Tetrahedral intermediates zwitterionic

Complete understanding of the shapes of the curves in Fig. 8.4 requires a kinetic expression somewhat more complicated than we wish to deal with here. The nature of the extremities of the curves can be understood, however, on the basis of qualitative arguments. The rate decreases with a decrease in pH in the acidic region because formation of the zwitterionic tetrahedral intermediate is required for expulsion of the... 

Aminolysis of esters often reveals general base catalysis and, in particular, a contribution to the reaction rate fi om terms that are second-order in the amine. The general base is believed to function by deprotonating the zwitterionic tetrahedral intermediate. Deprotonation of the nitrogen facilitates breakdown of the tetrahedral intermediate, since the increased electron density at nitrogen favors expulsion of an anion ... 

The factors involved in the attack of nitrogen nucleophiles on carbonyl compounds, e.g. the p/fa of the nitrogen, and the thermodynamics of the formation of neutral (T ) versus zwitterionic (T ) tetrahedral intermediates, have been discussed in terms of their influence on the form of the pH-rate profile. ... 

Kinetic studies of the reaction of Z-phenyl cyclopropanecarboxylates (1) with X-benzylamines (2) in acetonitrile at 55 °C have been carried out. The reaction proceeds by a stepwise mechanism in which the rate-determining step is the breakdown of the zwitterionic tetrahedral intermediate, T, with a hydrogen-bonded four-centre type transition state (3). The results of studies of the aminolysis reactions of ethyl Z-phenyl carbonates (4) with benzylamines (2) in acetonitrile at 25 °C were consistent with a four- (5) and a six-centred transition state (6) for the uncatalysed and catalysed path, respectively. The neutral hydrolysis of p-nitrophenyl trifluoroacetate in acetonitrile solvent has been studied by varying the molarities of water from 1.0 to 5.0 at 25 °C. The reaction was found to be third order in water. The kinetic solvent isotope effect was (A h2o/ D2o) = 2.90 0.12. Proton inventories at each molarity of water studied were consistent with an eight-membered cyclic transition state (7) model. 

Thiophenyl acetates (366 R = Me) and propionates (366 R = Et) react with electrogenerated polysulflde ions S3 in DMF to yield thiocarboxylate ions, thiolate ions, and phenyl tetrasulfanide (367), the last deriving from the reaction of thiolate ions with sulfur (Scheme 48). Smdies of the aminolysis by a set of substimted anilines of Y-aryl dithio-2-thiophenates (368 X = S) and dithio-2-furoates (368 X = O) in acetonitrile have shown that the rate-determining step in these reactions is the departure of the thiophenolate ion from the zwitterionic tetrahedral intermediate T= = (Scheme 49). Experiments with deuteriated anilines yielded k i/IcQ values of 1.7-1.9,... 

A large body of work has indicated the involvement of zwitterionic tetrahedral intermediates in a number of systems. The n-butylaminolysis of substituted phenyl esters (Scheme 2) in acetonitrile has been studied by Williams group.4 A zwitterionic tetrahedral intermediate (T ) is implicated in the mechanism and its formation may be... 

The formation of the tetrahedral intermediate 138 may be preceded by the zwitterionic complex 139, as the first step of the nucleophilic attack on the partially positive carbon of the carbonyl group. 

DFT was employed to study the mechanism of ammonolysis of phenyl formate in the gas phase, and the effect of various solvents on the title reaction was assessed by the polarizable continuum model (PCM). The calculated results show that the neutral concerted pathway is the most favourable one in the gas phase and in solution.24 The structure and stability of putative zwitterionic complexes in the ammonolysis of phenyl acetate were examined using DFT and ab initio methods by applying the explicit, up to 7H20, and implicit PCM solvation models. The stability of the zwitterionic tetrahedral intermediate required an explicit solvation by at least five water molecules with stabilization energy of approximately 35 kcalmol-1 25... 

The aminolysis of Y-phenyl X-benzoates by piperidine in 20 mol% DMS0-H20 at 25 °C proceeded, on the basis of a curved Brpnsted-type plot, via a zwitterionic tetrahedral intermediate with a change in the RDS the curvature centre of the plots was at p Ka = 6.4 regardless of the electronic nature of the substituent X in thebenzoyl moiety 27 The rates of aminolysis of a series of Y-phenyl benzoates by acylic secondary amines were compared with new results for similar reactions with Y-phenyl diphenylphosphi-nates (discussed further in the section Phosphates and Phosphinates). The results showed that the C=0 compounds were more reactive than the P=0 compounds 28... 

