Synthesis of New Functionalized Organophosphorus Acids and their Derivatives

Abstract

Functionalized organophosphorus acids and their derivatives are of great interest as chelating ligands, bioactive substances with various properties and the key compounds for the synthesis of phosphorus containing peptides. We have developed the convenient methods of the synthesis of new functionalized organophosphorus acids and their derivatives using a series of PH-acids and their esters with highly reactive fragments PH and POSi as well as phosphorus containing arnines with fragments PCHNH and PCHNSi. These organophosphorus synthons react smoothly with α-heterosubstituted derivatives of various amines and amides, functionalized alkenes and their oxides, as well as with acyl and sulfonyl chlorides giving the perspective compounds with high yields. New available types of new functionalized organophosphorus acids and their derivatives are presented below.     

Synthesis of functionalized 1‐trimethylsiloxy‐substituted O‐trimethylsilyl alkylphosphonites and their derivatives

Nucleophilic addition of trimethylsilyl esters of tricoordinate organophosphorus acids to various functionalized aldehydes with vinyl, aryl, and heterocyclic fragments is proposed as a convenient method for the synthesis of new 1‐trimethylsiloxysubstituted alkylphosphonites and their derivatives at mild conditions. Also the new functionalized derivatives of these phosphonites, including amino groups as well as certain properties of these compounds as important precursors of new functionalized 1‐hydroxyalkylorganophosphorus acids, are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:352–359, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20430     

Synthesis and reactivity of substituted alkoxymethylphosphonites and their derivatives

Alkoxy‐substituted methylphosphonites and their derivatives are prepared using an organomagnesium method of synthesizing the organophosphorus compounds and alkoxymethylation of various PH acids and their derivatives. Also, certain properties of these promising compounds as important precursors of new functionalized organophosphorue compounds with alkoxymethyl fragments are presented. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:281–289, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21015     

Synthesis of the new adducts of imines and enamines with PH acids and their derivatives

Nucleophilic or radical addition of esters of trivalent organophosphorus acids with PH fragments to various imines and enamines is proposed as convenient methods for the synthesis of new substituted aminomethyl organophosphorus compounds with three‐, four‐, and five‐coordinated phosphorus. Also the new functionalized derivatives of these compounds with acyl and methanesulfonyl moieties are synthesized, and some properties of the obtained compounds are presented. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:70–80, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20513     

A New Synthetic Route to Diastereomerically Pure Cyclopropane-Phosphorus Derivatives Utilizing the Chiron 5-L-Men-thyloxy-3-bromo-2(5H)-furanone and Racemic Dialkyl α-Hydroxyalkanephosphonate

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Synthesis of new organophosphorus‐substituted derivatives of ethanesulfonic acid

Nucleophilic addition of trimethylsilyl esters of hypophosphorus acid to trimethylsilyl ester and diethylamide of vinylsulfonic acid is proposed as convenient methods for the synthesis of new 2‐sulfonylethylphosphonites and their derivatives under mild conditions. Also the new functionalized derivatives of these phosphonites, including aminomethyl fragments as well as certain properties of these compounds as important precursors of new organophosphorus‐substituted derivatives of ethanesulfonic acid, are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:470–473, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20448     

Synthesis and Reactivity of the New Trimethylsilyl Esters of Aminomethylenebisorganophosphorus Acids

The interaction of trimethylsilyl esters of trivalent organophosphorus acids containing PH and POSiMe₃ fragments in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst is proposed as a convenient method for the synthesis of new trimethylsilyl esters of aminomethylenebisorganophosphorus acids with three and four coordinated phosphorus. Also the new functionalized derivatives of the aminomethylenebisphosphinic acids with substituted hydroxymethyl moieties are synthesized, and some properties of the obtained compounds are presented.     

