Vanillic alcohol

Hydroxymethylation of 2-Methoxyphenol with Formaldehyde to Yield Vanillic Alcohols A Comparison Between Homogeneous and Heterogeneous Acid Catalysis... 

Khymenets, O., Joglar, J., Clapes, P., Parella, T., Covas, M.-I. and de la Torre, R., Biocatalyzed synthesis and structural characterization of monoglucuronides of hydroxytyrosol, tyrosol, homo-vanillic alcohol, and 3-(4 -hydroxyphenyl)propanol. Adv. Synth. Catal., 2006, 348, 2155. 

Obviously, it is very desirable to substitute these modes of benzylic ether preparation by an heterogeneous catalysis process. Clays (50) and resins (51, 52) which were the first solid acid catalysts used have given low or moderate yields. The first experiments with zeolites were carried out by Rhodia (53, 54) on the etherification of vanillic alcohol (A) in a batch reactor over a HBEA zeolite with a Si/Al ratio of 12.5 ... 

The etherification of vanillic alcohol with ethanol was compared over three large pore zeolites HBEA, HFAU and HMOR and over an average pore size zeolites (HMFI) with different Si/Al ratios. Whatever the large pore zeolite and its Si/Al ratio, a total conversion of the benzylic alcohol and a 100% yield in ether are obtained. With the HMFI samples, conversion and yields were equal to 55% only for an Si/Al ratio of 15 and to approximately 70% for Si/Al = 40. It could be expected that the reaction is limited by diffusion of the bulky reactant and product molecules in the narrow pores of this zeolite. 

To estimate the effect of reaction time on activity and selectivity of HBEA (12.5), this zeolite was recovered by filtration after 5 hours reaction and reused several times under the same operating conditions batch reactor, 80°C, 7.5 g of vanillic alcohol and 35 g of ethanol. Only a small decrease in conversion was observed from 98% to 88%, 86% and 84%, the selectivity remaining close to 100%. Furthermore, the activity is completely recovered after calcination under air flow for 5 hours. The slow deactivation of the HBEA zeolite is most likely due to a partial blockage of the access to the active sites by heavy secondary products ( coke ). 

The formation of acyl conjugates of vanillamine (capsaicinoids, 20) or vanillic alcohol (capsinoids, 21) with various Cg/Ci3 alkenoic and alkanoic acids is a unique chemical trait of plants from the genus Capsicum. Hot peppers are characterized by the presence of vanillyl conjugates of the amide type, absent or replaced by their nonpungent ester isosters (capsinoids) in bell (sweet) peppers [19]. Indeed, the difference between the sensory properties of capsaicin (la) and its naturally occurring ester analog capsiate (22) is a remarkable example of the biological relevance of isosterism. 

Moreau C. Finiels A. Razigade S., Gilbert L., Fajula F, Jacquot R., Spagnol M., selective hydroxymethylation of guaiacol to vanillic alcohols in the presence of H-Mordenite in catalysis of organic reactions, Marcel Dekker, Inc. New York, Chapter 5, p. 51-62, 1998. Barthel N., These de doctoral, Universite de Montpellier II-ENSCM, France, 1999. Jacquot R., Spagnol M., French patent WO 99/64385, priority 11/06/1998, to Rhodia Wu X., Anthony R.G., J. Catal., 184, 294-297 (1999). 

The liquid-phase hydroxyalkylation of 2-methoxyphenol with aqueous solutions of fonnaldehyde (formalin), catalyzed by solid acid materials, was investigated. Zeolitic catalysts, especially H-mordenites, yield the best results in terms of reactant conversion and selectivity to 3-methoxy-4-hydroxybenzyl alcohol (p-vanillol). Important reaction parameters are the formaldehyde-to-guaiacol ratio, the stirring rate and the reaction tenqjerature. The reaction scheme consists of parallel reactions for the formation of vanillic alcohol isomers and of monoarylic by-products, obtained by reaction between vanillols and methanol or hemiformal contained in formalin. The consecutive reactions mainly involve the transformation of p-vanillol to monoaryl and to diaryl compounds, the latter obtained by condensation of two vanillol molecules. 

Barrel-fermented wines overall have less wood aroma than the same wines barreled after alcoholic fermentation (Chatonnet et al, 1992). This phenomenon is essentially linked to the reduction of vanillin by yeasts into vanillic alcohol, which is almost odorless. Furanic aldehydes are also reduced into alcohols. 

