Synthesis of Aromatic Nitriles Using Nonmetallic Cyano‐Group Sources

Aromatic nitriles are prepared efficiently through transition‐metal‐mediated cyanation of aryl (pseudo)halides with metallic cyano‐group sources, such as CuCN, KCN, NaCN, Zn(CN)₂, TMSCN, or K₄[Fe(CN)₆]. However, this approach often suffers from drawbacks, such as the formation of stoichiometric amounts of metal waste, the poisoning of the metal catalysts, or the generation of toxic HCN gas. As a result, a range of “nonmetallic” organic cyano‐group sources have been explored for the cyanation of aryl halides and arene C? H bonds. This Minireview summarizes types of nonmetallic cyano‐group sources and their applications in the preparation of aryl nitriles.     

Palladium-catalyzed cyanation of aryl halides using K4[Fe(CN)6] as cyanide source, water as solvent, and microwave heating

A methodology for the cyanation of aryl iodides and activated aryl bromides is reported using water as the solvent and K₄[Fe(CN)₆] as the cyanide source. Reactions are complete within 20 min.     

Efficient cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by a palladium-indolylphosphine complex

This study describes a general palladium-catalyzed cyanation of aryl bromides using K₄[Fe(CN)₆] as the cyanide surrogate. The reactions can be successfully conducted under mild reaction conditions (at 50 °C) in mixed solvents (water/MeCN = 1:1) without any surfactant additives, and afford the desired aryl nitriles in good-to-excellent yields. Particularly noteworthy is that this system allows the mildest reaction temperature reported so far for palladium-catalyzed cyanation of aryl bromides with K₄[Fe(CN)₆] source in general. Common functional groups, including keto, aldehyde, free amine, and heterocyclic substrates are compatible under this system. Interestingly, the phosphine ligands bearing -PCy₂ moiety, which usually show excellent activity in aryl halide couplings, are found less effective than the corresponding ligands with -PPh₂ group.     

An efficient palladium catalytic system for microwave assisted cyanation of aryl halides

Application of a new catalytic system for cyanation reaction of various aryl halides using K₄[Fe(CN)₆] as cyanating source was examined. The reactions were performed under microwave irradiation and results showed that application of this catalytic system and DMF at 130 °C minimized the reaction times from hours to minutes in good to excellent yields.     

Copper-catalyzed cyanation of benzyl chlorides with non-toxic K4[Fe(CN)6]

Copper-based catalysts were firstly introduced into the cyanation of benzyl chlorides with non-toxic K₄[Fe(CN)₆]. The presented method avoids the use of extremely poisonous alkali cyanides and precious palladium catalysts. No other reagent apart from CuI, K₄[Fe(CN)₆] and toluene was used in the cyanation, showing that the presented protocol is simple and practical. A series of benzyl chlorides were smoothly cyanated in up to 85% yield under the optimal conditions.     

Ligand-free CuI-catalyzed cyanation of aryl halides using K4[Fe(CN)6] as cyanide source and water as solvent

A methodology for the cyanation of aryl iodides is reported using copper iodide as the catalyst, K₄[Fe(CN)₆] as the cyanide source, and small quantities of water and tetraethylene glycol as the solvent. Reactions are complete within 30 min of microwave heating at 175 °C. A simple work-up procedure has also been devised.     

Microwave-enhanced cyanation of aryl halides with a dimeric <Emphasis Type="Italic">ortho</Emphasis>-palladated complex catalyst

Abstract  

A new dimeric ortho-palladated complex of 2-methoxyphenethylamine was synthesized and characterized and its application as a cyanation catalyst was investigated. The main advantages of this catalyst are its easy preparation, handling, stability, and moisture insensitivity. Thus, [Pd{C₆H₃(CH₂CH₂NH₂)-4-OMe-5-κ ²-C,N}(μ-Br)]₂ showed excellent catalytic activity for the cyanation of aryl iodides and bromides with K₄[Fe(CN)₆], in DMF in the presence of K₂CO₃ under microwave irradiation and conventional heating at 130 °C to give the desired cyanoarene products in good to high yields. The less reactive aryl chlorides also react with K₄[Fe(CN)₆] to give moderate yields of the aromatic nitriles. The effects of various parameters such as solvent, base, and amount of catalyst were studied. The reaction is suitable for a wide variety of substituted aryl halides with different electronic properties. Application of microwave irradiation improved the yields of the reactions and reduced the reaction times from hours to minutes.     

