hello bees,
for your weekend otto has some nice results. relax and read...
in a dream 6 g of 82 % 5-bromovanillin
[1], 8 g of NaOH, 100 mg of copper powder and 60 ml water were heated to 120°C in pressure tubes
[2] for 24 hours. the resulting black solution was acidified with HCl which caused a sticky grewish-black precipitate to form. the mixture was checked against pH-paper to be acidic, diluted with 150 ml water and extracted 7 times
[3] by means of ethyl acetate. the combined organic phases were then dried over MgSO4
[4] and evaporated to dryness to yield 4 g of an almost black solid having the smell of vanillin
[5].
to 4 g of previously prepared 5-hydroxyvanillin and 10 g (72 mmol) of K2CO3 in a 250 ml RBF equipped with reflux condenser, bubble valve
[6] and magnetic stirrer there were added 9 ml (72 mmol) of dimethyl sulfate
[7] and the mixture was heated to 80 °C using an oil bath for half an hour. at this point 6 ml of water were added and stirring was applied overnight at 80°C.
[8]to the still hot solution there was added HCl until acidic. the aqueous phase was then cooled to r.t. and extracted 3 times using DCM
[9]. the combined extracts were dried over MgSO4 and evaporated to a brown solid
[10].
this was subjected to column chromatography (silica gel, Merck, type 60; eluent: hexane/ethyl acetate 4:1). the following fractions were collected:
- 0,4 g 3,4,5 TMB-acid methyl ester, mp 77-79°C (lit. 81°C)
- 0,2 g 3,4,5 TMB-acid methyl ester + 3,4,5 TMB-aldehyde ~ 1 : 2
-
3,5 g 3,4,5 TMB-aldehyde, mp 67-71°C (lit. 77°C) - 0,5 g 3,4 DMB-aldehyde + 3,4,5 TMB-aldehyde ~ 1 : 2
[11]isolated over-all-yield: 3,5 g of snow white crystals of 3,4,5 TMB-aldehyde (69 % th.) [12]marks[1] the 5-bromovanillin was made by stirring vanillin in a solution of KClO3, H2SO4 and KBr in water at r.t. the vanillin didn't dissolve, reaction was almost complete the next day. the product obtained thus was only ~80% pure (vanillin and the corresponding acids).
[2] the amount is four times of what fits into ottos pressure tube. so he did it four times. alternatively refluxing the mixture in inert atmosphere can be applied. for details see
https://www.thevespiary.org/rhodium/Rhodium/chemistry/mmda.mescaline.html
[3] dont shake! otto ended up with an emulsion that refused to separate. setting the sepfunnel into intense rotation worked. it might be that actually 5 extractions are sufficient or even three. the first and the seventh extract only were checked by GC. the latter contained almost nothing. this is about when extracts are near to colorless.
[4] otto is shure that this step can be omitted if next reaction will be applied immediately.
[5] the powder contains mainly 5-hydroxyvanillin amongst vanillin and 5-hydroxyvanillic acid. this was checked by GC.
[6] to prevent additional air from entering the reaction vessel. inert atmosphere is not needed though.
[7] procedure and respective amounts are adapted from
Patent US4065504
, discussed previously on the hive (
Post 299247
(flipper: "patent 4065504", Methods Discourse) by flipper in thread "How to prepare hydroxyvanillin")
[8] before adding water the mixture is a whet dark solid and stirring is not really possible. the reaction time is likely to be shorter, otto simply went to bed.
[9] twice may be enough, other solvents may be used...
[10] the powder contains mainly 3,4,5 TMB-aldehyde amongst 3,4 DMB-aldehyde and 3,4,5 TMB-acid methyl ester. checked by GC.
[11] apparently separation was poor. the 3,4 DMB-aldehyde was actually coming within the 3,4,5 TMB-aldehyde fractions.
[12] calculated from 6 g of 82% 5-bromovanillin. actually the yield must have been higher (somewhere around 75%) since some 3,4,5 TMB-aldehyde was collected within other fractions.
conclusions / outlookhe ba-bees!
finally otto methylated the 5-hydroxyvanillin! excess dimethyl sulfate overnight is brute force, there was no hydroxy-product (like syringaldehyde) found. thus base wash of the methylation product was skipped.
the patent is right. it works as described, no solvent (other than water). the yield is pleasant and with a little more care (better 5-Br-vanillin preparation according to uemura or rhodiums site) otto thinks 80% from vanillin to the 3,4,5 TMB-aldehyde can be achieved and chromatography won't be needed.
the procedure would be fully OTC by replacing the DMS.
it took otto some time time to figure out that the one byproduct was the 3,4,5 TMB-acid methyl ester. long time he thought this was the methylated 5-Br-vanillin, left in the aromatic substitution as he assumed in his
Post 298744
(otto: "ottos low yields in methylation", Methods Discourse). but the mp of 5-Br-vanillin is reported in literature many times as being 66°C, so the 79°C for otto's crystals didnt fit.
so the exchange of the aromatic bromine in 5-Br-vanillin in the first step is complete. the acid was already present in otto's 5-Br-vanillin.
all the hydroxy- and methoxy-aldehydes turned out to be not so sensitive. they can be easily handled with.
otto