Phosphorus Heterocycles Research Articles

Synthesis of Blue-Luminescent Seven-Membered Phosphorus Heterocycles.

A facile synthetic procedure to prepare π-extended seven-membered phosphorus heterocycles, both symmetric and asymmetric, is reported. The prepared molecules present a persistent nonplanar framework and are soluble in a wide variety of solvents. The seven-membered phosphorus heterocycles can be electrochemically reduced and oxidized, and photoluminesce with a blue color.

Borane‐Mediated Vinylphosphane Cycloaddition to Conjugated Ynones

Dimesitylvinylphosphane 4 reacts with a small series of conjugated ynones and B(C6F5)3 to give the five‐membered heterocyclic phosphorus containing products 8. The reaction of allyldimesitylphosphane with dimethylacetylene dicarboxylate and B(C6F5)3 follows a related pathway to give the six‐membered phosphorus containing product 12.

Phosphorus Post-Functionalization of Diphosphahexaarenes.

Diphosphahexaarenes are highly stable π‐extended frameworks containing two six‐membered phosphorus heterocycles that have emerged recently. Herein, we present a detailed investigation on the post‐functionalization reactions of their phosphorus centers with special emphasis on the selectivity of the processes and the impact of the phosphorus functionalizations into the physicochemical properties. These studies reveal that indeed the phosphorus atoms of the diphosphahexaarenes are readily available to be functionalized with quaternizing and oxidizing agents as well as borane groups without compromising the stability of the system. In addition, the optoelectronic properties of the diphosphahexaarenes are impacted by the phosphorus post‐modifications.

Reaction of 2-imino-2H-chromene-3-carboxamide with some phosphorus esters: Synthesis of some novel chromenes containing phosphorus heterocycles and phosphonate groups and their antioxidant and cytotoxicity properties

Novel chromenyl α-aminophosphonic acid 4 and dialkyl chromenyl phosphonate 6 have been obtained. In addition, some novel types of chromene fused with phosphorus heterocycles such as chromeno[4,3-c][1,2]azaphospholes 5 and 7, chromeno[2,3-d][1,3,2]diazaphosphinine 8 and 1,2-oxaphosphinino[3,4-c]pyridine 10 have been synthesized. The methodology depended on treatment of 2-imino-2H-chromene-3-carboxamide (1) with some phosphorus esters. The synthesized compounds were evaluated for antioxidant and cytotoxic activities. Among the synthesized compounds, compound 5 exhibited the most antioxidant activity with IC50 = 2.8 μg/mL in comparison with ascorbic acid as standard antioxidant. Also, compound 5 had significant cytotoxic effects against four cancer cell lines. Its IC50 values ranged between 4.96 and 7.44 μg/mL in comparison to doxorubicin (IC50 = 0.426–0.493 μg/mL).

Dismantling the Hyperconjugation of π-Conjugated Phosphorus Heterocycles.

The development of π-extended phosphorus heterocycles has been rapidly increasing because of their unique optoelectronics properties, which are very often considered to be a consequence of special hyperconjugative interactions. However, the latter interactions have primarily been investigated within the five-membered species, phospholes, and they are often conceptually extrapolated to the rest of π-extended phosphorus heterocycles (including six-membered P-heterocycles) despite evident structural differences. Herein, we report, for the first time, a detailed investigation that sheds light on the hyperconjugative effects of a series of phosphorus heterocyclic systems by means of EDA and NBO calculations within a DFT framework. Our results lay the foundations for the future design of π-extended phosphorus heterocycles with improved optoelectronics properties.

Antitumor activities of new iso(thio)cyanates and their nitrogen and sulphur heterocyclic phosphorus derivatives

