Reaction Of Pentafluoropyridine Research Articles

Perfluoropyridylation of indoles via reaction of perfluorinated pyridines with indole compounds

The reaction of perfluoropyridines with indoles and bis(indolyl)methanes (BIMs) was investigated. The aromatic nucleophilic substitution of pentafluoropyridine with indoles occurs at the 4-position of pyridine ring by nitrogen site of indolyl anion, while reaction with 2,3,5,6-tetrafluoro-4-(phenylsulfonyl)pyridine gave a mixture of products arising substitution at 2-position of pyridine ring and replacement of phenylsulfonyl group. Furthermore, the reaction of pentafluoropyridine with BIMs yielded mixture of mono- and bis-perfluoropyridyl products.

Survey reactivity of 5-substituted tetrazoles toward pentafluoropyridine

Reactivity of some 5-substituted tetrazoles with pentafluoropyridine under basic conditions in acetonitrile was investigated. The reaction of pentafluoropyridine with tetrazoles regioselectively occurs at the 4-position of pyridine ring by N2 in the tetrazole ring. Tetrazoles with substituents at the position 5 such as Ph, 4-NO2C6H4, 4-CF3CONHC6H4, 4-ClC6H4CH2, EtOOCCH2, and 5-tetrazolyl−CH2 gave products containing unchanged tetrazole moiety. In contrast, tetrazole with substituents at the position 5 such as 3-(5-tetrazolyl)C6H4, 4-MeOC6H4, and 3-CF3CONHC6H4, gave hydrazide products via degradation of tetrazole ring.

Reactions of pentafluoropyridine with amidoximes

In this paper, site reactivity of amidoximes with pentafluoropyridine under basic conditions in dry CH3CN was investigated. The aromatic nucleophilic substitution of pentafluoropyridine with amidoximes occurs in the 4-position of the pyridine ring by the oxygen site of amidoximes and followed by reaction of other sites, depending on reaction conditions. Substituted imidamide systems 4a–g were readily accessed using a 1:1 molar ratio of pentafluoropyridine and amidoximes in concentrated acetonitrile and in reflux condition for 6 h, while reaction of pentafluoropyridine with amidoximes in 1:1 molar ratio and in diluted acetonitrile under reflux condition for 24 h gave novel pyridooxadiazine system 4h, i. Pentafluoropyridine reacts also with amidoximes in 2:1 molar ratio under dry conditions to afford the bis-perfluoropyridyl imidamide systems 4j, k.

Synthesis, Characterization and Crystal Structure of 1,4,5,8-Tetrakis(Perfluoropyridin4-yloxy) Naphthalene

1,4,5,8-tetrakis(perfluoropyridin-4-yloxy)naphthalene (tetra-PPN) was synthesized via a one-pot pseudo-five-component reaction of pentafluoropyridine and 5,8-dihydroxy-1,4-tetralindione under basic conditions in DMF. The asymmetric unit contains one half-mol ecule of tetra-PPN and data reveals that half of the molecule being related to the other via inversion symmetry. A detailed analysis of the intermolecular interactions of the compound has been performed using Hirshfeld surfaces. The optimized geometrical parameters and calculated spectroscopic features obtained by quantum chemical calculations using density functional (DFT) methods. In addition, to support the experimental results, the 19F NMR values are obtained using B3LYP method. The obtained results are compared with experimental values show a very good agreement with the experimental data.

Reaction of hydroxyl-quinoline with pentafluoropyridin.

Reaction of pentafluoropyridine with 2 or 8-hydroxyl-quinoline under basic conditions in acetonitrile gives 4-oxy quinoline 2,3,5,6-tetrafluoropyridine derivatives in good yields. All the compounds were characterized using 1H, 13C, 19F-NMR and MS spectroscopy.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3410-z) contains supplementary material, which is available to authorized users.

Reaction of hydroxylated naphtoquinones/antraquinones with pentafluoropyridine.

In this study, the reaction of pentafluoropyridine with hydroxylated naphtoquinones and hydroxylated antraquinones was investigated under basic conditions in DMF. One or two hydroxyl group in naphtoquinones and antraquinones react with pentafluoropyridine to give mono and di-tetrafluoropyridyl naphtoquinones/antraquinones. All the compounds were characterized using 1H, 13C and 19F-NMR spectroscopy.

Synthesis of 2,3,5,6-tetrafluoro-pyridine derivatives from reaction of pentafluoropyridine with malononitrile, piperazine and tetrazole-5-thiol.

Some pentafluoropyridine derivatives have been synthesized by the reaction of pentafluoropyridine with appropriate C, S and N-nucleophile such as malononitrile, 1-methyl-tetrazole-5-thiol and piperazine. These reactions provided 4-substituted 2,3,5,6-tetrafluoropyridine derivatives in good yields. All the compounds were characterized using 1H, 13C and 19F-NMR spectroscopy and X-ray crystallography.

