Vanillin

Description

Vanillin is found in many plants, such as the tuber of Rhizoma Gastrodiae (Tian Ma), the whole herb of Equisetum (Mu Zei), Ulva pertusa (Kong Shi Chun), and sugar beets, vanilla beans, Peru balsam, and so on .

Description

Vanillin, as its name implies, is the major flavor component of vanilla. The three oxygen atoms in this small aromatic compound are in different functional groups: alcohol, aldehyde, and ether. It is a white crystalline solid with a melting point of 81–83 oC.
The Aztecs used vanilla to flavor chocolate as early as the 16th century, but vanillin was not isolated until 1858, when French biochemist Nicolas-Theodore Gobley crystallized it from vanilla extract. In 1874, German scientists Ferdinand Tiemann and Wilhelm Haarmann determined its structure and synthesized it from coniferin, a component of pine bark.
Flash forward to today: Almost all vanillin used in foods is manufactured, mostly from petrochemical feedstocks. But the food industry is on a tear to label more and more products as consisting entirely of “natural” ingredients. This trend puts the agricultural industry under pressure to genetically modify plants to produce greater amounts of vanillin. To find out how they’re doing it, see Melody Bomgardner’s?cover story?in the September 12 issue of C&EN.

Chemical properties

White, crystalline needles; sweetish smell. Soluble in 125 parts water, in 20 parts glycerol, and in 2 parts 95% alcohol; soluble in chloroform and ether. Combustible.

Chemical properties

White or cream, crystalline needles or powder with characteristic vanilla odor and sweet taste.

Chemical properties

Vanillin is found in many essential oils and foods but is often not essential for their odor or aroma. However, it does determine the odor of essential oils and extracts from Vanilla planifolia and Vanilla tahitensis pods, in which it is formed during ripening by enzymatic cleavage of glycosides.
Vanillin is a colorless, crystalline solid (mp 82–83°C) with a typical vanilla odor. Because it possesses aldehyde and hydroxy 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 hydroxy group. Since vanillin is a phenol aldehyde, it is stable to autoxidation and does not undergo the Cannizzaro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxy group and by aldol condensation at the aldehyde group. Several of these derivatives are intermediates, for example, in the synthesis of pharmaceuticals.

Chemical properties

A great variety of vanilla plants bearing the vanilla pods, or siliques, exist. Those mentioned above are the most important species. Of special value are those cultivated in Mexico, Madagascar, Java, Tahiti, the Comoro Islands and Réunion. The cultivation of vanilla beans is very long and laborious. The plant is a perennial herbaceous vine that grows up to 25 m in height and needs suitable supports in order to grow. Fecundation of flowers is performed (November to December) by perforating the membrane that separates the pollen from the pistil. This is an exacting task requiring skilled hand labor. Natural fecundation occurs when a similar operation is carried out by birds or insects that perforate the membrane in search of food. After a few months, clusters of hanging pods (siliques) are formed; these start to yellow at the lower tip from August to September. At this point, the siliques are harvested and undergo special treatment that develops the aroma. The siliques are placed in straw baskets and dipped into hot water to rupture the inner cell wall. After a few months, the aroma starts developing. Then the siliques are exuded by intermittent exposure to sunlight (by alternately covering and uncovering the siliques with wool blankets). When exudation is complete, the siliques are oiled with cocoa oil to avoid chapping during drying and are finally dried to a suitable residual moisture content. In the final stage of the preparation, the best quality siliques form a vanilla “brine” that crystallizes on the surface of the bean. Generally, the processing of vanilla bean takes more than a year. The most important commercial qualities are brined vanilla, bastard vanilla and vanilla pompona. The bean is the only part used. Vanilla has a sweet, ethereal odor and characteristic flavor.

Chemical properties

Vanillin has a characteristic, creamy, vanilla-like odor with a very sweet taste.

Physical properties

Appearance: white or light yellow needle crystal or crystal powder, with a strong aroma. The relative density is about 1.060. Solubility: It is not only soluble in ethanol, chloroform, ether, carbon disulfide, glacial acetic acid, and pyridine but also in oil, propylene glycol, and hydrogen peroxide in alkaline solution. It can slowly oxidize in the air, can be unstable under illumination, and should be stored in a dark condition. Melting point: the melting point is 81°C.

