Zwitterion mechanism

The isomerization of alkyiisothiazoles has been studied and leads to alkylthiazoles. The isomerization seems to occur by a zwitterion mechanism (Scheme 1). 

Scheme 20. Desulfination reactions. (A) acid-catalyzed zwitterion mechanism, (B) Se2 mechanism.

Pyridines with an a- or y-carboxymethyl group (e.g. 685) undergo facile decarboxylation by a zwitterion mechanism (685 — 688) somewhat similar to that for the decarboxylation of 3-keto acids (cf. Section 3.2.3.1.1). Carboxymethylpyridines often decarboxylate spontaneously on formation thus, hydrolysis of (689) gives (690). The corresponding 2- and 4-pyridone and 2- and 4-pyrone acids are somewhat more stable, e.g. (691) decarboxylates at 170°C. 3-Pyridineacetic acid shows no pronounced tendency to decarboxylate. 

The cycloaddition of formaldehyde and ketene has been studied by ab initio methods.22 A two-step zwitterionic mechanism is suggested for dichloromethane solvent, while the gas-phase reaction is concerted but asynchronous. 

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). 

Dimethyl acetylenedicarboxylate (DMAD) reacts with isoquinoline in the presence of ethyl bromopyruvate to yield pyrrole[2.1 -a]isoquinolincs in excellent yields <2006TL6037>. A zwitterionic mechanism is proposed, and implies an enolate intermediate (Scheme 22). The oxidation in the final step occurs spontaneously without addition of any reagent. 

Fig. 8. 3. Zwitterion mechanism of the decomposition of neutral carbonic acid (derivatives) in a heterocumulene and a hetereo-nucleophile—examples carbonic acid (B), carbonic acid monomethylester (E), carbonic acid mono-tert-butylester (H), carbamic acid (K), and urea (M).

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-... 

Over the years several different mechanisms for the singlet oxygen ene reaction have been considered as depicted in Sch. 2. Biradical (mechanism B in Sch. 2) [10,11] and zwitterionic (mechanism C in Sch. 2) mechanisms have been considered as very unlikely for a variety of reasons including the facts that Markovnikov directing effects are not observed [4], radical scavengers have no influence on the reaction, only minor solvent effects are observed [12-14], and cis-trans isomerizations of the substrates do not occur [6], A dioxetane intermediate (mechanism D in Sch. 2) was considered very early [6] but this suggestion was dismissed when isolated dioxetanes were shown to cleave to the carbonyl compounds rather than rearrange to the allylic... 

The chemistry of the ozonization of olefins has been reviewed (I, 2, 5). Although the exact details of the mechanism(s) have not been elucidated, the Criegee zwitterion mechanism plays an important role in olefin ozonization. According to this mechanism, ozonization occurs in the manner shown in Figure 2. 

Direct initiation by monomeric Lewis acids could also occur by a zwitterionic mechanism [146,147]. The initially formed zwitterion could then rearrange to a species identical to that formed by disproportionation [Eq. (33)]. 

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... 

Assumptions concerning a possible zwitterionic mechanism were made by a number of authors for different cases of anionic and cationic polymerization68-73. This mechanism was well substantiated for the anionic polymerization of diethyl vinyl-malonate under the action of triphenylphosphine68, and 0-propiolactone under the action of trimethylamine69 and betaine70. ... 

It is clear that further work will be required to elucidate the details of the mechanistic pathway for the polymerization of carbon suboxide. Both the mechanism proposed by Ulrich (39) and the above zwitterionic mechanism lead to a functionality of two ketenyl groups per molecule. 

Benzylideneanilines have been added across 2,3-dihydrofurans to produce bicyclic azetidines regio- and stereoselectively a zwitterionic mechanism is proposed. An extensive range of reaction parameters have been calculated for the Mannich reaction of benzoxazole with formaldehyde/dimethylamine. A molybdenum bis(imide) has been used to catalyse C=N bond formation in imine-imine metathesis reactions of synthetic interest the approach has been extended to alkylidene-imine, imide-imine, and imide-imide metatheses. 1-Substituted 1-phenyl-... 

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... 

Recently, the synthesis of the first truly high-molecular-weight alternating copolymer, namely the copolymer of conidine (l-azabicyclo 4,2,0 octane) and p-propio-lactone by a zwitterionic mechanism was reported80) ... 

These workers suggested that these methylisothiazoles 41-43 transpose via tricyclic zwitterionic intermediates (Scheme 6) analogous to the intermediates invoked to rationalize the phototransposition reactions of 2-phenylthiophene [27]. Although this tricyclic zwitterion mechanism accounts for the isothiazole to thiazole and the isothiazole to isothiazole phototranspositions reported for 5-methylisothiazole 43, it also predicts that 3- and 4-methylisothiazoles 41 and 42 should also phototranspose to other isotMazole isomers. 

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