The Zwitterionic Mechanism

The most familiar example of zwitterionic [t 2 -f r 2]-cycloaddition is that of tetracyanoethylene (TONE) to activated ethylenes, such as vinyl ethers. Huisgen [28] has carefully reviewed the experimental evidence, which is due in large measure to him and his collaborators. It can be summarized briefly as follows  

As a rule, cycloaddition is only partially stereoselective, though examples are cited in which stereoselectivity, which decreases with solvent polarity, is essentially complete. However, as Bartlett has pointed out [23] In general, configuration loss appears to be a sufficient but not a necessary criterion for stepwise cycloaddition, at least when the intermediate is a dipolar ion . 

A kinetic analysis of the isomer ratios in the product and the unconsumed enol ether shows zwitterion formation to be reversible. In highly polar solvents, the cyclobutane opens in a slow back reaction to the same zwitterion that is an intermediate in its formation. 

The large substituent effect and strong dependence of the rate on solvent polarity support substantial charge separation in the transition state. The consistently large negative entropy and volume of activation are also in accord with this interpretation. 

The zwitterions can be trapped by alcohols and their stereochemistry deduced from the structure of the products. 

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The zwitterionic mechanism can account for the retention in the tetramethylguanidine reaction if the positive charge is carried by the two more basic dimethylamino groups rather than by the nitrogen bound to the /J-carbon of (116). 

Dehydration of urea to carbodiimide (HN=C=NH) or its more stable tautomer cyanoamide (H2N-C=N) cannot be achieved via the zwitterion mechanism of Figure 8.3. It would have to proceed via the zwitterion HN -C (=NH)-OH2 , in which—for electronegativity reasons—both formal charges would occupy worse positions than in the zwitterion O -C (=NH)-NH3 , which is an intermediate in the transformation of urea into biuret upon heat-... 

Homoallylic type alcohols (67), on the other hand, give predominantly cyclopentenones independent of substitution (equation 37). In Ae 3-hydroxyalkyl-substituted systems, presumably allene oxide (68) is the intermediate. Thus it would appear Aat the initial site of allene oxidation is not critical to the success of the reaction. Either precursor (58) or (59) is expected to give the observed stereochemical relationships of the newly formed stereocenters by the concerted mechanism. Finally, Cha has noted that the two intermediates may lead to different stereochemical relationships by the zwitterionic mechanism. This assumes a specific pathway for breakdown of (58) or (59). That stereochemical information is preserved in the reaction is shown by the selective transformations in equation (38). 

From the effect of solvent on the volumes of activation, it was argued that the zwitterion mechanism, (3) and (4), was in better agreement with the data . It is seen from Table 45 that for malonic acid, the volume of activation decreases as the polarity of the solvent decreases. A similar decrease in AF with decreasing solvent polarity was observed in the reaction of n-butyl bromide with pyridine to give N-... 

However, the zwitterion mechanism appears attractive for picolinic and related acids. The volumes of activation for decarboxylation of picolinic are large and positive. This is consistent with release of solvent in going to the transition state as is indicated in reaction (4) of the zwitterion mechanism. The rate data for the decarboxylation of quinaldinic acids fits attractively into the zwitterion mechanism. The ratio of rate coefficients for the decarboxylation of zwitteron ion (I) to that of quinaldinic acid (II) shows a minimum value of 57 in quinoline solvent at 145.8 The anion of quinaldinic acid shows no detectable decomposition in... 

In octanoic acid solvent, alkyl substitution of malonic acids causes a small decrease in AG and thus an increase in rate as seen from Table 47. This is in contrast to the alkyl substituent effect in water (Table 46). The enthalpy of activation is clearly more favorable for decarboxylation of alkyl malonic acids than malonic acid in octanoic acid. Both Ai/ and AG are less favorable for decarboxylation of malonic acid in octanoic acid compared to water. This is expected on the basis of either the concerted (2) or the zwitterion mechanism (3) and (4). Association of the carboxyl groups of malonic acid with the octanoic acid solvent would thwart the attainment of the concerted transition state. Also generation of the zwitterion would be suppressed in octanoic acid. It is clear that additional work is required... 

