And substituent effects

Hammett s equation, and substituent effects, 137-43 heteromolecules, 130 Holleman s product rule, 3 hyperconjugation, in nitration of alkyl-benzenes, 165-7 in nitration of positive poles, 169... 

A nitro group behaves the same way m both reactions it attracts electrons Reaction is retarded when electrons flow from the aromatic ring to the attacking species (electrophilic aromatic substitution) Reaction is facilitated when electrons flow from the attacking species to the aromatic ring (nucleophilic aromatic substitution) By being aware of the connection between reactivity and substituent effects you will sharpen your appreciation of how chemical reactions occur... 

Representative chemical shifts from the large amount of available data on isothiazoles are included in Table 4. The chemical shifts of the ring hydrogens depend on electron density, ring currents and substituent anisotropies, and substituent effects can usually be predicted, at least qualitatively, by comparison with other aromatic systems. The resonance of H(5) is usually at a lower field than that of H(3) but in some cases this order is reversed. As is discussed later (Section 4.17.3.4) the chemical shift of H(5) is more sensitive to substitution in the 4-position than is that of H(3), and it is also worth noting that the resonance of H(5) is shifted downfield (typically 0.5 p.p.m.) when DMSO is used as solvent, a reflection of the ability of this hydrogen atom to interact with proton acceptors. This matter is discussed again in Section 4.17.3.7. 

Table 14.1. Prediction of C chemical shift of c/s-l,2-dimethylcyclohexane in the frozen state, using the cyclohexane shift of 8c = 27.6 and substituent effects (e.g. Ref. 6, p. 316)...

Linear Free-Energy Relationships and Substituent Effects... 

Saito, R., Hirano, T., Niwa, H., and Ohashi, M. (1997). Solvent and substituent effects on the fluorescent properties of coelenteramide analogues. J. Chem. Soc., Perkin Trans. 2, pp. 1711-1716. 

Kinetic studies are of little value in attempting to determine the extent of complex formation in the reaction path of electrophilic substitution. The reasons for this have been adequately presented elsewhere29 and the conclusions are that, unless the formation of the complex is rate-determining, the kinetic form is independent of complex formation. Further, the influence of complex formation on reaction rates only comes from the factors which lead in the first place to complex formation, and substituent effects are inadequate for showing the extent of complex formation though when they indicate similar effects on substitution and complex formation they provide evidence that the latter is a pathway of the former. 

Aromatic compounds can be hydroxylated, benzoxylated and acetoxylated and the isomer distributions and substituent effects indicate that the reaction is an electrophilic substitution132. Very little kinetic work has been carried out so that the nature of the electrophile is in some doubt. 

Furthermore, solvent, temperature and substituent effects on pXHB are also presented and dual substituent parameters have been introduced into two carbonyl series (CH3)2NC(0)X (X = CF3, CH2C1, H, CH3, NMe2) and CH3C(0)X (X = CH3CO, CF3, H, F, CH3, OCH3, NMe2) and related to the following equation ... 

Carbocation-carbanion zwitterionic intermediates were proposed for the thermal cleavage of several cyclic compounds. In most of these reactions the ionically dissociating bond belongs to one of four strained ring systems, i.e. cyclopropane (13), cyclobutane (14), cyclobutene (15) or norbornadiene (16). The mechanism is distinguished from the formation of a diradical intermediate through homolysis in terms of solvent and substituent effects... 

Table 9.5 Counterion and substituent effect on enolization selectivity. ...

Information on the mechanism is mainly obtained from kinetic solvent and substituent effects, i.e. from p- and m-values, as discussed below. These coefficients are therefore a composite of p- and m-values for CTC and ionization steps as shown in (9). Obviously, neither Pctc nor mCTC is available... 

KSIEs for the reaction of aromatic olefins, 1,1-diphenylethylene and a-methylstyrene (Table 21) are significantly smaller they can be related to transition states earlier than those in the aliphatic series. Unfortunately, for the reactions of highly reactive aromatic olefins or enol ethers, whose low sensitivity to solvent and substituent effects indicates very early transition states, there are not enough KSIE data to confirm this conclusion. 

The kinetics, activation parameters, and substituent effects attending the acyl rearrangements of acyloxycarbenes have been analyzed in detail from both the experimental and theoretical viewpoints further discussion will appear below in Section VHD. 

Table 12.2 NMR data and substituent effects of the observed dihydride intermediates.

For some compounds NMR data were collected to determine the equilibrium constants for the tautomerism between the azide form such as for 30 and the tetrazole derivative 31 (Scheme 3). Similar investigations were conducted for the compounds 28 and 29 and the solvent effects and substituent effects are discussed <1996JHC747>. 

Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

M. Narisada, T. Yoshida, M. Ohtani, K. Ezumi, M. Takasuka, Synthesis and Substituent Effects on Antibacterial Activity, Alkaline Hydrolysis Rates, and Infrared Absorption Frequencies of Some Cephem Analogues Related to Latamoxef (Moxalactam) , J. Med. Chem. 1983, 26, 1577-1582. 

The early experiments concerned with proton transfer from hydrogen-bonded acids did not provide information which permitted a choice between the two mechanisms (Kresge, 1973). These experiments included the measurement of kinetic isotope effects (Haslam et al., 1965b Eyring and Haslam, 1966 Haslam and Eyring, 1967), activation parameters (Haslam et ai, 1965a), the effect of different solvents (Jensen et al., 1966) and substituent effects in the intramolecularly hydrogen-bonded acid (Miles et al.,... 

ESR and CIDNP studies intended to detect the radical intermediates failed [63], Conjugate addition of a vinylcuprate reagent to an enone takes place with retention of the vinyl geometry indicating that no vinyl radical intermediate is involved [64, 65], Kinetic isotope effects and substituent effects in cuprate addition to benzophenone indicate that C-C bond formation is rate-determining, which is not consistent with the involvement of a radical ion pair intermediate [66]. 

Undoubtedly, further work will be necessary in order to get a solid background for silyl radical cyclizations. In particular, further investigations on the nature of the pendant alkenyl substituent as well as on the ring size and substituent effects on the silicon in the ring expansion can be expected in the future. 

---