Nucleophilic Tendencies

It has been mentioned that some free radicals (e.g., chloro) are electrophilic and some (e.g., tert-hvAy ) are nucleophilic. It must be borne in mind that these tendencies are relatively slight compared with the electrophilicity of a positive ion or the nucleophilicity of a negative ion. The predominant character of a free radical is neutral, whether it has slight electrophilic or nucleophilic tendencies. 

This simple observation has led to a reassessment of the chemistry of those rate and equilibrium processes which involve anions in solution (Parker, 1962, 1965a, 1965b). Comparison of rates of 8 2 reactions in protic and in dipolar aprotic solvents produce some new conclusions about reaction mechanisms, nucleophilic tendencies, leaving group tendencies, steric effects, salt effects, and solvent affects. This article discusses several comparisons of this type. 

The effect of solvent on nucleophilic tendencies relative to SCN is shown by solvent activity coefficients. Equation (40) is derived from equation (9) and applies to reactions of methyl iodide with a series of... 

This ratio can be as large as 10 , which explains some of the observations shown in Table 21. For example, the nucleophilic tendency of acetate ion, relative to thiocyanate ion, is decreased by a factor of ca. 10 on transfer from DMF to methanol. 

The nucleophilic order I > SCN > Br > Cl, (Table 21) for a variety of reactions at saturated carbon in protic solvents is well established (Hine, 1962) and has been regarded in the past as strong evidence for polarizability (Edwards and Pearson, 1962) as a factor in determining nucleophilic tendencies towards carbon. However, this series is reversed (Parker 1961a Coniglio et al., 1966 Parker, 1965a) on transfer from methanol to DMF, because log yci-/ y cN- —4-1, log yBr-/ y cN- Is — 2-3, and log y / yscif-1 +0-1 (Table 5). 

Some nucleophilic tendencies towards carbon are shown in Table 21. They vary by a factor of only ca. 10 within any one solvent, from the least reactive (2,4-dinitrophenoxide in MeOH) to the most reactive (e.g. CeHsS" in MeOH). If, as shown, solvation effects can produce changes of 10 in nucleophilic tendencies then it is clearly pointless, unless solvent is specified and its effect taken into account, to discuss rate data, for reactions in methanol and in other protic solvents, in terms of intrinsic properties of the nucleophile, such as structure, charge type, polarizability, hardness and softness, size, a-e fects, ability to adjust valence shells to transition state requirements, bond strength, and so on. Solvation of the nucleophile is a major factor in determining nucleophilic tendencies. 

Powerful inorganic acceptors like the halogens, certain transition metal complexes, and negatively charged counterions with negligible nucleophilic tendency like BFT, CIOT, PFg, AsFg, NOj, CH SO, etc. result in fully ionic phenazine compounds. The physical properties of phenazine salts with inorganic anions have not been extensively or systematically studied. We mention below materials whose structures have been determined. 

The most important chemical property of the carbonyl group is its tendency to undergo nucleophilic addition reactions of the type represented m the general equation... 

On curing, amino resins not only react with the nucleophilic sites (hydroxyl, carboxyl, amide) on the other film formers in the formulation, but also self-condense to some extent. Highly alkylated amino resins have less tendency to self-condense (33,34) and are therefore effective cross-linking agents, but may require the addition of a strong acid catalyst to obtain acceptable cure even at bake temperatures of 120—177°C. 

Chapters 1 and 2. Most C—H bonds are very weakly acidic and have no tendency to ionize spontaneously to form carbanions. Reactions that involve carbanion intermediates are therefore usually carried out in the presence of a base which can generate the reactive carbanion intermediate. Base-catalyzed condensation reactions of carbonyl compounds provide many examples of this type of reaction. The reaction between acetophenone and benzaldehyde, which was considered in Section 4.2, for example, requires a basic catalyst to proceed, and the kinetics of the reaction show that the rate is proportional to the catalyst concentration. This is because the neutral acetophenone molecule is not nucleophihc and does not react with benzaldehyde. The much more nucleophilic enolate (carbanion) formed by deprotonation is the reactive nucleophile. 

Another factor which strongly affects the reactivity of these carboxylic acid derivatives is the leaving-group abihty of the substituents. The order is Cl > OAr > OR > NR2 > 0 so that not only does the ease of forming the tetrahedral intermediate decrease in the order Cl>0Ar>0R>NR2>0 , but the tendency for subsequent elimination to occur is also in the same order. Because the two factors work together, there are large differences in reactivity toward the nucleophiles. 

The simplest method for obtaining selective fluonnation is to conduct reactions under conditions that invigorate the electrophilicity of fluorine In practice this method entails the creation of anionic or strongly nucleophilic reactive centers on substrate molecules while suppressing or reducing the tendency toward radical attack Numerous examples of seleetive fluorine attack on carbanionic, amido and carboxylato species are documented Especially abundant is alpha fluonnation of nitroalkanes in polar solvents [42 43, 44, 45 46] (equations 10-14)... 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

Rhodocene, [Rh()7 -C5H5)2], is also known but is unstable to oxidation and has a tendency to form dimeric species. Claims for the existence of iridocene probably refer to Ir " complexes. However, the yellow rhodicenium and iridice-nium cations are certainly known and are entirely analogous to the cobalticenium cation in their resistance to oxidation and susceptibility to nucleophilic attack. 

The behavior of the chloropyridines and their nitro-substituted derivatives is apparently similar, the 2-chloro compounds having less tendency to show autocatalytic behavior than the 4-chloro analogues with a given nucleophile. For 4-chloropyridines the reaction may be further complicated by self-quaternization. ... 

Heterocyclic compounds may show a higher tendency than carbocycles to react with nucleophiles according to the addition-elimination mechanism than via arynes. 

One significant difference between nitrocarboaromatics and aromatic azines is the tendency of the activating center of the latter to react with electrophiles or compounds capable of hydrogen bonding, thereby accelerating nucleophilic substitution. 

A nucleophilic compound or a group is attracted by a nuclei and has the tendency to share or donate electrons. 

Primary and secondary aikoxy radicals generally show a reduced tendency to abstract hydrogen or to undergo 3-scission when compared to the corresponding i-alkoxy radical.1"3 402 This has been correlated with the lesser nucleophilicity of these radicals.427... 

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