- 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.
- Jmai, Momtez,Efrit, Mohamed Lotfi,Dubreuil, Didier,Blot, Virginie,Lebreton, Jacques,M'rabet, Hédi
-
p. 978 - 995
(2021/08/06)
-
- Preparation method of diethyl p-toluenesulfonyloxymethylphosphonate
-
The invention relates to a preparation method of diethyl p-toluenesulfonyloxymethylphosphonate. The method comprises the following steps of under the protection of nitrogen, adding diethyl phosphite into a reaction container, then sequentially adding carbonate and tetrabutylammonium bromide, and dropwise adding a formaldehyde aqueous solution while stirring, continuously adding the carbonate and the formaldehyde aqueous solution in batches, after the reaction endpoint is reached, adding methylbenzene, adding paratoluensulfonyl chloride while stirring, and reacting, dropwise adding an alkali solution, after dropwise adding, keeping the temperature until the reaction end point, and standing, separating liquid, placing an upper-layer organic phase for later use, and extracting a lower-layer water phase with methylbenzene, and combining the two organic phases, adding a sodium chloride aqueous solution for washing, and concentrating an organic layer under reduced pressure to obtain a liquid product. Energy consumption does not need to be additionally increased in the reaction, so that frozen saline water required for cooling in the traditional process is abandoned, and the energy consumption is greatly reduced; compared with the traditional process with the step of about 85% of the yield, the yield is improved by 10-15%, the economic value of the product is greatly improved, and environmental protection is facilitated.
- -
-
Paragraph 0092-0096; 0106-0109; 0115-0118
(2021/07/17)
-
- An improved synthesis of adefovir and related analogues
-
An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach.
- Jones, David J.,O’Leary, Eileen M.,O’Sullivan, Timothy P.
-
supporting information
p. 801 - 810
(2019/04/17)
-
- Synthesis method of diethyl (tosyloxy)methylphosphonate
-
The invention discloses a synthesis method of diethyl (tosyloxy)methylphosphonate. The method takes diethyl phosphite, paraformaldehyde, paratoluensulfonyl chloride, inorganic base and the like as rawmaterials, and the product is obtained by carrying out carrying out aftertreatment operations such as aqueous phase condensation, an esterification two-step reaction and layering. The method has thecharacteristics of being enough in raw materials source, low in price, high in safety of synthetic process, high in product yield, less in pollution caused by three wastes, environmentally-friendly, and the like, thus having a higher industrial value.
- -
-
Paragraph 0027-0034
(2019/01/14)
-
- Preparation method of adefovir dipivoxil crystals
-
The invention belongs to the technical field of drug preparation and in particular relates to a preparation method of adefovir dipivoxil crystals. The preparation method comprises the following steps: synthesizing diethyl phosphite; synthesizing diethyl (p-phenylsulfonyloxy)methylphosphonate; synthesizing 9-(2-hydroxyethyl) adenine; synthesizing 4,9-[2-(diethylphosphonomethoxy)ethyl]adenine; synthesizing adefovir; synthesizing adefovir dipivoxil. Compared with the prior art, the preparation method of the adefovir dipivoxil crystals, provided by the invention, takes acetonitrile as a water-soluble organic medium, and the difficulty that DMF (Dimethyl Formamide) is difficult to remove is overcome; ethyl acetate is used for replacing isopropyl acetate in a previous process, isopropyl ether is used for replacing ethyl ether and ethanol is used for replacing acetone; the preparation method is simple to operate; the obtained product has good purity and high yield; the industrialized production is easy to realize and the production cost is reduced.
- -
-
Paragraph 0017-0019
(2017/07/21)
-
- Method of preparing tenofovir
-
The invention provides a method for preparing tenofovir. The method is characterized by comprising the following steps: 1) reacting 9-(2-hydroxy propyl) adenine with a compound as shown in the formula (1) in the specification in the presence of magnesium alkoxide to prepare tenofovir ethyl ester, wherein Y is selected from methyl, trifluoromethyl, phenyl or 4-trifluoromethylphenyl; 2) hydrolyzing the tenofovir ethyl ester in the presence of a dealkylation reagent to prepare tenofovir. The method for preparing tenofovir provided by the invention has the advantages of safe process, good product quality, high yield and suitability for industrialization.
