Nucleophilicity scales

Kevin and co-workershave developed nucleophilicity scales based on the solvolysis of cationic substrates R-X, the leaving group being neutral rather than anionic. Their/V ,jO+ scale is defined in Eq. (8-72). 

The second well-known electrophilicity or nucleophilicity scale was by Legon and Millen [13,14]. In this scale, the assigned intrinsic nucleophilicity is derived from the intermolecular stretching force constant k, recorded from the rotational and infrared (IR) spectra of the dimer B. .. HX formed by the nucleophile B and a series of HX species (for X halogens) and other neutral electrophiles. The nucleophilicity number in this case is obtained from the empirical relation... 

Recently, Jaramillo et al. [43] introduced a nucleophilicity scale, depending on the electrophilic partner, and suggested that the nucleophilicity index can be written as... 

Nucleophilicity Scales in Four-coordinate Planar Substitution 312... 

Activation of the aromatic ring towards nucleophilic attack is required for all these reactions to proceed at reasonable rates and is commonly provided by strongly electron-withdrawing substituents. Reactivity also strongly depends on the leaving group and on the nucleophile. Scales of activating power of... 

Dinitrobenzofuroxan (DNBF) is known as a superelectrophile due to its high reactivity both as an electrophile and in its pericyclic addition reactions. NMR studies show that reaction with 2-aminothiazole and its 4-methyl derivative yield anionic carbon-bonded adducts such as (11) by reaction at the 5-position, whereas the 4,5-dimethyl derivative reacts via the exocyclic amino group. Kinetic studies of the first two compounds, both in acetonitrile and in 70 30 (v/v) water-DMSO, have been used to assess their carbon nucleophilicities and place them on the Mayr nucleophilicity scale.55 In a related study, the nucleophilic reactivity, in acetonitrile, of a series of indoles with both DNBF and with benzhydryl cations have been compared and used to determine nucleophilicity parameters for the indoles.56... 

The nucleophilicity scale based on the stretching frequency of the hydrogen bond between a nucleophile and an acid (Nu-HX) 97 was tested against experiment using the hard acids HF, HCN, and BF3 and the soft acid BH3.98 The correlation with the hard acids is excellent but fails when a soft acid is used. A new nucleophilicity index, or = 7 (/xa - /t. )2/I M + b)2] 7a, where //A, and //B, are the chemical potentials of the nucleophilic and electrophilic molecules, respectively, and ijA and i B are their respective hardnesses, has been proposed. This gives the relative nucleophilicity that is... 

Other theoretical studies discussed above include investigations of the potential energy profiles of 18 gas-phase identity S 2 reactions of methyl substrates using G2 quantum-chemical calculations," the transition structures, and secondary a-deuterium and solvent KIEs for the S 2 reaction between microsolvated fluoride ion and methyl halides,66 the S 2 reaction between ethylene oxide and guanine,37 the complexes formed between BF3 and MeOH, HOAc, dimethyl ether, diethyl ether, and ethylene oxide,38 the testing of a new nucleophilicity scale,98 the potential energy surfaces for the Sn2 reactions at carbon, silicon, and phosphorus,74 and a natural bond orbital-based CI/MP through-space/bond interaction analysis of the S 2 reaction between allyl bromide and ammonia.17... 

As already established for combinations of cations with n-nucleo-philes [33,160,219], the situation is less complicated for the reactions of carbocations with 7r-systems. Solvent polarity plays only a minor role (Section III.D.3) and, for many 7r-systems, the relative reactivity has been found to be electrophile-independent (Fig. 10, Section III.D.4.b). Also for these systems, the construction of a universal nucleophilicity scale is not unproblematic, however. Remember Fig. 11, which shows that An2CH + reacts 3.4 times faster with allyltrimethylsilane than with 2-methyl-2-bu-... 

With the purpose of increasing the range of available block copolymers, comonomers other than methacrylates and acrylates can also be involved in sequential polymerization, provided that they are susceptible to anionic polymerization. Dienes, styrene derivatives, vinylpyridines , oxiranes and cyclosiloxanes are examples of such comonomers. The order of the sequential addition is, however, of critical importance for the synthesis to be successful. Indeed, the pX a of the conjugated acid of the living chain-end of the first block must be at least equal to or even larger than that of the second monomer. Translated to a nucleophilicity scale, this pK effect results in the following order of reactivity dienes styrenes > vinylpyridines > methacrylates and acrylates > oxiranes > siloxanes. 

