Isomerization pathways

A recent paper by Singh et al. summarized the mechanism of the pyrazole formation via the Knorr reaction between diketones and monosubstituted hydrazines. The diketone is in equilibrium with its enolate forms 28a and 28b and NMR studies have shown the carbonyl group to react faster than its enolate forms.Computational studies were done to show that the product distribution ratio depended on the rates of dehydration of the 3,5-dihydroxy pyrazolidine intermediates of the two isomeric pathways for an unsymmetrical diketone 28. The affect of the hydrazine substituent R on the dehydration of the dihydroxy intermediates 19 and 22 was studied using semi-empirical calculations. ... 

The present characterization studies have motivated us to investigate in the future the optimum edeination and reduction temperatures to maximize the isomerization pathway, while keeping coke deposition and hydrogenolysis to a minimum. Our results suggest that compromises are expected to be made to achieve those goals. 

Fig. 16. Some of the isomerization pathways of benzene and xylene through ring permutation.

This particular isomerization pathway is supported by ah initio calculations. The energies of isomers and various transition states along the... 

These features do not preclude (1) and (2) (or their near equivalent) as a pathway for hydrogenation provided (1) is irreversible, but they do preclude alkyl reversal as an isomerization pathway. Over chromia, Burwell et al. (3) suggest that allyl species may furnish an isomerization pathway, viz ... 

Butene as the feed alkene would thus—after hydride transfer—give 2,2,3-TMP as the primary product. However, with nearly all the examined acids, this isomer has been observed only in very small amounts. Usually the main components of the TMP-fraction are 2,3,3-, 2,3,4-, and 2,2,4-TMP, with the selectivity depending on the catalyst and reaction conditions. Consequently, a fast isomerization of the primary TMP-cation has to occur. Isomerization through hydride- and methyl-shifts is a facile reaction. Although the equilibrium composition is not reached, long residence times favor these rearrangements (47). The isomerization pathways for the TMP isomers are shown schematically in Fig. 3. 

Figure 4.17 Cracking and isomerization pathways of paraffins in hydrocracking (M, metallic site A, acidic site).

The propargylic trichlorotin intermediate isomerizes to the more stable allenyltri-chlorotin species on standing or being warmed to 0 °C. The isomerization, which is highly stereoselective, takes place with retention. A possible transmetallation and isomerization pathway is illustrated in Scheme 9.21. 

Skeletal ring contraction steps of primary C7 and Cg rings are more probable than bicyclic intermediates (132b). Aromatization of methylcyclo-pentane indicated no carbonium mechanism with a nonacidic catalyst. Instead, Pines and Chen (132b) proposed a mechanism similar to that defined later as bond shift. This is a methyl shift. Two additional isomerization pathways characteristic of chromia have also been demonstrated vinyl shift (94) and isomerization via C3 and C4 cyclic intermediates (90a). These were discussed in Section III. 1,1-Dimethylcyclohexane and 4,4-dimethyl-cyclohexene gave mainly toluene over various chromia catalysts. Thus, both skeletal isomerization and demethylation activities of chromia have been verified. The presence of an acidic almnina support enhances isomerization dual function effects are thus also possible. 

Figure 4. One-dimensional MNDO isomerization pathways for tetra-methyl tetrahedrane and its radical cation. For the definition of the coordinate a cf. ( ) Cl denotes calculations including limited configuration interaction (see text).

Summarizing facts and speculations despite the crudeness of the model chosen, the relative thermal stcibilities of both isomers, FSSF and F2SS are correctly reproduced by the CNDO hypersurface calculations, and also the surprising likeness of their ionization patterns (33-35). Whatever the real isomerization pathway may be, the chances for the experimentalist to ever isolate the molecules H2S=S and Cl2S=S under normal reaction conditions are predicted to be close to zero - another recommendation to avoid futile experimental efforts by precalculating hypersurfaces. 

The stilbenes have played a crucial role in the development of modern photochemistry. Direct or triplet sensitized irradiation of trans-stilbene (t-1) in dilute solution results in isomerization to cis-stilbene (c-1) as the exclusive uni-molecular photochemical reaction (1-3). Direct irradiation of c-1 results in isomerization to both t-1 and trans-4a,4b-di-hydrophenanthrene (2), which revert to c-1 both thermally and photochemically and can be trapped by oxidants such as iodine or oxygen to yield phenanthrene (3) (4-6). Triplet sensitized irradiation of c-1 yields only t-1. These unimolecular isomerization pathways are summarized in eq. 1. 

Very recently, an experimental study reported by Xu et al. [65] has highlighted the importance of the isomerization pathways in the reaction between ketenes and imines. According to this analysis, the cis/trans ratio is closely related to the rate constants of the direct ring closure (ki) and the isomerization of the zwitterionic intermediate (58) (k2), as indicated in (2) and Scheme 13. 

More recently, we have found that the role of the isomerization pathways in the reaction between ketenes and imines can be extended to the (E)/(Z) isomerization of imines themselves [68]. Thus, the stereocontrol observed in the reaction between methoxyketene 41 and (E)-imines (62a,b) was attributed to the competition between the energy barriers associated with the formation of intermediates (63a,b) and (65a,b) and the energies of activation corresponding to the isomerisation of (E)-imines (62a,b). Inclusion of isomerisation processes involving both imines (62a,b) and zwitterionic intermediates (63a,b) and (65a,b) led to a more complex kinetic analysis. As the final steps leading to (3-lactams (64) can be considered irreversible, the formation of both cis- and trans-(64) can be described by (3) and (4) ... 

There is a general agreement on the stepwise nature of the [2+2] cycloaddition between ketenes and imines. The first step consists of a nucleophilic attack of the iminic lone pair on the v/ -hybridized atom of the ketene to form a zwitterionic intermediate. The subsequent four-electron conrotatory electrocyclization leads to the corresponding (3-lactam. The final stereochemical outcome of the reaction depends on the combination of the following features (1) endo/exo attack of the imine on the ketene (2) inward outward disposition of the substituents at the conrotatory transition structure and (3) relevance of the isomerization pathways, including those of the starting imines. 

Ferreti and coworkers110 have carried out an analysis of over 300 crystal structures of species which contain the R(X=)C—NR1R2 molecular fragment. In this survey it was found that, in the crystal, inter- or intramolecular forces can induce out-of-plane deformations of the fragment, so that the cis-trans isomerization pathway involves a transition state 21b. 

We have noted that all three-bladed propellers with D3 skeletons are in some ways structurally analogous. The analogy extends to their isomerization pathways. We will investigate the nature of this relationship by discussing the concept of stereochemical correspondence and then illustrating its application to propeller molecules. 

S. G. Kirillova, V. M. Andrianov, and R. G. Zhbankov, Structure effects on isomerization pathways and vibrational spectra of epoxysaccharides a numerical study, Theor. Chem. Acc., 101 (1999) 215-222. 

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