90436-77-4

Upstream product

• 868-85-9 Dimethyl phosphite 
• 552-89-6 2-nitro-benzaldehyde 
• 96-36-6 methyl phosphite 

Downstream Products

• 1208065-72-8 dimethyl [(2-nitrophenyl)(6-oxo-6λ5-dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)ethyl]phosphonate 

Relevant academic research and scientific papers

An efficient and simple strategy toward the synthesis of highly functionalized compounds

The expedient syntheses of small libraries of ((β-ethoxycarbonyl, -cyano and -acetyl)propyloxy) methylphosphonate scaffolds bearing olefin, sulfanyl, or amine functions are described. All these new derivatives are readily produced from easily available starting reagents (aldehydes, electron-poor olefins, and dialkylphosphites) following a three steps reaction sequence of condensations, SN2′-type reaction and a conjugated thia- or aza-Michael 1,4-addition with aromatic and aliphatic thiol or amine nucleophiles.

Synthesis and anticancer cytotoxicity with structural context of an α-hydroxyphosphonate based compound library derived from substituted benzaldehydes

We synthesized substituted benzaldehyde derived α-hydroxyphosphonates (αOHP), α-hydroxyphosphonic acids (αOHPA) and α-phosphinoyloxyphosphonates (αOPP) and characterized their cytotoxicity against a panel of cancer cell lines. A library containing 56 analogues was screened against Mes-Sa parental and Mes-Sa/Dx5 multidrug resistant uterine sarcoma cell lines, using a fluorescence-based cytotoxicity assay. The cytotoxicity screening revealed that dibenzyl-αOHPs and dimethyl-α-diphenyl-OPPs were the most active clusters, which encouraged us to synthesize further dibenzyl-α-diphenyl-OPP derivatives that elicited pronounced cell killing. Further structure-activity relationships showed the relevance of hydrophobicity and the position of substituents on the main benzene ring as determinants of toxicity. The most active analogs proved to be equally, or even more toxic to the multidrug resistant (MDR) cell line Mes-Sa/Dx5, suggesting these compounds may overcome P-glycoprotein mediated multidrug resistance by evading the drug transporter.

Rational synthesis of α-hydroxyphosphonic derivatives including dronic acids

New, green methods have been elaborated for the syntheses of α-hydroxyphosphonates and α-hydroxymethylenebisphosphonic derivatives (HMBPs, dronates). α-Hydroxyphosphonates were prepared via the Pudovik reaction, while the synthesis of HMBPs has been performed in the three-component reaction of carboxylic acids, phosphorus trichloride and phosphorus acid.

Magnetic Fe3O4 nanoparticle-supported phosphotungstic acid as a recyclable catalyst for the kabachnik-fields reaction of isatins, imines, and aldehydes under solvent-free conditions

Magnetic-nanoparticle-supported phosphotungstic acid has been used to efficiently catalyze the hydrophosphonylation reaction of isatins, imines, and aldehydes using dimethyl and diethyl phosphite as a nucleophile to give the corresponding α-hydroxy and α-amino phosphonates in excellent yields for a wide range of substrates. The reaction conditions were simple, green, and efficient. The catalyst was recycled up to five times with retention of its activity. Based on the NMR spectroscopy studies, a probable catalytic cycle was proposed.

Synthesis, characterization and catalytic properties of magnetic nanoparticle supported guanidine in base catalyzed synthesis of α-hydroxyphosphonates and α-acetoxyphosphonates

Magnetic nanoparticle Fe3O4-immobilized guanidine (MNPs-Guanidine) as a novel magnetically interphase nanocatalyst was synthesized and characterized. MNPs-Guanidine catalyzed the synthesis of α-hydroxyphosphonates from aldehydes and

Synthesis and antimicrobial activity of bisphosphonates

Dimethyl [(substitutedphenyl)(6-oxo6λ5dibenzo[d,f][1,3,2] dioxaphophepin-6-yl)methyl]phosphonates (5a-j) were synthesised through a three step process involving preparation of dimethyl hydroxy(substitutedphenyl) methylphosphonates (4a-j) and their reactio

The preparation of dimethyl α-hydroxyphosphonates and the chemical shift non-equivalence of their diastereotopic methyl ester groups

Dimethyl α-hydroxyalkyl-, α-hydroxybenzyl-, α-hydroxyfurfuryl-, and α-hydroxy-α-thienylmethyl-phosphonates have been prepared in good yield by the alumina-catalyzed reaction of dimethyl phosphite with the corresponding alkanals, aryl aldehydes (or aryl methyl ketones), furfuraldehyde, and 2- or 3-thiophenecarboxaldehyde, respectively, thus confirming the general utility of this synthetic procedure. The 1H and 13C nmr spectra of the products exhibit characteristic chemical shift non-equivalence of the diastereotopic methyl ester groups, for which a tentative order of non-equivalence is reported and discussed. Copyright Taylor & Francis Group, LLC.