Studies on the Synthesis of Specifically Fluorinated 4‐Amino‐ pyridine Derivatives by Regioselective Nucleophilic Aromatic Substitution and Catalytic Hydrodefluorination

AbstractThe reactions of pentafluoropyridine and 2,4,6‐trifluoropyridine with a series of primary and secondary amines were studied. Whereas the nucleophilic aromatic substitution of pentafluoropyridine occurs with high regioselectivity in all cases, providing the expected 4‐aminopyridine derivatives in excellent yields, the regioselectivity of 2,4,6‐trifluoropyridine is dependent on the steric hindrance of the attacking nucleophile. Small nucleophiles such as morpholine attack the 4‐position of the pyridine ring with high preference, but more bulky diamines attack the 2‐ and 4‐positions leading to the formation of three regioisomeric products. (R,R)‐1,2‐Diaminocyclohexane as moderately bulky diamine reacted with 2,4,6‐trifluoropyridine to afford the desired bis(4‐aminopyridinyl)cyclohexane derivative in 30% yield. For hydrodefluorination two methods were examined. A two‐step procedure employing hydrazine and subsequently copper(II) sulfate removed just one fluorine substituent, but is not sufficiently high yielding for the reduction of more complex substrates. With the system titanocene difluoride as pre‐catalyst and diphenylsilane as reducing agent we were able to selectively remove fluorine substituents at positions C‐2 and C‐4 of a variety of 4‐aminopyridine derivatives. This protocol allows the synthesis of compounds such as the divalent chiral 4‐(dimethylamino)pyridine (DMAP) analogue (R,R)‐trans‐N,N′‐dimethyl‐N,N′‐bis(pyridin‐4‐yl)cyclohexane‐1,2‐diamine with fair overall yield.magnified image

ChemInform Abstract: Environmental Friendly Synthesis of Bis‐perfluoropyridine and Pyrimidine in Water.

AbstractThe title compounds are easily and efficiently obtained by reaction of pentafluoropyridine (I) or tetrafluoropyrimidine (VIII) with mono and bidentate N‐nucleophiles using water as green solvent.

Reaction of pentafluoropyridine with oxime nucleophiles via SNAr reactions for preparation of new p-substituted tetrafluoropyridyl derivatives

A new and improved preparation of perfluoropyridin-4-yloxy imino compounds from pentafluoropyridine is described. Pentafluoropyridine was used as the starting material for the preparation of a range of pyridine derivatives that bear mono-substituent. The nucleophilic substitution of pentafluoropyridine with oximes occurs at the 4-position of pyridine ring by the oxygen site of oxime. Therefore, in this work, we wish to report an efficient synthetic route of the oxime-containing perfluoroheteroaromatic systems for the first time. .

C–H and C–F Bond Activations at a Rhodium(I) Boryl Complex: Reaction Steps for the Catalytic Borylation of Fluorinated Aromatics

Treatment of the rhodium(I) boryl complex [Rh(Bpin)(PEt3)3] (1, pin = pinacolato = O2C2Me4) with pentafluorobenzene, 1,3,5-trifluorobenzene, 1,3-difluorobenzene, or 3,5-difluoropyridine led to C–H activation reactions to give the aryl complexes [Rh(C6F5)(PEt3)3] (4), [Rh(2,4,6-C6F3H2)(PEt3)3] (5), [Rh(2,6-C6F2H3)(PEt3)3] (6), and [Rh{4-(3,5-C5NF2H2)}(PEt3)3] (8). For 5, 6, and 8 consecutive reactions with in situ generated HBpin occurred to yield [Rh(H)(PEt3)3] (7) and boronic esters. The boryl complex 1 gave with hexafluorobenzene or perfluorotoluene the C–F activation products [Rh(C6F5)(PEt3)3] (4) and [Rh(4-C6F4CF3)(PEt3)3] (9), respectively. The complexes 5, 6, and 9 react with B2pin2 to yield 1 and boronic ester derivatives. On the basis of these stoichiometric reactions catalytic C–H and C–F borylation reactions using 1 or 7 were developed to generate 2-Bpin-1,3,5-C6F3H2, 2-Bpin-1,3-C6F2H3, and 4-Bpin-C6F4CF3 from 1,3,5-trifluorobenzene, 1,3-difluorobenzene, or perfluorotoluene and B2pin2. On treatment of pentafluoropyridine with B2pin2 in the presence of 1 or 7 as catalyst 2-Bpin-C5NF4 was synthesized by C–F borylation at the 2-position. Using 2,3,5,6-tetrafluoropyridine, B2pin2, and catalytic amounts of 7 led to a C–H borylation reaction at the 4-position. 4-Bpin-C5NF4 can also be prepared by the reaction of 2,3,5,6-tetrafluoropyridine with stoichiometric amounts of HBpin or by the reaction of pentafluoropyridine with an excess of HBpin in the presence of 7, whereas the reaction of pentafluoropyridine with stoichiometric amounts of HBpin and 5 mol % 7 resulted in the formation of 2,3,5,6-tetrafluoropyridine via hydrodefluorination reaction at the 4-position. This regioselectivity contrasts the borylation of pentafluoropyridine at the 2-position with 1 as catalyst. Overall, the obtained fluorinated aryl boronic ester derivatives might serve as versatile building blocks.

