Nucleophilicity relative order

The new reaction appears to be a simple one-step procedure, which is particularly suitable for tertiary alkyl-aryldiazenes for which alternative synthetic routes are less convenient. However, aryl radicals or alkyl radicals in which the carbon-centered radical is bonded to an electron-withdrawing group (COOR, COR, CONR2, CN, S02R, etc.) do not add to diazonium salts or give only poor results (Citterio et al., 1982 c). This indicates that the radical must be a relatively strong nucleophile in order to be able to react with a diazonium ion. 

According to the theory of nucleophilicity (Edwards and Pearson, 1962 Bunnett, 1963 Pearson et al., 1968), the relative order of nucleophilicity relative to the major groups in biological molecules can be summarized as follows ... 

There would seem to be two positions one can take with respect to the interpretation of the behavior revealed by Figs 1 and 2. The first, which would undoubtedly be favored by proponents of HSAB, is that the large deviations of the points for soft-base nucleophiles in Fig. 2 show that HSAB considerations do play an important role in determining the relative order of reactivity of a series of nucleophiles in nucleophilic substitutions at different electrophilic centers when those centers differ significantly in their degree of hardness , and that the failure to observe sizeable deviations from the correlation line in Fig. 1... 

This observation has been rationalized on the basis of the relative proton affinities (PA) of the substrates and that of the nucleophile. In fact, the relative order of proton affinities reveals that /M(C2H5C1) > PA(H20) > P/f(CH3CI). Thus, for the first case, rapid proton transfer dominates over nucleophilic displacement, since proton transfer involving species which do not require any electronic or bond reorganization will in general be much faster than a displacement. 

The a-oxidation of aldehydes was later further extended to the use of ketones as nucleophiles. In order to develop this reaction into a useful process, a considerable effort was made to optimize the reaction conditions as several different problems arose these included a lower reaction rate and yields because of the formation of the di-addition product at the two enolizable carbon atoms and lower 0/N-selectivity. Hayashi et al. [16a] and Cordova et al. [16c] partly solved these problems by using a relatively large excess of ketone and by applying the slow addition method leading to good chemical yields (44-91%), with near-enantiopure products being obtained (96-99% ee). 

The purine ring system undergoes substitution by both nucleophilic and electrophilic reagents, although with the latter the substituted atom is usually nitrogen rather than carbon. Attempts, made by various schools of theoretical chemistry, to predict the relative order... 

Since there are no extensive studies on the relative aromaticity of the heterocycles covered in this chapter, the relative order of aromaticity of these systems has been gleaned from disparate studies. A priori, the combined effects of the 7i-electron-deficient five-membered heterocycles annelated to a pyridine nucleus provides a series of bicyclic heterocycles with low reactivity towards electrophiles. In the presence of suitable leaving groups, they are prone to undergo nucleophilic substitution. Since these heterocycles are readily obtained from either appropriately substituted pyridines or five-membered heterocycles, methods for direct functionalization of the parent heterocycles are not frequently studied. Based on the diversity of reactions these heterocycles undergo, it can be inferred that the pyridofuroxans are the least aromatic. 

If the atom that is forming the new bond to carbon is the same over a range of nucleophiles—it might be oxygen, for example, and the nucleophiles might be HO-, PhO-, AcO-, and TsO-—then nucleophilicity does parallel basicity. The anions of the weakest acids are the best nucleophiles, The order for the nucleophiles we have just mentioned will be HO > PhO- > AcO- > TsO-. The actual values for the rates of attack of the various nucleophiles on MeBr in EtOH relative to the rate of reaction with water (= 1) are given in Table 17.14... 

In non-aqueous media the relative order of reactivity of the attacking halide ions, as nucleophiles in these processes, is F > Cl > 1 [83]. This in itself indicates that the... 

On the other hand, some electrophilic silyl compounds react rapidly with a large variety of nucleophiles. The relative order of reactivity of si-... 

