Dialkyl Phosphonates Research Articles

Siladifluoromethylation and Deoxo-trifluoromethylation of PV-H Compounds with TMSCF3: Route to PV-CF2- Transfer Reagents and P-CF3 Compounds.

A method for siladifluoromethylation of dialkyl phosphonates and secondary phosphine oxides with TMSCF3 to produce nucleophilic PV-CF2- transfer reagents is disclosed, with multigram scale reactions included. Condition-dependent divergent reactivity under the established conditions is demonstrated by the formation of trifluoromethylphosphines. Both one-pot transformations are operationally simple and employ inexpensive materials. Mechanistic investigations suggest the divergent reactivity originates from a common intermediate, with Li+ concentration directing the chemoselectivity.

Photoinduced Transition-Metal-Free Cross-Coupling of Aryl Halides with H-Phosphonates.

Photoinduced transition-metal- and photosensitizer-free cross-coupling of aryl halides (including Ar-Cl, Ar-Br, and Ar-I) with H-phosphonates (including dialkyl phosphonates and diarylphosphine oxides) is reported. Various functional groups were tolerated, including ester, methoxy, dimethoxy, alkyl, phenyl, trifluoromethyl, and heterocyclic compounds. This simple and green strategy provides a practical pathway to synthesize arylphosphine oxides.

Ni-Catalyzed C-P Coupling of Aryl, Benzyl, or Allyl Ammonium Salts with P(O)H Compounds.

A methodology that allows for the construction of C-P bonds via the nickel-catalyzed cross-coupling of organoammonium salts with appropriate phosphorus nucleophiles has been developed. Aryl-, pyridyl-, benzyl-, and allyl-ammonium triflates can be employed as the electrophiles. The employed phosphorus-based nucleophiles included diaryl/dibutyl phosphine oxide, dialkyl phosphonates, and ethyl phenylphosphinate. Functional groups OMe, CN, CF3, F, Cl, C(O)NMe2, and C(O) tBu were tolerated.

Synthesis and biological activity of dehydrophos derivatives.

The synthesis of dehydrophos derivatives featuring modified peptide chains, characterized by the presence of substituents in the vinyl moiety, or possessing a phosphonic acid monoalkyl ester other than the monomethyl ester one, has been accomplished by a versatile procedure based on Horner-Wadsworth-Emmons olefination with suitable aldehydes and on the selective hydrolysis of the dialkyl phosphonate group. Such derivatives have been tested against a series of bacterial strains, using the naturally occurring peptide, dehydrophos, for comparison. Thus, the effects of the aforementioned structural variations on antimicrobial activity have been studied.

Characterization of Dialkyl Phosphites by Gas Chromatography–Mass Spectrometry

The homologous series of dialkyl phosphonates (CnH2n + 1O)2PH=O] (2 ≤ n ≤ 9) (dialkyl phosphites is their commonly used trivial name) was characterized by electron ionization mass spectra and retention indices (RIs) on an RTX-5 standard nonpolar stationary phase. It was established that, in the presence of even one chiral center in the alkyl fragments (for example, in sec-alkanol esters), dialkyl phosphonates were detected in the form of several chromatographic signals due to diastereomers with differences in the retention indices from 4 to 21. The four-coordinated phosphorus atom is the second chiral center. The homologous increments of the retention indices of di-n-alkyl phosphonates (iRI ± sRI = 29 ± 9) and esters having one (–4 ± 10) and two (–61 ± 14) branching points in the carbon skeletons of alkyl fragments were evaluated. These values, which were calculated based on data for a limited number of homologues, make it possible to characterize any compounds from the test series. It was found that the relationship М ≈ 0.14(RI – iRI) + y makes it possible to uniquely determine the molecular weights of analytes according to chromatographic data under the condition of rounding the results to the nearest value of M comparable with y = 12 to the modulus 14 [М ≡ 12(mod14)].

DDQ-Mediated Cross-Dehydrogenative-Coupling Reaction of Secondary Amines with Dialkyl Phosphonates

This work reports a DDQ-mediated cross-dehydrogenative-coupling reaction of secondary amines with dialkyl phosphonates under mild conditions. This reaction proceeds efficiently without involving visible light or transition-metal catalysis. This new approach provides efficient access to biologically important α-aminophosphonates.

