Synthesis and Spectral Characterization of Some Novel Phosphonyl‐ and Phosphoryl Pyrazole Compounds

1,3‐Diphenyl‐1H‐pyrazole‐4‐carbaldehyde ( 1 ) reacted with aniline, 2‐substituted anilines, and P,P‐dimethylphosphinic hydrazide in the presence of diethyl phosphite to give acyclic α‐aminophosphonate 2 , cyclic α‐aminophosphonates 4–6 , and α‐hydrazinophosphonate 7 , respectively. Also, treatment of aldehyde 1 with cyanoaceto‐hydrazide, acetophenone, and malononitrile afforded the condensation products 8 , 16 , and 21 , respectively, which in turn, reacted with diethyl phosphite and P,P‐dimethylphosphinic hydrazide. The reaction of diethyl phosphite with the hydrazone 8 and chalcone 16 yielded the novel phosphorus heterocycles 13 and 18 , respectively, while its reaction with the dicyanoarylidene 21 produced the dicyanopyrazolyl phosphonate 22 . On the other hand, treatment of the hydrazone 8 with P,P‐dimethylphosphinic hydrazide gave the unexpected P,P‐dimethylphosphinic hydrazone 15 , which reacted with diethyl phosphite forming α‐hydrazinophosphonate 7 . Furthermore, the interesting N‐phosphoryl pyrazoles 20 and 24 were resulted in good yield via cycloaddition of P,P‐dimethylphosphinic hydrazide to the chalcone 16 and dicyanoarylidene 21 , respectively. Structures of all newly synthesized compounds were confirmed by considering the data of IR spectroscopy, MS, and ¹H‐, ¹³C‐, and ³¹P‐NMR spectroscopy, as well as that of elemental analyses.     

Synthesis of α‐aminophosphonates from α‐hydroxyphosphonates; a theoretical study

Two types of reactions, namely the Pudovik reaction of benzaldehyde and acetophenone with diethyl phosphite as well as the substitution of the α‐hydroxyphosphonates so‐formed by primary amines to afford α‐aminophosphonates, were evaluated by quantum chemical calculations at the B3LYP/6‐31G(d,p) level. An unexpected neighboring group effect was found to enhance the substitution. A series of new α‐aminophosphonates was synthesized by the microwave‐assisted substitution of α‐hydroxyphosphonates by alkylamines.     

NbCl5: an efficient catalyst for one‐pot synthesis of α‐aminophosphonates under solvent‐free conditions

NbCl₅ has been found to be a very effective catalyst for the synthesis of a variety of α‐aminophosphonates through the Kabachnik–Fields reaction of carbonyl compound, amine and diethyl phosphite under solvent‐free conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

An Eco‐friendly Three Component Manifold for the Synthesis of α‐Aminophosphonates under Catalyst and Solvent‐free Conditions,X‐ray Characterization and Their Evaluation as Anticancer Agents

A series of α‐aminophosphonates were synthesized through one‐pot condensation of aryl aldehydes, aryl amines and diethyl phosphite in the absence of any catalyst and organic solvents. All the synthesized α‐aminophosphonates were characterized by spectral and elemental analysis and in the case of compound 4j by X‐ray crystallography. Some of these new α‐aminophosphonate derivatives were found to have cytotoxic activity on the cancer cell line DU145 in vitro by the MTT method.     

Clean Procedure for the Synthesis of Α‐Aminophosphonates Catalyzed by Choline‐Based Ionic Liquid

A sulfated choline‐based ionic liquid [Ch‐OSO₃H] was prepared and used as a novel catalyst for the synthesis of α‐aminophosphonates via a one‐pot three‐component reaction with aldehydes, amines, and triethyl phosphite/diethyl phosphite at room temperature under solvent‐free conditions or in aqueous media. The reaction was completed in short times and products could be simply separated from the reaction mixture in good to excellent yields. The catalyst could be recycled and reused for several times without noticeably reducing catalytic activity.     

Synthesis of O,O‐Diphenyl N‐trichlorogermanylpropiono‐α‐aminophosphonates

A variety of novel O,O‐Diphenyl N‐(trichlorogermanyl)propiono‐α‐aminophosphonates were synthesized by the reaction of β‐(trichlorogermanyl) propionyl chloride with diphenyl α‐aminophosphonates in the presence of triethylamine. The structures of all of the products were confirmed by ¹H‐NMR spectroscopy, elemental analyses, and IR spectroscopy. Data of ¹H‐NMR and IR spectroscopic determinations indicated the title compounds to be pentacoordinated organogermanium compounds. The results of bioassay showed that some of the title compounds possess potential anticancer activity. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 5–8, 1999     

P‐Dodecylbenzenesulfonic Acid: A Highly Efficient Catalyst for One‐Pot Synthesis of α‐Aminophosphonates in Aqueous Media

