Diazonium salts, aryl mechanism

Two mechanisms are among those that have been postulated for decomposition of aryl diazonium salts in aqueous solution containing nucleophilic anions, A ... 

Some observations are important for improvement of the yield and for the elucidation of the mechanism of the Meerwein reaction. Catalysts are necessary for the process. Cupric chloride is used in almost all cases. The best arylation yields are obtained with low CuCl2 concentrations (Dickerman et al., 1969). One effect of CuCl2 was detected by Meerwein et al. (1939) in their work in water-acetone systems. They found that in solutions of arenediazonium chloride and sodium acetate in aqueous acetone, but in the absence of an alkene, the amount of chloroacetone formed was only one-third of that obtained in the presence of CuCl2. They concluded that chloroacetone is formed according to Scheme 10-50. The formation of chloroacetone with CuCl2 in the absence of a diazonium salt (Scheme 10-51) was investigated by Kochi (1955 a, 1955 b). Some Cu11 ion is reduced by acetone to Cu1 ion, which provides the electron for the transfer to the diazonium ion (see below). 

For aryl halides and sulfonates, even active ones, a unimolecular SnI mechanism (lUPAC Dn+An) is very rare it has only been observed for aryl triflates in which both ortho positions contain bulky groups (fe/T-butyl or SiRs). It is in reactions with diazonium salts that this mechanism is important ... 

See Glaser, R. Horan, C.J. Nelson, E.D. Hall, M.K. J. Org. Chem., 1992,57, 215 for the influence of neighboring group interactions on the electronic stmcture of diazonium ions. Aryl iodonium salts Ar2l also undergo substitutions by this mechanism (and by a free-radical mechanism). 

In each case the mechanism involves generation of an aryl radical from a covalent azo compound. In acid solution diazonium salts are ionic and their reactions are polar. When they cleave, the product is an aryl cation (see p. 852). However, in neutral or basic solution, diazonium ions are converted to covalent compounds, and these cleave to give free radicals ... 

Examples of the three mechanistic types are, respectively (a) hydrolysis of diazonium salts to phenols89 (b) reaction with azide ion to form aryl azides90 and (c) reaction with cuprous halides to form aryl chlorides or bromides.91 In the paragraphs that follow, these and other synthetically useful reactions of diazonium intermediates are considered. The reactions are organized on the basis of the group that is introduced, rather than on the mechanism involved. It will be seen that the reactions that are discussed fall into one of the three general mechanistic types. 

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

These reactions are related to the reaction of aryl diazonium salts with iodide yielding iodoaryls, the mechanism of which seems to be a one-electron transfer (radical) reaction and not a nucleophilic displacement. Just as iodide is easily oxi- zed to iodine by the aryl diazonium cation, 2.4.6-triphenyl-X -phosphorin is oxidized to the radical cation 58. 

Another very versatile reaction, leading to l-carbo-l-hetero-X -phosphorins, was found by Schaffer when he reacted X -phosphorins with aryl-diazonium salts in the presence of alcohols. This reaction proceeds probably by an analogous mechanism. It is described on p. 64. 

The most satisfactory method of preparation of a copper(i) cyanide solution is to dissolve the copper(i) cyanide (90 g, 1 mol) in a solution of sodium cyanide (125 g, 2.5 mol) (CAUTION) in 600 ml of water. If it is desired to avoid the preparation of solid copper(i) cyanide, the following procedure may be adopted. Copper(i) chloride, prepared from 35 g of copper(n) sulphate pentahydrate as described under 22 above, is suspended in 60 ml of water contained in a 500-ml round-bottomed flask, which is fitted with a mechanical stirrer. A solution of 18.5 g of sodium cyanide (96-98%) in 30 ml of water is added and the mixture is stirred. The copper(i) chloride passes into solution with considerable evolution of heat. As the copper(i) cyanide is usually employed in reactions with solutions of aryl diazonium salts it is usual to cool the resulting copper(i) cyanide solution in ice. 

