|Vanillin Basic information|
|Synonyms:||2-Methoxy-4-formylphenol;3-Methoxy-4-hydroxybenzaldehyde (vanillin);4-Formyl-2-methoxyphenol;Protocatechualdehyde, methyl-;Vanillin Powder;Vanillin cas:121-33-5;Vanillin NAT;Vanillin 97+%|
|Product Categories:||Aromatic Aldehydes & Derivatives (substituted);Analytical Chemistry;Food and Feed Additive;FINE Chemical & INTERMEDIATES;Food & Feed ADDITIVES;TLC Stains;FOOD ADDITIVES;PHARMACEUTICALS;Food & Flavor Additives;Aromatics;Intermediates & Fine Chemicals;Isotope Labelled Compounds;Flavor;Inhibitors;organic chemical;Aldehydes;Bioactive Small Molecules;Building Blocks;C8;Carbonyl Compounds;Cell Biology;Chemical Synthesis;Organic Building Blocks;Pharmacopoeia;Pharmacopoeia A-Z;V;Polyether Antibiotics;Analytical Reagents;Analytical/Chromatography;by Application;Derivatization Reagents;Derivatization Reagents HPLC;HPLC Derivatization Reagents;Nutrition Research;Phytochemicals by Plant (Food/Spice/Herb);Vaccinium myrtillus (Bilberry);Zingiber officinale (Ginger)|
|Vanillin Chemical Properties|
|Melting point||81-83 °C(lit.)|
|Boiling point||170 °C15 mm Hg(lit.)|
|vapor density||5.3 (vs air)|
|vapor pressure||>0.01 mm Hg ( 25 °C)|
|FEMA||3107 | VANILLIN|
|refractive index||1.4850 (estimate)|
|solubility||methanol: 0.1 g/mL, clear|
|pka||pKa 7.396±0.004(H2O I = 0.00 t = 25.0±1.0) (Reliable)|
|color||White to pale yellow|
|PH||4.3 (10g/l, H2O, 20℃)|
|Water Solubility||10 g/L (25 ºC)|
|Sensitive||Air & Light Sensitive|
|Stability:||Stable. May discolour on exposure to light. Moisture-sensitive. Incompatible with strong oxidizing agents, perchloric acid.|
|CAS DataBase Reference||121-33-5(CAS DataBase Reference)|
|NIST Chemistry Reference||Benzaldehyde, 4-hydroxy-3-methoxy-(121-33-5)|
|EPA Substance Registry System||Vanillin (121-33-5)|
|Autoignition Temperature||>400 °C|
|Hazardous Substances Data||121-33-5(Hazardous Substances Data)|
|Toxicity||LD50 orally in rats, guinea pigs: 1580, 1400 mg/kg (Jenner)|
|Vanillin Usage And Synthesis|
|Summary||Vanillin is the artificial synthesis of the first kind of flavor, synthesized by the German M. Harman, and G-Dr. Twyman in 1874. Usually It is divided into methyl vanillin and ethyl vanillin.
1. Methyl vanillin: white or slightly yellow crystalline, with vanilla aroma and rich milk fragrance, is the largest varieties of perfume industry, is the main ingredients of universal favorite creamy vanilla flavor. Its use is very extensive, such as in food, chemical, tobacco industry as spices, flavoring agent or a flavor enhancer, which is the majority in food consumption of drinks, candy, cakes, biscuits, bread and roasted seeds. There are no relevant reports that vanillin was harmful to the human body.
