Secondary Phosphine Chalcogenides Research Articles

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.

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.

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).

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%.

Oxidative Cross-Coupling of Cysteamine with Secondary Phosphine Chalcogenides: Aspects of Reaction Chemoselectivity

Cysteamine (2-aminoethanethiol) undergoes oxidative cross-coupling with secondary phosphine sulfides and phosphine selenides under mild conditions (room temperature, 2–5 h, CCl4/Et3N) to give products of monocoupling at the amino group (ethylchalcogenophosphinic amides with free SH functions) and dicoupling (l-chalcogenophosphorylamino-2-chalcogenothioethanes) in 72–85% total yield. Under similar conditions, stirring an equimolar mixture of bis(2-phenylethyl)phosphine sulfide (or selenide), 1-butylamine, and 1-butanethiol leads to the chemoselective formation of the corresponding chalcogenophosphinic amides in high yield.

Catalyst-free addition of secondary phosphine chalcogenides to pyrazolecarbaldehydes

(Chalcogenophosphoryl)(hydroxyl)methyl-substituted pyrazoles were obtained by catalyst-free reaction between 4- and 5-pyrazolecarbaldehydes and secondary phosphine chalcogenides R2P(X)H [R = Ph, (CH2)2Ph, X = O, S, Se] at 23–50 °C in toluene.

Acetylene-Triggered Reductive Incorporation of Phosphine Chalcogenides into a Quinoline Scaffold: Toward SNHAr Reaction.

Quinolines react with acylacetylenes and secondary phosphine chalcogenides at 20-75 °C to afford N-acylvinyl-2(1)-chalcogenophosphoryldihydroquinolines in good and excellent yields. Unlike the pyridine-derived similar intermediates, which eliminate E-alkenes to give aromatic chalcogenophosphorylpyridines, thereby completing SNHAr reaction, with quinolines, the reaction stops at the formation of the above phosphorylated N-acylvinyl-dihydroquinolines, thus representing a pendant SNHAr process. This reaction opens a one-pot atom-economic single-step access to pharmaceutically targeted phosphorylated functionalized dihydroquinolines and isoquinolines.

Unexpected Reaction of Secondary Phosphine Chalcogenides with Acridine

Secondary phosphine chalcogenides reacted with acridine under mild conditions according to the nucleophilic addition scheme to form 9-chalcogenophosphoryl-9,10-dihydroacridines.

Синтез и антимикробная активность новых фосфорсодержащих производных пиридина

The directed synthesis of new pharmacophoric molecules is one of the urgent tasks of organic chemistry. A special place in this area is occupied by vital nitrogen-containing heterocycles and their derivatives, on the basis of which new promising precursors of drugs are created. For example, pyridinium salts are part of such well-known drugs as pyridoxine, mexidol and metadoxine. Phosphorus-containing pyridine derivatives, among which compounds with cytotoxic and antimicrobial properties have been identified, are also being actively studied now. Thus, the development of convenient approaches for obtaining new functional phosphorus-containing pyridine derivatives is an important and timely task. Special attention is paid to synthetic methods that correspond to the PASE (pot, atom and step economy) paradigm. Using this approach, we have synthesized hydrochlorides and tosylates of 4-bis(2-phenylethyl)chalcogenophosphoryl-pyridine, not described previously, by practically quantitative interaction of the available 4-bis(2-phenylethyl)chalcogenophosphorylpyridines with hydrochloric or 4-methylbenzenesulfonic acids at room temperature or slight heating (40-45 °C). The reaction proceeds regioselectively on the nitrogen atom of the base pyridine. The second reaction center in the 4-bis(2-phenylethyl)chalcogenophosphorylpyridine molecule, chalcogenophosphoryl group, does not participate in the studied process, even when using an excess of hydrochloric acid. The starting 4-bis(2-phenylethyl)chalcogenophosphorylpyridines are easily obtained on the basis of the original reaction of pyridine with secondary phosphine chalcogenides with the assistance of electron-deficient acetylenes. Using the example of microorganisms of different taxonomic groups: Bacillus subtilis B-406, Enterococcus durans B-603, Penicillium citreo-viride F-1777, Escherichia coli B-1238, we have found that the target hydrochlorides and tosylates of 4-bis(2-phenylethyl)chalcogenophosphorylpyridine exhibit pronounced antimicrobial activity against non-spore gram-positive microorganisms.