Reaction of nucleophilic active phosphacumulenes with iso(thio)cyanates were performed. Novel heterocyclic four-membered or six-membered compounds containing sulfur and nitrogen nucleus namely, thietane, azetidine and thiazinane were prepared. Moreover, the thiocarbamoyl derivatives were produced from the reaction of the stable phosphonium ylides with the iso(thio)cyanate derivatives. Besides the cytotoxic activity of iso(thio)cyanate derivatives and some new organophosphorus compounds were determined, using MTT assay against human HepG2 hepatocellular carcinoma and MCF-7 adenocarcinoma breast cancer cell lines in comparison with the activity of the known anticancer drug 5-flurouracil as a reference drug. All the tested compounds showed concentration dependent increase in the growth inhibition percentage against HepG2 and MCF-7 cancer cell lines. Moreover, the synthesized thietanes and thiazinanes revealed anticancer activity with IC50 (20, 8.9, 12.7, 32.5 µg/mL) respectively against HepG2 and (20, 10.3, 20 and 20 µg/mL) respectively against MCF-7 cancer cell lines. The newly synthesized azetidines showed anticancer activity with IC50 (13.5 and 32.5 µg/mL) against HepG2 and IC50 (10 and 25.9 µg/mL) against MCF-7 cancer cell lines. Moreover, azetidinedione compound exhibited more potent activity than the azetidinone with both types of cancer cell lines. In addition the cytotoxic activity of the iso(thio)cyanates , and malonamic acid methyl ester compounds were also investigated. 4-Methoxyphenylisothiocyanate and methylisothiocyanate, with IC50 (25.9, 12.3 and 40, 20 µg/mL) respectively against HepG2 and MCF-7 cancer cells were reported. 1,2-Dichloro-4-isocyanatobenzene was simillar in potency to the known anticancer drug 5-flurouracil with IC50 (5.3 µg/mL) versus 5 µg/mL for 5-flurouracil against MCF-7. While, malonamic acid methyl ester compound had no effect on both types of cancer cell lines.

From Phosphaphenalenes to Diphosphahexaarenes: An Overview of Linearly Fused Six‐Membered Phosphorus Heterocycles

The chemistry of linearly fused systems based on six‐membered phosphorus heterocycles is currently experiencing an astonishing evolution. Even though the phosphorus analogs of naphthalene and anthracene were first synthesized in the late 1960s, laterally fused phosphorus heterocycles have recently demonstrated outstanding performances as biomarkers, sensors, and luminescent systems for organic electronics. In this microreview, we provide a comprehensive revision of relevant linearly fused systems based on six‐membered phosphorus heterocycles from their origin to the latest advances on the largest derivatives.

Lighting with organophosphorus materials: solution-processed blue/cyan light-emitting devices based on phosphaphenalenes.

A family of electroluminescent organophosphorus materials for solution-processed organic light-emitting diodes is reported. The investigated systems present a six-membered phosphorus heterocycle fused with a pyrrole or benzopyrrole moiety. The materials exhibit high thermal stability and are soluble in a variety of organic solvents. Already in very simple OLED architectures, the novel electroluminescent materials display blue or cyan luminescence; i.e. color coordinates x = 0.18; y = 0.21 and x = 0.22; y = 0.30, respectively, with performances that are in the range of state-of-the-art phosphazene materials. In electrofluorochromic devices, the color emission coordinates of the organophosphorus materials are tuned upon applying an electric potential. These findings set the bedrock for the development of new generations of organophosphorus light-emitting devices.

Organophosphorus-B(C6F5)3 adducts: towards new solid-state emitting materials.

The coordination of B(C6F5)3 to materials based on six-membered phosphorus heterocycles via P[double bond, length as m-dash]O bonds tunes their physicochemical properties both in solution and in the solid state, remarkably improving their performances in light-emitting layers.

Diphosphahexaarenes as Highly Fluorescent and Stable Materials

AbstractOligoarenes are regarded as subunits of π‐extended carbon nanoforms, such as graphene and nanotubes, with exceptional technological importance. Fused arenes can thus provide fundamental insight into the nature of the electronic properties of fused polyaromatic rings and pave the way for the design of extended graphene‐like materials. However, large π‐extended arenes often show low stability. Herein we report the straightforward preparation of linearly fused diphosphahexaarenes containing two six‐membered phosphorus heterocycles. They are highly stable towards air, water, and light over months in both solution and the solid state. Single‐crystal X‐ray crystallography confirmed the molecular structure of all derivatives. Investigations of their optoelectronic properties revealed that the diphosphahexaarenes exhibit ambipolar redox behavior and high fluorescence quantum yields. Embedding six‐membered phosphorus rings into large acenes thus opens up new opportunities for the investigation of polyaromatic systems.

Diphosphahexaarenes as Highly Fluorescent and Stable Materials.

Oligoarenes are regarded as subunits of π-extended carbon nanoforms, such as graphene and nanotubes, with exceptional technological importance. Fused arenes can thus provide fundamental insight into the nature of the electronic properties of fused polyaromatic rings and pave the way for the design of extended graphene-like materials. However, large π-extended arenes often show low stability. Herein we report the straightforward preparation of linearly fused diphosphahexaarenes containing two six-membered phosphorus heterocycles. They are highly stable towards air, water, and light over months in both solution and the solid state. Single-crystal X-ray crystallography confirmed the molecular structure of all derivatives. Investigations of their optoelectronic properties revealed that the diphosphahexaarenes exhibit ambipolar redox behavior and high fluorescence quantum yields. Embedding six-membered phosphorus rings into large acenes thus opens up new opportunities for the investigation of polyaromatic systems.

