- Synthesis and selected reactions of 4-(Diethoxyphosphorylmethyl)-3-furoic acid
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Reduction of 4-(ethoxycarbonyl)-3-furoyl chloride with sodium borohydride in dioxane-DMF mixture leads to an ethyl 4-hydroxymethylfuran-3-carboxylate. The treatment of the latter with thionyl chloride at boiling yields the corresponding chloromethyl derivative. The obtained chloride reacts with one equivalent of sodium iodide in acetone at room temperature to form iodomethylfuran. Halomethylfurans synthesized are phosphorylated with sodium diethyl phosphite and triethyl phosphite to give ethyl 4- (diethoxyphosphorylmethyl)- 3-carboxylate. The hydrolysis of this substance with one equivalent of potassium hydroxide in ethanol gives the corresponding furoic acid. Treating this substance in succession with ethyl chloroformate and sodium azide yields furoyl azide which while heating in toluene undergoes rearrangement to phosphorus-containing 3- furylisocyanate. Heating the latter with a mixture of acetic acid and acetic anhydride gives N-[4- (diethoxyphosphorylmethyl) furyl-3]acetamide. 4-(Diethoxyphosphorylmethyl)-3- furoic acid reacts with thionyl chloride to form the corresponding furoyl chloride. Its reduction with sodium borohydride in dioxane-DMF mixture leads to the phosphorylated 3-furylmethanol. Aminomethylation of its acetate with dimethylmethyleneiminium chloride in acetonitrile does not proceed at the ring. Instead of that the unstable ester of 3-(dimethylamino) propionic acid and the phosphorylated 3-furylmethanol are formed. In slightly basic medium free Mannich base decomposed to give the starting acetate. Pleiades Publishing, Ltd., 2012.
- Pevzner
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Read Online
- Use of microwave irradiation for sugar and nucleoside phosphonates synthesis
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Sugar and nucleoside phosphonates have been prepared using a microwave-assisted reaction. The comparison of thermal and microwave experimental conditions of the Michaelis-Arbuzov reaction is reported.
- Peyrottes, Suzanne,Gallier, Franck,Béjaud, Jér?me,Périgaud, Christian
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Read Online
- Synthesis and reactions of 3,3-difluoroallylphosphonates and 3,3-difluoroallyltriphenylphosphonium bromide
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3,3-Difluoroallyltriphenylphosphonium bromide (1) and 3,3-difluoroallylphosphonates, 2, have been prepared by the reaction of CH2=CHCF2Br with phosphites or triphenylphosphine in good yield.Wittig reaction of 1 with aldehydes gave the corresponding dienes (ArCH=CHCH=CF2) 4; however, Wadsworth-Emmons reaction of 2 with aldehydes failed to produce the dienes.
- Qiu, Weiming,Burton, Donald J.
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Read Online
- Intensified Continuous Flow Michaelis-Arbuzov Rearrangement toward Alkyl Phosphonates
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Herein is described the development of an intensified continuous flow process for the preparation of a library of alkyl phosphonates through a Michaelis-Arbuzov rearrangement. A careful process optimization and thorough analysis of the competitive reactions led to a very attractive protocol with unprecedented productivities (up to 4.97 kg of material per day) and a low environmental footprint with the absence of solvent, additives, catalysts, and waste. In-line low-field 31P NMR monitoring was conveniently implemented for rapid optimization and process monitoring. Two key alkyl phosphonate intermediates were also assessed for the unprecedented diazene dicarboxylate-mediated electrophilic amination under continuous flow conditions toward the α-aminophosphonic acid derivatives of Pphenylalanine and Palanine, bioisosters of the natural amino acids phenylalanine and alanine, respectively.
- Monbaliu, Jean-Christophe M.,Toupy, Thomas
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supporting information
p. 467 - 478
(2022/02/25)
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- Selective esterification of phosphonic acids
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Here, we report straightforward and selective synthetic procedures for mono-and diesteri-fication of phosphonic acids. A series of alkoxy group donors were studied and triethyl orthoacetate was found to be the best reagent as well as a solvent for the performed transformations. An important temperature effect on the reaction course was discovered. Depending on the reaction temperature, mono-or diethyl esters of phosphonic acid were obtained exclusively with decent yields. The sub-strate scope of the proposed methodology was verified on aromatic as well as aliphatic phosphonic acids. The designed method can be successfully applied for small-and large-scale experiments without significant loss of selectivity or reaction yield. Several devoted experiments were performed to give insight into the reaction mechanism. At 30?C, monoesters are formed via an intermediate (1,1-diethoxyethyl ester of phosphonic acid). At higher temperatures, similar intermediate forms give diesters or stable and detectable pyrophosphonates which were also consumed to give diesters.31P NMR spectroscopy was used to assign the structure of pyrophosphonate as well as to monitor the reaction course. No need for additional reagents and good accessibility and straightforward purification are the important aspects of the developed protocols.
- Brodzka, Anna,Koszelewski, Dominik,Ostaszewski, Ryszard,Trzepizur, Damian
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- Microwave-assisted ionic liquid-catalyzed selective monoesterification of alkylphosphonic acids—an experimental and a theoretical study
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It is well-known that the P-acids including phosphonic acids resist undergoing direct es-terification. However, it was found that a series of alkylphoshonic acids could be involved in mo-noesterification with C2–C4 alcohols under microwave (MW) irradiation in the presence of [bmim][BF4] as an additive. The selectivity amounted to 80–98%, while the isolated yields fell in the range of 61–79%. The method developed is a green method for P-acid esterification. DFT calculations at the M062X/6–311+G (d,p) level of theory (performed considering the solvent effect of the corresponding alcohol) explored the three-step mechanism, and justified a higher enthalpy of activation (160.6–194.1 kJ·mol–1) that may be overcome only by MW irradiation. The major role of the [bmim][BF4] additive is to increase the absorption of MW energy. The specific chemical role of the [BF4] anion of the ionic liquid in an alternative mechanism was also raised by the computations.
