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Vanillin is an
organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
with the molecular formula . It is a
phenolic aldehyde Phenolic aldehydes are derivatives of phenol. Phenolic aldehydes can be found in wines and cognacs. Examples : * Hydroxybenzaldehydes * Dihydroxybenzaldehydes * Vanillin and isovanillin * 2,3,4-trihydroxybenzaldehyde can be isolated from ''Ant ...
. Its
functional groups In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...
include
aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
,
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
, and
ether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R†...
. It is the primary component of the ethanolic extract of the
vanilla bean Vanilla is a spice derived from orchids of the genus ''Vanilla'', primarily obtained from pods of the flat-leaved vanilla ('' V. planifolia''). ''Vanilla'' is not autogamous, so pollination is required to make the plants produce the f ...
. Synthetic vanillin is now used more often than natural vanilla extract as a
flavoring A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive that is used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of ...
in foods, beverages, and pharmaceuticals. Vanillin and
ethylvanillin Ethylvanillin is the organic compound with the chemical formula, formula (C2H5O)(HO)C6H3CHO. This colorless solid consists of a benzene ring with hydroxyl, ethoxy, and aldehyde, formyl groups on the 4, 3, and 1 positions, respectively. It is a Hom ...
are used by the food industry; ethylvanillin is more expensive, but has a stronger
note Note, notes, or NOTE may refer to: Music and entertainment * Musical note, a pitched sound (or a symbol for a sound) in music * ''Notes'' (album), a 1987 album by Paul Bley and Paul Motian * ''Notes'', a common (yet unofficial) shortened versi ...
. It differs from vanillin by having an ethoxy group (−O−CH2CH3) instead of a methoxy group (−O−CH3). Natural
vanilla extract Vanilla extract is a Solution (chemistry), solution made by maceration (food), macerating and percolation, percolating vanilla, vanilla pods in a solution of ethanol and water. It is considered an essential ingredient in many Western desserts, es ...
is a mixture of several hundred different compounds in addition to vanillin. Artificial vanilla flavoring is often a solution of pure vanillin, usually of synthetic origin. Because of the scarcity and expense of natural vanilla extract, synthetic preparation of its predominant component has long been of interest. The first commercial synthesis of vanillin began with the more readily available natural compound
eugenol Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, ...
(4-allyl-2-methoxyphenol). Today, artificial vanillin is made either from
guaiacol Guaiacol () is an organic compound with the formula C6H4(OH)(OCH3). It is a phenolic compound containing a methoxy functional group. Guaiacol appears as a viscous colorless oil, although aged or impure samples are often yellowish. It occurs wid ...
or
lignin Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidit ...
. Lignin-based artificial vanilla flavoring is alleged to have a richer flavor profile than that from guaiacol-based artificial vanilla; the difference is due to the presence of
acetovanillone Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties. History Apocynin w ...
, a minor component in the lignin-derived product that is not found in vanillin synthesized from guaiacol.