Occurrence

Vanillin occurs widely in nature; it has been reported in the essential oil of Java citronella (Cymbopogon nardus Rendl.), in benzoin, Peru balsam, clove bud oil and chiefly vanilla pods (Vanilla planifolia, V. tahitensis, V. pompona); more that 40 vanilla varieties are cultivated; vanillin is also present in the plants as glucose and vanillin. Reported found in guava, feyoa fruit, many berries, asparagus, chive, cinnamon, ginger, Scotch spearmint oil, nutmeg, crisp and rye bread, butter, milk, lean and fatty fish, cured pork, beer, cognac, whiskies, sherry, grape wines, rum, cocoa, coffee, tea, roast barley, popcorn, oatmeal, cloudberry, passion fruit, beans, tamarind, dill herb and seed, sake, corn oil, malt, wort, elderberry, loquat, Bourbon and Tahiti vanilla and chicory root.

History

Vanillin is known as one of the first synthetic spices. In the perfume industry, it is known as vanillic aldehyde. As early as 1858, French chemist Gby (NicolasTheodore Gobley) obtained pure vanillin for the first time by the method of rectification. Due to less production yield of natural vanillin, it spurred the search for a chemical synthesis method of vanillin production. In 1874, German scientist M.?Haarman and co-workers deduced the chemical structure of vanillin and discovered a new way to produce vanillin with abietene as the raw material . In 1965, Chinese scientists found that vanillin has antiepileptic effect and accomplished a study on the pharmacology and toxicology of vanillin from edible to officinal. They also found that vanillin has certain antibacterial activity, making it a suitable drug formulation for the treatment of skin disease. Vanillin can be used as intermediate for synthesis of a variety of drugs, such as berberine and antihypertensive drug L-methyldopa, methoxy-pyrimidine, and heart disease drug papaverine .

The Uses of Vanillin

Labelled Vanillin. Occurs naturally in a wide variety of foods and plants such as orchids; major commercial source of natural vanillin is from vanilla bean extract. Synthetically produced in-bulk fro m lignin-based byproduct of paper processes or from guaicol.

The Uses of Vanillin

The primary component of Vanilla bean extract.

The Uses of Vanillin

An intermediate and analytical reagent.

The Uses of Vanillin

Pharmaceutic aid (flavor). As a flavoring agent in confectionery, beverages, foods and animal feeds. Fragance and flavor in cosmetics. Reagent for synthesis. Source of L-dopa.

The Uses of Vanillin

Vanillin is a flavorant made from synthetic or artificial vanilla which can be derived from lignin of whey sulfite liquors and is syntheti- cally processed from guaiacol and eugenol. the related product, ethyl vanillin, has three and one-half times the flavoring power of vanillin. vanillin also refers to the primary flavor ingredient in vanilla, which is obtained by extraction from the vanilla bean. vanillin is used as a substitute for vanilla extract, with application in ice cream, desserts, baked goods, and beverages at 60–220 ppm.

What are the applications of Application

Vanillin is an intermediate and analytical reagent

Definition

ChEBI: A member of the class of benzaldehydes carrying methoxy and hydroxy substituents at positions 3 and 4 respectively.

Production Methods

Vanillin occurs naturally in many essential oils and particularly in the pods of Vanilla planifolia and Vanilla tahitensis. Industrially, vanillin is prepared from lignin, which is obtained from the sulfite wastes produced during paper manufacture. Lignin is treated with alkali at elevated temperature and pressure, in the presence of a catalyst, to form a complex mixture of products from which vanillin is isolated. Vanillin is then purified by successive recrystallizations.
Vanillin may also be prepared synthetically by condensation, in weak alkali, of a slight excess of guaiacol with glyoxylic acid at room temperature. The resultant alkaline solution, containing 4- hydroxy-3-methoxymandelic acid is oxidized in air, in the presence of a catalyst, and vanillin is obtained by acidification and simultaneous decarboxylation. Vanillin is then purified by successive recrystallizations.

