Nitriles from diazonium salts

Hydrolysis of nitriles yields carboxylic acids. The synthesis of nitriles from diazonium salts thus provides us with an excellent route from nitro compounds to carboxylic acids. For example ... 

Nitriles of the aromatic acids may be obtained fiom the sulfonic acids or from diazonium salts. Hydrolysis of the nitrile produces the carboxylic acid ... 

Many aryl nitriles are obtained from diazonium salts by treatment with copper(l) cyanide. Hydroxy and amino nitriles are obtained from addition reactions to carbonyl compounds. 

Aromatic nitriles generally cannot be prepared from the unreactive aryl halides (Sec. 25.5). Instead they are made from diazonium salts by a reaction we shall discuss later (Sec. 23.13). Diazonium salts are prepared from aromatic... 

As already mentioned, aromatic nitriles are made, not from the unrcactive aryl halides, but from diazonium salts (Sec. 23.13). 

Nitriles can be obtained from diazonium salts by the Sandmeyer method, which involves treatment with copper(i)in the hot.793 An example of this valuable reaction is the preparation of 0-nitrobenzonitrile from 0-nitroaniline 794... 

Treatment of diazonium salts with cuprous, Cu(I), salts generates aryl halides. When 398 reacts with CuCl (cuprous chloride) or CuBr (cuprous bromide), the products are chlorobenzene or bromobenzene via what is probably a radical reaction.29l jhis conversion is known as the Sandmeyer reaction. 2 The use of copper powder rather than cuprous salts for this transformation is often called the Gattermann reaction. 93,292b,c Aryl iodides are also produced from diazonium salts by reaction with potassium iodide (KI) but the actual reactive species may be l3-.294,295 Treatment of aniline derivative 403 with sodium nitrite and HCl followed by treatment with KI, for example, gave a 89% yield of 404.Aryl nitriles are generated under Sandmeyer conditions using cuprous cyanide (CuCN), as in the conversion of 405 to benzonitrile derivative 407 via diazonium chloride, 406. 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

DTA examination of a 35% solution of the diazonium salt in sulfuric acid showed 3 exotherms, corresponding to hydrolysis of the nitrile group (peak at 95°), decomposition of the diazonium salt (peak at 160°) and loss of the nitro group (large peak at 240°C). Adiabatic decomposition of the solution from 50°C also showed 3 steps, with induction periods of around 30, 340 and 380 min, respectively. 

Apart from complex formation involving metal ions (as discussed in Chapter 4), crown ethers have been shown to associate with a variety of both charged and uncharged guest molecules. Typical guests include ammonium salts, the guanidinium ion, diazonium salts, water, alcohols, amines, molecular halogens, substituted hydrazines, p-toluene sulfonic acid, phenols, thiols and nitriles. 

Since A,A -disubstituted hydrazines are readily available from a variety of sources (see Volume I, Chapter 14), their dehydrogenation constitutes a widely applicable route to both aliphatic and aromatic azo compounds. Such oxidative procedures are of particular value in the aliphatic series because so many of the procedures applicable to aromatic compounds, such as the coupling with diazonium salts, have no counterpart. The oxidation reactions permit the formation not only of azoalkanes, but also of a host of azo compounds containing other functional groups, e.g., a-carbonyl azo compounds [83], a-nitrile azo compounds [84], azo derivatives of phosphoric acid [85], phenyl-phosphoric acid derivatives [86],... 

This route is particularly valuable for substituents that cannot easily be added by electrophilic substitution such as OH or CN. Table 2.2 gives you a selection of reagents. For the addition of CN, Cl or Br, copper (I) derivatives usually give the best results. So the aryl nitrile 46 might come from amine 47 via a diazonium salt and routine disconnections lead us back to toluene. 

Many derivatives of 2,4,6-triphenylaniline, such as the azo dyes or the halogenides (F, Cl, Br) as well as the nitrile have been prepared by Saure 25 from its diazonium salt. 

Certain olefinic nitriles ate readily available from a-chloro-/S ylpro-pionitriles obtained by the addition of diazonium salts to acrylonitrile. Dehydrohalogenation is effected by boiling with diethylaniline. ... 

Indoles have been prepared from reactions of o-aminophenylketones with reactive , or stable " arsonium ylides. Oxo-stabilized ylides reacted with 2-chloro-oximes to give trans-5-acyl-A -isoxazolines, and isoxazoles have been obtained from reactive arsonium ylides and a-isonitrosoketones, and from triphenylarsonium methylide and nitrile oxides The latter ylide reacts similarly with nitrile imines to give pyrazoles. With triphenylarsonium benzylides and benzoylylides,benzene diazonium salts give 1,3,4,6-substituted 1,4-dihydro-1,2,4,5-tetrazines in a reaction in which initial coupling of the reagents is followed by a dimerisation. ... 

Nitriles are usually prepared either by reacting the corresponding halide or diazonium salts with a cyanide salt or by dehydrating an amide. Hence, possible contaminants are the respective halide or alcohol (from hydrolysis), phenolic compounds, amines or amides. Small quantities of phenols can be removed by chromatography on alumina. More commonly, purification of liquid nitriles or solutions of solid nitriles in a solvent such as diethyl ether is by shaking with dilute aqueous sodium hydroxide, followed by washing successively with water, dilute acid... 

---