Ванилин

Описание

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 .

Химические свойства

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.

Физические свойства

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.

Вхождение

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.

История

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 .

Использование

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.

Определение

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

Методы производства

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.

Показания

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

Общее описание

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

Реакции воздуха и воды

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

Профиль реактивности

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).

Пожароопасность

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

Фармацевтические приложения

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.

Клиническое использование

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.

Профиль безопасности

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.

Безопасность

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

Метаболизм

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).

хранилище

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.

Методы очистки

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

Несовместимости

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

Регуляторный статус

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.