Org. Synth. 1956, 36, 16
Submitted by Th. J. de Boer and H. J. Backer1
Checked by James Cason, Max J. Kalm, and R. F. Porter.
Caution! Diazomethane is toxic and prone to cause development of specific sensitivity; in addition, it is potentially explosive. Hence one should wear heavy gloves and goggles while performing this experiment and should work behind a safety screen or a hood door with safety glass. Also, it is recommended that ground joints and sharp surfaces be avoided. Thus all glass tubes should be carefully fire-polished, connections should be made with rubber stoppers, and separatory funnels should be avoided, as should etched or scratched flasks. Furthermore, at least one explosion of diazomethane has been observed at the moment crystals (sharp edges!) suddenly separated from a supersaturated solution. Stirring by means of a Teflon-coated magnetic stirrer is greatly to be preferred to swirling the reaction mixture by hand, for there has been at least one case of a chemist whose hand was injured by an explosion during the preparation of diazomethane in a hand-swirled reaction vessel.
It is imperative that diazomethane solutions not be exposed to direct sunlight or placed near a strong artificial light, because light is thought to have been responsible for some of the explosions that have been encountered with diazomethane. Particular caution should be exercised when an organic solvent boiling higher than ether is used. Because such a solvent has a lower vapor pressure than ether, the concentration of diazomethane in the vapor above the reaction mixture is greater and an explosion is more apt to occur.
explosions take place during its distillation. Hence diazomethane
should not be distilled unless the need justifies it. An ether solution of diazomethane
satisfactory for many uses can be prepared as described by Arndt,2
is added to a mixture of ether
and 50% aqueous potassium hydroxide
and the ether
solution of diazomethane
is subsequently decanted from the aqueous layer and dried over potassium hydroxide pellets
(not sharp-edged sticks!). When distilled diazomethane
is required, the present procedure is particularly good because at no time is much diazomethane
present in the distilling flask.
The hazards associated with diazomethane
have been discussed by Gutsche,3
has reported on a fatal case of diazomethane
A 125-ml. distilling flask is fitted with a condenser set for distillation and with a long-stem dropping funnel. The condenser is connected by means of an adapter to a 250-ml. Erlenmeyer flask. Through a second hole in the stopper of the Erlenmeyer flask is placed an outlet tube bent so as to pass into and nearly to the bottom of a second Erlenmeyer flask which is not stoppered. Both receivers are cooled in an ice-salt mixture; in the first is placed 10 ml. of ether (Note 1), and in the second 35 ml. of ether. The inlet tube passes below the surface of the ether in the second flask.
In the distilling flask are placed a solution of 6 g. of potassium hydroxide
dissolved in 10 ml. of water, 35 ml. of Carbitol (Note 2)
, 10 ml. of ether (Note 1)
, and the "Teflon"-coated bar of a magnetic stirrer (Note 3)
. The dropping funnel is attached and adjusted so that the stem is just above the surface of the solution in the distilling flask. There is placed in the dropping funnel a solution of 21.5 g. (0.1 mole) of p-tolylsulfonylmethylnitrosamide (p.943)
in 125 ml. of ether (Note 4)
. The distilling flask is heated in a water bath (Note 3)
at 70–75°, the stirrer is started, and the nitrosamide solution is added at a regular rate during 15–20 minutes. As soon as all the nitrosamide solution has been added, additional ether (Note 1)
is placed in the dropping funnel and added at the previous rate until the distillate is colorless. Usually 50–100 ml. additional of ether
is required. The distillate contains 2.7–2.9 g.
) of diazomethane
, as determined by titration2 (Note 5)
and (Note 6)
If an alcohol-free solution of diazomethane
is required, absolute ether
should be used throughout this preparation.
The Carbitol (monoethyl ether of diethylene glycol) was the Carbide and Carbon Chemicals Company
product, which was distilled before use, b.p. 192–196°.
