The Vespiary

Vanillin from Guaiacol (2-MeO-phenol)

A solution of glyoxylic acid produced in the known manner from 15g of oxalic acid by electrolytic reduction (Berichte, Vol. 37, pp 3190) is neutralized with NaOH and a concentrated solution of 10g of guaiacol (2-methoxyphenol) is added. The product is left to itself for some days at room temperature and is thereupon acidified with acetic acid. The guaiacol that hasn't reacted is removed by steam distillation, whereby 3.2g of guaiacol are recovered. The residue from the distillation is now made slightly alkaline again, 25g of powdered CuSO₄ and 70mL of 15% NaOH solution are added. The mixture is then stirred for some hours at  90-100°C. The copper sludge is filtered off using vacuum and the filtrate is acidified and extracted with benzene. On evaporation of the benzene solution 8g of vanillin are obtained, which is vacuum distilled (135-140°C/5 mmHg). The distillate solidifies to a crystalline mass which on recrystallization from toluene yields pure vanillin (m.p. 81°C)

Reference:

Patent GB401562 (http://l2.espacenet.com/dips/viewer?PN=GB401562&CY=gb&LG=en&DB=EPD)

I am much more interested in this:

A solution of glyoxylic acid produced in the known manner from 15g of oxalic acid by electrolytic reduction
(Berichte, Vol. 37, pp 3190)

I assume its in German.  Glyoxylic acid could bee one of the most handy reagents ever, especially if we can make it easily from the otc oxalic acid.

Ooops I used tfse and look at what we have.

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Al/Hg reduction of Oxylic acid to glyoxylic acid :o)

Glyoxylic acid.   
Dukai, Jozsef; Varkonyi-Rozsa, Agnes; Barath, Mrs. Miklos.  (Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt., Hung.).    Hung. Teljes  (1979),     20 pp.  CODEN: HUXXBU  HU  15960  19790127  Patent  written in Hungarian.

Patent HU15960 (http://l2.espacenet.com/dips/viewer?PN=HU15960&CY=gb&LG=en&DB=EPD)

Patent HU173712 (http://l2.espacenet.com/dips/viewer?PN=HU173712&CY=gb&LG=en&DB=EPD)

Abstract
X:CHCO₂H (X = O, H₂NCONHN, and H₂NCSNHN) and 2-hydroxyquinoxaline were prepd. by Hg or Hg²⁺ activated Al redn. of oxalic acid (I).  Thus, a mixt. of 2.5 L MeOH, 35 g 99.5% Al turnings, and 10 mL 1% HgCl₂ in MeOH was stirred 10-15 min, stirred 6 h at 20-30°C with 296 g I, kept overnight, filtered, and the MeOH replaced by H₂O.  The soln. was passed through Varion KS (H⁺) cation-exchange resin, concd. at 40-50°C to deposit unreacted I, and filtered to give a soln. contg. 75-80 g glyoxylic acid.


This one might bee even better.

Glyoxalic acid.   
Jpn. Kokai Tokkyo Koho  (1983), 6 pp.

Patent JP58198437 (http://l2.espacenet.com/dips/viewer?PN=JP58198437&CY=gb&LG=en&DB=EPD)

  A2  19831118  (Japanese).

Abstract
OHCCO₂H (I) was prepd. by reaction of aq. oxalic acid (II) with Cl.  Thus, Cl was introduced to 1850.2 g aq. soln. contg. 5.03% II and 0.48% I over 19 h at 15-18° to give 1984.3 g aq. soln. contg. 5.08% I.  Conversion of II and selectivity for I were 92.8% and 83.4%, resp.

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Somebees (antoncho?  ;) ) really need to get on this glyoxylic acid synthesis of benzaldehydes.  Search for "glyoxylic" in tfse and you'll find some very bee friendly reactions.

Vanillin can also be made from Guaiacol using the Reimer-Tiemann (it WILL add para).

Note to everybody: There is no reason whatsoever to synthesize vanillin itself, as it can be had OTC for almost free...

Glyoxylic Acid
CAS [79-14-1]

Chemical Properties

Glyoxylic acid contains two functional groups: the carbonyl group, which undergoes reactions characteristic of aldehydes , and the carboxylic acid group The aldehyde group reacts readily with nucleophilic reagents; the hydrated aldehyde and the hemiacetal react similarly. With ambident nucleophiles, the carboxylic group may also react, leading to intramolecular ring formation. Various heterocyclic compounds can be obtained by coupling polynucleophiles with glyoxylic acid: o-phenylenediamine [95-54-5] gives 2-hydroxyquinoxaline [1196-57-2]; with urea [57-13-6] and an acid catalyst, allantoin [97-59-6] is obtained in 60 % yield [8].