Synthesis of new organophosphorus compounds using the atherton–todd reaction as a versatile tool

This article discusses the behavior of seven organophosphorus compounds under Atherton–Todd conditions. Therefore, the reactivity and selectivity of different (phen)oxaphosphinines, dioxaphosphinines, dioxaphosphinanes, and diphenylphosphine oxide with three nucleophiles were systematically studied. The results prove the versatility of the Atherton–Todd reaction to a broad range of organophosphorus compounds with different phosphorus environments and reactive P H bonds. The nucleophiles studied in this article were chosen as model substrates for amines and alcohols. Because organophosphorus molecules are important and versatile compounds, for a broad field of applications, novel synthetic approaches are of interest to both academia and industry. As an example, the single‐step synthesis of the bridged 1,3‐phenylene bis(diphenylphosphinate) with potential flame‐retardant properties was added to this study. In addition, the reaction is utilized for the synthesis of a novel organophosphorus anhydride. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:216–222, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21006     

A New Approach to the Asymmetric Reaction of the Chiron 5－L－Menthyloxy－2（5H）－furanones with Horner－Emmons Reagent

The asymmetric reaction of the chiron 2(5H )-furanones (4a-4c) with the Horner-Emmons reagents (5a-5b) has been investigated. The newly chirai organophosphorus derivatives 6 and 7 were obtained using the phosphoryl-stabilized carbanion as a building block in DMSO under mild conditions. Through the asymmetric introduction, the Horner-Emmons reagent could be transformed to a chiral building block to afford the novel functionalized phosphorus derivatives. The structures of the synthesized compounds 6 and 7 were identified on the basis of their elementary and spectroscopic data, such as IR,^1H NMR, ^13C NMR, MS and X-ray crystallography. These resuits provided a valuable approach to the synthesis of potentially interesting chirai organophosphorus derivatives and probing their biological activities.     

Tetracoordinate phosphorus cage compounds with endocyclic P–C bonds: Synthesis and reactivity

The survey summarizes modern methods of synthesis and reactivity of tetracoordinated phosphorus cage compounds containing one or more endocyclic P–C bonds (phosphine oxides, phosphinates and phosphonates, phosphatripticenes and others). Intramolecular cyclization reactions including electrophilic aromatic substitution with unsaturated organophosphorus compounds, reactions of P–H-derivatives with carbonyl compounds as well as cycloaddition reactions involving I–IV-coordinated phosphorus derivatives are considered.     

Organophosphorus Synthesis Without Phosphorus Trichloride: The Case for the Hypophosphorous Pathway

Abstract

The vast majority of organophosphorus compounds is currently synthesized from phosphorus trichloride (PCl₃), even though the final consumer products do not contain reactive phosphorus–chlorine bonds. In order to bypass phosphorus trichloride, significant interest has been devoted to functionalizing elemental phosphorus (P₄, the precursor to PCl₃), red phosphorus (P_red), or phosphine (PH₃). Yet, other industrial-scale precursors are hypophosphorous derivatives (H₃PO₂ and its alkali salts), but their use as phosphorus trichloride replacements has been completely overlooked. Here, the case is made for an alternative approach to the industrial synthesis of organophosphorus compounds based on hypophosphites.     

Cationic nitrile‐functionalized Ag(I)‐ and Hg(II)‐N‐heterocyclic carbene complexes of CCC,CNC, and NCN pincer‐type carbene ligands: Synthesis,crystal structures,and characterization

Three nitrile‐functionalized (benz)imid‐ zaolium derivatives with CCC, CNC, and NCN coordination pockets have been synthesized and isolated as the bromide salts and are converted into their hexafluorophosphate counterparts ( 5–7 ) by ligand metathesis. N‐heterocyclic carbene Ag(I)‐ and Hg(II)‐complexes ( 8–10 and 11–13 ) are readily formed in good to excellent yields from ligand precursors 5–7 and Ag₂O and Hg(OAc)₂, respectively. All reported compounds have been characterized by various spectral and analytical techniques, such as FTIR, ¹H, and ¹³C NMR spectroscopy and X‐ray diffraction studies. Solid‐state structures of carbene precursors 5 , 7 , and an Ag(I)–carbene complex 10 have been determined crystallographically. Single crystal X‐ray crystallography of complex 10 reveals the chelation of carbene carbons to metal center in almost a linear manner. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:486–497, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21041     

