Versus nucleophilic amination

Scheme 128 Ring opening reactions of 2-nitFothiophenes versus nucleophilic substitution at C-5, in reactions with secondary amines [183]...

AT-heterocyclic carbenes show a pure donor nature. Comparing them to other monodentate ligands such as phosphines and amines on several metal-carbonyl complexes showed the significantly increased donor capacity relative to phosphines, even to trialkylphosphines, while the 7r-acceptor capability of the NHCs is in the order of those of nitriles and pyridine [29]. This was used to synthesize the metathesis catalysts discussed in the next section. Experimental evidence comes from the fact that it has been shown for several metals that an exchange of phosphines versus NHCs proceeds rapidly and without the need of an excess quantity of the NHC. X-ray structures of the NHC complexes show exceptionally long metal-carbon bonds indicating a different type of bond compared to the Schrock-type carbene double bond. As a result, the reactivity of these NHC complexes is also unique. They are relatively resistant towards an attack by nucleophiles and electrophiles at the divalent carbon atom. 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

In an earlier report Bach and coworkers suggested that MesN and MesP had nearly the same gas-phase barriers with peroxyformic acid (AA 5 = 0.5 kcalmol", MP4//MP2/6-31G ) and that their relative reactivity in protic solvent is better attributed to a much greater ground-state solvation of the more basic tertiary amine than the polarizability of the phosphorus. In a more recent study, a 3.3 kcalmol" barrier difference was observed with HCO3H in favor of the P nucleophile at B3LYP/6-31- -G(d,p) (3.0 versus —0.3 kcalmol". Table 12). Thus, the less reactive f-BuO—OH is a more discriminating oxidant with a later TS and the difference in barrier heights for N versus P oxidation widens. These data also point out that rate differences should be compared for a common set of nucleophiles and that when you use oxidants of different reactivity you should... 

Steric effects reduce rate and equilibrium constants of nucleophilic additions but the question how the intrinsic barrier is affected does not always have a clear answer. Comparisons of intrinsic rate constants for the addition of secondary alicyclic amines versus primary aliphatic amines suggest that k0 is reduced by the F-strain. This implies that the development of the F-strain at the transition state is quite far advanced relative to bond formation. The effects of other types of steric hindrance on k0 such as prevention of coplanarity of Y in the adduct or even prevention of jt-overlap between Y and the C=C double bond in the alkene have not been thoroughly examined and hence are less well understood. 

Figure 2. Schematic representation of the electrostatic effect on a plot of log k0(C=C) versus log k C-H). The upper line refers to addition of an anionic nucleophile where electrostatic stabilization does not occur the lower line refers to amine addition. 8 log k0el becomes less negative for better tt...

The propensity for C-N versus N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d dy orbital of Ta(silox)3 precedes oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Arylamine N-H versus C-N activation is therefore a consequence of... 

In the kinetically controlled process, serine and cysteine proteases catalyze acyl transfer from activated carboxy components to various acceptors. The initially formed acyl-enzyme intermediate can be competitively deacylated by water (hydrolysis) or by an amine nucleophile (aminolysis). The yield of the peptide bond formation depends on two factors (1) the relative rate of hydrolysis and aminolysis, which is determined by the nucleophilicity of water versus that of the nucleophile and (2) the molar ratio of water and the nucleophile [62]. The ratio between aminolysis and hydrolysis of the acyl-enzyme intermediate is generally... 

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