Preparation

Commercial vanillin is obtained by processing waste sulfite liquors or is synthesized from guaiacol. Preparation by oxidation of isoeugenol is of historical interest only.
1) Preparation from waste sulfite liquors: The starting material for vanillin production is the lignin present in sulfite wastes from the cellulose industry. The concentrated mother liquors are treated with alkali at elevated temperature and pressure in the presence of oxidants. The vanillin formed is separated from the by-products, particularly acetovanillone (4-hydroxy-3- methoxyacetophenone), by extraction, distillation, and crystallization. A large number of patents describe various procedures for the (mainly) continuous hydrolysis and oxidation processes, as well as for the purification steps required to obtain high-grade vanillin . Lignin is degraded either with sodium hydroxide or with calcium hydroxide solution and simultaneously oxidized in air in the presence of catalysts. When the reaction is completed, the solid wastes are removed. Vanillin is extracted from the acidified solutionwith a solvent (e.g., butanol or benzene) and reextractedwith sodium hydrogen sulfite solution. Reacidification with sulfuric acid followed by vacuum distillation yields technical-grade vanillin, which must be recrystallized several times to obtain food-grade vanillin.Water, to which some ethanol may be added, is used as the solvent in the last crystallization step.
2) Preparation from guaiacol: Severalmethods can be used to introduce an aldehyde group into an aromatic ring. Condensation of guaiacol with glyoxylic acid followed by oxidation of the resulting mandelic acid to the corresponding phenylglyoxylic acid and, finally, decarboxylation continues to be a competitive industrial process for vanillin synthesis.
a. Vanillin from guaiacol and glyoxylic acid: Currently, guaiacol is synthesized from catechol, which is mainly prepared by acid-catalyzed hydroxylation of phenol with hydrogen peroxide. In China, a guaiacol prepared from o-nitrochlorobenzene via o-anisidine is also used. Glyoxylic acid is obtained as a by-product in the synthesis of glyoxal from acetaldehyde and can also be produced by oxidation of glyoxal with nitric acid. Condensation of guaiacol with glyoxylic acid proceeds smoothly at room temperature and in weakly alkaline media. A slight excess of guaiacol is maintained to avoid formation of disubstituted products; excess guaiacol is recovered. The alkaline solution containing 4-hydroxy- 3-methoxymandelic acid is then oxidized in air in the presence of a catalyst until the calculated amount of oxygen is consumed [358]. Crude vanillin is obtained by acidification and simultaneous decarboxylation of the (4-hydroxy-3-methoxyphenyl)glyoxylic acid solution.
This process has the advantage that, under the reaction conditions, the glyoxyl radical enters the aromatic guaiacol ring almost exclusively para to the phenolic hydroxy group. Tedious separation procedures are thus avoided. b. Vanillin from guaiacol and formaldehyde: An older process that is still in use consists of the reaction of guaiacolwith formaldehyde or formaldehyde precursors such as urotropine, N,N-dimethyl-aniline, and sodium nitrite .

Indications

It can be used to treat various types of epilepsy and attention deficit hyperactivity disorder and vertigo.

Composition

In addition to vanillin (approximately 3%), vanilla contains other aromatic principles: vanillin, piperonal, eugenol, glucovanillin, vanillic acid, anisic acid and anisaldehyde. Although vanillin is associated with the characteristic fragrance of the plant, the quality of vanilla bean is not associated with the vanillin content. Bourbon beans contain a high amount of vanillin compared to Mexican and Tahiti beans.

Aroma threshold values

Detection: 29 ppb to 1.6 ppm; recognition: 4 ppm

Taste threshold values

Taste characteristics at 10 ppm: sweet, typical vanilla-like, marshmallow, creamy-coumarin, caramellic with a powdery nuance.

Synthesis Reference(s)

The Journal of Organic Chemistry, 46, p. 4545, 1981 DOI: 10.1021/jo00335a045

General Description

Certified pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to pharmacopeia primary standards

Air & Water Reactions

Slowly oxidizes on exposure to air. . Slightly water soluble.

Reactivity Profile

Vanillin can react violently with Br2, HClO4, potassium-tert-butoxide, (tert-chloro-benzene + NaOH), (formic acid + Tl(NO3)3). . Vanillin is an aldehyde. Aldehydes are readily oxidized to give carboxylic acids. Flammable and/or toxic gases are generated by the combination of aldehydes with azo, diazo compounds, dithiocarbamates, nitrides, and strong reducing agents. Aldehydes can react with air to give first peroxo acids, and ultimately carboxylic acids. These autoxidation reactions are activated by light, catalyzed by salts of transition metals, and are autocatalytic (catalyzed by the products of the reaction).

Fire Hazard

Flash point data for Vanillin are not available, however Vanillin is probably combustible.

Flammability and Explosibility

Non flammable

Pharmaceutical Applications

Vanillin is widely used as a flavor in pharmaceuticals, foods, beverages, and confectionery products, to which it imparts a characteristic taste and odor of natural vanilla. It is also used in perfumes, as an analytical reagent and as an intermediate in the synthesis of a number of pharmaceuticals, particularly methyldopa. Additionally, it has been investigated as a potential therapeutic agent in sickle cell anemia and is claimed to have some antifungal properties.
In food applications, vanillin has been investigated as a preservative.
As a pharmaceutical excipient, vanillin is used in tablets, solutions (0.01–0.02% w/v), syrups, and powders to mask the unpleasant taste and odor characteristics of certain formulations, such as caffeine tablets and polythiazide tablets. It is similarly used in film coatings to mask the taste and odor of vitamin tablets. Vanillin has also been investigated as a photostabilizer in furosemide 1% w/v injection, haloperidol 0.5% w/v injection, and thiothixene 0.2% w/v injection.

