- Functional bisphosphonate synthesis for the development of new anti-resorption bone drug candidates
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Herein we present the synthesis of β-mono and β-bis-substituted vinylidenebisphosphonate esters bearing a carboxylic ester moiety to be used as building blocks for further functionalizations. Reactions of these new bisphosphonate scaffolds through hydrogenation of the unsaturated CC bond and through metal mediated addition of aryl boronic acids and indoles provide a wide range of new bisphosphonate products as potential leads to contrast osteoporosis.
- Bortolamiol, Enrica,Chiminazzo, Andrea,Sperni, Laura,Borsato, Giuseppe,Fabris, Fabrizio,Scarso, Alessandro
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- Bisphosphonic Compounds. Part 3. Preparation and Identification of Tetraalkyl Methylene- and (α-Halomethylene)bisphosphonates by Mass Spectrometry, NMR Spectroscopy and X-Ray Crystallography
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The preparation and identification of tetraalkyl methylenebisphosphonates (XYC2; X = Y = H, Cl or Br and R = alkyl) have been studied.Detailed procedures are given for the synthesis of XYC2 (X = Y = H; R = hexyl; X = Y = Cl or Br and R = Me). 1H, 13C and 31P NMR data are reported including 1JCH, 2JCP', 3JCP and 2JPP coupling constants.The fragmentation of 19 XYC2 has been studied in the gas phase.The solid state structures are given for two compounds (X = Y = Cl, R = Pri and X = Y = Br, R = Me).
- Vepsaelaeinen, Jouko,Nupponen, Heikki,Pohjala, Esko,Ahlgren, Markku,Vainiotalo, Pirjo
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- One-Pot, Highly Regioselective 1,3-Dipole Cycloaddition Promoted by Montmorillonite for the Synthesis of Spiro[indole-pyrrolizine], Spiro[indole-indolizine], and Spiro[indole-pyrrolidine] gem -Bisphosphonates
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Various spiro[indole-pyrrolizine], spiro[indole-indolizine], and spiro[indole-pyrrolidine] gem-bisphosphonates were prepared by multicomponent reactions between isatins, tetraethyl vinylidenebis(phosphonate), and amino acids in the presence of montmorillonite. The one-pot reactions proceeded by 1,3-dipole cycloadditions of azomethine ylides formed in a decarboxylative manner. The proposed mechanism is in line with experimental data that confirmed that the azomethine ylide is formed in a decarboxylative manner; this provides new insight into the underlying mechanisms of such cycloadditions. The method has many notable features, such as a broad substrate scope, high efficiency, and high regioselectivity.
- Li, Guozhu,Wu, Mingshu,Liu, Fengjiao,Jiang, Jie
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- Improved preparation of diethyl bromomethylphosphonate and diiodomethane-catalyzed triethylphosphite Michaelis-Arbuzov isomerization
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An improved method to prepare diethyl bromomethylphosphonate and a new method for the isomerization of triethyl phosphite into diethyl ethylphosphonate are reported.
- Ezquerra,Yruretagoyena,Moreno-Manas,Roglans
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Read Online
- An efficient and facile access to substituted 1e,3e-dienylphosphonates via horner-wadsworth-emmons olefination of α,β-unsaturated aldehydes with tetraethyl methylenebisphosphonate
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An operationally simple and high-yielding synthetic method for 1E,3E-dienylphosphonates has been developed through the Horner-Wadsworth-Emmons olefination of α,β-unsaturated aldehydes with tetraethyl methylenebisphosphonate, in heterogeneous medium, in th
- Yahyaoui, Marwa,Touil, Soufiane,Samarat, Ali
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- Synthesis of novel phosphonated tripodal ligands for actinides chelation therapy
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Efficient synthetic routes for preparation of a new family of aldehyde-bisphosphonate conjugates were presented. These compounds appeared as promising intermediates for incorporation of bisphosphonate moiety in various substrates under mild conditions. We report here a first application to the synthesis of a series of three phosphonated tripods designed for actinides chelation therapy.
- Chaleix, Vincent,Lecouvey, Marc
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- One-pot alkylidenediphosphorylation of nucleophiles
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Direct phosphonylalkylidenephosphinylation of nucleophiles is achieved by one-pot mono dialkylphosphonoalkylation of dichlorophosphates or methylphosphonic dichloride followed, in situ, by nucleophilic substitution of the chlorine atom of the alkylidenediphosphorylated intermediate.