Valeraldehyde, p28 Valeric acid, p38 Valeronitrile, p35 Valeryl chloride, p45 Vanillic acid, hi43 Vanillin, hl42 Vanillyl alcohol, hl45 Veratraldehyde, d492 Veratric acid, d496 Veratrole, d493 Veronal, d330... 

The biocatalytic reduction of carboxylic acids to their respective aldehydes or alcohols is a relatively new biocatalytic process with the potential to replace conventional chemical processes that use toxic metal catalysts and noxious reagents. An enzyme known as carboxylic acid reductase (Car) from Nocardia sp. NRRL 5646 was cloned into Escherichia coli BL21(DE3). This E. coli based biocatalyst grows faster, expresses Car, and produces fewer side products than Nocardia. Although the enzyme itself can be used in small-scale reactions, whole E. coli cells containing Car and the natural cofactors ATP and NADPH, are easily used to reduce a wide range of carboxylic acids, conceivably at any scale. The biocatalytic reduction of vanillic acid to the commercially valuable product vanillin is used to illustrate the ease and efficiency of the recombinant Car E. coli reduction system." A comprehensive overview is given in Reference 6, and experimental details below are taken primarily from Reference 7. 

The HPLC system used a mobile phase consisting of CH3CN/H2O/HCOOH (20 80 1, v/ v/v). Quantitation of standards and samples was achieved by isocratic elution over a C18,5 pm, Econosil HPLC column at a flow rate of 0.4 mL min. HPLC retention volumes and detection wavelengths for standards were as follows vanrllyl alcohol, 1.7 mL and 277 nm vanillic acid, 2.5 mL and 260 nm and vanillin, 4.1 mL and 284 nm. 

TLC analysis of samples was conducted on silica-gel plates carefully spotted with 10-20 pg of standard compounds, and 30 pL of bioconversion reaction samples. Plates developed with 75 25 1 (v/v/v) CH2CI2/CH3CN/HCOOH solvent may be visualized with a 254 nm UV lamp and/or by spraying with a 30 % w/v phosphomolybdic acid/ 95% ethanol spray reagent followed by gentle heating. Rf values of standards are vanillyl alcohol, 0.8 vanillic acid, 0.5 and vanillin 0.4. 

Most of the vanillic acid was reduced by E. coli containing Car in 2 h to vanillin (80 %) and vanillyl alcohol (20 %). Car does not reduce aldehydes to alcohols. However, E. coli s endogenous aldehyde reductase/dehydrogenase reduces vanillin to vanillyl alcohol. The broad substrate specificity of Car enables the wide application of this biocatalyst to other important applications, such as enantiomeric resolution of isomers such as ibuprofen and the reductions of many other natural and synthetic carboxylic acids. 

It has now been found that the quinones 13, 14 and 15 from the aerobic oxidation of veratryl alcohol by lignin peroxidase were also reduced by fungal mycelium to yield the corresponding hydroquinones. For quinone 14 this reduction had already been reported by Buswell et al. (17) in a study of vanillic acid metabolism. 

Properties. Vanillin is a colorless crystalline solid mp 82-83 °C) with a typical vanilla odor. Because it possesses aldehyde and hydroxyl substituents, it undergoes many reactions. Additional reactions are possible due to the reactivity of the aromatic nucleus. Vanillyl alcohol and 2-methoxy-4-methylphenol are obtained by catalytic hydrogenation vanillic acid derivatives are formed after oxidation and protection of the phenolic hydroxyl group. Since vanillin is a phenol aldehyde, it is stable to autoxidation and does not undergo the Cannizzarro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxyl group and by aldol condensation at the aldehyde group. Several of these derivatives are intermediates, for example, in the synthesis of pharmaceuticals. 

Other monolignols formed during the dehydrogenation of coniferyl alcohol are conifer aldehyde (VII), trans- and m-ferulic acid (XV, XVI), vanillin (traces), and vanillic acid (traces). 

In a later paper (7) they discussed the treatment of some lignin model compounds (e.g., vanillic acid and vanillyl alcohol) with sulfite liquors under varying pulping conditions. Their results indicated that pyrocatechol groups may be formed in lignin during semichemical sulfite pulping. 

Vanillic Acid and Unknowns. The vanillic acid reference spot has an Rf value of 0.39 (Table VI) as does one of the compounds from the reaction mixture. However, as Table VI shows, the colors of these spots, after applying the location sprays, have been recorded as being slightly different. Therefore, although the results so far indicate that vanillic acid might be a product of the reaction of vanillyl alcohol and alkali, spectral analyses of the eluates of the chromatographic spots at the Rf value of 0.39 is necessary for confirmation. 

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