- -
-
Paragraph 0055; 0056; 0057
(2017/08/25)
-
- A method for the synthesis of adenine derivative
-
The invention discloses the technical field of medicines and particularly discloses a new prodrug, namely (R)-9-(2-(phosphonyl methoxyl)propenyl) adenine, a cyclodextrin inclusion compound of the prodrug and a non-toxic and pharmaceutically acceptable salt of the prodrug. The prodrug disclosed by the invention can be metabolized into PMPA in vivo, and has the bioavailability of about 39%, and the bioavailability of the prodrug is better than that of tenofovir disoproxil fumarate (Bis-(POC)-PMPA); and the prodrug has more excellent antiviral activity and better safety compared with the tenofovir disoproxil fumarate.
- -
-
Paragraph 0016; 0019-0020
(2017/04/03)
-
- Wittig–Horner mediated synthesis of 4-vinyl sulfide derivatives of pyrazoles
-
The synthesis of a series of 4-vinyl sulfide derivatives of 1,3-diarylpyrazoles, including their corresponding sulfoxides and sulfones, is reported. Access to the target vinyl sulfides was stereoselectively achieved, in moderate to good yields, by the n-BuLi-mediated Wittig–Horner reaction of 4-formylpyrazoles with arylthiophosphonates and α-chloroarylthiophosphonates in dimethoxyethane. Their oxidation with H2O2in AcOH and mCPBA in CH2Cl2afforded satisfactory yields of the expected vinyl sulfoxides and vinyl sulfones, respectively. Enrichment in the more stable isomers during both oxidation processes was detected and a plausible general mechanistic explanation was given to these observations.
- Padilha, Gustavo,Kaufman, Teodoro S.,Silveira, Claudio C.
-
p. 3349 - 3353
(2016/07/12)
-
- Method of preparing tenofovir
-
The invention provides a method for preparing tenofovir. The method is characterized by comprising the following steps: 1) reacting 9-(2-hydroxy propyl) adenine with p-fluorobenzenesulfonyl diethyl methylphosphonite in the presence of magnesium alkoxide to prepare tenofovir ethyl ester; 2) hydrolyzing the tenofovir ethyl ester in the presence of a dealkylation reagent to prepare tenofovir. The method for preparing tenofovir provided by the invention has the advantages of safe process, good product quality, high yield and suitability for industrialization.
- -
-
Paragraph 0051; 0052
(2017/02/02)
-
- Diethyl p-toluenesulfonyloxy methylphosphonate synthesis method
-
The invention relates to the technical field of medicine, and specifically relates to a synthesis method of diethyl p-toluenesulfonyloxy methylphosphonate. The method comprises the following steps: (1) diethyl hydroxymethylphosphonate is synthesized, wherein diethyl phosphite, a solvent, a catalyst and paraformaldehyde are sequentially added into a reactor; heating is carried out and a reaction is allowed; filtering is carried out after the reaction; the solvent is removed through distillation, and the remaining substance is diethyl hydroxymethylphosphonate; and (2) diethyl p-toluenesulfonyloxy methylphosphonate is synthesized, wherein diethyl hydroxymethylphosphonate prepared in the step (1) is cooled; dichloromethane and p-toluenesulfonyl chloride are added; an acid binding agent is dropped in, and stirring is continuous for 1.5-2.5h after dropping; heating is carried out and a reaction is allowed; after the reaction, extraction, water washing and distillation are carried out, and the remaining substance is a crude product; and purification is carried out, such that a diethyl p-toluenesulfonyloxy methylphosphonate product is obtained. The method provided by the invention has the advantages of low energy consumption, simple product post treatment, high yield and high product purity. The yield can be higher than 80%. The purity can be higher than 99%.