Structural Diversity and Dynamics of Nickel Complexes with Ambidentate Phosphorus Heterocycles

The reaction of [Ni(C2H4)(dtbpe)] with 1-alkyl-1,2-diphospholes afforded [Ni(1-alkyl-1,2-diphosphole)(dtbpe)] complexes. Both DNMR experimental and DFT calculation results have shown that in solution these complexes are in an equilibrium of two P–P side-on η2-coordinated 1-alkyl-1,2-diphosphole isomers. In one form, unusual η2 bonding occurred at a P2–P1 side, presumably at the expense of a vicinal P2–C1 π bond, and it could be characterized as a phosphametallacycle with the formal oxidation state of Ni(II). In the second isomer with the Ni(0) state, Ni bonds to the ligand through two σ interactions with phosphorus lone pairs. The P2 chemical shift, being heavily dependent on structure, can be used to monitor these isomer populations.

Expanding the chemistry of ring-fused 1,4-diphosphinines by stable mono anion formation.

A new sulfur-enriched tricyclic 1,4-diphosphinine (2) was synthesized and novel reactivity studies on the phosphorus heterocycle were performed: a weak anionic nucleophile (KHMDS) adds selectively thus forming a stable anionic 1,4-diphosphinine derivative (3b) which was fully characterized. The substitution potential of 3b was demonstrated using Ph2PCl to give 4b, while oxidation of 3b using elemental iodine furnished cleanly the P-P coupling product 5.

Highlights on π-systems based on six-membered phosphorus heterocycles.

π-Extended molecules based on six-membered phosphorus heterocycles are exceptional systems due to their unique structural and chemical properties. Even though the first six-membered phosphorus heterocycles were synthesized in the 1950s-1960s, their chemistry is currently experiencing a renaissance with the focus on materials science. In this perspective, we highlight relevant systems that emphasize the potential of these particular organophosphorus materials for different fields of research, from bio- to optoelectronic applications. We also discuss their properties and outline our personal outlook on the future efforts toward the next generation of improved organophosphorus materials.

2-(Trimethylsilyl)-λ3 -Phosphinine: Synthesis, Coordination Chemistry, and Reactivity.

The [4+2] cycloaddition reaction between 2-pyrone and Me3 Si-C≡P gives the corresponding 2-(trimethylsilyl)-λ3 -phosphinine in good yields as a rather air and moisture stable, colorless oil. Insight into the regioselectivity of the pericyclic reaction was obtained with the help of deuterium-labeling experiments. The silyl-phosphinine acts as a ligand for the preparation of a Cu(I) and the first crystallographically characterized phosphinine-Ag(I) complex. The title compound was further used as a starting material for an alternative preparation of the parent phosphinine C5 H5 P by means of protodesilylation with HCl. C5 H5 P reacts with CuBr⋅S(CH3 )2 to give an infinite Cu(I)Br coordination polymer. DFT calculations shed light on the influence of the -Si(CH3 )3 group on the electronic properties of the aromatic phosphorus heterocycle.

Triazaphospholenium Tetrafluoroborate: A Phosphorus Analogue of a 1,2,3-Triazole-Derived Carbene.

3H-1,2,3,4-Triazaphosphole derivatives can be selectively alkylated with Meerwein's reagent at the most nucleophilic nitrogen atom. According to the principle of valence isoelectronicity, the corresponding phosphorus heterocycle represents the first formal phosphorus analogue of the well-known 1,2,3-triazolylidenes (mesoionic carbenes). Theoretical calculations revealed that the cation in triazaphospholenium tetrafluoroborate is an aromatic system with a high degree of π-conjugation. First investigations showed that the cationic phosphorus heterocycle can stabilize a [Cu2 Br4 ]2- dianion by formation of a neutral coordination compound with an unusual bonding situation between phosphorus and copper(I).

A Theoretical Study on the Conformation of 5- and 6-Membered P-Heterocycles: 1- Substituted 2,3,4,5-Tetrahydro-1H-Phosphole 1-Oxides and 1,2,3,4,5,6-Hexahydrophosphinine 1-Oxides