2. Ethyl vanillin: white to micro yellow needle crystal or crystalline powder, similar to vanilla beans, aroma than methyl vanillin thicker. It is a broad-spectrum flavors, which is one of the world's most important synthetic spice, is an important and indispensable raw material for food additives industry. The aroma is 3-4 times than the vanillin, with aromas of vanilla bean aroma and long-lasting fragrance. Widely used in food, chocolate, ice cream, drinks and cosmetics play aroma and flavour. Also ethyl vanillin also is feed additives, electroplating industry of brightening agent, the pharmaceutical industry of intermediates. C. Guaiacol glyoxylate route By using guaiacol and glyoxylic acid as raw material then by condensation, oxidation and decarboxylation made to vanillin. This method is mainly composed of French Rhone-Poulenc company research and development, and production in large scale. The use of glyoxylic acid from maleic acid methyl ester was prepared by two ozone decomposition (German patent 3224795). The synthetic route has the advantages of wide material source, less reaction steps, low cost, less three wastes pollution. Therefore, it is considered to be the most appropriate method.
|Vanilla extract||Vanilla is a member of the orchid family, a sprawling conglomeration of some 25,000 different species. Vanilla is a native of South and Central America and the Caribbean; and the first people to have cultivated it seem to have been the Totonacs of Mexico’s east coast. The Aztecs acquired vanilla when they conquered the Totonacs in the 15th Century; the Spanish, in turn, got it when they conquered the Aztecs.
Vanilla is a complex blend of flavour and fragrance ingredients extracted from the seed pods of the vanilla orchid, containing at a guess somewhere between 250 and 500 different flavor and fragrance components. The most important ingredient in this blend is vanillin. However, because of the cost and supply chain variability of natural vanilla, most products that want to impart the aroma of vanilla do not in fact use vanilla but rather synthetic vanillin (99% of all vanillin consumed worldwide) made primarily from petrochemicals or chemically derived from lignin.
Vanillin is mainly used as a flavouring agent, primarily in foods and beverages such as chocolate and dairy products, but also to mask unpleasant tastes in medicines or livestock fodder. It is also an intermediate in the manufacture of certain pharmaceuticals and agrochemicals.
Vanillin and vanilla extracts have an estimated annual total volume of 16,000 metric tonnes, worth some USD 650 million in total. Natural vanilla extract represents less than 1% by volume, though it is more important in terms of value. Sales prices range from about USD 1,500 per kg for natural vanilla extract to USD 10-20 per kg for synthetic vanillin.
The primary market opportunity is in providing a competitively priced product, with good aroma properties, made from a natural and sustainable source. Evolva believes such properties will allow fermentation-derived vanillin to be used in a wide variety of food and other products. Evolva does not believe that such a product will significantly replace vanilla obtained from the orchid.
|Important spices||Vanillin is commonly known as vanilla powder, cloud Nepal with powder, vanilla extract, is extracted from the Rutaceae vanilla bean, is a kind of important spices, is one of synthetic fragrances yield the largest varieties, mixing chocolate, ice cream, chewing gum, pastry and tobacco essence of important raw materials. Naturally occurring in pods of vanilla planifolia, and clove oil, oakmoss oil, balsam of Peru, tolu balsam storax.
Vanillin has strong and unique vanilla bean aroma, aroma stability, under the high temperature, less volatile. It is vulnerable to light, and gradually oxidized in the air, easy to change color at encountering alkali or alkaline material. Aqueous solution reacts with ferric chloride to produce blue purple solution. Can be used for many fragrance formulas, but mainly used for edible essence. Especially widely used in the candy, chocolate, soft drinks, ice cream, wine, and in the smoke flavor.There is no restrictions imposed on the use of IFRA. But because of easy cause discoloration, we should pay attention to use in white fragrant product.
