Nucleophile strength

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

The reaction temperature varies between -40 and 110 °C, depending on the reactivity of both counterparts, amine and chlorophosphane. As usual, aliphatic amino groups react faster than aromatic and heteroaromatic ones due to their greater nucleophilic strength. These differences in reactivity allow chemose-lective phosphinous amide formation, as that represented in Scheme 2 where the P-N bond is formed exclusively at the aliphatic NH2 group of 2 but not at the heteroaromatic NH2, whose lone pair is extensively delocalized in the electron-withdrawing purine ring [35]. 

In contrast to the lability of certain dN adducts formed by the BHT metabolite above, amino acid and protein adducts formed by this metabolite were relatively stable.28,29 The thiol of cysteine reacted most rapidly in accord with its nucleophilic strength and was followed in reactivity by the a-amine common to all amino acids. This type of amine even reacted preferentially over the e-amine of lysine.28 In proteins, however, the e-amine of lysine and thiol of cysteine dominate reaction since the vast majority of a-amino groups are involved in peptide bonds. Other nucleophilic side chains such as the carboxylate of aspartate and glutamate and the imidazole of histidine may react as well, but their adducts are likely to be too labile to detect as suggested by the relative stability of QMs and the leaving group ability of the carboxylate and imidazole groups (see Section 9.2.3). 

Electron-withdrawing substituents reduce the nucleophilic strength of N but favor N —H breaking. Ring transformations of hydrazones (33) are catalyzed by Cu"-acetate <93JCS(Pl)249i>. 

C2H5)3As] which carry no charge on the donor atom and which have little attraction for the proton. Thus compared to Pt11, CH3+ is only a moderately soft acid. It is thus apparent that nucleophilic strength at one substrate should not parallel the strength at another unless the two substrates are of comparable hardness or softness. 

The nucleophile S 2 requires a strong nucleophile, while nucleophilic strength doesn t affect 5 1. 

Monocationic acyl ions are readily prepared as persistent species in solutions of low nucleophile strength.68 These acyl ions have been thoroughly characterized by IR and NMR spectroscopy, and several acyl ion salts have been characterized by X-ray crystallography. The monocationic acyl ions are often prepared in situ from carboxylic acids, esters, or anhydrides, by the action of a strong Brpnsted acid, or the ions can be prepared from ionization of an appropriate acid halide with a strong Lewis acid. Both methods have been used to prepare acyl-centered dications, some of which can be considered distonic superelectrophiles. As described previously, dicarboxylic acids cleave to the bis-acyl ions in superacid (FSChH-SbFs) provided that the acyl cations are separated by at least three methylene units (eq 54).55 The first bis-acyl dications were reported by Olah and Comisarow, being prepared by the reactions of dicarboxylic acid fluorides with superacidic SbFs (eq 72).69... 

In any series of anions, nucleophilic strength parallels basicity if the nucleophilic centre is the same atom, e.g., the nucleophilic strengths of the following oxygen compounds (RO > HO RCOy) matches their order of basicity. 

Nucleophile strength increases down a column of the periodic table (in solvents that can hydrogen bond, such as water and alcohols). For example,... 

SnI Nucleophile strength is unimportant (usually weak). Sn2 Strong nucleophiles are required. 

Further indirect evidence for the postulated nucleophilic behavior of Cl" and OH" has been obtained from a series of experiments in which NF3 was allowed to react with solutions containing anions of varying nucleophilic strength. It was found that for those species tested the extent of reaction within a given time and temperature range increased monotonically with the accepted value (5) of the nucleophilicity of the anion. Furthermore, although NF3 did not react with acid solutions of weak nucleophiles, the reaction rate with halides was increased by the... 

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