Nitriles and Isocyanides

Nitriles have been synthesized by a variety of methods. The formation of nitriles by the alkylation of potassium cyanide using solid-liquid phase-transfer catalysis without added solvent is 

A variety of alkyl, aryl, and heteroaryl aldoximes have been 

Recently reported methods of preparing a,3-unsaturated nitriles 

Y-Unsaturated nitriles have been prepared from allenes and 

6—unsaturated nitronates using low-valent titanium the nitronates are generated by the catalysed addition of allylic 

Classically, nitriles have been prepared in Sfj2-displacements of either active halides or sulphonate esters by cyanide anion. 

Sodium cyanide substitutions of benzylic halides in the presence of benzyltriethylammonium chloride thus serves as a typical example.More recently use has been made of supported cyanide reagents, but attempts to do so have often been problematical. 

This has been exemplified by the use of potassium cyanide impregnated on amberlite XAD-2 resin. Both benzyl and n-alkyl halides 

Cyanotrimethylsilane and Lewis acids have been shown to be effective in the cyanation of alkyl halides. Use of this silane and tin tetrachloride in refluxing dichloromethane allowed synthesis of bridge-head adamantoid nitriles from the chlorides and/or 292 

Direct cyanation of alcohols occurs with use of lithium cyanide 

Many methods are available for the dehydration of aldoximes to nitriles new alternatives include N-trifluoroacetylimidazole, and chloromethylenedimethyl-ammonium chloride as reagents to effect this transformation under mild conditions. A new method for the direct conversion of aromatic aldehydes to the corresponding nitriles in high yields involves the use of pyridine hydrochloride in the presence of nitroethane. The method is, however, less convenient for the preparation of aliphatic nitriles because of partial hydrolysis of the product, or incomplete reaction. 

Cyanohydrins are commonly obtained from the reaction of aldehydes or ketones with hydrogen cyanide. This methodology has now been extended to the asymmetric addition of hydrogen cyanide to benzaldehyde catalysed by cyclo-(L-phenylalanyl-L-histidine) to give the (/ )-antipode in extremely high optical yield. 

Acyl cyanides are the starting materials for a new synthesis of cyanohydrin esters via a two-phase reduction with sodium borohydride in the presence of tetra-n-butylammonium bromide. 

Functional group replacement by cyano is an important synthetic transformation since it frequently allows homologation by hydrolysis to the carboxylic acid, or by reduction to an amine. The replacement of sulphinyl by cyano via trimethyl-silylcyanide thus provides a preparation of aliphatic cyanomethyl ethers, and this useful reagent has been further employed to provide cyclic a-acylaminonitriles by the replacement of methoxy-groups. The replacement of a primary amino-group by cyano is an often sought after transformation, and 

Similarly, the transformation of alcohols to nitriles is a much sought after transformation, and a new procedure now allows the direct one-step conversion by the use of sodium cyanide-trimethylsilyl chloride and a catalytic amount of sodium iodide in dimethylformamide-acetonitrile. 

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BH4 [69532-06-5]. The methyl compound has exhibited insertion reactivity, including aldehydes, ketones, nitriles, and isocyanides (29). Stable metaHacycle... 

While alkynes, nitriles, and isocyanides have long been known to insert a cage carbon into polyboranes (COMC (1982) 5.4.2.6.1 and 5.4.2.6.2), the use of aldehydes to insert a cage carbon was first reported by Bernd Brellochs in 1997 (Figure 5).86 Good yields of 10-vertex monocarbaboranes were obtained from B10H14 with KOH and many aldehydes and this reaction was thus coined the Brellochs reaction. 87... 

D. Barton u. W. D. Ollis, Imines, Nitrones, Nitriles and Isocyanides in Comprehensive Organic Chemistry, Vol. 3, Part 8, Pergamon Press, Oxford New York Toronto Sydney - Paris Frankfurt 1979. 

Sodium cyanide solution dissolves certain metals (I) with absorption of oxygen, e.g.. gold, silver, mercury, lead, and (2) with evolution of hydrogen, e.g.. copper, nickel, iron. zinc, aluminum, magnesium and solid sodium cyanide, when heated with certain oxides, e.g.. lead monoxide PhO. stannic oxide SnO.. yields the metal of the oxide, e.g.. lead. tin. respectively. and sodium cyanate NaCNO. Two classes of esters arc known, cyanides or nitriles, and isocyanides, isonitriles or carbylatnincs. the latter being very poisonous and of marked nauseating odor... 

