Interchange pathways

In order to study the 1-methylpyrazole to 1-methylimidazole phototransposition process with minimum substituent perturbation, the phototransposition chemistry of 3,4-dideuterio-l-methylpyrazole (1-3,4d2) has been studied. This labelling pattern allows distinction between the three pathways since Scheme 17 shows that the conversion of 1 to 2 via the three pathways is accompanied by transposition of C-5 of the reactant to ring position 5 by the N-2-C-3 interchange pathway or to ring positions 2 or 4 if the transposition occurs by electrocyclic ring closure followed by one or two nitrogen migrations respectively. 

A more significant difference between 1 -methylpyrazole and isothiazole photochemistry, however, appears to be the minor role of the N-2-C-3 interchange pathway in isothiazole chemistry. Thus, although N2-C3 interchange is a major transposition pathway in pyrazole chemistry, it is only a minor pathway upon irradiation of phenylisothiazoles in benzene solution. In fact, 4-phenylisothiazole (55), the compound most expected to react via the N-2-C-3 interchange pathway, was the only isomer that did not yield a transposition product upon irradiation in benzene solution (Scheme 27). This is not due to the photostability of the compound. Indeed, 55 is the most reactive of the six isomers. Nevertheless, even after consumption of 85% of 55, no phototransposition product could be detected. 

N-2-C-3 interchange pathway. Although phototransposition was enhanced by the addition of base to the reaction medium, when the irradiation was carried out in ether or in methanol containing a small quantity of aqueous HC1 (Scheme 34), the phototransposition was completely quenched and the only product observed was a large yield of the photocleavage product (57H). 

In benzene solution 56 phototransposes (Scheme 38) only by the electrocyclic ring closure-heteroatom migration pathway to yield 51, 52 and 54 in 2%, 15%, and 5% yields respectively. In the presence of TEA, however, the major product (Scheme 39) of the photoreaction of 56 is 5-phenylthiazole (53) formed in 14% yields, with 52 and 54 formed in 4% and 5% yields respectively. 4-Deuterio-5-phenylisothiazole (56-4d) also phototransposed (Scheme 40) to 4-deuterio-5-phenylthiazole (53-4d), confirming that this product was formed by the N-2-C-3 interchange pathway, and 52-5d and 54-4d as expected for products formed by the electrocyclic ring closure-heteroatom migration mechanistic pathway. 

The value of the equilibrium constant for an encounter is certainly of prime importance in the discussion of interchange pathways of complex formation. This was first suggested, in fact by Werner [4] as early as in 1912. Most of the work on ligand substitution in complexes is based on the assumption that encounter equilibria could be calculated from the ion-pairing equation of Fuoss [5] which was derived in turn from a consideration of diffusion-controlled reactions by Eigen [6]. At zero ionic strength, the encounter equilibrium constant, Kp is given as... 

The best studied cases where interchange pathways may occur are those in which there is competition between I (actually an Id, dissociative interchange) and D mechanisms (Scheme 7.1)... 

Plots of kobs versus [substrate] exhibited curvature (e.g. Figure 2.10), which was attributed to a contribution from a (substrate-independent) dissociative pathway and a contribution from a (substrate and substrate concentration dependent) interchange pathway (Eqn (2.5) and Scheme 2.8). 

As noted above, one of the first indications that photogenerated "unsaturated" metal carbonyls such as Cr(CO)5 were indeed solvent coordinated was the demonstration in flash photolysis experiments that the rates of the back reactions with CO as well as reactions with other other ligands are markedly dependent on the nature of the solvent medium. For example the second order rate constant k2 for eq. 5 was reported to be 3.6 x 10 M s in cyclohexane[34] and 3 x 10 M s in perfluoro-methylcyclohexane [25]. The reaction kinetics are second order, for the large part, the substitution mechanisms of these intermediates reacting with CO or other substrates are not yet fully elucidated. However, recent kinetics studies by Dobson and coworkers [35] of the reaction of Cr(CO)5S with S = n-heptane or chlorobenzene with 1-hexene or piperidine as a trapping agent have led to the conclusion that the substitution reactions occurred via competitive dissociative and interchange pathways. Complementary studies... 

Demonstration of the nature of the intermediates is in general a very difficult experimental task, therefore most ligand substitution reactions are assumed to be interchange processes. Nonetheless, kinetic studies often permit us to establish the intimate reaction mechanism which assigns to the interchange pathways either an associative or a dissociative character. 

Ammine and Amine Complexes. Formation of the phosphate complex, [Cr(NH3)5(H2P04)] , from the reaction of [Cr(NH3)50H] ion with phosphate (pH 1-2) proceeds via parallel ion pair and ion dipole interchange pathways (Scheme 8). From kinetic studies at / = 1.0 mol dm" [LiC104], the... 

Exchange reactions of arenes have been reviewed. The exchange of monoalkenes with styrene in [Fe(CO)4(CH2==CHPh)] is dissociative, [Fe(CO)4] being formed. However, replacement of a,p-unsaturated ketones by 1,3-dienes (or polyenes) on an Fe(CO)3 center occurs by both a dissociative and an interchange pathway (see Scheme 2). Two pathways also exist for the replacement... 

Barltrop and colleagues also observed that 3-cyano-l,5-dimethylpyrazole 8 undergoes photoisomerization to yield 9 and 10 (Scheme 5), which can be formed by the 2,3-interchange pathway and the one-step nitrogen... 

Thus, whereas 1,5-dimethylpyrazole 14 transposes by the P > and P7 pathways to yield 1,5-, 1,2-, and 1,4-dimethylimidazoles 17,15, and 16, respectively, 1,3-dimethylpyrazole 12 transposes only via the P4 and P5 pathways to form 1,2- and 1,4-dimethylimidazoles 15 and 16, respectively. Finally, 1,4-dimeth-ylpyrazole 13 transposes to a single product, 1,4-dimethylimidazole 16, presumably via the P4 N2-C3 interchange pathway. 

From these studies, a general mechanistic scheme for the P4 N2-C3 interchange pathway is emerging. As shown in Scheme 15, photocleavage of the N1-N2 bond in 28 is suggested to result in the formation of a species I-l that was described as either a biradical or as a P-iminovinyl nitrene. The isomerization of terminal vinyl nitrenes to nitriles is a well-documented reaction. Accordingly, nitrene I-l would be... 

The photoisomerization of isothiazole 5 to thiazole 6 (Scheme 3) was the first reported phototransposition in the isothiazole-thiazole heterocyclic system. Later work published during the period 1971 to 1978 by Lablache-Combier and co-workers, by Vernin and colleagues,"" andby Maeda and Kojima " also showed that methylisothiazoles phototranspose to methylthiazoles and that phenyl-substituted isothiazoles and thiazoles also undergo phototransposition reactions. A surprising finding, however, was that phenyhsothiazoles were not observed to react via the N2—C3 interchange pathway, an important pathway in pyrazole photochemistry. Furthermore, a common conclusion of these studies was that these photoisomerizations proceed by way of tricyclic zwitterionic intermediates, which had no counterparts in pyrazole photochemistry. 

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