Vanillin is also an important foundation for edible spices, spices, almost all flavors, most used in food industry. Food flavors are widely used in bread, butter, cream and brandy etc. The addition amount of cakes, biscuits is 0.01~0.04%, candy is 0.02~0.08%, which is one of the most the baked food with spices, can be used for chocolate, biscuit, cake, ice cream and Boudin. Before use, it is dissolved in warm water, the effect is much better. The highest amount of baked food is 220mg/kg, chocolate is 970mg/kg. As fixative agent, coordination agent and modifier are widely used in cosmetics, also is the important flavoring agent for food and drink. it is used in medicine. L-DOPA (L-dopa), methyldopa. Also used for nickel, chrome metal plating brightener.
|Physicochemical properties||Vanillin has strong and unique vanilla beans, naturally found in vanilla and clove oil, oil, oakmoss, balsam of Peru, and the rest of tolu balsam. Sulfite solution or red pulp softwood lignin sulfonate, under the alkaline conditions, reacted by high-pressure oxidation hydrolysis precipitation to get white to light yellow crystalline powder or acicular crystal. From petroleum ether precipitation can also generate tetragonal crystal. It has Aroma, Bitter sweet. In the air, it is gradually oxidized. In case of light, it generated decomposition. In case of alkali, it generated discoloration. The relative molecular mass is 152.15. The relative density is 1.056. melting point is different form tetragonal crystalline to another, tetragonal crystal is 81 to 83℃. Acicular crystal ranged from 77 to 79℃, the boiling point is 285℃ (in CO2 gas), 170℃ (2 x 103Pa), 162℃ (1.33 x 103Pa), 146 C (0.533 x 103Pa). It can generate sublimation without decomposition. The flash point is162 ℃. Slightly soluble in cold water, soluble in hot water, soluble in ethanol, ethyl ether, propylene Ketone, benzene, chloroform, carbon disulfide, glacial acetic acid, pyridine and volatile oil. Water and FeCl3 generate blue purple solution. For rats, by oral LD 50 1580mg/kg, mice is by percutaneous LD 50 1500mg/kg.
Industrial production method is that eugenol in the presence of potassium hydroxide, produce to ISO eugenol, then reacted with acetic anhydride formation of isoeugenol acetate, followed by oxidation and hydrolysis reaction to produce. It is an important raw material for mixing chocolate, ice cream, chewing gum the pastry and tobacco flavor. It can also be used as cosmetics fragrance coordination agent and a flavor enhancer. It is also the pharmaceutical raw materials of industry.
In recent years, it appeared a new fashion in the commodity of vanillin. Use oil of clove or basil oil provided out of eugenol as raw material, vanillin obtained by isomerization and oxidation, as it can be regarded as a natural equivalent quality, therefore it is called natural vanillin and into the spice market, its price is about 5 times that of the synthetic product.
|Action and use||Flavors: vanillin is edible flavouring agent, with vanilla bean aroma and strong desire for milk fragrance, is an important and indispensable raw material for food additives industry, widely used in all need to increase milk fragrance flavor flavoring in food, such as cake, cold drinks, chocolate, candy, biscuits, instant noodles, bread and tobacco, flavoring liquor, toothpaste, soap, cosmetics, perfume, ice cream, drinks and cosmetics play aroma and flavour. Also it can be used for soap, toothpaste, perfume, rubber, plastic, pharmaceutical products. It Accord with FCCIV standard.|
|Side Effects||General Side Effects
Using of vanillin in large quantity(over 30g a time) could lead to headache, nausea, vomiting, difficulty breathing, and even kidney damage.Don’t get too frightened, vanillin isn’t one of the most toxic food additives you’ll find and in fact usually won’t trigger much more than a headache or allergic reaction in sensitive folks. Usually, switching from artificial vanilla extract to pure vanilla extract is all that is needed to avoid issues. Many connoisseurs of the vanilla bean claim vanillin to be an inferior product to pure vanilla extract anyway. If you’re making an attempt to eat quality food, you probably won’t encounter much vanillin anyway.
Special Groups Precaution
Special groups refer to newborns, children, pregnant and any other applicable vulnerable groups.
There is no evidence that Vanillin could have any negative effects on these vulnerable groups. It should be safe to use Vanillin in food for newborns and pregnant. However, we still recommend consumers to consult professionals before using large quantity of Vanillin for long period in food for newborns or pregnant.