The reaction of cyanide ion with substituted benzhydryl carbenium ions to form nitriles and isocyanides is controlled by the rates of reaction at carbon and nitrogen.124 In slow reactions, far from the diffusion limit, the attack is completely at the cyanide carbon. Very fast reactions, with little or no reaction barrier reacting at the diffusion-controlled limit, occur at both the N and the C of the cyanide ion. XN2 reactions occur almost exclusively at carbon regardless of the substrate or source of the cyanide ion. The HSAB principle cannot predict the products of these reactions. 

Another class of heteroleptic complexes contains 7T-donors and is of the form ThR[N(Si(CH3)3)2]3, where R = CH3 [69517-13-7], H [70605-07-1], or BH4 [69532-06-5]. The methyl compound has exhibited insertion reactivity, including aldehydes, ketones, nitriles, and isocyanides (29). Stable metallacycle... 

Isocyanides, when bound to weak tt-donor metal centers, can also undergo addition of protic nucleophiles (HNu) to form aminocarbene M=C(Nu)NHR species. Hence, a parallelism of behavior is observed for nitriles and isocyanides. In both ligands, either the electrophilic or the nucleophilic addition occurs at the unsaturated atom at the jS-position that exhibits a higher reactivity than the metal coordinated terminal atom. 

The isomerism existing in the case of cyanides or nitriles and isocyanides or iso-nitriles, which we have just discussed, is found also, in part, in their oxidation products the iso-cyanates and in analogous sulphur compounds the thio-cyanates and iso-thio-cyanates. We have referred to the fact that hydrocyanic acid like hydrochloric acid yields an oxygen acid which though unknown itself is represented by well known salts. 

Nitriles and isocyanides are among the most versatile organic substrates and are widely employed as starting materials in both industry and laboratory (e.g., for production of amides via hydrolysis of nitriles [1] or application of isocyanides in multicomponent reactions [2-4]). The transformation of these synthons offers an attractive route for the creation of novel C-X (X = C, N, O, andS) bonds, in particular, through reactions of nucleophilic addition or a dipolar cycloaddition (DCA)... 

The main drawback associated with the reactions of nitriles and isocyanides is their insufficient electrophilic activation (toward nucleophilic addition) or a very moderate dipolarophilicity (toward a DCA). This problem can be successfully overcome by coordination of the substrate to a metal center (Scheme 13.1) [1, 5, 7-9]. Under these conditions, the integration between nitriles (or isocyanides) proceeds at metal centers, giving new species, which, in contrast to metal-catalyzed processes, persist in the coordination state after coupling. In many instances, these metal-mediated processes allow the performance of certain reactions that are not feasible without the involvement of metal, and provide the stabilization of organic species that do not exist in a free state [1, 5-10]. 

Several types of reactivity for metal-bound nitriles and isocyanides should be recognized [1, 7, 8]. For instance, the nucleophilic addition to metal-bound nitriles allows the generation of imine complexes [1], electrophiUc addition produces metal-bound azavinylidenes [1], and the DCA results in coordinated heterocycUc imines (Route I, Scheme 13.1) [5, 6, 10]. With respect to the metal-ligated isocyanides, the addition of nucleophiles furnishes complexes with acycUc aminocarbenes [7, 9, 11], electrophilic addition gives aminocarbynes [8, 12], while the DCA brings about the formation of A-heterocyclic carbene derivatives (Route II, Scheme 13.1) [6, 10]. 

Scheme 13.1 Metal-mediated dipolar cycloaddition to nitriles and isocyanides and dipoles employed. (See insert for color representation...

METAL-MEDIATED [2 H- 3] DIPOLAR CYCLOADDITION TO NITRILES AND ISOCYANIDES SYNTHETIC STUDIES... 

METAL-MEDIATED [2 + 3] CYCLOADDITION TO NITRILES AND ISOCYANIDES THEORETICAL STUDIES 177... 

In this chapter, we examined the recent data on DCA to metal-bound nitriles and isocyanides that allow the generation of new heterocyclic sttuctures. In case of cycloaddition to metal-bound nitriles [1, 5, 6, 10], the obtained heterocyclic ligands can be often isolated as free species, and this approach represents an alternative (to a pure organic) route for their preparation. At... 

Efficient One-Pot Synthesis of N-Containing Heterocycles by Multicomponent Coupling of Silicon-Tethered Diynes, Nitriles, and Isocyanides through Intramolecular Cyclization of Iminoacyl-Zr Intermediates. 

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