Synthesis of Bis(imidazole‐2‐thion‐4‐yl)phosphanes

Novel bis(imidazole‐2‐thion‐4‐yl)‐ phosphanes ( 2a–d ) were synthesized via lithiation of the precursor imidazole‐2‐thiones followed by the phosphanylation reaction. Oxidation of bis(imidazole‐2‐thion‐4‐yl)phosphane 2b–d with elemental sulfur and selenium led selectively and in good yields to the P‐thio ( 3b–d ) and P‐seleno ( 4c ) derivatives of bis(imidazole‐2‐thion‐4‐yl)phosphanes, respectively. The treatment of 2a,c with phosphorus trichloride gives the corresponding P‐chloro derivatives 5a,c . These compounds were unambiguously characterized by elemental analyses, spectroscopic and spectrometric methods, in addition by single‐crystal X‐ray structure analysis in the case of 2d . © 2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–7, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21043     

Study of reaction between activated acetylenes and N,N′‐diethyl‐2‐thiobarbituric acid in the presence of isocyanides or triphenylphosphine

In a series of separate experiments reaction between N,N′‐diethyl‐2‐thiobarbituric acid and acetylenic diesters in the presence of isocyanides or triphenylphosphine led to highly functionalized 4H‐pyrano[2,3‐d]thiopyrimidine or 1,4‐di‐ionic organophosphorus derivatives. The ¹H NMR spectra of diethyl‐7‐(2,6‐dimethylphenylamino)‐4‐oxo‐2‐thio‐ 1,3‐diethyl‐4H‐pyrano[2,3‐d]pyrimidine‐5,6‐dicarboxylate showed dynamic NMR effect that was attributed to restricted rotation around the aryl‐nitrogen single bond. Activation free energy (ΔG^≠) for this process is about 54.85 ± 2 kJ mol⁻¹. Betaines as 1,4‐diionic organophosphorus compounds in this reaction are possessed of two vicinal stereogenic centers and exist in the solution as a mixture of two diastereoisomers. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:228–235, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20601     

New Types of Functionally Substituted Methylphosphonites and Their Derivatives

Abstract

Organophosphorus compounds containing a functional group in the a-position of the alkyl radical are of great interest in both theoretical fundamental investigations and for practical applications. Functionally substituted methyl-phosphonites and their derivatives, belonging to this broad class of organophosphorus compounds, are convenient objects for investigating mutual effects of trivalent phosphorus and a heteroatom, or functional groups attached to it in the a-position. They have also become key substances in obtaining new organophosphorus compounds. Functionally sub-stituted compounds of tetracoordinated phosphorus have been intensively investigated in recent years; rather convenient methods of synthesis of these compounds have been proposed and their properties have been studied in detail¹. However, the corresponding compounds of tricoordinated phosphorus are not available or difficult to obtain. Recently we re-ported on the properties of halogen-substituted methylphos-phines and their derivatives². The present paper is devoted to the synthesis and investigation of the reactivity of alkoxy-, dialkylamino- and carbonyl substituted methylphos-phonites and their derivatives. In synthesis of alkoxymeth-ylphosphonites and their analogs we were the first to use labile alkoxymethylmagnesium chlorides in the reactions with tricoordinated phosphorus acid chlorides³. Previously unknown dialkoxymethylphosphonites and their analogs were obtained from hypophosphorous acid and trialkylorthofor-mates. The process of esterification and dialkoxymethylat-ion of hypophosphorous acid, being dependent on a catalyst, proceeds in different ways and results in the formation of dialkoxymethylphosphonite structures     

