A Mechanistic Study on the Formation of Dronic Acids

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 using also phosphorous acid as the P-reactant if sulfolane is applied as the medium. The energetics of the two protocols were evaluated by high-level quantum chemical calculations on the formation of fenidronic acid and benzidronic acid. The second option, involving (HO)2P‑O‑PCl2 as the nucleophile, was found to be more favorable over the first variation, comprising Cl2P‑O‑SO2Me as the real reagent, especially for the case of benzidronate.

Synthesis, Structural Characterization, and Biological Activities of Organically Templated Cobalt Phosphite (H2DAB)[Co(H2PO3)4]·2H2O

A novel hybrid cobalt phosphite, (H2DAB)[Co(H2PO3)4]·2H2O, has been synthesized by using slow evaporation method, in the presence of cobalt nitrate, phosphorous acid and 1,4- dia-minobutane (DAB= 1,4- diaminobutane) as a structure-directing agent. Single crystal X-ray diffraction analysis showed that the compound crystallizes in the P-1(n.2) triclinic space group, with the following unit cell parameters (Å, °) a = 5.4814 (3), b = 7.5515 (4), c = 10.8548 (6), α = 88.001 (4), β = 88.707 (5), γ = 85.126 (5), and V= 447.33 (4) Å3. The crystal structure was built up from cor-ner-sharing [CoO6] octahedra, forming chains parallel to [001], which are interconnected by H2PO3 pseudo-tetrahedral units. The deprotonated cations, residing between the parallel chains, interacted with the inorganic moiety via hydrogen bonds leading thus to the formation of the 3D crystal structure. The Fourier transform infrared spectrum showed characteristic bands corresponding to the phosphite group and the organic amine. The thermal behavior of the compound consisted mainly of the loss of its organic moiety and the water molecules. The biological tests exhibited significant activity against Candida albicans and Escherichia coli strains in all used concentrations, while less inhibitory activity was pronounced against Staphylococcus epidermidis and Saccharomyces cerevisiae, and in the case of multi-cellular organisms, no activity against the nematode model Steinernema feltiae was detected.

Sustainable Production of Reduced Phosphorus Compounds: Mechanochemical Hydride Phosphorylation Using Condensed Phosphates as a Route to Phosphite

Phosphorus removal and recovery technologies have been implemented to tackle the anthropogenic eutrophication caused by phosphate runoff into waterways. In pursuit of a better utilization of the phosphates recovered from waste water treatment, we herein report that condensed phosphates can be employed to phosphorylate hydride reagents under solvent-free mechanochemical conditions to furnish phosphite (HPO3)2−, a versatile chemical with phosphorus in the +3 oxidation state. Hydride phosphorylation, as a two-electron one-proton reduction of a main group element oxide, constitutes a direct parallel with CO2 reduction to formate. Using potassium hydride as the hydride source, sodium trimetaphosphate (Na3P3O9 ), triphosphate (Na5P3O10), and pyrophosphate (Na4P2O7) engendered phosphite in 44, 58, and 44% yields based on total P content, respectively, under their optimal conditions. Formation of overreduced products including hypophosphite (H2PO2−) was identified as a competing process, and mechanistic investigation revealed that hydride attack on in situ generated phosphorylated phosphite species is a potent pathway for overreduction. The phosphite generated from our method could be easily isolated in the form of barium phosphite, a useful intermediate for production of phosphorous acid. This method circumvents the need to pass through white phosphorus (P4) as a high energy intermediate and mitigates involvement of environmentally hazardous chemicals. A bioproduced polyphosphate from baker’s yeast was demonstrated to be a viable starting material for the production of phosphite. This example demonstrates the possibility of accessing reduced phosphorus compounds in a more sustainable manner, and more importantly, closing the modern phosphorus cycle.

Phosphonate treatment effects on Phytophthora root rot control, phosphite residues and Phytophthora cactorum inoculum in young apple orchards

Phytophthora root rot, caused by Phytophthora cactorum, is an economically important disease on young apple trees. Limited information is available on the effect of different phosphonate application methods and dosages on disease control, fruit- and root phosphite concentrations and soil- and root pathogen inoculum levels. Evaluation of phosphonate treatments in three apple orchard trials (two in the Grabouw and one in the Koue Bokkeveld region) showed that foliar sprays (ammonium- or potassium phosphonate), trunk sprays and trunk paints, were equally effective at increasing trunk diameter in one trial and yield in a second trial over a 25-month period. Foliar ammonium- and potassium phosphonate sprays (12 g phosphorous acid/tree), and two different dosages of the ammonium phosphonate sprays (~ 4.8 g or 12 g phosphorous acid/tree) were all equally effective at improving tree growth. The addition of a bark penetrant (polyether-polymethylsiloxane-copolymer) to trunk sprays did not improve the activity of trunk sprays. The low dosage ammonium phosphonate foliar spray (~4.8 g a.i./tree) was the only treatment that in general yielded significantly lower root phosphite concentrations than the other phosphonate treatments. Root phosphite concentrations were significantly positively correlated (P < 0.0001) with an increase in trunk diameter and negatively with P. cactorum root DNA quantities (P ≤ 0.001). Phosphite fruit residues were less than 31 ppm for all treatments, with the trunk paint treatment (80 g phosphorous acid/tree applied annually) yielding significantly lower residues than the higher dosage foliar sprays (~12 g a.i/tree). Twenty-one months post-treatment, most of the phosphonate treatments in all of the trials similarly significantly reduced P. cactorum DNA quantities estimated directly from roots, but not from soil based on soil baiting DNA analysis. Pathogen quantities in fine feeder roots did not differ significantly from those in higher-order roots (< 5 mm dia.). Phytophthora cactorum DNA quantities estimated using DNA quantification directly from roots were significantly correlated (P < 0.0001) with those obtained through root leaf baiting DNA analysis, and to a lesser extent with soil leaf baiting DNA quantities (P = 0.025).

On the Acid Sites of Phosphorous Modified Zeosils

The acid sites of phosphorus-containing zeosils were probed through a combination of solid acid characterization, density functional theory calculations, and kinetic interrogations, establishing their weakly Brønsted acidic character. Due to the disparity in acid-site strength, P-zeosils catalyzed the probe chemistry of isopropanol dehydration slower than aluminosilicate zeolites by an order of magnitude on an active site basis. Propene selectivity during isopropanol dehydration remained 20-30% higher than that of aluminosilicates, illustrating the distinct nature of the weakly acidic phosphorus active sites that favored unimolecular dehydration routes. Regardless of the confining siliceous environment, the nature of phosphorous active sites was unchanged, indicated by identical apparent uni- and bi-molecular dehydration energy barriers. Kinetic isotope experiments with deuterated isopropanol feeds implicated an E2-type elimination to propene formation on phosphorus-containing materials. Comparison of KIEs between phosphorus-containing zeosils and aluminosilicates pointed to an unchanged isopropanol dehydration mechanism, with changes in apparent energetic barriers attributed to weaker binding on phosphorous-active sites that lead to a relatively destabilized alcohol dimer adsorbate. Both ex-situ alkylamine Hofmann elimination and in-situ pyridine titration characterization methods exhibited phosphorous acid site counts dependent on probe molecules identity and/or concentration, underpinning the limitations of extending common characterization techniques for Brønsted-acid catalysis to weakly acidic materials.