On heating, glyoxylic acid disproportionates to a mixture of glycolic acid [79-14-1] and oxalic acid [144-62-7]; glyoxylic acid is also easily oxidized to oxalic acid by nitric acid.
Reactions that have been used industrially include the Mannich reaction and amidoalkylation. Thus, with phenol and ethylenediamine in alkaline medium, glyoxylic acid leads to the sodium salt of N,N¢-ethylenebis[2-(2-hydroxyphenyl)glycine] (EHPG), which forms complexes with iron (III) [9].
Glyoxylic acid, phenol, and ammonia react to give 4-hydroxyphenylglycine, an intermediate for the semisynthetic penicillin amoxicillin [10]

At slightly alkaline pH, glyoxylic acid reacts with amides such as acrylamide [79-06-1] to form acrylamidoglycolic acid (AGA), which is used as a copolymerizable cross-linking agent [11]
Several derivatives of AGA have found industrial application; e.g., the methyl ether ester is used in coatings and paint for automobiles.
Glyoxylic acid combines with phenol in alkaline medium to give 4-hydroxymandelic acid with good selectivity [12].
The reaction with phenols is used in several industrial syntheses of benzaldehydes. For example, guaiacol [90-05-1] is converted to vanillin [121-33-5] by oxidative decarboxylation of the corresponding mandelic acid [13].

The mandelic acid intermediate may be modified further: reaction of phenol and glyoxylic acid in the presence of a reducing agent such as phosphorus – iodine leads directly to hydroxyphenylacetic acid [14] , a building block for pharmaceuticals such as Atenolol.

With thiophene, this reaction yields 2-thi-enylacetic acid, which is used to prepare the semisynthetic cephalosporins cephalothin and cefoxitin.
Glyoxylic acid and hydrochloric acid can be used to chloroalkylate aromatic compounds [15].
Glyoxylic acid undergoes the aldol reaction; the corresponding benzoylacrylic acids are obtained with acetophenones [16]:


Glyoxylic acid is treated with Wittig ylides to form carboxyl functional polyenes of the vitamin A type [17].

Esters of glyoxylic acid, obtained by dehydrative distillation of the hemiacetal esters in the presence of phosphorus pentoxide, can be polymerized under the action of a base. After saponification, the resulting polymers show useful chelating properties with the advantage of good biodegradability [18] , [19]. Low molecular mass polyglyoxylates have been proposed as substitutes for sodium tripolyphosphates (TPP) in detergents to control water hardness.

Production

Glyoxylic acid is produced industrially by oxidation of glyoxal in aqueous solution with 65 % nitric acid in mole ratios of 1 : 1 to 1 : 1.5 between 40 and 90 °C. The main byproduct of this process is oxalic acid, which is separated by low-temperature crystallization. The solution is then purified by passage through an anion-exchange resin or by electrodialysis, which removes the residual nitric acid.
Glyoxal can also be oxidized at the anode of a two-compartment electrolytic cell in the presence of chloride ion [20]. Glyoxylic acid may be synthesized by catalytic oxidation of ethylene or acetaldehyde, but the selectivity is low and these routes have not been used industrially.
The cathodic reduction of oxalic acid gives a very good chemical yield (85 %), but this technique encounters problems with passivation of the lead electrodes [21] , [22].
Another method is oxidative cleavage of maleic acid or its esters by ozone. This process, has been adapted to the preparation of hemiacetal esters [23].



[8]  BASF, DE-OS

Patent DE1939924 (http://l2.espacenet.com/dips/viewer?PN=DE1939924&CY=gb&LG=en&DB=EPD)

, 1969 (W. Mesch, O. A. Grosskinsky, N. Lösch).
[9]  Ciba-Geigy,

Patent US4130582 (http://l2.espacenet.com/dips/viewer?PN=US4130582&CY=gb&LG=en&DB=EPD)

, 1977 (H. E. Petree, H. Myatt, A. M. Jelenevsky).
[10]  Beecham,

Patent GB978178 (http://l2.espacenet.com/dips/viewer?PN=GB978178&CY=gb&LG=en&DB=EPD)

, 1962 (J. H. C. Nayler, H. Smith).
[11]  Nobel Bozel,

Patent FR1411715 (http://l2.espacenet.com/dips/viewer?PN=FR1411715&CY=gb&LG=en&DB=EPD)

, 1964.
[12]  Soc. Française Hoechst,

Patent FR2440350 (http://l2.espacenet.com/dips/viewer?PN=FR2440350&CY=gb&LG=en&DB=EPD)

