Basic Kinetics

TMED, (CH3)2NCH2CH2N(CH3)2. B.p. 122 C a hygroscopic base which forms a hydrocarbon-soluble stable chelate with lithium ions and promotes enhanced reactivity of compounds of lithium, e.g. LiAlH4, UC4H9, due to enhanced kinetic basicity of the chelate. Used in polymerization catalysts, tetramethyl lead, TML 5 lead tetramethyl. 

Scales for bases that are too weak to study in aqueous solution employ other solvents but are related to the equilibrium in aqueous solution. These equilibrium constants provide a measure of thermodynamic basicity, but we also need to have some concept of kinetic basicity. For the reactions in Scheme 5.4, for example, it is important to be able to make generalizations about the rates of competing reactions. 

If the equilibrium were established rapidly, reduction of the free ketone as it formed would result in a substantial loss of product. Lithium enolates are more covalent in character than are those of sodium and potassium and consequently are the least basic of the group. This lower thermodynamic basicity appears to be paralleled by a lower kinetic basicity several workers have shown that lithium enolates are weaker bases in the kinetic sense than are those of sodium and potassium." As noted earlier, conjugated enones... 

Now we can understand the difference between nucleophilicity and basicity. Nncleophilicity measures how fast things happen, which is called kinetics. Basicity measnres stability and the position of equilibrium, which is called thermodynamics. Throughout your course, you will see many reactions where the prodnct is determined by kinetic concepts, and yon will also see many reactions where the prodnct is determined by thermodynamic concepts. In fact, there will even be times where these two factors are competing with each other and you will need to make a choice of which factor wins kinetics or thermodynamics. 

Roitman and Cram (1971) have shown that the kinetic basicity of potassium alkoxide increases on complexation with dicyclohexyl-18-crown-6 ([20] + [21]). Both the rate of isotopic exchange and the rate of racemization of (—)-4-biphenylylmethoxydeuteriomethane [163] by t-BuOK in t-BuOH were found to increase by factors between 30 and 17 000. Isotopic exchange was... 

As little as 10 M of an impurity with the kinetic basicity of Et N would explain the observed rate variation. The addition... 

Nitrogen heteroaromatics are expected to be useful probases. The cathodic reduction of phenazine, (31), resembles closely that of (29a) [70,71], and the kinetic basicity of (31) is comparable to that of (29a) [54]. However, application of (31) as a PB in electrosynthesis has not been reported, and there is only a single report concerning the use of the radical anion of acridine, (32), as an EGB [72]. 

Molecular Interactions Reaction Kinetics Basic Spectroscopy X-ray Crystallography Lanthanide and Actinide Elements Maths for Chemists Bioinorganic Chemistry Chemistry of Solid Surfaces Biology for Chemists Multi-element NMR... 

Recent developments include the measurement of the kinetic basicities of EGB s by convenient electroanalytical methods. The establishment of a scale of EGB basicities will in turn facilitate the measurement of kinetic acidities of carbon acids. 

It may not always be clear from the conditions for electrochemical generation which species is the effective EGB. In some cases a possible complication is fast disproportionation of radical-anion to dianion (Scheme 12). This can mean that for electrogeneration at, say, the first reduction potential E Jl) it is possible for either the radical-anion or the dianion to act as base, depending on the relative rates of protonation by acid HA (k and kp, the value of the disproportionation constant (Kj), and the rate at which equilibrium between radical-anion and dianion is attained. In principle, of course, it is also possible that electrogeneration at E p2) could lead to a situation where radical-anion was the effective base as a consequence of rapid reproportionation causing it to be present in high concentration, thus offsetting its probably much lower kinetic basicity. These points are discussed in more detail on p. 157. 

There are two reasons for considering the mechanisms in this detail. Firstly, the potential at which preparative experiments are carried out is determined by which is the basic species. Secondly, methods for determining the rate of protonation (k ) depend on a knowledge of the mechanism. The rate of protonation of an EGB by an acid of known pK is the most convenient measure of basicity (kinetic basicity). 

The little quantitative information that is available concerning EGB s is summarised in Table 16. Fortunately a recent development is the application of electroanalytical methods for the determination of basicity, usually as kinetic basicity. 

Values of kp emerging from these studies indicate that the (fluoren-9-ylidene)-methane dianions will deprotonate acids in the range pK, 1117 at useful rates. Furthermore there is an indication (Fig. 4) that the kinetic basicity of such EGB s may be roughly correlated with the second reduction potential, E (2). This possible correlation needs further rigorous examination as more reliable kinetic information is obtained the k values used in Fig. 4 are not corrected for the competition from reproportionation. 

In the near future it is expected that the measurement of kinetic basicity of EGB s will become routine and precise. When available for synthetically useful EGB s the data will be used to optimise the choice of probase and carbon acid and to explore factors (e.g. choice of cation) which influence basicity. Where good Bronsted correlations are observed it will be possible to use data on the basicity of EGB s to... 

When the metalation of 2-fluoropyridine (8) was carried out at lower temperatures (-60°C), aside from the product of addition 13, evidence for the DoM product 12 was obtained by a TMSC1 quench experiment (Scheme 4). Complete chemospecificity was achieved only with the more selective LDA base at -75°C. [81JOC4494,81JOM(215)139]. Whereas the soft character of n-BuLi favors nucleophilic reactivity, the hard LDA leads to preferential protophilic attack. The stronger kinetic basicity... 

Understanding the behavior of organic bases in solution requires some knowledge of their gas phase (intrinsic) basicities (proton affinities (PA)). These can be determined by ICR methods or by variable-temperature pulsed high-pressure mass spectrometry. Both methods afford basicities (termed thermodynamic vs. kinetic basicity), which have been compared in (91JOC179). 

This reaction type, known as directed ortho metalation reaction, requires strong bases, normally an alkyllithium reagent (most lithium dialkylamides are of insufficient kinetic basicity). Alkyllithium bases show high solubility in organic solvents due to association into aggregates of defined structure, typically as hexamers in hydrocarbon solvents e. g. hexane or tetramers-dimers in polar solvents e. g. THF (see Chapter 5). 

In order to further develop the field of enantioselective catalytic deprotonation, it was necessary to develop bulk bases that show low reactivity toward the epoxide but have the ability to regenerate the chiral catalyst. Thus, the bulk bases should show low kinetic basicity toward the substrate, but be thermodynamically and kinetically basic enough to be able to regenerate the chiral lithium amide from the amine produced in the rearrangement. 

Crotonyl Enolate Aldol Reactions. Boron enolates of the A/-crotonyloxazolidinones have been shown to afford the expected. n-aldol adducts (eq 36). The propensity for selfcondensation during the enolization process is minimized by the use of triethylamine over less kinetically basic amines. 

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