Kolbe nitrile synthesis
Encyclopedia
The Kolbe nitrile synthesis is a method for the preparation of alkyl nitriles
by reaction of the corresponding alkylhalide with a metal cyanide
. A side product for this reaction is the formation of an isonitrile because the cyanide ion is an ambident nucleophile and according to Kornblum's rule is capable of reacting with either carbon or nitrogen. The reaction is named after Hermann Kolbe.
The ratio in which both isomer
s form depends on the solvent
and the reaction mechanism
. With the application of alkali cyanides such as sodium cyanide
and polar solvents the reaction type is an SN2 reaction
whereby the alkylhalide is attacked by the more nucleophilic carbon atom of the cyanide ion. This type of reaction together with dimethyl sulfoxide
as a solvent is a convenient method for the synthesis of nitriles.
When silver cyanide
is reacted with diethyl ether
as a solvent the reaction runs according to an SN1 reaction
mechanism: the product is mainly isonitrile due to the attack of the more nucleophilic nitrogen atom.
In particular primary alkyl halogenides and benzyl
halogenides give good chemical yields when reacted with alkali cyanides to form nitriles. Secondary alkylhalides, on the other hand, only react to form undesirable tertiary halides.
Once formed the nitriles can be converted to the corresponding carboxylic acid
s by hydrolysis
and then to more functional group
s. In this way the Kolbe Nitrile synthesis is an important method in homologization.
Nitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...
by reaction of the corresponding alkylhalide with a metal cyanide
Cyanide
A cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....
. A side product for this reaction is the formation of an isonitrile because the cyanide ion is an ambident nucleophile and according to Kornblum's rule is capable of reacting with either carbon or nitrogen. The reaction is named after Hermann Kolbe.
The ratio in which both isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
s form depends on the solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
and the reaction mechanism
Reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
. With the application of alkali cyanides such as sodium cyanide
Sodium cyanide
Sodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications...
and polar solvents the reaction type is an SN2 reaction
SN2 reaction
The SN2 reaction is a type of nucleophilic substitution, where a lone pair from a nucleophile attacks an electron deficient electrophilic center and bonds to it, expelling another group called a leaving group. Thus the incoming group replaces the leaving group in one step...
whereby the alkylhalide is attacked by the more nucleophilic carbon atom of the cyanide ion. This type of reaction together with dimethyl sulfoxide
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
as a solvent is a convenient method for the synthesis of nitriles.
When silver cyanide
Silver cyanide
Silver cyanide is the chemical compound with the formula AgCN. This white solid forms upon treatment of solutions containing Ag+ with cyanide. This precipitation step is used in some schemes to recover silver from solution...
is reacted with diethyl ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
as a solvent the reaction runs according to an SN1 reaction
SN1 reaction
The SN1 reaction is a substitution reaction in organic chemistry. "SN" stands for nucleophilic substitution and the "1" represents the fact that the rate-determining step is unimolecular...
mechanism: the product is mainly isonitrile due to the attack of the more nucleophilic nitrogen atom.
In particular primary alkyl halogenides and benzyl
Benzyl
In organic chemistry, benzyl is the term used to describe the substituent or molecular fragment possessing the structure C6H5CH2-. Benzyl features a benzene ring attached to a CH2 group.-Nomenclature:...
halogenides give good chemical yields when reacted with alkali cyanides to form nitriles. Secondary alkylhalides, on the other hand, only react to form undesirable tertiary halides.
Once formed the nitriles can be converted to the corresponding carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s by hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
and then to more functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s. In this way the Kolbe Nitrile synthesis is an important method in homologization.