- ábrányi-Balogh, Péter,Drahos, László,Harsági, Nikoletta,Henyecz, Réka,Keglevich, Gy?rgy
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- Preparation method of phosphorus flame retardant diethyl ethylphosphonate
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The invention provides a preparation method of a phosphorus-based flame retardant diethyl ethylphosphonate, and the method comprises the following steps: mixing phosphorus trichloride, organic amine and petroleum ether, dropwisely adding absolute ethyl alcohol, and carrying out heat preservation reaction to obtain diethyl ethylphosphonate after the reaction is finished. The method is low in reaction temperature, short in reaction time and low in raw material cost, so that compared with the prior art, the method has the advantages of low energy consumption and low production cost.
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Paragraph 0018-0021
(2020/04/22)
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- METHOD FOR PRODUCING ORGANOPHOSPHORUS COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing an organophosphorus compound which has excellent energy efficiency without containing a halogenated alkyl or a by-product derived from a halogenated alkyl. SOLUTION: There is provided a method for producing an organophosphorus compound by reacting a trivalent organophosphorus compound represented by the following general formula (1) in the presence of a super strong acid and/or at least one acid catalyst containing a solid superstrong acid catalyst to generate a pentavalent organophosphorus compound represented by the following general formula. (where Z1 represents OR2 or R2; Z2 represents OR3 or R3; R1, R2 and R3 represent an alkyl group, an alkenyl group or the like; when R2 and R3 are an alkyl group or the like, R2 and R3 may be bonded to each other to form a cyclic structure; and R1 may be a hydrogen atom.) SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0044; 0056-0068; 0079-0081
(2020/05/02)
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- Solvent-Free Michaelis-Arbuzov Rearrangement under Flow Conditions
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The first solvent- and catalyst-free procedure for the Michaelis-Arbuzov reaction under flow conditions was developed. A variety of alkylphosphonic esters could be obtained using this protocol starting from the corresponding trialkyl phosphites and even catalytic amounts of alkyl halides with very short reaction times (8.33-50 min) and excellent conversions. In general, this protocol works effectively when the alkyl halide is used in catalytic amounts as low as 5-10% only if it concerns the synthesis of homo alkylphosphonates. One equivalent and an excess of alkyl halides should be used in the reaction with alkyl phosphite if the alkyl group of the selected substrates differ. Thus, it provides a sustainable, fast alternative to the existing methods for the preparation of alkylphosphonates. The isolation of the reaction products is straightforward due to the lack of solvents and a high purity of the obtained products (conv ≥ 99%), and notably, in the catalytic procedures there are only traces of alkyl halides formed after the reaction is complete. The reactions conducted using a glass microreactor chip with an internal volume of 250 μL allow the production of 1.6-1.95 g of organophosphorus esters per hour.
- Jasiak, Aleksandra,Mielniczak, Grazyna,Owsianik, Krzysztof,Koprowski, Marek,Krasowska, Dorota,Drabowicz, Józef
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p. 2619 - 2625
(2019/02/26)
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- ZWITTERIONIC NANOPARTICLES
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The present invention relates to a zwitterionic nanoparticle, the zwitterionic nanoparticle comprising at least one nanoparticle and a zwitterionic case enclosing the nanoparticle. Furthermore, the present invention relates to a composition, a method of binding a zwitterionic nanoparticle and the use of a zwitterionic nanoparticle.
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Paragraph 0191-0202
(2019/12/24)
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- Water determines the products: An unexpected Br?nsted acid-catalyzed PO-R cleavage of P(iii) esters selectively producing P(O)-H and P(O)-R compounds
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Water is found able to determine the selectivity of Br?nsted acid-catalyzed C-O cleavage reactions of trialkyl phosphites: with water, the reaction quickly takes place at room temperature to afford quantitative yields of H-phosphonates; without water, the reaction selectively affords alkylphosphonates in high yields, providing a novel halide-free alternative to the famous Michaelis-Arbuzov reaction. This method is general as it can be readily extended to phosphonites and phosphinites and a large scale reaction with much lower loading of the catalyst, enabling a simple, efficient, and practical preparation of the corresponding organophosphorus compounds. Experimental findings in control reactions and substrate extension as well as preliminary theoretical calculation of the possible transition states all suggest that the monomolecular mechanism is preferred.
- Li, Chunya,Wang, Qi,Zhang, Jian-Qiu,Ye, Jingjing,Xie, Ju,Xu, Qing,Han, Li-Biao
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supporting information
p. 2916 - 2922
(2019/06/18)
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- Alcohol-based Michaelis-Arbuzov reaction: An efficient and environmentally-benign method for C-P(O) bond formation
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The famous Michaelis-Arbuzov reaction is extensively used both in the laboratory and industry to manufacture tons of widely-used organophosphoryl compounds every year. However, this method and the modified Michaelis-Arbuzov reactions developed recently still have some limitations. We now report a new alcohol-version of the Michaelis-Arbuzov reaction that can provide an efficient and environmentally-benign method to address the problems of the known Michaelis-Arbuzov reactions. That is, a wide range of alcohols can readily react with phosphites, phosphonites, and phosphinites to give all the three kinds of phosphoryl compounds (phosphonates, phosphinates, and phosphine oxides) using an n-Bu4NI-catalyzed efficient C-P(O) bond formation reaction. This general method can also be easily scaled up and used for further synthetic transformations in one pot.