- -
-
Paragraph 0033
(2016/11/07)
-
- Industrialization production technology for tenofovir disoproxil fumarate
-
The invention relates to an industrialization production technology for tenofovir disoproxil fumarate. The production technology comprises the following steps that firstly, R-1,2-polylene glycol, diethyl carbonate and sodium ethoxide are added into a reaction kettle; absolute ethyl alcohol and diethyl phosphite are added into the reaction kettle and stirred, paraformaldehyde and triethylamine are added after stirring is completed, after the complete reaction is achieved, anhydrous sodium sulfate is added, drying, filtering and steaming are carried out, and a steamed product is a diethyl p-toluenesulfonyloxymethylphosphonate fine product; adenine, R-propylene carbonate, DMF and NaOH are added into the reaction kettle, after the complete reaction is achieved, magnesium tert-butoxide is added, p-toluenesulfonyloxy phosphonate is dropwise added, after the complete reaction is achieved, acetic acid is added, vacuum concentration is carried out, hydrochloric acid is added, filtering is carried out, solids are filtered out and dried at the normal pressure, and a PMPA fine product is obtained. The industrialization production technology has the advantages of being high in yield and product purity, low in impurity content and capable of being completely applied to industrialization production.
- -
-
Paragraph 0012-0013
(2017/04/11)
-
- METHOD OF MAKING HYDROXYMETHYLPHOSPHONATE, POLYURETHANE FOAM-FORMING COMPOSITIONS, POLYURETHANE FOAM AND ARTICLES MADE THEREFROM
-
There is provided herein a method of making hydroxymethylphosphonate comprising reacting paraformaldehyde, at least one dialkyl phosphite and at least one trialkyl phosphite, in the presence of at least one amine catalyst.
- -
-
Page/Page column 18; 19
(2014/05/07)
-
- Copper-catalyzed synthesis of α-hydroxy phosphonates from H-phosphonates and alcohols or ethers
-
Easy PC: α-Hydroxy phosphonates were synthesized by copper/tert-butyl hydroperoxide (TBHP)-catalyzed oxidative addition reactions of H-phosphonates with alcohols or ethers. Diverse α-hydroxy phosphonates were obtained from substituted benzyl alcohols or alkyl alcohols and alkyl ethers in moderate to good yields. Copyright
- Zhao, Zengxiang,Xue, Wanhua,Gao, Yuxing,Tang, Guo,Zhao, Yufen
-
supporting information
p. 713 - 716
(2013/05/09)
-
- Novel dialkyl vinyl ether phosphonate monomers: Their synthesis and alternated radical copolymerizations with electron-accepting monomers
-
Three new vinyl ether monomers containing phosphonate moieties were synthesized from transetherification reaction. We showed that the yield was dependent on the spacer length between the vinyl oxy group and the phosphonate moieties: when the spacer is a single methylene side reaction may occur, leading to the formation of acetal compounds. Free-radical copolymerizations of phosphonate-containing vinyl ether monomers with maleic anhydride were carried out, leading to alternated copolymers of rather low molecular weights (from 1000 to 7000 g/mol). Both gel permeation chromatography and 31P NMR analyses enhanced possible intramolecular transfer reactions occurring from the phosphonate moieties. Kinetic investigation showed that the electron-withdrawing character of the phosphonate moieties tends to decrease the rate of copolymerization. Nevertheless, almost complete monomers conversion was reached after 30 min of reaction with dimethyl vinyloxyethylphosphonate (VEC 2PMe). Then, radical copolymerization of VEC2PMe with a series of electron-accepting monomers, that is, dibutyl maleate, dibutylitaconate, itaconic anhydride, butyl maleimide, and methyl maleimide, led to a series of alternated copolymers. From kinetic investigation, we showed that the higher the electron-accepting effect, the faster the vinyl ether consumption and the higher the molecular weights.
