 99%) and paraformaldehyde (>95%) are placed in the dessicator, sheltered of wet air.
[Edite le 31-3-2008 par Methyl.Magic]
[Edite le 31-3-2008 par Methyl.Magic]Methyl.Magic - 31-3-2008 at 11:35
200ml of fluka-quality anhydrous MeOH is poued in a 750ml four-necked flask fitted with a reflux condenser,mechanical stirrer, a nitrogen inlet and an
alcohol thermometer. 1,75 g (71.3 mmol) of Mg turning are added.
The suspension is heated with an oil bath to reflux. The Mg didnt seem to be dissolving in the hot MeOH, so I decided to add a mini pearl of iodine.
It was effective, the Mg was dissolving in MeOH. I left the MeOh refluxing for 1 hour (T= 61°C). When all the Mg was dissolved, the solution is
grey and cloudy.
Next 15,1 g (11.9 mmol) of 4-MP are added in small portions to the magesium methoxide mixture. When I brought the spoon containing the 4-MP close to
the flask , the letter was immediately melting before dropped to the solution.
The solution become cream-like.
The reflux condenser is replaced with a deflagmator and almost 210ml of MeOH is boiled off.
250 ml of toluène is poured into the flask, and the methanol/toluène azeotrope is boiled off un til te temperature raised to 95-100°C. The
temperature is hold at 98°C for the formylation. The nitrogen inert flux is increased from 0,2 l/min to 1,5 ml/min .
Now ~2g of roughly crushed PFA powder (dampened with toluene) is added to the mixture every 10min. The solution became immediatly yellow/orange but
not dark ! I replaced the reflux condenser for another hour. Note : when I opened the flask no formaldehyde odor was detected.
When the reaction is over, the mixture was cooled at RT all over the night. The yellow m-vanillin magnesium salt are pratically insoluble in
toluène.
Methyl.Magic - 31-3-2008 at 11:49
Today I decided to filtered the precipitate on a buchner under vacuum. The precipitate is a yellow-colored wax. the filtrate is orange.
The cake is crushed as much as possible and stored in the dessicator under vacuum.
The resulting filtrate is acidified with 10% HCl. The aquous layer is incolore.
I'm going to isolate the product tomorrow. I'll post pics !Klute - 31-3-2008 at 12:56
Nice work!!
It funny to see the different aspect using this substrate..
On the second hand, i don't think isolating the magnesium salt was such a good idea: these salts a very air sensitive, even when dry. I think you
should have directly acidified the whole mixture, and at least washed it with dilute acid, water and dried it before storing it that way... Stirring
for too long before acidification leads to formation of dimers!
I once left the acidified mixture to stir for several hours, and that gave me a thick brown polymeric mess, the excess paraformaldehyde reacting
with the aldehyde to form polymers..... I hope your product won't be too degraded.. In acid-free solution in toluene, the aldehyde can be kept a
while without too much damage.
Also, i would advise you not to acidify solution containg formaldehyde with HCl, as it can cause formation of very toxic choloromethyl ethers. H2SO4
is used in the litterature.
I'm impatient to read the continuation! Nice to see people performing reactions and sharing the results!Sandmeyer - 31-3-2008 at 13:58
What is the reference for the method you used? It's a good idea to actually isolate the product and record the yield before publishing (it's far more
important than pictures!).PainKilla - 31-3-2008 at 14:11
The toluène from the orange solution (filtrate) was boiled off with a rotavapor under reduced pressure (at 200 mbar). A bit of the solution was
lost because of boilling delay . ~10ml of orange oil (#1) was recovered ;11,8 g (77,6 mmol).
The not-completly-dried magnesium salt of m-vaniline (5,65 g) was dissolved in 5% sulfuric acid and extracted 2x with diethylether. The two organic
layers was combined ad extrected with 2x 50 ml of salty water. Ether was dried over MgSO4 and distilled with a rotavapor to give 3,57 (23,5 mmol) g of
a yellow oil (#2).
Summary
n (4-Methoxyphenol) = 119 mmol ( 1 eq )
n (Mg) = 71,3 mmol (1,2 eq)
n (Paraformaldehyde ) = 438 mmol (3,7 eq)
Temp. during introduction of PFA : 82°C
YIELD : 15,37g = 84,9 %
The two oil : The left one = #1, the right one = #2
The two oil are yellow/range colored, the oil #2 is slightly lighter than the #1. Both are stored at -5 °C. In the bottle #2 a small amount of
white crystals appeared . A vacuum distillation is necessairy to get pure m-vanilline but not performed. I think I 'll try to analyze the two oil to
know how much unreacted 4-MP are present in each oil.
The smell of pure oil is very very low, but when one drop is added on water, beautiful lovely exhalations of sweet vanillia-like odors are given off
in the room. This is difficult to say if m-vaniline smells like love or love smells like this essential oil !
Thanks for the visit and for spelling out my bad english.
Methyl.MagicKlute - 5-4-2008 at 05:54
Nice!
I am surprised you didn't get more degradation of the magnesium salt. That could means that the filtered salt could directly be used in subsequent
reactions. But i would preferably qstay of the safe side and directly acidify, extract, and vacuum distill the product.
The article claims that hardly any to not at all starting phenol is recovered. The impurities mainly consist of bridged methylene dimers and
benzylic alcohols.
I think this product has a mp of 16°C or something, so impurities must depress it to the point were it hardly cristallizes at -5
°C. I would be very interested by the results of the analysis, to see what kind/amount of impurities are present in the crude product.
Thanks for the pictures and the hard work!Methyl.Magic - 5-4-2008 at 06:16
The magnesium salt has been stored in a dessicator over an inert athmosphere (nitrogen).
The official mp of m-vaniline is 4 'C .
I forgot to precise that when the toluene solution was left for 1 night, the next day a small amount of crystal have been precipited (perhaps polymer
?? ). My mistake : the flask wasn't stored under nitrogen athmosphere.Klute - 5-4-2008 at 07:57
Ah ok, that should have kept it stable.
Sorry, i must have got the mp confused with another compound.
It's nice to see this reaction is starting to get the attention it deserved! I'm pretty sure it can be applied to thiophenols also. It will be tried
out in the futur.mechem - 5-4-2008 at 15:14
Hi
Nice pictures, looks like the 2-hydroxy-5-methoxybenzaldehyde needs vacuum distillation though. It should come over between 124-129C at 10mm/Hg. Best
flush through with nitrogen first.devongrrl - 9-5-2011 at 04:26
Quote:
The reflux condenser is replaced with a deflagmator
What's a deflagmator ?watson.fawkes - 9-5-2011 at 04:52