Natural history

Although it is generally accepted that vanilla was domesticated in
Mesoamerica Mesoamerica is a historical region and cultural area that begins in the southern part of North America and extends to the Pacific coast of Central America, thus comprising the lands of central and southern Mexico, all of Belize, Guatemala, El S ...
and subsequently spread to the
Old World The "Old World" () is a term for Afro-Eurasia coined by Europeans after 1493, when they became aware of the existence of the Americas. It is used to contrast the continents of Africa, Europe, and Asia in the Eastern Hemisphere, previously ...
in the 16th century, in 2019, researchers published a
paper Paper is a thin sheet material produced by mechanically or chemically processing cellulose fibres derived from wood, Textile, rags, poaceae, grasses, Feces#Other uses, herbivore dung, or other vegetable sources in water. Once the water is dra ...
stating that vanillin residue had been discovered inside jars within a tomb in
Israel Israel, officially the State of Israel, is a country in West Asia. It Borders of Israel, shares borders with Lebanon to the north, Syria to the north-east, Jordan to the east, Egypt to the south-west, and the Mediterranean Sea to the west. Isr ...
dating to the 2nd millennium BCE, suggesting the possible cultivation of an unidentified, Old World-endemic ''
Vanilla Vanilla is a spice derived from orchids of the genus ''Vanilla (genus), Vanilla'', primarily obtained from pods of the flat-leaved vanilla (''Vanilla planifolia, V. planifolia''). ''Vanilla'' is not Autogamy, autogamous, so pollination ...
'' species in
Canaan CanaanThe current scholarly edition of the Septuagint, Greek Old Testament spells the word without any accents, cf. Septuaginta : id est Vetus Testamentum graece iuxta LXX interprets. 2. ed. / recogn. et emendavit Robert Hanhart. Stuttgart : D ...
since the Middle
Bronze Age The Bronze Age () was a historical period characterised principally by the use of bronze tools and the development of complex urban societies, as well as the adoption of writing in some areas. The Bronze Age is the middle principal period of ...
. Traces of vanillin were also found in wine jars in
Jerusalem Jerusalem is a city in the Southern Levant, on a plateau in the Judaean Mountains between the Mediterranean Sea, Mediterranean and the Dead Sea. It is one of the List of oldest continuously inhabited cities, oldest cities in the world, and ...
, which were used by the Judahite elite before the city was destroyed in 586 BCE. Vanilla beans, called ''tlilxochitl,'' were discovered and cultivated as a flavoring for beverages by native Mesoamerican peoples, most famously the Totonacs of modern-day
Veracruz Veracruz, formally Veracruz de Ignacio de la Llave, officially the Free and Sovereign State of Veracruz de Ignacio de la Llave, is one of the 31 states which, along with Mexico City, comprise the 32 Political divisions of Mexico, Federal Entit ...
, Mexico. Since at least the early 15th century, the
Aztecs The Aztecs ( ) were a Mesoamerican civilization that flourished in central Mexico in the post-classic period from 1300 to 1521. The Aztec people included different ethnic groups of central Mexico, particularly those groups who spoke the ...
used vanilla as a flavoring for
chocolate Chocolate is a food made from roasted and ground cocoa beans that can be a liquid, solid, or paste, either by itself or to flavoring, flavor other foods. Cocoa beans are the processed seeds of the cacao tree (''Theobroma cacao''); unprocesse ...
in drinks called ''xocohotl''.