- Ma, Xiantao,Xu, Qing,Li, Huan,Su, Chenliang,Yu, Lei,Zhang, Xu,Cao, Hongen,Han, Li-Biao
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supporting information
p. 3408 - 3413
(2018/08/06)
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- Direct Aryloxylation/Alkyloxylation of Dialkyl Phosphonates for the Synthesis of Mixed Phosphonates
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A strategy for the direct functionalization strategy of inertial dialkyl phosphonates with hydroxy compounds to afford diverse mixed phosphonates with good yields and functional-group tolerance has been developed. Mechanistic investigations involving both NMR studies and DFT studies suggest that an unprecedented highly reactive PV species (phosphoryl pyridin-1-ium salt), a key intermediate for this new synthetic transformation, is generated in situ from dialkyl phosphonate in the presence of Tf2O/pyridine.
- Huang, Hai,Denne, Johanna,Yang, Chou-Hsun,Wang, Haobin,Kang, Jun Yong
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supporting information
p. 6624 - 6628
(2018/05/14)
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- Hydrophosphonylation of Alkynes with Trialkyl Phosphites Catalyzed by Nickel
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The use of simple and inexpensive NiCl2?6 H2O as a catalyst precursor for C?P bond formation in the presence of commercially available trialkyl phosphites (P(OR)3, R=Et, iPr, Bu, SiMe3) along with several alkynes is presented. Control experiments showed the in situ formation of (RO)2P(O)H as the species that undergo the addition into the C≡C bond at the alkynes to yield the product of P?H addition. The hydrophosphonylation of diphenylacetylene with P(OEt)3, P(OiPr)3, and P(OSiMe3)3 proceeds in high yields (>92 %) without the need of a specific solvent or ligand. This method is useful for the preparation of organophosphonates for both phenylacetylene as a terminal alkyne model and internal alkynes in yields that range from good to modest.
- Islas, Rosa E.,García, Juventino J.
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p. 4125 - 4131
(2017/10/09)
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- Synthesis method of glufosinate ammonium intermediate alkyl phosphodiester compound
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The invention discloses a synthesis method of a glufosinate ammonium intermediate alkyl phosphodiester compound. According to the method, phosphite trimester and halogenated hydrocarbon or alcohol or phenol are subjected to substitution reaction so as to obtain the glufosinate ammonium intermediate alkyl phosphodiester. The method takes phosphite trimester as the raw material to carry out substitution reaction with halogenated hydrocarbon or alcohol or phenol at certain temperature to obtain the corresponding product alkyl phosphodiester, and the product can be further prepared into glufosinate ammonium. The method changes the existing process of using methyl diethyl phosphite to prepare glufosinate ammonium, has the characteristics of low production cost, safety and environmental protection, and at the same time avoids the risk in the process of industrialization.
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Paragraph 0021; 0022
(2017/04/18)
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- Fragmentation-Related Phosphonylation of Nucleophiles Utilizing P-Alkyl 2,3-oxaphosphabicyclo[2.2.2]octene 3-oxide Precursors
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New P-alkyl 2,3-oxaphosphabicyclo-[2.2.2]octene 3-oxides were synthesized by the Bayer-Villiger oxidation of the corresponding 7-phosphanorbornene 7-oxides and were used as precursors for reactive alkylmetaphosphonates useful in the phosphonylation of alcohols. This is the first case that the reactivity of the two regioisomers formed by O-insertion was differentiated and that the fragmentation-related phosphonylation leading to phosphonic acid-esters was achieved under microwave-assisted conditions.
- Kovács, Tamara,Fül?p, Laura Szandra,Keglevich, Gy?rgy
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- Synthesis of ethyl 4,5-bis(diethoxyphosphorylmethyl)-3-furoate
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Preparative procedure for 4,5-bis(diethoxyphosphorylmethyl)-3-furoate from 4-chloromethyl-3-furoate is developed. It includes substitution of chlorine with iodine, phosphorylation by means of the Arbuzov reaction, chloromethylation of 4-(diethoxyphosphorylmethyl)-3-furoate in the position 5 of the furan ring, substitution of chlorine with iodine in the obtained chloromethyl derivative, and repeated phosphorylation with triethyl phosphite. It was found that ethyl 4-(diethoxyphosphorylmethyl)-5(chloromethyl)-3-furoate reacts with sodium diethyl phosphite by two pathways. Besides usual nucleophilic substitution leading to phosphonate, transfer of the reaction center in the position 2 of the furan ring takes place. The ambident diethylphosphite anion in this case reacts at the oxygen to give tertiary phosphite. The latter is oxidized with the air oxygen to form ethyl 2-(diethoxyphosphoryloxy)-4-(diethoxyphosphorylmethyl)-5-methyl-3-furoate. Unlike that analogous iodomethyl phosphonate is phosphorylated selectively under the conditions of the Arbuzov reaction.
- Pevzner
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- An optimized and scalable synthesis of propylphosphonic anhydride for general use
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Abstract Propylphosphonic anhydride (T3P) is an effective coupling and dehydrating agent, which has been used for a large number of chemical transformations. An efficient and versatile synthetic method is described to synthesize propylphosphonic anhydride (T3P) in pure form, in an overall yield of 51% in four steps from commercially available diethyl phosphonate.
