A concise synthesis of protected diethyl 1-amino-2-hydroxyalkylphosphonates

An efficient diastereoselective synthesis of 5-substituted (2-thioxo-oxazolidin-4-yl)phosphonic acid diethyl esters from metallated diethyl isothiocyanomethylphosphonate and aldehydes has been developed. The three-step transformation of oxazolidine-2-thione derivatives into N-Boc 1-amino-2-hydroxyalkylphosphonic acid diethyl esters is also described.     

Synthesis and structure of diethyl 2-oxo-1-oxaspiro[4,5]decane-3,4-dicarboxylate

Ethyl 1-oxaspiro[2,5]octane-2-carboxylate reacts with diethyl sodiomalonate in toluene to give diethyl 2-oxo-1-oxaspiro[4,5]decane-3,4-dicarboxylate, which on distillation under goes partial de-ethoxycarbonylation to give ethyl 2-oxo-1-oxaspiro[4,5]decane-4-carboxylate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 28–32, January, 1991.     

2-(1-Chloroalkyl)furans in the reaction with sodium diethyl phosphite

2-(1-Chloroethyl) and 2-(1-chloro-2-methylpropyl)furans react with sodium diethyl phosphite to give two products, 2-(1-diethoxyphosphorylmethyl)furan and 2-alkyl-5-(diethoxyphosphoryloxy)furan. The fraction of the latter product increases with increasing size of the alkyl radical. 2-Methyl substitution in the substrate completely suppresses phosphate formation. 2-(1-Chloroethyl)-5-(2-methylpropyl)furan under the action of sodium diethyl phosphite eliminates hydrogen chloride to give the corresponding alkene.     

Catalyst-free transformations of diethyl 2-ethoxymethylenemalonate and diethyl polyfluorobenzoylmalonates in water

The unusual transformation of diethyl 2-ethoxymethylenemalonate into triethyl 1,3,5-benzenetricarboxylate is described. This one-pot reaction proceeds in water without any catalyst in a good yield. One of the proposed intermediates of this process is also used under similar conditions to give the desired trisubstituted benzene. A catalyst-free, efficient, practical, and convenient process in water based on deethoxycarbonylation has been developed to form ethyl polyfluorobenzoylacetates in a high yield from diethyl polyfluorobenzoylmalonates.     

New analogues of fosfomycin—synthesis of diethyl (1R,2R)- and (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised via the intramolecular Williamson reaction from 3-O-protected (trityl or TBDMS) or even unprotected diethyl (1S,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonate, which was obtained from the known diethyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3-trihydroxypropylphosphonate. On the other hand, the cis-analogue, diethyl (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonate, could only be prepared from diethyl (1R,2R)-2-hydroxy-1-mesyloxy-3-trityloxypropylphoshonate.     

Unusual behavior of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one towards some phosphorus reagents: Synthesis of novel diethyl 2-phosphonochromone,diethyl 3-phosphonopyrone and 1,3,2-oxathiaphosphinines

The chemical reactivity of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) towards some phosphorus reagents was studied. The enaminone 1 was cyclized into diethyl 2-phosphonochromone 2 via its treatment with diethyl phosphite in basic medium. However, its reaction with triethoxy phosphonoacetate gave the substituted pyrone phosphonate 3. In addition, two novel examples of 4-(dimethylamino)-6-(2-hydroxyphenyl)-2-sulfido-4H-1,3,2-oxathia-phosphinines 6 and 7 were obtained from treatment of enaminone 1 with O,O-diethyl dithiophosphoric acid and Lawesson’s reagent. When enaminone 1 was also treated with phosphorus decasulfide, it was turned into 4H-thiochromene-4-thione while its treatment with phosphorus tribromide, phosphorus oxychloride, or phenylphosphonic dichloride, 4H-4-oxo-chromene was isolated in all cases. The possible reaction mechanisms of the formation of these products were discussed. The structures of newly isolated products were established by elemental analysis and spectral tools.     

