212266-63-2Relevant academic research and scientific papers
N-phosphorylated nitrogen mustards; Preparation of 2-chloroethyl-and bis(2-chloroethyl)-amides with the benzodiazaphosphorinone ring system
Sonnenburg, Ralf,Borkenhagen, Frank,Neda, Ion,Thoennessen, Holger,Jones, Peter G.,Schmutzler, Reinhard
, p. 11 - 26 (2007/10/03)
The reaction of isatoic acid anhydride 1 with NaH/BrCH2CH2Cl furnished the N-(2-chloroethyl) substituted derivative 2, which was allowed to react with methylamine to form N-(2-chloroethyl)-N'-methylanthranilamide 3. Treatment of 3 with PCl3 furnished the 1,3,2-diazaphosphorin-4-one 4, which reacted with bis(2-chloroethyl) amine hydrochloride to form the P-bis(2-chloroethyl)amino derivative 5 by substitution at phosphorus. Oxidation of 5 with the hydrogen peroxide/urea 1:1 adduct led to the phosphoryl species 6. The σ4P-derivative 7 was formed by hydrolysis of 4 with small amounts of water. Treatment of the P-chloro derivative 8 with (CH3)3SiOCH3 furnished the methoxy-substituted compound 9, which formed the phosphoryl derivative 10 upon reaction with SO2Cl2. The previously known bis(2-chloroethyl)amino-substituted 1,3,2-benzodiazaphosphorin-4-on-2-oxide 11 was synthesized by reaction of 10 with bis(2-chloroethyl)amine hydrochloride/triethylamine. The P-2-chloroethylamino-substituted derivative 12 was obtained by treatment of 8 with 2-chloroethylamine hydrochloride/triethylamine. The structures of 3, 4 and 5 were confirmed by single crystal X-ray structure determination. In 3 the molecules are linked into chains by hydrogen bonds of the form N-H...O=C between amide groups. The heterocycles of 4 and 5 display half-boat conformation with the P atom out of plane.
