Irreversible Addition Reactions

Thus far, we have looked mainly at the reactions of oxygen, sulfur, and nitrogen nucleophiles with carbonyl compounds. All of these (and cyanide) have at least the potential to be leaving groups, once they are protonated. However, if we add carbanionic or hydridic nucleophiles to the carbonyl group, there are no circumstances in which these can behave as leaving groups. So additions of this type of nucleophile are nonreversible. 

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Irreversible Addition Reactions A General Synthesis of Alcohols... 

FIGURE 19.85 Two irreversible addition reactions to the carbonyl group of an a,P-unsaturated carbonyl compound. 

Thus, in spite of its lack of reactivity, iodine reacts chemically with unsaturated compounds, whereby the silica gel of the TLC layer can sometimes be assigned a catalytic role [11, 12]. Irreversible oxidations and electrophilic substitution and addition reactions have been observed on the interaction of iodine with tertiary nitrogen compounds such reactions possibly depend on particular steric relationships or are favored by particular functional groups [13, 14]. 

The pathway of gluconeogenesis in the liver and kidney utilizes those reactions in glycolysis which are reversible plus four additional reactions that circumvent the irreversible nonequilibrium reactions. 

Incorporation of lsO into the ketone occurs hardly at all under these conditions, i.e. at pH 7, but in the presence of a trace of acid or base it occurs [via the hydrate (13)] very rapidly indeed. The fact that a carbonyl compound is hydrated will not influence nucleophilic additions that are irreversible it may, however, influence the position of equilibrium in reversible addition reactions, and also the reaction rate, as... 

Grignard reagents act as strong nucleophiles and the addition reaction is essentially irreversible. The end-products of addition, after aqueous hydrolysis (of, for example, R3C—OMgX), are alcohols (R3C—OH). It is, however, important to emphasise that the utility of Grignard, and similar, additions to C=0 is as a general... 

Van Koten et al. reported on a negative dendritic effect in the Kharasch addition reaction. [3 9,40] A fast deactivation for the carbosilane dendrimer supported NCN pincer catalyst (Figures 4.28 and 4.29) was observed by comparison with a mononuclear analogue. This deactivation is expected to be caused by irreversible formation of inactive Ni(III) sites on the periphery of these dendrimers. 

In selective etherification, it is important to distinguish between reversible and irreversible reactions. The former class comprises etherifications with dimethyl sulfate, halogen compounds, oxirane (ethylene oxide), and diazoalkanes, whereas the latter class involves addition reactions of the Michael type of hydroxyl groups to activated alkenes. In this Section, irreversible and reversible reactions are described separately, and a further distinction is made in the former group by placing the rather specialized, diazoalkane-based alkylations in a separate subsection. 

The second reaction studied using lipase as catalyst was the reversible re-gioselective esterification of propionic acid and 2-ethyl- 1,3-hexanediol [180]. While the previously described reaction was almost irreversible, this reaction is equilibrium limited with an apparent equilibrium constant of 0.6 0.1. In addition, the accumulated water inhibits the enzyme. Therefore, only the removal of the water from the reaction zone assures high enzymatic activity as well as drives the reaction beyond thermodynamic equilibrium. Experiments with two... 

In the Michael addition reaction depicted in eq. [146] the diastereomeric sulfoxides 312 are formed under kinetic control conditions, therefore, the addition of sodium diethyl malonate is an irreversible process. On the contrary, addition of sodium methoxide to the sulfoxide 311 is a thermodynamically controlled process and leads to a mixture of diastereomeric ]3-methoxysulfoxides 313 in a 31 69 ratio (320). 

A semibatch reactor is run at constant temperature by varying the rate of addition of one of the reactants, A. The irreversible, exothermic reaction is first order in reactants A and B. 

In principle, all carbonyl addition reactions could be reversible but, in practice, many are essentially irreversible. Let us consider mechanisms for the reverse of the nucleophilic addition reactions given above. For the base-catalysed reaction, we would invoke the following mechanism ... 

Along the same line, the reactions of vinyl fluorides with nucleophiles often involve addition-elimination processes. The addition reaction generates a carban-ion, and this latter induces the loss of a fluoride. As the loss of a fluoride ion is irreversible, the equilibrium is displaced toward the formation of the carbanion and, consequently, the reaction is very efficient. These reactions are often concerted ones (Figure 1.11). 

Kinetic control can be achieved by slow addition of the ketone to an excess of strong base in an aprotic solvent. Kinetic control requires a rapid, quantitative and irreversible deprotonation reaction 2-6. The use of a very strong, sterically hindered base, such as lithium diisopropylamide or triphenylmethyllithium (trityllithium), at low temperature (— 78 °C) in an aprotic solvent in the absence of excess ketone has become a general tool for kinetic control in selective enolate formation. It is important to note that the nature of the counterion is sometimes important for the regioselectivity. Thus, lithium is usually better than sodium and potassium for the selective generation of enolates by kinetic control. 

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