- Pizova, Hana,Bobal, Pavel
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p. 2014 - 2017
(2015/03/30)
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- Direct conversion of phosphonates to phosphine oxides: An improved synthetic route to phosphines including the first synthesis of methyl JohnPhos
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The synthesis of tertiary phosphine oxides from phosphonates was achieved reliably and in good to excellent yields using stoichiometric amounts of alkyl or aryl Grignard reagents and sodium trifluoromethanesulfonate (NaOTf). In the absence of the NaOTf additive, covalent coordination oligomers of magnesium and phosphorus species dominate the reaction, producing very low yields of phosphine oxide, but high conversions of the phosphonate starting material. Mechanistic studies revealed that a five-coordinate phosphorus species - not a phosphinate - is the reaction intermediate. A diverse array of phosphonates was converted to phosphine oxides using a variety of Grignard reagents for direct carbon-phosphorus functionalization. This new methodology especially simplifies the synthesis of dimethylphosphino (RPMe2)-type phosphines by using air-, water-, and silica-stable intermediates. To highlight this reaction, a new Buchwald-type ligand ([1,1′-biphenyl]-2-yldimethylphosphine, or methyl JohnPhos) and a classic bidentate phosphine, bis(diphenylphosphino)propane (dppp), were synthesized in excellent yields.
- Kendall, Alexander J.,Salazar, Chase A.,Martino, Patrick F.,Tyler, David R.
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supporting information
p. 6171 - 6178
(2015/02/19)
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- Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1 inhibitors
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Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.
- Németh, Gábor,Greff, Zoltán,Sipos, Anna,Varga, Zoltán,Székely, Rita,Sebestyén, Mónika,Jászay, Zsuzsa,Béni, Szabolcs,Nemes, Zoltán,Pirat, Jean-Luc,Volle, Jean-No?l,Virieux, David,Gyuris, ágnes,Kelemenics, Katalin,áy, éva,Minarovits, Janos,Szathmary, Susan,Kéri, Gy?rgy,Orfi, László
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p. 3939 - 3965
(2014/06/09)
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- Mild and efficient esterification of alkylphosphonic acids using polymer-bound triphenylphosphine
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Mild and efficient esterification of alkylphosphonic acids using primary alcohols, iodine, imidazole and polymer-bound triphenylphosphine is developed.
- Purohit, Ajay Kumar,Pardasani, Deepak,Tak, Vijay,Kumar, Ajeet,Jain, Rajeev,Dubey, Devendra Kumar
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experimental part
p. 3795 - 3797
(2012/09/21)
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- Two-carbon homologation of aldehydes and ketones to α,β- unsaturated aldehydes
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Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β- unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2- phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.
- Petroski, Richard J.,Vermillion, Karl,Cosse, Allard A.
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experimental part
p. 5062 - 5078
(2011/08/21)
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- Molecular and supramolecular control of the work function of an inorganic electrode with self-assembled monolayer of umbrella-shaped fullerene derivatives
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The surface properties of inorganic substrates can be altered by coating with organic molecules, which may result in the improvement of the properties suitable for electronic or biological applications. This article reports a systematic experimental study on the influence of the molecular and supramolecular properties of umbrella-shaped penta(organo)[60]fullerene derivatives, and on the work function and the water contact angle of indium-tin oxide (ITO) and gold surfaces. We could relate these macroscopic characteristics to single-molecular level properties, such as ionization potential and molecular dipole. The results led us to conclude that the formation of a SAM of a polar compound generates an electronic field through intermolecular interaction of the molecular charges, and this field makes the overall dipole of the SAM much smaller than the one expected from the simple sum of the dipoles of all molecules in the SAM. This effect, which was called depolarization and previously discussed theoretically, is now quantitatively probed by experiments. The important physical properties in surface science such as work function, ionization potential, and water contact angles have been mutually correlated at the level of molecular structures and molecular orientations on the substrate surface. We also found that the SAMs on ITO and gold operate under the same principle except that the "push-back" effect operates specifically for gold. The study also illustrates the ability of the photoelectron yield spectroscopy technique to rapidly measure the work function of a SAM-covered substrate and the ionization potential value of a molecule on the surface.
- Lacher, Sebastian,Matsuo, Yutaka,Nakamura, Eiichi
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supporting information; experimental part
p. 16997 - 17004
(2011/12/13)
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- Efficient and 'green' microwave-assisted synthesis of haloalkylphosphonates via the Michaelis-Arbuzov reaction
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This paper deals with a novel, efficient and environmentally friendly synthesis of dialkyl haloalkylphosphonates via a microwave-assisted Michaelis-Arbuzov reaction. The approach is solventless, requires only one equivalent of each of the starting compounds, and provides high yields of pure products from which the impurities are easy to remove. The process has been optimised for batch and flow reactors and is especially profitable for the production of key intermediates in synthesis of Ethephon or acyclic nucleoside phosphonates such as adefovir, tenofovir, and cidofovir. The Royal Society of Chemistry.
