Phosphine Chalcogenides Research Articles

Theoretical Investigation Non-covalent Interactions of N-(diphenylphosphinothioyl)-2-pyrazinecarboxamide

Abstract. Phosphine chalcogenides can form reliable and reproducible supramolecular synthons through noncovalent interactions that can be employed for designing high dimensional supramolecular architectures. Here, we systematically study the influence of non-covalent interactions in the fabrication of these synthons and the stability of the crystalline structure of (N2C4H3)C(O)NHP(S)(C6H5)2 (1) through non-covalent interactions (NCI) analysis, molecular Hirshfeld surfaces and the corresponding two-dimensional (2D) fingerprint plots. The theoretical studies were employed to further confirm the presence of these synthons by comparing the stabilization energies of the dimers and monomers. The nature and electronic structure of the phosphor-chalcogenid bond in (N2C4H3)C(O)NHP(E)(OC6H5)2(E = S(1), O(2), and Se (3)) have also been evaluated by QTAIM, NBO, MEP, and HOMO-LUMO energy gaps.

Nucleophilic substitution of hydrogen in pyridine and its derivatives by organophosphorus nucleophiles in the presence of electron-deficient acetylenes

The review considers publications on a new easy functionalization of pyridinoids (pyridines, quinolines, isoquinolines, acridine, phenanthridine) by the electron-deficient acetylene (esters of acetylenecarboxylic acids, acylacetylenes, cyanoacetylenes)/P-nucleophile (phosphine chalcogenides, H -phosphonates) system. Particular attention is paid to the SN H reaction of regioselective cross-coupling of pyridines with secondary phosphine chalcogenides, initiated by acylacetylenes and leading to the formation of 4-chalcogenophosphorylpyridines. In these processes, acetylenes act as trimodal adjuvants by (1) activating the pyridine ring towards P-nucleophiles, (2) deprotonating the P-H bond, and (3) facilitating the nucleophilic addition of the P-centered anion to the heterocyclic fragment, followed by the release of selectively reduced (to E -alkenes) acetylenes.

Hydrophosphorylation of C=O/N Bonds Using Organophosphine Oxides or Sulfides

Abstractα‐Functionalized phosphorus compounds are an important class of biologically relevant molecules. The synthesis of these compounds often proceeds through the hydrophosphorylation of a C=E bond, with the most well‐known transformation being the Kabachnik‐Fields reaction. The nature of the phosphorus reagent is an important aspect of the hydrophosphorylation reaction. The Kabachnik‐Fields reaction uses H‐phosphonates (RO)2P(O)H, and similarities are often applied to 2° phosphine chalcogenides (R2P(Ch)H). However, the reactivities of the P−C and P−OR molecules differ quite dramatically, which changes the operative mechanism as well as subsequent downstream chemistry. We provide an in‐depth analysis of hydrophosphorylation of C=E (E=O, N) bonds with organophosphine chalcogenides. Additional discussion and a critical appraisal are provided on the similarities and differences between the H‐phosphonate and phosphine chalcogenide chemistry.

Phosphine chalcogenides and their derivatives from red phosphorus and functionalized pyridines, imidazoles, pyrazoles and their antimicrobial and cytostatic activity

Tertiary phosphine oxides, phosphine sulfides, and phosphine selenides containing pyridine, imidazole, and pyrazole groups have been synthesized via the reaction of elemental phosphorus or secondary phosphine oxides with functional pyridines, imidazoles, and pyrazoles. Alkyl tris(2-pyridylethyl)phosphonium iodide and bromide are also obtained by quaternization of the corresponding phosphine. Antimicrobial activity of the synthesized compounds, including nitrogen-containing heterocycles, phosphorus, selenium, and sulfur, with respect to Enterococcus durans, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa microorganisms is evaluated. It is found that phosphine chalcogenides bearing imidazole (14, 19), pyrazole (13), and pyridine fragments (5, 9) and phosphonium salts (11, 12) can be considered as new promising antibacterial agents. For some synthesized compounds, LC50 is determined. Phosphine oxide with methylpyrazole fragments (13) and phosphonium salts (11, 12) show strong profile of antimicrobial activity, and cytotoxic effect of phosphonium bromide having a long chain radical (12) is by order of magnitude higher than that of cisplatin. We believe that the results obtained may contribute to the development of highly effective agents for the treatment and prevention of bacterial infections and cancers.