- Grison, Claude,Coutrot, Philippe,Joliez, Stephane,Balas, Laurence
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- Bisphosphonate units in the main polymer chain: The first synthesis
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Radical copolymerization of tetraethyl vinylidene phosphonate (B) with vinyl monomers has been described for the first time. In copolymerization with vinyl acetate (V) strictly alternating copolymer was formed even when [V] 0/[B]0 was equal to 80. In copolymerization with acrylic acid (A) copolymers of the general structure -[(B)1A x)]n- were formed. The number of A units (x) was shown to depend on the [A]0/[B]0 ratio in the monomers feed. The reactivity ratio rA was determined as equal to 2.1 and on this basis, the distribution of x as a function of [A]0/[B]0 was found. Bisphosphonic units were deblocked and the corresponding polyacids were analyzed by NMR spectra. Mn > 0.5 × 106 were measured by SEC for copolymers of B with A.
- Penczek, Stanislaw,Kaluzynski, Krzysztof,Pretula, Julia
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Two original acid derivatives of methylene diphosphonic acid (MDP) with two inequivalent phosphorus atoms have been synthesised: [(thiophosphonato)-methyl] phosphonic acid, (MDPS), and [(isopropylamido phosphonato)-methyl] phosphonic acid, (MDPN). A potentiometric study allowed to define the stoechiometry of the complex formed between MDP and magnesium (II) in alcaline medium and a 31P NMR study proved the dissymetric structure of this MDPMg2+ complex. The displacement of the coordination equilibrium between Black Eriochrome T and magnesium (II) permitted to compare the coordination strength of MDP, MDPS and MDPN with the cation Mg2+.
- Etienne,Rubini,Bessiere,Walcarius,Grison,Coutrot
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Read Online
- High yield synthesis of tetraethyl alkylenediphosphonates via the Michaelis-Arbuzov reaction
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A high-yield synthesis of tetraethyl alkylenediphosphonates was achieved via the Michaelis-Arbuzov reaction. Application of optimized reaction conditions for a series of homologous alkylenediphosphonates establishes the generality of the approach.
- Griffith, Julie A.,McCauley, David J.,Barrans Jr., Richard E.,Herlinger, Albert W.
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Read Online
- Challenging synthesis of bisphosphonate derivatives with reduced steric hindrance
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An alternative approach is reported for the synthesis of methyl ester protected bisphosphonate building blocks, such as methylene bisphosphonate, vinylidenebisphosphonate and aryl substituted prochiral vinylidenebisphosphonates, that cannot be obtained directly from dimethyl phosphite and dichloromethane.
- Chiminazzo, Andrea,Sperni, Laura,Fabris, Fabrizio,Scarso, Alessandro
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supporting information
(2021/04/12)
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- Modification of Amorphous Mesoporous Zirconia Nanoparticles with Bisphosphonic Acids: A Straightforward Approach for Tailoring the Surface Properties of the Nanoparticles
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The use of readily prepared bisphosphonic acids obtained in few steps through a thio-Michael addition of commercially available thiols on tetraethyl vinylidenebisphosphonate enables the straightforward surface modification of amorphous mesoporous zirconia nanoparticles. Simple stirring of the zirconia nanoparticles in a buffered aqueous solution of the proper bisphosphonic acid leads to the surface functionalization of the nanoparticles with different kinds of functional groups, charge and hydrophobic properties. Formation of both chemisorbed and physisorbed layers of the bisphosphonic acid take place, observing after extensive washing a grafting density of 1.1 molecules/nm2 with negligible release in neutral or acidic pH conditions, demonstrating stronger loading compared to monophosphonate derivatives. The modified nanoparticles were characterized by IR, XPS, ζ-potential analysis to investigate the loading of the bisphosphonic acid, FE-SEM to investigate the size and morphologies of the nanoparticles and 31P and 1H MAS NMR to investigate the coordination motif of the phosphonate units on the surface. All these analytical techniques demonstrated the strong affinity of the bisphosphonic moiety for the Zr(IV) metal centers. The functionalization with bisphosphonic acids represents a straightforward covalent approach for tailoring the superficial properties of zirconia nanoparticles, much straightforward compared the classic use of trisalkoxysilane or trichlorosilane reagents typically employed for the functionalization of silica and metal oxide nanoparticles. Extension of the use of bisphosphonates to other metal oxide nanoparticles is advisable.
