Triethyl Phosphite Research Articles

ChemInform Abstract: Efficient One‐Pot Synthesis of β‐Hydroxyphosphonates: Regioselective Nucleophilic Ring Opening Reaction of Epoxides with Triethyl Phosphite Catalyzed by Al(OTf)3.

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An Efficient Synthesis and Antibacterial Screening of Novel Oxazepine α-Aminophosphonates by Ultrasound Approach

An efficient synthesis of novel α-aminophosphonates by the reaction of quino[2,3-b][1,5]benzoxazepines with triethyl phosphite in the presence of the easily available, inexpensive, and nontoxic catalyst p-toluene sulphonic acid (p-TSA). This method affords the α-aminophosphonates under the influence of ultrasound irradiation in solvent-free conditions, in short reaction times (4–6 min), high yields (80–90%), with improved purity. The synthesized α-aminophosphonates show antibacterial activity against Gram-positive and Gram-negative bacteria. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Microwave‐assisted Cadogan reaction for the synthesis of 2‐aryl‐2H‐indazoles, 2‐aryl‐1H‐benzimidazoles, 2‐carbonylindoles, carbazole, and phenazine

Abstract magnified image The Cadogan reaction, a widely accepted route for the synthesis of nitrogen containing heterocycles, is modified by using microwave radiation as the source of heat instead of the conventional heating by reflux in a nitrogen atmosphere for several hours. Appropriate starting materials were mixed with triethyl phosphite or triphenylphosphine and irradiated with microwaves for several minutes at a specific power to give the desired products. The indazoles were prepared by irradiating N‐(2‐nitrobenzylidene) anilines with triethyl phosphite at 200 W for 12–14 min to give 85–92% product yields. Irradiation of the mixture of N‐benzylidene‐2‐nitroanilines and triphenylphosphine at 200 W for 3–5 min yielded 93–96% of the benzimidazoles. The carbonylindoles were obtained in 61–68% yields by irradiating 2‐nitrochalcone or alkyl 2‐nitrocinnamates and triphenylphosphine with microwaves at 80–200 W for 8–11 min. The mixture of 2‐nitrobiphenyl and triphenylphosphine yielded 96% of carbazole when irradiated with microwaves at 200 W for 2 min while 75% of phenazine was obtained by irradiating the mixture of 2‐nitrodiphenylamine and triphenylphosphine with microwaves at 200 W for 3.5 min. These results show that microwave‐assisted Cadogan reactions gave better product yields at shorter reaction times. J. Heterocyclic Chem., (2009).

Synthesis of new β- and γ-aminopyrrolidinephosphonates via 1,3-dipolar cycloaddition of substituted vinylphosphonates

Synthesis of α- and β-(aminomethyl)vinylphosphonates was achieved from vinyl bromide via a cross-coupling reaction with triethyl phosphite and by cross-metathesis of allyl bromide and vinylphosphonate, respectively. The 1,3-dipolar cycloaddition of these vinylphosphonates with a dipole in the presence of trifluoroacetic acid afforded selectively the β-aminopyrrolidinephosphonates. Syntheses of cis- and trans-γ-aminopyrrolidinephosphonates are also described.

Phosphonylation of 2‐Amino‐ and 2‐Amido‐3‐bromopyridines and 2‐Amino‐3‐chloroquinoxalines with Triethyl Phosphite

