Dediazoniation reaction rates

Dediazoniation reactions rates were carried out in NaOAc and NaPAA at various pH s. NaOAc solutions are self buffered, and NaPAA solutions were buffered with 1 x 10" M HEPES. Reactions were monitored at 40 + 0.1 C,... 

All these results are consistent with the hypothesis that aryl cations react in aqueous media at diffusion-controlled rates with all nucleophiles that are available in the immediate neighbourhood of the diazonium ion. On this basis Romsted and coworkers (Chaudhuri et al., 1993a, 1993b) used dediazoniation reactions as probes of the interfacial composition of association colloids. These authors determined product yields from dediazoniation of two arenediazonium tetrafluoroborates containing ft-hexadecyl residues (8.15 and 8.16) and the corresponding diazonium salts with methyl groups instead of Ci6H33 chains. ... 

Kinetics have been measured for the dediazoniation reactions of 2- and 3-methyl-benzenediazonium cations in water and in aqueous methanol. The results are consistent with a heterolytic mechanism involving rate-determining formation of reactive aryl cations which show little discrimination for nucleophiles present. Results for the dediazoniation of 4-nitrobenzenediazonium ions in aqueous acid catalysed by Cu(II) chloride are also consistent with a heterolytic pathway at low acidity and with conditions designed to avoid the formation of Cu(I) the reaction may yield chloroarenes in high yield. Activation parameters have been reported for the decomposition of some arenediazonium tetrafluoroborates in polar solvents. The results are generally consistent with heterolysis, although in ethanol there is competition from a radical mechanism, with characteristically different activation parameters, which leads to hydrodediazoniation f... 

Zollinger [15], to interpret the product yield results. The yields of phenol product, z-ArOH, from reaction with water and halo product, z-ArX, from reaction with Br or Cl are assumed to be determined primarily by the position of equilibrium between the ion-molecule and ion-ion pairs. The dediazoniation rate constant for each pair is probably of secondary importance for these dediazoniations because dediazoniation reactions are notoriously insensitive to the polarity of the reaction medium (see later). For several decades the basic consensus on the dediazoniation mechanism has been the rate-determining loss of N2 to give a highly reactive aryl cation intermediate that is trapped extremely rapidly and competitively by available nucleophiles [15]. However, more recent ah initio calculations provide support for a bimolecular mechanism in which C—N bond cleavage is almost complete and bond formation with the nucleophile has barely begim [16]. Because both mechanisms lead to the same definition for the selectivity of the reaction toward competing nucleophiles [Eq. (1)], the bimolecular pathway for dediazoniation is not included in Scheme 1. 

The rapid formation of the (Z)-diazoate is followed by the slower (Z/J )-isomeri-zation of the diazoate (see Scheme 5-14, reaction 5). Some representative examples are given in Table 5-2. Both reactions are first-order with regard to the diazonium ion, and the first reaction is also first-order in [OH-], i.e., second-order overall. So as to make the rate constants k and k5 directly comparable, we calculated half-lives for reactions with [ArNj ]0 = 0.01 m carried out at pH = 9.00 and 25 °C. The isomerization rate of the unsubstituted benzenediazonium ion cannot be measured at room temperature due to the predominance of decomposition (homolytic dediazoniations) even at low temperature. Nevertheless, it can be concluded that the half-lives for (Z/ )-isomerizations are at least five powers of ten greater than those for the formation of the (Z)-diazohydroxide (reaction 1) for unsubstituted and most substituted benzenediazonium ions (see bottom row of Table 5-2). Only for diazonium ions with strong -M type substituents (e.g., N02, CN) in the 2- or 4-position is the ratio r1/2 (5)/t1/2 (1) in the range 6 x 104 to 250 x 104 (Table 5-2). 

Broxton and Roper measured the rate of dissociation (A 3) of the (ii)-diazo ether, A 2, and the rate of the protection reaction (A p), i.e., the transformation of the (Z)-into the (ii)-ether ( protection because the diazo ether is protected against dediazoniation almost completely if present as the ( >isomer). Rate constants kx and k are known from Ritchie and Virtanen s work (1972). The results demonstrate firstly that the initial reaction of the diazonium ion takes place in such a way that almost exclusively the (Z)-ether is formed directly (ki/k3 = 120). The protection rate constant kp is a simple function of the intrinsic rate constants as shown in Scheme 6-4. 