- Hossain, Khohinur,Florean, Luca,Del Tedesco, Anna,Cattaruzza, Elti,Geppi, Marco,Borsacchi, Silvia,Canton, Patrizia,Benedetti, Alvise,Riello, Pietro,Scarso, Alessandro
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supporting information
p. 17941 - 17951
(2021/11/20)
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- C-Alkyl-bis-phosphoryl chelating systems for the potential recovery of strategic metals
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Methylene-bis-phosphonic acid and derivatives are used as complexing agents, diagnostics, therapeutics and show interesting virustatic properties. We describe the syntheses of mono- and di-substituted bisphosphonates and mono- and disubstituted diethyl ((diphenylphosphoryl)methyl)phosphonate as possible chelating systems for the recovery of strategic metals.
- Babouri, Rachida,Halidou Dougourikoye, Abdoul Razak,Ilagouma, Amadou TidJani,Pirat, Jean-Luc,Virieux, David,Volle, Jean-No?l
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- Diketopyrrolopyrrole Bis-Phosphonate Conjugate: A New Fluorescent Probe for In Vitro Bone Imaging
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The synthesis of a conjugate molecule between an unusual red-fluorescent diketopyrrolopyrrole (DPP) unit and a bis-phosphonate (BP) precursor by a click-chemistry strategy to target bone tissue and monitor the interaction is reported. After thorough investigation, conjugation through a triazole unit between a γ-azido rather than a β-azido BP and an alkyne-functionalized DPP fluorophore group turned out to be the winning strategy. Visualization of the DPP-BP conjugate on osteoclasts and specific antiresorption activity were successfully demonstrated.
- Chiminazzo, Andrea,Borsato, Giuseppe,Favero, Alessia,Fabbro, Chiara,McKenna, Charles E.,Dalle Carbonare, Luca Giuseppe,Valenti, Maria Teresa,Fabris, Fabrizio,Scarso, Alessandro
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supporting information
p. 3617 - 3626
(2019/02/19)
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- Tetraethyl n-tosyl-l-alanyloxyindole methyl methylene diphosphonate and preparation method thereof, impurities of Tenofovir and preparation method of impurities
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The invention provides tetraethyl n-tosyl-l-alanyloxyindole methyl methylene diphosphonate (formula I shown in the description) and a preparation method thereof, and belongs to the technical field ofchemical pharmacy. The invention further provides impurities of Tenofovir (formula II shown in the description) and a preparation method of the impurities. The impurities of Tenofovir as impurity comparison products are conducive to the quality control and safety of Tenofovir disoproxil fumarate bulk drugs and Tenofovir.
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Paragraph 0082; 0083; 0084; 0085
(2019/05/04)
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- Novel Easily Recyclable Bifunctional Phosphonic Acid Carrying Tripeptides for the Stereoselective Michael Addition of Aldehydes with Nitroalkenes
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A novel bifunctional organocatalyst library combining both aminocatalysis and phosphonic acid activation was used for the first time as an efficient tool for the stereoselective Michael addition of aldehydes with several aromatic nitroalkenes with good selectivities up to 95:5 dr and 93:7 er. Due to their high water solubility, the catalysts were easily recyclable and could be reused over several cycles without any significant loss of selectivity.
- Cortes-Clerget, Margery,Gager, Olivier,Monteil, Maelle,Pirat, Jean-Luc,Migianu-Griffoni, Evelyne,Deschamp, Julia,Lecouvey, Marc
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supporting information
p. 34 - 40
(2016/01/25)
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- A catalytic Michael/Horner-Wadsworth-Emmons cascade reaction for enantioselective synthesis of thiochromenes
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A catalytic enantioselective sulfa-Michael/Horner-Wadsworth-Emmons reaction cascade has been developed, taking advantage of phosphonate as an electrophilic activator and a traceless binding site. Using a chiral bifunctional urea derivative as the catalyst, a variety of aryl and heteroaryl substituted thiochromenes was obtained in excellent yield with a high level of enantioselectivity. Copyright
- Choudhury, Abhijnan Ray,Mukherjee, Santanu
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supporting information
p. 1989 - 1995
(2013/08/23)
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- Efficient synthesis of isoxazolidine-substituted bisphosphonates by 1,3-dipolar cycloaddition reactions
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Several bisphosphonates bearing a substituted isoxazolidine ring have been synthesized in good yield by direct 1,3-dipolar cyclization reaction, under microwaves catalysis, in the absence of solvent. The method allows the simultaneous incorporation, on the geminal position of the bisphosphonate framework, of a basic nitrogen and of an oxygen atom, as third hook. Hydrophobicity-hydrophilicity of BPs is discussed with the help of distribution coefficients.