, 1978 (A. Schouteeten, Y. Christidis).
[13]  Haarmann & Reimer, DE-OS

Patent DE2115551 (http://l2.espacenet.com/dips/viewer?PN=DE2115551&CY=gb&LG=en&DB=EPD)

, 1971 (K. Bauer, W. Steuer).
[14]  Soc. Française Hoechst,

Patent FR2470127 (http://l2.espacenet.com/dips/viewer?PN=FR2470127&CY=gb&LG=en&DB=EPD)

, 1979 (J. C. Vallejos, Y. Christidis).
[15]  Soc. Française Hoechst,

Patent FR2376112 (http://l2.espacenet.com/dips/viewer?PN=FR2376112&CY=gb&LG=en&DB=EPD)

, 1976 (E. Herman, H. Diery, M. Soreau, Y. Christidis).
[16]  Roussel-Uclaf,

Patent FR2504005 (http://l2.espacenet.com/dips/viewer?PN=FR2504005&CY=gb&LG=en&DB=EPD)

, 1981 (Y. Christidis, R. Fournex, C. Tournemine).
[17]  Hoffmann La Roche,

Patent US4224244 (http://l2.espacenet.com/dips/viewer?PN=US4224244&CY=gb&LG=en&DB=EPD)

, 1980 (W. Bollag, R. Ruegg, G. Ryser).
[18]  Monsanto,

Patent US4144226 (http://l2.espacenet.com/dips/viewer?PN=US4144226&CY=gb&LG=en&DB=EPD)

, 1977 (M. M. Crutchfield, V. D. Papanu, C. B. Warren).
[19]  Procter & Gamble,

Patent US4284524 (http://l2.espacenet.com/dips/viewer?PN=US4284524&CY=gb&LG=en&DB=EPD)

, 1980 (L. A. Gilbert).
[20]  Chlorine Engineers and Daicel Chem.,

Patent FR2443517 (http://l2.espacenet.com/dips/viewer?PN=FR2443517&CY=gb&LG=en&DB=EPD)

, 1979 (H. Harada, K. Hirao, M. Ichino, T. Mitani).
[21]  I. V. Kudryashov et al., Tr. Mosk. Khim. Tekhnol. Inst. 49 (1965) 111 – 115;Chem. Abstr. 65 3328 d.
[22]  K. Scott, Chem. Eng. Res. Des. 64 (1986) no. 4, 266 – 272.
[23]  Lentia,

Patent DE3224795 (http://l2.espacenet.com/dips/viewer?PN=DE3224795&CY=gb&LG=en&DB=EPD)

, 1982 (A. Sajtos, M. Wechsberg, E.
  Roithner).


Other References:

Zur Kenntnis der Glyoxylsäure
Hans Meyer
Chem. Ber. 34, 3593-93 (1904)

https://www.thevespiary.org/rhodium/Rhodium/pdf/glyoxylic.ber.37.3592.1904.pdf (https://www.thevespiary.org/rhodium/Rhodium/pdf/glyoxylic.ber.37.3592.1904.pdf)

Patent US4692226 (http://l2.espacenet.com/dips/viewer?PN=US4692226&CY=gb&LG=en&DB=EPD)

Abstract:
This process, carried out at a temperature of 0 DEG to 30 DEG C. in an electrolyzer outfit consisting of at least one anode compartment containing an anode and anolyte, comprising an aqueous acid solution, at least one cathode compartment containing a cathode and catholyte, comprising an aqueous solution of oxalic acid and, between the two compartments, at least one separator, is characterized by the fact that the anode is made of a solid conductor uniformly coated with lead dioxide. This patent contains a lot of other references

Patent DE347605 (http://l2.espacenet.com/dips/viewer?PN=DE347605&CY=gb&LG=en&DB=EPD)

A very simple electrochemical reduction with a divided cell (lead ; mercury)

Important uses:

Pyrocatechol  [120-80-9] --> 1,2- Methylendioxybenzene [274-09-9] --> 3,4-Methylendioxy Mandelic acid  --> Piperonal

Patent DE2754490 (http://l2.espacenet.com/dips/viewer?PN=DE2754490&CY=gb&LG=en&DB=EPD)

Patent EP1229031 (http://l2.espacenet.com/dips/viewer?PN=EP1229031&CY=gb&LG=en&DB=EPD)

 US Pat 2003/0013897

Patent DE2703640 (http://l2.espacenet.com/dips/viewer?PN=DE2703640&CY=gb&LG=en&DB=EPD)

Patent US4157333 (http://l2.espacenet.com/dips/viewer?PN=US4157333&CY=gb&LG=en&DB=EPD)

Patent US5095128 (http://l2.espacenet.com/dips/viewer?PN=US5095128&CY=gb&LG=en&DB=EPD)