- Jansa, Petr,Holy, Antonin,Dracinsky, Martin,Baszczynski, Ondrej,Cesnek, Michal,Janeba, Zlatko
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supporting information; experimental part
p. 882 - 888
(2011/06/20)
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- Dissection of complex molecular recognition interfaces
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The synthesis of a family of zinc porphyrins and pyridine ligands equipped with peripheral H-bonding functionality has provided access to a wide range of closely related supramolecular complexes featuring between zero and four intramolecular H-bonds. An automated UV/vis titration system was used to characterize 120 different complexes, and these data were used to construct a large of number of different chemical double mutant cycles to quantify the intramolecular H-bonding interactions. The results probe the quantitative structure-activity relationship that governs cooperativity in the assembly of complex molecular recognition interfaces. Specifically, variations in the chemical structures of the complexes have allowed us to change the supramolecular architecture, conformational flexibility, geometric complementarity, the number and nature of the H-bond interactions, and the overall stability of the complex. The free energy contributions from individual H-bonds are additive, and there is remarkably little variation with architecture in the effective molarity for the formation of intramolecular interactions. Intramolecular H-bonds are not observed in complexes where they are geometrically impossible, but there are no cases where excellent geometric complementarity leads to very high affinities. Similarly, changes in conformational flexibility seem to have limited impact on the values of effective molarity (EM). The major variation that was found for all of the 48 intramolecular interactions that were examined using double mutant cycles is that the values of EM for intramolecular carboxylate ester-phenol H-bonds (200 mM) are an order of magnitude larger than those found for phosphonate diester-phenol H-bonds (30 mM). The corresponding intermolecular phosphonate diester-phenol H-bonds are 2 orders of magnitude more stable than carboxylate ester-phenol H-bonds, and the large differences in EM may be due to some kind of compensation effect, where the stronger H-bond is harder to make, because it imposes tighter constraints on the geometry of the complex.
- Hunter, Christopher A.,Misuraca, Maria Cristina,Turega, Simon M.
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scheme or table
p. 582 - 594
(2011/04/16)
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- Synthesis of an analogue of the bisphosphonate drug Ibandronate for targeted drug-delivery therapeutic strategies
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An analogue of the bisphosphonate drug Ibandronate was prepared and coupled via a cleavable ester function to a bromoacetyl linker with specific reactivity for thiol groups. This compound should find useful applications in therapeutic strategies aiming to deliver bisphosphonate drugs specifically to cancer cells making use of proteins as vectors. The specific delivery of bisphosphonates to cancer cells instead of bone, the usual site of accumulation of these cytotoxic drugs, could greatly widen their therapeutic applications.
- Camper, Nicolas,Scott, Christopher J.,Migaud, Marie E.
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experimental part
p. 949 - 955
(2010/08/04)
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- Interaction of α,α-difluoroazides with trivalent phosphorus compounds and triphenylantimony
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α,α-Difluoroazides react with triphenylantimony and various compounds of trivalent phosphorus according to the oxidative fluorination scheme. In the case of trivalent phosphorus compound the primary products are phosphazenes, phosphazides or difluorophosphoranes that may undergo further transformations to the corresponding fluorine derivatives of pentavalent phosphorus. Pleiades Publishing, Ltd., 2010.
- Lermontov,Polivanova,Shkavrov
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experimental part
p. 1646 - 1651
(2011/02/18)
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- Room-temperature alternative to the arbuzov reaction: The reductive deoxygenation of Acyl phosphonates
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The reductive deoxygenation of acyl phosphonates using a Wolff-Kishner-like sequence is described. This transformation allows direct access to alkyl phosphonates from acyl phosphonates at room temperature. The method can be combined with acyl phosphonate synthesis into a one pot, four-step procedure for the conversion of carboxylic acids into alkyl phosphonates. The methodology works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazone-forming reactions.
- Kedrowski, Sean M. A.,Dougherty, Dennis A.
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supporting information; experimental part
p. 3990 - 3993
(2010/11/02)
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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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- Polyketide building blocks via diastereoselective nitrile oxide cycloadditions with homoallylic alcohols and monoprotected homoallylic diols
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A modular approach to δ2-isoxazolines, latent aldol adducts and polyketide building blocks, is reported. The magnesium-mediated, hydroxyl-directed method allows for the diastereoselective access to a wide variety of masked β-hydroxy ketones, starting from readily available aliphatic and aromatic oximes, homoallylic alcohols and monoprotected homoallylic diols. The utility of the prepared δ2-isoxazolines as polyketide building blocks is demonstrated by their ready conversion into the corresponding β-hydroxy ketones. The anti-diastereoselectivity of the reaction was established by derivatization, NOE studies and comparison of known compounds. A rationale for the observed diastereoselectivity is proposed.
- Lohse-Fraefel, Nina,Carreira, Erick M.
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supporting information; experimental part
p. 12065 - 12081
(2010/05/18)
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- Studies on the efficient generation of phosphorus-carbon bonds via a rearrangement of PIII esters catalysed by trimethylhalosilanes
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Halotrimethylsilanes Me3SiX (X = Br, I) catalyse rearrangements of tricoordinate phosphorus esters R′R″P-OR into the corresponding phosphoryl systems R′R″P(O)R. This provides a simple and efficient route to a variety of structures containing phosphorus-carbon bonds, under mild conditions and with good yields. The reaction mechanism was investigated in detail by 31P NMR spectroscopy and independent synthesis of the reaction intermediates. It has been demonstrated that the primary products of this catalytic reaction are halogeno PIII structures R′R″PX and silyl ethers ROSiMe3 and that they subsequently react to give the corresponding phosphorus silyl esters - Me 3SiOPR′R″-and alkyl halides RX. At higher temperatures these intermediates then react to form R′R″P(P)R compounds. This paper also features the surprising observation that when esters Ph 2POR and halotrimethylsilanes Me3SiX (X = Br, I) are used in 2:1 ratio, phosphonium salts Ph2R2P+X - and trimethylsilyl diphenylphosphinate - Ph2P(O) OSiMe3 - are formed as the major products. Experimental evidence indicates that the mechanisms of both reactions are fundamentally different from that of the Michaelis-Arbuzov reaction. Me3SiCl is not reactive and this paper explains why.
