Kinetics nucleophiles

All these facts—the observation of second order kinetics nucleophilic attack at the carbonyl group and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown m Figure 20 5 Like the acid catalyzed mechanism it has two distinct stages namely formation of the tetrahedral intermediate and its subsequent dissociation All the steps are reversible except the last one The equilibrium constant for proton abstraction from the carboxylic acid by hydroxide is so large that step 4 is for all intents and purposes irreversible and this makes the overall reaction irreversible... 

When 2,2-dichloro-3-phenylpropanal 203 is subjected to standard reaction conditions with chiral triazolium salt 75c, the desired amide is produced in 80% ee and 62% yield Eq. 20. This experiment suggests that the catalyst is involved in an enantioselec-tive protonation event. With this evidence in hand, the proposed mechanism begins with carbene addition to the a-reducible aldehyde followed by formation of activated car-boxylate XLII (Scheme 32). Acyl transfer occurs with HOAt, presumably due to its higher kinetic nucleophilicity under these conditions, thus regenerating the carbene. In turn, intermediate XLin then undergoes nucleophilic attack by the amine and releases the co-catalyst back into the catalytic cycle. 

Decomposition of Caro s acid is catalysed by acetone.324 A kinetic study in aqueous alkaline medium indicates simple second-order kinetics. Nucleophilic addition of S052- to the carbonyl carbon leads to oxirane by reaction with another SOs2- to give... 

In Sj 2 reactions and Sj,Ar reactions in which bond-formation is the rate-determining step, the differential solvation in the transition state is usually much smaller than the differences in levels of solvation of the anionic nucleophiles between protic and aprotic solvents. Therefore in dipolar aprotic solvents the activation energy AE is lowered and these reactions consequently proceed a good deal faster in such solvents (Figure 2). This is true of azide ion which is in general a stronger kinetic nucleophile in aprotic than in protic solvents. 

The rates of addition of nucleophiles to carbonyl groups and the rates of elimination from the tetrahedral intermediates constitute another class, probably similar to the activated aromatic nucleophilic substitution. The carbonyl group is an electrophile, and no obvious source of any barrier exists, outside of desolvation. Therefore, a resemblance to Ritchies systems is found. No obvious relation between our kinetic nucleophilic characters (Nx) and the additions occurs, but a possible parallel to the equilibrium methylating powers, KYX (in Tables I and II), of the conjugate methylating agent of the... 

From the Pellerite and Brauman (8) application of Marcus theory to SN2 methyl-transfer reactions, the kinetic barrier is made up of an intrinsic barrier for the reaction that is decreased by the magnitude of the reaction exothermicity. Because the exothermicities of the reactions with 02 are the lowest (by upward of 20 kcal/mol) compared to the other anions of high kinetic nucleophilicity, the intrinsic barriers for these SN2 reactions with 02 are the smallest. Thus, 02 can be called a super SN2 nucleophile. 

The reactions of (C6H5)2C- with CH3Br and CH3C1 were studied to determine the kinetic nucleophilicity of (C6H5)2C in SN2 displacements ... 

The reaction of (C6H5)20- with CF3C02CH3 was examined to determine the kinetic nucleophilicity of PH20- toward carbonyl addition in competition with the highly exothermic SN2 methyl transfer ... 

Sn2 Nucleophilicity of (CH30)2P0. To determine the intrinsic SN2 kinetic nucleophilicity of (CH30)2P0, we investigated the reactions of the anion with the series of CH3X molecules listed in Table V. The rates of these reactions vary from modest with the most reactive CH3I molecules to slow with CH3Br to no observed reaction with CH3C1. From the results, we conclude that the phosphoryl anion is kinetically a poor nucleophile in SN2 displacement reactions. 

The thermodynamics are very different in the gas phase (Figure 4). Proton transfer is much less endothermic (AH° = +6 kcal/mol, see under Kinetics) nucleophilic displacement is much more exothermic (AH° = — 56 kcal/mol) (J), and the measured rate constant demonstrates that the barrier must be low. 

X10, calculated from the fit of the data to Eq. (47). As one would expect, the kinetic nucleophilicity of HNO2 is less, but not infinitely less, than that of NO2. 

The observation of second-order kinetics, nucleophilic attack at the carbonyl group, and the involvement of a tetrahedral intermediate are accommodated by Mechanism 19.4. 

Edwards " proposed that a kinetic nucleophilicity should be correlated by a combination of the factors mentioned earlier for a particular metal center, using the equation... 

Sommer has described a general exhaustive alkylation procedure for the direct synthesis of quaternary ammonium compounds. As protonation of sterically hindered amines is only slightly affected hysteric hindrance, whereas kinetic nucleophilicity is greatly decreased, the use of a sterically hindered base of greater base strength than the substrate amine will bind up the acid generated on alkylation this system allows quaternization under mild conditions, with the minimum of manipulation. 

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