Nucleophic substitution

Sometimes it is convenient to synthesise an activated alcohol that can be used in nucleophic substitution reactions like an alkyl halide. Mesylates and tosylates are such sulphonate compounds which serve this purpose. They can be synthesised by action of alcohols with sulphoxyl chlorides in the presence of a base like pyridine or triethylamine (Following fig.). The base serves to mop up the HC1 that is formed and avoids acid-catalysed rearrangement reactions. 

The startling observation made in this work was that meta derivatives were more reactive toward photosubstitution than ortho and para isomers, as shown below for the photoreaction of dimethoxynitrobenzene and methyl amine, in contradistinction to the rules of classical ground state nucleoph " substitution ... 

In 1946, Moses W. Goldberg (1905-1964) and Leo H. Sternbach from Hoffmann-La Roche filed the first of several patent applications relating to the synthesis of biotin (Fig. 7.48). The starting material was fumaric acid, which was tra/is-dibrominated. NucleophEic substitution with benzylamine, cyclisation with phosgene and treatment with acetic anhydride gave the cis-substituted meso-imidazolidinone, which was converted with cydohexanol into the halfester. The enantiomers were then separated with (-)-ephedrine. Alternatively,... 

In conclusion, do the similarities and differences in the reactivity patterns for these reactive species with organic halides indicate a basic relationship or are these similarities fortuitous and does nature provide distinct pathways of comparable energy. Of the three mechanistic possibilities considered for radical anions, electron transfer, radical-like and nucleophic substitution, electron transfer is indicated for highly exothermic reactions, and a radical-like process is likely for the less... 

Aromatic substitution reactions are often complicated and multistep processes. A correlation, however, in many cases can be found between the charged attacking species and the electron density distribution in the molecule attacked during electrophilic and nucleoph c substitution. No such correlation is expected in radical substitution where the attacking particles are neutral, rather a correlation between the reactivities of separate bonds and a free valency index of the bond order. This allows the prediction of the most reactive bonds. Such an approach has been used by researchers who applied quantum calculations to estimate the reactivities of the isomeric thienothiophenes and to compare them with thiophene or naphthalene. " Until recently quantum methods for studying reactivities of aromatics and heteroaromatics were developed mainly in the r-electron approximation (see, for example, Streitwieser and Zahradnik ). The M orbitals of a sulfur atom were shown not to contribute substantially to calculations of dipole moments, polarographic reduction potentials, spin-density distribution, ... 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

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