On the other hand, with aryl sulfonates (58) (R = aryl), nucleophilic substitution occurs with preferential sulfur-oxygen bond cleavage since aryl substituents show little tendency to undergo nucleophilic attack (Scheme 44). The relative order of nucleophilicity towards the sulfur atom is similar to that obtaining at a carbonyl carbon atom4b and is reported to be as shown in Figure 3. 

Quantitative Scales of Solvent Nucleophilicity. Solvolytic studies in solvents of low nucleophilicity led to renewed interest in quantitative measures of solvent nucleophilicity. Peterson and Waller (44) derived a scale of solvent nucleophilicity (Npw) from the rates of displacement by solvent of tetramethylenehalonium ions (VI) in liquid sulfur dioxide. The reaction is approximately half-order in carboxylic acid, possibly because dimer-monomer preequilibrium occurs (44). More recently, hydrolysis of the iodonium salt (VIII) in competition with anionic or solvent nucleophiles was studied. A scale of nucleophilicity relative to water was obtained by quan-... 

Common ion rate depression for solvolysis of RX with the same R but with different leaving groups X was followed only for a single system. From the a values obtained in the solvolysis of ( )- and (Z)-l,2-dianisyl-2-phen-ylvinyl-X, 16, in AcOH-AcO- (equation 9), relative reactivities toward the derived ion 17 were measured (74) (nucleophile, relative reactivity) OMs-, 0.16 OAc, 1.0 Cl , 15.2 Br 45.5 and AcOH, 0.0024. From other data, I will probably be at the top of a similar order (75) and 2,4,6-trinitrobenzene-sulfonate at the bottom (76). 

Nucleophilicities relative to a standard solvent can be quantified by the Swain-Scott equation (12)66, in which k and k0 are the second-order rate constants for reactions of the nucleophile and solvent respectively, and s is a measure of the sensitivity of the substrate to nucleophilicity n. By this definition, the nucleophilicity of the solvent is zero. For all reactions examined, there will be competition between attack by solvent (present in large excess) and reaction with added anionic nucleophiles. Hence, only n values well above zero can be obtained with satisfactory reliability. In the original work66, the solvent was water and all but one of the substrates were neutral s was defined as 1.0 for methyl bromide and was calculated to be 0.66 for ethyl tosylate the lowest reliable n value reported was 1.9 for picrate anion, but a value of < 1 for p-tosylate anion was reported66 in a footnote. 

The reactions involving 64, 66, and 68 used three different types of nucleophiles, cyanide, an azide, and an alkoxide. The ability to evaluate the relative strength and effectiveness of various nucleophiles is obviously as important for Sn2 reactions as it was for nucleophilic acyl substitution reactions. A general list of nucleophiles in order of their ability to form bonds to sp carbon in a Sn2 reaction is ... 

There are obviously several parameters contributing to nucleophilic strength. A few general statements can be made concerning the relative orders of nucleophilic strength. 

The displacement of bromine, in the relative order 2 > 3 > 4, by an enolate or related anion under irradation, known as an SrnI process (Substitution Radical Nucleophilic, unimolecular), involves photostimulated transfer of an electron from the enolate to the heterocycle, loss of bromide to generate a pyridyl radical which then combines with a second mol of enolate, generating the radical anion of product, transfer of an electron from which sustains the chain process.The equivalent photo-catalysed displacement of bromide by hydroxide gives 3-hydroxypyridine. ... 

Carbon nucleophiles are able to react with heteroaromatic W-oxides, and these addition-elimination transformations have been found to proceed effectively in the presence of the phosphonium salt PyBroP (Scheme 36) [74]. A series of carbonyl compounds capable of enolization have been involved in the reaction with pyridine A-oxides to give 2-substituted pyridines in moderate yields, and in all these cases, it proved necessary to use threefold excess of nucleophile relative to the A-oxide in order to avoid further addition of the reaction product to the starting azine A-oxide. 

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