Electron-deficient aryl diazonium salts such as the pentafluoro derivative can offer the attractive option to conduct radical arylations as chain reactions with an SrnI mechanism (Scheme 35) [151]. In these special cases, only catalytic amounts of an initiating reductant, such as sodium iodide, are required. In the propagation step, the diazonium salt 92 acts as oxidant for the cyclohexadienyl intermediate 93. Rearomatization of 93 to 94 as well as the generation of a new pentafluorophenyl radical are achieved through this step. 

A practical access to 2-biphenyl alcohols 95 has been discovered by Petrillo (Scheme 36) [152]. Azo sulfides 96, which are employed as masked diazonium salts, do not undergo azo coupling reactions. In combination with 4-substituted phenolates 97, photochemically initiated arylations can even be conducted as chain processes according to the SrnI mechanism. Given their high reductive potential, the cyclohexadienyl intermediates 98 are able to rearomatize by a single electron... 

The carbanion is in an sp2 orbital in the plane of the ring. Indeed, this intermediate is very similar to the aryl cation intermediate in the Sjvjl mechanism from diazonium salts. That had no electrons in the sp2 orbital the carbanion has two. 

The proposed mechanism for a standard Heck reaction is depicted in Scheme 6.5. Generally, a haloalkene or haloarene undergoes oxidative addition to an in situ generated, coordinatively unsaturated 14-electron palladium(O) complex, but other substrates such as tosylates, triflates or diazonium salts can also be applied. Subsequent, sy -insertion into the C=C double bond of a complexed olefin yields a t7-(j -alkenyl) or (j- aryl)alkylpalladium complex. If no hydrogen atom in a pseudo cis-position relative to the palladium is present, an internal rotation step is required prior to syw-elimination of the olefin to afford the traws-olefin product and a palladium(II) hydride complex. The latter is restored to the initial Pd(0) species by base-induced reductive elimination.137"401... 

Shortly after the discovery of this reaction, a number of observers questioned whether radicals were intermediates or whether the reaction proceeded by purely cationic chemistry by the aryl cation mechanism (Scheme 2). If this were the case, then the formation of products such as the alcohols 4 would proceed equally well in the absence of TTF. The vigor of the effervescence seen immediately on addition of TTF, together with the long-term stability of solutions of the diazonium salts in solution in moist acetone and other solvents in the absence of TTF, immediately disproves this, but additional experiments were performed to show the special character of TTF in the reactions. 

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). 

In the Sandmeyer reaction, the cold diazonium salt solution is run into a solution of the copper(I) halide dissolved in the halogen acid. The complex, which usually separates, is decomposed to the aryl halide by heating the reaction mixture. The mechanism (Scheme 8.16) involves generation of an aryl radical by electron transfer from Cu(I), which then reacts with the halide ion. 

Aryl diazonium salts react with a variety of reagents to form products in which Z (an atom or group of atoms) replaces Ng, a very good leaving group. The mechanism of these reactions varies with the identity of Z, so we will concentrate on the products of the reactions, not the mechanisms. 

In appropriately polar solvents, diazonium salts decompose to nitrogen and aryl cations, and formation of arenes may take place by transfer of hydrogen from the reducing agent or from the solvent. Depending on reaction conditions, an ionic mechanism (equation 87)," or a radical mechanism (equation 88) " may be operating, and experimental evidence is claimed for both. However, the radical mechanism seems to have more support. 

The diazonium group can be replaced by a number of groups. " Some of these are nucleophilic substitutions, with S l mechanisms (p. 432), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has been shown that the Sj-jl mechanism is favored by solvents of low nucleophilicity, while those of high nucleophilicity favor free-radical mechanisms. The N2 group can be replaced by CP, Br, and CN, by a nucleophilic mechanism (see OS IV, 182), but the Sandmeyer reaction is much more useful (14-20). Transition metal catalyzed reactions are known involving aryl-diazonium salts, and diazonium variants of the Heck reaction (13-10) and Suzuki coupling (13-12) were discussed previously. As mentioned on p. 866 it must be... 

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