GRAS Affirmation: Yes
Generally recognized as safe(GRAS) is a FDA designation that a specific substance or ingredient is generally considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act (FFDCA) food additive tolerance requirements. Vanillin is considered safe by FDA according to existing data and granted GRAS status.
|Vanitrope||Vanitrope has a strong and enduring clove and vanilla aroma, the aroma intensity is from 16 to 25 times of vanillin. Vanitrope was early developed. in the twenties of the 20th century. Early synthetic route is that safrole oil as raw material, the alcohol solution of potassium hydroxide reacted hot pressing enable to open ring, and then used sodium ethyl sulfate to make the hydroxy ethylation, finally in the ethanol solution with sulfuric acid hydrolysis to obtain the vanitrope. But due to the lack purity of aroma of the product, so it is very little actual application.
In the fifties of the 20th century, it developed from eugenol preparation of vanitrope synthetic route (U. S. patent 2663741), only then can realize the industrial production.
Catechol flavor chemists,successfully developed by more cheap raw materials of pyrocatechol in the Soviet Union in 1960s.
First with allyl chloride to catechol mono alkylation, and the yield is 75%; followed by rearrangement reaction and yield is 35%~38%; then by using ethyl sodium sulfate for single ethylation, yield is 82%. Finally with potassium hydroxide isomerization will get vanitrope, yield is 84%, after recrystallization of the crude product melting point 85.5 to 86℃.
Vanitrope applied in candy, beverage, ice cream and other food flavoring formulations, the FEMA number is 2922. It also can be used in cosmetics and soap fragrance formula. It not only can used as a spice, but also can be used as a synergistic agent and antioxidant.
Former Soviet Union perfumers hold different views of vanitrope aroma properties. They added it to the chocolate and other food flavor. It is found that the goods are not vanillin aroma, so that it cannot in the flavor of food as a substitute for vanillin. But when used for flavoring test of scented soap, found that soap has strong clove and vanilla aroma like it. The differences with vanillin and isoeugenol, vanitrope to alkali, light, oxidation is very stable, soap like storage does not change color. Therefore vanitrope should be used in fragrance formulations, particularly appropriate for fantasy flavor.
|Industrial production methods vanillin||Industrial production of vanillin has more than 100 years of history, people have studied the ways and methods of many synthetic preparations, but the application in a large-scale industrial production are mainly the following three methods.
A. lignin route
In papermaking industry, sulfite pulp waste liquid containing wood lignosulfonates as raw material, the alkaline and high temperature and high pressure was hydrolysis dehydration, and then again oxidation. Canada and the United States mainly adopted the production method of vanillin.
B. Guaiacol formaldehyde route
Guaiacol is the most important raw material for synthesis of vanillin, guaiacol, formaldehyde, the nitroso dimethylaniline as raw material of synthetic route, also known as the nitroso process. The former Soviet Union and China mainly adopts the method.
C. Guaiacol glyoxylate route
By using guaiacol and glyoxylic acid as raw material then by condensation, oxidation and decarboxylation made to vanillin.
This method is mainly composed of French Rhone-Poulenc company research and development, and production in large scale. The use of glyoxylic acid from maleic acid methyl ester was prepared by two ozone decomposition (German patent 3224795).
The synthetic route has the advantages of wide material source, less reaction steps, low cost, less three wastes pollution. Therefore, it is considered to be the most appropriate method.
|Content analysis||The method one: UV absorption Spectrophotometry.
Preparation of Standard solution: taking accurately medicines ginseng than vanillin standard about 100mg, into a 250ml volumetric flask, with constant volume with methanol, mixed. The solution 2.0ml, into a 100 ml volumetric flask, with methanol fixed volume mixing.
The liquid sample preparation: weighed accurately sample of about 100mg, the preparation method and the standard solution preparation are the same.