UV induced hydrophosphination of dimethyl 2-vinylcyclopropane-1,1-dicarboxylate towards phosphine chalcogenides.

Dimethyl 2-vinylcyclopropane-1,1-dicarboxylate underwent a hydrophosphination reaction with either a primary or secondary phosphine under photolytic conditions. Notably, a free radical initiator was not required. The resulting tertiary phosphines were derivatized using S8 to afford moisture and air stable yellow or colorless oils in a 27%-73% isolated yield. A series of control reactions were performed, and we propose that this UV induced hydrophosphination reaction proceeds through a radical mechanism.

Catalyst‐ and Solvent‐Free Hydrophosphorylation of Aldimines with Secondary Phosphine Chalcogenides: Synthesis of Tertiary α‐Aminophosphine Oxides, Sulfides and Selenides

AbstractSecondary phosphine chalcogenides mildly (no catalysts and solvents, 20–65 °C, 0.25–65.5 h) react with aldimines to deliver the hitherto unknown α‐aminophosphine oxides, sulfides and selenides in good to excellent yields.

Structural and Electronic Effects on Phosphine Chalcogenide Stabilized Silicon Centers in Four-Membered Heterocyclic Cations.

Understanding the interplay of structural and electronic parameters in the stabilization of Lewis acidic silicon centers is crucial for stereochemical questions and applications in bond activation and catalytic transformations. Phosphine chalcogenide functionalized (Ch = O, S, and Se) hydrosilanes having tert-butyl and 2,4,6-trimethoxyphenyl (TMP) substituents on the silicon atom were synthesized, and the ring-closing reactions to afford the heterocyclic four-membered CPChSi cations were investigated. Synthetic access was only achieved for the sulfur- and selenium-based cations. A thorough study by means of single-crystal X-ray structure determination, NMR spectroscopic data, and density functional theory (DFT) calculations provided insight into important electronic and structural parameters affecting the stability of the intramolecularly stabilized cations. Detailed structural considerations were made on the contributions to the ring strain (angular strain and steric repulsion). Thermochemical investigations showed that the substituents on the silicon and phosphorus atoms play an important role for the stability of the cationic heterocycles. In the absence of large steric repulsions through bulky substituents (methyl groups on silicon and tert-butyl groups on phosphorus), an intrinsic stability sequence of the intramolecular Ch-Si coordination depending on the chalcogen atom in the direction Se ≤ S < O can be observed. However, the order is reversed (O < S < Se) in the case of strong repulsions between sterically demanding substituents (tert-butyl groups on both silicon and phosphorus atoms). Natural bond orbital (NBO) analysis supported the explanations for the observed deshielding trends in 31P NMR spectroscopy and revealed that the O-Si bond is more ionic in nature compared to the S-Si and Se-Si bonds, with the latter exhibiting higher covalent character due to a more efficient charge transfer through a σ-type nCh → pSi interaction.

Studying Lipophilicity Trends of Phosphorus Compounds by 31P-NMR Spectroscopy: A Powerful Tool for the Design of P-Containing Drugs.

Systematically studying the lipophilicity of phosphorus compounds is of great importance for many chemical and biological fields and particularly for medicinal chemistry. Here, we report on the study of trends in the lipophilicity of a wide set of phosphorus compounds relevant to drug design including phosphates, thiophosphates, phosphonates, thiophosphonates, bis-phosphonates, and phosphine chalcogenides. This was enabled by the development of a straightforward log P determination method for phosphorus compounds based on 31P-NMR spectroscopy. The log P values measured ranged between -3.2 and 3.6, and the trends observed were interpreted using a DFT study of the dipole moments and by H-bond basicity (pKHB) measurements of selected compounds. Clear signal separation in 31P-NMR spectroscopy grants the method high tolerability to impurities. Moreover, the wide range of chemical shifts for the phosphorus nucleus (250 to -250 ppm) enables a direct simultaneous log P determination of phosphorus compound mixtures in a single shake-flask experiment and 31P-NMR analysis.