Synthesis of Some Di‐ and Tetraphosphonic Acids by Suzuki Cross‐Coupling

Five diphosphonic acids, namely, benzene‐1,4‐bis‐p‐phenylphosphonic acid (1), anthracene‐9,10‐bis‐p‐phenylphosphonic acid (2), benzene‐1,2‐bis‐p‐phenylphosphonic acid (3), benzene‐1,3‐bis‐p‐phenylphosphonic acid (4), and biphenyl‐4,4′‐bis‐p‐phenylphosphonic acid (5) as well as three tetraphosphonic acids, namely, benzene‐1,2,4,5‐tetrakis‐p‐phenylphosphonic acid (6), tetrabiphenylsilane tetrakis‐4‐phosphonic acid (7), and pyrene‐1,3,6,8‐tetrakis‐p‐phenylphosphonic acid (8) and their dimethyl esters 1a–8a were prepared via Suzuki cross‐coupling reactions involving p‐dimethylphosphonatophenylboronic acid and brominated aromatics. The Suzuki cross‐coupling occurs under milder conditions than the transition metal catalyzed Arbuzov reaction usually applied for the preparation of dialkyl phosphonates. For the same starting material both reactions are complementary and yield phosphonic acids with different spacer lengths, which was exemplified for tetrakis(4‐bromophenyl)silane. Suzuki cross‐coupling gives rise to 7, whereas the Arbuzov reaction produces tetraphenylsilane tetrakis‐4‐phosphonic acid.

Phosphonated Lipids as Primary Plasticizers for PVC with Improved Flame Retardancy

Bio‐based plasticizers bearing moieties exhibiting flame retardancy properties [dimethyl (methyl oleate)phosphonate (PMO), diethyl (methyl oleate)phosphonate (PMO2), dimethyl (methyl linoleate)phosphonate (PML), dimethyl (dimethyl oleate)phosphonate (PDE)] are synthesized from methyl oleate, methyl linoleate, and oleic diacid through free‐radical addition of dialkyl phosphonates. Soft PVC is prepared from PMO, PMO2, PML, and PDE primary plasticizers and compared to materials containing usual diisononyl phthalate DINP. Rheological behavior, thermal stability, mechanical properties, and flame resistance performances of these PVC films are carefully investigated. The presence of the phosphonate group into the plasticizer structure explains the best thermal stability of the PVC films based on phosphonated plasticizer than that of based on DINP. Regarding all these results, PMO and PDE can be considered as efficient flame retardant primary plasticizers for PVC and can substitute phthalates in soft PVC based materials.Practical Applications: These biobased additives are elaborated as plasticizers for PVC improving flame retardancy.Lipids were investigated as additives for polymeric materials. Looking at replacing phthalates in soft PVC formulations, phosphonated lipids demonstrate both a flame‐retardant efficiency and plasticizing properties (mechanical properties, gelation temperature) for this polymer.

Direct Aryloxylation/Alkyloxylation of Dialkyl Phosphonates for the Synthesis of Mixed Phosphonates

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 Tf2 O/pyridine.

Direct Aryloxylation/Alkyloxylation of Dialkyl Phosphonates for the Synthesis of Mixed Phosphonates

AbstractA 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.

HPLC-MS separation and detection of dialkyl phosphonates and trialkyl phosphites in reaction mixtures of 1-alkanols with phosphorous trichloride

