Diazomethane is an organic chemical compound with the formula 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 universally used as a solution in diethyl ether. The compound is a popular methylating agent in the laboratory, but it is too hazardous to be employed on an industrial scale without special precautions.
Use
For safety and convenience diazomethane is always prepared as needed as a solution in
diethyl ether and used as such. It converts carboxylic acids to methyl esters and
phenols into their
methyl . The reaction is thought to proceed via proton transfer from carboxylic acid to diazomethane to give a
methyldiazonium cation, which reacts with the carboxylate ion to give the methyl ester and nitrogen gas. Labeling studies indicate that the initial proton transfer is faster than the methyl transfer step.
Since proton transfer is required for the reaction to proceed, this reaction is selective for the more acidic carboxylic acids (p
Ka ~ 5) and phenols (p
Ka ~ 10) over aliphatic alcohols (p
Ka ~ 15).
In more specialized applications, diazomethane and other diazoalkyl reagents are used in the Arndt–Eistert reaction and the Büchner–Curtius–Schlotterbeck reaction for homologation of various compounds.
Diazomethane reacts with alcohols or in presence of boron trifluoride (BF3) to give methyl .
Diazomethane is also frequently used as a carbene source. It readily takes part in 1,3-dipolar cycloadditions.
Preparation
Laboratory scale
A wide variety of routes have been developed for the laboratory production of diazomethane.
In general, the synthesis of these all involves the addition of
methylamine to an electron-deficient species, before treatment with
nitrite and mineral acid (
nitrous acid) to form an
N-methyl nitrosamide. Diazomethane is prepared by hydrolysis of an ethereal solution of these
N-methyl nitrosamides with aqueous base. Examples include:
-
N-nitroso- N-methylurea (NMU),
-
N-Nitroso-β-methylaminoisobutyl methyl ketone (Liquizald), another early precursor which remains in use in the present day.
-
N, N-dimethyl- N, N-dinitrosoterephthalamide (DMDMT)
-
N-methyl- N'-nitro- N-nitrosoguanidine (MNNG),
-
Diazald (Diazald),
Diazomethane reacts with alkaline solutions of D2O to give the deuterated derivative CD2N2.
Industrial use
The ease with which diazomethane explodes makes it too hazardous to handle in large quantities. Despite this, it can be used on an industrial scale using on-demand
flow chemistry. In these processes the rate of production is matched by the rate of consumption, such that the amount of diazomethane present at any one time is very low.
Analysis
The concentration of CH
2N
2 can be determined in either of two convenient ways. It can be treated with an excess of
benzoic acid in cold Et
2O. Unreacted
benzoic acid is then
back titration with standard NaOH. Alternatively, the concentration of CH
2N
2 in Et
2O can be determined spectrophotometrically at 410 nm where its extinction coefficient, ε, is 7.2.
The gas-phase concentration of diazomethane can be determined using photoacoustic spectroscopy.
Related compounds
Diazomethane is both isomeric and
isoelectronic with the more stable
cyanamide, but they do not interconvert.
Many substituted derivatives of diazomethane have been prepared:
-
The very stable (CF3)2CN2 (2-diazo-1,1,1,3,3,3-hexafluoropropane; b.p. 12–13 °C),
-
Ph2CN2 (diazodiphenylmethane; m.p. 29–30 °C).
-
(CH3)3SiCHN2 (trimethylsilyldiazomethane), which is commercially available as a solution and is as effective as CH2N2 for methylation.
-
PhC(H)N2, a red liquid b.p.< 25 °C at 0.1 mmHg.
Safety
Diazomethane is toxic by inhalation or by contact with the skin or eyes (TLV 0.2 ppm). Symptoms include chest discomfort, headache, weakness and, in severe cases, collapse.
[Muir, GD (ed.) 1971, Hazards in the Chemical Laboratory, The Royal Institute of Chemistry, London.] Symptoms may be delayed. Deaths from diazomethane poisoning have been reported. In one instance a laboratory worker consumed a hamburger near a fumehood where he was generating a large quantity of diazomethane, and died four days later from fulminating
pneumonia.
[LeWinn, E.B. "Diazomethane Poisoning: Report of a fatal case with autopsy", The American Journal of the Medical Sciences, 1949, 218, 556-562.] Like any other
alkylating agent it is expected to be carcinogenic, but such concerns are overshadowed by its serious acute toxicity.
CH2N2 may explode in contact with sharp edges, such as ground-glass joints, even scratches in glassware.
The compound explodes when heated beyond 100 °C, exposed to intense light, alkali metals, or calcium sulfate. Use of a blast shield is highly recommended while using this compound.
Proof-of-concept work has been done with microfluidics, in which continuous point-of-use synthesis from N-methyl- N-nitrosourea and 0.93 M potassium hydroxide in water was followed by point-of-use conversion with benzoic acid, resulting in a 65% yield of the methyl benzoate ester within seconds at temperatures ranging from 0 to 50 °C. The yield was better than under capillary conditions; the microfluidics were credited with "suppression of hot spots, low holdup, isothermal conditions, and intensive mixing."
Isomers
The stable compound
cyanamide, whose minor tautomer is
carbodiimide, is an isomer of diazomethane. Less stable but still isolable isomers of diazomethane include the cyclic
Diazirine and isocyanoamine (
isodiazomethane).
In addition, the parent
nitrilimine has been observed under matrix isolation conditions.
External links
