Reactions of 5(4H)-Oxazolones with Wittig-Horner Reagents: Novel Synthesis of Dioxopyrrolidinephosphonates and Phosphonoalkanoates with Anticipated Schistosomicidal Activity

Abstract

Abstract4-Benzylidene-2-phenyl-5(4H)-oxazolones react with Wittig-Horner reagents in the presence of alcoholic sodium alkoxide to give novel dioxopyrrolidinephosphonates, diethyl [3-(benzoylamino)- 1-cyano-2-oxo-4-phenylbut-3-en-1-yl]phosphonate and phosphonoalkenoate derivatives. Both the phosphonate adducts and the ester products were also isolated from the reaction of oxazolones with triethyl phosphonoacetate using alcoholic sodium ethoxide and/or sodium hydride as a base. Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic results. The biological evaluation of the new compounds is reported.

On the Redox Reaction of 1,2-Bis(diphenylphosphino) Alkanes Toward o-, and p-Quinones

“…The structural assignment for compound 20 is based upon elemental analysis and spectroscopic (IR, 1 H, 13 C, 31 P NMR) as well as MS data (cf . Experimental Section).…”

“…The reactions of trivalent phosphorus compounds with ortho-and para-quinones have been studied in considerable detail by Ramirez and his coworkers. 10 In view of this and in continuation of our work in organophosphorus chemistry [11][12][13][14][15][16][17] , it was of considerable interest to study the reactivity of bis(diphenylphosphino)alkanes 1a,b toward quinones (2-7) (Figure 1). …”

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…173 By using 5(4H)-oxazolones 259 and Wittig−Horner reagents such as 260 in the presence of sodium alkoxide in alcoholic solutions, it is possible to access dioxopyrrolidinephosphonates 261. 174 Although the yields of the obtained products are very good, this reaction is limited to these pyrrolidinylphosphonates because of the nature of the phosphonate anion or the base if the substituents in the oxazolone change, different acyclic products can be obtained (Scheme 53). The phosphonylated pyrrolidines were tested on Schistosoma mansoni worms, and it was found that they induce in vitro antischistosomal activity with 100% mortality in a concentration of 10 μg/mL.…”