Process of preparing 1,3-bis(2-chloroethyl)-1-nitrosourea

Chemistry of carbon compounds – Miscellaneous organic carbon compounds – C-metal

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424322, C07C12715

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active

040284107

ABSTRACT:
A method of producing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by nitrosation of 1,3-bis(2-chloroethyl)-urea utilizing as a nitrosating agent dinitrogen trioxide (N.sub.2 O.sub.3) in molar excess of theoretical wherein the molar excess of N.sub.2 O.sub.3 ranges from 10-200% and preferably from 10-20%. The nitrosation reaction is conventionally carried out in the cold from 0.degree. C to -20.degree. C and a non-aqueous solvent is utilized. The preferred non-aqueous solvent is of the chlorinated variety; i.e., methylene dichloride. Other preferred solvents include related halogenated compounds such as ethylene dichloride, nitro-compounds such as nitromethane, acetonitrile, and simple ethers such as ethyl ether. Other less preferred but operable compounds include esters such as ethyl acetate, simple ketones such as acetones, and chloroform. Solvents to be avoided are olefins, unsaturated ethers and other unsaturated compounds, amines, malonate esters, acid anhydrides, and solvents which would interact with the reactant N.sub.2 O.sub.3 and the urea as well as the product nitrosourea.

REFERENCES:
patent: 3465025 (1969-09-01), Brownstein et al.
Johnston et al., J. Med. Chem., vol, 18, No. 1, 1975, pp. 104-106.
Montero et al., C. R. Acad. Sc. Paris, t. 279, Series C, 1974, pp. 809-811.
Ryan et al., CA 17: 1792-1793 (1923).

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