硅胶功能化的N-丙哌嗪固载钯纳米粒子作为有效的多相催化剂用于氰化反应(英文)

An efficient heterogeneous Pd catalytic system has been developed, based on immobilization of Pd nanoparticles (PNPs) on a silica-bonded N-propylpiperazine (SBNPP) substrate. The SBNPP substrate effectively stabilizes the PNPs and improves their stability against aggregation. The catalytic activity of this catalyst was investigated in the cyanation of aryl halides with K4[Fe(CN)6 ] as the cyanide source. The catalyst could be recycled several times without appreciable loss of catalytic activity.     

Efficient cyanation of aryl halide with K4[Fe(CN)6]⋅3H2O catalyzed by a P–O bidentate chelate palladium complex under air

Cyanation of aryl halide with K₄[Fe(CN)₆]?3H₂O has been carried out in the presence of a high‐activity catalyst: an air‐stable P–O bidentate chelate palladium complex. This method is applicable to both activated and deactivated aryl halides, and even a variety of aromatic nitriles are obtained in good yields under aerobic conditions. Copyright © 2014 John Wiley & Sons, Ltd.     

A palladium-catalyzed one-pot procedure for the regioselective dimerization and cyanation of indoles

A one-pot method for the regioselective dimerization and cyanation of indoles has been developed. The reaction uses safe and nontoxic K₄[Fe(CN)₆]·3H₂O as the cyanating agent which introduces selectively a cyano group into the 3-position of biindoles with high efficiency.     

Design of a palladium nanocatalyst produced from Schiff base modified dialdehyde cellulose and its application in aryl halide cyanation and reduction of nitroarenes

In this paper, a versatile heterogeneous catalyst system (Pd-DAC-Sch) based on stabilization of palladium nanoparticles on dialdehyde cellulose Schiff base (DAC-Sch) was developed and characterized thoroughly by a variety of spectroscopic (FT-IR, XRD, ¹³C CPMAS, and TG) and microscopic (SEM/EDS and TEM) methods. Then the prepared Pd-DAC-Sch system was evaluated as a heterogeneous nanocatalyst for aryl halide cyanation in the presence of K₄[Fe(CN)₆] and for reduction of nitroarenes to amines using NaBH₄ in water at room temperature. Pd-DAC-Sch nanocatalyst efficiently cyanated various aryl halides by providing satisfactory reaction yields of 87–98%. Moreover, Pd-DAC-Sch catalyzed 4-nitrophenole (4-NA), 2-nitroaniline (2-NA), and 4-nitroaniline (4-NA) reductions in short reaction time. More importantly, Pd-DAC-Sch nanocatalyst was reapplied up to six successive runs by giving a yield of 86% without any important changes in its morphology and structure. This paper shows that Pd-DAC-Sch is a highly effective, reusable, chemically stable, and therefore a useful nanocatalyst.

     

Pd-catalyzed cyanation of benzyl chlorides with nontoxic K4[Fe(CN)6]

Non-toxic K₄[Fe(CN)₆] was demonstrated to be effective as a green cyanating agent for the cyanation of alkyl halides using PPh₃/Pd(OAc)₂ as a catalyst system. The presented method allowed a series of benzyl chlorides to be smoothly cyanated in up to 88% yield. In order to avoid or suppress the deactivation of the catalyst, the reaction was required to be performed in a stringent inert ambiance.     

Highly efficient nickel/phosphine catalyzed cross-couplings of diarylborinic acids with aryl tosylates and sulfamates

