Cyanide, cuprous reaction with aryl halides

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reactionP Reactivity is in the order I > Br > Cl > F, indicating that the SnAt mechanism does not apply.Other cyanides (e.g., KCN and NaCN), do not react with aryl halides, even activated ones. However, alkali cyanides do convert aryl halides to nitrilesin dipolar aprotic solvents in the presence of Pd(II) salts or copper or nickel complexes. A nickel complex also catalyzes the reaction between aryl triflates and KCN to give aryl nitriles. Aromatic ethers ArOR have been photochemically converted to ArCN. 

The reaction begins with conversion of the aniline (1) to the diazo compoimd (2). Usually in the same pot, 2 is then treated with the cuprous halide or cyanide to form the aryl halide or cyanide (3). 

After the reaction of an aryl halide with cuprous cyanide to form a nitrile, added ethylenediamine complexes with cuprous and cupric ions and facilitates isolation of the nitrile (see Ferric chloride). 

Special solvent. Newman - recommends N-methyl-2-pyrrolidone as solvent for the reaction of an aryl halide with cuprous cyanide to produce the corresponding nitrile. Dimethylformamide (b.p. 153°) has been suggested as a better solvent than originally used pyridine (b.p. 115°), but l-methyl-2-pyrrolidone has an even higher boiling point and seems still more satisfactory. An example is the synthesis of... 

The reaction of cuprous cyanide with an aryl halide to produce a nitrile gives an intermediate complex of the nitrile with cuprous haUde. Friedman and Shechter found that the nitrile can be liberated from the complex very easily by addition of... 

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. 

Aryl halides are inert to reaction with cyanide ion under normal Sn2 conditions (chap. 2, sec. 2.11), but they do reaet when heated with cuprous salts like cuprous cyanide (CuCN). Reaction of 1-bromonaphthalene (13) with CuCN at 202°C gave an 89% yield of the aryl nitrile (14). This transformation is called the Rosenmund-von Braun reaction and can be applied to a wide range of aryl halides. The aryl nitriles produced can be used in a variety of reactions. This transformation does not work when potassium or sodium cyanide is used. An amine base is usually added to facilitate the reaction. 

A standard condition has been optimized for this reaction, in which the aryl amine is diazotized in 10 times its amount of acetic acid, followed by the addition of one equivalent of cuprous halide in hydrohalic acid. Under these conditions, the acetate salt of aryl amine is relatively soluble, and less froth and tarry material are formed during diazo transformation. In addition, chlorination, bromination, and iodonation of p-haloaniline to dihalobenzenes under such standard conditions give almost comparable average yields. Other modifications of this reaction include the formation of phenyl selenocyanate by the reaction with potassium selenocyanate, and aryl nitrile by the reaction with nickel cyanide. Moreover, this reaction has been extended to the preparation of phenyl thiocyanate, phenyl isothiocyanate and aromatic sulfonyl chloride. ... 

The most important member of the group is an effective synthesis of aryl nitriles that involves heating the aryl halide with cuprous cyanide. Some examples of the reaction are given in Scheme 7.9. 

Another common transformation of diazonium salts is their conversion to aryl halides by reaction with cuprous salts (CuX), in what is known as the Sandmeyer reaction, named after Traugott Sandmeyer (Switzerland 1854-1922). This means that the Ar-NH2 ArX conversion is possible, where Ar = an aryl group. When 132 is treated with cuprous bromide (CuBr), the product is bromobenzene (18). The reaction works with many other cuprous salts as well, including cuprous chloride (CuCl). A variation of this reaction treats the diazonirun salt with cuprous cyanide (CuCN) to give a nitrile. In this manner, 4-methylanihne (24) is treated with HCI and NaN02 and then with CuCN to give 4-methyl-l-cyanobenzene (134). 

It has been known for a long time that the nucleophilic substitution of aromatic halides is strongly catalyzed by the presence of certain copper salts. Perhaps the most useful of the synthetic procedures based on this observation is the synthesis of aryl nitriles by reaction of aryl bromides with cuprous cyanide. The reaction is usually accomplished in dimethylformamide or a similar solvent. More recently. 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

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