- Bortolini,Mulani,De Nino,Maiuolo,Nardi,Russo,Avnet
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experimental part
p. 5635 - 5641
(2011/08/22)
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- Microwave michaelis-becker synthesis of diethyl phosphonates, tetraethyl diphosphonates, and their total or partial dealkylation
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Diethyl phosphonates and tetraethyl alkyldiphosphonates were efficiently and rapidly prepared via the Michaelis-Becker reaction, under microwave irradiation. These compounds were then hydrolyzed to phosphonic and diphosphonic acids or selectively monodealkylated to give monoesters of phosphonic acids and symmetrical diethyl esters of diphosphonic acids. These reactions were also achieved rapidly in satisfactory yields with microwave methodology. This methodology was applied with success to the functionalization of a polymer resin.
- Meziane, Dalila,Hardouin, Julie,Elias, Abdelhamid,Guenin, Erwann,Lecouvey, Marc
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experimental part
p. 369 - 377
(2010/07/16)
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- Synthesis of methylene bisphosphonates from carbon disulfide and phosphites via desulfurization: A mechanistic study
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The reaction of carbon disulfide with an excess of sodium dialkylphosphite in an aprotic solvent led to the formation of the carbanion of methylene bisphosphonate and sodium thiophosphate. The mechanistic study of this unexpected reaction, using both 31P
- Heuze,Lemarie,Vazeux,Gulea,Masson,Sene,Jaffres,Alberti,MacCiantelli
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experimental part
p. 820 - 829
(2009/12/03)
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- Enantioselective organocatalytic conjugate addition of aldehydes to vinyl sulfones and vinyl phosphonates as challenging michael acceptors
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Chiral amines with a pyrrolidine framework catalyze the enantioselective conjugate addition of a broad range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to >99% ee. This novel process provides synthetically useful chiral γ-gem-sulfonyl or phosphonyl aldehydes which can be widely functionalized with retention of the enantiomeric excess. Mechanistic insights including DFT calculations are explored in detail.
- Sulzer-Mosse, Sarah,Alexakis, Alexandre,Mareda, Jiri,Bollot, Guillaume,Bernardinelli, Gerald,Filinchuk, Yaroslav
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supporting information; experimental part
p. 3204 - 3220
(2009/12/03)
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- Aminoalkylbis(phosphonates): Their complexation properties in solution and in the solid state
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Five geminal bis(phosphonates) containing an amino group in the α, γ or δ position of the carbon chain have been synthesised and their acid-base and complexation properties with Cu2+, Zn2+, Ca2+, Mg2+ and Na+ ions studied by potentiometry. Determination of the stability constants of the complexes with divalent metal ions is complicated by the formation of precipitates. The results of these studies show a negligible effect of the hydroxo group in the α position on the acid-base and complexation properties of the ligands. The presence of an amino group in the α position, however, decreases the basicity, which results in a lower complexation ability of the bis(phosphonates). The crystal structures of the three ligands with different degrees of protonation have also been determined. The structure of the triammonium salt of aminomethylbis(phosphonic acid) shows that the proton is bound to the nitrogen atom in monoprotonated species. The structure of the Cu2+ complex of pamidronate [(Cu2(H2pam) 2}·H2O]n shows the presence of dimeric units with a relatively short distance (2.99 A) between the metal centres. These units form a coordination polymeric chain. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Kubicek, Vojtech,Kotek, Jan,Hermann, Petr,Lukes, Ivan
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p. 333 - 344
(2007/10/03)
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- Complexes of (EtO)2P(O)CH2P(O)(OEt)2 with lanthanide nitrates
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The preparation of complexes of (EtO)2P(O)CH2P(O) (OEt)2 = L, with lanthanide nitrates is described. Stable complexes with composition LnL2(NO3)S can be isolated for Ln = La-Eu and fully characterised. For Ln = Gd-Lu solid compounds could not be isolated. Conductivity and 31P NMR spectroscopy indicate structural changes in solution between the lighter and heavier lanthanides and, whilst electrospray mass spectrometry confirms a dramatic difference in behaviour with complexes of the heavier lanthanides readily decomposing via loss of EtNO3, other experiments show that this does not occur under the conditions of complex formation. The single crystal X-ray structures for Ln = La and Sm show the nitrates and OEt groups to be in close proximity. The changes in spectroscopic properties correlate well with the difficulties in isolating the complexes of heavier metals, and are possibly due to the formation of dimeric complexes rather than loss of ethyl nitrate.
