The Koenigs–Knorr reaction in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

is the

substitution reaction A substitution reaction (also known as single displacement reaction or single substitution reaction) is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group. Substitution reactions ar ...

of a

glycosyl In organic chemistry, a glycosyl group is a univalent free radical or substituent structure obtained by removing the hydroxyl () group from the hemiacetal () group found in the cyclic form of a monosaccharide and, by extension, of a lower ol ...

halide In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fl ...

with an

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

to give a

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

. It is one of the oldest glycosylation reactions. It is named after Wilhelm Koenigs (1851–1906), a student of von Baeyer and fellow student with

Hermann Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and List of Nobel laureates in Chemistry, 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fisch ...

, and Edward Knorr, a student of Koenigs. In its original form, Koenigs and Knorr treated ''acetobromoglucose'' with alcohols in the presence of

silver carbonate Silver carbonate is the chemical compound with the formula Ag2 C O3. This salt is yellow but typical samples are grayish due to the presence of elemental silver. It is poorly soluble in water, like most transition metal carbonates. Preparation a ...

. Shortly afterwards Fischer and Armstrong reported very similar findings. In the above example, the stereochemical outcome is determined by the presence of the neighboring group at C2 that lends anchimeric assistance, resulting in the formation of a 1,2-trans stereochemical arrangement.

Esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

(e.g.

acetyl In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

, benzoyl, pivalyl) generally provide good anchimeric assistance, whereas

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� ...

s (e.g.

benzyl In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group (). Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a substituent ...

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

etc.) do not, leading to mixtures of

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

Mechanism

In the first step of the

mechanism Mechanism may refer to: *Mechanism (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...

, the glycosyl bromide reacts with

upon elimination of

silver bromide Silver bromide (AgBr), a soft, pale-yellow, water-insoluble salt well known (along with other silver halides) for its unusual sensitivity to light. This property has allowed silver halides to become the basis of modern photographic materials. AgB ...

and the silver carbonate anion to the oxocarbenium ion. From this structure a dioxolanium ring is formed, which is attacked by methanol via an mechanism at the carbonyl carbon atom. This attack leads to the inversion. After deprotonation of the intermediate oxonium, the product glycoside is formed. : Mechanismus Koenigs-Knorr-Methode V1

The reaction can also be applied to carbohydrates with other protecting groups. In the oligosaccharide synthesis in place of the methanol other carbohydrates are used, which have been modified with protective groups in such a way that only one hydroxyl group is accessible.

History

The method was later transferred by Emil Fischer and Burckhardt Helferich to other chloro-substituted purines and produced thus for the first time synthetic nucleosides. It was later improved and modified by numerous chemists.

Alternative reactions

Generally, the Koenigs–Knorr reaction refers to the use of glycosyl chlorides, bromides and more recently iodides as glycosyl donors. The Koenigs–Knorr reaction can be performed with alternative promoters such as various heavy metal salts including mercuric bromide/

mercuric oxide Mercury(II) oxide, also called mercuric oxide or simply mercury oxide, is the inorganic compound with the formula Hg O. It has a red or orange color. Mercury(II) oxide is a solid at room temperature and pressure. The mineral form montroydite is ...

, mercuric cyanide and silver triflate. When mercury salts are used, the reaction is normally called the Helferich method. Other glycosidation methods are

Fischer glycosidation Fischer glycosidation (or Fischer glycosylation) refers to the formation of a glycoside by the reaction of an aldose or ketose with an alcohol in the presence of an acid catalyst. The reaction is named after the German chemist, Emil Fischer, winner ...

, use of glycosyl acetates,

thioglycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

s, glycosyl trichloroacetimidates, glycosyl fluorides or n-pentenyl glycosides as

glycosyl donor A glycosyl donor is a carbohydrate mono- or oligosaccharide that will react with a suitable glycosyl acceptor to form a new glycosidic bond. By convention, the donor is the member of this pair that contains the resulting anomeric carbon of the new g ...

s, or intramolecular aglycon delivery.

References

{{DEFAULTSORT:Koenigs-Knorr reaction Carbohydrate chemistry Substitution reactions Name reactions