- Dabkowski, Wojciech,Ozarek, Alfred,Olejniczak, Sebastian,Cypryk, Marek,Chojnowski, Julian,Michalski, Jan
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experimental part
p. 1747 - 1756
(2009/09/25)
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- PROCESS FOR MAKING DIHYDROCARBYL HYDROCARBONPHOSPHONATES
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This invention provides a process for the preparation of a dihydrocarbyl hydrocarbonphosphonate. The process comprises forming a reaction mixture from components comprising (i) at least one dihydrocarbyl phosphite, (ii) at least one alkali metal hydrocarbyloxide, and (iii) at least one alcohol, so that a dihydrocarbyl hydrocarbonphosphonate is formed.
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Page/Page column 9
(2009/01/24)
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- Direct aldehyde homologation utilized to construct a conjugated-tetraene hydrocarbon insect pheromone
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New phosphonate reagents were developed for the two-carbon homologation of aldehydes to methyl-or ethyl-branched unsaturated aldehydes and used in the practical synthesis of (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8-undecatetraene (1), a pheromone of the beetle Carpophilus lugubris. The phosphonate reagents, diethyl ethylformyl-2-phosphonate dimethylhydrazone and diethyl 1-propylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of dilute HCl and petroleum ether. This robust two-step process replaces the standard three-step aldehyde homologation route using ester-based Horner-Wadsworth-Emmons reagents. The new synthesis of compound 1 from (2E)-2-methyl-2-butenal was run on a 10-g scale and required just five steps (two cycles of condensation and deprotection, followed by a final Wittig olefination) instead of the usual seven. In addition, the Wittig olefination step was simplified and its E-isomer selectivity was improved. The overall yield for the entire synthetic pathway was increased from 20% to 37%, enhancing the commercial potential of Carpophilus pheromones.
- Petroski, Richard J.,Bartelt, Robert J.
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p. 2282 - 2287
(2008/02/09)
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- Improvement of the synthesis of sugar phosphonates using microwave irradiations
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Sugar and nucleoside phosphonates have been prepared using a microwave-assisted reaction. Results concerning optimization of the reaction for various substrates as well as comparison of thermal and microwave experimental conditions of the Michaelis-Arbuzov reaction is reported. Copyright Taylor & Francis Group, LLC.
- Peyrottes, Suzanne,Gallier, Franck,Papillaud, Alain,Bejaud, Jerome,Perigaud, Christian
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p. 1513 - 1515
(2008/09/18)
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- P-Toluenesulfonic acid-Celite as a reagent for synthesis of esters of alkylphosphonic acids under solvent-free conditions
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The coupling reaction of alkylphosphonic acids and alcohols on the surface of p-toluenesulfonic acid-Celite under mild and solvent-free conditions gave the corresponding phosphonates in excellent yields. This method provides a useful rapid synthesis of phosphonates for use in the unambiguous identification of chemical warfare agents.
- Gupta, Arvind K.,Kumar, Rajesh,Dubey, Devendra K.,Kaushik
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p. 328 - 331
(2008/02/10)
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- Multicomponent synthesis of dihydropyrimidines and thiazines
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A broad range of differently substituted dihydropyrimidines and thiazines can be efficiently prepared by using a four-component reaction between phosphonates, nitriles, aldehydes, and iso(thio)cyanates. The scope and limitations of this multicomponent reaction are fully described. Variation of all four components has been investigated. The nitrile and aldehyde inputs can be varied extensively, but variation of the phosphonate input remains limited. An interesting rearrangement leading to phosphoramidates has been observed, Furthermore, the multicomponent reaction seems to be restricted to the use of isocyanates with strongly electron-withdrawing substituents, but an interesting additional exchange reaction under microwave conditions leads to dihydropyrimidines with less electron-withdrawing substituents at N3. In addition, a diastereoselective formation of dihydropyrimidines has been observed when using a chiral aldehyde as the input. Finally, by changing the isocyanate component to an isothiocyanate, thiazines are efficiently formed instead of the corresponding thio-dihydropyrimidines.
- Vugts, Danielle J.,Koningstein, Manoe M.,Schmitz, Rob F.,De Kanter, Frans J. J.,Groen, Marinus B.,Orru, Romano V. A.
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p. 7178 - 7189
(2007/10/03)
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- An efficient method for the esterification of phosphonic and phosphoric acids using silica chloride
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Silica chloride is used as an effective heterogeneous catalyst for the rapid esterification of alkyl/aryl phosphonic/phosphoric acids to their corresponding alkyl/aryl phosphonates/phosphates under mild conditions with quantitative yields.
- Sathe, Manisha,Gupta, Arvind K.,Kaushik
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p. 3107 - 3109
(2007/10/03)
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- Metallo-phosphorylation of alkenes: a highly regioselective reaction of zirconocene-alkene complexes with chlorophosphate
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Zirconocene-alkene complexes Cp2Zr(CH2{double bond, long}CHR) reacted with chlorophosphate to form zircono-ethylphosphonate with high regioselectivity, which is versatile and could be converted into various functionalized organophosphonates.
- Lai, Chunbo,Xi, Chanjuan,Chen, Weixuan,Hua, Ruimao
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p. 6295 - 6302
(2007/10/03)
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- Electrocatalytic eco-efficient functionalization of white phosphorus
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The novel eco-efficient methods to transform white phosphorus into the esters of phosphoric, phosphorous and phosphonic acids, tertiary phosphines and other organophosphorus compounds under conditions of electrochemical catalysis were elaborated. The mechanism of these processes was investigated using the method of cyclic voltammetry and preparative electrolysis.
- Budnikova, Yulia H.,Yakhvarov, Dmitry G.,Sinyashin, Oleg G.
