Carbonium ions reactions with nucleophiles

Kinetic data on acetate displacement from C-3 using a number of sulfur and nitrogen nucleophiles in aqueous solution at near neutral pH demonstrate that the reaction proceeds by an 5 1 mechanism (B-72MI51004). The intermediate in this reaction is depicted as a dipolar allylic carbonium ion (9) with significant charge delocalization. Of particular significance in this regard is the observation that the free carboxylate at C-4 is required since... 

Condensation reactions of carbonium ions compete with sulfonation and their frequency is increased with increasing acidity. Carbon-carbon bonds are formed most commonly when the benzylium ions react with the weakly nucleophilic 1- and 6-(or 5-)positions of other phenylpropane units (Fig. 

Since a requirement of the SnI mechanism is the reaction of the carbonium ion with nucleophiles in a fast step subsequent to rate-determining ionization, it would be desirable to have independent data relative to the trapping of carbonium ions by nucleophiles. Triarylmethyl cations react with nucleophiles at rates sufficiently slow to be studied by conventional means, and have provided much information concerning the effectiveness of various nucleophilic species. This will be discussed in the next section of this chapter. The simpler carbonium ions are more reactive, and special techniques must be employed to determine their extremely rapid rates of reaction with nucleophiles. Benzyl cation has been generated by pulse radiolysis in 1,2-dichloroethane, and the absolute rate constants for its reaction with methanol, ethanol, bromide, and iodide ion measured.The second-order rate constants for this group of nucleophiles fall in the range 10 -10 sec ... 

The other common mechanism for substitution at saturated carbon, SnI (3.81a) also has its analogue in phosphorus chemistry. Moreover it is generally believed that, in the case of both elements, substitution reactions intermediate in mechanism between SnI and Sn2 may sometimes take place. In carbon chemistry, the SnI mechanism involves an intermediate planar carbonium ion. Since the nucleophilic entering group may attack either face of the planar carbonium ion with equal probability, a racemic mixture is expected to be obtained. In practice this is not always achieved completely, because the nucleophile may have attacked before the carbonium ion was produced. 

On the other hand, the metabolization to C7 as well as to C9 carbonium ions (especially the speed rate of this metabolization) and the subsequent reaction with nucleophiles are seen as a key step concerning the level of toxicity. The concrete binding situation concerning the ester function can be found analyzing the X-ray data. Interpretation of the bond lengths shown in Fig. 13.5 leads to the following results ... 

As predicted from the pKr+ values (Table 7.4) the S-di-p-methoxybenzhydryl group [18] is cleaved much more rapidly than other S-benzhydryl thioethers. Konig et al. [55] report complete removal in 2 hr with trifluoroacetic acid (70 ) or in 10 min with added anisole. Photaki et al. [58] report 80% removal in 2 hr (20-25°) with trifluoroacetic acid and 15% phenol. The pKr value of this cation predicts it to be more stable than the S-trityl cation which in turn su ests a more rapid conversion of the conjugate acid of the thioether to the carbonium ion and thiol and a selectivity comparable with trityl in the reaction with nucleophiles. This prediction is not entirely borne out by facts and indeed the S-di-p-methoxybenzhydryl group falls between the benzhydryl and trityl in reactivity. This lowered reactivity is probably due to the presence of significant concentrations of the less reactive dication. 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

The susceptibihty of dialkyl peroxides to acids and bases depends on peroxide stmcture and the type and strength of the acid or base. In dilute aqueous sulfuric acid (<50%) di-Z fZ-butyl peroxide is resistant to reaction whereas in concentrated sulfuric acid this peroxide gradually forms polyisobutylene. In 50 wt % methanolic sulfuric acid, Z fZ-butyl methyl ether is produced in high yield (66). In acidic environments, unsymmetrical acychc alkyl aralkyl peroxides undergo carbon—oxygen fission, forming acychc alkyl hydroperoxides and aralkyl carbonium ions. The latter react with nucleophiles,... 

It was pointed out earlier that the low nucleophilicity of fluoride ion and its low concentration in HF solutions can create circumstances not commonly observed with the other halogen acids. Under such conditions rearrangement reactions either of a concerted nature or via a true carbonium ion may compete with nucleophilic attack by fluoride ion. To favor the latter the addition of oxygen bases, e.g., tetrahydrofuran, to the medium in the proper concentration can provide the required increase in fluoride ion concentration without harmful reduction in the acidity of the medium. 