- Lees, Anthony M. J.,Kresinski, Roman A.,Platt, Andrew W. G.
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p. 1457 - 1463
(2007/10/03)
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- Synthesis of P-chiral enephosphonic acid derivatives
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An efficient and convenient synthesis of chiral enephosphonic acid derivatives (enephosphonates, enephosphonamides, enephosphinates) was reported by a two-step procedure involving alkylidenediphosphorylation of nucleophiles followed by a Horner-Emmons olefination. Depending on the selected strategy, the synthesis could be executed according to a one-pot or a twostep reaction sequence. Regioselectivity of Horner-Emmons reaction and 31P-NMR study of diphosphorylated anions were described.
- Grison, Claude,Comoy, Corinne,Chatenet, David,Coutrot, Philippe
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- Microwave irradiation in organophosphorus chemistry 1: The Michaelis-Arbuzov reaction
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A diverse series of phosphonate esters have been prepared using a domestic microwave oven. The microwave enhanced Michaelis-Arbuzov reaction shows remarkable rate acceleration under microwave irradiation and allows the facile synthesis, and in certain cases easy workup, of alkyl, α-substituted and aryl phosphonates.
- Kiddle, James J.,Gurley, Alison F.
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p. 195 - 205
(2007/10/03)
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- A new and efficient electrosynthesis of 2-substituted 1,1- cylopropanediylbis(phosphonates)
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Various 2-substituted cyclopropanediylbis(phosphonates) were easily and rapidly prepared under mild conditions in acetonitrile, by electrolysing tetraethyl dichloromethylbis(phosphonate) in the presence of Michael acceptors in a two-compartment cell. A particular mechanism was proposed in the case of methyl acrylate.
- Goumain, Sophie,Jubault, Philippe,Feasson, Christian,Collignon, Noel
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p. 1903 - 1906
(2007/10/03)
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- Synthesis of analogues of porphobilinogen
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Syntheses are described of several analogues of porphobilinogen intended as substrates and/or inhibitors of porphobilinogen deaminase (hydroxymethylbilane synthase). 2-Methylporphobilinogen 12 has been synthesised from α-methylpyrrole 6, whereas a phosphonate analogue 20 of porphobilinogen, 8,9-didehydroporphobilinogen 26 and 9-fluoroporphobilinogen 38 have all been made from the 1H-pyrrolo[2,3-c]pyridine 14. The best route to 38 avoids fluoroacrylate 28 because of loss of fluorine during reduction of the double bond.
- Leeper, Finian J.,Rock, Martin,Appleton, Diana
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p. 2633 - 2642
(2007/10/03)
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- Free radical desulfenylation and deselenylation of α-sulfur and α-seleno substituted phosphonates with the n-Bu3SnH/AIBN reagents system.
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Selestive desulfenylation and deselenylation of α-sulfur- and α-seleno-substituted phosphonates under free radical condition are described.Chemoselectivity and scope of title reaction were studied using phosphonates additionaly functionalized in the α-position alkyl, phenyl,ethoxy,chloro,carbonyl and sulfenyl groups.It was found the reduction of a halogen tolerates the presence of the sulfenyl group and the latter could be reduced in the presence of the sulfinyl and sulfonyl moieties.Moreover,one sulfenyl group was selectively removed from α-phosphoryl dithioacetals and the phenylsulphenyl group was reduced preferentially in the presence of the methylsulfenyl one. Key words:Desulfenylation,deselenylation,α-phosphoryl sulfides,α-phosphoryl selenides, tri-n-butyltinhydride,α,α-azaisobutyronitrile.