Synthetic history

Vanillin was first isolated as a relatively pure substance in 1858 by Théodore Nicolas Gobley, who obtained it by evaporating a vanilla extract to dryness and recrystallizing the resulting solids from hot water. In 1874, the German scientists Ferdinand Tiemann and Wilhelm Haarmann deduced its chemical structure, at the same time finding a synthesis for vanillin from coniferin, a
glucoside A glucoside is a glycoside that is chemically derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes. Th ...
of isoeugenol found in
pine A pine is any conifer tree or shrub in the genus ''Pinus'' () of the family Pinaceae. ''Pinus'' is the sole genus in the subfamily Pinoideae. ''World Flora Online'' accepts 134 species-rank taxa (119 species and 15 nothospecies) of pines as cu ...
bark. Tiemann and Haarmann founded a company Haarmann and Reimer (now part of Symrise) and started the first industrial production of vanillin using their process (now known as the Reimer–Tiemann reaction) in
Holzminden Holzminden (; ) is a town in southern Lower Saxony, Germany. It is the capital of the district of Holzminden (district), Holzminden. It is located on the river Weser, which at this point forms the border with the state of North Rhine-Westphalia. ...
, Germany. In 1876, Karl Reimer synthesized vanillin (2) from guaiacol (1). By the late 19th century, semisynthetic vanillin derived from the eugenol found in
clove oil Cloves are the aromatic flower buds of a tree in the family Myrtaceae, ''Syzygium aromaticum'' (). They are native to the Maluku Islands, or Moluccas, in Indonesia, and are commonly used as a spice, flavoring, or fragrance in consumer products, ...
was commercially available. Synthetic vanillin became significantly more available in the 1930s, when production from clove oil was supplanted by production from the
lignin Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidit ...
-containing waste produced by the
sulfite pulping process The sulfite process produces wood pulp that is almost pure cellulose fibers by treating wood chips with solutions of sulfite and bisulfite ions. These chemicals cleave the bonds between the cellulose and lignin components of the lignocellulose. A ...
for preparing wood pulp for the
paper industry The pulp and paper industry comprises companies that use wood, specifically pulpwood, as raw material and produce pulp, paper, paperboard, and other cellulose-based products. Manufacturing process In the manufacturing process, pulp is intro ...
. By 1981, a single pulp and paper mill in
Thorold, Ontario Thorold is a city in Ontario, Canada, located on the Niagara Escarpment. It is also the seat of the Regional Municipality of Niagara. The Welland Canal passes through the city, featuring lock 7 and the Twin Flight Locks. History The first surv ...
, supplied 60% of the world market for synthetic vanillin. Hocking 1997. However, subsequent developments in the wood pulp industry have made its lignin wastes less attractive as a raw material for vanillin synthesis. Today, approximately 15% of the world's production of vanillin is still made from lignin wastes, Fache et al 2015 while approximately 85% is synthesized in a two-step process from the
petrochemical Petrochemicals (sometimes abbreviated as petchems) are the chemical products obtained from petroleum by refining. Some chemical compounds made from petroleum are also obtained from other fossil fuels, such as coal or natural gas, or renewable s ...
precursors
guaiacol Guaiacol () is an organic compound with the formula C6H4(OH)(OCH3). It is a phenolic compound containing a methoxy functional group. Guaiacol appears as a viscous colorless oil, although aged or impure samples are often yellowish. It occurs wid ...
and
glyoxylic acid Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. Str ...
. Esposito 1997. Beginning in 2000, Rhodia began marketing biosynthetic vanillin prepared by the action of microorganisms on
ferulic acid Ferulic acid is a hydroxycinnamic acid derivative and a phenolic compound. It is an organic compound with the formula (CH3O)HOC6H3CH=CHCO2H. The name is derived from the genus '' Ferula'', referring to the giant fennel ('' Ferula communis''). Cl ...
extracted from
rice bran Bran, also known as miller's bran, is the component of a cereal grain consisting of the hard layersthe combined aleurone and pericarpsurrounding the endosperm. Corn (maize) bran also includes the pedicel (tip cap). Along with the germ, it is ...
. This product, sold at
USD The United States dollar (symbol: $; currency code: USD) is the official currency of the United States and several other countries. The Coinage Act of 1792 introduced the U.S. dollar at par with the Spanish silver dollar, divided it int ...
$700/kg under the trademarked name Rhovanil Natural, is not cost-competitive with petrochemical vanillin, which sells for around US$15/kg. However, unlike vanillin synthesized from lignin or guaiacol, it can be labeled as a natural flavoring.


