Synthesis and Spectral Studies of 2,10-Dichloro-6-Bis(2-Chloroethyl)Amino-4,8-Dinitrodibenzo[ d , g ][1,3,6,2]-Dioxathiaphosphocin, 2,10-Dichloro-6-Bis(2-Chloroethyl)Amino-4,8-Dinitrodibenzo[ d , g ][1,3,6,2]Dioxathiaphosphocin 6-Oxide, 2-Bis(2-Chloroethyl)Amino-2,3-Dihydro-5-Thiophenoxy-1 H -1,3,2-Benzodiazaphosphole 2-Oxide, 2-Bis(2-Chloroethyl)Amino-1,2,3,4-Tetrahydro-1,3,2-Benzodiazaphosphorinane 2-Oxide, 5-Bromo-5-Nitro-2-Bis(2-Chloroethyl)Amino-1,3,2-Dioxaphosphorinane 2-Oxide, and 8-Bis(2-Chloroethyl)Amino-16 H -Dinaphtho[2,1- d :1′,2′- g ]1,3,2-Dioxaphosphocin 8-Oxide--Potential Anticancer Agents

Abstract

Several novel bis(2-chloroethyl)aminophosphoryl-containing compounds have been prepared as potential anticancer agents. 2,10-Dichloro-6-[bis(2-chloroethyl)]amino-4,8-dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphocin 6-oxide ( 5 ), 2-bis(2-chloroethyl)amino-1,3, 2-dioxaphosphorinane 2-oxide ( 13 ), and 8-bis(2-chloroethyl)amino-6 H -dinaphtho[2,1-d:1',2']1,3,2-dioxaphosphocin 8-oxide ( 15 ) were synthesized from a reaction of equimolar quantities of the corresponding precursor diols 3 , 12 , and 14 with coreagent N,N-bis(2-chloroethyl)phosphoramidic dichloride ( 1 ) at various temperatures in dry toluene/ether in the presence of triethylamine. In addition, 2-bis(2-chloroethyl)amino-2,3-dihydro-5-thiophenoxy- 1 H-1,3,2-benzodiazaphosphole 2-oxide ( 9 ) and 2-bis(2-chloroethyl)amino-1,2,3,4-tetrahydro-1,3,2-benzodiazaphosphorinane 2-oxide ( 11 ) were derived from 4-thiophenoxy-1,2-diphenyldiamine ( 8 ) and 2-aminobenzylamine ( 10 ) respectively, under similar conditions. Interestingly, attempted oxidation of 5 to the corresponding sulfone 7 by H 2 O 2 (30%) in acetic acid yielded only sulfoxide 6 {2,10-dichloro-6-bis(2-chloroethyl)amino-4,8-dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphocin 6-oxide}. In an alternative approach, oxidation of 5,5'-dichloro-3,3'-dinitro-2,2'-dihydroxydiphenyl sulfide ( 3 ) with H 2 O 2 (30%) in acetic acid formed the corresponding sulfone 4 . However, attempted cyclization of 4 with 1 , in the presence of triethylamine, to give the sulfone expected from 5 was unsuccessful. NMR analysis of 6 suggests the presence of two conformers in solution.

Keywords:

• Bis-(2-chloroethyl)aminodioxathiaphosphocins/dioxaphosphocin/benzodiazaphosphole/dioxaphosphorinane 1/5/6/8-oxides
• Mass Spectral Data
• Nmr