Reduction of phosphine sulfides and selenides by samarium(

The reductive action of the bulky SmII formamidinate complex [Sm(dippForm)2(thf)2] (dippForm− = HC(Ndipp)2 −, dipp = 2,6-diisopropylphenyl; thf = tetrahydrofuran) (1) on a series of phosphine chalcogenides (R3PE = Ph3PO, Ph3PS, Ph3PSe, n Bu3PS, n Bu3PSe) as well as Ph3AsS, has been investigated. The reactions are fast for the phosphine derivatives with E = Se and for Ph3AsS, and slow for the phosphine sulfides. They lead to mixtures of binuclear mono- and dichalcogenide complexes [(Sm(dippForm)2)2(µ-En )] (E = S (2), Se (3); n = 1, 2). The ratio of species with (µ-E) or (µ-η2:η2-E2) bridges depends on the nature of the chalcogenide reactant and its concentration, but even under its local excess the formation of the monochalcogenide is preferential. Both types of species form isostructural solid solutions. The dense outer packing of dippForm ligands in the complexes 2 and 3, leaving enough free space in the centre of the molecule, is thought to be the main reason for the geometrical similarity of mono- and dichalcogenides and for their ready co-crystallization. A reaction scheme is proposed, involving the coordination of the starting chalcogenide to the SmII centre with successive formation of E-centered transient radical species [Sm(dippForm)2(E˙)]. Contrary to the phosphine/arsine sulfides and selenides, the product of phosphine oxide coordination, [Sm(dippForm)2(OPPh3)] (4), was shown to be stable, while a similar complex with two phosphine oxide ligands, [Sm(dippForm)2(OPPh3)2] (5), was fortuitously crystallized at lower temperatures.

Theoretical studies on structure-directing interactions of diphenyl N-(2-pyrazinyl carbonyl) phosphoramidate

Herein, we report the strength of structure-directing interactions in the crystal packing of diphenyl N-(2-pyrazinyl carbonyl) phosphoramidate (1) through computing their binding energies by DFT. Further, the non-covalent interaction (NCI) analysis, molecular Hirshfeld surfaces, and the corresponding two-dimensional fingerprint plots are obtained to gain a deep understanding of the importance of these interactions in the stability of a crystal structure. Despite the important role of the phosphorus—chalcogenid bond in optimizing tertiary phosphine chalcogenides, their computational studies have been lagging far behind. The nature and electronic structure of this bond in (N2C4H3)C(O)NHP(E)(OC6H5)2 (E = O (1), S (2), and Se (3)) are evaluated by QTAIM, MEP, and HOMO—LUMO energy gaps.

Synthesis of Tertiary Phosphine Chalcogenides and Their Derivatives with Azine and Azole Groups from Red Phosphorus and Functionalized Pyridines, Imidazoles, Pyrazoles and Their Antimicrobial and Cytostatic Activity

Synthesis of Tertiary Phosphine Chalcogenides and Their Derivatives with Azine and Azole Groups from Red Phosphorus and Functionalized Pyridines, Imidazoles, Pyrazoles and Their Antimicrobial and Cytostatic Activity

Tris(tetramethylguanidinyl)phosphine: The Simplest Non-ionic Phosphorus Superbase and Strongly Donating Phosphine Ligand.

We report the synthesis and properties of the much sought‐after tris(1,1,3,3‐tetramethylguanidinyl) phosphine P(tmg)3, a crystalline, superbasic phosphine accessible through a short and scalable procedure from the cheap and commercially available bulk chemicals 1,1,3,3‐tetramethylguanidine, tris(dimethylamino)‐phosphine and phosphorus trichloride. The new phosphine exhibits exceptional electron donor properties and readily forms transition metal complexes with gold(I), palladium(II) and rhodium(I) precursors. The formation of zwitterionic Lewis base adducts with carbon dioxide and sulfur dioxide was explored. In addition, the complete series of phosphine chalcogenides was prepared from the reaction of P(tmg)3 with N2O and the elemental chalcogens.

Electron-Deficient Acetylenes as Three-Modal Adjuvants in SNH Reaction of Pyridinoids with Phosphorus Nucleophiles.

