Nucleophilic attack carbonium ions

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). 

When acid-catalyzed ring opening is not synchronous with nucleophilic attack, the intermediate carbonium ion can undergo rearrangement (193,195) (66JOC3941, 73CJC1448). 

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 formation of 88 is postulated to be occurring by the nucleophilic attack of a hydride ion (47), abstracted from the secondary amine, on the a-carbon atom of the iminium salt (89). The resulting carbonium ion (90) then loses a proton to give the imine (91), which could not be separated because of its instability (4H). In the case of 2-methyIhexamethylenimine, however, the corresponding dehydro compound /l -2-methylazacyclo-heptene (92) was isolated. The hydride addition to the iminium ion occurs from the less hindered exo side. 

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 mechanism of the aromatic substitution may involve the attack of the electrophilic NOj ion upon the nucleophilic aromatic nucleus to produce the carbonium ion (I) the latter transfers a proton to the bisulphate ion, the most basic substance in the reaction mixture... 

This reaction proceeds via the transition state illustrated in Fig. 10.2. An Sn2 reaction (second order nucleophilic substitution) in the rate limiting step involves the attack of the nucleophilic reagent on the rear of the (usually carbon) atom to which the leaving group is attached. The rate is thus proportional to both the concentration of nucleophile and substrate and is therefore second order. On the other hand, in an SnI reaction the rate limiting step ordinarily involves the first order formation of an active intermediate (a carbonium ion or partial carbonium ion, for example,) followed by a much more rapid conversion to product. A sampling of a and 3 2° deuterium isotope effects on some SnI and Sn2 solvolysis reactions (i.e. a reaction between the substrate and the solvent medium) is shown in Table 10.2. The... 

In 5, coordination through O polarizes the C = O bond producing the incipient carbonium ion, which is more susceptible to nucleophilic attack. In 6, there is intramolecular attack by coordinated OH on the N-bonded monodentate amino acid. In 7, only a small rate enhancement would be anticipated from intermolecular attack on the N-bonded monodentate. In these representations, X is OR, but anticipating the next section, it might also be NHR. These interpretive problems are illustrated in the hydrolysis of complexes of the type 8, where again any of three mechanisms corresponding to 5-7 could apply. 

This is a widely observed type of reaction for oxetanes and 2-oxetanones and has many variations. The typical pattern involves electrophilic attack on the ring oxygen atom of oxetanes to form an unstable oxetanium ion. The latter either undergoes C—O ring scission to a carbonium ion which then combines with a nucleophile, or nucleophilic attack by even very weak nucleophiles at the a-carbon atom. For clarity, these reactions will be arranged according to the nature of the overall process. 

The diol-epoxide contains a reactive carbon center, namely the C-10 position, which can open to form a carbonium ion that is susceptible to nucleophilic attack (Scheme 3.4). The predominant nucleophile among DNA bases is guanine, which preferentially interacts with the carbonium ion at the N2-amine position of guanine to form the BaP-N 2-guanine adduct. The epoxide bond of the diol-epoxide metabolite is particularly resistant to hydrolysis because it is located in the Bay region of the BaP molecule, where steric hindrance prevents the attack of hydrolytic enzymes, such as epoxide hydrolase. 

Only carbonium ions and alkylating agents of similar high reactivity, such as trialkyloxonium cations133, will attack the very weakly nucleophilic carboxylic acid group at a useful rate under normal conditions. Ester formation by alkylation of the carboxyl oxygen atom normally involves the carboxylate anion, viz. 

Shafizadeh5 has suggested that a unimolecular (SNO reaction is operative. In this type of reaction, the rate-determining step would be the formation of a carbonium ion, with the removal of the ethylthio group subsequent attack on this ion by the nucleophile would be rapid. In an SNj reaction, the removal of the ethylthio group and the attack by the nucleophile would be simultaneous. The SNi reaction seems more probable here. 

Any discussion of the mechanism of xanthine oxidase should attempt to incorporate the special features of xanthine oxidase (and xanthine dehydrogenase and aldehyde oxidase) which are not present, for example, in sulfite oxidase. There are two such features at least (a) the involvement of two protons rather than the one found for sulfite oxidase, and (b) the presence of the cyanolyzable sulfur atom. The mechanistic features discussed so far involve the abstraction of two electrons and a proton. This means that a carbonium ion is generated, which could undergo attack by a nucleophile. Thus, the presence of a nucleophile at the active site could lead to the formation of a covalent intermediate that will break down to give the products.1032 The nucleophile could either be the cyanolyzable sulfur atom or a group associated with the second proton. A possible scheme is shown in Figure 41. 

The reactions of carbonium ions occur via transition states having precise stereochemistry in which the electron pair of the attacking nucleophile must be col inear with the empty p-orbital of the electron-poor carbon atom. Thus, powerful stereoelectronic effects control these reactions. 

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