A highly efficient one‐pot three‐component reaction of aldehydes or ketones, amines, and trimethyl or triethyl phosphite catalyzed by p‐dodecylbenzensulfonic acid is developed for the synthesis of α‐aminophosphonates at room temperature in water. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:174–178, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21079     

A Critical Overview of the Kabachnik–Fields Reactions Utilizing Trialkyl Phosphites in Water as the Reaction Medium: A Study of the Benzaldehyde‐Benzylamine Triethyl Phosphite/Diethyl Phosphite Models

α‐Aminophosphonates may be synthesized by the three‐component condensation of oxo‐compounds, amines, and dialkyl phosphites or trialkyl phosphites. In the latter case, mostly water is the reaction medium and a catalyst is also needed. This approach has been studied critically by us, exploring the background of this version of the Kabachnik–Fields condensation. The possibilities for the Kabachnik–Fields condensation of benzaldehyde, benzylamine, and triethyl phosphite or diethyl phosphite including the accomplishment in water were studied in detail.     

Silica gel and polystyrene supported aluminum chloride as heterogeneous catalysts for the preparation of α‐aminophosphonates

Silica gel supported aluminum chloride (SiO₂‐AlCl₃) and cross‐linked polystyrene‐supported aluminum chloride (PS‐AlCl₃) are environment‐ friendly heterogeneous catalysts for the condensation of amines and aldehydes with diethyl phosphite to afford α‐aminophosphonates. These solid acid catalysts are stable (as bench top catalysts) and can be easily recovered and reused without appreciable change in their efficiency. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:418–422, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20629     

One‐pot synthesis of primary 1‐aminophosphonates: Coupling reaction of carbonyl compounds,hexamethyldisilazane, and diethyl phosphite catalyzed by Al(OTf)3

Al(OTf)₃ has been utilized as a new and efficient catalyst for the selective synthesis of primary 1‐aminophosphonates by a one‐pot coupling reaction of various types of aldehydes/ketones, hexamethyldisilazane, and diethyl phosphite under solvent‐free conditions. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:109–115, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20517     

A study on the kabachnik‐‐fields reaction of benzaldehyde,cyclohexylamine, and dialkyl phosphites

The Kabachnik–Fields reaction of benzaldehyde, cyclohexylamine, and dimethyl phosphite carried out at 80°C in acetonitrile takes place via an imine (PhCN ^cHex) intermediate, as the monitoring by in situ Fourier transform IR spectroscopy suggested. The corresponding α‐hydroxyphosphonate was also formed in a quantity of 13% that was not converted to α‐aminophosphonate under the conditions applied. The outcome was similar to the Kabachnik–Fields reaction with diethyl phosphite as the P‐component. Molecular modeling and subsequent DFT calculations carried out under solventless conditions supported the experimental results and indicated the formation of a high number of ideally positioned H bonds as the key determinant for the conformation of the starting, intermediate, and product states. The relative energies of the possible intermediates were in accord with the observation that the formation of the α‐hydroxyphosphonate is a “dead‐end” route. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:171–178, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20767     

α‐Aminophosphonates and α‐Aminophosphine Oxides by the Microwave‐Assisted Kabachnik–Fields Reactions of 3‐Amino‐6‐methyl‐2 H‐pyran‐2‐ones

The microwave‐assisted Kabachnik–Fields reaction of a series of 3‐amino‐6‐methyl‐2H‐pyran‐2‐ones, paraformaldehyde, and dialkyl phosphites or diphenylphosphine oxide led to α‐aminophosphonates or α‐aminophosphine oxides, respectively. The α‑aminophosphonates were obtained under solvent‐free conditions, whereas the α‑aminophosphine oxides in acetonitrile. The novel products were characterized by NMR and mass spectral data. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:221–225, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21086     

Rationalization of the stereochemistry of an addition of dialkyl phosphites to certain chiral aldimines: The experimental and theoretical approach

The absolute configuration of an α‐P stereogenic center in two diastereomeric O,O‐dialkyl α‐aminophosphonates ( 3 ), arising from an induced 1,3‐asymmetric phosphite addition to the CN bond of furfural‐derived Schiff bases ( 1 ), was established from single product ¹H NMR data. Such spectra were interpreted with anisotropic shielding in relation to the AM1 and MNDO/d structures of 3 ; the former ones turned out to be closer to the obtained experimental results (¹H NMR spectra of 3 , crystallographic database study). Since favored 3‐21G geometries of starting imines 1 were modeled as well, it was inferred that a stereochemical outcome of this reaction is governed by Cram selectivity. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:120–125, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10005     

Synthesis and antitumor activity of novel α‐aminophosphonates from diterpenic dehydroabietylamine