- Iftene, Fadela,David, Ghislain,Boutevin, Bernard,Auvergne, Remi,Alaaeddine, Ali,Meghabar, Rachid
-
experimental part
p. 2432 - 2443
(2012/07/28)
-
- METHOD OF MAKING HYDROXYMETHYLPHOSPHONATE, POLYURETHANE FOAM-FORMING COMPOSITIONS POLYURETHANE FOAM AND ARTICLES MADE THEREFORM
-
A method of making hydroxymethylphosphonate comprising heating paraformaldehyde in a solvent to a desired reaction temperature, wherein the solvent is present in at least an amount necessary to solvate or suspend the paraformaldehyde; adding at least one alkyl phosphite to the heated paraformaldehyde, to provide hydroxymethylphosphonate, the alkyl phosphite being added to the heated paraformaldehyde at a rate which will avoid or inhibit the production of a significant exotherm and resulting high/significant level of acid by-product(s), there being present in the reaction medium at least one hindered amine catalyst in which the nitrogen in the amine is directly bound to a secondary and/or tertiary carbon of an organic group; and, optionally, following the completion of the addition, heating the reaction mixture to an elevated temperature.
- -
-
Page/Page column 16
(2010/08/04)
-
- Method of making hydroxymethylphosphonate, polyurethane foam-forming compositions, polyurethane foam and articles made therefrom
-
A method of making hydroxymethylphosphonate comprising heating paraformaldehyde in a solvent to a desired reaction temperature, wherein the solvent is present in at least an amount necessary to solvate or suspend the paraformaldehyde; adding at least one alkyl phosphite to the heated paraformaldehyde, to provide hydroxymethylphosphonate, the alkyl phosphite being added to the heated paraformaldehyde at a rate which will avoid or inhibit the production of a significant exotherm and resulting high/significant level of acid by-product(s), there being present in the reaction medium at least one hindered amine catalyst in which the nitrogen in the amine is directly bound to a secondary and/or tertiary carbon of an organic group; and, optionally, following the completion of the addition, heating the reaction mixture to an elevated temperature.
- -
-
-
- Thermolyses of α-phosphorylmethyl tetrazolyl sulfoxides in the presence of 2,3-dimethyl-1,3-butadiene and their reactions with several amines
-
We have synthesized α-(phosphoryl)methyl tetrazolyl sulfoxides and examined the reactivities in the thermolyses and in the presence of several amines, such as aniline, benzylamine, piperidine, pyrrolidine, and morpholine. Thermolyses of the derivatives in the presence of 2,3-dimethyl-1,3-butadiene afforded 2-phosphoryl substituted 4,5-dimethyl-3,6-dihydro-2H-thiopyran S-oxide. In addition, novel phosphinecarbothioamides were obtained in the reaction of the derivatives with amines.
- Morita, Hiroyuki,Tashiro, Shintaro,Takeda, Masahiro,Fujimori, Ken,Yamada, Nobuhiko,Chanmiya Sheikh,Kawaguchi, Hiroyuki
-
p. 3589 - 3595
(2008/09/20)
-
- Synthesis, reactivity and stereochemistry of new phosphorus heterocycles with 5- or 6-membered rings
-
Syntheses of novel phosphorus heterocycles containing α-amino or α-hydroxyphosphonic or phosphinic acids motifs are developed. 2,3-dihydro-1,3-oxaphospholes (1) and 1,4,2-oxazaphosphinanes (2) exhibit a reactive part, respectively the enolether moiety and the P-H bond, which allows various structural modifications: (i) for 1a, by introduction of amino substituents, (ii) for 2a, by hydroxy- or aminoalkylation, by Michael addition or by P-arylation. These reactions present generally a good or even an excellent kinetic diastereoselectivity which can often be predicted by molecular models of the transition states.