However, measurements of substituent effects supported the hypothesis that the aryl cation is a key intermediate in dediazoniations, provided that they were interpreted in an appropriate way (Zollinger, 1973a Ehrenson et al., 1973 Swain et al., 1975 a). We will first consider the activation energy and then discuss the influence of substituents, as well as additional data concerning the aryl cation as a metastable intermediate (kinetic isotope effects, influence of water acitivity in hydroxy-de-di-azoniations). Finally, the cases of dediazoniation in which the rate of reaction is first-order with regard to the concentration of the nucleophile will be critically evaluated. 

If the deuterium isotope effect on the rearrangement rate ( H/ D3)r is larger than unity and is approximately equal to that on the rate of dediazoniation ( H/ D3)S, it can be concluded that the ion-molecule pair 8.13 is the more likely intermediate for the rearrangement reaction. On the other hand, an isotope effect on the rearrangement rate that is smaller than or equal to unity would indicate the involvement of the benzenespirodiazirine cation 8.17 as an intermediate. 

Dediazoniations that follow a homolytic mechanism are, however, always (as far as they are known today) faster than heterolytic dediazoniations. A good example is afforded by the rates in methanol. In a careful study, Bunnett and Yijima (1977) have shown that the homolytic rate is 4-32 times greater than the heterolytic rate, the latter being essentially independent of additives and the atmosphere (N2, 02, or argon). In water the rate of heterolytic dediazoniation, measured at pH <3, is lower than that of the homolytic reactions that take place in the range pH 8-11 (Matrka et al., 1967 Schwarz and Zollinger, 1981 Besse and Zollinger, 1981). 

We have mentioned in Section 8.6 that there is a fairly good correlation between the nucleophilicity of the solvent and the rate of homolytic dediazoniation. In this and the following section such reactions are discussed in more detail and general conclusions are drawn concerning mechanisms. 

Broxton and Bunnett (1979) determined the products of the reaction of 4-chloro-3-nitrobenzenediazonium ions with ethoxide ion in ethanol, which is exactly analogous to the reaction in methanol discussed earlier in this section. These authors found 12.8% 4-chloro-3-nitrophenetole, 83% 2-chloronitrobenzene, and 0.8% 2-nitrophenetole. When the reaction was carried out in C2H5OD, the first- and second-mentioned products contained 99% D and 69% D respectively. Dediazoniation in basic ethanol therefore results in a higher yield of hydro-de-diazoniation with this diazonium salt compared with the reaction in methanol. This is probably due to the slightly higher basicity of the ethoxide ion and to the more facile formation of the radical CH3-CHOH (Packer and Richardson, 1975). Broxton and McLeish (1983 c) measured the rates of (Z) — (E) interconversion for some substituted 2-chlorophenylazo ethyl ethers in ethanol. 

In Section 8.3 the mechanism of heterolytic dediazoniation of arenediazonium ions was discussed, and it was shown that the hypothesis of Crossley et al. (1940) that the aryl cation is the characteristic metastable intermediate in those reactions was not consistent with some experimental facts found in 1952 by Lewis and Hinds. Nevertheless, these facts did not have significant influence on the scientific community, which continued to accept the original and apparently convincing hypothesis of the rate-limiting formation of an aryl cation as an intermediate as correct . The incom-patabilities of various mechanistic hypotheses with experimental facts were, however, discussed in some detail only two decades later (Zollinger, 1973 a). Another year passed before I performed a crucial experiment that refuted a number of hypotheses (Bergstrom et al., 1974, 1976). ... 

Coming back to the mechanism of dediazoniation, mechnism B in Scheme 9-2 is consistent with all experimental data known in 1973. Mechanism B was, indeed, mentioned in that paper (Zollinger, 1973 a) as an explanation, but not proposed as the explanation because it violated the common knowledge mentioned above. If that reverse reaction of the phenyl cation is faster than the forward reaction with water or metal halides, the rate is dependent on the concentrations of compounds involved only in the second step of the mechanism, even if that step is much faster than the first (forward) step. 