Synthesis of some fluorinated thiazolopyridine from pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine

In this study, the reaction of pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine with difunctional nitrogen and sulfur nucleophiles such as thiourea, thioamide derivatives, and unsymmetrical bidentate nitrogen nucleophiles such as diamino-triazole and amino-imidazole in the presence of sodium carbonate was investigated.

Environmental Friendly Synthesis of Bis-Perfluoropyridine and Pyrimidine in Water

An easy, efficient and simple approach for the synthesis of some perfluoropyridine and pyrimidine derivatives by reaction of pentafluoropyridine and tetrafluoropyrimidine with mono and bidentate N-nucleophiles in the presence of potassium carbonate in water as a green solvent, at room temperature is reported. The structures of some products were unambiguously confirmed by X-ray crystallography. INTRODUCTION Organic reactions in aqueous media have attracted considerable attention in recent years, since they offer a powerful tool for minimizing waste production and harmful organic solvent dispersal.1 Some particular properties of water make this solvent very attractive (e.g., non-toxicity, non-inflammability, high heat capacity, possibility of controlling pH, isolating insoluble solid products by filtration and recycling inorganic catalysts and itself), allowing organic processes in aqueous medium to be safer, very efficient, and highly selective.2 Because water is natural, abundant, cheap, and readily available, it is thought to be an ideal solvent for both laboratory and industrial chemical processes.3 It is not only abundant, inexpensive, and environmentally benign but it also shows novel reactivity and selectivity for simple synthesis of biologically active compounds in the pharmaceutical or agrochemical industries.4-7 In fact, as clearly stated by Sheldon, it is generally recognized that “the best solvent is no solvent and if a solvent is needed it should preferably be water”.8 Traditionally, organic reactions are carried out in organic solvents (e.g., THF, DMF) and oftentimes at temperatures above ambient,9 although use of (potentially toxic) organic solvents is always the norm, which by definition fails to meet the 12 Principles of Green Chemistry.10 Syntheses of polyfunctional heterocyclic fused ring systems with low molecular weight are important in life science industries.11,12 Pentafluoropyridine has attracted considerable interest due to its synthetic utility. Various multi-functional pyridine derivatives and construction of new heterocyclic and macrocyclic systems could be accessed from simple reaction conditions.13-20 These were including reaction of various 738 HETEROCYCLES, Vol. 91, No. 4, 2015

A mild method for the synthesis of a novel dehydrobutyrine-containing amino acid

Dehydrobutyrine is an amino acid that is present in a range of peptide natural products. Reaction of pentafluoropyridine with threonine and subsequent E1cb-type elimination allowed the preparation of novel dehydrobutyrine-containing amino acids under mild conditions.

ChemInform Abstract: Survey of Reactivity of Some Enolates with Pentafluoropyridine and 4‐Phenylsulfonyl‐2,3,5,6‐tetrafluoropyridine.

AbstractThe reaction of pentafluoropyridine with enolates takes place at the 4‐position of the pyridine ring [cf.

Synthesis and molecular structure of a perfluorinated pyridyl carbanion

Reaction of pentafluoropyridine with sodium nitromethanide allowed the isolation and characterisation of the first perfluorinated pyridyl carbanion system, sodium nitrobis(perfluoropyridin-4-yl)methanide, by X-ray crystallography.

ChemInform Abstract: Synthesis and Structural Study of Bis‐perfluoropyridyl Bridged by 1,4 and 1,2 Dihydropyridine.

AbstractThe reaction of pentafluoropyridine (I) with 2‐ and 4‐aminopyridines (II) and (IV) is described.

Ultrasound promoted facile synthesis of some pentafluoropyridine derivatives at ambient conditions

Some pentafluoropyridine derivatives have been synthesized by the reaction of pentafluoropyridine with appropriate mono and bidentate nucleophile under ultrasonic irradiation. This new methodology provides good to excellent yields in short reaction times (25–120 min) at room temperature.

Polyfunctional molecules in processes of aromatic nucleophilic substitution 3. Pentaf luoropyridines as scaffolds for synthesis of liquid-phase combinatorial libraries based on S N Ar processes

A possibility of using polyfluorinated pyridines as multiply modified molecules, i.e., scaffolds, in processes of aromatic nucleophilic substitution (S N Ar) for the synthesis of liquid-phase combinatorial libraries was studied. The real and “virtual” combinatorial libraries of diaryl ethers were synthesized by the reactions of pentafluoropyridine with phenol and its derivatives. Some criteria for the estimation of the quality of the libraries were formulated. A rational methodology for the preparation of representative combinatorial mixtures on the basis of processes of the S N Ar type in polyfluorinated arenes was proposed. The libraries can be used in highly efficient biological screening of low-molecular-weight regulators of transferase functioning.

Polyfunctional Tetrahydropyrido[2,3‐b]pyrazine Scaffolds from 4‐Phenylsulfonyl Tetrafluoropyridine.

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