It is a suitable solvent to render the reactants mutually soluble. Aqueous alkali with an ether
solution of the nitrosamide does not yield diazomethane
The same results may be obtained by an occasional careful agitation of the flask by hand; however, an explosion during this agitation by hand would be unfortunate. If the flask is placed in contact with the bottom of a beaker
containing the heated water, and the magnetic stirring unit is placed in contact with the beaker, the bar may be spun satisfactorily. The checkers used the magnetic stirring apparatus, no. 9235-R, supplied by the A. H. Thomas Company, Philadelphia, Pa., and heated the water bath with the thermostated electric immersion heater, "Chill Chaser," model S-1005, supplied by the Still-Man Company, New York 56, N. Y. Satisfactory results should also be obtained by use of a combined heater and magnetic stirrer, such as no. 25210T supplied by the Will Corporation, New York 12, N. Y.
Nitrosamide prepared as described (p. 943)
, not recrystallized, is suitable for the present preparation. The solubility of the nitrosamide in ether
drops sharply with temperature; below 20°, more than the specified amount of ether
may be required, especially if recrystallized nitrosamide is used.
If an entirely dry solution of diazomethane
is required, round pellets of potassium hydroxide
should be used.2
The submitters reported that, in cases where the presence of alcohol in diazomethane
solutions is not objectionable, they utilized ethanol
as the solvent for the reaction mixture in which the diazomethane
was prepared. They believe that ethanol
has an advantage over Carbitol
in that mixing of the reactants is achieved readily during the distillation, since the mixture is not viscous (see Caution
They used the same apparatus as described in the present procedure with the following exceptions: (1) the reaction flask was of 200-ml. capacity
, (2) the first receiver was an empty 500-ml. Erlenmeyer flask, and the second flask of 100-ml. capacity
contained 40 ml. of ether
, and (3) a magnetic stirrer was not employed. In the reaction flask was placed a solution of 10 g. of potassium hydroxide
in 15 ml. of water and 50 ml. of 95% ethanol
. The water bath was heated to 60–65° and a solution of 43 g. (0.2 mole) of p-tolylsulfonylmethylnitrosamide (p.943)
in 200 ml. of ether
was added from the dropping funnel in 45 minutes. After all had been added, ether (about 30 ml.)
was introduced through the dropping funnel until the condensing ether
became colorless. The combined solutions in the receivers contained 5.9–6.1 g.
) of diazomethane
The more important methods of preparation of diazomethane
include those from nitrosomethylurea
,5 N-nitroso-β-methylaminoisobutyl methyl ketone
It also has been prepared from N-nitrosoacetamide
or other alkaline reagents,11
from nitrosyl chloride
from the reaction of bis-(N-methyl-N-nitroso) terephthalamide
and by treatment of the sodium salt of formaldehyde oxime
The advantage of the present method15
resides in the stability of the starting material and the manipulative advantage resulting from its solubility in organic solvents.
This preparation is referenced from:
- Org. Syn. Coll. Vol. 4, 78
- Org. Syn. Coll. Vol. 4, 221
- Org. Syn. Coll. Vol. 4, 943
- Org. Syn. Coll. Vol. 5, 231
- Org. Syn. Coll. Vol. 5, 351
- Org. Syn. Coll. Vol. 5, 877
- Org. Syn. Coll. Vol. 5, 1099
- Org. Syn. Coll. Vol. 6, 386
- Org. Syn. Coll. Vol. 6, 432
- Org. Syn. Coll. Vol. 6, 576
- Org. Syn. Coll. Vol. 6, 613
- Org. Syn. Coll. Vol. 8, 196
Chemical Abstracts Nomenclature (Collective Index Number);
potassium hydroxide pellets (1310-58-3)
nitrosyl chloride (2696-92-6)
Methane, diazo- (334-88-3)
N-Nitroso-β-methylaminoisobutyl methyl ketone (16339-21-2)
monoethyl ether of diethylene glycol (111-90-0)
sodium salt of formaldehyde oxime
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