Occurrence

Vanillin is most prominent as the principal flavor and aroma compound in
vanilla Vanilla is a spice derived from orchids of the genus ''Vanilla (genus), Vanilla'', primarily obtained from pods of the flat-leaved vanilla (''Vanilla planifolia, V. planifolia''). ''Vanilla'' is not Autogamy, autogamous, so pollination ...
. Cured vanilla pods contain about 2% by dry weight vanillin. Relatively pure vanillin may be visible as a white dust or "frost" on the exteriors of cured pods of high quality. It is also found in '' Leptotes bicolor'', a species of orchid native to Paraguay and southern Brazil, and the Southern Chinese red pine. At lower concentrations, vanillin contributes to the flavor and aroma profiles of foodstuffs as diverse as
olive oil Olive oil is a vegetable oil obtained by pressing whole olives (the fruit of ''Olea europaea'', a traditional Tree fruit, tree crop of the Mediterranean Basin) and extracting the oil. It is commonly used in cooking for frying foods, as a cond ...
,
butter Butter is a dairy product made from the fat and protein components of Churning (butter), churned cream. It is a semi-solid emulsion at room temperature, consisting of approximately 81% butterfat. It is used at room temperature as a spread (food ...
,
raspberry The raspberry is the edible fruit of several plant species in the genus ''Rubus'' of the Rosaceae, rose family, most of which are in the subgenus ''Rubus#Modern classification, Idaeobatus''. The name also applies to these plants themselves. Ras ...
, and
lychee Lychee ( , ; ''Litchi chinensis''; ) is a monotypic taxon and the sole member in the genus ''Litchi'' in the soapberry family, Sapindaceae. There are three distinct subspecies of lychee. The most common is the Indochinese lychee found in So ...
fruits. Aging in oak barrels imparts vanillin to some
wine Wine is an alcoholic drink made from Fermentation in winemaking, fermented fruit. Yeast in winemaking, Yeast consumes the sugar in the fruit and converts it to ethanol and carbon dioxide, releasing heat in the process. Wine is most often made f ...
s,
vinegar Vinegar () is an aqueous solution of diluted acetic acid and trace compounds that may include flavorings. Vinegar typically contains from 5% to 18% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting ...
, and spirits. In other foods, heat treatment generates vanillin from other compounds. In this way, vanillin contributes to the flavor and aroma of
coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...
,
maple syrup Maple syrup is a sweet syrup made from the sap of maple trees. In cold climates, these trees store starch in their trunks and roots before winter; the starch is then converted to sugar that rises in the sap in late winter and early spring. Ma ...
, and
whole-grain A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm. As part of a general healthy diet, consumption of whole grains is associated wit ...
products, including corn
tortilla A tortilla (, ) is a thin, circular unleavened flatbread from Mesoamerica originally made from maize hominy meal, and now also from wheat flour. The Aztecs and other Nahuatl speakers called tortillas ''tlaxcalli'' (). First made by the indi ...
s and
oatmeal Oatmeal is a preparation of oats that have been dehusked, steamed, and flattened, or a coarse flour of hulled oat grains ( groats) that have either been milled (ground), rolled, or steel-cut. Ground oats are also called white oats. Steel- ...
.


Production


Natural production

Natural vanillin is extracted from the seed pods of ''
Vanilla planifolia ''Vanilla planifolia'' is a species of vanilla orchid native to Mexico, Central America, Colombia, and Brazil. It is one of the primary sources for vanilla flavouring, due to its high vanillin content. Common names include flat-leaved vanilla, ...
'', a vining
orchid Orchids are plants that belong to the family Orchidaceae (), a diverse and widespread group of flowering plants with blooms that are often colourful and fragrant. Orchids are cosmopolitan plants that are found in almost every habitat on Eart ...
native to Mexico, but now grown in tropical areas around the globe.
Madagascar Madagascar, officially the Republic of Madagascar, is an island country that includes the island of Madagascar and numerous smaller peripheral islands. Lying off the southeastern coast of Africa, it is the world's List of islands by area, f ...
is presently the largest producer of natural vanillin. As harvested, the green seed pods contain vanillin in the form of glucovanillin, its β--
glucoside A glucoside is a glycoside that is chemically derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes. Th ...
; the green pods do not have the flavor or odor of vanilla. Walton 2003. Vanillin is released from glucovanillin by the action of the enzyme β-glucosidase during ripening and during the curing process. After being harvested, their flavor is developed by a months-long curing process, the details of which vary among vanilla-producing regions, but in broad terms it proceeds as follows: First, the seed pods are blanched in hot water, to arrest the processes of the living plant tissues. Then, for 1–2 weeks, the pods are alternately sunned and sweated: during the day they are laid out in the sun, and each night wrapped in cloth and packed in airtight boxes to sweat. During this process, the pods become dark brown, and
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s in the pod release vanillin as the free molecule. Finally, the pods are dried and further aged for several months, during which time their flavors further develop. Several methods have been described for curing vanilla in days rather than months, although they have not been widely developed in the natural vanilla industry, with its focus on producing a premium product by established methods, rather than on innovations that might alter the product's flavor profile.


