Zollinger studies

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

Many studies of such acid-base equilibria of substituted benzenediazonium ions have been reported since the first investigation by Wittwer and Zollinger (1954), namely by Lewis and Suhr (1958 a), Littler (1963), Ritchie and Wright (1971 a, 1971 b), Machackova and Sterba (1972 a), Beranek et al. (1973), Jahelka et al. (1973 a), Vir-tanen and Kuokkanen (1977), BagaPs group (Luchkevich et al., 1986 and references therein), and in DMSO by Petrov et al. (1973). 

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). 

A quantitative study of the azo coupling reactions of heterocyclic diazo compounds was made by Sawaguchi et al. (1971), who measured the coupling rates of seventeen heterocyclic diazonium ions with R-acid (2-naphthol-3,6-disulfonic acid) and compared them with those of the benzenediazonium ion with the same coupling component. All the heterocyclic diazonium ions investigated react faster with R-acid than does the benzenediazonium salt. More recently, Diener and Zollinger (1986) confirmed Sawaguchi s results and interpreted them in more detail. 

In studies aimed at understanding the influence of structure on the reactivity of diazonium ions, Diener and Zollinger (1986) found that the NMR chemical shifts of the aromatic or heteroaromatic parent compounds provided a novel probe. This method can be applied both to substituted benzenediazonium ions and to various heteroaromatic diazonium ions, and it also provides semiquantitative information on the relative reactivities of the l,3,4-triazole-2-diazonium ion (12.5) and its deprotonated zwitterion (12.6). 

Structure 12.148 was already supported by results from Stamm and Zollinger s investigation (1957) in which activation entropies were determined. The mechanism was corroborated by further activation entropy studies (Demian, 1972, 1973 Demian et al., 1983) and investigations on the 2/4-ratio of coupling of 1-naphthylamine carried out by Hashida et al. (1975 b). 

The reversibility of an azo coupling reaction was studied quantitatively by Diener and Zollinger (1986 see this book, Sec. 3.4, Scheme 3-39). 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

The pioneering studies were by Meiander Melander Ark. Kemi 1950,2, 211 Berglund-Larsson Melander Ark. Kemi 1953, 6, 219. See also Zollinger, Adv. Phys. Org. Chem. 1964, 2, 163-200. 

Fischer and Zollinger have studied the reaction of p-chlorobenzenediazonium chloride with 2-naphthol-l-sulfonate. A very interesting dependence of the reaction products and reaction rate on the solvent was observed The initiaUy formed complex 102 decomposes under ring fragmentation in aqueous base (see (44) in Sect. 2.2.3) it does not react in water, ethanol or dimethylsulfoxide, reacts very slowly in acetone or glacial acetic acid to give a small amount of azo compound 7dJ, while in dichloromethane, chloroform, benzene or pyridine quantitative, though slow, formation of the azo compoimd is observed. Ba on kinetic measurements an Sisil-type mechanism was postulated for the formation of the azo dye 103 from the CT-complex 102... 

As azo coupling reactions with rate-limiting proton transfers are catalyzed by general bases, they follow Bronsted s catal is law. This was previously demonstrated in 1955 and studied in more detail by Zollinger et al. in 1969-1974 Four... 

Halogens as electrofugic leaving groups were studied by Fischer and Zollinger The rates of substitution of the group X in l-X-2-naphthol-6-sulfonic acid by... 

Among other kinetic studies of picryl chloride and I-chloro-2,4 dinitro-benzene with bases the works should be mentioned of Parker and Read [112) and Zollinger and co-workers [113] which have shown a much higher reactivity of picryl chloride. The reactions are greatly influenced by solvent and in some instances l-chloro-2,4-dlnitrobenzeneisinore reactive than picryl cliloride [114). 

Eu E, Venzon DJ, Serrano J, et al. Prospective study of the clinical course, prognostic factors, causes of death and survival in patients with longstanding Zollinger-Ellison syndrome. J Clin Oncol 1999 17 615-630. 

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