Phosphorylation of Acetylaminophenols with Secondary Phosphine Chalcogenides: Synthesis of O-(Acetylamino)phenyl Chalcogenophosphinates

Oxidative cross-coupling of 4-acetylaminophenol (paracetamol) and its structural isomers (2- and 3-acetylaminophenols) with secondary phosphine chalcogenides at room temperature in the CCl4–Et3N system produced O-(acetylamino)phenyl chalcogeneophosphinates in a 80% yield.

Catalyst-Free Phosphorylation of Acridine with Secondary Phosphine Chalcogenides: Nucleophilic Addition vs SNHAr Reaction.

Acridine adds secondary phosphine chalcogenides HP(X)R2 (X = O, S, Se; R = Ar, ArAlk) under catalyst-free conditions at 70-75 °C (both in the presence and absence of the electron-deficient acetylenes) to give 9-chalcogenophosphoryl-9,10-dihydroacridines in 61-94% yields. This contrasts with pyridines, which under similar conditions undergo an SNHAr reaction, wherein electron-deficient acetylenes play the role of oxidants. For acridine, the SNHAr step has been accomplished by the oxidation of the intermediate 9-phosphoryl-9,10-dihydroacridines (X = O) with chloranil.

Solvent-free synthesis of 4-chalcogenophosphorylpyridines via[formula omitted] reaction of pyridines with secondary phosphine chalcogenides

Solvent- and catalyst-free synthesis of 4-chalcogenophosphorylpyridines by oxidative regioselective cross-coupling of pyridines with secondary phosphine chalcogenides using 1,3-diphenylprop-2-yn-1-one as a trigger and oxidant under mild conditions (70–75°C, 5.5–7 h) is reported.

Chemoselective Cross-Coupling of Secondary Phosphine Chalcogenides with Aminophenols: Synthesis of Aminophenylchalcogenophosphinic Acids O-Esters

Chemoselective reaction of secondary phosphine chalcogenides with 2-aminophenol under mild conditions (room temperature, 2–4 h, CCl4–Et3N) led to the formation of aminophenylchalcogenophosphinic acids O-esters in a yield of up to 80%.

Three-Component Reaction of 4-Methylpyridine with Alkyl Propiolates and Secondary Phosphine Chalcogenides

The reaction between 4-methylpyridine, alkyl propiolates, and secondary phosphine oxides proceeded as N-vinylation-C-phosphorylation with stereo- and regioselective formation of (E)-N-ethenyl-C2- phosphoryl-1,2-dihydropyridines [when using bis(2-phenylethyl)phosphine oxide] or (E)-N-ethenyl-C4- phosphoryl-1,4-dihydropyridines (when using diphenylphosphine oxide). The process occurred at 60–62°C within 3 h to give functional dihydropyridines in 40–82% yield. Under similar conditions, bis(2-phenylethyl) phosphine sulfide and selenide reacted with alkyl propiolates preferably by nucleophilic PH-monoaddition at the triple bond.

Metal-free site selective cross-coupling of pyridines with secondary phosphine chalcogenides using acylacetylenes as oxidants

Pyridines undergo site selective cross-coupling with secondary phosphine chalcogenides (oxides, sulfides, and selenides) in the presence of acylphenylacetylenes under metal-free mild conditions (70-75 °C, MeCN) to afford 4-chalcogenophosphoryl pyridines in up to 71% yield. In this new type of SNHAr reaction acylacetylenes act as oxidants, being stereoselectively reduced to the corresponding olefins of the E-configuration.

