[80-11-5]  · C8H10N2O3S  · N-Methyl-N-nitroso-p-toluenesulfonamide  · (MW 214.27)

(precursor of diazomethane1a)

Alternate Names: Diazald; p-tolylsulfonylmethylnitrosamide.

Physical Data: mp 61-62 °C.

Solubility: sol petroleum ether, ether, benzene, alcohol, CHCl3, CCl4; insol H2O.

Form Supplied in: pale yellow powder; commercially available.

Preparative Methods: prepared by the reaction of p-Toluenesulfonyl Chloride with methylamine, followed by nitrosation with Sodium Nitrite in glacial acetic acid.1c

Purification: recrystallization is best achieved by dissolving the reagent in hot ether (1 mL g-1), adding an equal volume of petroleum ether (or pentane), and cooling in a refrigerator overnight.1c

Handling, Storage, and Precautions: store in a brown bottle. Has a shelf-life of at least 1 year at rt. For longer periods of storage, it is recommended that the reagent be purified by recrystallization1c and refrigerated. Toxic; severe skin irritant; handle only in a fume hood.

General Discussion.

Diazomethane is a yellow gas (bp -23 °C, mp -145 °C) with the dipole structure CH2=N+=N- ⇂ +CH2-N=N- ⇂ -CH2-N=N+. This versatile compound behaves as a methylene precursor with release of nitrogen and also functions as a 1,3-dipole in a variety of reactions, as documented in several reviews.2 Diazomethane itself is both highly toxic and unpredictably explosive, and has been suggested to be a carcinogen.3 Great care must be taken in handling this substance. However, these risks are minimal when diazomethane is prepared and handled as a dilute solution in an inert solvent such as ether using the proper equipment as discussed below (for further discussion, see Diazomethane). A large number of compounds which previously served as diazomethane precursors can be represented by the formula RN(NO)Me, where R can be sulfonyl, carbonyl, imidoyl, or similar electron-withdrawing groups. Among these the reagent, N-methyl-N-nitroso-p-toluenesulfonamide, introduced by de Boer and Backer in 1954,1a is the most common reagent used for the preparation of diazomethane. However, in some cases N-[N-Methyl-N-nitroso(aminomethyl)]benzamide and 1-Methyl-3-nitro-1-nitrosoguanidine have advantages as diazomethane precursors. In addition, N-methyl-N-nitroso-p-toluenesulfonamide does suffer from some drawbacks, including its relatively short shelf life (1-2 years) and its mutagenic activity.4

Diazomethane is prepared as a dilute solution in ether by the decomposition (eq 1) of N-methyl-N-nitroso-p-toluenesulfonamide catalyzed by alkali hydroxide.

This preparation and all reactions involving diazomethane should be carried out in an efficient fume hood and behind a sturdy safety shield. Rough surfaces and strong sunlight are known to initiate detonation. Carefully fire-polished glassware for diazomethane preparation is commercially available.5 A typical experimental procedure is as follows.1b A 125 mL, 3-neck flask is charged with a solution of 6 g of potassium hydroxide in 10 mL of water, 35 mL of 2-(2-ethoxyethoxy)ethanol (carbitol), and 10 mL of ether, and is then fitted with an efficient condenser set downward for distillation. The condenser is connected to two receiving flasks in series, both cooled in an ice-salt bath. The second receiver contains 25 mL of ether and the inlet tube should dip below the surface of the solvent. The generating flask is heated in a water bath at about 70 °C, stirring is started (Teflon-coated magnetic stirring bar), and a solution of 21.4 g (0.1 mol) of N-methyl-N-nitroso-p-toluenesulfonamide in 125 mL of ether is added from the dropping funnel over about 20 min. The rate of addition should about equal the rate of distillation. When the dropping funnel is empty, 50-100 mL of additional ether is added slowly. The distillation is continued until the distilling ether is colorless. The combined ethereal distillate contains 2.7-2.9 g (64-69%) of diazomethane. The content of diazomethane in the codistilled ethereal solution can be determined by titration; excess benzoic acid is added to the solution (to react with diazomethane) and the excess acid is titrated with a standard solution of NaOH. If moisture must be removed from the ethereal diazomethane solution, the drying agent of choice is KOH pellets. It is recommended that diazomethane solutions be used immediately and not stored, even at low temperature.

An alternative popular procedure for the generation of small quantities (1-50 mmol) of diazomethane from Diazald employs a commercial mini-Diazald apparatus with a dry-ice/acetone cold finger in place of the water-jacketed condenser.5 The generation of diazomethane is carried out by treatment of the Diazald with KOH in aqueous ethanol.2g

1. (a) de Boer, T. J; Backer, H. J. RTC 1954, 73, 229. (b) de Boer, T. J.; Backer, H. J. OSC 1963, 4, 250. (c) de Boer, T. J.; Backer, H. J. OSC 1963, 4, 943.
2. (a) Gutsche, C. D. OR 1954, 8, 364. (b) Eistert, B.; Regitz, M.; Heck, G.; Schwall, H. MOC 1968, 10/4, 482. (c) Fieser L. F.; Fieser F. FF 1967, 1, 191. (d) Pizey, J. S. Synthetic Reagents; Wiley: New York, 1974; Vol 2, Chapter 2, p 65. (e) Herrmann, W. A. AG(E) 1978, 17, 800. (f) Adam, W.; De Lucchi, O. AG(E) 1980, 19, 762. (g) Black, T. H. Aldrichim. Acta 1983, 16, 3.
3. Schoental, R. Nature (London) 1960, 188, 420.
4. (a) Bignami, M.; Carere, A.; Conti, G; Conti, L.; Crebelli, R.; Frabrizi, M. Mutat. Res. 1982, 97, 293. (b) Druckrey, H.; Preusmann, R. Nature (London) 1962, 195, 1111.
5. Aldrich Chemical Company, Inc.

Yoshiyasu Terao & Minoru Sekiya

University of Shizuoka, Japan

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