Carbonium ions nucleophilic substitution reactions

The rate of a unimolecular substitution depends only upon the concentration of the substrate, and not upon the concentration of the nucleophile. Such reactions are called unimolecular nucleophilic substitution reactions, SN1. The first step is a heterolytic cleavage of the carbon/heteroatom bond, to result in a carbonium ion. 

Formation of the phosphonium compound itself may occur in a number of ways. The simplest route—bimolecular, nucleophilic substitution (SN2) by a trivalent phosphorus ester—is the type most commonly encountered (eq. 3a). For reagents capable of facile carbonium ion formation, the reaction follows an SNl pathway (eq. 3b). 

Secondary j -deuterium kinetic isotope effects arise when the hydrogen(s) on the jS-carbon (adjacent to the carbon where the C—X bond rupture is progressing) are replaced by deuterium(s). These isotope effects kulk o) are greater than unity for nucleophilic substitution reactions. In addition, the magnitude of the isotope effect increases as the amount of positive charge (carbonium-ion character) on the a-carbon in the transition state 2 is increased. For example, the isotope effect per CD3 group increases from about 1.03... 

Not shown in the description above, but assumed to be important, is solvation at the rear side of in the ion pairs. According to this scheme, attack by a nucleophile or solvent can occur on the covalent substrate, the intimate ion pair, the solvent-separated ion pair, or on the dissociated carbonium ion. Nucleophilic attack on the covalent substrate or on the intimate ion pair will be akin to a displacement process, and will take place with inversion of configuration. At the solvent-separated ion-pair stage, collapse of the solvent shell can occur from the front to produce retention of configuration or from the back to produce inversion, or the carbonium ion can become symmetrically solvated to produce racemic product. The macroscopic properties of the nucleophilic substitution reaction result from competition among these various rate processes. 

The solvolysis reactions of cyclopropylmethyl systems also provide evidence for the intermediacy of carbonium ions in nucleophilic substitution reactions. We have seen in Table 5.2 that the stabilizing effect a cyclopropyl group exerts on a carbonium ion is appreciable. A similar effect is evident on comparing rates of hydrolysis of cyclopropylmethyl compounds with model aliphatic compounds. The tertiary p-nitrobenzoates represented by the structure 1 had the relative rates indicated for hydrolysis in 80% aqueous dioxane at 60°C ... 

Up to this point in our discussion, we have considered only carbonium ions in which the cationic carbon is -hybridized or nearly so, and in which the geometry at the cationic center is planar. When either of these conditions is not met, the carbonium ion is of higher energy. Discussing first the geometric requirement, one of the classic experiments of organic chemistry was that carried out by Bartlett and Knox, who showed the inertness of 1-chloroapocamphane toward nucleophilic substitution reactions" " ... 

Solvolysis reactions in media of low nucleophilicity are characterized by increased tendencies toward carbonium ion rearrangements and increased racemiza-tion when optically active substrates are employed. We have seen examples of extensive rearrangements in our discussion of carbonium ions generated in superacid media, in which the observed ion was quite often the most stable possible ion of a particular system. A later section of this chapter deals with the stereochemistry of nucleophilic substitution reactions, and examples of solvent nucleophilicity effects on stereochemistry will be encountered there. 

Nucleophilic substitution reactions that occur under conditions of amine deamination often differ significantly in stereochemistry, compared with that seen in halide or arenesulfonate solvolysis. The results of four key substrates are summarized in Table 5.13. It can be seen (entry 1) that displacement of nitrogen on the 1-butyldiazonium ion is much less stereospecific than the 100% inversion observed on acetolysis of the corresponding brosylate. Similarly, the secondary system (entry 2) affords 2-butyl acetate with only 28% inversion of configuration. Furthermore, a crossover to net retention of configuration is observed as the alkyl group becomes better able to stabilize a carbonium ion. The small net retention (10%) observed in deamination of 1-phenylethylamine increases to 28% retention in the tertiary benzylic system 2-phenyl-2-butylamine. 

Secondary isotope effects are also observed with isotopic substitution at carbon atoms relatively remote from the reaction site. These effects have been studied especially thoroughly in the case of nucleophilic substitution reactions. When deuterium is introduced at the carbon two atoms down the chain (the p carbon), significant secondary isotope effects are observed when carbonium ions are formed as intermediates. It is generally believed that hyperconjugative interactions with the carbonium ion site are responsible for the changes in vibrational force constants... 

It is clear that since carbonium ions are key intermediates in many nucleophilic substitution reactions, we will need to develop a grasp of the structural properties of carbonium ions and, in particular, the nature of substituent effects. The critical step of any ionization mechanism for nucleophilic substitution is the generation of a tricoordinate carbocation in the rate-determining step. It is essential, then, that... 

Nucleophilic substitution reactions that occur under conditions of amine diazotization often differ significantly in stereochemistry, as compared with that seen in halide or arenesulfonate solvolysis. Diazotization occurs via an N-nitroso amine which decomposes to a carbonium ion, molecular nitrogen, and water ... 

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 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... 

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67 Perchloro-organic chemistry structure, spectroscopy and reaction pathways, 25, 267 Permutations isomerization of pentavalent phosphorus compounds, 9, 25 Phase-transfer catalysis by quaternary ammonium salts, 15, 267 Phenylnitrenes, Kinetics and spectroscopy of substituted, 36, 255 Phosphate esters, mechanism and catalysis of nucleophilic substitution in, 25, 99 Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in permutational isomerization, 9, 25 Photochemistry, of aryl halides and related compounds, 20, 191 Photochemistry, of carbonium ions, 9, 129... 

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... 

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