Nitriles useful reactions

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Nitdles may be prepared by several methods (1). The first nitrile to be prepared was propionitdle, which was obtained in 1834 by distilling barium ethyl sulfate with potassium cyanide. This is a general preparation of nitriles from sulfonate salts and is referred to as the Pelou2e reaction (2). Although not commonly practiced today, dehydration of amides has been widely used to produce nitriles and was the first commercial synthesis of a nitrile. The reaction of alkyl hahdes with sodium cyanide to produce nitriles (eq. 1) also is a general reaction with wide appHcabiUty ... 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

The Fiesselmann reaction has been extensively used with p-halovinyl esters, ketones,aldehydes and nitriles as reaction partners for thioglycolic acid and its derivatives. This reaction with P-halovinyl aldehydes has been extensively explored as a result of the availability of P-chloro-a,P-unsaturated aldehydes via the Vilsmeier... 

Among the most useful reactions of nitriles are hydrolysis to yield first an amide and then a carboxylic acid plus ammonia, reduction to yield an amine, and Grignard reaction to yield a ketone (Figure 20.3). 

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. 

As noted in Section 11.2.2, nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides can be catalyzed by the presence of copper metal or copper salts.137 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reactions are usually carried out at elevated temperature in DMF or a similar solvent. 

Among the most exciting frontiers in boratabenzene chemistry is the development of transition metal-boratabenzene complexes as catalysts. As early as 1984, it had been demonstrated that these adducts can accelerate useful reactions— specifically, Bonnemann established that (C5H5B-Ph)Co(cod) serves as a catalyst for pyridine-forming cyclotrimerization reactions of alkynes and nitriles.39... 

Further development of this idea led to the proposal (56) that reactive B=C groups, for instance carbonyl systems, would be able to activate alcohol acceptors AH by generating a related A—B—C—H intermediate (Scheme 8, path I). It seemed that chloral might act as a catalyst along these lines. However, it turned out that the rate of decay in the transition state is too low in all systems tested thus far. Therefore, the carbonyl compound is more or less a substitute for a Lewis acid catalyst, as indicated in Scheme 8, path II. The high reactivity and diastereoselectivity in chloral-catalyzed reactions is attributable to the nitriles used as solvents in these reactions [see Section III.3.b and Ref. (62)]. 

Scheme 8.9, Reaction sequence in the indirect eleclrachemicai oxidation of primary amines to nitriles using bromide ion as mediator.

A number of organic species, including amides, oximes, and nitriles, undergo reductive amination, a variety of reduction reactions that produce cimines. In general, these processes involve imines, R=N-R, or related species. Reduction processes include hydrogenation using Raney nickel as the catalyst (for nitriles), the reaction with sodium/EtOH (for oximes), and the use of lithium aluminum hydride, LiAlH (for amides or nitriles). Figure 13-16 illustrates the preparation of amphetamine by reductive amination. 

When substrates such as ot-chiral allylic alcohols are used, reactions with achiral nitrile oxides are affected both by alkoxide formation and the use of wellcoordinating cations (136-138). In some cases, hydrogen bonding with the nitrile oxide s oxygen atom can also play an important role (135). 

Cyanomethyl)zinc bromide, BrZnCH2CN (1). The reagent converts alkyl, ally lie, or propargylic iodides in the presence of HMPT to nitriles. The reaction is particularly useful for synthesis of y,5-unsaturated nitriles.5 Example ... 

The one-pot conversion of an aromatic carboxylic acid into the corresponding nitrile may be effected by reaction with ammonia in the presence of ethyl polyphosphate64 the initial stage is the formation of the amide and this is followed by dehydration to the nitrile. The reaction has been used successfully with a range of aromatic carboxylic acids. 

A mixture of 50 per cent sulphuric acid and glacial acetic acid may be used with advantage in the case of diflicultly-hydrolysable aromatic nitriles. The reaction product is poured into water, and the organic acid is separated from any unchanged nitrile or from amide by means of sodium carbonate solution. 

Nitriles. Aldehydes can be converted directly in satisfactory yield into nitriles by reaction with hydroxylamine hydrochloride at 90-140° when N-methylpyrrolidone is used as solvent. 

Hepteny radical cyclizations proceed about 40 times slower than the 5-hexenyl counterpart. Therefore, in most cases, a rate-enhancing factor is required to achieve a synthetically useful reaction. The most common rate-enhancing factors are a,f)-unsaturated esters, nitriles, and ketones, or other electron withdrawing groups. a,p-Unsaturated esters are the most widely employed precursors. 

Various alkyl and aryl azides have been transformed into the corresponding nitriles using bromine trifluoride in moderate to good yields (30-60%).25 The reaction is general and gives positive results with aliphatic, aromatic, cyclic, functionalized, and optically active azides. Two alternative mechanisms have been proposed. 

Hexafluoroarsenate salts 74 and 75 are prepared from the relevant nitriles using S2NAsF6 as the source of the dithianitronium cation (SNS+). Further reaction with 2equiv of SbPh3 gives radicals 76 and 77. Such reactivity can be confirmed by ESR spectroscopy, prior to quantitative isomerism, which takes place at room temperature <1986CC140>. 

Figure 7.2 illustrates the phosphorus pentoxide-mediated dehydration of a primary amide to a nitrile, using the transformation of nicotine amide (A) into nicotine nitrile (B) as an example. The reaction of phosphorus pentoxide at the carboxyl oxygen furnishes the partially ring-opened iminium ion E (simplified as F) via the polycyclic iminium ion C. E is deprotonated to give the mixed anhydride G from imidic acid and phosphoric acid. Imidic acids are characterized by the functional group R-C(=NH)-OH. This anhydride is transformed into the nitrile B by an El elimination via the intermediate nitrilium salt D. Nitrilium salts are iV-pro-tonated or V-alkylated nitriles. 

The amide is an intermediate in the hydrolysis, and because it is less reactive than the nitrile, the reaction can often be stopped at the amide stage, if so desired, by using milder reaction conditions, such as shorter reaction times, lower temperatures, or weaker base ... 

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