Operation: Take from the solution into a 1 cm quartz cells. Determine absorbance at the maximum absorption wavelength of about 308 nm. Press type calculation sample vanillin (C8H8O3) content (x) (mg):
C-vanillin in standard solution concentration, g/ml;
Au-The absorbance of sample liquid;
As-The absorbance of standard solution.
Methods two: Accord by gas chromatography (GT-10-4) with non-polar column determination method.
|Toxicity||LD50 orally in rats, guinea pigs: 1580, 1400 mg/kg (Jenner)|
|Limited use||FEMA (mg/kg): soft drinks 63; cold 95; candy 200; baking food 220; pudding class 120, chewing gum, 270; chocolate 970; decorating layer 150; margarine 0.20; syrup 330~20000.
According to the provisions of FAO/WHO: The allowable amount is 70mg/kg for fast food, of canned baby foods and cereals (1992).
|Industry development||China is a big country of world vanillin export, the domestic demand was 2350 tons in 2002, accounted for 30% production, 70% of the remaining was for export. In 1988 only exported 2.73 tons, 1700 tons in 1993, 4653 tons in 2002. From 1993 to 2002, China's export volume of vanillin grew at an average annual rate of rate of 12%. In North America, Europe, Southeast Asia and other markets enjoy a good reputation.
In 2012, global vanillin demand is about 17500 tons, which developed countries demand is in equilibrium state, and developing demand of vanillin increased significantly, making the total demand of vanillin still in growth period. The actual total demand of China currently has reached 3000 tons. At present, the per capita amount is still slightly lower than the global per capita use.
Major domestic suppliers of Jiaxing City, China Chemical Co., Ltd. is now the world's largest vanillin professional manufacturer. In 2014, company with an annual output of methyl vanillin is 10000 tons, 2000 tons of ethyl vanillin, which more than 80% of products are for export.
At abroad, there mainly are France Rhodia Inc., Norwegian Bao very company, Ube three vanillin production companies. Among them, Rhodia, France is the world's most famous vanillin production enterprises, annual production capacity is 8000 tons, the distribution device in France and the United States. in addition to the Norwegian company Bao Selig using lignin production of vanillin, domestic and international companies used guaiac wood phenol-aldehyde acid production of vanillin.
|Chemical property||White needle crystal, with Fragrant smell. Soluble in water of 125 times, 20 times of ethylene glycol and 2 times of 95% ethanol, insoluble in chloroform.|
|Uses||1. Used as a flavor, fragrance, pharmaceutical intermediates.
2. It is to obtain the incense powder, bean fragrant spices. Often used in the fragrance foundation with. It is widely used in almost all the flavor that doubles as a combination of such as violet, Cymbidium, sunflower, Oriental flavor. And piperonal, isoeugenol benzyl ether, coumarin, musk and others are set incense, modifier and mixture, can also be used to cover up bad breath. In edible, smoke flavor as well as wide application, but the amount is larger. In vanilla bean type, cream, chocolate, too Princess flavor are need to use spices.
3. Vanillin is China's regulations allow the use of edible spices, as a fixative agent, is the preparation of the main raw material of vanilla flavor. It can also be directly used in biscuits, cakes, candy, drinks and other food flavoring. Dosage according to the normal production needs, generally in the chocolate 970mg/kg; 270mg/kg in chewing gum; 220mg/kg in pastry, biscuit; 200mg/kg in candy; 150mg/kg in condiment~95mg/kg in cold drinks.
4. GB 2760 1996 provisions allow the use of edible spices. Widely used in the preparation of vanilla, chocolate, butter flavor, the amount is up to 25%~30%, or directly used in biscuits, pastries, dosage is 0.1%~0.4%, cold drink is 0.01%~0.3%, candy is 0.2%~0.8%, especially containing dairy products.