Publications covering a new easy metal-free functionalization of pyridinoids (pyridines, quinolines, isoquinolines, acridine) under the action of the system of electron-deficient acetylenes (acetylenecarboxylic acid esters, acylacetylenes)/P-nucleophiles (phosphine chalcogenides, H-phosphonates) are reviewed. Special attention is focused on a SNH reaction of the regioselective cross-coupling of pyridines with secondary phosphine chalcogenides triggered by acylacetylenes to give 4-chalcogenophosphorylpyridines. In these processes, acetylenes act as three-modal adjuvants (i) activating the pyridine ring towards P-nucleophiles, (ii) deprotonating the P-H bond and (iii) facilitating the nucleophilic addition of the P-centered anion to a heterocyclic moiety followed by the release of the selectively reduced acetylenes (E-alkenes).

Carbonyl Compounds: Reactants, Catalysts and Products

Ultra-branched mixed tetradentate tripodal phosphines and phosphine chalcogenides have been synthesized by the exhaustive regioselective addition of secondary phosphines, phosphine sulfides and phosphine selenides to available tris(4-vinylbenzyl)phosphine oxide under free-radical conditions (UV irradiation or AIBN) in good to excellent yields.

Transition-metal complexes of group 12 with 1,1'-bis(phosphanyl)ferrocene ligands.

The syntheses of four new cadmium and zinc complexes with 1,1'-bis(phosphanyl)ferrocene ligands and their phosphine chalcogenide derivatives are reported. The complexes were characterized by elemental analyses and IR, 1H NMR, 31P NMR and electronic absorption spectroscopy. The crystal structures of dichlorido[1-diphenylphosphinoyl-1'-(di-tert-butylphosphanyl)ferrocene-κ2O,P]cadmium(II), [CdCl2{(C17H14OP)(C13H22P)Fe}] or CdCl2(κ2P,O-dppOdtbpf) (1), bis[μ-(tert-butyl)(1'-diphenylphosphinoylferrocen-1-yl)phosphinato-κ3O,O':O'']bis[chloridozinc(II)], [Zn2{(C9H13O2P)(C17H14OP)Fe}2Cl2] or [ZnOCl{κ2O,O'-Ph2POFcPO2(t-Bu)}]2 (2), 1,1'-bis(di-tert-butylthiophosphinoyl)ferrocene, [Fe(C13H22PS)2] or dtbpfS2 (3), and [1,1'-bis(dicyclohexylphosphanyl)ferrocene-κ2P,P'][chlorido/cyanido(0.25/1.75)]zinc(II), [Zn(CN)1.75Cl0.25{(C17H26P)2Fe}] or Zn(CN)2(κ2-dcpf) (4), were determined crystallographically. Compound 1 has tetrahedral geometry in which the CdII centre is coordinated by one dppOdtbpf ligand in a κ2-manner and by two Cl atoms, while compound 2 displays a centrosymmetric dimeric unit in which two oxide atoms bridge the two Zn atoms to generate an eight-membered ring. Compound 3 revealed a sandwich structure with both phosphane groups sulfurized. In compound 4, the ZnII atom adopts a tetrahedral geometry by coordinating to the 1,1'-bis(dicyclohexylphosphanyl)ferrocene ligand in a κ2-manner and to two cyanide ligands.

Metal-free SHN cross-coupling of pyridines with phosphine chalcogenides: polarization/deprotonation/oxidation effects of electron-deficient acetylenes

Terminal acylacetylenes act as trimodal auxiliaries in SHN cross-coupling of pyridines with phosphine chalcogenides. The reaction proceeds via phosphorylation of the pyridine 2 position followed by 2 → 4-migration of phosphoryl moieties.

Oxidative cross-coupling of secondary phosphine chalcogenides with amino alcohols and aminophenols: aspects of the reaction chemoselectivity

Secondary phosphine chalcogenides react with primary amino alcohols under mild conditions (room temperature, molar ratio of the initial reagents 1 : 1) in a CCl4/Et3N oxidizing system to chemoselectively deliver amides of chalcogenophosphinic acids with free OH groups. Under similar conditions, mono-cross-coupling between secondary phosphine chalcogenides and 1,2- or 1,3-aminophenols proceeds only with the participation of phenolic hydroxyl to give aminophenylchalcogenophosphinic O-esters. The yields of the synthesized functional amides or esters are 60-85%.