- Cristau, Henri-Jean,Pirat, Jean-Luc,Virieux, David,Monbrun, Jér?me,Ciptadi, Ciptadi,Bekro, Yves-Alain
-
p. 2472 - 2481
(2007/10/03)
-
- Lanthanide(III) Complexes of Novel Mixed Carboxylic-Phosphorus Acid Derivatives of Diethylenetriamine: A Step towards More Efficient MRI Contrast Agents
-
Three novel phosphorus-containing analogues of H5DTPA (DTPA = diethylenetriaminepentaacetate) were synthesised (H6L1, H5L2, H5L3). These compounds have a -CH2-P(O)(OH)-R function (R = OH, Ph, CH2NBn2) attached to the central nitrogen atom of the diethylenetriamine backbone. An NMR study reveals that these ligands bind to lanthanide(III) ions in an octadentate fashion through the three nitrogen atoms, a P-O oxygen atom and four carboxylate oxygen atoms. The complexed ligand occurs in several enantiomeric forms due to the chirality of the central nitrogen atom and the phosphorus atom upon coordination. All lanthanide complexes studied have one coordinated water molecule. The residence times (τM 298) of the coordinated water molecules in the gadolinium(III) complexes of H6L1 and H5L2 are 88 and 92 ns, respectively, which are close to the optimum. This is particularly important upon covalent and noncovalent attachment of these Gd3+ chelates to polymers. The relaxivity of the complexes studied is further enhanced by the presence of at least two water molecules in the second coordination sphere of the Gd3+ ion, which are probably bound to the phosphonate/phosphinate moiety by hydrogen bonds. The complex [Gd(L 3)(H2O)]2- shows strong binding ability to HSA, and the adduct has a relaxivity comparable to MS-325 (40 s-1mM -1 at 40MHz, 37°C) even though it has a less favourable τM value (685 ns). Transmetallation experiments with Zn 2+ indicate that the complexes have a kinetic stability that is comparable to-or better than-those of [Gd(dtpa)(H2O)]2- and [Gd(dtpa-bma)(H2O)].
- Kotek, Jan,Lebduskova, Petra,Hermann, Petr,Vander Elst, Luce,Muller, Robert N.,Geraldes, Carlos F. G. C.,Maschmeyer, Thomas,Lukes, Ivan,Peters, Joop A.
-
p. 5899 - 5915
(2007/10/03)
-
- Synthesis of dialkyl-hydroxymethylphosphonates in heterogeneous conditions
-
This article describes the synthesis of a series of dialkyl-hydroxymethylphosphonates bearing various alkyl ester groups by the Pudovik reaction. The employed method uses anhydrous potassium carbonate as a catalyst in heterogeneous (solid/liquid) or mixed (solid/liquid and homogenous) conditions. All these syntheses are performed without any phase transfer agent and involve an anionic intermediate in a low polar or apolar solvent. These different products, obtained with high yields, have been characterised by 1H and 31P NMR and also by mass spectrometry. A study of fragmentation in the FAB ionisation process is given.
- Jeanmaire, Thomas,Hervaud, Yves,Boutevin, Bernard
-
p. 1137 - 1145
(2007/10/03)
-
- Synthesis of 2-phosphono alkyl 1,2-benzisoselenazol-3(2H)-ones
-
A series of 2-phosphonoalkyl 1,2-benzisoselenazol-3(2H)-ones were designed and synthesized via reaction 2-chloroselenobenzoyl chloride with 1-hydrazinobenzyl phosphonate. The structures of all new compounds were confirmed by spectroscopic methods and microanalyses.
- Hu, Liming,Lu, Shengmei,Yang, Fengling,Feng, Juhong,Liu, Zhaojie,Xu, Hansheng,He, Hongwu
-
p. 2785 - 2790
(2007/10/03)
-
- 2-Pyridylphosphonates: A new type of modification for nucleotide analogues
-
Suitably protected dithymidine H-phosphonates afforded the corresponding dinucleoside 2-pyridylphosphonates upon treatment with N-methoxypyridinium tosylate in acetonitrile in the presence of 1,8-diazabicylo[5.4.0]undec-7-ene (DBU). The reaction was rapid (ca. 5 min), practically quantitative and proceeded stereospecifically, most likely with retention of configuration at the phosphorus centre.
- Johansson, Tommy,Kers, Annika,Stawinski, Jacek
-
p. 2217 - 2220
(2007/10/03)
-
- α-Functionalized phosphonylphosphinates: Synthesis and evaluation as transcarbamoylase inhibitors
-
Diverse α-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.