5. An important synthetic fragrance, widely used in daily life activities. It is used as food, tobacco and wine with a fine wisely. In the food industry usage amount is large for the preparation of the vanilla, chocolate, butter flavor, the amount is up to 25-30%, directly on a cookie, cake, dosage is 0.1-0.4%, cold is 0.01-0.3%, candy is 0.2-0.8, especially is containing dairy products. It is used for chemical analysis, tests for protein nitrogen heterocyclic indene, phloroglucinol and tannic acid. In the pharmaceutical industry, it is used for production of antihypertensive drug methyldopa, catechols L-dopa medication, and Catalin and diaveridine.
6. Used as a reagent in organic analysis standard.
7. Tests for protein, nitrogen heterocyclic indene, pyrogallol, tannic acid, iron ions. from benzoic acid in the determination of chloride, spices, organic trace analysis determination of methoxy standard.
|Methods of production||1.N N-,dimethylaniline with hydrochloric acid was acidated to salt, with sodium nitrite nitrification out to nitroso-N, N-nitrobine hydrochloride, which with guaiacol and formaldehyde were condensated at 41-43℃. Then, it with benzene extracted. The first distillation with benzene, and then the second distillation, water recrystallization, 50℃ drying to obtain the product. Sulfite pulp waste liquid containing birch cypress structure units of lignin sulfonate, in alkaline conditions oxidation and hydrolysis can be obtained and the raw material consumption (kg/t) guaiacum phenol (98%) in 1460 sodium nitrite 640, N,N-methyl aniline (98%), 974 of hydrochloric acid (30%), 6000 (99%) of 320.
2.The vanilla bean extract.
By theo-aminoanisole by diazonium hydrolysis into guaiacol, in the presence of nitroso dimethylaniline and catalyst, with formaldehyde condensation, or react with chloroform in Catalyzed by potassium hydroxide and after extraction separation, vacuum distillation and crystallization purification. Also available wood pulp waste liquid, eugenol, guaiacol, safrole were made.
3. Using lignin as raw material
Vanillin can be preparation from paper plant sulfite pulping waste liquor containing lignin. General waste liquid contains solid matter 10%~12%, of which 40%~50% is lignin sulfonic acid calcium. The waste liquid is concentrated to 40%~50% solid form, adding NaOH of 25% of lignin amount, and heating to 160 to 175 ℃ (about 1.1~1.2 MPa), air oxidation for 2h, the conversion rate is generally up to 8%~11%. Oxide with benzene extract vanillin, and water vapor distillation method for the recovery of benzene in the oxide with sodium bisulfite to generate sub hydrogen sulfate salt and impurity separated, and then the decomposition of sulfuric acid to vanillin. Finally, it is by vacuum distillation and recrystallization to obtain the product.
Use guaiacol as raw materials
Chloral guaiacol method and trichloro acetaldehyde in the presence of sodium carbonate or potassium carbonate, heating to 27℃ was synthesized through the condensation of 3-methoxy-4-hydroxyphenyl trichloro methyl carbinol, not reaction guaiac wood phenol water vapor distillation removed. In the presence of caustic soda, nitrobenzene as oxidant, heat to 150 ℃ oxidative cleavage of vanillin was obtained; Can also be used Cu-CuO-CoCl2 as catalyst and 100℃ in the air oxidation, after reaction with benzene extraction of vanillin, by vacuum distillation and recrystallization purification so as to obtain the finished product.
Glyoxylic acid method: in glyoxylic acid solution followed by adding guaiacol, sodium hydroxide and sodium carbonate, and at 30 to 33℃ by condensation to 3-methoxy-4-hydroxy phenyl glycollic acid by solvent extraction of guaiacol reaction after adding sodium hydroxide solution, nitrobenzene sulfonic acid and calcium hydroxide in Q presence heated to 100℃ for oxidation and pyrolysis to vanillin. Oxidation products were neutralized with two chlorine ethane extraction of vanillin, crude product by vacuum distillation and recrystallization was finished.