Biosynthesis

Although the exact route of vanillin biosynthesis in ''V. planifolia'' is currently unknown, several pathways are proposed for its biosynthesis. Vanillin biosynthesis is generally agreed to be part of the phenylpropanoid pathway starting with -phenylalanine, which is deaminated by
phenylalanine ammonia lyase The enzyme phenylalanine ammonia lyase (EC 4.3.1.24) catalyzes the conversion of L-phenylalanine to ammonia and ''trans''-cinnamic acid.: :L-phenylalanine = ''trans''-cinnamate + NH3 Phenylalanine ammonia lyase (PAL) is the first and committe ...
(PAL) to form t-
cinnamic acid Cinnamic acid is an organic compound with the formula phenyl, C6H5-CH=CH-Carboxylic acid, COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxy ...
. The ''para'' position of the ring is then hydroxylated by the
cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
enzyme cinnamate 4-hydroxylase (C4H/P450) to create ''p''-
coumaric acid Coumaric acid is a phenolic derivative of cinnamic acid having a hydroxy group as substituent at one of the aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of un ...
. Then, in the proposed ferulate pathway, 4-hydroxycinnamoyl-CoA ligase (4CL) attaches ''p''-coumaric acid to
coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...
(CoA) to create ''p''-coumaroyl CoA. Hydroxycinnamoyl transferase (HCT) then converts ''p''-coumaroyl CoA to 4-coumaroyl
shikimate Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''shik ...
/ quinate. This subsequently undergoes oxidation by the P450 enzyme coumaroyl ester 3’-hydroxylase (C3’H/P450) to give caffeoyl shikimate/quinate. HCT then exchanges the shikimate/quinate for CoA to create caffeoyl CoA, and 4CL removes CoA to afford caffeic acid. Caffeic acid then undergoes
methylation Methylation, in the chemistry, chemical sciences, is the addition of a methyl group on a substrate (chemistry), substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replac ...
by caffeic acid O-
methyltransferase Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ro ...
(COMT) to give ferulic acid. Finally, vanillin synthase hydratase/lyase (vp/VAN) catalyzes hydration of the double bond in ferulic acid followed by a retro-aldol elimination to afford vanillin. Vanillin can also be produced from vanilla glycoside with the additional final step of deglycosylation. In the past ''p''-hydroxybenzaldehyde was speculated to be a precursor for vanillin biosynthesis. However, a 2014 study using
radiolabelled A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to exp ...
precursor indicated that ''p''-hydroxybenzaldehyde is not used to synthesise vanillin or vanillin glucoside in the vanilla orchids.


Chemical synthesis

The demand for vanilla flavoring has long exceeded the supply of vanilla beans. , the annual demand for vanillin was 12,000 tons, but only 1,800 tons of natural vanillin were produced. The remainder was produced by
chemical synthesis Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...
. Vanillin was first synthesized from eugenol (found in oil of clove) in 1874–75, less than 20 years after it was first identified and isolated. Vanillin was commercially produced from eugenol until the 1920s. Later it was synthesized from lignin-containing "brown liquor", a byproduct of the
sulfite process The sulfite process produces wood pulp that is almost pure cellulose fibers by treating wood chips with solutions of sulfite and bisulfite ions. These chemicals cleave the bonds between the cellulose and lignin components of the lignocellulose. A ...
for making
wood pulp Pulp is a fibrous Lignocellulosic biomass, lignocellulosic material prepared by chemically, semi-chemically, or mechanically isolating the cellulose fiber, cellulosic fibers of wood, fiber crops, Paper recycling, waste paper, or cotton paper, rag ...
. Counterintuitively, though it uses waste materials, the lignin process is no longer popular because of environmental concerns, and today most vanillin is produced from
guaiacol Guaiacol () is an organic compound with the formula C6H4(OH)(OCH3). It is a phenolic compound containing a methoxy functional group. Guaiacol appears as a viscous colorless oil, although aged or impure samples are often yellowish. It occurs wid ...
. Several routes exist for synthesizing vanillin from guaiacol. At present, the most significant of these is the two-step process practiced by Rhodia since the 1970s, in which guaiacol (1) reacts with
glyoxylic acid Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. Str ...
by
electrophilic aromatic substitution Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is attached to an aromatic ring, aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitut ...
. The resulting
vanillylmandelic acid Vanillylmandelic acid (VMA) is a chemical intermediate in the synthesis of artificial vanilla flavorings and is an end-stage metabolite of the catecholamines (epinephrine, and norepinephrine). It is produced via intermediary metabolites. Chemica ...
(2) is then converted by 4-Hydroxy-3-methoxyphenylglyoxylic acid (3) to vanillin (4) by oxidative decarboxylation. : Although guaiacol can be obtained by pyrolysis of wood, the type intended for vanillin production is mainly produced by petrochemistry.