<正>4-Methoxy-4′-methylbiphenyl(3aa) [1] MeO White solid(0.324 g, 82% from aryl tosylate, 0.356 g, 90% from aryl sulfamate); m.p. 111–112 °C; 1H NMR(400 MHz,CDCl3) δ 7.50(d, J = 8.4 Hz, 2H), 7.44(d, J = 8.0 Hz, 2H), 7.21(d, J = 8.0 Hz, 2H), 6.95(d, J = 8.8 Hz, 2H), 3.82(s, 3H), 2.37(s, 3H); 13 C NMR(100 MHz, CDCl3) δ 159.0, 138.0, 136.4, 133.8, 129.5, 128.0, 126.6, 114.2, 55.4, 21.1. 4,4′-Dimethylbiphenyl(3ab) [1] White solid(0.320 g, 88% from aryl tosylate, 0.346 g, 95% from aryl sulfamate); m.p. 122–123 °C; 1H NMR(400 MHz,CDCl3) δ 7.47(d, J = 8.0 Hz, 4H), 7.22(d, J = 8.0 Hz, 4H), 2.37(s, 6H); 13 C NMR(100 MHz, CDCl3) δ 138.4, 136.8, 129.5, 126.9, 21.2.     

Preparation of57Fe enriched K4[Fe(CN)6] and K3[Fe(CN)6]

A simple method to prepare⁵⁷Fe enriched K₄[Fe(CN)₆] and K₃[Fe(CN)₆] is described. The yields of the products are much better than those reported in the literature so far. The enrichment is essential for⁵⁷Fe Mössbauer investigation in a variety of Prussiate type complexes and other inorganic compounds which are conveniently prepared from K₄[Fe(CN)₆] and K₃[Fe(CN)₆]. K₄[Fe(CN)₆] was obtained by reacting freshly prepared Fe(OH)₃ with glacial acetic acid and treating with iron acetate in boiling aqueous solution of KCN. The novel feature of the procedure to obtain K₃[Fe(CN)₆] is that the oxidation of K₄[Fe(CN)₆] has been carried out in the solid state by passing chlorine gas over the powdered specimen. K₃[Fe(CN)₆] was crystallised from alkaline solution of this oxidised powder. The compounds were characterised by Mössbauer spectroscopy.     

Study of the antioxidant activity and total polyphenol concentration of medicinal plants

Infusions of medicinal plants are investigated by potentiometry using a system of K₃[Fe(CN)₆]/K₄[Fe(CN)₆]. Models of some flavonoids, phenol carbonic acids, ascorbic acid, and their mixtures are studied. The total polyphenol concentration in these samples is determined by the Folin–Ciocalteu method. Dependences of antioxidant activity on extraction time are obtained.     

Cyanation of Aryl Bromides with K4[Fe(CN)6] Catalyzed by Dichloro[bis{1‐(dicyclohexylphosphanyl)piperidine}]palladium,a Molecular Source of Nanoparticles,and the Reactions Involved in the Catalyst‐Deactivation Processes

Dichloro[bis{1‐(dicyclohexylphosphanyl)piperidine}]palladium [(P{(NC₅H₁₀)(C₆H₁₁)₂})₂PdCl₂] ( 1 ) is a highly active and generally applicable C? C cross‐coupling catalyst. Apart from its high catalytic activity in Suzuki, Heck, and Negishi reactions, compound 1 also efficiently converted various electronically activated, nonactivated, and deactivated aryl bromides, which may contain fluoride atoms, trifluoromethane groups, nitriles, acetals, ketones, aldehydes, ethers, esters, amides, as well as heterocyclic aryl bromides, such as pyridines and their derivatives, or thiophenes into their respective aromatic nitriles with K₄[Fe(CN)₆] as a cyanating agent within 24 h in NMP at 140 °C in the presence of only 0.05 mol % catalyst. Catalyst‐deactivation processes showed that excess cyanide efficiently affected the molecular mechanisms as well as inhibited the catalysis when nanoparticles were involved, owing to the formation of inactive cyanide complexes, such as [Pd(CN)₄]^2?, [(CN)₃Pd(H)]^2?, and [(CN)₃Pd(Ar)]^2?. Thus, the choice of cyanating agent is crucial for the success of the reaction because there is a sharp balance between the rate of cyanide production, efficient product formation, and catalyst poisoning. For example, whereas no product formation was obtained when cyanation reactions were examined with Zn(CN)₂ as the cyanating agent, aromatic nitriles were smoothly formed when hexacyanoferrate(II) was used instead. The reason for this striking difference in reactivity was due to the higher stability of hexacyanoferrate(II), which led to a lower rate of cyanide production, and hence, prevented catalyst‐deactivation processes. This pathway was confirmed by the colorimetric detection of cyanides: whereas the conversion of β‐solvato‐α‐cyanocobyrinic acid heptamethyl ester into dicyanocobyrinic acid heptamethyl ester indicated that the cyanide production of Zn(CN)₂ proceeded at 25 °C in NMP, reaction temperatures of >100 °C were required for cyanide production with K₄[Fe(CN)₆]. Mechanistic investigations demonstrate that palladium nanoparticles were the catalytically active form of compound 1 .     