AbstractThe Tavs reaction of 2‐amino‐ and 2‐acylamido‐3‐bromopyridines 1 and 2 with triethyl phosphite in the presence of palladium acetate or chloride allows the synthesis of 2‐amino‐ and 2‐acylamidopyridine‐3‐phosphonates 3 and 4. A second ring nitrogen atom causes strong activation and leads to excellent yields in the phosphonylation of 2‐amino‐3‐chloroquinoxalines. 2,3‐Dichloroquinoxaline does not need a catalyst and undergoes double phosphonylation with sodium diethyl phosphite under Michaelis–Becker conditions. The results show an activating influence of pyridine nitrogen (–M) and deactivating influence of the amino group (+M). The reactivity of 1 and 2 in the Tavs coupling is compared with that of the 3‐NH‐2‐bromopyridine position isomers and 2‐bromoanilines and discussed in terms of the opposite effects of pyridine and amino(amido) nitrogen and different position of the N atoms towards the reaction site. The advantage of the Tavs reaction is the easy optimization because neither auxiliary ligands are required nor a base to trap the halide or a solvent. Triethyl phosphite itself acts as ligand and forms Pd0{P(OEt)3}n in the initial phase of the reaction. The structures of the products and the expected intramolecular N–H···O=P hydrogen bridging bonds were proven by solution NMR and by X‐ray crystal structure analysis of single crystalline 3c.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Biomorphous porous hydroxyapatite-ceramics from rattan (Calamus Rotang)

The three-dimensional, highly oriented pore channel anatomy of native rattan (Calamus rotang) was used as a template to fabricate biomorphous hydroxyapatite (Ca(5)(PO(4))(3)OH) ceramics designed for bone regeneration scaffolds. A low viscous hydroxyapatite-sol was prepared from triethyl phosphite and calcium nitrate tetrahydrate and repeatedly vacuum infiltrated into the native template. The template was subsequently pyrolysed at 800 degrees C to form a biocarbon replica of the native tissue. Heat treatment at 1,300 degrees C in air atmosphere caused oxidation of the carbon skeleton and sintering of the hydroxyapatite. SEM analysis confirmed detailed replication of rattan anatomy. Porosity of the samples measured by mercury porosimetry showed a multimodal pore size distribution in the range of 300 nm to 300 microm. Phase composition was determined by XRD and FT-IR revealing hydroxyapatite as the dominant phase with minimum fractions of CaO and Ca(3)(PO(4))(2). The biomorphous scaffolds with a total porosity of 70-80% obtained a compressive strength of 3-5 MPa in axial direction and 1-2 MPa in radial direction of the pore channel orientation. Bending strength was determined in a coaxial double ring test resulting in a maximum bending strength of approximately 2 MPa.

Alum Catalyzed Convenient Synthesis of Quino[2,3-b][1,5 benzoxazepine α-Aminophosphonate Derivatives

We have described an efficient synthesis of quino[2,3-b][1,5]benzoxazepine α-aminophosphonate derivatives by the nucleophilic addition of triethyl phosphite to substituted quino[2,3-b][1,5]benzoxazepines promoted by easily available, inexpensive and mild catalyst KAl(S<TEX>$O_4)_2{\cdot}12H_2$</TEX>O(alum). The reactions proceed smoothly at room temperature under solvent-free reaction conditions and providing high yield of product in very short reaction time.

Experimental Chemotherapy againstTrypanosoma cruziInfection Using Ruthenium Nitric Oxide Donors

The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L]n+, where the ligand (L) is N-heterocyclic H2O, SO(3)(2-), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50try) and cytotoxicity data on mammalian V-79 cells (IC50V79), the in vitro therapeutic indices (TIs) (IC50V79/IC50try) for these compounds were calculated. Compounds that exhibited an in vitro TI of > or = 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50(try/epi) of < or = 100 microM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH3)4isn](BF4)3 (isn, isonicotinamide) and trans-[Ru(NO)(NH3)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD50) for both compounds are higher than 125 micromol/kg, the in vivo TIs (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(NH3)4isn](BF4)3 and 658 for trans-[Ru(NO)(NH3)4imN](BF4)3. Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi-glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

A Simple and Efficient Access to α-Amino Phosphonates from N-Benzyloxycarbonylamino Sulfones Using Indium(III) Chloride†Studies on Novel Synthetic Methodologies. 188.

Treatment of N-benzyloxycarbonylamino sulfones with triethyl phosphite catalyzed by InCl3 produces the corresponding protected alpha-amino phosphonates in high yields (71-92%).