The nitroso process: 30% hydrochloric acid166kg and water 200kg are added into the reaction kettle, cooled to l0℃, dropping two methyl aniline 61.5kg in 2h the temperature is less than 25%, then continue stirring 20min. water solution is cooled to 6 ℃ after infusion of sodium nitrite 75kg with 25% water solution, the temperature control and continue to stir 1h. filter p-nitroso two methyl aniline hydrochloride at 7~10 ℃, adding a quantitative Ethanol and concentrated hydrochloric acid, diluted in solid, the nitroso two methyl aniline.
Guaiacol and p-nitroso two methyl aniline condensation: The 26kg of urotropine dissolved in 34kg water mixture, then add 126kg guaiacol and 63kg ethanol, stored in headtank standby. The income of the nitroso dimethylaniline dihydrochloride and ethanol mixture of 550Kg will join the reaction kettle, heating to 28℃ after adding metal salt catalyst, and then heated to 35 to 36 ℃ when dropping guaiac wood phenol mixture (3~3.5h), keeping the temperature in 40 to 43 ℃, drop after adding continue to stirring 1h of reaction. Then add 100kg diluted 40 ℃water, stirring and 15min content in liquid condensation of vanillin should be above 11%.
Use benzene as solvent. the rotary liquid-liquid extraction column continuous countercurrent extraction the above condensation liquid. Benzene extraction fluid contains a large number of hydrochloric acid, water washing, and then alkali neutralization to ph=4; Climbing film evaporator distillation recovery of benzene and water vapor rush steam 1h to remove residual benzene; decompression steam to water and finally in 120 to 150 ℃ (666.6Pa) rapid steaming out crude vanillin, freezing point is 70℃ or so. The crude product was dissolved in 70 ℃ in toluene, filtering after cooling to 18 to 20℃, suction and washing with a small amount of toluene to vanillin. Then the second vacuum distillation, from 130 to 140℃ (266.6~399.9Pa) fractions and dissolved in dilute ethanol 60~70 ℃, slowly cooled to 16 to 18 ℃, the crystallization (1H). Using the centrifuge filter, and use a little dilute ethanol washing. At the end of 50 to 60 ℃, hot air drying 12 h products. According to guaiacol, the yield can reach more than 65%.
Use p-hydroxybenzaldehyde as raw materials, through single bromination, methoxylation reaction to preparate vanillin. In a 250ml flask, added 16g (0.131mo1) of p-hydroxybenzaldehyde and 90ml solvent. After the dissolution of the people 6.8mL (0.131mol) bromine and heated to 40~45℃ and reaction for 6h. Solvent residue and vacuum pumping, boiling water, hot filtering, filtrate cooling crystallization, filtration and drying of white crystalline 3-bromo-4-hydroxy benzaldehyde, the melting point is 123 to 124 ℃, the yield is 90%.
In 250ml flask, join 12g (0.0597mol) of the product, sodium methanol solution of methylmercury 45ml (0.230mol) 28.24%, and 0.2gCuCl, 35mLDMF. In 115 ℃ reaction for 1.5h and pull the solvent, the residue with 18% hydrochloric acid to pH=4~5, and then hot benzene extraction for 3 times, points to water, benzene layer reduced pressure distillation to benzene, coffee colored liquid. Which was dissolved in hot dilute alcohol solution, cooling to separate white crystallization, filtering, and drying to obtain the product of vanillin 8.3g, melting point is 81 to 82 ℃, 99.5% purity yield is 91.1%.
|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.|
|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.
|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.|
|Uses||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.|
|Uses||An intermediate and analytical reagent.|
|Uses||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.|
|Uses||The primary component of Vanilla bean extract.|
|Uses||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.|
|Definition||ChEBI: A member of the class of benzaldehydes carrying methoxy and hydroxy substituents at positions 3 and 4 respectively.|
|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 . 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 .
|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.
|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|
|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.|
|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).
|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
|Chemical 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.|