Preparation of 3,4,5-trimethoxybenzaldehyde

[Rhodium]

To 300g gallic acid in 300ml H2O was added 900ml warm 50% NaOH while bubbling alkaline pyrogallol-washed nitrogen through the solution and then 900g Me2SO4 within 1h at 40-50°C. The mixt. cooled and 75 g. NaOH added, the mixt. refluxed for 3 hrs. and cooled again, 900ml conc HCl with 1 kg crushed ice added, the ppt. sepd., washed with H2O, dissolved in 2000ml 40% EtOH, and kept 12 hrs. at 0°C pptg. 3,4,5-trimethoxybenzoic acid.

200 g 3,4,5-trimethoxybenzoic acid was refluxed with 114g SOCl2 for 2 h, excess SOCl2 distd. off at reduced pressure, the mixt. cooled, and the solidified product suspended in petroleum ether, refluxed 10 min. with 1% activated carbon, filtered, and cooled to 0°C yielding 3,4,5-trimethoxybenzoyl chloride.

To 150g 3,4,5-trimethoxybenzoyl chloride in 2100ml Et2O was added slowly with stirring 120g aniline in 510ml Et2O and the mixt. allowed to stand 1h, filtered, stirred with 2% NaCl, filtered, and washed with NaCl soln. yielding the anilide, of which (100 g) with 75 g PCl5, warmed to 70°C to evolve HCl and heated further to dist. off excess PCl5 yielded the imidochloride. To 90 g if the imidochloride in 2000ml Et2O was added an ethereal SnCl2 soln., the mixt. held at 0° for 12 hrs., the pptd. Sn salt sepd., washed with Et2O, and refluxed with AcOH-HCl-H2O (200:175:325 ml) for 1h, cooled, diluted with H2O and extd. 3 times with Et2O, dried. and crystd. to yield 3,4,5-trimethoxybenzaldehyde.

Reference: Arch. ital. sci. farmacol. [3] 2, 376-83 (1952); Chem Abs 3314h (1956)

[demorol]

Thanks Rhodium! I have some gallic acid and I just wanted to post a question what to do with it. Now, I just have one question. Since in most drug syntheses is used non-iodized NaCl, can I use regular NaCl in this one, or is iodine a problem again.Give me some chemicals and I'll give you pleasure.

[Rhodium]

Iodized salt is okay to use here. Another variation of the procedure can be found here:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mescaline.txt

[PrimoPyro]

Would the alkoxys interfere with reducing the carboxyl to an aldehyde with calcium formate described awhile ago for benzoic acid? (whew, long sentence   )

If the trimethoxy-benzoic acid is basified with calcium carbonate to the salt, then reacted with calcium formate, it should reduce to the aldehyde, the same way for benzoic acid, correct?

Me hopes so.

SOCl2 = yucky.
Ca(OOCH)2 =    + OTC via some 'tone an' shock  

                                                  PrimoPyro
Vivent Longtemps la Ruche! STRIKE For President!

[Rhodium]

No, I don't believe the alkoxys will stand in your way. Where is that procedure posted? It seems like a twisted canizzaro rxn...

[PrimoPyro]

Post 227441

(halfapint: "Re: Alternative Way To Make Benzaldehyde", Chemistry Discourse)
Vivent Longtemps la Ruche! STRIKE For President!

[halfapint]

Re:

Post 227441

(halfapint: "Re: Alternative Way To Make Benzaldehyde", Chemistry Discourse)
This rxn is real enough, but I've become more gloomy about its prospects. It's a dry decomposition reaction, read that as sorta high temperature. My attempt to get an aldehyde from the calcium salt of asarylic acid, mixed with an equivalent of calcium formate, ended with just a few beads of liquid in the condenser. Evidently my hotplate just wasn't getting hot enough. Heating mantle has a short, and not much open flame work happens around here.

Have found yet another old text reference: Textbook of Organic Chemistry, E. Wertheim, 1939, p.523.

The following methods are available for the preparation of the aromatic aldehydes...
(4) Aromatic aldehydes are formed (usually in very low yield) by heating the calcium salts of aromatic acids with calcium formate:
(C₆H₅COO)₂Ca + (HCOO)₂Ca --> 2(CaCO₃) + 2(C₆H₅CHO) Benzaldehyde
This reaction has its identical counterpart in the aliphatic series.

The part I emphasized is what makes me glum. I get happier when a ref states "usually in very high yield."

turning science fact into <<science fiction>>