Synthesis of 1H-isochromen-1-ylphosphonates via AgOTf-catalyzed reaction of 2-alkynylbenzaldehyde with diethyl phosphite

Tandem cyclization-addition reaction of 2-alkynylbenzaldehyde with diethyl phosphite catalyzed by AgOTf at room temperature was developed, which afforded the desired 1H-isochromen-1-ylphosphonates in moderate to good yields.     

Synthesis and resolution of diethyl (1S,2S)-1-amino-2-vinylcyclopropane-1-phosphonate for HCV NS3 protease inhibitors

We herein describe an efficient synthesis of optically active diethyl 1-amino-2-vinylcyclopropane-1-phosphonate (analogous to 1-amino-2-vinylcyclopropane-1-carboxylate). The racemic phosphonate diethyl ester was obtained from an imine derived from aminomethylphosphonate diester and trans-1,4-dibromo-2-butene. Crystallizations of the dibenzoyl-l-tartaric acid salt allowed for separation of enantiomers. The enantiomerically pure material was used to synthesize an extremely potent tripeptide phosphonate inhibitor of HCV NS3 protease. X-ray crystal structure of the inhibitor bound to the HCV NS3 protease confirmed the absolute stereochemistry of the title compound.     

Solution conformations of 2-amino-1-hydroxy-2-aryl ethylphosphonic acids and their diethyl esters

Conformations of 2-amino-1-hydroxy-2-aryl ethylphosphonic acids (in D₂O) and their diethyl esters (in CDCl₃ and CD₃OD) were determined by means of NMR on the basis of dependence between observed values of coupling constants (³J_PC, ³J_HH and ³J_PH) and corresponding dihedral angles. In case of diethyl esters we observed that the conformation was stabilised by the formation of the intramolecular hydrogen bond between (NH₂)?(OH) moieties in both solvents, whereas for acids formation of hydrogen bond between NH₃⁺?PO groups predominates.     

Mechanism of the reaction of 3,3-dimethyl-2-trimethylsiloxy-1-trimethylsilyl-1-phosphabut-1-ene with diethyl phosphite

The reaction of a stable two-coordinate phosphorus compound, 3,3-dimethyl-2-trimethylsiloxy-1-trimethylsilyl-1-phosphabut-1-ene, with diethyl phosphite was studied in terms of the density functional theory [DFT B3PW91/6-31G(d)]. A two-step mechanism of the reaction was established.     

A concise synthesis of diethyl 1-(tert-butoxycarbonylamino)-1-alkenylphosphonates

An efficient completely diastereoselective synthesis of (Z)- and (E)- N-Boc 1-aminoalkenylphosphonic acid diethyl esters from easily available 5-substituted (2-thioxo-oxazolidin-4-yl)phosphonic acid diethyl esters has been developed.     

Surface tension of diethyl carbonate, 1,2-dimethoxyethane and diethyl adipate

The surface tension was investigated with a differential capillary rise method in the temperature range from 273 to 373 K for diethyl carbonate, 278 to 373 K for 1,2-dimethoxyethane, and 293 to 373 K for diethyl adipate, respectively. The uncertainties of the temperature and surface tension were estimated to be within ±10 mK and ±0.2 mN m⁻¹, respectively. A surface tension correlation was developed as a function of temperature with the experimental data, and the average absolute deviations were 0.04, 0.07 and 0.09 mN m⁻¹ for diethyl carbonate, 1,2-dimethoxyethane and diethyl adipate, respectively.     

BF3·Et2O catalyzed intramolecular cyclization of diethyl 2-(dialkoxyphosphorylethynyl)-2-arylaminomalonates to 3-phosphonylated indoles

The boron trifluoride diethyl etherate catalyzed intramolecular cyclization of diethyl 2-(dialkoxyphosphorylethynyl)-2-arylaminomalonates afforded a series of novel 3-phosphonylated indoles, diethyl 2-[3-(dialkoxyphosphoryl)-1H-indol-2-yl]propanedioates. Decarboxylation of the latter compounds resulted in the formation of ethyl 2-[3-(dialkoxyphosphoryl)-1H-indol-2-yl]acetates.     