Untersuchung der Aussalz- bzw. Dehydratationswirkung des Kaliumhydroxids auf Kalium-eisen(II)-cyanidlösungen

Zusammenfassung Mittels physikalisch-chemischer Analyse wurde das System K₄Fe(CN)₆/KOH/H₂O untersucht. Es wurde gezeigt, daß bei 30° bzw. 40°C KOH stark aussalzend auf die Kaliumeisen(II)-cyanidlösungen wirkt, wobei die feste Gleichgewichtsphase nicht dehydratisiert wird, sondern als K₄Fe(CN)₆·3H₂O erhalten bleibt. In der Isotherme bei 60°C bleibt die feste Phase — bis zur KOH-Konzentration 15% — K₄Fe(CN)₆·3H₂O. Über diese Konzentration hinaus tritt Entwässerung ein und die feste Phase stellt K₄Fe(CN)₆ dar. Es wurde festgestellt, daß die Eisen(II)-cyanwasserstoffsäure (in kleinen Konzentrationen) die Löslichkeit des Kaliumeisen(II)-cyanids erhöht.

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Investigation of the salting out and dehydratation effect of potassium hydroxide upon solutions of K₄Fe(CN)₆

The system K₄Fe(CN)₆/KOH/H₂O was investigated by means of physico-chemical analysis. It was shown that at 30° and 40°C KOH has a strong salting out effect upon the solutions of K₄Fe(CN)₆, but the equilibrium solid phase is not dehydrated and remains K₄Fe(CN)₆·3H₂O. In the isotherm at 60°C the solid phase remains K₄Fe(CN)₆·3H₂O up to a concentration of 15% KOH. Beyond this concentration dehydration occurs and the solid phase represents K₄Fe(CN)₆. It was found that H₄Fe(CN)₆ acid (in small concentrations) increases the solubility of K₄Fe(CN)₆.

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Mit 4 Abbildungen     

Microwave-enhanced synthesis of aryl nitriles using dimeric orthopalladated complex of tribenzylamine and K4[Fe(CN)6]

The activity of palladacycle [Pd{C₆H₄(CH₂N(CH₂Ph)₂)} (μ-Br)]₂ complex was investigated in the synthesis of benzonitriles under both conventional and microwave irradiation conditions and their results were compared together. This complex is an efficient, stable, and non-sensitive to air and moisture catalyst for the cyanation reaction. The substituted benzonitriles were produced of various aryl halides in excellent yields and short reaction times using a catalytic amount of [Pd{C₆H₄(CH₂N(CH₂Ph)₂)} (μ-Br)]₂ complex and K₄[Fe(CN)₆] in DMF at 130 °C. In comparison to conventional heating conditions, the reactions under microwave irradiation gave higher yields in shorter reaction times.     

Potentiometric method for determination of kinetic characteristics of radical reactions in aqueous media

Kinetic features of the reactions of K₄[Fe(CN)₆] with radicals initiated by water-soluble azo-initiator 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 °C were studied using the potentiometric method. Potassium ferrocyanide was shown to be a radical acceptor, whereas K₃[Fe(CN)₆] formed by the oxidation with the radicals in combination with K₄[Fe(CN)₆] is an electrochemical system, the study of which makes it possible to determine kinetic characteristics of radical reactions. The rate constants for the reactions of peroxide radicals RO₂ · with K₄[Fe(CN)₆] were calculated.     

A facile microwave-assisted palladium-catalyzed cyanation of aryl chlorides

We report an efficient method for the preparation of aryl nitriles from aryl chlorides under either microwave assisted or thermal conditions. A catalyst system comprising tris(dibenzylidene acetone)dipalladium (Pd₂(dba)₃) and 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) is shown to effectively promote cyanation of various aryl chlorides with Zn(CN)₂ as the cyanide source.