Organophosphorus Chemistry 2021

Forty years have passed since a real "phosphabenzene" (a phosphinine) was prepared for the first time applying steric protection methodology with the sterically demanding 2,4,6-tri-tertiary-butylphenyl ("supermesityl") group [...].

access to these macromolecular materials is especially needed. Salamonczyk introduced an easy and highly efficient method for synthesizing new polyanionic dendrimers as potential broadspectrum antiviral drugs [4]. The mild conditions of the coupling and deprotection reactions provided highly pure and water-soluble macromolecular materials in good overall yields. The important advantage of the presented strategy is direct access to the polyanionic material at each generation of the prepared dendrimer. This approach seems to be a general methodology that enables the transformation of practically any macromolecular compound terminated with hydroxy functions into its polyanionic derivative. Moreover, it offers the possibility to make discrete modifications layer-by-layer (i.e., P=O, P=S, and/or carbon branching) within the same dendrimer skeleton, key for a structure-activity relationship study.
Nycz et al. summarized the available results on molecules containing the >P(=O)-P(=O)< fragment, which notably resembles the structure of the >P(=O)-O-P(=O)< moiety [5]. Both structural motifs are essential building blocks for many important molecules found in nature and the field of medicinal chemistry. The review covers the strategies related to synthesizing hypodiphosphoric acid (former name hypophosphoric acid), its ester form, and diphosphine dioxides. Last but not least, a few properties and applications of the compounds with the outlined structures are presented.
The next article discusses the Pudovik reaction between α-oxophosphonates (ZC(O)P(O)(OEt) 2 , Z = Me or Ph) and Y 2 P(O)H reagents (Y = EtO, MeO, and Ph) that may lead to the corresponding adducts (Y 2 P(O)C(OH)ZP(O)(OEt) 2 ), a kind of dronic acid derivatives, and/or their rearranged versions [6]. The outcome mostly depended on the Z substituent, the quantity of the dialkylamine catalyst, and, to a lesser extent, the nature of other substituents, as well as the temperature and the solvent. In a few cases, time also influenced the course of the reaction. In cases where Z = Me, the adducts were the primary products, but with suitable modifications, the reactions could be tuned to yield the rearranged derivatives. At the same, in cases where Y = Ph, the corresponding adducts were only intermediates that were converted spontaneously to their rearranged versions. This phenomenon was explained by electronic factors. In reaction with dimethyl phosphite and diphenylphosphine oxide, the rearranged species comprised two isomers.
Dronic acid derivatives, important drugs against bone diseases, may be synthesized from the corresponding substituted acetic acid either by reaction with phosphorus trichloride in methanesulfonic acid as the solvent or by also using phosphorous acid as the P-reactant if sulfolane is applied as the medium [7]. The possible mechanistic pathways leading to fenidronic acid and benzidronic acid were computed considering the reaction of benzoic acid or phenylacetic acid and derivatives with PCl 3 in MSA or with PCl 3 /P(OH) 3 in sulfolane. It was found that the corresponding acyl chlorides should be considered as the starting compounds, and PCl 3 or its condensed derivative with MSA or H 3 PO 4 (Cl 2 P-O-SO 2 Me or Cl 2 P-O-P(OH) 2 , respectively) may be the nucleophile. The multistep formation of the bis adducts was, in most cases, endothermic, and the exothermic final hydrolyses could be the driving force for the series of reactions. In the case of benzidronic acid, the activation Gibbs free energies were lower for all steps than for fenidronic acid. It is noteworthy that in the case of using PCl 3 /P(OH) 3 in sulfolane, the formation of the adducts was exothermic. It turned out that the setup with PCl 3 /P(OH) 3 in sulfolane involving (HO) 2 P-O-PCl 2 as the nucleophile is the energetically preferable option. Hence, in the synthesis of dronic acid derivatives, this approach is recommended.

Conflicts of Interest:
The author declares no conflict of interest.