YX Scales of Solvent Ionizing Power

Publisher Summary This chapter discusses the development of tetrazole chemistry from 1965 to 1975. Over the years, it has been noted that the field has grown rapidly, with regard to the industrial interest that the tetrazoles command. Some of the significant areas in this field include the applications of modern physical techniques to tetrazole derivatives and studies of pharmacologically active tetrazoles, particularly, replacement of the carboxylic acid group in known active molecules by its analog—the tetrazole ring. Tetrazole essentially is an aromatic azapyrrole nucleus, which exist in two tautomeric forms. The chapter also describes physicochemical studies. These studies include nuclear magnetic resonance spectroscopy and theoretical calculations, mass fragmentation, tetrazole complexes and crystal structures, and photolysis and tetrazole radicals. Tetrazole can be synthesized by several methods that are also presented in the chapter. In the context of azide-tetrazole isomerism, it is observed that polar solvents tend to favor the tetrazole form and nonpolar solvents the azide form. Another factor that influences this isomerism is the syn-anti isomerism about the C=N moiety.

Recent Advances in Tetrazole Chemistry

Publisher Summary This chapter focuses on the status of reactivity–selectivity relationships by exploring the basis and variety of such relationships, and outlines the limitations of this principle. A qualitative statement of reactivity–selectivity principle is that highly reactive species are unselective in their choice of reactants compared to stable and, therefore, unreactive species. In a particular reaction series, an increase in the reactivity of one of the reactants results in a corresponding decrease in the selectivity of that species. In certain mechanistic areas, for example electrophilic substitution and carbene chemistry, mechanistic information can be derived by the reactivity–selectivity principle, which serves as a key probe into the stability and the structure of highly active species. The observation of a reactivity–selectivity relationship for a given reaction series suggests a certain uniformity in mechanism; a sudden break or the total failure to obtain such a relationship suggests the opposite. In view of the basic nature of the assumptions on which the reactivity–selectivity principle is based, reactivity–selectivity relationships serve as a probe into some of the fundamental tenets of theoretical chemistry. Some limitations of this principle are that it only applies to processes which obey a rate- equilibrium relationship; it only operates for relatively simple processes; reactions in which solvation factors contribute substantially to the overall energy change may also bring about a breakdown in the principle. The utility of the reactivity–selectivity principle is illustrated for a number of diverse areas of mechanistic interest.

The Reactivity—Selectivity Principle and its Mechanistic Applications

Publisher Summary This chapter presents the cross-interaction constants and discusses their applications for the characterization of TS structures for various types of reactions. Applications of the various cross-interaction constants to the elucidation of reaction mechanisms are discussed in the chapter. The use of the sign and magnitude allows us to predict the reaction types (IB- or TB-controlled in group-transfer and nucleophilic displacement reactions) and TS structures semiquantitatively. One of the most extensively investigated reactions in chemistry is nucleophilic substitution (S N ). In addition, S N -type reactions are most suitable for the application of cross-interaction constants as a measure of the TS structure. For these reasons, cross-interaction constants are determined and the TS structures are discussed for a large number of S N reactions in greater detail. As in any application of selectivity parameters from linear free energy relationships, cross-interaction constants reflect the TS structure only for the rate-determining step of a reaction. This means that interpretation of cross-interaction constants will not be clearcut and easy in a complex reaction, which proceeds in many steps with no identifiable single rate-determining step.

Cross-interaction constants and transition-state structure in solution

Publisher Summary Solvolytic reactions frequently are used to derive structure/reactivity relationships and the results are implicitly assumed to be independent of the solvent The solvent acts as a kinetically significant nucleophile in the overall solvolysis process for many simple secondary substrates, and this appears to be the major cause of the variation in relative rates with changes in solvent For solvolytic reactions that proceed via carbocations or ion pairs, it is of interest to compare the solvent effects with those obtained in strongly acidic media such as “magic acid” and in the gas phase Despite minor mechanistic differences, it is clear that solvation of charged intermediates must greatly reduce the energies of solvolytic reactions compared with the corresponding gas phase reaction As solvolytic reactions involve the nucleophilic “push” and electrophilic “pull,” it is possible to derive quantitative empirical measures of the role of solvent molecules as ionizing medium, electrophile and nucleophile By comparing the sensitivity of various reactions to solvent polarity or “ionizing power” and nucleophilicity, it is possible to deduce mechanistic information, which can supplement other evidence for reaction mechanisms The addition of salts can affect both the rate and the course of solvolytic reactions and provides very important evidence for ion-pair intermediates The SN1 and SN2(intermediate) mechanism of solvolytic reactions, mechanisms of solvolysis of secondary substrates, and correlation of solvolysis rates are described in the chapter