Efficient one-pot synthesis of β-hydroxyphosphonates: regioselective nucleophilic ring opening reaction of epoxides with triethyl phosphite catalyzed by Al(OTf) 3

A variety of β-hydroxyphosphonates were produced in high yields by ring opening reaction of different types of epoxides with di/trialkyl phosphite esters catalyzed by Al(OTf) 3. The reactions proceeded with complete chemo- and regioselectivity to give the title compounds. This method is new, simple and efficient for the one-pot synthesis of β-hydroxyphosphonates via direct C–P bond formation.

Alum: An efficient catalyst for one-pot synthesis of α-aminophosphonates

Alum (KAl(SO 4) 2·12H 2O) is an inexpensive, efficient, non-toxic and mild catalyst for the one-pot synthesis of α-aminophosphonates. A three component reaction of an aldehyde/ketone, an amine and triethyl phosphite was carried out under solvent-free conditions to afford the corresponding α-aminophosphonates in short reaction times and high yields with the green aspects by avoiding toxic catalysts and solvents.

Synthesis of uracil nucleotide analogs with a modified, acyclic ribose moiety as P2Y 2 receptor antagonists

A series of new uracil nucleotide analogs (monophosphates, triphosphates, and phosphonates) was synthesized, in which the ribose moiety was replaced by acyclic chains, including branched or linear alkyl or dialkylether linkers. 1-ω-Bromoalkyluracil derivatives ( 2) were converted to the corresponding alcohols by treatment with sodium hydroxide and subsequently phosphorylated using phosphorus oxychloride followed by hydrolysis to yield the monophosphates, or by coupling with diphosphate to form the triphosphates. Reaction of 2 with triethyl phosphite followed by deprotection with trimethylsilyl bromide led to the ω-phosphonylalkyluracil derivatives. These products could be further phosphorylated by converting them into their imidazolides and subsequent treatment with diphosphate yielding the corresponding UTP analogs. Nucleoside analogs with an oxygen atom in the 2′-position, which are more similar to the natural ribosides, were synthesized from silylated uracil and trimethylsilyl iodide-treated 1,3-dioxolane, or 1,3-dioxane, respectively, and subsequently phosphorylated by standard procedures. The nucleotide analogs were investigated in a functional assay at NG108-15 cells, a neuroblastoma × glioma hybrid cell line which expresses the UTP- and ATP-activated nucleotide receptor subtype P2Y 2. The acyclic nucleotide analogs were generally weaker ligands than UTP, and—in contrast to UTP—they were antagonistic. The most potent compound was diphosphoric 5-(2,4-dioxo-3,4-dihydropyrimidin-1(2 H)-yl)pentylphosphonic anhydride ( 5c) with an IC 50 value of 92 μM showing that the replacement of the α-phosphate by phosphonate, which leads to enhanced stability, was well tolerated.

1-Benzyl-3-Methyl Imidazolium Hydrogen Sulphate [bnmim][HSO4] Promoted Synthesis of α-Aminophosphonates

We have demonstrated a one-pot three component coupling of an aldehydes, an amines, and triethyl phosphite using 1-benzyl-3-methyl imidazolium hydrogen sulphate [bnmim][][<TEX>$HSO_{4}$</TEX>] as an efficient catalyst. All the reactions proceed under solvent-free conditions at room temperature. This methodology afforded the corresponding <TEX>$\alpha$</TEX>-aminophosphonates in shorter reaction times with excellent yields.

An Efficient Synthesis of Tetraalkyl 2,3,4,5-Thiophenetetracarboxylate Derivatives

A facile and direct synthetic entry to tetraalkyl 2,3,4,5-thiophenetetracarboxylate derivatives is described. This involves the reaction of dialkyl acetylenedicarboxylates with elemental sulfur in the presence of triethyl phosphite or an N-heteroaromatic compound such as isoquinoline, 1-methyl-1H-imidazole, or pyridine as catalyst.