Formation of diethyl 2-amino-1-cyclopentenylphosphonates: a simple synthesis with a unique mechanism

Reaction of diethyl 5-chloro-1-pentynylphosphonate with primary and secondary amines produces novel 2-amino-1-cyclopentenylphosphonates, 1, in excellent isolated yields (79-88%). Calculations supported by experimental facts point to a two-step mechanism: an initial amine addition to give a zwitterionic intermediate followed by cyclization and proton transfer. Calculations rule out the formation of an enamine as an intermediate.     

Synthesis of 1,2-dihydroisoquinolin-1-ylphosphonates via three-component reactions of 2-(2-formylphenyl)ethanone, amine, and diethyl phosphite

Synthesis of 1,2-dihydroisoquinolin-1-ylphosphonates via CuI-catalyzed three-component tandem reactions of 2-(2-formylphenyl)ethanone, amine, and diethyl phosphite is described. The reactions proceed smoothly under mild conditions leading to the desired products in good yields.     

Synthesis of indenes via palladium-catalyzed carboannulation of diethyl 2-(2-(1-alkynyl)phenyl)malonate and organic halides

Highly substituted indenes have been prepared in good yields by the palladium-catalyzed carboannulation of diethyl 2-(2-(1-alkynyl)phenyl)malonate with aryl, benzylic, and alkenyl halides. The reaction conditions and the scope of the process were examined, and a possible mechanism is proposed.     

Stobbe-like condensation reactions of the anion of diethyl (2-carboethoxy)benzylphosphonate with some aromatic and heterocyclic aldehydes

Deprotonation of diethyl (2-carboethoxy)benzylphosphonate using sodium ethoxide followed by reaction of the carbanion with furfural or aryl aldehydes gives diethyl (E)-1-(2′-carboxyphenyl)-1-phosphono-2-arylethenes that are formed via intramolecular Stobbe-like condensation reactions.     

Determination of acetone, 2-butanone, diethyl ketone and BTX using HSCC-UV-IMS

A combination of a custom-designed ion mobility spectrometer (IMS) with a UV ionization source and a high speed capillary column (HSCC) has been developed as an analytical device for the sensitive detection of volatile organic compounds (VOCs), e.g. 2-propanone (acetone), 2-butanone and 3-pentanone (diethyl ketone) in the gas phase. A fast separation of the three selected substances and benzene, toluene and m-xylene (BTX) - all of which occur in human breath - has been achieved within less than four minutes at a carrier gas flow rate of 4.5 mL x min(-1). Multi-dimensional correlations presented support the interpretation of the acquired spectra of mixtures. Method detection limits were 2.7 microg x L(-1) for acetone and 2-butanone and 3.0 microg x L(-1) for diethyl ketone in nitrogen, respectively. The assay linear dynamic range is 4-320 microg x L(-1).     

Synthesis of diethyl 6-aryl-2-oxo-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates

Reaction of diethyl oxalylacetate sodium salt with aromatic aldehydes and urea led to the formation of diethyl 6-aryl-2-oxo-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates.     

Cyclocondensation of 2-hydrazinoperimidine with diethyl oxalate and ethyl pyruvate

Refluxing 2-hydrazinoperimidine (1) with excess amount of diethyl oxalate (2a) gave ethyl 1H-1,2,4-triazolo[4,3-a]perimidine-3-carboxylate (4a) in 84% yield. On the other hand, heating 1 with ethyl pyruvate (2b) in glacial acetic acid afforded 3-methyl-1,2,4-triazino[4,3-a]perimidin-4(1H)-one (6b) in 92% yield. Structures of the products were investigated by spectral and elemental analysis.