Wood-based vanillin

15% of the world's production of vanillin is produced from
lignosulfonates Lignosulfonates (LS) are water-soluble anionic polyelectrolyte polymers: they are byproducts from the production of wood pulp using sulfite pulping. Most delignification in sulfite pulping involves acidic cleavage of ether bonds, which connect m ...
, a byproduct from the manufacture of
cellulose Cellulose is an organic compound with the chemical formula, formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of glycosidic bond, β(1→4) linked glucose, D-glucose units. Cellulose is an important s ...
via the
sulfite process The sulfite process produces wood pulp that is almost pure cellulose fibers by treating wood chips with solutions of sulfite and bisulfite ions. These chemicals cleave the bonds between the cellulose and lignin components of the lignocellulose. A ...
. The sole remaining producer of wood-based vanillin is the company
Borregaard Borregaard is a Norway, Norwegian company, established in 1889 in the southeastern town of Sarpsborg in Østfold county. Its main products were traditionally pulp and paper. The company later started producing Chemical industry, chemicals based ...
located in
Sarpsborg Sarpsborg ( or ), historically Borg, is a List of cities in Norway, city and Municipalities of Norway, municipality in Østfold Counties of Norway, county, Norway. The administrative centre of the municipality is the city of Sarpsborg. Sarpsbor ...
,
Norway Norway, officially the Kingdom of Norway, is a Nordic countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. The remote Arctic island of Jan Mayen and the archipelago of Svalbard also form part of the Kingdom of ...
. For this kind of use, softwood is preferred because there are more guaiacyl units convertible to vanillin. Early production of wood-based vanillin would involve four plants: a sulfite pulp mill, a fermentation plant, a vanillin plant, and a Kraft (sulfate) pulp mill. The sulfite mill provides the brown liquor to the fermentation plant, which makes use of the residual sugar. The spend liquor is sent to the vanillin plant, which uses alkaline oxidation with air at 160–170 °C and 10–12 atm pressure, toluene extraction, and back-extraction with NaOH to obtain a crude sodium vanillate. Addition of
sulfurous acid Sulfuric(IV) acid (United Kingdom spelling: sulphuric(IV) acid), also known as sulfurous (UK: sulphurous) acid and thionic acid, is the chemical compound with the chemical formula, formula . Raman spectroscopy, Raman spectra of solutions o ...
affords easy separation of the soluble sulfide addition compound of vanillin from insoluble impurities such as
acetovanillone Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties. History Apocynin w ...
. The vanillin is extracted, and the remaining liquor is sent to the Kraft mill for burning to recover energy and sodium sulfide, both important for a Kraft mill. This process went out of favor in North America due to the large amounts of caustic liquids that needs to be disposed by the mill at the end: 160 kg for every 1 kg of vanillin produced. The recovery of sodium sulfide also became less and less profitable as the sodium-to-sulfur ratio became more and more unbalanced. Borregaard is able to keep operating because it runs its own pulp mill. They have improved a process from Monsanto by using ultrafiltration to concentrate the incoming
lignosulfonates Lignosulfonates (LS) are water-soluble anionic polyelectrolyte polymers: they are byproducts from the production of wood pulp using sulfite pulping. Most delignification in sulfite pulping involves acidic cleavage of ether bonds, which connect m ...
, which reduces the amount of NaOH used and waste produced. The basic chemistry is unchanged: alkaline oxidation using a metal catalyst such a copper salt. According to ''Scientific American'', vanillin produced this way contains armoatic impurities that add strength and creaminess to its flavor. This is probably due to
acetovanillone Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties. History Apocynin w ...
being present.