- Balczewski,Piotr
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p. 113 - 122
(2007/10/03)
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- Free radical reaction of α-haloalkylphosphonates with alkenes and alkynes: A new approach to modified phosphonates
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A new approach to the synthesis of phosphonates 3 functionalized in the α- and γ-phosphonate positions by alkyl, ethoxy, butoxy, acetoxy, acetyl and cyanide groups and allylphosphonate 6 is described. It is based on the radical reaction of α-halosubstituted phosphonates 1 (X = Cl, Br, I) with the terminally unsubstituted alkenes 2 (1-heptene, ethoxyethene, butoxyethene, acetoxyethene, acrylonitrile, methyl vinyl ketone) and alkyne 5 (hept-1-yne). The reaction involving the tin hydride method (Bu3SnH/AIBN) was more effective with alkenes than with alkynes (40-72% versus 20-30%). With electron-rich alkenes, chloro- and bromomethylphosphonates 1 (X = Cl, Br) gave higher yields than iodomethylphosphonate 1 (X = I). Diethyl methylphosphonate 4, as a reduction product of 1, accompanied 3 and 6 in the above reactions. The yield of 4 could be reduced by optimizing the reaction conditions.
- Balczewski,Mikolajczyk
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p. 392 - 396
(2007/10/02)
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- Synthesis and biological activities of (4,6-di-O-phosphonato-β-D-mannopyranosyl)methylphosphonate as an analogue of 1L-myo-inositol 1,4,5-trisphosphate
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The synthesis of the α and β anomers of the title compound (1) was accomplished from D-mannose.In the key step, the phosphonate analogues of the mannopyranosyl phosphates were prepared by a direct Wadsworth-Emmons condensation of a protected mannose derivative (8) with tetraethyl methylenebisphosphonate under two-phase conditions.In vitro bioassays have shown that the β-anomer (1a) is a potent inhibitor of Ins(1,4,5)P3 3- kinase and inhibits other enzymes.
- Chung, Sung-Kee,Moon, Sung-Hwan
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- Studies on organophosphorus compounds 68. A new and facile synthetic approach to alkylidenebisphosphonates
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Condensation of aldehydes with diethyl phosphite followed by sulfonylation of the α-hydroxy group formed with methanesulfonyl chloride and subsequent substitution by another molecule of diethylphosphite provides corresponding alkylidenebisphosphonates in one-pot procedure with good yield.
- Li, Chaozhong,Yuan, Chengye
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p. 1515 - 1516
(2007/10/02)
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- Bisphosphonic acid derivatives and their use
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The invention relates to novel methylene bisphosphonic acid derivatives carrying a styrene group attached to the methylene carbon. The novel compounds are useful e.g. for functionalizing polymers of styrene type, especially macroporous styrene polymers, by copolymerizing the novel derivative with styrene and optional crosslinking agents. The invention also provides for new crosslinking agents especially suitable for the said purpose.
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- PHOSPHONIC SYSTEMS. 6. DIETHL 2-METHYLPENTENYLPHOSPHONATES AS A MODEL FOR STUDIES OF THE STABILITY OF UNSATURATED PHOSPHONIC ESTERS
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The composition of a thermodynamically controlled mixture of diethyl esters of α,β and β,γ-unsaturated phosphonates was determined by NMR spectroscopy and gas chromatography.The location of the double bond is determined by alkyl substitution and by hyperconjugation, but not by the position of the phosphorus-containing group. Key Words: Alkenylphosphonates; prototropic equilibria.
- Belciug, M. P.,Modro, A. M.,Modro, T. A.,Rohwer, E. R.,Zwierzak, A.
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- A Cheap One-Pot Approach to Tetraethyl Methylenediphosphonate
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A cheap procedure for the preparation of tetraethyl methylenediphosphonate is described.