To evaluate the rationality and separation conditions of alkyl esters of phosphorous P(III) and P(V) acids using reversed phase HPLC with mass spectrometric detection, the analyses of reaction mixtures of two 1-alkanols (1-butanol and 1-heptanol) with PCl 3 in the presence of N,N-dimethyl aniline (for pH correction) have been carried out. In accordance with the previous results, these mixtures preferably contain trialkyl phosphites (RO) 3 P and dialkyl phosphonates (RO) 2 PH=O. However, the results of HPLC-MS analyses indicate the prevalence of oxidation products P(III) ® P(V) in the composition of these mixtures, namely trialkyl phosphates (RO) 3 OP. In accordance with this scheme, the appearance of diheptyl phosphate (C 7 H 15 O) 2 P(=O)-OH is caused by the oxidation of diheptyl phosphonate. Possible reasons of such discrepancies in the composition of reaction mixtures are discussed. One of them may be oxidation of P(III) derivatives by air oxygen during storage, or, tentatively, due to electrochemical reactions during electrospray ionization. The reaction mixture of 1-heptanol with PCl 3 contains two components with the same molecular weights ( M = 294) and identical mass spectra, but strongly different retention parameters ( t R 5.4 and 16.0 min). The second of them is diheptyl phosphonate. To explain the appearance the first of them, existence of more hydrophilic prototropic tautomer (C 7 H 15 O)P-OH (contains hydroxyl group in the molecule) was proposed. Comparing the analytical results obtained in positive and negative modes of detection indicates that the first of them seems to be more effective for detection of alkyl esters of P(III) and P(V) phosphorous acids. Keywords : Trialkyl phosphites, dialkyl phosphonates, reversed phase HPLC, MS-detection, determination in reaction mixtures, oxidation products DOI: http://dx.doi.org/10.15826/analitika.2018.22.3.014 (Russian) Igor G. Zenkevich, Tatiana I. Pushkareva, Vlada E. Nosova St. Petersburg State University, Universitetskii prosp., 26, St. Petersburg, 198504, Russian Federation

Phosphonic acid: preparation and applications.

The phosphonic acid functional group, which is characterized by a phosphorus atom bonded to three oxygen atoms (two hydroxy groups and one P=O double bond) and one carbon atom, is employed for many applications due to its structural analogy with the phosphate moiety or to its coordination or supramolecular properties. Phosphonic acids were used for their bioactive properties (drug, pro-drug), for bone targeting, for the design of supramolecular or hybrid materials, for the functionalization of surfaces, for analytical purposes, for medical imaging or as phosphoantigen. These applications are covering a large panel of research fields including chemistry, biology and physics thus making the synthesis of phosphonic acids a determinant question for numerous research projects. This review gives, first, an overview of the different fields of application of phosphonic acids that are illustrated with studies mainly selected over the last 20 years. Further, this review reports the different methods that can be used for the synthesis of phosphonic acids from dialkyl or diaryl phosphonate, from dichlorophosphine or dichlorophosphine oxide, from phosphonodiamide, or by oxidation of phosphinic acid. Direct methods that make use of phosphorous acid (H3PO3) and that produce a phosphonic acid functional group simultaneously to the formation of the P–C bond, are also surveyed. Among all these methods, the dealkylation of dialkyl phosphonates under either acidic conditions (HCl) or using the McKenna procedure (a two-step reaction that makes use of bromotrimethylsilane followed by methanolysis) constitute the best methods to prepare phosphonic acids.

Reactions of dialkyl (3,5-di-tert-butyl-4-oxocyclohex-2,5-dienylidenemethyl)phosphonates with alcohols and some transformations of the adducts

Reactions of dialkyl [(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]phosphonates with butyl, benzyl and propargyl alcohols in the presence of catalytic amounts of trifluoromethanesulfonic acid resulted in the formation of nucleophilic 1,6-addition products. Azide-alkyne cycloaddition reaction of dimethyl (3,5-di-tert-butyl-4-hydroxyphenyl)(prop-2-ynyloxy)methylphosphonate with benzyl azide and 1,3-bis-(2-azidoethoxy)benzene in the presence of copper sulfate and sodium ascorbate afforded 1,2,3-triazoles with sterically hindered phenol fragments.

Preparation of Dialkyl (2,2,2-Trifluoroethyl)phosphonates by Cu-Promoted Reactions of 1,1-Dichloro-2,2,2-trifluoroethane with HP(O)(OR)2

Cu-promoted reactions of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) with dialkyl phosphonates produced dialkyl (2,2,2-trifluoroethyl)phosphonates efficiently under mild conditions by successively activating the two inert C–Cl bonds in HCFC-123. These reactions can be efficiently carried out on a >30 g scale with moderate to good yields.