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p. 2416 - 2425
(2007/10/03)
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- Surface-mediated solid phase reactions: A simple, efficient and base-free synthesis of phosphonates and phosphates on Al2O3
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Al2O3-supported solvent free condensation of alkylphosphonic dichlorides with alcohols at room temperature yielded phosphorus esters in excellent yields.
- Acharya, Jyotiranjan,Shakya, Purushottam D.,Pardasani, Deepak,Palit, Meehir,Dubey, Devendra K.,Gupta, Arvind K.
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p. 194 - 196
(2007/10/03)
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- FLUORINATED PHOSPHONIC ACIDS
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Fluorinated phosphonic acid compounds, useful as treatments for substrate surfaces, have the formula (I) : wherein: R?1? is a straight chain alkylene group having from 3 to 21 carbon atoms, an oxa-substituted straight chain alkylene group having from 2 to 20 carbon atoms, or a thia-substituted straight chain alkylene group having from 2 to 20 carbon atoms; R?2? is a perfluoroalkyl group having from 4 to 10 carbon atoms; R?3? is hydrogen, an alkali metal cation, or an alkyl group having from 1 to 6 carbon atoms; and M is hydrogen or an alkali metal cation, with the proviso that if R?1? is an unsubstituted straight chain alkylene group, then the sum of carbon atoms in R?1? and R?2? combined is at least 10.
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- Electrochemical synthesis of phosphorus esters from white phosphorus in the presence of copper complexes and ethanol
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In the presence of white phosphorus the redox potentials of the copper ions change and the potential of the reduction wave of CuI/Cu 0 shifts noticeably toward more positive values. The Cu I-P4 complex is characterized by a lower value of the electrochemical gap, that is, higher polarizability and reactivity compared to those of the free CuI cation. Phosphorus esters can be synthesized from P4 and ethanol. The latter is in the composition of the copper(II) complexes, which act as a catalyst-charge mediator.
- Budnikom,Kafiyatullina,Sinyashin,Abdreimova
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p. 929 - 938
(2007/10/03)
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- Reaction of 2,4-Difunctional Esters of 5-tert-Butylfuran-3-carboxylic Acid with Nucleophilic Reagents
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Ethyl 5-tert-butyl-4-(chloromethyl)-2-methylfuran-3-carboxylate was brominated with N-bromosuccinimide to obtain the corresponding 2-bromomethyl derivative. The latter is selectively phosphorylated with trimethyl and triethyl phosphites by the bromomethyl group. The resulting [4-(chloromethyl) furyl]methylphosphonates in the presence of secondary amines and sodium butanethiolate behave as alkylating agents, while sodium phenolate causes their decomposition. 4-Acetoxymethyl- and 4-phenoxymethyl derivatives of the starting product are also selectively brominated with N-bromosuccinimide by the 2-methyl group. The first of the 2-(bromomethyl)furans formed is smoothly phosphorylated with trimethyl phosphite, while the second one under the action of triethyl phosphite gives a mixture of phosphorylation and debromination products. In all the cases, an additional electron-acceptor group in position 4 of alkyl 2-(bromomethyl)-5-tert-butylfuran-3-carboxylate considerably accelerates the Arbuzov reaction.
- Pevzner
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p. 413 - 417
(2007/10/03)
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- Convenient one pot synthesis of phosphonites and H-phosphinates
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A convenient and simple one-pot method is described for the synthesis of phosphonites [RP(OEt)2, 1] and H-phosphinates [HP(O)R(OEt), 2] from triethyl phosphite and appropriate Grignard reagents.
- Petnehazy, Imre,Jaszay, Zsuzsa M.,Szabo, Andrea,Everaert, Kinga
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p. 1665 - 1674
(2007/10/03)
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- Studies toward the synthesis of α-fluorinated phosphonates via tin-mediated cleavage of α-fluoro-α-(pyrimidin-2-ylsulfonyl) alkylphosphonates. Intramolecular cyclization of the α-phosphonyl radicals
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Treatment of the α carbanions generated from several α-(pyrimidin-2-ylsulfonyl)alkylphosphonates with Selectfluor gave high yields of the α-fluoro-α-(pyrimidin-2-ylsulfonyl)alkylphoshonates, which were desulfonylated [Bu3SnH/2,2'-azobisisobutyronitrile (AIBN)/benzene or toluene/Δ to give α-fluoroalkylphosphonates. "Catalytic" tin hydride, generated from tributyltin chloride and excess polymethylhydrosiloxane in the presence of potassium fluoride, also effected removal of the π-deficient α-(pyrimidin-2-ylsulfonyl) group from the phosphonate esters. Substitution of Bu3SnD for Bu3SnH gave access to α-deuterium-labeled phosphonates. Prolonged treatment of α-(pyridin-2-ylsulfonyl)alkylphosphonate with excess Bu3SnH/AIBN or catalytic tin hydride also effected desulfonylation but in moderate yields. This represents a mild new methodology for removal of the synthetically useful π-deficient heterocyclic sulfone moiety and an alternative route for the preparation of α-fluorinated phosphonates. Desulfonylation is suggested to proceed via attack of tin radical at an oxygen (or sulfur) atom of the sulfonyl group to give a stabilized α-phosphonyl radical intermediate. The latter was found to undergo 5-exo-trig ring closure to give the corresponding 2-methylcyclopentylphosphonates. Treatment of diethyl 1-bromohex-6-enylphosphonate with Bu3SnH/AIBN produced an analogous mixture of ring-closure products. Treatment of [(2-bromo-5-methoxyphenyl)(fluoro)(pyrimidin-2-ylsulfonyl)]methylphosphonate with Bu3SnH resulted in an intramolecular radical [1,5]-ipso substitution reaction and migration of the pyrimidinyl ring to give fluoro[5-methoxy-2-(pyrimidin-2-yl)phenyllmethylphosphonate.
