[59665-02-0]  · C9H11N3O2  · N-[N-Methyl-N-nitroso(aminomethyl)]benzamide  · (MW 193.23)

(precursor of diazomethane1)

Alternate Name: N-[(methylnitrosoamino)methyl]benzamide.

Physical Data: mp 128-131 °C.

Solubility: sol acetone, ethanol, dioxane, chloroform; slightly sol ether; insol water, petroleum ether.

Form Supplied in: crystalline solid; commercially available.

Preparative Method: by nitrosation of N-[(methylamino)methyl]benzamide hydrochloride, which is itself obtained from methylamine hydrochloride, formaldehyde, and benzamide.2

Handling, Storage, and Precautions: stable at rt for many years. Storage in a brown bottle is recommended. Although the mutagenicity of this reagent has not been reported, like all nitroso compounds it should be treated as a highly toxic substance. All handling should be conducted in an efficient fume hood.

General Discussion.

This reagent was introduced1 in 1976 as a new type of Diazomethane precursor which may be regarded as a modified Mannich base. It liberates diazomethane in the presence of alkali hydroxide, presumably through b-elimination to form N,N-methylenebisbenzamide and formaldehyde (eq 1).

The generation of diazomethane with this reagent proceeds similarly to that of N-Methyl-N-nitroso-p-toluenesulfonamide, and the procedure can be performed by the use of the same apparatus. The following improved procedure is recommended over that originally described. In a flask are placed a solution of 3 g of potassium hydroxide in 4 mL of water, 5 mL of 2-(2-methoxyethoxy)ethanol, and 10 mL of ether, and a condenser is connected to two receiving flasks in series, both cooled in ice-salt baths. The second receiver contains 10 mL of ether and an inlet tube which dips below the surface of the solvent. The mixture is heated in a water bath at about 70 °C with magnetic stirring, and a solution of 5.8 g (0.03 mol) of N-[(methylnitrosoamino)methyl]benzamide in 40 mL of 2-(2-methoxyethoxy)ethanol diluted with 40 ml of ether is added from a dropping funnel over about 20 min. The dropping funnel is rinsed with 30-50 mL of additional ether. The distillation is continued until the distilling ether is colorless. The combined distillate contains 0.77-0.82 g (61-65%) of diazomethane.

A drawback of this reagent is that its poor solubility in ether requires the use of a mixed solvent system of 2-(2-methoxyethoxy)ethanol and ether as described above. In place of 2-(2-methoxyethoxy)ethanol, 2-methoxyethanol (bp 125 °C) (in which the reagent is somewhat more soluble) can be also used. An analog possessing high solubility in ether has been reported: isopropyl N-[(methylnitrosoamino)methyl]carbamate,4 i-PrOCONHCH2N(NO)Me. However, this reagent has been reported to exhibit significant mutagenicity.3

1. (a) Sekiya, M.; Ohashi, Y.; Terao, Y.; Ito, K. CPB 1976, 24, 369. (b) Sekiya, M. Yuki Gosei Kagaku Kyokaishi 1980, 38, 176 (CA 1980, 93, 94 722).
2. Watase, Y.; Terao Y.; Sekiya, M. CPB 1973, 21, 2775.
3. Morita, T.; Sawaki, M.; Mifuchi, I. CPB 1981, 29, 1758.
4. Yamashita H.; Ito, K.; Terao, Y.; Sekiya, M. CPB 1979, 27, 682.

Yoshiyasu Terao & Minoru Sekiya

University of Shizuoka, Japan

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