Pyridine ring cleavage

In a continuation of this work, the degradation of pyridine was studied in the presence of Nocardia strain Zl. Glutaric acid semialdehyde was produced as an intermediate product. The C2-N pyridine ring cleavage was evidenced by the formation of an intermediate product with five atoms. Therefore, the authors proposed the pathway shown in Fig. 28, for the metabolism of pyridine by Nocardia strain Zl. 

Not all seemingly similar pyridine ring cleavages follow this pattern, however. The most fascinating one is the migration-coupled pyridine ring opening reported by Hitosi Nozaki, Kiitiro Utimoto et After consecutive treatment of 6-bromopyrid-2-... 

The cleavage of fused pyrazines represents an important method of synthesis of substituted pyrazines, particularly pyrazinecarboxylic acids. Pyrazine-2,3-dicarboxylic acid is usually prepared by the permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring resembles the pyridine ring in its stability rather than the other diazines, pyridazine and pyrimidine. Fused systems such as pteridines may easily be converted under either acidic or basic conditions into pyrazine derivatives (Scheme 75). 

As already noted, the lability of the isoxazole nucleus toward the action of nucleophilic agents distinguishes this heterocyclic system from those of other azoles and of pyridine. The conditions which lead to ring opening, and the products of ring cleavage are quite varied and depend on the position and the nature of substituents, although it is invariably the N—0 bond which is broken. 

Quatemization of the isoxazole nitrogen atom makes the ring particularly susceptible toward nucleophilic attack there is a certain analogy here with pyridine. The cleavage of the ring proceeds extremely readily in quaternary salts of isoxazole, even occurring by the action of such weak nucleophilic agents as the anions of carboxylic acids. 

A large diversity of microorganisms has been shown to degrade pyridine. Numerous studies have been performed and a large number of metabolites have been detected. The proposed hypothetical pathway was constructed to fit all the results. Certain set of intermediates were identified for specific microorganisms and some enzymes were also identified or detected (e.g., aliphatic intermediates). However, the mechanism(s) of cleavage of the pyridine ring remain(s) unknown. 

On the basis of a simple three-phase model (i.e. electrode, monolayer of modifier, solution), the authors calculations suggested that the initially formed layer of SSBipy on the surface was formed without bond cleavage and with the pyridine rings essentially flat on the surface. 

Thiadiazolines are less stable compared to 1,2,4-thiadiazoles and this can be attributed to the loss of aromatic character. They are readily cleaved at the N-S bond under fairly mild conditions (H2S in pyridine) in some cases, the product from ring cleavage can recyclize to give new heterocyclic ring systems. The 3-imino-l,2,3-thiadiazoline 24 when reduced with H2S affords the two J-triazine derivatives 25 and 26 (Scheme 3) <1996CHEC-II(4)307>. 

Recent developments are ring-cleavage reactions of the heterocycles [R2M-SbR2]w with 4-(dimethylamino)pyridine leading to base-stabilized monomers, [L — R M-SbR, (R = Me, SiMe3 R = Me, Et, i-Bu M = A1, Ga).83,84 Reaction of [L-Al(Me2)-Sb(SiMe3)2] [L = 4-(dimethylamino)pyr-idine] with [Ni(CO)4] leads to the corresponding tricarbonyl nickel complex (Equation 4).85... 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

Additional examples of the utility of ring cleavage and recyclization of 4(5Ff)-oxazolones to prepare interesting heterocycles have been described (Scheme 6.16). Ttreatment of 4-aminothymol 53 with 54 in refluxing pyridine yields the 4-imidazolidinones 55 evaluated as antimicrobial and antimbercular agents. The authors listed an extensive series of analogues (25 compounds) but reported a yield for only one example, 55 (63% for Ri = Ph, R2 = 4-MeO—CeKt). Condensation of 2-phenyl-4(5F/)-oxazolone 56 with substituted hydrazines affords excellent yields of the 1,2,4-triazoles 57, important precursors to the previously unknown l(r/)-l,2,4-triazole-5-carboxaldehydes 58. Representative examples are shown in Table 6.3 (Fig. 6.8). 

D-Marmitolbexanitrate. This compd in pyridine evolved gases (NO, N20 N) and mannitol - 1,2 4,5,6 - pentanitrate and CgH5N.HN03, after dilution with water. Approx 2 moles of CgHgN suffered ring cleavage, 0.25 mole of the hexani-trate was completely denitrated, and 0.75 mole of pentanitrate was formed (Ref 3)... 

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