Background: The conformation of ring compounds including different heterocycles may bear useful information. The conformational situation of P-heterocycles is a less studied field, practically there are only data for compounds with more heteroatoms (O and N beside P) in the ring. Objective: To fill this gap, we wished to evaluate the conformational situation of saturated P-heterocycles, such as 2,3,4,5-tetrahydro-1H-phosphole 1-oxides and 1,2,3,4,5,6-hexahydrophosphinine 1-oxides by theoretical calculations. Method: The B3LYP/6-311++G(2d,2p) method was used during the quantum chemical calculations aiming at the evaluation of the energetics of the possible conformational equilibriums and geometry of the conformers in the gas phase. Results: Theoretical calculations suggested that while the two optically inactive cis diastereomers of 1- substituted 3,4-dimethyl-2,3,4,5-tetrahydro-1H-phosphole 1-oxides exist as balanced conformational equilibria, the racemic trans forms are present as shifted equilibria towards the more stable conformers. At the same time, both the cis and trans racemic diastereomers of the monomethyl analogues may be described by equilibria biased towards the conformers with equatorial methyl groups. The 3-methyl-1,2,3,4,5,6- hexahydrophosphinine oxide diastereomers also involve biased equilibria. The energetics of the conformational interconversions in the gas phase were demonstrated by novel 3D diagrams. Conclusion: It is a surprising experience that in the saturated P-hetero ring in tetrahydrophosphole oxide derivatives, the P-center does not undergo a configurational change during the interconversions. This is, however, not the case with the 3-methyl-1,2,3,4,5,6-hexahydrophosphinine oxide rings, where the P-center is also “flexible”. Within the P(O)OH moiety of the 5-ring phosphinic acids, an intramolecular transfer of the proton is possible only on energy investment. At the same time, in an intermolecular relationship, the proton transfer is free. Keywords: Phosphorus heterocycles, conformational analysis, quantum chemistry, energetics, stereostructure, proton transfer.

One-Pot Catalyst-Free Domino Condensation/Intramolecular 1,3-Dipolar Cycloaddition: Highly Stereoselective Access to Phosphadihydrocoumarin-Fused N,N-Bicyclic Pyrazolidin-3-ones

A concise, atom-economic, and highly regio/stereoselective synthetic strategy was developed for the construction of phosphorus- and nitrogen-fused polycyclic skeleton derivatives. The one-pot, two-step, catalyst-free domino condensation/intramolecular cycloaddition reaction of various substituted 2-(vinylphosphoryloxy)benzaldehydes with pyrazolidin-3-one took place at room temperature. Three new bonds (C–C, 2 × C–N) and two new nitrogen and phosphorus heterocycles were simultaneously constructed. The reaction is particularly attractive due to features such as low cost, mild conditions, atom economy, high stereoselectivity, and potential biological activity of the product.

Reaction of 2-cyano-3-(4-oxo-4H-chromen-3-yl)prop-2-enamide with some phosphorus reagents: synthesis of some novel diethyl phosphonates, 1,2,3-diazaphosphinanes, 1,2,3-thiazaphosphinine and 1,2-azaphospholes bearing a chromone ring

Novel chromonyl phosphonic acid 3, diethyl chromonyl phosphonate 4, and diethyl chromonyl pyridinyl phosphonate 5 were obtained from treatment of 2-cyano-3-(4-oxo-4H-chromen-3-yl) prop-2-enamide (2) with phosphorous acid and its diesters. Also, an efficient route to functionalized phosphorus heterocycles such as 1,2,3-diazaphosphinane, 1,2,3-thiazaphosphinine and 1,2-azaphosphole bearing a chromone ring was achieved via reaction of compound 2 with some phosphorus sulfides and phosphorus tribromide. A key part of the reaction mechanisms is discussed. Structures of the new synthesized products were established on the basis of spectral data (IR, ESI-MS, 1H-, 13C and 31P-NMR spectra). An efficient route to functionalized phosphorus heterocycles such as 1,2,3-diazaphosphinane, 1,2,3-thiazaphosphinine and 1,2-azaphosphole bearing a chromone ring was achieved via reaction of 2-cyano-3-(4-oxo-4H-chromen-3-yl)prop-2-enamide with some phosphorus sulfides and phosphorus tribromide.

Annulated 1,3,4-Azadiphospholides: Heterocycles with Widely Tunable Optical Properties.

Phosphorus heterocycles find applications in the synthesis of π-conjugated compounds and as precursors for optoelectronic materials such as organic light-emitting diodes (OLEDs), electronic switches, and transistors. A high-yield, one-pot synthesis of anionic annulated 1,3,4-azadiphospholides from Na(OCP) and 2-chloropyridines is presented. The synthesis proceeds without the use of transition metals and tolerates a wide range of substrates. Cyano-substituted compounds are especially deeply colored and have absorption maxima which range from λmax =525 to 596 nm. The optical properties are dominated by the spatial separation of an electron acceptor and donor unit within one molecule (push-pull chromophore). The anionic 1,3,4-azadiphospholides are silylated to neutral siloxy compounds with a strong blue-shifted absorption. This reaction can be reversed by addition of fluoride ions, which allows fluoride ions to be detected in optically low concentrations.