N for nucleophiles

The order of reactivity observed, azide hydroxide cyanide, is opposite to that observed for these nucleophiles toward methyl iodide (see Table 5.3, p. 208). Since N+ for a nucleophile is independent of the cation and does not correlate either with basicity of the nucleophile or with the equilibrium constant for bonding to the cation, Ritchie believes the most important determinant of nucleophilicity toward cations to be the solvation energy of the nucleophile. The overall reaction appears to 

Assessments of solvent nucleophilicities are also available, again by comparing the rates of substitution of standard substrates in various media. A useful measure of solvent nucleophilidty is one based on the Winstein-Grunwald relationship 

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Table 7-5. Values of N+ for nucleophilic systems at 23 °C (after Ritchie, 1972).

The electron pair of the C-O bond can be regarded as having been donated by the hydroxide ion, while the electron pair of the C-Br bond departs with the leaving bromide ion. The name for this type of reaction is abbreviated SN, S for substitution and N for nucleophilic. 

We can use the overall reaction order to distinguish between the two possible mechanisms, A and B. Experimentally, the rate of formation of methanol is found to be proportional to the concentrations both of chloromethane and of hydroxide ion. Therefore the reaction rate is second order overall and is expressed correctly by Equation 8-2. This means that the mechanism of the reaction is the single-step process B. Such reactions generally are classified as bimolecular nucleophilic substitutions, often designated SN2, S for substitution, N for nucleophilic, and 2 for bimolecular, because there are two reactant molecules in the transition state. To summarize For an SN2 reaction,... 

The frontier orbital theory predicts the reactivity order, > Ca > N > C, for electrophilic attack and Cmeso > C Ca > N for nucleophilic attack.2,19 In general, these predictions are observed experimentally, for example, Mg(porphin) is brominated to give Mg(a,/J,y,<5-tetrabromopor-phin). However, the site of reaction is highly dependent on steric and electronic factors, and may be summarized as follows.2... 

The reaction of methyl bromide with hydroxide ion is an example of an S 2 reaction, where S stands for substitution, N for nucleophilic, and 2 for bimolecu-lar. Bimolecular means that two molecules are involved in the rate-determining step. In 1937, Edward Hughes and Christopher Ingold proposed a mechanism for an Sn2 reaction. Remember that a mechanism describes the step-by-step process by which reactants are converted into products. It is a theory that fits the experimental evidence that has been accumulated concerning the reaction. Hughes and Ingold based their mechanism for an Sn2 reaction on the following three pieces of experimental evidence ... 

It is convenient to categorize reactions with concise descriptive labels. For substitution reactions we often use the notation SxM, in which the letter S indicates a substitution reaction. The subscript x indicates something of the mechanism, such as N for nucleophilic or E for electrophilic. M usually indicates the molecularity of the reaction, the nature of the reacting species, or additional information. The most familiar terms for substitution reactions are SnI (for substitution nucleophilic unimolecular ), as shown in equation 8.4,... 

At one extreme, bond breaking and bond forming occur simulfaneously. Thus, departure of the leaving group is assisted by the incoming nucleophile. This mechanism is designated Sf 2, where S stands for Substitution, N for Nucleophilic, and 2 for a bimolecular reaction. This type of substitution reaction is dassilied as bimolecular because both the haloalkane and nucleophile are involved in the rate-determining step. 

This one-step reaction is termed the Sjf2 reaction S for substitution (displacement), N for nucleophilic, and 2 for bimolecular. It is bimolecular because the slow step—the only step—involves a collision of two species. 

If this intermediate, in turn, is more n idly attacked by water or hydroxide ion than the original ester, the overall reaction will be faster in the presence of the nucleophile than in its absence. These are the requisite conditions for nucleophilic catalysis. Esters of relatively acidic alcohols (in particular, phenols) are hydrolyzed by the nucleophilic catalysis mechanism in the presence of imidazole ... 

The ortho indirect deactivating effect of the two methyl groups in 2,6-dimethyl-4-nitropyridine 1-oxide (163) necessitates a much higher temperature (about 195°, 24 hr) for nucleophilic displacement of the nitro group by chloride (12iV HCl) or bromide ions N HBr) than is required for the same reaction with 4-nitropyridine 1-oxide (110°). With 5-, 6-, or 8-methyl-4-chloroquinolines, Badey observed 2-7-fold decreases in the rate of piperidino-dechlorination relative to that of the des-methyl parent (cf. Tables VII and XI, pp. 276 and 338, respectively). 

Allylic bromides can also serve as progenitors for nucleophilic organochromium reagents. An elegant example is found in Still and Mobilio s synthesis of the 14-membered cembranoid asperdiol (4) (see Scheme 2).7 In the key step, reduction of the carbon-bromine bond in 2 with chromium(n) chloride in THF is attended by intramolecular carbonyl addition, affording a 4 1 mixture of cembranoid diastereoisomers in favor of the desired isomer 3. Reductive cleav-... 

For substituted anilines (Thompson and Williams, 1977) and for 1-naphthylamine and a series of derivatives thereof (Castro et al., 1986a), k2 and the ratio Ar 2/Ar3 have been determined for nucleophilic catalysis with Cl-, Br-, SCN-, and SC(NH2)2. The values of k2 correspond fairly well to those found for the diazotization of aniline, but those of Ar 2/Ar3 increase markedly in the above sequence (Table 3-1). As k3 is expected to be independent of the presence of Cl- or Br- and to show little dependence on that of SCN- or thiourea, the increase in k 2/k3 for this series must be due mainly to 2. Indeed, the value of log(Ar 2/Ar3) shows a linear correlation with Pearson s nucleophilicity parameter n (Pearson et al., 1968). This parameter is based on nucleophilic substitution of iodine (as I-) in methyl iodide by various nucleophiles. The three investigations on nucleophilic catalysis of diazotization demonstrate that Pearson s criteria for bimolecular nucleophilic substitution at sp3 carbon atoms are also applicable to substitution at nitrogen atoms. 

The parameter 5 is a measure of the susceptibility of the substrate to nucleophilic attack, and n a measure of the nucleophilic reactivity as defined by a reference reaction. The rate constants for attack at saturated carbon are used to define the values of n.14 Table 10-4 lists the values of n for certain nucleophiles. This particular compilation lists the... 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

The description of the carbon-oxygen double bond is analogous, but in addition to the cr-bonds there are unshared pairs of electrons on oxygen so that two excited states are possible, n-n and n-n. For n-n excitation the resultant half-vacant orbital on oxygen should possess electrophilic reactivity, and the electron rich -system should have nucleophilic characteristics. 62>... 

We note in this context that k /kw is greater than unity both for nucleophilic attack upon neutral aromatic substrates, e.g. 2,4-dinitrochloro-benzene and cationic N-alkylpyridinium ions (Tables 3 and 4). 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

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