Salts substitution equilibria

This equilibrium applies to a mixture of an acid HA and its salt, say MA. If the concentration of the acid be ca and that of the salt be c5, then the concentration of the undissociated portion of the acid is (cfl — [H + ]). The solution is electrically neutral, hence [A ] = cs + [H + ] (the salt is completely dissociated). Substituting these values in the equilibrium equation (18), we have ... 

Of course, in aqueous solution the reactants and the products exist wholly or partly in their ionized forms the acid, nitrite, and salt exist as H+X , Na+N02, and Na+X , while the diazonium salts are practically completely ionized and the amine is in equilibrium with the corresponding ammonium ion, Ar—NH3. The question of which of these various species are involved in the substitution proper will be dealt with in Chapter 3. Although it is generally desirable to introduce ionized forms into equations, this is inappropriate for the overall equation for the diazotization process, as will become apparent in the discussion of the reaction mechanism (Ch. 3) and from the following remarks. 

The fundamental understanding of the diazonio group in arenediazonium salts, and of its reactivity, electronic structure, and influence on the reactivity of other substituents attached to the arenediazonium system depends mainly on the application of quantitative structure-reactivity relationships to kinetic and equilibrium measurements. These were made with a series of 3- and 4-substituted benzenediazonium salts on the basis of the Hammett equation (Scheme 7-1). We need to discuss the mechanism of addition of a nucleophile to the P-nitrogen atom of an arenediazonium ion, and to answer the question, raised several times in Chapters 5 and 6, why the ratio of (Z)- to ( -additions is so different — from almost 100 1 to 1 100 — depending on the type of nucleophile involved and on the reaction conditions. However, before we do that in Section 7.4, it is necessary to give a short general review of the Hammett equation and to discuss the substituent constants of the diazonio group. 

More recently, Bagal and coworkers (Luchkevich et al., 1991) obtained similar results in a kinetic investigation of the coupling reactions of some substituted benzenediazonium ions with 1,4-naphtholsulfonic acid, and with 1,3,6-, 2,6,8-, and 2,3,6-naphtholdisulfonic acids. The kinetic results are consistent with the transient formation of an intermediate associative product. The maximum concentration of this product reaches up to 94% of the diazonium salt used in the case of the reaction of the 4-nitrobenzenediazonium ion with 1,4-naphtholsulfonic acid (pH 2-4, exact value not given). The authors assume that this intermediate is present in a side equilibrium, i. e., the mechanism of Scheme 12-77 mentioned above rather than that of Scheme 12-76, and that the intermediate is the O-azo ether. 

In some cases, the Q ions have such a low solubility in water that virtually all remain in the organic phase. ° In such cases, the exchange of ions (equilibrium 3) takes place across the interface. Still another mechanism the interfacial mechanism) can operate where OH extracts a proton from an organic substrate. In this mechanism, the OH ions remain in the aqueous phase and the substrate in the organic phase the deprotonation takes place at the interface. Thermal stability of the quaternary ammonium salt is a problem, limiting the use of some catalysts. The trialkylacyl ammonium halide 95 is thermally stable, however, even at high reaction temperatures." The use of molten quaternary ammonium salts as ionic reaction media for substitution reactions has also been reported. " " ... 

O-Substituted oxime derivatives are synthetically useful in a wide variety of transformations. Hoffman and Butani have observed that reaction of a series of aldehydes and ketones with the potassium salt of Af,0-bis(trimethylsilyl)hydroxylamine 4a or 4b (a rapid equilibrium between 4a and its Af,N-bis(silylated) isomer 4b probably exists in solution) gave high yields of the corresponding oximate anion 5, formed via the Peterson-type reaction, together with the silyl ether 6. Anion 5 could be protonated to the oxime 7 or trapped in situ with a variety of electrophiles to give 0-substituted oxime derivatives (Scheme 6). 

The marked stability of dihydrodiazepines and dihydrodiazepinium salts and their ready formation in aqueous solution are reflected in the stability constants for their formation. These have been measured [68JCS(B)I536] for a range of methyl-substituted salts and refer to the following equilibrium ... 

This ready nucleophilic substitution at the 6-position is surprising since this position is electron-rich in both dihydrodiazepines and dihydrodiaze-pinium salts and is the site at which electrophilic substitution occurs. The likely explanation is that in the presence of base some prototropic rearrangement of the normal dihydrodiazepine base into a bis-imino form takes place. Although the equilibrium concentration of the bis-imine is likely to be very small (it has not been observed spectroscopically) it would be strongly electrophilic at the 6-position owing to the combined effects of the bromine atom and the two azomethine groups, and could well be the reactive species in the nucleophilic substitution of the bromine atom ... 

A quite consistent relationship is found in these and related data. Conditions of kinetic control usually favor the less substituted enolate. The principal reason for this result is that removal of the less hindered hydrogen is faster, for steric reasons, than removal of more hindered protons. Removal of the less hindered proton leads to the less substituted enolate. Steric factors in ketone deprotonation can be accentuated by using more highly hindered bases. The most widely used base is the hexamethyldisilylamide ion, as a lithium or sodium salt. Even more hindered disilylamides such as hexaethyldisilylamide7 and bis(dimethylphenylsilyl)amide8 may be useful for specific cases. On the other hand, at equilibrium the more substituted enolate is usually the dominant species. The stability of carbon-carbon double bonds increases with increasing substitution, and this effect leads to the greater stability of the more substituted enolate. 

This theory agrees with the later results of van Tamelen and Baran (58JA4659), who were able to get N-benzylcytisin (43) from the bicyclo-substituted pyridinium salt 42 via Decker oxidation. Since formation of an anhydro base 45 is violated according to Bredt s rule, an equilibrium between 44 and a C-6 pseudobase can exist, the latter being dehydrated to yield 43 (Scheme 9). 

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