Displacement reactions, nucleophilic multiple

For nucleophilic displacement reactions, some relationship might be expected between the ability of an anion A to act as nucleophile and the dissociation constant of the acid HA the best nucleophiles should be the anions of the weaker acids. For an uncharged nucleophile B there should be a relationship with the dissociation constant of the conjugate acid BH. Nucleophilicity is often treated in terms of Bronsted-type relationships, but deviations and sometimes almost complete breakdown are found when wide ranges of substrates and nucleophiles are considered. Nucleophilicity is a more complex function of structure than acid-base behavior. This situation has led to the development for such reactions of a special system of correlation analysis, which involves scales of nucleophilicity constants. The first of these, the n scale, was proposed by Swain and Scott in 1953 and was based on methyl bromide as a standard substrate for an LFER. Other scales have subsequently been developed and applied in both simple and multiple regression. 

Nucleophiles can donate a lone pair of electrons to form a bond to an atom (usually carbon), by displacing a leaving group (nucleophilic substitution), by breaking a multiple bond (nucleophilic addition) or by adding to a carbocation (second step of an SnI reaction),... 

The sulfone is a versatile functional group comparable to the carbonyl functionality in its ability to activate molecules for further bond construction, the main difference between these two groups being that the sulfone is usually removed once the synthetic objective is achieved. The removal most commonly involves a reductive desulfonylation process with either replacement of the sulfone by hydrogen (Eq. 1), or a process that results in the formation of a carbon-carbon multiple bond when a P-functionalized sulfone, for example a (3-hydroxy or (3-alkoxy sulfone, is employed (Eq. 2). These types of reactions are the Julia-Lythgoe or Julia-Paris-Kocienski olefination processes. Alkylative desulfonylation (substitution of the sulfone by an alkyl group, Eq. 3), oxidative desulfonylation (Eq. 4), and substitution of the sulfone by a nucleophile (nucleophilic displacement, Eq. 5) are also known. Finally, p-eliminations (Eq. 6) or sulfur dioxide extrusion processes (Eqs. 7, 8 and 9) have become very popular for the... 

The reaction of tabun with nucleophiles is more complex than that of the simple phos-phorylfluoridates. The courses of such reactions are pH dependent and, according to the conditions, cleavage of either the P—N bond or the P—CN bond can predominate , as shown in Scheme 11. At low pH, in aqueous acid, protonation of the basic nitrogen atom leads to initial P—N cleavage with loss of dimethylamine, with further displacement of cyanide and ultimately the ethoxy group (under more forcing conditions). Under basic conditions, cyanide ion is displaced preferentially. At pH 7, the hydrolysis is slow and proceeds by non-selective multiple reaction pathways. 

The ease with which a given 8 2 displacement occurs depends on multiple factors, such as the nucleophilicity of the incoming nucleophile (which depends on both its electronic and steric character), steric hindrance at the electrophilic carbon center, the effectiveness of the leaving group, and the solvent and other environmental effects. By defining a standard substrate and standard reaction conditions, the reactivity of different nucleophiles may be quantified. One such measure of nucleophilicity is the Swain-Scott nucleophilicity constant n, for which methyl iodide is chosen as the standard substrate and reaction rates are measured in methanol at 25 °C ... 

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