In studies of the reactions of S-(4-nitrophenyl) 4-methylthiobenzoate with a series of six secondary alicyclic amines and a series of eight pyridines in 44 wt% ethanol-water at 25 °C, the Brpnsted-type plots were non-linear with the curvature centre defined as pK(j located at pK.d 9.7 and 9.4 for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a zwitterionic tetrahedral intermediate on the reaction path and, as the basicity of the amine increases, a change in rate-determining step from its breakdown to its formation.47... 

Two classical tools, the intermolecular stretching force constants of H-bonded complexes and the molecular electrostatic potential, were used to develop a nucleophilicity index, which was validated against kinetic data recorded for the aminolysis of S-methyl 2,4-dinitrophenylthiocarbamate.51 Aminolysis of iV-phenylthionocarbamates by ben-zylamines in MeCN proceeded by a stepwise mechanism in which the rate-determining step was the breakdown of the zwitterionic tetrahedral intermediate.52... 

Studies of the ability of the lipase B from Candida antarctica (CAL-B) to catalyse the enantioselective aminolysis of esters by cis- and firms-2-phenylcycloalkanamines (54 n = 1, 3, 4) have been followed up by molecular modelling approaches in order to probe the lipase-catalysed aminolysis mechanism. CAL-B possesses a typical serine-dependent triad, so it was possible, with access to an X-ray crystal structure of CAL-B, to model a series of phosphonamidates (55 n = 1, 3, 4) as analogues of the tetrahedral intermediate (TI) resulting from attack of the amine on the carbonyl of the acyl-enzyme. The results suggested as the most plausible intermediate for the CAL-B-catalysed aminolysis a zwitterionic TI resulting from the direct His-assisted attack of the amine on to a C=0 group of the acyl-enzyme.80... 

The mechanism of catalysis of ester aminolysis by weak amine bases of substituted phenylquinoline-6- and -8-carboxylates were evaluated, and the solvent effects were examined by semiempirical SM2.1/AM1, ab initio SCIPCM [124] and PS-Solv [125]. All these models predicted that a zwitterionic tetrahedral intermediate should be formed in this reaction. The results did not support the proposed earlier proton slide mechanism and allowed to propose a mechanism which was fully consistent with the experimental observations [126]. 

The aminolysis of a series of. S -2,4-dintirophcnyl 4-Y-benzoates (60 Y = Me, H, Cl, NO2) with a series of substituted pyridines at 25 °C in 44% ethanol-water proceeded stepwise through a zwitterionic tetrahedral intermediate, the rate-determining step changing from its breakdown to its formation as the basicity of the amine increased.49 However, the aminolysis of the same series of benzoates (60) with secondary alicyclic amines in the same solvent was judged to be concerted, and the reasons for the proposed change in mechanism were discussed.50... 

An interesting mechanistic application of free energy relationships in calculating rate constants concerns the reactivity of the putative intermediate in the reaction of imidazole with 4-nitrophenyl acetate. The putative stepwise process (Scheme 15) involves a zwitterionic tetrahedral intermediate which would decompose to the product A-acetylimidazole, subsequently hydrolysing to acetate ion and imidazole. 

The aminolysis of carboxylic esters to which the reaction of Fischer carbene complexes with amines has frequently been compared, typically proceeds by a similar mechanism with rate-limiting deprotonation of the corresponding zwitter-ionic tetrahedral intermediate (59) and so do many SnAt reactions where the deprotonation of the zwitterionic Meisenheimer complex (e.g., 60) is rate... 

The hydrolysis of simple imines occurs readily in aqueous acid, and has been studied in detail by kinetic methods. The precise mechanism is a function of the reactant structure and the pH of the solution. The overall mechanism consists of an addition of water to the C=N bond, followed by expulsion of the amine from a tetrahedral intermediate. There are at least four variants of the tetrahedral intermediate that differ in the extent and site of protonation. In the general mechanism below, the neutral intermediate is labeled TI° and the zwitterionic form is labeled. There are two possible monoprotonated forms, one protonated on oxygen (TI +) and one protonated on nitrogen (TI +). 

The rates of the various steps are a function of the pH of the solution, the basicity of the imine, and the reactivity of the aldehyde. Imine protonation enhances reactivity toward either water or hydroxide ion as nucleophiles. Ai-Protonation in the tetrahedral intermediate makes the amine a better leaving group. The zwitterionic intermediate... 

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