Summary of electrophilic substitution reactions

Summary of Electrophilic Substitution Reactions of A -iV-Dimethylaniline and Acetanilide t ... 

Table 5—Summary of Electrophilic Substitution Reactions of Phenol, Diphenyl Ether, and Anisole... 

Substituent effect, additivity of, 570 electrophilic aromatic substitution and, 560-563 summary of. 569 Substitution reaction, 138 Substrate (enzyme), 1041 Succinic acid, structure of, 753 Sucralose, structure of. 1006 sweetness of, 1005 Sucrose, molecular model of. 999 specific rotation of, 296 structure of, 999 sweetness of, 1005 Sugar, complex, 974 d, 980 L, 980... 

This short summary has aimed to highlight a few of the more important aspects of the orientation of electrophilic substitution of pyridines and their benzo analogues. Strictly, reactions that involve metallation could be treated under this heading but they will be considered as involving a nucleophilic attack at a ring hydrogen (see Section 2.05.5). Electrophilic cyclizations of a substituent on to a pyridine will be mentioned briefly, but Chapter 2.06 should be consulted for those reactions. 

It is well known that not all attempts to explain the reactivity of individual positions in electrophilic substitution reactions have been successful. There are three main lines along which attempts have been made to remove discrepancies between theory and experiment (for a summary, see ref. 147) (1) introduction into the HMO treatment of additional empirical parameters (inductive effect), (2) invoking the addition-elimination mechanism, and (3) invoking different reactivity of the protonated and unprotonated forms. 

In the above examples, the nucleophilic role of the metal complex only comes after the formation of a suitable complex as a consequence of the electron-withdrawing effect of the metal. Perhaps the most impressive series of examples of nucleophilic behaviour of complexes is demonstrated by the p-diketone metal complexes. Such complexes undergo many reactions typical of the electrophilic substitution reactions of aromatic compounds. As a result of the lability of these complexes towards acids, care is required when selecting reaction conditions. Despite this restriction, a wide variety of reactions has been shown to occur with numerous p-diketone complexes, especially of chromium(III), cobalt(III) and rhodium(III), but also in certain cases with complexes of beryllium(II), copper(II), iron(III), aluminum(III) and europium(III). Most work has been carried out by Collman and his coworkers and the results have been reviewed.4-29 A brief summary of results is relevant here and the essential reaction is shown in equation (13). It has been clearly demonstrated that reaction does not involve any dissociation, by bromination of the chromium(III) complex in the presence of radioactive acetylacetone. Furthermore, reactions of optically active... 

A reaction that has been discussed in terms of high acid concentrations is the nitration that takes place upon electrolysis of a suspended aromatic hydrocarbon in dilute (1-2 m) nitric acid (for summaries, see Allen, 1958 Fichter, 1942 Tomilov, 1961 Tomilov and Fiochin, 1963). The proposal has been that nitric acid would be formed in high concentration in the anode region, thus causing nitration in an ordinary electrophilic substitution reaction. This is an entirely reasonable idea, as it has since been shown (Cauquis and Serve, 1970) that nitrate ion is oxidized to dinitrogen pentoxide using nitromethane as a solvent (59). In an aqueous solution this... 

In summary, all the early kinetic and spectroscopic evidence support the contention that the nltronlum Ion Is the effective electrophilic agent. Moreover, the rate data for the nitration reaction presented in Table I and illustrated In Figure 1 are representative of the normal reactivity pattern observed for many other electrophilic substitution reactions as shown by the results displayed in Figures 2 and 3. 

These reactions in weakly alkaline solutions are faster than the heterolytic (Dn + AN)-like hydroxy-de-diazoniation, which, for most diazonium ions, (depending on their electrophilicity), is dominant below pH 2-4. As shown by Ishino et al. (1976), an increase in rate, corresponding to the occurence of other mechanisms in addition to the heterolytic hydroxy-de-diazoniation, is observable at pH 3.7-7.0. The increase is dependent on the substituent in the specifically substituted benzenediazo-nium ion. The slope d(log )/d(pH) was found to be in the range 0.22-1.09 (see summary of the work of Ishino et al. by Zollinger, 1983, p. 624). 

In summary, then, the orientation of electrophilic thallation can be controlled by an appropriate manipulation of reaction conditions. Under conditions of kinetic control, ortho substitution results when chelation of the electrophilic reagent (TTFA in the studies described above) with the directing substituent permits intramolecular delivery of the electrophile, and para substitution results when such capabilities are absent this latter result is an expression of the very large steric requirements of the bulky thallium electrophile. Under conditions of thermodynamic control, however, meta substitution is observed. 

In summary (Scheme 15), 2-lithiopiperidines and 2-lithiopyrrolidines appear to be very versatile nucleophiles for the elaboration of these heterocyclic systems, affording a variety of 2-substituted heterocycles in excellent yields. The stereoselectivity of the reaction is near 100% in the piperidine series with most carbonyl electrophiles (retention of configuration) and alkyl halides (inversion of configuration). In the pyrrolidine series, the selectivity is also near 100% with carbonyl electrophiles (retention), but less selective (inversion predominates) with alkyl halides (less problematic with Af-aUylpyrrolidines). 

Table XXIV provides a summary of the p values for the electrophilic substitutions of thiophene derivatives when available, the p values for the corresponding reactions of benzene derivatives are also recorded for comparison.

In summary, the calculated electrophilicity index, to, for a series of substituted ethylenes may be used to make reliable estimates of the intrinsic electronic contributions to the <7p constants of Hammett equation for a series including 42 functional groups commonly present in organic compounds. The computed trjto) parameters account for the intrinsic electronic substituent effects, which are contained in the experimental values of the <7p substituent constants. This useful predictive tool to assess the reactivity pattern of gas-phase reactions or those reactions that take place in solvents of very low polarity. 

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