The first step, which is rate determining, is an ionization to a carbocation (carbonium ion in earlier terminology) intermediate, which reacts with the nucleophile in the second step. Because the transition state for the rate-determining step includes R-X but not Y , the reaction is unimolecular and is labeled S l. First-order kinetics are involved, with the rate being independent of the nucleophile identity and concentration. 

Evidence that the actual methylation of the anion can be divided into SnI, Eq. (3), and Sx2 types, Eq, (4), is provided by a whole series of investigations. " The terms S l and 8 2 must be taken to mean reactions with, respectively less or greater nucleophilic participation of the anion in the transition state. The importance of oriented ion pairs" in the solvents of low polarity frequently used in reactions involving diazomethanc, e.g., the ions formed by a diazoalkane and benzoic acid in ether, should be emphasized. The expression oriented ion pair means that, because of insufficient solvation, the ions are not individually solvated but exist as ion pairs within a solvent cage. The orientation within the ion pair is defined electrostatically, and this orientation fixes the path for the productdetermining step. Several indications (cf, foo otes 22-24) in the literature indicate the occurrence of carbonium ions and oriented ion pairs in Broensted-type equilibria of the type of Eq. (2). 

The two main reasons for studying the reversible reaction (3) were (a) to complete the picture of the Koch reaction in terms of quantitative information and (b) to set up a scale of reactivity towards a neutral nucleophile for carbonium ions of different structure. The first item is important from a practical point of view because there are reactions competing with the carbonylation step (3), which can be divided into intramolecular and intermolecular processes. Rearrangement of the intermediate alkylcarbonium ion, e.g. 

Perhaps the most important single function of the solution environment is to control the mode of decomposition of reaction intermediates and hence the final products. This is particiflarly true in the case of electrode reactions producing carbonium ion intermediates since the major products normally arise from their reaction with the solvent. It is, however, possible to modify the product by carrying out the electrolysis in the presence of a species which is a stronger nucleophile than the solvent and, in certain non-nucleophilic solvents, products may be formed by loss of a proton or attack by the intermediate on further starting material if it is unsaturated. The major reactions of carbonium ions are summarized in Fig. 6. 

The effect of structure of the alkyl group on the stability of monoalkyl-thallium(III) compounds can best be understood by reference to the different mechanisms by which these compounds undergo decomposition. A number of authors have attributed the instability of monoalkylthallium(III) compounds to facile C—T1 bond heterolysis and formation of carbonium ions [Eq. (25)] (52, 66, 79). This explanation is, however, somewhat suspect in cases where primary carbonium ions would be involved and either the two-step sequence shown in Eqs. (26), (27), or the fully synchronous 8 2 displacement shown in Eq. (28), is more compatible with the known facts. Examination of the oxythallation reactions that have been described reveals that Eq. (27) [or, for concerted reactions, Eq. (28)] can be elaborated, and that five major types of decomposition can be recognized for RTlXj compounds. These are outlined in Scheme 8, where Y, the nucleophile... 

Since the results of our experiments with isolated rat liver fractions supported a reaction sequence Initiated by microsomal oxidation of the nitrosamine leading to formation of a carbonium ion, the results of the animal experiment suggested that in the intact hepatocyte, one of the earlier electrophilic intermediates (II, III or V, Figure 1) is intercepted by nucleophilic sites in DNA (exemplified here by the N7 position of guanine) before a carbocation is formed. 

An explanation not easily distinguishable from the one involving resonance with a carbonium ion structure in the transition state is that the reactive species is an ion pair in equilibrium with the covalent molecule. This is quite likely in a solvent insufficiently polar to cause dissociation of the ion pairs. Examples of second order nucleophilic displacements accelerated by the sort of structural change that would stabilize a carbonium ion are of fairly frequent occurrence. Allyl chloride reacts with potassium iodide in acetone at 50° seventy-nine times as fast as does -butyl chloride.209 Another example is the reaction of 3,4-epoxy-1 -butene with methoxide ion.210... 

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