- Flohr, Alexander,Aemissegger, Andreas,Hilvert, Donald
-
p. 2633 - 2640
(2007/10/03)
-
- Design and synthesis of macrocyclic ligands for specific interaction with crystalline ettringite and demonstration of a viable mechanism for the setting of cement
-
Cementitious materials are among those most widely used by mankind while being among the least well understood. The detailed physicochemical processes involved in the hydration and setting of cement slurries are very complex, and a clearly defined quantitative account is still lacking: indeed, even the composition of the cement powder itself is not known exactly. Still less has there been any understanding of the mechanism by which numerous known retarders of the cement setting process act. In this article, we detail the synthesis of novel macrocyclic organophosphonate retarders 1a and 2a which were developed by rational methods. Attempts to synthesise these compounds as phosphonate ester derivatives were universally unsuccessful, however direct modification of the parent hexaaza-(3) and trioxatriaza-18-crown-6 (5) derivatives was successful, to provide the phosphonic acids 1b and 2b respectively. Subsequent testing of these compounds showed their ability to inhibit the growth of crystalline ettringite and delay the setting of cement. These results support the hypothesis that the formation of crystalline ettringite is the rate determining step in the setting of cement.
- Griffin, Jonathan L. W.,Coveney, Peter V.,Whiting, Andrew,Davey, Roger
-
p. 1973 - 1981
(2007/10/03)
-
- Phosphonic acid-substituted benzazepinone-n-acetic acid derivatives process for their preparation and pharmaceutical compositions comprising them
-
Compounds having NEP-inhibitory activity, corresponding to the formula I in whichR 1 is hydrogen or a group forming a biolabile phosphonic acid ester,R 2 is hydrogen or a group forming a biolabile phosphonic acid ester and R. sup.3 is hydrogen or a group forming a biolabile carboxylic acid esterand physiologically acceptable salts of acids of formula I, and pharmaceutical compositions comprising these compounds.
- -
-
-
- Phosphosulfonate herbicides
-
This invention pertains to phosphosulfonates, having the general formula STR1 wherein Y is phenyl, naphthyl, benzyl, a (C5 -C8)cycloalkyl, a 5-membered heteroaromatic ring, a 6-membered heteraromatic ring, a fused 5,6-membered heteroaromatic ring, or a fused 6,6-membered heteroaromatic ring; and X is oxygen or sulfur; and R1 and R2 are each independently selected from substituted or unsubstituted alkyl, alkoxy, alkylthio, alkenyloxy, alkynyloxy, haloalkoxy, cyanoalkoxy, alkoxyalkoxy, cycloalkyloxy, cycloalkylalkoxy, alkylideneiminooxy, chloro, amino, phenyl or phenoxy; or R1 and R2 are both alkoxy, taken together with the phosphorus atom to form a 6-membered oxygen-containing ring; compositions containing these compounds and their use as herbicides.
- -
-
-
- Synthesis and Biological Activity of the Diphosphorylphosphonate Derivatives of (+)- and (-)-cis-9-(4'-hydroxycyclopent-2'-enyl)guanine
-
The carbovir triphosphate analogue 10 and its enantiomer 11 have been synthesized and tested as inhibitors of HIV-reverse transcriptase; the enantiomer 11, more remotely resembling natural nucleotides in stereochemical terms, is surprisingly the more active compound.
- Merlo, Valeria,Roberts, Stanley M.,Storer, Richard,Bethell, Richard C.
-
p. 1477 - 1482
(2007/10/02)
-
- Studies on organophosphorus compounds 68. A new and facile synthetic approach to alkylidenebisphosphonates
-
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
-
p. 1515 - 1516
(2007/10/02)
-
- Method for preparing a phosphonic acid ester
-
A method is provided for preparing a phosphonic acid ester having the structure STR1 wherein R1 is farnesyl or a derivative or analog thereof, and R2 is lower alkyl, by treating a farnesyl halide R1 Hal(Hal=Cl,Br,I) with an alkoxide of the structure STR2 wherein M is an alkali metal and R2c is lower alkyl. The resulting phosphonic acid ester is an intermediate in preparing a squalene synthetase inhibitor which is used for inhibiting cholesterol biosynthesis.