- Wnuk, Stanislaw F.,Bergolla, Luis A.,Garcia Jr., Pedro I.
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p. 3065 - 3071
(2007/10/03)
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This paper describes the synthesis and the characterization by 1H and 31P NMR of several monosalts and monoacids issued from phosphonates bearing alkyl groups (C1 to C18) or alkylene groups (allyl or vinyl). Functional compounds (alcohol or acetate) were also used and the results demonstrate the reaction selectivity. The method involves sodium iodide in ketones (acetone or 2-butanone) under reflux. It is very selective for monosalts, but only methyl phosphonates are very reactive. The corresponding acids were then obtained in quantitative yields with a cation exchange resin (sulfate acid).
- Boutevin,Hervaud,Jeanmaire,Boulahna,Elasri
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- Synthesis of 1H-1,3-benzazaphospholes: Substituent influence and mechanistical aspects
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Various substituted carboxylic acid 2-chloro- and 2-bromoanilides 1a-j react with triethylphosphite in the presence of anhydrous NiCl2 or NiBr2 to give o-acylamido-benzenephosphonic acid esters 2a-g and 2j. Yields depend strongly on the substituents. 2-Fluoro-4,6-dibromoacetanilide 1g reacts only at 6-position, indicating an o-directed process. Based on substituent effects, we infer a mechanism via Ni(0) intermediates that insert into the carbon-halogen bond. The N-tertiary 2-bromoformanilide 4 does not undergo phosphonylation to 5 in the presence of the Ni-catalyst but reacts in the presence of Pd-catalysts. The subsequent reduction of the N-secondary o-acylamido-benzenephosphonic acid esters 2 with excess LiAlH4 is coupled with an intramolecular cyclisation to the 1H-1,3-benzazaphospholes 6 whereas the N-tertiary derivative 5 does not undergo cyclisation upon reduction. NMR data and the crystal structure of 6d are reported.
- Heinicke, Joachim,Gupta, Nidhi,Surana, Anushka,Peulecke, Normen,Witt, Brigitte,Steinhauser, Kinga,Bansal, Raj K,Jones, Peter G
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p. 9963 - 9972
(2007/10/03)
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- Metallo-phosphorylation of olefins: Reaction of diethyl chlorophosphate with Zirconocene-ethylene complex
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Zirconocene-ethylene complex Cp2Zr (CH2 = CH2) reacted with chlorophosphate to form zircono-ethylphosphonate, which could be converted into various functionalized ethylphosphonates.
- Xi,Ma,Li
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p. 2554 - 2555
(2007/10/03)
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- Triethylborane-initiated room temperature radical addition of hypophosphites to olefins: Synthesis of monosubstituted phosphinic acids and esters
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A novel and practical approach to monosubstituted phosphinic acid (alkylphosphonous acid) derivatives from hypophosphite salts or esters is described. Phosphorus-centered radical formation is initiated with Et3B/O2, and the reaction is conveniently conducted at room temperature in an open flask. In contrast to previously reported conditions for the radical reaction of hypophosphorous acid and sodium hypophosphite (peroxide initiators, acid catalysis, heat), the method proceeds under neutral conditions and therefore tolerates a wide range of functional groups. Previously inaccessible phosphinic acids can be prepared in a single step from cheap starting materials. Excellent selectivity is observed for monoaddition, and symmetrical dialkyl phosphinates do not form in significant amounts. Monosubstituted phosphinic acids are usually obtained in better than 90% purity by a simple extractive workup; however, isolated yields are diminished if the substituent is polar. Because radicals derived from hypophosphites are electrophilic, the reaction is limited to the use of electron-rich olefins. The reaction conditions can also be employed in the room temperature radical reduction of alkyl halides and provide an exceptionally mild and environmentally friendly alternative to the use of tributyltin hydride. The remarkable mild nature of the reaction conditions allows for the radical reaction of sensitive alkyl hypophosphites to occur, in which case, a catalytic amount of Et3B suffices to deliver alkyl phosphinate esters in reasonable yield.
- Deprele,Montchamp
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p. 6745 - 6755
(2007/10/03)
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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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- Conjugate additions of 1-propenylphosphonates to metalated Schollkopf's bis-lactim ether: Stereocontrolled access to 2-amino-3-methyl-4- phosphonobutanoic acids
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Diastereoselectivity in the conjugate addition of metalated Schollkopf's bis-lactim ethers 5a-e to (E)- and (Z)-1-propenylphosphonates 4a,b was studied experimentally and theoretically and utilized to achieve a direct and stereocontrolled synthesis of all four diastereoisomers of 2-amino-3-methyl- 4-phosphonobutanoic acid, 6a,b and their enantiomers. The relative stereochemistry was assigned from an NMR study of cyclic derivatives 13a,b. According to semiempirical calculations, both in vacuo (PM3) or a dielectric continuum (PM3/COSMO), initial lithium-phosphoryl coordination, without an energy barrier, to form a solvated chelate complex is followed by the rate- determining reorganization to the 1,4-addition product through an eight- membered transition state. The translation of the Z,E geometry into a syn,anti configuration at the adducts originates from an orientational preference in the transition state for a compact disposition of the reaction partners.
- Ojea, Vicente,Ruiz, Maria,Shapiro, Gideon,Pombo-Villar, Esteban
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p. 1984 - 1995
(2007/10/03)
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