Synthesis of vanillin

Van den Heuvel RRH, Fraaije MW, Laane C, van Berkel WJH (2001) Enzymatic synthesis of vanillin. J Agric Food Chem 49 2954-2958... 

Scheme 13.10 Chemical synthesis of vanillin from various sources...

Ghate M, Kulkarni MV, Shobha R, Kattimani SY (2003) Synthesis of vanillin ethers from 4-(bromomethyl) coumarins as anti-inflammatory agents. Eur J Med Chem 38 297... 

The classical synthesis of vanillin from eugenol or isoeugenol was developed in 1896 and it remained the preferred method for about 50 years. Vanillin is now prepared industrially in large amounts by the Reimer-Tiemann reaction, starting with... 

The same group has demonstrated the microbial synthesis of vanillin in an E. coli mutant [83] but the yield and titer (6.2 g L 1) were too low to be of immediate practical value. A completely microbial route to gallic acid [84], which is currently isolated from natural sources [85], produced 20 g L 1 of the desired product in the presence of considerable amounts of side-products [84]. 

For the synthesis of flavour-active compounds numerous methodologies have been developed [17], In many cases natural products served as starting materials such as eugenol from clove oil for the synthesis of vanillin. In case of complex stereochemistry natural materials are still welcome for the synthesis of valuable flavour compounds such as nootkatone, which is obtained by oxidation from valencene. 

Interest in the selective oxidation of glyoxal (ethanedial) into glyoxalic acid (also called glyoxylic and oxo-acetic acid) is stimulated by the fact that it is an important intermediate in the cosmetic and food industries, e.g., for the synthesis of vanillin [379]. Vorlop and co-workers [369] showed that when glyoxal is oxidised rupture of the C-C bond is the predominant reaction, producing formic acid and the desired product, glyoxalic acid, is observed in minor amount only (see Fig. 6.15). 

Synthesis of vanillin from guaiacol Reimer and Tiemann... 

Substituted mandelic acids are key compounds in the synthesis of vanillin from phenols. However, the KIE observed during the oxidative degradation of mandelic acid into benzaldehyde is extremely dependent on the experimental conditions. 

To conclude, it is interesting to discuss in more detail the synthesis of vanillin from 4-hydroxy-3-methoxymandelic acid. According to scheme 1, glyoxylic acid reacts with guaiacol to give the substituted mandelic acid. 

A great amount of work has been done on the synthesis of vanillin from... 

Natural vanilla flavor and natural vanillin are in high demand and alternative production routes such as using PTC or microbial systems are being sought [60]. De novo synthesis of vanillin and vanilla plant cells and plant callus tissue are important commercial products biosynthesized by PTC. Alternatively, hair roots of vanilla plant have been used as a biocatalyst to convert the precursor ferulic acid into vanillin [104]. 

Use 1. as well as the methyl ether are used in perfumery (carnation odor). I. is also employed as a conservation agent and an intermediate in the synthesis of vanillin. 

Rh6ne-Poulenc has developed an elegant process for the synthesis of vanillin,... 

Frost developed another fermentative process for the synthesis of vanillin. [153] In this case, the starting material is the inexpensive glucose, which is converted into vanillin with genetically modified Escherichia coli. The reduction to vaniUin is catalysed by an acetaldehyde-dehydrogenase enzyme from the fungus Neuro-spora crassa. 

For the synthesis of vanillin itself, there follows, in a separate step, a further enzymatic reduction ofthe carboxylic function. To recover the NADP+, the reaction product is stirred for 7 hours at 30 °C together with glucose in the presence of the arylaldehyde-dehydrogenase from Neurospora crassa and glucose phosphate dehydrogenase. 

The separate reduction of vanillic acid with an enzyme from Neurospora crassa poses a major drawback to the whole process. For an industrially viable process, it is essential to carry through all the steps of the biotechnological synthesis of vanillin with a single intact organism. 

Vanillin is the second largest food additive used each year. As a consequence of limited natural sources of this ubiquitous flavor and fragrance, the bulk of commercial vanillin is synthesized from phenol (19). A two-step synthesis of vanillin from glucose via DHS intermediacy was recently reported (Figure 3) (17). DHS dehydratase-catalyzed conversion of DHS into PCA is followed by formation of the methyl ether, catalyzed by catechol-O-methyltransferase, an enzyme not native to E. coli but for which the gene (comt) has been cloned from rat liver (20). In a separate step, incubation of the resulting vanillic acid with aryl-aldehyde dehydrogenase (21) affords vanillin. 

Figure 3. Synthesis of vanillin from DHS. Enzymes (a) DHS dehydratase (aroZ) (b) catechol-O-methyltransferase (comt) (c) aryl-aldehyde dehydrogenase (d) glucose 6-phosphate dehydrogenase, glucose 6-phosphate.

Today many attempts are made to make the synthesis of vanillin as sustainable as possible and in line with green chemistry principles. ... 

The only viable conversion of lignin into a single aromatic compound is the synthesis of vanillin, which is a very useful commodity, but not in the realm of polymer chemistry. A recent investigation reports its oxidation to vanillic acid [74] and another, the use of this compound for leather tanning [75]. 

AugugUaro V, Camera-Roda G, Loddo V, Palmisano G, Pahnisauo L, Parriuo F aud Puma M A (2011), Synthesis of vanillin in water by TiOj photocatalysis , AppZ Catal B-Environ, 111-112,555-561. 

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