- -
-
-
- Phosphorus-containing squalene synthetase inhibitors
-
Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure STR1 wherein m is 0, 1, 2 or 3; n is 0, 1, 2, 3 or 4; Y1 and Y2 are H or halogen; R2, R3 and R4 may be the same or different and are independently H, metal ion, C1 to C8 alkyl or C3 to C12 alkenyl; X is O, S, NH or NCH2 R15 wherein R15 is H or C1 to C5 alkyl; and R1 is R5 --Q1 --Q2 --Q3 -- wherein R5, Q1, Q2 and Q3 are as defined herein; and when m is o, X is other than S; and if m is o and X is 0, then n is 1, 2, 3 or 4; including all stereoisomers thereof.
- -
-
-
- Phosphosulfonate herbicides
-
This invention pertains to phosphosulfonates, having the general formula STR1 wherein Y is phenyl, naphthyl, benzyl, a (C5 -C8)cycloalkyl, a 5-membered heteroaromatic ring, a 6-membered heteraromatic ring, a fused 5,6-membered heteroaromatic ring, or a fused 6,6-membered heteroaromatic ring; and X is oxygen or sulfur; and R1 and R2 are each independently selected from substituted or unsubstituted alkyl, alkoxy, alkylthio, alkenyloxy, alkynyloxy, haloalkoxy, cyanoalkoxy, alkoxyalkoxy, cycloalkyloxy, cycloalkylalkoxy, alkylideneiminooxy, chloro, amino, phenyl or phenoxy; or R1 and R2 are both alkoxy, taken together with the phosphorus atom to form a 6-membered oxygen-containing ring; compositions containing these compounds and their use as herbicides.
- -
-
-
- ORGANIC PHOSPHORUS COMPOUNDS 102. AMINOOXYALKYLPHOSPHONIC ACIDS AND DERIVATIVES
-
Condensation of α-hydroxyalkylphosphonates, 1, with N-hydroxy-phthalimide using Mitsunobu's condition yields 1-phthalimido-N-oxyalkylphosphonates, 2, which on treatment with hydrazine give 1-aminooxyalkylphosphonates, 3.Hydrolysis of these with HCl produces 1-aminooxyalkylphosphonic acids, 4, in good yields.The reactions of 3 with dinitrodiphenyl ether, isocyanides, aldehydes and ketones are also reported. 1-Aminooxy-2-phenylethylphosphonic acid, 4g, is only a weak inhibitor of PAL, but 4i is a good inhibitor of anthocyanin synthesis.4g exhibits weak antifungal activity (against Botrytis cinerea) and 5a and 5b show herbicidal activity against dicotyledonous weeds. Key words: 1-Aminooxyalkylphosphonates; 1-aminooxyalkylphosphonic acids; physical properties; NMR-spectra; biological activity.
- Maier, Ludwig,Spoerri, H.
-
-
- Phosphate and phosphonate compounds
-
There are disclosed novel phosphorous-containing compounds including and derived from hydrogen phosphonates. The compounds of the present invention can be prepared by reacting a hydrogen phosphonate with: (a) an ethylene derivative in a Michael reaction, (b) an amine or amide and formaldehyde in a Mannich reaction, (c) an aldehyde or ketone, (d) a halogen, (e) carbon tetrachloride and an alkylamine, and (f) carbon tetrachloride and a hydroxyphosphonate. Halophosphonates produced according to procedure (d) can also be used in reactions with (a) alkylamines and (b) hydroxyphosphonates or epoxides to produce the compounds of the present invention.
- -
-
-
- Phosphonate containing phosphonates
-
There are disclosed novel phosphorus-containing compounds including and derived from hydrogen phosphonates. The compounds of the present invention can be prepared by reacting a hydrogen phosphonate with: (a) an ethylene derivative in a Michael reaction, (b) an amine or amide and formaldehyde in a Mannich reaction, (c) an aldehyde or ketone, (d) a halogen, (e) carbon tetrachloride and an alkylamine, and (f) carbon tetrachloride and a hydroxyphosphonate. Halophosphonates produced according to procedure (d) can also be used in reactions with (a) alkylamines and (b) hydroxyphosphonates or epoxides to produce the compounds of the present invention.