Regio-Controlled Michaelis-Arbuzov Reactions of 3-(halomethyl)-coumarins

3-(Iodomethyl)coumarins and 3-(chloromethyl)coumarins, obtained chemoselectively via Baylis–Hillman reactions of salicylaldehyde derivatives with t-butyl acrylate, can be reacted with triethyl phosphite to afford regioisomeric Michaelis-Arbuzov products. Under nitrogen, the 3-(iodomethyl)coumarins undergo direct displacement of iodide to afford the expected 1′-phosphonated derivatives. The reactions with 3-(chloromethyl)coumarins in air, however, proceed with overall allylic rearrangement to afford the regioisomeric 3-methyl-4-phosphonated derivatives.

Bioactive Hydroxyapatite Coating on Titanium-Niobium Alloy through a Sol-Gel Process

Hydroxyapatite (HA) was coated on the surface of a titanium-niobium (Ti-Nb) alloy by a sol-gel process. Triethyl phosphite and calcium nitrate were used as the phosphorus (P) and calcium (Ca) precursors respectively to prepare a Ca/P sol solution. The Ti-Nb alloy was dip-coated in the sol and heated at 600°C for 30 minutes. X-ray diffraction (XRD) analysis indicated the major phase constituent of the coating after heat treatment was HA. Scanning electron microscopy (SEM) observation showed that a few cracks were distributed on the HA coating. The in-vitro bioactivity of the HA coated Ti-Nb alloy was assessed using a cell culture of SaOS-2 osteoblast-like cells. The density of cell attachment was determined by MTT assay; the cell morphology was observed by SEM. Results indicated that the density of cell attachment on the surface of the Ti-Nb alloy was significantly increased by HA coating. Cell morphology observation showed that cells attached, spread and grew well on the HA coated surface. It can be concluded that the HA coating improved the in-vitro bioactivity of Ti-Nb alloy effectively.

Indium Trichloride Catalyzed One-Pot Synthesis of New (2-Amino-3-cyano-4H-chromen-4-yl) Phosphonic Acid Diethyl Ester

A one-pot synthesis of new (2-amino-3-cyano-4H-chromen-4-yl) phosphonic acid diethyl ester was achieved in good yields by indium trichloride catalyzed three-component reaction of salicylaldehyde and malononitrile with triethyl phosphite.

Reactions of β-aminovinyl bromodifluoromethyl ketones with alkyl phosphites: Perkow versus Arbuzov

New bromodifluoromethyl enaminones 1a–1f and γ-bromo-β-morpholinopropenyl fluoromethyl ketones 2a, 2b were synthesized. N-Substituted bromodifluoromethyl enaminones 1a–1d do not react with triethyl or diethyl phosphites, whereas N-acylated enaminones 1e, 1f gave difluorodienyl phosphates 4a, 4b as Perkow rearrangement products. Fluoroketone 2a reacts easily with triethyl phosphite according to the Arbuzov protocol and a perspective building block – trifluoromethyl-containing phosphonate 7a is formed.

On the reaction of 4-chloromethylene-2,6-di-tert-buthylcyclohexa- 2,5-dien-1-one with P(III) acids esters

Proceeding with investigations on reactions of organic halides with aprotic reagents [1, 2], we pioneered in studying reactions of 4-chloromethylene2,6-di-tert-butylcyclohexa-2,6-dien-1-one I (chloromethylenequinone) with P(III) acids esters, such as triethyl phosphite IIа and ethyl diphenylphosphinite IIb. Phosphorylated ylides VII were established to be the main products of the reaction of chloromethylenequinone I with esters II in a 1:2 ratio. We suppose that ylide VII is formed by the following two-stage scheme: DOI: 10.1134/S1070363209010307

Ethyl 3,7-dichloroquinoline-8-carboxylate

The title compound, C12H9Cl2NO2, was prepared by the esterification of 3,7-dichloro­quinoline-8-carboxylic acid with triethyl phosphite. The crystal structure is stabilized by aromatic π–π stacking between the benzene and the pyridine rings of neighbouring mol­ecules [centroid–centroid distances = 3.716 (2) and 3.642 (2) Å]. In addition, weak inter­molecular C—H⋯N hydrogen bonds are present in the structure.