The relative nucleophilicities of anionic reagents towards standard vinylic substrates have been tabulated and from these it is apparent that azide ion is a moderately strong nucleophile in protic solvents, and even stronger in dipolar aprotic solventsThe need for caution in construction of such nucleophilicity scales has been stressed, however, since trends appear to be dependent on the structure of the substrate and some anomalies in the effects of solvent have been noted. 

Recent works of Mayr and co-workers4-14 have illustrated this trend. In fact, these authors have established, in contrast to the accepted opinion about the relative character of the experimental electrophilicity/nucleophilicity scales for many reactions in organic and organometallic chemistry, that it would be possible to define nucleophilicity and electrophilicity parameters that are independent of the reaction partners. Mayr et al. proposed that the rates of reactions of carbocations with uncharged nucleophiles obey the linear free energy relationship given by 4-14... 

That a relative nucleophilicity scale based on one solvent and one substrate may not be applicable for different conditions and systems is clearly demonstrated by the work of Beltrame et al. (1968). 

The piperiaiae(DMF)/ N7(98%DMr) ratios for (125a), (125b) and (125c) at 0°are 10,1-3 and 0-08, respectively, i.e. decrease in the same order and to about the same degree as the ratios in ethanol. While the change in the ratio in dimethylformamide may be accounted for by the enhancement of reactivity in the (slightly aqueous) dipolar aprotic solvent (Parker, 1965), the occurrence of the same trend in ethanol, and especially the dependence on the structure of the attacked substrate, points to the need for caution in the construction of nucleophilicity scales. 

The final chapter of this section is by Rappoport and is concerned with nucleophilic reactions at vinylic carbon. Two reaction types are considered, those of neutral vinyl derivatives and those of vinyl cations. Correlation of rates for these reactions with both Ritchie and Swain-Scott equations was attempted without success. Rappoport concludes that these reactions are subject to a complex blend of polar, steric, and symbiotic effects and that a quantitative nucleophilicity scale toward vinylic carbon cannot be constructed . This conclusion is reminiscent of the earlier observation of Pearson (see the introduction to the section on the Brpnsted equation) and the later observation of Ritchie (Chapter 11) regarding the difficulty of correlating nucleophilic reactivity with a single equation. Rappoport finds another familiar situation when he explores the relationship between reactivity and selectivity for the vinyl substrates sometimes the RSP is obeyed and sometimes it is not. 

A comparison of the rates of solvolysis of the tert-butyldimethylsulfonium ion and the 1-adamantyldimethylsulfonium ion presents strong evidence that the solvent dependence of the tert-butyldimethylsulfonium ion solvolysis rates is governed primarily by solvent nucleophilicity effects. Leaving-group contributions based upon 1-adamantyldimethylsulfonium ion solvolyses are better incorporated into the establishment of the solvent nucleophilicity scale based upon triethyloxonium ion solvolysis. Alternative solvent nucleophilicity scales based upon the solvolysis of S-methylbenzo-thiophenium ions are discussed. Analyses of the extent of nucleophilic participation by the solvent in the solvolyses of methyldiphenyl-sulfonium and benzhydryldimethylsulfonium ion will be presented. The relative nucleophilicities of various anionic and neutral nucleophiles toward the triethyloxonium ion in ethanol have been determined. 

Solvent Nucleophilicity Scales Based upon R-X+ Substrates... 

From the deviations, a scale of nucleophilicity was derived. Halogenated acetic acids were included, on the basis of reactivities with halonium ions. Other scales appeared from the Schleyer group (5, 6) at about the same time. The various nucleophilicity scales were used to correlate solvolysis rates by now familiar four-parameter equations AG = N + mY or AG = sN + mY. (G — free energy N = solvent nucleophilicity Y = solvent ionizing power s = sensitivity m = sensitivity.) Previously, parameters for such equations had not been determined. 

We next investigate the effect of the ratio R in equation 5. In the original nucleophilicity scales, the nucleophilicities of acetic and formic acids were set equal, based on interpretations of solvolysis data in the literature and on the nucleophilicities of these in S02 solvent, a property perhaps somewhat distantly related to the nucleophilicity in a pure solvent. We have now calculated yA as a function of R yA changes sign at an R value near 1.2 (Figure 7). Equation 3 shows that N values become scaled A values when yA becomes 0 at an R value near 1.2. We note that changing R is merely a roundabout way to vary the proportion of A and B in the N and Y parameters. 

The probes and methods for determining the relative nucleophilicities of nucleophiles toward electrophilic olefins and toward vinyl cations were examined. Literature data were used in an attempt to construct a substrate-independent nucleophilicity scale toward vinylic carbon. 

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