Vanillin via the method of Guyot and Gry

[GC_MS]

SWIM found some copies of an old book describing synthetic routes to aromatic aldehydes and ketones. Too bad SWIM only has two chapters, and doesn't have the complete title of the book anymore   . The following method - synthesis of vanillin according to Guyot and Gry - has a referention to the original article: B. S. Ch., p 902 (1910). OK, let's start...

(dranzlajdet from French   )

Synthèse de la vanilline par la méthode de Guyot et Gry (Synthesis of vanillin according to Guyot and Gry)

The autors have demonstrated (a) that aromatic phenols and amines condense with alfa,beta-diketone ethers, resulting in  acidyl-phenylglycolic ethers:

R₁-CO-CO-CO₂R₂ + C₆H₅-R₃ -> (R₁-CO-)(HO-)C(-CO₂R₂)(-C₆H₄-R₃)

which can set free the corresponding aldehyde by hydration (by addition of sulfuric acid):

(R₁-CO-)(HO-)C(-CO₂R₂)(-C₆H₄-R₃) + H₂O -> CO + R₂OH + R₁COOH + C₆H₄R₃CHO

The strong reaction of sulfuric acid makes that the reaction sometimes has to occur via intermediary steps: phenylglyxolic acids by oxyhydration:

(R₁-CO-)(HO-)C(-CO₂R₂)(-C₆H₄-R₃) + H₂O + O -> R₂OH + R₁COOH + R₃-C₆H₄-CO-COOH

and by transformation of this substance to the aldehyde with paratoluidine (elimination of CO):

R₃-C₆H₄-CO-COOH -> CO₂ + R₃-C₆H₄-CHO

Or the acidyl phenylglycolic ether can be treated with KOH. In a first phase, there is a saponification, followed by alkaline oxidation and conversion into the aldehyde:

(R₁-CO-)(HO-)C(-CO₂R₂)(-C₆H₄-R₃) + 2 KOH -> R₃-C₆H₄-CHOH-COOH + O -> CO₂ + H₂O + R₃-C₆H₄-CHO

The synthesis of vanillin is based on the condensation of guaiacol with alfa,beta-diketone Bouveault ethers, aka ethylmesoxalate diethylester:

Et-OOC-CO-CO-COO-Et

1. Condensation of gaiacol and ethylmesoxalate diethylester (EMDE)

We make a solution of 250g ZnCl₂ in 500g acetic acid and add 1 mol EMDE, a little bit of ureum to destroy nitric compounds which could affect the ether, and consequently 1 mol guaiacol. Condensation occurs at room temperature. The mixture is set aside for 15 days. Water saturated with sea salt is added (about 1/4th of the total volume). The yield was about 75-80%, the crystal needles melted at 64C.

2. Transformation to vanilloylcarbonic acid

The phenyl glycolic ether is treated with Cu-acetate while heating. The solution will become cloudy and vanilloyl carbonate will precipitate as a Cu-salt:

(HO-)(MeO-)C₆H₃(-OH)(-COOEt)(-CO-R) + O + H₂O -> EtOH + RCOOH + C₆H₃(-OH)(-OMe)(-CO-COOH)

3. Transformation of vanilloylcarbonic acid to vanille

It is sufficient to heat the vanilloylcarbonic acid to its fusion point to set free the corresponding aldehyde:

C₆H₃(-OH)(-OMe)(-CO-COOH) -> C₆H₃(-OH)(-OMe)(-CHO)

(Consult Bouveault, B.S.Ch, p. 365, 940, 943 (1897)). This chemist (Bouveault, note by SWIM) advises using dimethylaniline, but in the case of vanillin, the yields aren't very good. He gets 98% when using dimethylparatoluidine, where the para-position of the phenyl is occupied. The reaction occurs at ca. 170C.

4. Additional notes

Preparation of EDME: (read Bouveault, B.S.Ch. p. 956, 968 (1903)) We prepare isonitroso ethylmalonate:

AzOH=C-(COOR)₂

80g of ethylmalonaat is dissolved in 100g absolute EtOH and 0.5 mol sodium ethylate is added. In the solution, gas bubbles (methylnitrite) are noted. The solution is heated when it becomes yellow. The temperature should be kept between 25C and 30C. The solution is distilled under reduced presure and the nitrated ether is set free by adding HCl.
    Boiling point 12 mmHg: 172C
    Yield: 85-90%
Methylnitrite is prepared. 80g of sodium nitrite is mixed in 550g water, 64g sulfuric acid and 25g MeOH.
Last step to get EDME: the iso-nitroso group is saponified with nitrogen peroxide, N₂O₄. This reaction is very violent and contains explosion danger. The reaction yields the hydrated EDME.

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(a) C.R. t. 149, 788.

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Some notes:
- B.S.Ch. = Bulletin de la Société chimique
- C.R. = Comptes rendus de l'Académie des Sciences
- guaiacol: guaiacol aka 2-methoxyphenol aka o-hydroxyanisole. Merck # 4457 for more information   .
- SWIM didn't find anything about making vanillin from guaiacol using TFSE, so here you have one method. There are some others as well, but this seems to have been a popular one about a centennium ago. SWIM didn't try it himself (yet), the given yields are copied from the text.
- Enjoy  
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