Heterocyclic Ring Cleavage

Compounds with aromatic carboxylic molecules with heterocyclic rings are subject to metabolism by microorganisms. In pesticides with such heterocyclic rings, the path followed by the degradation process is complicated by the heteroatoms, usually N, O, and S, which contribute individual characteristics to the decomposition reactions. These compounds may contain one or more rings (mostly aromatic), and the rings generally have five to six members. 

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Most enzymes that catalyze the cleavage of heterocyclic compounds are scantily understood and most of them have not even been identified. Different types of enzymes are involved in various heterocyclic ring cleavage reactions (see schemes in Fig. 33). 

Figure 33. Reactions catalyzed by N-heterocyclic ring cleavage dioxygenases.

Aromatic and heterocyclic cleavage involves a hydrocarbon being separated from an oxygen atom, which functions to link it to another moiety of the molecule this process may lead to a decrease in the initial toxicity. The metabolic effects of microorganisms differ with the molecular configuration of the product, which affect aromatic or heterocyclic ring cleavage differently. 

Active Raney nickel induces desulfurization of many sulfur-containing heterocycles thiazoles are fairly labile toward this ring cleavage agent. The reaction occurs apparently by two competing mechanisms (481) in the first, favored by alkaline conditions, ring fission occurs before desul-, furization, whereas in the second, favored by the use of neutral catalyst, the initial desulfurization is followed by fission of a C-N bond and formation of carbonyl derivatives by hydrolysis (Scheme 95). 

The importance of this group of reactions to the chemistry of isoxazoles is shown by the considerable amount of effort expended on this topic (63AHC(2)365,79AHC(25)147). The lability of the isoxazole nucleus towards nucleophiles and bases distinguishes this heterocycle from other azoles. The conditions which lead to ring cleavage are quite varied and depend on the position and the nature of the substituents. 

In contrast to the well-defined photochemical behavior of 1-azirines the thermal reactions of these compounds have been studied less thoroughly (68TL3499). The products formed on photolysis of azirines can best be rationalized in terms of an equilibration of the heterocyclic ring with a transient vinylnitrene. Thus, products formed from the thermolysis of azirines are generally consistent with C—N cleavage. For example, the vinylnitrene generated from the thermolysis of azirine (149) can be trapped with phosphines (72CCS6S). 

Decarboxylation of isoxazole-3-carboxylic acids is related to the nucleophilic cleavage of the isoxazole ring as far as the nature of the reaction products is concerned. It occurs at temperatures above 200°C and is accompanied by the cleavage of the nitrogen-oxygen bond of the heterocyclic ring to yield a j8-ketonitrile. It was first reported by Claisen with 5-methyl- and 5-phenyl-isoxazole-3-carboxylic acids (153- 154).Under the reaction conditions, j8-ketonitriles condense... 

The isoxazoline ring is also readily cleaved by such reducing agents as do not affect the isoxazole ring. Thus, for example, the treatment of isoxazolines (186) with LiAlHj proceeds with a smooth cleavage of the heterocyclic ring to form substituted 3-amino-propan->l-ols... 

In recent years a number of new isoquinoline alkaloids of untypical structures, i.e., structures with open heterocyclic rings, have been isolated from natural sources. These bases were named secoisoquinoline alkaloids because they were believed to be produced in vivo from classic isoquinoline alkaloids as a result of various degradation processes causing oxidative cleavage of some bonds. 

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