Synthesis of nitriles

The Kolbe synthesis of nitriles is an important method for the elongation of an alkyl chain by one carbon center (see also the Arndt-Eistert synthesis). The nitrile 2 can for example easily be converted to the corresponding carboxylic acid by hydrolysis. 

Synthesis of nitriles from aldoxime with aldoxime dehydratase ... 

The dehydration reaction of aldoxime to form nitriles using the resting cells of Rhodococcus sp. YH3-3 was optimized. We found that the enzyme was induced by aldoxime and catalyzed the stoichiometric synthesis of nitriles from aldoximes at pH 7.0 and 30°C. Phenylacetonitrile once synthesized from phenylacetaldoxime was hydrolyzed to phenylacetic acid, since the strain has nitrile degradation enzymes such as nitrile hydratase and amidase. We have been successful in synthesizing phenylacetonitrile and other nitriles stoichiometrically by a selective inactivation of nitrile hydratase by heating the cells at 40°C for 1 h. Various nitriles were synthesized under optimized conditions from aldoximes in good yields. 

The synthesis of nitriles from halides is valuable in medicinal chemistry because nitriles are flexible building blocks readily converted into carboxylic acids, amides, amines, or a variety of heterocycles, e. g. thiazoles, oxazolidones, triazoles, and tetrazoles. The importance of the tetrazole group in medicinal chemistry is easily understood if we consider that it is the most commonly used bioisostere of the carboxyl group. 

Dehydration of O-silylated hydroxamic acids is used as a general method in the synthesis of nitrile oxides (95) in the presence of trilluoromethanesulfonic anhydride and triethylamine. 

Actually, nitronates are the closest related derivatives of nitronic acids, that is, aci forms of AN, which exist in labile equilibrium with true AN. Some derivatives of nitronic acids, —CH=N(0)0X, where OX is the good leaving group, are evident intermediates in the most well-developed procedures for the synthesis of nitrile oxides from primary AN. In this chapter, special emphasis is given to particular nitronates, which are generated from a-functionalized AN and can also be considered as precursors of a-functionalized nitrile oxides. 

Acidic zeolites, K-10 clay and silica are highly active and selective catalysts for the dehydration/Beckmann rearrangement reactions of aldoxhnes (benzaldoxime and 4-methoxybenzaldoxime) for the synthesis of nitriles and amides . 

Efficient One Pot Synthesis of Nitriles from Aldehydes in Solid State Using Peroxymonosulfate on Alumina (Bose and Narsaiah, 1998)... 

Scheme 2.2.7.16 Synthesis of nitrile (R)-30 through intermediate epoxide (S)-29a.

SYNTHESIS OF NITRILES BY REACTION OF p-XYLENE WITH NO OVER Cr -Al CATALYSTS S. ZINE1 and A. GHORBEL2... 

A 2-Dehydroquinuclidinyl-2- and 3-carboxamides were formed from the corresponding esters by the action of alcoholic ammonia.47,49 Quinuclidinecarboxylic esters were also used in the preparation of hydrazides and their hydrazones,95,132 and the amides in the synthesis of nitriles.47,49,90... 

At that time, however, these reactions were not brought to the level of preparative synthesis of nitriles. The main obstacle seemed to be further transformation of the nitriles to acids. In some cases, upon treating al-doximes with alkalies, it was not at all possible to fix nitriles since they immediately converted to acids. The anti(E)-isomers exhibit an enhanced reactivity in these cases. Thus, when boiled in 2 N NaOH, -aldoximes are slowly converted to a mixture of the corresponding carboxylic acids and sy/i(Z)-aldoximes to evolve ammonia (36JA1227). Under these conditions for 4 hr the - and Z-benzaldoximes undergo 13 and 48% conversion to form benzoic acid in 10 and 38% yield, respectively. Analogously, the -and Z-oximes of furfural, under the same conditions for 1.5 hr, are converted to furan-2-carboxylic acid in 33 and 62% conversion and 18 and 49% yield, respectively. 

S. M. Dirk and J. M. Tour, Synthesis of Nitrile Terminated Potential Molecular Electronic Devices, Tetrahedron 59, 287-293 (2003). 

Langer, P. Doring, M. Seyferth, D. Gorls, H. Synthesis of nitrile oligomers through multiple anion capture reactions of allene dianions. Eur.J. Org. Chem. 2003, 1948-1953. 

Many publications are devoted to the synthesis of nitrile complexes, carried out by the immediate (direct) interaction of RCN and MX , mostly in the absence of a solvent [10, p. 95]. A series of N-donors, N-containing heterocyclic donors, whose complexes frequently model biologically important objects (Sec. 2.2.42), should be mentioned apart. The following compounds belong to this type azoles 188, azines 189, and their amino derivatives 572. Their interaction with metal salts takes place usually without a solvent with the use of liquid heterocyclic ligands, for example pyridine [10, ch. 4, p. 107 11], in alcohol or alcohol-aqueous mediums in cases of crystalline ligands (3.10)—(3.12). The specific conditions are presented in the literature, cited in Sec. 2.2.4.2. 

Nitriles can be prepared by the SN2 reaction of a cyanide ion with a primary alkyl halide. However, this limits the nitriles that can be synthesised to those having the following general formula RCH2CN. A more general synthesis of nitriles involves the dehydration of primary-amides with reagents such as thionyl chloride or phosphorus pentoxide ... 

Tosylhydrazones can be silylated with (fert-bufyldimethylsilyl)trifluoromethanesulfonate (Me2teriBuSi03SCF3) on the sulfonamide nitrogen. This is how the starting material for a broadly applicable alkane synthesis is produced ( Figure 1.49). Due to their ability to undergo reductive cyanization (Figure 17.69) mesitylene sulfonyl hydrazones allow for a two-step synthesis of nitriles from ketones. 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

This type of reaction is now of major industrial importance because it constitutes a straiglitforward synthesis of nitriles. Wlien it is applied to a diolefm, such as butadiene, it leads to the formation of dinitriles, which are precursors of valuable monomers for the preparation of polymers (butadiene leads to adipo-nilrile. a nylon-b, fvprecursor). Du Font developed the first commercial process using butadiene and HCN for adiponitrile synthesis from butadiene, but this process does nut proceed through a hydrocyanation reaction it is. in fact, a copper-catalyzed halogenation reaction followed by a cyanaikm reaction (tquaiion (16)) of the chlorinated intermediate (Fquation (17)). 

A synthesis of nitriles from the cyanohydrins of aromatic aldehydes via the reduction of the corresponding a-halo cyanides has been proposed. As an example, benzaldehyde cyanohydrin is converted by the action of thionyl chloride to phenylchloroacetonitrile (80%). This substance is reduced with zinc in acetic acid to phenylacetonitrile (70%). ... 

A new method, employing 0-(2-aminobenzoyl)hydroxylamine and BF3 Et20, has been discovered for the synthesis of nitriles from aldehydes yields are 78-94 % (Eq. 90) [147]. 

Hayatsu R., Studier M. H., Matsuoka S., and Anders E. (1972) Origin of organic matter in early solar system VI. Catalytic synthesis of nitriles, nitrogen bases and porphyrin-like pigments. Geochim. Cosmochim. Acta 36, 555-571. 

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