Organic catalysis of phospha-aldol condensation

Phospha-aldol reaction of dialkylphosphites with carbonyl compounds is catalyzed by cinchonine alkaloids and thier modified derivatives to give optically active hydroxyphosphonates. The use of diastereomeric pairs of alkaloids allowed obtaining both optic

Phospho-transfer catalysis on the asymmetric hydrophosphonylation of aldehydes

We report here a precise, in situ 31P{1H}-NMR method of assaying enantiopurity of α-hydroxyphosphonate esters, the products of the carbonyl hydrophosphonylation (Pudovik) reaction. This method is based upon a diazaphospholidine chiral derivatising agent (CDA) which satisfies all of the criteria for a precise assay; (i) derivatisation of α-hydroxyphosphonate esters is both rapid and clean, (ii) kinetic resolution is absent and (iii) 31P{1H} chemical shift dispersions are excellent (> 5ppm). Calibration of this assay has been achieved by cross-referencing the 31P{1H}-NMR signals obtained for the CDA-derivatised ester of (MeO)2PC=O)CHPh(OH) to optical rotation measurements from scalemic material obtained upon lipase catalysed hydrolysis (F-AP 15, Rhizopus oryzae) of (MeO)2P(=O)CHPh(OAc). Analysis of NMR chemical shift and coupling parameters for a closely related series of derivatised α-hydroxyphosphonate esters support further configuration assignments on the basis of inference. We report also on the configurational stability of α-hydroxyphosphonate esters in the presence of acids, organonitrogen bases and metal salts. 2H-labelling and carbonyl crossover experiments reveal that low levels of epimerisation (α) of α-hydroxyphosphonate esters is possible under certain conditions of catalysis and within certain limits. A design strategy for the construction of catalyst systems in the Pudovik reaction is outlined based upon a combination of Lewis acidic (E) and Lewis basic (N) sites. Four types of catalyst are outlined, members of two distinct Classes I and II according to the nature of the acid and base sites, along with our investigations of representative examples of each Class. A variety of Class I.1 systems based on β-amino alcohols (one hydrogen bonding E site and one organonitrogen N site), have been assayed in the model reaction between (MeO)2P(O)H and PhCHO. Results suggest that catalysis of the Pudovik reaction is clean and efficient in certain cases but that catalytic activity is strongly dependent upon the nature of the basic (N) nitrogen centre. Moreover, only low levels ( 50% more strongly (K11 0.53 mol-1 dm3) than dimethyl-H-phosphonate (K11 0.34 mol-1 dm3, 298 K) and to catalyse the hydrophosphonylation reaction between these two substrates with a second order rate constant comparable to that of triethylamine (both k2 5.9 × 10-2 mol-1 dm3 h-1, 293 K). However, one of the major limitations of this model is that competitive product inhibition dominates after some 15 turnovers (75% completion). Model studies reveal that hydrophosphonylation catalysis via a nitrogen Lewis base is accelerated up to 10-fold upon the introduction of [Zn(OSO2CF3)2] as co-catalyst. Consequently, Class II.1 systems employ metal salts [Zn(OSO2CF3)2] as Lewis acidic E sites and chiral co-catalysts capable of binding to the metal and also acting as Lewis basic N sites. Such systems catalyse the addition of (MeO)2P(O)H to PhCHO cleanly with modest turnover numbers (2P(O)H to PhCHO to afford (MeO)2P(O)CHPh(OH) with an average turnover rate (over a 1 h reaction time at 298 K) of 115 h-1 compared to ca. 1 h-1 for NEt3 under analogous conditions. Chiral variants are proposed.

Accurate In Situ 31P Assay of Enantiopurity in α-Hydroxyphosphonate Esters using a Diazaphospholidine Derivatizing Agent

A rapid, convenient and efficient in situ assay of enantiomeric excess in α-hydroxyphosphonate esters is reported exploiting 31P NMR analysis of the diastereoisomers formed upon condensation with a phosphorochloridite reagent containing a chiral diazaphospholidine ring.Use of this chiral framework affords chemical shift dispersions > 5 ppm between diastereoisomers, Accurate integrations are thus possible once account is taken of differential n.O.e. effects and spin lattice T1 relaxation times of the phosphorus nuclei.