The Reichstein process in

chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...

is a combined

chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...

and

microbial A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

method for the production of

ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...

from

D-glucose Glucose is a simple sugar with the Chemical formula#Molecular formula, molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis f ...

that takes place in several steps. This process was devised by

Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

winner

Tadeusz Reichstein Tadeusz Reichstein (20 July 1897 – 1 August 1996) was a Polish-Swiss chemist and the Nobel Prize in Physiology or Medicine laureate (1950), which was awarded for his work on the isolation of cortisone. Early life Reichstein was born into a Pol ...

and his colleagues in 1933 while working in the laboratory of the

ETH (colloquially) , former_name = eidgenössische polytechnische Schule , image = ETHZ.JPG , image_size = , established = , type = Public , budget = CHF 1.896 billion (2021) , rector = Günther Dissertori , president = Joël Mesot , a ...

Zürich Zürich () is the list of cities in Switzerland, largest city in Switzerland and the capital of the canton of Zürich. It is located in north-central Switzerland, at the northwestern tip of Lake Zürich. As of January 2020, the municipality has 43 ...

Reaction steps

The reaction steps are: *

hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a Catalysis, catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or S ...

of D-

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

to D-

sorbitol Sorbitol (), less commonly known as glucitol (), is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alcohol g ...

, an

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...

with

nickel Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow to ...

as a

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

under high temperature and high pressure. * Microbial

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...

of sorbitol to L-

sorbose Sorbose is a ketose belonging to the group of sugars known as monosaccharides. It has a sweetness that is equivalent to sucrose (table sugar). The commercial production of vitamin C Vitamin C (also known as ascorbic acid and ascorbate) ...

with

acetobacter ''Acetobacter'' is a genus of acetic acid bacteria. Acetic acid bacteria are characterized by the ability to convert ethanol to acetic acid in the presence of oxygen. Of these, the genus ''Acetobacter'' is distinguished by the ability to oxidize ...

at pH 4-6 and 30 °C. *

protection Protection is any measure taken to guard a thing against damage caused by outside forces. Protection can be provided to physical objects, including organisms, to systems, and to intangible things like civil and political rights. Although th ...

of the 4

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 ...

groups in sorbose by formation of the

acetal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments no ...

with

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

and an

acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

to Diacetone-L-sorbose (2,3:4,6−Diisopropyliden−α−L−sorbose) *

Organic oxidation Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions carr ...

with

potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, that dissolves in water as K+ and , an intensely pink to purple solution. Potassium permanganate is widely used in the c ...

(to Diprogulic acid) followed by heating with water gives the 2-Keto-L-gulonic acid * The final step is a ring-closing step or gamma

lactonization Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

with removal of water. * Intermediate 5 can also be prepared directly from 3 with

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

and

platinum Platinum is a chemical element with the symbol Pt and atomic number 78. It is a dense, malleable, ductile, highly unreactive, precious, silverish-white transition metal. Its name originates from Spanish , a diminutive of "silver". Platinu ...

: The microbial oxidation of sorbitol to sorbose is important because it provides the correct

stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...

Importance

This process was patented and sold to

Hoffmann-La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

in 1934. The first commercially sold vitamin C product was either ''Cebion'' from

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

Redoxon Redoxon was the brand name of the first artificially synthesized ascorbic acid (vitamin C). Redoxon was first marketed to the general public by Hoffman-La Roche in 1934, making it the first mass-manufactured synthetic vitamin in history. The bran ...

from Hoffmann-La Roche. Even today industrial methods for the production of ascorbic acid can be based on the Reichstein process. In modern methods however, sorbose is directly oxidized with a platinum catalyst (developed by Kurt Heyns (1908–2005) in 1942). This method avoids the use of protective groups. A side product with particular modification is 5-Keto-D-gluconic acid. A shorter biotechnological synthesis of ascorbic acid was announced in 1988 by Genencor International and

Eastman Chemical Eastman Chemical Company is an American company primarily involved in the chemical industry. Once a subsidiary of Kodak, today it is an independent global specialty materials company that produces a broad range of advanced materials, chemicals and ...

. Glucose is converted to 2-keto-L-gulonic acid in two steps (via 2,4-diketo-L-gulonic acid intermediate) as compared to five steps in the traditional process. Though many organisms synthesize their own vitamin C, the steps can be different in plants and mammals. Smirnoff concluded that “..little is known about many of the enzymes involved in ascorbate biosynthesis or about the factors controlling flux through the pathways". There is interest in finding alternatives to the Reichstein process. Experiments suggest that genetically modified bacteria might be commercially usable.Hancock, Robert D. und Viola, Roberto. (2002): ''Biotechnological approaches for L-ascorbic acid production''. In: ''Trends in Biotechnology'' 20(7); S. 299–305; ;

References

Literature

* Boudrant, J. (1990): ''Microbial processes for ascorbic acid biosynthesis: a review''. In: ''Enzyme Microb Technol. 12(5); 322–9; ; * Bremus, C. ''et al.'' (2006): ''The use of microorganisms in L-ascorbic acid production''. In: ''J Biotechnol.'' 124(1); 196–205; ;

External links

* http://www.chemieunterricht.de/dc2/asch2/a-synthe.htm
Der Schweizerische Weg zur Viamin-C-Synthese
{{DEFAULTSORT:Reichstein Process Organic reactions