The Nierenstein reaction is 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 ...
describing the conversion of an
acid chloride
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
into a
haloketone
In organic chemistry, an α-haloketone is a functional group consisting of a ketone group or more generally a carbonyl group with an α-halogen substituent. α-haloketones are alkylating agents. Prominent α-haloketones include phenacyl bromide ...
with
diazomethane
Diazomethane is the chemical compound CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow gas; thus, it is almost u ...
. It is an
insertion reaction
An insertion reaction is a chemical reaction where one chemical entity (a molecule or molecular fragment) interposes itself into an existing bond of typically a second chemical entity ''e.g.'':
: + \longrightarrow
The term only refers to the ...
in that the
methylene group
In organic chemistry, a methylene group is any part of a molecule that consists of two hydrogen atoms bound to a carbon atom, which is connected to the remainder of the molecule by two single bonds. The group may be represented as , where the '< ...
from the diazomethane is inserted into the carbon-chlorine bond of the acid chloride.
Reaction mechanism
The reaction proceeds through a
diazonium salt
Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.
General properti ...
intermediate formed by
nucleophilic acyl substitution
Nucleophilic acyl substitution describe a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl deriv ...
of the chloride with diazomethyl anion. The chloride then displaces the diazo group in an
SN2 reaction
The SN2 reaction is a type of reaction mechanism that is common in organic chemistry. In this mechanism, one bond is broken and one bond is formed in a concerted way, i.e., in one step. The name SN2 refers to the Hughes-Ingold symbol of the m ...
, with N
2 as the
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
.
![Nierenstein Reaktionsmechanismus-1](https://upload.wikimedia.org/wikipedia/commons/0/0c/Nierenstein_Reaktionsmechanismus-1.svg)
If excess diazomethane is present during the reaction, it can act as a base, abstracting a hydrogen from the diazonium-salt intermediate. The result is a neutral diazoketone, which does not react with the chloride. Instead, the byproduct, diazonium-methyl from the other diazomethane molecule, can be attacked by the chloride to produce
chloromethane
Chloromethane, also called methyl chloride, Refrigerant-40, R-40 or HCC 40, is an organic compound with the chemical formula . One of the haloalkanes, it is a colorless, odorless, flammable gas. Methyl chloride is a crucial reagent in industrial ...
. The unreactive diazoketone can be re-activated and reacted by treatment with
hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chloride ga ...
to give the normal Nierenstein product.
In some cases, even limiting the amount of diazomethane gives a reaction process that stalls via the neutral diazoketone pathway, requiring the addition of HCl gas to rescue it.
Scope
One original 1924 Nierenstein reaction:
and a reaction starting from
benzoyl bromide going haywire with formation of the
dioxane
1,4-Dioxane () is a heterocyclic organic compound, classified as an ether. It is a colorless liquid with a faint sweet odor similar to that of diethyl ether. The compound is often called simply dioxane because the other dioxane isomers ( 1,2- ...
dimer:
See also
*
Maximilian Nierenstein
Maximilian Nierenstein (also known as Moses Max Nierenstein or Max Nierenstein; 1877–1946) was a professor of biochemistry at the University of Bristol.
He is known for the Nierenstein reaction, an organic reaction describing the conversion of ...
*
Curtius rearrangement
The Curtius rearrangement (or Curtius reaction or Curtius degradation), first defined by Theodor Curtius in 1885, is the thermal decomposition of an acyl azide to an isocyanate with loss of nitrogen gas. The isocyanate then undergoes attack by a va ...
*
Wolff rearrangement
The Wolff rearrangement is a reaction in organic chemistry in which an α-diazocarbonyl compound is converted into a ketene by loss of dinitrogen with accompanying 1,2-rearrangement. The Wolff rearrangement yields a ketene as an intermediate produ ...
*
Arndt–Eistert reaction
In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. Named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978), the method entails treating an acid ...
: where acid chlorides react with diazomethane to give chain extended carboxylic acids via a rearrangement
References
{{Reflist
Substitution reactions
Name reactions