A series of novel α‐aminophosphonates were synthesized from diterpenic dehydroabietylamine, and their structures were characterized by IR, ¹H NMR, and ³¹P NMR spectroscopy. Their antitumor activities against SMMC7721 liver cancer cells were evaluated by the MTT method. Compounds 4 and 6 exhibited higher activities even at very low concentrations, and the inhibition ratios reached 75% and 79% at 0.1 µM, respectively. The inhibition ratio of compound 9 reached 99% after 72‐h incubation. α‐Aminophosphonates with a fluorine atom and a nitro group fused to the benzene ring exhibited higher activities. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:512–516, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20471     

A Quick and Clean Procedure for Synthesis of α‐Aminophosphonates in Aqueous Media

A green and efficient procedure for the synthesis of α‐aminophosphonates has been developed in water as a green and nonhazardous solvent, from condensation between aromatic aldehydes, aniline, and triphenyl phosphite at 80°C. This methodology has a number of advantages including clean reaction conditions, easy work‐up, and environmentally friendly.     

The synthesis and reactivity of alkyl‐aminosubstitutedmethylenediphosphonates

Reactions of diethyl phosphite with Vilsmeier reagents, RCONR¹R²/POCl₃, afforded various alkylaminosubstitutedmethylenediphosphonates in acceptable yields, which (R = H) were then reacted with aldehydes under the conditions of the Wittig–Horner reaction to furnish vinylphosphonates, and which (R = H) underwent alkylation with alkyl halides to give alkylaminosubstitutedmethylenediposphonates 8 . (Z)‐Vinylphosphonates could be converted to (E)‐isomers in refluxing ethyl acetate.© 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 271–276, 1999     

Zn(OAc)2•2H2O‐catalyzed synthesis of α‐aminophosphonates under neat reaction

A series of novel α‐aminophosphonates have been prepared by one‐pot three‐component condensation in the presence of a zinc acetate (Zn(OAc)_2•2H₂O) catalyst at 50°C under solvent‐free conditions with excellent yields. The major advantages of the present method are high yields, a short reaction time, and solvent‐free reaction conditions. Their antimicrobial activity was evaluated, and some of them showed significant activity. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:160–165, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20765     

A convenient synthesis of substituted 3‐alkoxycarbonyl‐β,γ‐unsaturated esters with predominant Z‐selectivity

The consecutive reaction of bis[2,2,2‐trifluoroethyl]phosphite with sodium hydride, dimethyl maleate, and aldehydes gives 3‐alkoxycarbonyl‐β,γ‐unsaturated esters with predominant Z‐selectivity in 62–94% yields (Z/E = 85–60:15–40). The Z‐ and E‐isomer can be separated conveniently by column chromatography. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:276–279, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10142     

Synthesis of Substituted N‐Formylaminomethylenediphosphonates and Their Derivatives

The convenient methods for the synthesis of new trimethylsilyl esters of aminomethylenediphosphonic acids are elaborated. The new substituted N‐formylaminomethylenediphosphonates are obtained via the interaction of trimethylsilyl esters of methylenediphosphonic acids with a mixture of triethyl orthoformate and ethanol. Also boron trifluoride–diethyl etherate as an effective catalyst is used for the interaction of hydrochlorides of ethoxymethylene imines with diethyl trimethylsilyl phosphite. The corresponding aminomethylenediphosphonic acids are presented.     

Synthesis and evaluation of new phosphonic acid‐functionalized acrylamides with potential biomedical applications

Phosphorus‐containing acidic monomers are able to interact with the inorganic phase of mineralized tissues such as enamel, dentin, and bone. From this perspective, three phosphonic acid‐containing acrylamide monomers with different lengths of alkyl chains were synthesized to be used for both self‐etching dental adhesives and mineralized hydrogel scaffolds. Monomers were synthesized by the reaction of α‐aminophosphonates (diethyl aminomethylphosphonate, diethyl 2‐aminobutan‐2‐ylphosphonate, and diethyl 2‐aminooctan‐2‐ylphosphonate) with acryloyl chloride followed by the hydrolysis of phosphonate groups by using trimethylsilyl bromide. The properties such as pH in the range of mild self‐etching adhesives, hydrolytic stability, high rate of copolymerizations with 2‐hydroxyethyl methacrylate (HEMA) and HEMA/glycerol dimethacrylate, giving high‐molecular‐weight polymers on thermal polymerization, and strong decalcification ability of hydroxyapatite make these monomers good candidates for self‐etching adhesives, although no appreciable effect of the number and size of the α‐substituents was observed. Hydrogel scaffolds containing phosphonic acid groups were fabricated, characterized, and mineralized. Altogether, the results suggest that these phosphonic acid‐containing monomers have suitable properties to be used in fabrication of biomaterials for both dental and bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2755–2767