Pharmacology

Lethal or sublethal doses of vanillin administered orally to anaesthetized rabbits produced sudden depression of the blood pressure and stimulated respiration (Deichmann & Kitzmiller, 1940). Similar results were obtained in dogs (Caujolle et al. 1953).
Vanillin produced only a small increase in bile output when administered iv to rats (Rohrbach & Robineau, 1958), and induced some choleretic activity when injected ip into rats in doses of 10-250 mg/kg (Pham-Huu-Chanh, Bettoli-Moulas & Maciotta-Lapoujade, 1968). Injected sc in doses of 1 mg/day for 4 days into immature female rats, it caused a decrease in the ovarian- and an increase in the uterine-weight response to exogenous gonadotropic hormone (Kar, Mundle & Roy, 1960). Vanillin had no effect on the nervous system of fish (Bohinc & Wesley-Hadzija, 1956). In dietary concentrations of 0.05 and 0.1% it had a cariostatic effect in hamsters without impairing growth (Stralfors, 1967).
Vanillin administered as an aerosol had no effect on normally-functioning isolated perfused guineapig lungs and did not prevent spontaneous pneumoconstriction (Pham-Huu-Chanh, 1963 & 1964).
It did not act as a cross-linking (tanning) agent for corium and aorta, since in 0.15 M solution it did not increase the observed in vitro hydrothermal shrinkage temperatures of goat skin and human, bovine and canine aortae (Milch, 1965). It decreased slightly the déformability of dense red cell packs (Jacobs, 1965), and in 1-2 mM concentration produced 50-100% inhibition of collageninduced platelet aggregation in human blood (Jobin & Tremblay, 1969).

Clinical Use

Vanillin tablet has been used in the treatment of epilepsy and has a better therapeutic effect. Some patients have a minor dizziness response occasionally in the clinic.

Safety Profile

Moderately toxic by ingestion, intraperitoneal, subcutaneous, and intravenous routes. Experimental reproductive effects. Human mutation data reported. Can react violently with Br2, HClO4, potassium-tert-butoxide, tert- chlorobenzene + NaOH, formic acid + thallium nitrate. When heated to decomposition it emits acrid smoke and irritating fumes. See also ALDEHYDES.

Safety

There have been few reports of adverse reactions to vanillin, although it has been speculated that cross-sensitization with other structurally similar molecules, such as benzoic acid, may occur.
Adverse reactions that have been reported include contact dermatitis and bronchospasm caused by hypersensitivity.
The WHO has allocated an estimated acceptable daily intake for vanillin of up to 10 mg/kg body-weight.
LD50 (guinea pig, IP): 1.19 g/kg
LD50 (guinea pig, oral): 1.4 g/kg
LD50 (mouse, IP): 0.48 g/kg
LD50 (rat, IP): 1.16 g/kg
LD50 (rat, oral): 1.58 g/kg
LD50 (rat, SC): 1.5 g/kg

Synthesis

From the waste (liquor) of the wood-pulp industry; vanillin is extracted with benzene after saturation of the sulfite waste liquor with CO2. Vanillin is also derived naturally through fermentation.

Metabolism

Early observers noted conversion of vanillin to vanillic acid which was excreted mainly as the free acid, a conjugated ethereal sulphate or glucurovanillic acid (Preusse, 1880). In man, vanillin is broken down by the liver to vanillic acid which is excreted in the urine. Human liver homogenates readily convert vanillin to vanillic acid in vitro (Dirscherl & Brisse, 1966). Endogenous vanillic acid production and excretion in man from body catecholamines amounts to <0.5 mg/day, compared with the normal contribution from dietary sources of about 9 mg/day (Dirscherl & Wirtzfeldt, 1964).

storage

Vanillin oxidizes slowly in moist air and is affected by light.
Solutions of vanillin in ethanol decompose rapidly in light to give a yellow-colored, slightly bitter tasting solution of 6,6’-dihydroxy- 5,5’-dimethoxy-1,1’-biphenyl-3,3’-dicarbaldehyde. Alkaline solutions also decompose rapidly to give a brown-colored solution. However, solutions stable for several months may be produced by adding sodium metabisulfite 0.2% w/v as an antioxidant.
The bulk material should be stored in a well-closed container, protected from light, in a cool, dry place.

Purification Methods

Crystallise vanillin from water or aqueous EtOH, or by distillation in vacuo.[Beilstein 8 IV 1763.]

Incompatibilities

Incompatible with acetone, forming a brightly colored compound. A compound practically insoluble in ethanol is formed with glycerin.

Regulatory Status

GRAS listed. Included in the FDA Inactive Ingredients Database (oral solutions, suspensions, syrups, and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.