Acidity structure reactivity effects

The reaction is less selective than the related benzoylation reaction (/pMe = 30.2, cf. 626), thereby indicating a greater charge on the electrophile this is in complete agreement with the greater ease of nuclophilic substitution of sulphonic acids and derivatives compared to carboxylic acids and derivatives and may be rationalized from a consideration of resonance structures. The effect of substituents on the reactivity of the sulphonyl chloride follows from the effect of stabilizing the aryl-sulphonium ion formed in the ionisation step (81) or from the effect on the preequilibrium step (79). 

The Hammett equation is not the only LFER." ° Some, like the Hammett equation, correlate structural changes in reactants, but the Grunwald-Winstein relationship (see p. 452) correlates changes in solvent and the Brpnsted relation (see p. 337) relates acidity to catalysis. The Taft equation is a structure-reactivity equation that correlates only field effects. ... 

The most frequently encountered hydrolysis reaction in drug instability is that of the ester, but curtain esters can be stable for many years when properly formulated. Substituents can have a dramatic effect on reaction rates. For example, the tert-butyl ester of acetic acid is about 120 times more stable than the methyl ester, which, in turn, is approximately 60 times more stable than the vinyl analog [16]. Structure-reactivity relationships are dealt with in the discipline of physical organic chemistry. Substituent groups may exert electronic (inductive and resonance), steric, and/or hydrogen-bonding effects that can drastically affect the stability of compounds. A detailed treatment of substituent effects can be found in a review by Hansch et al. [17] and in the classical reference text by Hammett [18]. 

J. Nishikawa, K. Tori, 3-Substituent Effect and 3-Methylene Substituent Effect on the Structure-Reactivity Relationship of 7 beta-(Acylamino)-3-cephem-4-carboxylic Acid Derivatives Studied by Carbon-13 and IR Spectroscopies , J. Med. Chem. 1984, 27, 1657-1663. 

The conclusion that should be drawn from this discussion is that there are two kinds of acidity that must not be confused (1) an intrinsic acidity, which is best approximated by gas-phase measurements and which reflects the properties of the ions and molecules in isolation, and (2) a practical liquid-phase acidity in which solvation effects may play the dominant role. In interpretation of structure-reactivity relationships, the liquid-phase acidity will probably be misleading unless the structures being compared are very similar for thinking about chemical behavior in solution, however, the liquid-phase acidities are clearly the important ones. 

Numerous investigations of reactions of allyfic stannanes with aldehydes have demonstrated that changes in steric interactions and electronic effects are introduced by the coordination of Lewis acids. In fact, the oxocarbenium species serves as the reactive partner in the allylation process, and deficiencies of detailed knowledge regarding the structure, reactivity, and steric requirements of oxocarbenium complexes leads to some uncertainties in providing a simple model to forecast stereoselectivity. Based upon a body of results accumulated from a variety of investigators, the pre-complexation with a specific Lewis acid and aldehyde may sustain the inherent attributes of the synclinal transition state, or the coordination complex may present features that override this tendency in favor of antiperiplanar arrangements. 

Differences in Structure - Reactivity Patterns in Acid-catalysed and Spontaneous Hydrolyses - Effect of the Pre-equilibrium Protonation... 

The rates of reaction of other compounds were also measured relative to this reference compound. Results of such comparisons are presented in Figure 6. Empirical correlations between the kinetic effects of fulvic acid derived peroxy radicals and those of unique reference peroxy radicals indicate that even for this case structure-reactivity relationships can be applied for estimations. However, correlations established for waters containing different types of DOM appear to be somewhat different (Faust and Hoigne, 1987). In addition, because the light screening effects depend on the wavelength, depth functions for different water bodies would require information also on the wavelength dependences of the formation of this environmental factor. 

Curved Brpnsted plots or other structure-reactivity correlations are often taken as evidence for changes in transition-state structure with changing properties of the reactant that might be described by the Marcus equation (24) or other equations. However, it is important to evaluate other possible explanations for such curvature, including solvation effects that could decrease the reactivity of basic nucleophiles without any change in the structure of the transition state for nucleophilic attack. For example, solvation effects could provide a relatively simple explanation for the curvature of structure-reactivity correlations for reactions of basic oxygen anion nucleophiles with acyl compounds and carbon acids. 

Solvent Dependence of Reactivity. Solvolysis reactions were investigated to obtain structure-reactivity relationships, but these studies were complicated by the solvent dependence of relative rates (Table I). These results show a 1010 variation in relative rates of solvolyses of methyl and 2-adamantyl tosylates (2-AdOTs) in trifluoroacetic acid (TFA) compared with those of ethanolysis. Even for two secondary systems, relative rates for 2-AdOTs-(CH3)2CHOTs vary from 36 in trifluoroacetic acid to 0.0011 in ethanol (4). Hence, separate intrinsic structural effects must be separated from solvent-induced effects. 

Asymmetric alkylation of carboxylic acid derivatives has been studied intensively for about 20 years. [1] Numerous auxiliaries, tailor-made structures with high steric demands for effective RelSi face differentiation, have been synthesized and their efficiency tested. [1, 2] In recent years besides the preparative aspects of enolates, physico-chemical investigations into their structure-reactivity relationships have gained interest. [3] Crystal structure analyses, osmometric measurements, and NMR studies in solution are helpful in the investigation of the factors that may control enolate reactions. [3-5]... 

Structure was determined by X-ray analysis. A detailed paper on the intramolecular acylation of long-chain >-(2-thienyl)alkanoic acids at the 5-position in acetonitrile solution in the presence of trifluoroacetic anhydride and catalytic amounts of H3PO4 has appeared. The ring-sizes of the resulting (2,5)thiophenophan-l-ones ranged from 12 to 21. Reliable rate data and effective molarities were obtained, for use in structure-reactivity correlations. This cyclization procedure was used for the preparation of a key intermediate in a five-step synthesis of //-muscone. ... 

The structure-reactivity relationship for polyamine derivatives in activated ester hydrolysis was previously established [46]. Polyvinylamine (PVA), linear (LPEI) and branched (41% branching) polyethylene imine (BPEI) as well as their dodecyl- and imidazole-substituted derivatives with an approximate and equal degree of substitution (16-20%) were applied as catalysts. The compoundsp-NPA and 4-acetoxy-3-ni-trobenzoic acid (ANBA) as well as some of their homologues were used as substrates. At an excessive catalyst concentration relative to the substrate concentration, reactions proceeded at pseudo first order. In each series of polymers, the reaction rate constant was increased considerably by substitution of dodecyl (hydrophobic site) by imidazolyl (catalytic center) and when a charged substrate (electrostatic effect) was employed. At an equal degree of substitution, the catalytic activity increased in the following order LPEK PVA < BPEI. 

Results of a kinetic study of the acid-catalysed oxidation of benzaldehydes by pyri-dinium bromochromate in DMSO have been analysed via several structure-reactivity correlations, and solvent effects have been examined in 19 media. A substantial primary kinetic isotope effect is seen for PhCDO. 

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