Halides, aryl reaction with CuCN

The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

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). 

The palladium-catalyzed reaction of aryl halides with cyanides to give cyanobenzenes takes place under relatively mild conditions compared to the conventional method using a stoichiometric amount of CuCN [74]. Thus, palladium catalysis has been often employed. Recently, a number of effective methods for the cyanation have been reported. The reaction of aryl iodides with NaCN under two-phase conditions [75] and those of aryl triflates [76, 77] and aryl chlorides [78] with Zn(CN)2 occur with good efficiency, while these are considered to proceed via mechanism B. 

Aryl halides reaction with metal cyanides, often with another transition metal catalyst, to give aryl nitriles (aryl cyanides). Aryl halides react with Zn(CN)2 and a palladium catalyst, for example, to give the aryl nitrile. Similarly, aryl iodides react with CuCN and a palladium catalyst to give the aryl nitrile. Potassium cyanide (KCN) reacts in a similar manner with a palladium catalyst. " Sodium cyanide has been used with a copper catalyst and 20% The reaction of aryl iodides... 

Other copper nucleophiles such as R CuLi and R2Cu(CN)Li2 also undergo substitution reactions with aryl and alkenyl halides. Retention of double-bond geometry about alkenyl halides is observed. The mechanisms of the reactions of these other Cu(I) nucleophiles are likely very similar to the one shown for the reaction of CuCN and ArBr. 

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. 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

Arylcopper intermediates can be generated from organolithium compounds, as in the preparation of cuprates.95 These compounds react with a second aryl halide to provide unsymmetrical biaryls in a reaction that is essentially a variant of the cuprate alkylation process discussed on p. 680. An alternative procedure involves generation of a mixed diarylcyanocuprate by sequential addition of two different aryllithium reagents to CuCN, which then undergo decomposition to biaryls on exposure to oxygen.96 The second addition must be carried out at very low temperature to prevent equilibration with the symmetrical diarylcyanocuprates. 

Arylzinc species prepared via the sacrificial anode process and from aryl halides in the presence of a nickel 2,2 -bipyridine, as already reported in Section . .1, were found totally unreactive towards common electrophiles such as aldehydes, carboxylic anhydrides or activated alkyl halides. However, they react with some electrophiles when they are activated by the presence of a catalytic amount of copper salts (10 mol% Cul) together with tetramethylethylene diamine (1MEDA) as described by Knochel and Singer on the ArZnX—CuCN metal exchange47 or when the reaction is catalyzed by palladium complex. 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reaction Reactivity is in the order I > Br > Cl > F, indicating that the SNAr mechanism does not apply. Other cyanides (e.g., KCN and NaCN) do not react with aryl halides, even activated ones. This reaction has been done in ionic liquids using CuCN. ° The reaction has also been done in water using CuCN, a phase transfer catalyst, and microwave irradiation. 

Copper(I) salts such as CuCN and ROCu undergo aromatic substitution reactions very readily with ordinary aryl halides. The mechanism has not been established with certainty. One reasonable possibility is an SrnI mechanism. Another reasonable possibility involves oxidative addition of Ar X to N=C Cu(I) to give a Cu(III) complex, followed by reductive elimination of Ar-CN to give CuX. 

Aromatic and heteroaromatic halides fail to react with alkali metal cyanides under the conditions normally used for aliphatic nucleophilic displacement reactions. Traditionally, the preparation of aryl [ CJnitriles has been accomplished either by the Sandmeyer reaction or the Rosenmund-von Braun reaction. In the former, cyano-dediazoniation of aryl diazonium salts is accomplished with Cu CN or a mixture of and CuCN (or CuCl)... 

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