Structural effect in the reductive vinylation/phosphorylation of pyridines with alkyl propiolates and secondary phosphine chalcogenides: protonation vs. zwitterion generation

The non-catalyzed reaction of 2- and 3-substituted pyridines with alkyl propiolates and secondary phosphine chalcogenides (50–52 °C, MeCN) produces stereo-, regio- and chemoselectively 1-[(E)-2-(alkoxycarbonyl)ethenyl]-4-chalcogenophosphoryl- 1,4-dihydropyridines in 57–90% yields, the adducts of pyridines with alkyl propiolates being the zwitterionic intermediates. 4-Methylpyridine mainly catalyzes nucleophilic addition of secondary phosphine chalcogenides to alkyl propiolates.

Catalyst- and Solvent-Free Addition of the P–H Species to Alkenes and Alkynes: A Green Methodology for C–P Bond Formation

Traditional methods for C–P bond formation via direct addition of P–H species to unsaturated compounds are usually implemented in the presence of base and metal catalysts or radical initiators in various organic solvents. During the last five years, a novel efficient and general catalyst/initiator- and solvent-free version of the hydrophosphination and hydrophosphinylation of multiple C–C bonds with H-phosphines and their chalcogenides has begun to develop and it is attracting growing attention. This approach corresponds to the recently emerged pot-, atom-, and step-economy (PASE) green paradigm. This review covers the literature on the synthesis of useful and in-demand organophosphorus compounds via catalyst- and solvent-free addition of P–H species to alkenes and alkynes.1 Introduction2 Addition of Secondary Phosphines to Alkenes3 Hydrophosphinylation of Alkenes with Secondary Phosphine Chalcogenides3.1 Oxidative Addition of Phosphine Oxides to Vinyl Sulfides3.2 Addition of Secondary Phosphine Sulfides and Phosphine Selenides to Alkenes3.3 Addition of Secondary Phosphine Sulfides and Phosphine Selenides to Divinyl Chalcogenides3.4 Hydrophosphinylation of Alkenes with Secondary Phosphine/Chalcogen Pair (Three-Component Reactions)4 Addition of Secondary Phosphines to Alkynes5 Addition of Secondary Phosphine Chalcogenides to Alkynes6 Conclusion

Oxidative coupling of hydroxy- or aminoazobenzenes with secondary phosphine chalcogenides: Towards new media-responsive molecular switches

One or two chalcogenophosphinate groups were introduced to the azobenzene scaffold via the oxidative cross-coupling reaction of 4-amino-, 4-hydroxy- and 4,4′-dihydroxyazobenzenes with secondary phosphine chalcogenides using the CCl4/Et3N system under mild conditions in 41–95% yield. Cis-trans photoisomerization of the phosphorylated azobenzenes was reversibly controlled by alternating UV/Vis light irradiation. The chalcogenophosphinate group imparts the properties of media-responsive molecular photoswitches to the synthesized azobenzenes.

ChemInform Abstract: One‐Pot Regio‐ and Stereoselective Synthesis of Tertiary Phosphine Chalcogenides with (E)‐N‐Ethenyl‐1,2‐dihydroquinoline Functionalities.

AbstractThe synthesis of the title compounds via three‐component reaction between secondary phosphine chalcogenides quinoline or isoquinoline and alkyl propiolates or acetylene dicarboxylate is reported.

One-pot regio- and stereoselective synthesis of tertiary phosphine chalcogenides with (E)-N-ethenyl-1,2-dihydroquinoline functionalities

The three-component reaction between secondary phosphine chalcogenides, quinoline or isoquinoline and alkyl propiolates or acetylene dicarboxylates occurs under mild conditions, without a catalyst, to regio- and stereoselectively afford tertiary phosphine chalcogenides with (E)-N-ethenyl-1,2-dihydroquinoline functionalities in up to 93% yield.