Lewin and Cohen (1967) determined the products of dediazoniation of ben-zophenone-2-diazonium salt (10.42, Scheme 10-77) in five different aqueous systems (Table 10-7). About one-third of the yield is 2-hydroxybenzophenone (10.46) and two-thirds is fluorenone (10.45, run 1) copper has no effect (run 2). On the other hand, addition of cuprous oxide (run 3) has a striking effect on product ratio and rate. The reaction occurs practically instantaneously and yields predominantly fluorenone. As shown in Scheme 10-77, the authors propose that, after primary dediazoniation and electron transfer from Cu1 to 10.43 the sigma-complex radical 10.44 yields fluorenone by retro-electron-transfer to Cu11 and deprotonation. In the presence of the external hydrogen atom source dioxane (run 12) the reaction yields benzophenone cleanly (10.47) after hydrogen atom abstraction from dioxane by the radical 10.43. 

In 1988 Masoud and Ishak demonstrated that ( -arenediazo methyl ethers do not react with 2-naphthol in dry organic solvents such as dioxan, ethanol, 2-propanol, but only in the presence of water. The reactions are catalyzed by hydrochloric acid (even in the absence of water). Under such conditions almost quantitative yields of azo compounds were obtained. A careful and extensive kinetic investigation of the HCl-catalyzed dediazoniation of substituted benzenediazo methyl ethers, varying the HC1 concentration and the diazo ether/2-naphthol ratio (the latter either absent or in large excess), and comparing the observed rate constants with Hammett s acidity functions for dioxane and ethanol (see Rochester, 1970) indicated the mechanism shown in Schemes 12-8 to 12-10 (DE = diazo methyl ether, D+ = diazonium ion). 

Dediazoniation is an SN1 process for which the formation of an aryl cation is, at present, accepted as the first and rate-limiting step (Scheme 3).Ua.d.15il-e This aryl cation has been detected by ESR spectroscopy during the photodecomposition of arenediazonium tetra-fluoroborates at 77K.15f The nitrogen loss has been shown to be reversible, to some extent, by performing the reaction with a unsymmetrically 15N-labeled diazonium salt.151... 

No general pattern can be recognized in the reaction of azides with cycloalkenes. Angle strain can greatly enhance the rate of azide addition to cycloalkenes, as shown by work on norbornene and its derivatives (Huisgen et al., 1965), on hexa-methylbicyclo[2.2.0]hexa-2,5-diene (Dewar benzene) (Paquette et al., 1972) and related compounds (review Lwowski, 1984, p. 579ff). Normally, dihydrotriazoles are primary products, followed by a dediazoniation to aziridines. Diazo compounds are formed only in rare cases, e.g., with trifluoromethylated Dewar thiophenes (Kobayashi et al., 1977, 1980). 

We will discuss the dediazoniation step again in Section 7.3 in relation to the problem of the contribution of nucleophiles to the rate-limiting step under other reaction conditions than those used by Fishbein. 

Until the end of the 1970 s, interest in such reactions concentrated on catalysis by copper salts (review Burke and Grieco, 1979), obviously influenced by the long, broad, and successful experience with copper +- and copper-ions in aromatic diazo chemistry (Sandmeyer, Pschorr and Meerwein reactions, see Zollinger, 1994, Chapts. 8 and 10). A landmark was the discovery of Salomon and Kochi (1973), who found that cyclopropanations with diazomethane in the presence of copper(i) trifluoromethanesulfonate (triflate OTf) resulted in reduction of Cu + to Cu +, and that the rate of dediazoniation is inversely proportional to the alkene concentration. These results strongly indicate that formation of an alkene-Cu+ complex (8-47 2) precedes the complex formation with the diazoalkane. 

Redox potentials of the halide ions explain that direct electron release to the benzenediazonium ion takes place only with iodide (and astatide, At ). This corresponds well with experience in organic synthesis iodo-de-diazoniations are possible without catalysts, light or other special procedures. For bromo- and chloro-de-diazoniations, catalysis by cuprous salts (Sandmeyer reaction) is necessary. For fluorination, the Balz-Schiemann reaction of arenediazonium tetrafluoroborates in the solid state (thermolysis) or in special solvents must be chosen, i.e. a heterolytic dediazoniation without electron transfer. GaUi demonstrated that in chloro-de-diazoniations the yield is strongly dependent on the redox potential of electron transfer catalysts (highest yields with Cu" and Sn +), but that the rate of electron transfer influences the yield also. Electron transfer is likely to be the rate-limiting step of aryl radical formation in dediazoniations catalyzed by transition metal salts. 

Relative product yields from dediazoniation of l-ArN in H20-R 0H solution are proportional to rates of formation of these products from reaction with the aryl cation intermediate, l-Ar+ in the fast step. Scheme 4. The equation... 

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