Donald L Sharp

US Patent:

40284107, Jun 7, 1977

Filed:

Nov 13, 1974

Appl. No.:

5/523334

Inventors:

William H. Yanko - Centerville OH
Donald E. Sharp - Dayton OH

Assignee:

The United States of America as represented by the Secretary of the
Department of Health, Education and Welfare - Washington DC

International Classification:

C07C12715

US Classification:

260553R

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.