Carbon acids kinetic acidities

The easiest access to most benzyllithium, -sodium, or -potassium derivatives consists of the deprotonation of the corresponding carbon acids. Hydrocarbons, such as toluene, exhibit a remarkably low kinetic acidity. Excess toluene (without further solvent) is converted into benzyllithium by the action of butyllithium in the presence of complexing diamines such as A. Af.Af.jV -tetramethylethylenediamine (TMEDA) or l,4-diazabicyclo[2.2.2]octane (DABCO) at elevated temperatures1 a procedure is published in reference 2. 

Throughout these sections it has been assumed that protonation and association equilibria are established on time scales much shorter than those for the kinetic steps. For the usual protonations and ion-pairings that assumption will always be true, except when very rapid reactions are being studied by certain techniques presented in Chapter 11. On the other hand, if carbon acids are involved, or any sluggish association reactions, the assumption of rapid prior equilibria may not hold true. 

In this chapter it is clearly impossible to do more than sample the extensive literature on the carbon acidity of sulfinyl and sulfonyl compounds, as it illuminates the electronic effects of these groups, particularly in connection with linear free-energy relationships. There are three main areas to cover first, as already indicated, equilibrium acidities (pKa values) second, the kinetics of ionization, usually studied through hydrogen isotopic exchange and finally, the kinetics of other reactions proceeding via carbanionic intermediates. 

A study of the rates of water-catalyzed detritiation of six disulfonyl-activated carbon acids contains results of interest in connection with electronic effects192. Thus the carbanion stabilizing abilities of several groups as measured kinetically lie in the order SOzPh > SOzEt > S02Me. 

The first report of the use of bromine for the oxidation of sulphoxides appeared in 1966116. Diphenyl sulphone was isolated in 0.5-1% yield when the sulphoxide was treated with bromine in aqueous acetic acid for several hours. The yield was increased to about 5% by quenching the reaction with sodium carbonate. A kinetic study117 of a similar reaction involving dimethyl sulphoxide showed no significant yield improvement but postulated that the mechanism proceeds via an equilibrium step forming a bromosulph-onium type intermediate which reacted slowly with water giving dimethyl sulphone as indicated in equation (35). 

In considering relative acidity, classically it is only the thermodynamics of the situation that are of interest in that the pKa value for the acid (cf. p. 54) can be derived from the equilibrium above. The kinetics of the situation are normally of little significance, as proton transfer from atoms such as O, N, etc., is extremely rapid in solution. With carbon acids such as (1), however, the rate at which proton is transferred to the base may well be sufficiently slow as to constitute the limiting factor the acidity of (1) is then controlled kinetically rather than thermodynamically (cf. p. 280). 

TABLE 2. The nitrogen and carbon-13 kinetic isotope effects for the acid-catalyzed and for the thermal benzidine rearrangement of 2,2 -hydrazonaphthalene in 70% aqueous dioxane at 0°C and in 95% ethanol at 80 °C, respectively... 

Nitrogen, carbon-13 and carbon-14 kinetic isotope effects have been determined38 for the analogous acid-catalyzed ortho,ortho -rearrangement of the Af-2-naphthyl-Ar/-phenylhydrazine (equation 24). The labelled compounds required for this study were prepared by the sequence of reactions shown in Schemes 20-22. 

TABLE 3. The nitrogen, the carbon-13 and carbon-14 kinetic isotope effects found for the acid-catalyzed ortho,ortho1-rearrangement of iV-naphthyl-iV-phenyl-hydrazine in 60% aqueous dioxane at 0°C... 

The reaction was second order in acid and first order in substrate, so both rearrangements and the disproportionation reaction proceed via the doubly-protonated hydrazobenzene intermediate formed in a rapid pre-equilibrium step. The nitrogen and carbon-13 kinetic isotope effects were measured to learn whether the slow step of each reaction was concerted or stepwise. The nitrogen and carbon-13 kinetic isotope effects were measured using whole-molecule isotope ratio mass spectrometry of the trifluoroacetyl derivatives of the amine products and by isotope ratio mass spectrometry on the nitrogen and carbon dioxide gases produced from the products. The carbon-12/carbon-14 isotope... 

The most recent addition to Shine s extensive study of the benzidine-type rearrangements41 involved remeasuring the nitrogen and the carbon-13 and carbon-14 kinetic isotope effects at the 4- and at the 4- and 4 -carbons as well as determining the carbon-13 and carbon-14 isotope effects at the 1- and at the 1- and l -carbons in the benzidine rearrangement of hydrazobenzene (equation 30). The reaction, which was carried out in 75% aqueous ethanol that was 0.1 M in hydrochloric acid and 0.3 M in lithium chloride at 0°C, gave an 86% yield of benzidine (11) and a 14% yield of diphenyline (12). The kinetic isotope effects found for the formation of benzidine and diphenyline under these reaction conditions are presented in Table 5. 

Statement number 6 has to do with carbon acids and is supported by reference (7). There are, in fact, other references that suggest solvent plays a much more direct role in the kinetics of protonating carbanions than statement number 6 would imply. For example, there is evidence that nuclear reorganization and rehybridization of the carbon atom are too rapid to have much kinetic importance when compared with solvent reorientation. The strong dependence of carbanion protonation rates on the solvent supports this view. These rates are typically much faster in organic solvents, such as DMSO, than in water. A particular reaction that was studied in different solvents (17) is... 

However, this simple picture only applies to gases that do not undergo reactions in the boundary layers. For gases that do react, for example through hydration and acid-base reactions, the net flux depends on the simultaneous movement of all the solutes involved, and the flux will not be the simple function of concentration expressed in Equation (3.25). An example is CO2, which reacts with water to form carbonic acid and carbonate species-H2C03, HCOs and COs . The situation is complicated because the exchange of H+ ions in the carbonate equilibria results in a pH gradient across the still layer, and it is therefore necessary to account for the movement of H+ ions across the still layer as well as the movement of carbonate species. The situation is further complicated in the case of CO2 by the kinetics of hydration and dehydration, which may be slow in comparison with transport. 

The effect of steric hindrance on the rates and kinetic isotope effects for reactions of l-nitro-l-(4-nitrophenyl)alkanes and their deuterated analogues with two bicyclic guanidines of comparable basicity (l,5,7-triazabicyclo[4.4.0]dec-5-ene, TBD, and its 7-methyl derivative, MTBD) in THF has been studied. The results disagree with the notion that deuterium kinetic isotope effects are enhanced by steric hindrance, since for the reactions of MTBD with various carbon acids the KIEs decrease with steric hindrance in the carbon acid but the converse is true for reactions of TBD. 

As a result, these anions can gain exceptional stability and their carbon acids are unusually acidic. Because the above resonance forms probably play very important roles in stabilizing the anion, these species are not purely carbanions. However, thermodynamics favors reactions (protonation or alkylation) at carbon so their behavior is generally characteristic of carbanions. It also should be noted that kinetics often favor reaction at the heteroatom in these anions though leading to the less stable product. ... 

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