Synthesis and functionalization of Poly[5,5′‐(silylene)‐2,2′‐dithienylene]s using silyl triflate intermediates†

Treatment of 5,5′‐dilithio‐2,2′‐dithiophene with (dimethylamino)methylsily bis(triflate)‐ or α, ω‐bis(triflate)‐substituted trisilanes gave poly[5,5′‐(silylene)‐2,2′‐dithienylene]s in high yields. The amino–silyl bond was cleaved selectively by triflic acid, leading to triflate‐substituted derivatives. Conversion of these compounds with nucleophiles gave other functionalized polymers. Platinum‐catalyzed hydrosilylation reactions between silicon–vinyl and silicon–hydrogen derivatives result in polymer networks which may serve as interesting preceramic materials. The structures of the polymers were proven by NMR spectroscopy (²⁹Si, ¹³C, ¹H). Results of thermal gravimetric analysis (TGA), UV spectrometry and conductivity measurements are given. Copyright © 1999 John Wiley & Sons, Ltd.     

Synthesis of new functionalized mono‐ and bisphosphinates with 2,6‐di‐tert‐butyl‐4‐methylphenol fragments

Convenient procedures for the synthesis of functionalized mono‐ and bisphosphinates with 2,6‐di‐tert‐butyl‐4‐methylphenol (ionol) fragments, starting from the available 3,5‐di‐tert‐butyl‐4‐benzaldehyde and its derivatives, are proposed, and some properties of the new phosphorus‐substituted sterically hindered phenols are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:562–568, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20475     

Ruthenium‐Catalyzed ortho C−H Borylation of Arylphosphines

Efficient, phosphine‐directed ortho C?H borylation of arylphosphine derivatives was achieved using Ru catalysts for the first time. The reaction is applicable to various tertiary arylphosphine and arylphosphinite derivatives to give (o‐borylaryl)phosphorus compounds in high yields. This reaction enables easy access to a variety of functionalized phosphine ligands and ambiphilic phosphine boronate compounds, thus realizing a new late‐stage modification of phosphorus compounds.     

Synthesis and tuberculostatic activity of novel N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methylpyrimidine‐2‐carbohydrazide derivatives

The synthesis of N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methyl‐pyrimidine‐2‐carbohydrazide derivatives ( 5a and 5b ) was carried out. These compounds were used as starting materials to obtain methyl N′‐methylhydrazinecarbodithioates 6a and 6b , which, on reaction with either triethylamine or hydrazine, gave corresponding 1,3,4‐oxadiazioles 7a and 7b or 1,2,4‐triazoles 9a and 9b with the free NH₂ group at the N‐4 position, respectively. Compounds 8a – e , particularly containing cyclic amines at N‐4 of the 1,2,4‐triazole ring, were also obtained. Synthesized compounds were tested in vitro for their activity against Mycobacterium tuberculosis. The structure–activity relationship analysis for obtained compounds was done. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:223–230, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21008     

Synthesis and antimicrobial evaluation of new 1‐{[4‐(4‐Halogenophenyl)‐4H‐1,2,4‐ triazol‐3‐yl]sulfanyl}acetyl‐4‐substituted thiosemicarbazides and products of their cyclization

By the reaction of hydrazides of 4‐(4‐halogenophenyl)‐4H‐1,2,4‐triazol‐3‐yl‐sulfanyl acetic acid with isothiocyanate, 1‐acyl‐4‐substituted thiosemicarbazide derivatives ( 7–19 ) were obtained. The cyclization of compounds ( 7–19 ) in the presence of 2% NaOH led to the formation of compounds ( 20–26 ) containing two 1,2,4‐triazole rings connected by a methylenesulfanyl group. The new compounds were tested for their in vitro antimicrobial activity. Some of the tested compounds ( 9, 12, 18, 21, 22 ) showed activity against the reference strains of Gram‐positive bacteria with the MIC (minimal inhibitory concentration) = 125 to >1000 μg/mL. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:117–121, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20758