Medium Effects on the Rates and Mechanisms of Solvolytic Reactions

The specific rates of solvolysis of p-nitrobenzyl chloroformate are well correlated using the extended Grunwald-Winstein equation, with a high sensitivity (l) to changes in solvent nucleophilicity (N(T)) and a moderate sensitivity (m) to changes in solvent ionizing power (Y(Cl)). The values are consistent with a rate-determining association within an association-dissociation pathway. The selectivity values (S) for the attack at the acyl carbon show a modest preference for ethanol over water and a relatively high preference for ethanol over 2,2,2-trifluoroethanol (TFE). The solvolyses of benzyl chloroformate show similar characteristics in solvents of relatively high nucleophilicity and/or low ionizing power. In solvents with considerable fluoro alcohol content, an ionization mechanism, accompanied by loss of carbon dioxide, leads to benzyl chloride, benzyl alcohol, and benzyl alkyl ether. A new correlation now applies, with a much lower l value and somewhat higher m value. The S values for this pathway are close to unity, even in TFE-ethanol mixtures, consistent with the components of the binary solvent capturing a highly reactive carbocation.

Rate and product studies with benzyl and p-nitrobenzyl chloroformates under solvolytic conditions

Correlation of ethanolysis rates of adamantyl arenesulfonates

The extended Grunwald−Winstein equation has been applied to the specific rates of solvolysis of 2-phenyl-2-ketoethyl bromide and tosylate and the correlation parameters are consistent with an SN2 mechanism over the full range of solvents. The kOTs/kBr ratios are close to unity, consistent with this assignment. Comparisons with the specific rates of solvolysis of 2-phenylethyl bromide and methyl tosylate show only a modest influence upon introduction of the carbonyl group.

Correlation of the rates of solvolysis of 2-phenyl-2-ketoethyl bromide and tosylate.

A previous study of the methanolysis and phenolysis of acetyl chloride in acetonitrile has been extended to the influence of the substitution of up to two chlorine atoms or up to three methyl groups into the acetyl chloride. For each of the substrates so obtained, the methanolysis continues to exhibit pathways with both second-and third-order kinetics. The introduction of up to two methyl groups has only a minor influence but an appreciable fall in the magnitude of both rate coefficients is observed upon introduction of the third methyl group. The introduction of chlorine atoms leads to fairly large accelerations, and a tightening of the loose SN2 transition state or, possibly, a change to an addition–elimination mechanism. The phenolysis reactions, in the presence of methyl substituents, can be described at fairly low phenol concentrations in terms of second-order rate coefficients, which fall off slightly in value as methyl groups are introduced. In contrast to methanolysis, the phenolysis shows a large decrease in rate on introduction of an electron-withdrawing chlorine substituent; this reduction is consistent with a retardation of the electrophilically assisted ionization mechanism proposed for phenolysis of the parent substrate.

Nucleophilic substitution at trigonal carbon. Part 4. Substituent effects in the reactions of aliphatic acyl chlorides with methanol and phenol in acetonitrile

Chang-Bae Kim

Papers

Rate and product studies with benzyl and p-nitrobenzyl chloroformates under solvolytic conditions

Correlation of ethanolysis rates of adamantyl arenesulfonates

Correlation of the rates of solvolysis of 2-phenyl-2-ketoethyl bromide and tosylate.

Nucleophilic substitution at trigonal carbon. Part 4. Substituent effects in the reactions of aliphatic acyl chlorides with methanol and phenol in acetonitrile

Kinetics and mechanism of tetrazole formation from 1-adamantyl arenesulfonates in acetonitrile containing azide ion