Propylphosphonic anhydride (T3P®) mediated one-pot three-component synthesis of racemic dialkyl (2-substituted-3-oxo-2,3-dihydro-1H-isoindol-1-yl)phosphonates

A practical and efficient synthesis of racemic dialkyl (2-substituted-3-oxo-2,3-dihydro-1H-isoindol-1-yl) phosphonates has been developed via the three-component reaction of 2-formylbenzoic acid, various primary amines and trialkyl phosphites, using propylphosphonic anhydride (T3P®) as the condensing agent. The one-pot reaction was easily performed in boiling ethyl acetate.

Silver-Catalyzed, Aldehyde-Induced α-C-H Functionalization of Tetrahydroisoquinolines with Concurrent C-P Bond Formation/N-Alkylation.

The first facile and efficient silver-catalyzed, aldehyde-induced three-component reaction of N-unprotected tetrahydroisoquinolines, aldehydes, and dialkyl phosphonates has been developed, providing a general one-step approach to structurally diverse C1-phosphonylated THIQs accompanied by concurrent C-P bond formation/N-alkylation with remarkable functional group tolerance and excellent regioselectivity for endo products.

Investigation of Antifouling Properties of Surfaces Featuring Zwitterionic α‐Aminophosphonic Acid Moieties

Zwitterionic thin films containing α-amino phosphonic acid moieties were successfully introduced on silicon surfaces and their antifouling properties were investigated. Initially, the substrates were modified with a hybrid polymer, composed of poly(methylsilsesquioxane) (PMSSQ) and poly(4-vinyl benzaldehyde) (PStCHO). Next, a Kabachnik-Fields post-polymerization modification (sur-KF-PMR) of the functionalized aldehyde surfaces was conducted with different amines and dialkyl phosphonates. After subsequent deprotection reaction of dialkyl phosphonates, the obtained zwitterionic surfaces were characterized by various techniques and we found excellent antifouling properties of the resulting films.

Installation of Zwitterionic α‐Amino Phosphonic Acid Moieties on Surfaces via a Kabachnik‐Fields Post‐Polymerization Modification

An organic–inorganic hybrid polymer, composed of poly(methylsilsesquioxane) (PMSSQ) and poly(4‐vinyl benzaldehyde) (PStCHO), is prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization of 4‐vinyl benzaldehyde (StCHO) using a macro‐chain transfer agent (CTA) based on PMSSQ. The obtained PMSSQ–PStCHO is spin‐coated on substrates such as silicon wafers or copper plates to afford aldehyde‐functionalized surfaces. Successful Kabachnik‐Fields post‐polymerization modification (KF‐PMR) of the aldehyde‐functionalized surfaces is conducted with amines and dialkyl phosphonates, and characterized by surface analysis techniques including IR, energy‐dispersive X‐ray (EDX), and X‐ray photoelectron spectroscopy (XPS) measurements, documenting the installation of α‐amino phosphonates onto surfaces with practically quantitative conversion of aldehydes. In addition, the generated α‐amino phosphonates are successfully deprotected to afford the corresponding α‐amino phosphonic acids on surfaces, which make this route a reliable tool‐enabling surface functionalization with α‐amino phosphonic acids. image

ChemInform Abstract: Copper‐Catalyzed Synthesis of Mixed Alkyl Aryl Phosphonates.

AbstractThe reaction can be scaled up.

Synthesis of Multifunctional 3‐Amino‐4‐phosphono‐2‐quinolinones via Regioselective Ring Enlargement of Imino Isatins

AbstractMultifunctional 3‐amino‐4‐dialkylphosphono‐2‐quinolinones have been prepared by “one‐pot” nucleophilic addition and regioselective ring enlargement of imino isatins. The addition reaction between imino isatins and dialkyl (diazomethyl)phosphonate proceeds smoothly using potassium carbonate as a catalyst, and a subsequent regioselective ring expansion promotes by salicylic acid to afford the desired products in high yields.magnified image