Fermentation

The company Evolva has developed a genetically modified yeast which can produce vanillin. Because the microbe is a processing aid, the resulting vanillin would not fall under U.S. GMO labeling requirements, and because the production is nonpetrochemical, food using the ingredient can claim to contain "no artificial ingredients". The biosynthetic process starts with glucose, or any sugar that can be converted into erythrose 4-phosphate (which leads to 3-dehydroshikimic acid). The end product is 98% pure and is also considered natural in the EU. Using
ferulic acid Ferulic acid is a hydroxycinnamic acid derivative and a phenolic compound. It is an organic compound with the formula (CH3O)HOC6H3CH=CHCO2H. The name is derived from the genus '' Ferula'', referring to the giant fennel ('' Ferula communis''). Cl ...
(a chemical found in rice) as an input and a specific non GMO species of ''
Amycolatopsis ''Amycolatopsis'' is a genus of high GC-content bacteria within the family Pseudonocardiaceae. The genus is known for producing many types of antibiotics, including *Epoxyquinomicin, related to ''Amycolatopsis sulphurea'', are a class of weak ant ...
'' bacteria, vanillin can be produced. Many other bacteria, either GMO or non-GMO, can be used for the same purpose. However, because vanillin inhibits the growth of free-floating bacteria, yields have been low. This can be overcome through the formation of
biofilms A biofilm is a syntrophic community of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymer ...
, which has been done with the non-GMO '' B. subtilis'' strain CCTCC M2011162. However, using ferulic acid as the starting material does not qualify for "natural ingredient" in the EU. Biotransformation of eugenol (from cloves) into vanillin by non-GMO microorganisms has also been reported. The same has been reported for guaiacol and guaicyl lignin (from conifers). These starting materials do not qualify for "natural ingredient" in the EU.


Uses

The largest use of vanillin is as a flavoring, usually in
sweet Sweetness is a basic taste most commonly perceived when eating foods rich in sugars. Sweet tastes are generally regarded as pleasurable. In addition to sugars like sucrose, many other chemical compounds are sweet, including aldehydes, ketones, ...
foods. The
ice cream Ice cream is a frozen dessert typically made from milk or cream that has been flavoured with a sweetener, either sugar or an alternative, and a spice, such as Chocolate, cocoa or vanilla, or with fruit, such as strawberries or peaches. Food ...
and
chocolate Chocolate is a food made from roasted and ground cocoa beans that can be a liquid, solid, or paste, either by itself or to flavoring, flavor other foods. Cocoa beans are the processed seeds of the cacao tree (''Theobroma cacao''); unprocesse ...
industries together comprise 75% of the market for vanillin as a flavoring, with smaller amounts being used in
confection Confectionery is the art of making confections, or sweet foods. Confections are items that are rich in sugar and carbohydrates, although exact definitions are difficult. In general, however, confections are divided into two broad and somew ...
s and
baked goods Baking is a method of preparing food that uses dry heat, typically in an oven, but it can also be done in hot ashes, or on hot Baking stone, stones. Bread is the most commonly baked item, but many other types of food can also be baked. Heat is ...
. Vanillin is also used in the fragrance industry, in
perfume Perfume (, ) is a mixture of fragrance, fragrant essential oils or aroma compounds (fragrances), Fixative (perfumery), fixatives and solvents, usually in liquid form, used to give the human body, animals, food, objects, and living-spaces an agre ...
s, and to mask unpleasant odors or tastes in medicines, livestock
fodder Fodder (), also called provender (), is any agriculture, agricultural foodstuff used specifically to feed domesticated livestock, such as cattle, domestic rabbit, rabbits, sheep, horses, chickens and pigs. "Fodder" refers particularly to food ...
, and cleaning products. It is also used in the flavor industry, as a very important key note for many different flavors, especially creamy profiles such as
cream soda Cream soda (also known as creme soda) is a sweet soft drink. Generally flavored with vanilla and based on the taste of an ice cream float, a wide range of variations can be found worldwide. History and development A recipe for cream soda written ...
. Additionally, vanillin can be used as a general-purpose stain for visualizing spots on
thin-layer chromatography Thin-layer chromatography (TLC) is a chromatography technique that separates components in non-volatile mixtures. It is performed on a TLC plate made up of a non-reactive solid coated with a thin layer of adsorbent material. This is called the sta ...
plates. This stain yields a range of colors for these different components.


Biochemistry

Several studies have suggested that vanillin can affect the performance of
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
in laboratory conditions. Vanillin–HCl staining can be used to visualize the localisation of tannins in cells.