From decarboxylation rates of pyridazinylacetic acids, it is concluded that decarboxylation takes place preferentially by the zwitterionic mechanism.479,480 Pyridazine catalyzes ester hydrolysis.481... 

The heteroatom variants of the VCP-CP rearrangement generally operate either by a zwitterionic or a diradical-type mechanism The zwitterionic mechanism is more common and involves the heteroatom-assisted C—C cleavage of the three-membered ring to form an ylide, which undergoes electrocyclic ring closure to form the product (Scheme 11.28. Eq. 

An investigation on the nature of the reaction between CO2 and blends of DEA and MDEA in aqueous solution is presented in this paper. The concentration of the total amine mixture was varied from one to two molars with temperatures varying from 293K to 313 K. The kinetic parameters associated with this reaction were evaluated using the zwitterion mechanism. Based on the pseudo first-order regime, the apparent rate constant was calculated from the overall pseudo first order rate constant. The overall absolute error in the calculation of the overall pseudo first order rate constant was less than 7% which upholds the validity of the chosen reaction rate model. 

In aqueous mixtures of DEA + MDEA, the absorption of CO2 can be considered as a combination of several reactions involving CO2-DEA, CO2-MDEA and CO2-H2O. In case of DEA, it reacts with CO2 according to the zwitterion mechanism[9] ... 

The experimental evidence cited above indicates that this does not occur. As suggested at the right of Fig. 6.6, the in-plane glide (6i) begins well before the intended HOMO-LUMO crossing, which is avoided because all four MOs have the same irrep (o ) in The HOMO and LUMO of the extended tran-soid zwitterion are qualitatively similar to those in the biradical illustrated in Fig. 6.4, but are more widely separated in energy As a result, the orbital approximation - and the symmetry analysis based upon it - is no less reliable than for the biradical mechanism. The zwitterionic mechanism can be accomodated by Fig. 6.5, with self-evident modifications arising from the polar nature of the tetramethylene intermediate. ... 

The generally contrathermodynamic stereochemistry, as well as the disparate substituent, solvent and isotope effects, are consistent with the zwitterionic mechanism illustrated in Fig. 6.8 [56], in which the orbital symmetry analysis plays a small but essential role. It is assumed that substitutional desymmetriza-tion is insufficient to destroy the essential symmetry of the tt orbitals, which sets the reactants on a path in which the four interacting C atoms are initially coplanar, but are induced by orbital symmetry conservation to bond along the diagonal. The preferred direction of approach and the stereochemical consequences then follow directly. 

Although an mechanism cannot be excluded in the case of 18e, the zwitterionic mechanism is the only one which gives a coherent explanation of the reactivity of axial and equatorial halogen derivatives. However, the halogen stereochemistry plays an important role. An axial halogen favors the secondary substitution reactions and the formation of delocalized species these can lead... 

By GPC it was shown that all phosphorus detected in the raw polymer was either bound to the polymer as a phosphonium ion or existed as cation 2. Polymer-bound phosphorus was detected only at high temperatures or high concentrations of phosphine (as initiator). This was taken as evidence against the zwitterion mechanism. However, a more detailed look at the data given in Ref. [759] reveals that reactions of the following type could not be excluded (Figure 10). 

This reaction can take place at any time during polymerization or polymer recovery. Thus there exists no conclusive proof against the zwitterion mechanism. It is obvious that more work has to be done before this topic can be settled. 

K is the equilibrium constant for the zwitterionic forms if it is calculated from free energy data, those pertaining to the zwitterionic forms must be used. The same numerical result for the degree of total synthesis will be obtained whatever mechanism is formulated. If ions instead of zwitterions are considered to be the reactants, K and —AF will be different from those for the zwitterion mechanism, but there will be a change in the ionization term such that it will compensate exactly for the change in K. 

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