Gold(I)‐Catalyzed Intramolecular Hydroarylation of o‐Ethynylarylphosphonium Salt Leading to the Formation of Seven‐ and Six‐membered Phosphacycles

AbstractThe gold(I)‐catalyzed intramolecular hydroarylation of o‐ethynylarylphosphonium salt 1 gave phosphepinium 2 or phosphinium salt 3. The use of methylphosphonium salt instead of phosphine chalcogenide is key to success for the intramolecular hydroarylation. The substrate with 2‐methoxyphenyl group at the alkyne position preferentially provided seven‐membered phosphacycle 2, while that with a hydrogen did six‐membered phosphacycle 3. Theoretical calculations revealed that the activation energy of 6‐exo‐dig cyclization in the substrate with the aryl group increased due to the steric repulsion of the two aryl rings. Furthermore, the Wittig‐type reaction of phosphepinium salt 2 a afforded methyl‐substituted phosphepin oxide 4 a via the elimination of an aryl group.

Quantum Chemical Study of the Addition of Secondary Phosphine Chalcogenides to Vinyl Selenides

DFT quantum chemical calculations at the B3PW91/6-31G(d) level of theory have shown that the addition of secondary phosphine sulfides and phosphine selenides with alkyl, phenyl, and phenylalkyl substituents to pentyl vinyl and hexyl vinyl selenides follows a molecular mechanism against the Markovnikov rule through energetically favorable eight-membered transition state, leading to the formation of tertiary phosphine chalcogenides. Secondary phosphine selenides are more reactive than the corresponding phosphine sulfides.

Diverse Reactivity of a Rhenium(V) Oxo Imido Complex: [2 + 2] Cycloadditions, Chalcogen Metathesis, Oxygen Atom Transfer, and Protic and Hydridic 1,2-Additions.

We present a wide range of reactivity studies focused on the rhenium(V) oxo imido complex (DippN)(O)Re(BDI) (1, Dipp = 2,6-diisopropylphenyl and BDI = N,N'-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate). This complex, which was previously shown to possess a highly polarized Re oxo moiety, has proven to be a potent nucleophile and a valuable precursor to a variety of rare structural motifs in rhenium coordination complexes. For example, the Re oxo moiety of 1 undergoes [2 + 2] cycloadditions with carbodiimides, isocyanates, carbon dioxide, and isothiocyanates at room temperature. In the case of CO2, the cycloadduct with 1 (a carbonate complex) undergoes the facile ejection of CO2, demonstrating that this binding process is reversible. In the case of isothiocyanate, chalcogen metathesis with 1 takes place readily as the inclusion of a second equivalent of substrate in the reaction mixture rapidly yields a dithiocarbamate complex. This metathesis process was extended to the reactivity of 1 with phosphine chalcogenides, leading to the isolation of terminal sulfido imido and selenido imido complexes. Attempts to complete this series and generate the analogous terminal telluride led to the formation of a bidentate tritelluride (Te32-) complex. Triethylphosphine could only undergo oxygen atom transfer (OAT) with 1 under pressing thermal conditions that also led to C-N cleavage of the BDI ligand. In contrast, OAT between 1 and CO or 2,6-xylylisocyanide (XylNC) was found to be much more facile, proceeding within seconds at room temperature. While the addition of excess CO led to a rhenium(III) imido dicarbonyl complex, we found that the addition of 2 equiv of XylNC was necessary to promote OAT, resulting in the isolation of a rare example of a stable metal isocyanate complex. Our experimental observations of CO and XylNC and their OAT reactions with 1 inspired a mechanistic computational study to probe the intermediates and kinetic barriers along these reaction pathways. Finally, we describe 1,2-additions of both protic and hydridic substrates with the Re oxo moiety of 1, which most notably led to the syntheses of an uncommon example of a terminal rhenium hydroxide complex and an oxo-bridged Re-O-Zr hetero-bi-metallic complex that was generated using Schwartz's reagent (Cp2ZrHCl). A brief discussion of a potential alternative route to 1 is also presented.