Manufacturing

Vanillin has been used as a chemical intermediate in the production of
pharmaceuticals Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
,
cosmetics Cosmetics are substances that are intended for application to the body for cleansing, beautifying, promoting attractiveness, or altering appearance. They are mixtures of chemical compounds derived from either Natural product, natural source ...
, and other
fine chemicals In chemistry, fine chemicals are complex, single, pure chemical substances, produced in limited quantities in multipurpose plants by multistep batch chemical or biotechnological processes. They are described by exacting specifications, used f ...
. In 1970, more than half the world's vanillin production was used in the synthesis of other chemicals. As of 2016, vanillin uses have expanded to include
perfume Perfume (, ) is a mixture of fragrance, fragrant essential oils or aroma compounds (fragrances), Fixative (perfumery), fixatives and solvents, usually in liquid form, used to give the human body, animals, food, objects, and living-spaces an agre ...
s, flavoring and aromatic masking in medicines, various consumer and cleaning products, and
livestock Livestock are the Domestication, domesticated animals that are raised in an Agriculture, agricultural setting to provide labour and produce diversified products for consumption such as meat, Egg as food, eggs, milk, fur, leather, and wool. The t ...
foods. Vanillin is becoming a popular choice for the development of bio-based plastics.


Adverse effects

Vanillin can trigger
migraine headache Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...
s in a small fraction of the people who experience migraines. Some people have
allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...
to vanilla. They may be allergic to synthetically produced vanilla but not to natural vanilla, or the other way around, or to both. Vanilla orchid plants can trigger
contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes ...
, especially among people working in the vanilla trade if they come into contact with the plant's sap. An allergic contact dermatitis called vanillism produces swelling and redness, and sometimes other symptoms. The sap of most species of vanilla orchid which exudes from cut stems or where beans are harvested can cause moderate to severe dermatitis if it comes in contact with bare skin. The sap of vanilla orchids contains
calcium oxalate Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula or . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydr ...
crystals, which are thought to be the main causative agent of contact dermatitis in vanilla plantation workers. A pseudophytodermatitis called vanilla lichen can be caused by flour mites (''Tyroglyphus farinae'').


Ecology

''
Scolytus multistriatus ''Scolytus multistriatus'', the European elm bark beetle or smaller European elm bark beetle, is a bark beetle species in the genus '' Scolytus''. In Europe, while ''S. multistriatus'' acts as vector of the Dutch elm disease, caused by the Ascom ...
'', one of the vectors of the Dutch elm disease, uses vanillin as a signal to find a host tree during
oviposition The ovipositor is a tube-like organ used by some animals, especially insects, for the laying of eggs. In insects, an ovipositor consists of a maximum of three pairs of appendages. The details and morphology of the ovipositor vary, but typica ...
.


See also

*
Phenolic compounds in wine Phenolic compounds— natural phenol and polyphenols—occur naturally in wine. These include a large group of several hundred chemical compounds that affect the taste, color and mouthfeel of wine. These compounds include phenolic acids, sti ...
* Other
positional isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...
s: ** Isovanillin ** ''ortho''-Vanillin ** 2-Hydroxy-5-methoxybenzaldehyde ** 2-Hydroxy-4-methoxybenzaldehyde *
Benzaldehyde Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is among the simplest aromatic aldehydes and one of the most industrially useful. It is a colorless liquid with a characteristic almond-li ...
*
Protocatechuic aldehyde 3,4-Dihydroxybenzaldehyde, also known as protocatechuic aldehyde, is a phenolic aldehyde, a compound released from Cork (material), cork stoppers into wine. It is an isomer of 2,4-dihydroxybenzaldehyde. This molecule can be used as a precursor in ...
*
Syringaldehyde Syringaldehyde is an organic compound that occurs in trace amounts widely in nature. Some species of insects use syringaldehyde in their chemical communication systems. ''Scolytus multistriatus'' uses it as a signal to find a host tree during ovip ...


References

* * * * * * * * * * * * * * * * * * * * * *


Notes

{{Authority control Flavors Perfume ingredients Hydroxybenzaldehydes Vanilloids O-methylated natural phenols Vanilla Total synthesis Tree-derived bioactive compounds