- Hormi, Osmo E.O.,Pajunen, Esko O.,Avall, Ann-Kristin C.,Pennanen, Paivi
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p. 1865 - 1867
(2007/10/02)
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- Anti-inflammatory products derived from methylene-diphosphonic acid, and process for their preparation
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The present invention relates to products of the formula STR1 where R1 is H or alkyl, n is an integer from 0 to 10, and R2 is chosen from amongst H, unsubstituted or substituted alkyl radicals, a STR2 a substituted or unsubstituted phenyl radical, a STR3 where X is oxygen or sulfur, or a heterocyclic radical with 5 or 6 members, which may or may not be fused to a benzene ring and R3 is H or OH. The present invention also relates to a process for the preparation of the products of the formula (I), and to the drugs, having in particular an anti-inflammatory effect, containing a product of the formula (I).
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- SYNTHESIS OF α-HALOGENATED METHANEDIPHOSPHONATES
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Methanediphosphonate (MDP) anions can exhibit anti-viral activity, inhibit bone resorption, and act as ligands in radiopharmaceuticals. α-Halo-substitution provides MDP derivatives (XYMPD, where X = H, F, Cl or Br; Y = F, Cl or Br) with modified acid-base, steric and other properties.These compounds are conveniently made from the corresponding α-halogenated XYMDP esters (RO)2P(O)CXYP(O)(OR)2.Detailed procedures are given for synthesis of R4XYMDP for R = Pri and X, Y = H, Cl; Cl, Cl; H, Br; Br, Br; F, Cl; F, Br and Cl, Br in 88-96percent yield; for R = Et and X, Y = H, Cl; Cl, Cl; H, Br; Br, Br and Cl, F in 81-94percent yield; and for R = Me and X, Y = Cl, Cl and Br, Br in 72-80percent yield.NMR data (1H, 31P,13C, (19F)) are presented for the products obtained.The XYMDP acids (X, Y = H, Cl; Cl, Cl; H, Br; Br, Br; F, Cl; F, Br and Cl, Br) were prepared by HCl hydrolysis of a corresponding ester and characterized as tris(dicyclohexylammonium) salts by elemental analyses and 31P NMR.
- McKenna, Charles E.,Khawli, Leslie A.,Ahmad, Wan-Yaacob,Pham, Phuong,Bongartz, Jean-Pierre
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- ALKYLIDENEDIPHOSPHONATES ET VINYLPHOSPHONATES: UNE DEMARCHE SYNTHETIQUE SELECTIVE PAR VOIE CARBANIONIQUE
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Phosphonoalkylation of acylchloro-phosphates or -phosphinates in the presence of excess lithium diisopropylamide leads to direct generation of lithiated methylenediphosphonate anions.This stable type of anion can be either protonated in acidic medium to provide tetrasubstituted methylenediphosphonate or alkylated.When aliphatic or aromatic aldehydes are added spontaneous formation of vinylphosphonates is observed.This process is a simple and convenient route to diphosphonic as well as to vinylphosphonic compounds.
- Teulade, Marie-Paule,Savignac, Philippe,Aboujaoude, Elie Elia,Lietge, Stephane,Collignon, Noel
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p. 283 - 300
(2007/10/02)
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- CONVERSION DIRECTE "IN SITU" DES ALKYL EN VINYLPHOSPHONATES.
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Phosphorus acyl chlorides phosphonoalkylation leads to the direct generation of alkylidenediphosphonates anions convertible into vinylphosphonates.
- Aboujaoude, E. Elia,Collignon, N.,Lietje S.
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p. 4435 - 4438
(2007/10/02)
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- α-Substituted Phosphonates. 39. Methane-diphosphonic Esters by U.V.-Induced Michaelis-Becker-Reaction
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Dibromomethane resp. chlorbromomethane reacts with sodium dialkyl phosphite in heptane-/liq.NH3 or in liq.NH3 by u.v. irradiation at low temperatures to give in good yields methane diphosphonic acid tetraalkylesters 1.In the same manner with sodium diethyl thionophosphite the corresponding methane-bisthiophosphonic acid tetraethylester 4 is obtained.
- Czekanski, T.,Gross, H.,Costisella, B.
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p. 537 - 544
(2007/10/02)
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- Cosmetic deodorant preparations containing alkane diphosphonic acid esters
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Alkane diphosphonic acid esters having the formula STR1 wherein R is a straight- or branched-chain alkyl radical having 1 to 6 carbon atoms; and n is an integer of 1 to 6 are deodorants in anhydrous cosmetic preparations for the suppression of body odor.
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