- -
-
-
- Phosphate-containing and phosphonate-containing phosphate esters
-
There are disclosed multiphosphorus-containing compounds comprising phosphonate-containing or phosphate-containing phosphate esters. The compounds can be prepared by: (a) reacting a phosphonate-containing or phosphate-containing alcohol with phosphorus pentoxide following by reaction with an epoxide, (b) reacting a phosphonate-containing or phosphate-containing alcohol with a phosphorus oxyhalide, hydrolyzing any phosphorus halogen bonds and then reacting the resulting phosphoric acid derivative with an epoxide, (c) transesterifying a phosphonate-containing or phosphate-containing alcohol with a dialkyl phosphite, oxidizing the resulting compound to yield a phosphoric acid derivative and reacting the phosphoric acid derivative with an epoxide. The compounds are useful as flame retardant additives for polyurethanes and textiles.
- -
-
-
- SYNTHESIS AND REACTIVITY OF DIETHYL PHOSPHONOMETHYLTRIFLATE
-
Diethyl phosphonomethyltriflate, prepared from diethyl hydroxymethylphosphonate, readily reacts in good to excellent yields with a variety of oxygen and nitrogen nucleophiles.
- Phillion, Dennis P.,Andrew, Steven S.
-
p. 1477 - 1480
(2007/10/02)
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- PREPARATION OF 5'-O-PHOSPHONYLMETHYL ANALOGUES OF NUCLEOSIDE-5'-PHOSPHATES, 5'-DIPHOSPHATES AND 5'-TRIPHOSPHATES
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Reaction of a trialkyl phosphite (VI) or sodium salt of dialkyl phosphite (V) with bromomethyl acetate afforded dialkyl acetoxymethanephosphonates VII which were alcoholyzed to dialkyl hydroxymethanephosphonates VIII.Tosylation of the compounds VIII gave dialkyl p-toluenesulfonyloxymethanephosphonates IX which on reaction with 2',3'-O-isopropylideneribonucleosides (I), 2',3'-O-ethoxymethyleneribonucleosides (XI) or 3'-O-tetrahydropyranyl-2'-deoxyribonucleosides in the presence of sodium hydride, followed by acid hydrolysis, were converted into alkyl esters of 5'-O-phosphonylmethylnucleosides XII.Treatment of compounds XII with trimethylsilyl iodide led to 5'-O-phosphonylmethylnucleosides II and XIV.The ribo derivatives II were also obtained in low yields by reaction of compounds I with sodium chloromethanephosphonate in the presence of sodium hydride.Compound II reacted with morpholine in the presence of N,N'-dicyclohexylcarbodiimide to give morpholides XV which on treatment with phosphate afforded 5'-O-phosphorylphosphonylmethylribonucleosides XVI.Analogously, 5'-O-diphosphorylphosphonylmethylribonucleosides XVII were obtained from the derivatives XV by reaction with diphosphate.The compounds II are resistant towards E. coli alkaline phosphomonoesterase and snake venom and bull semen 5'-nucleotidase.E. coli alkaline phosphomonoesterase degrades the compounds XVI and XVII to compounds II and inorganic phosphate.
- Holy, Antonin,Rosenberg, Ivan
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p. 3447 - 3463
(2007/10/02)
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- Silyl Phosphites. XVIII. Versatile Utility of α-(Trimethylsilyloxy)-alkylphosphonates as Key Intermediates for Transformation of Aldehydes into Several Carbonyl Derivatives
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Carbonyl addition compounds of diethyl trimethylsilyl phosphite (DTMSP) with aldehydes were converted, by treatment with lithium diisopropylamide (LDA) followed by the successive alkylation and alkaline hydrolysis, to carbonyl derivatives involving aldehydes, unsymmetrical ketones, β,γ-unsaturated ketones, and carboxylic acids. β-Substituted carboxylic esters and γ-substituted lactones were prepared by use of the carbonyl addition compounds of DTMSP with α,β-unsaturated aldehydes.
- Sekine, Mitsuo,Nakajima, Masashi,Kume, Akiko,Hashizume, Akio,Hata, Tsujiaki
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p. 224 - 238
(2007/10/02)
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