Halides, aryl from diazonium salts

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

PREPARATION OF ARYL HALIDES 1. From diazonium salts. Discussed in Secs. 23.12 and 25.3. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

Aryldiazonium salts react with bis(dibenzylideneacetone)palladium to form arylpalladium salts and nitrogen. Therefore, diazonium salts may be employed to catalytically arylate alkenes under mild conditions. Since many aryl halides are made from diazonium salts this variation could even be more convenient than using aryl halides. The reaction proceeds in good to excellent yields in nonaqueous solvents, using sodium acetate as the base at room temperature with terminal alkenes and cyclopentene." Internal alkenes usually give poor yields, however. 

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... 

The advantages of the synthesis of aryl halides from diazonium salts will be discussed in detail in Sec. 25.3. Aryl fluorides and iodides cannot generally be prepared by direct halogenation. Aryl chlorides and bromides can be prepared by direct halogenation, but, when a mixture of 0- and p isomers is obtained, it is difficult to isolate the pure compounds because of their similarity in boiling point. Diazonium salts ultimately go back to nitro compounds, which are usually obtainable in pure form. 

The preparation of aryl halides from diazonium salts is more important than direct halogenation for several reasons. First of all, fluorides and iodides, which can seldom be prepared by direct halogenation, can be obtained from the diazonium salts. Second, where direct halogenation yields a mixture of ortho and para isomers, the ortho isomer, at least, is difficult to obtain pure. On the other hand, the ortho and para isomers of the corresponding nitro compounds, from which the diazonium salts ultimately come, can often be separated by fractional distillation (Sec. 11.7). For example, the o- and />bromotoluenes boil only three degrees apart 182° and 185°. The corresponding o- and -nitrotoluenes, however, boil sixteen degrees apart 222° and 238°. 

Primary amines are not usually made by reduction of amides (15) but by other reductive processes which are minor variations on this scheme. For unbranched amines (16) we can reduce cyanides. This method is especially suitable for benzylic amines since aryl cyanides (17) can be made from diazonium salts (see Chapter 2), and for the homologous amines (18) since cyanide ion reacts easily with benzyl halides. 

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. 

Diazonium salts are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature using Pd2(dba)3 as a catalyst in the absence of both phosphine ligand and base [44]. The reaction of diazonium salts means indirect substitution reaction of an amino group of anilines or aromatic nitro group with an alkene. The use of diazonium salts is synthetically more convenient than the use of aryl halides, because many aryl halides, particularly iodides, are prepared from diazonium salts. 

The reaction apparently involves free-radical mechanism, but arylcopper compounds take a part, at least under certain reaction conditions, as clearly demonstrated through Cohen s concise results [99,100]. The reaction was discovered as a side-reaction during probes of the Gatterman synthesis of aryl halides from diazonium salts and copper(l) halides. Probably the most known example is very practical preparation of diphenic acid (57) starting from anthranilic acid (58). The reaction is usually conducted by adding an aqueous diazotized anthranilic acid solution (diazonium salt 59) to the copper(l) reagent, in situ obtained by reduction of CUSO4 with an equimolar amount of hydroxylaminc in aqueous sodium hydroxide solution, to produce diphenic acid with a 80-90% yield [99,100], Scheme 25. 

Aryl bromides and iodides are usually prepared from diazonium salts by a copper-catalyzed process, a reaction commonly known as the Sandmeyer reaction. Under the classic conditions of the Sandmeyer reaction, the diazonium salt is added to a hot acidic solution of the cuprous halide.It is also possible to convert anilines to aryl halides by generating the diazonium ion in situ. Reaction of anilines with alkyl nitrites and cuprous halides in acetonitrile gives good yields of aryl bromides by a copper-mediated process which is mechanistically similar to that occurring under the usual Sandmeyer conditions. Diazonium salts can also be converted to... 

Aryl Halides from Diazonium Ion Intermediates. Replacement of diazonium groups by halides is a valuable alternative to direct halogenation for the preparation of aryl halides. Aryl bromides and chlorides are usually prepared by a reaction using the appropriate Cu(I) salt, which is known as the Sandmeyer reaction. Under the classic conditions, the diazonium salt is added to a hot acidic solution of the cuprous halide.99 The Sandmeyer reaction occurs by an oxidative addition reaction of the diazonium ion with Cu(I) and halide transfer from a Cu(III) intermediate. 

A second method for preparing aryl halides is the Sandmeyer reaction. During a Sandmeyer reaction, a diazonium salt reacts with copper (I) bromide, copper (I) chloride, or potassium iodide to form the respective aryl halide. The diazonium salt is prepared from aniline by reaction with nitrous acid at cold temperatures. 

Similar reactions have been carried out with naphthalene and thiophene. The method has been employed only to a limited extent 23 since its discovery, probably because it involves the isolation of the dry diazonium salts and because a number of aryldiazonium salts (from o- and p-toluidine and /3-naphthylamine) gave no biaryls but only the corresponding aryl halides. 

The mechanism of the Sandmeyer reaction involves the transfer of electron from Cu" " to diazonium salt. Elimination of nitrogen generates aryl free radical, which reacts with CuXCl to give aryl halide via either path a or path b (Scheme 2.33). 

Diselenides are generally prepared by the aerial oxidation of selenols or selenolates (see Section 2) or by the reaction of Li2Sc2, Na2Se2, or other 802 species with alkyl or aryl halides. In the latter case, elevated temperatures and DMF as the solvent are recommended. Aryl diselenides may also be obtained from the reaction of 802 with diazonium salts (Scheme 6). Relatively few unsymmetrical diselenides have been reported. Triselenides are also known but have not been as widely studied. 

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