Degenerate ring transformations

The rearrangement of thiophenes to the isomeric pyrroles has proven synthetically useful (Schemes 98a and 98b). In the absence of a suitable internal nucleophilic nitrogen, so-called degenerate ring transformations may occur (Schemes 98c and 98d). 

B. Classification of Degenerate Ring Transformations of Heterocyclic Systems... 

Degenerate ring transformations of heterocyclic systems that have been discovered to date can be classified in two main groups (1) Nucleophilic... 

From the examples presented in Schemes I.IO, I.ll, and 1.12, it is evident that the Go graphs in these degenerate ring transformations are all characterized by mirror plane symmetry. 

It became evident that the mechanism for the simple hydroxydechlorination replacement reaction decribed in Scheme II.7 occurs in a way very different from the aminodebromination of 2-bromopyridine, but very similar to that of 2-bromopyrimidine (see Section II,C,l,c). It is, however, good to stress the point that, although the aminodehydroxylation occurs according to an Sn(ANRORC) mechanism, it does not involve a degenerate ring transformation. 

These results clearly show that an unsubstituted C-2 position in 6-halogenopyrimidines is an important prerequisite for ring-opening processes that can lead to nucleophilic substitutions involving a degenerate ring transformation. 

An interesting consequence of the mechanism presented in Scheme 11.26 is that, in principle, from the intermediary 45 by ring closure a double N-labeled 2-aminopyrimidine 42 can also be obtained These results suggest that the formation of the 2-amino-4-phenylpyrimidine can occur according to two routes by an initial addition at C-6 (the main process. Scheme 11.25) and by initial addition at C-4 (the minor process. Scheme 11.26) (74RTC111). Both routes involve a degenerate ring transformation. 

A similar degenerate ring transformation was observed when 4-amino-6-chloro-l-methylpyrazolo[3,4-(f]pyrimidine was treated with dilute alkali. In this reaction as well, the expected product, 4-amino-6,7-dihydro-6-oxo-l-methylpyrazolo[3,4-(f]pyrimidine, was not obtained, but rather a rearranged isomer, i.e., 6-amino-4,5-dihydro-4-oxo-l-methylpyrazolo-[3,4- f] pyrimidine. The formation of this compound takes place according to the same mechanism as that postulated for the formation of 86 (Scheme 11.39) (54JOC1570). 

The reaction is one of the few examples of a degenerate ring transformation in pyrazine chemistry. Extensive investigations on the amination of 2-chloroquinoxaline have shown that in the formation of the 2-amino compound no Sn(ANRORC) process is involved (72RTC850). 

The occurrence of degenerate ring transformation reactions in the hy-drazinodehalogenation of halogeno-l,2,4,5-tetrazines (see Section II,D,3.) raised the question as to whether corresponding reactions would also occur with the less reactive halogenopyridazines. Extensive investigations on hy-... 

Comparison of this reactivity order with that found in the amination of 2-X-4-phenyl pyrimidines (SCH3 Br = Cl > F > SO2CH3 I > (013)3 > CN see Table 11.5 in Section ll,C,l,d) shows that these reactivity orders differ considerably. The fluoro substituent, especially, which has in the pyrimidine series about the same reactivity order as the chloro or bromo atom, shows in the 1,2,4-triazine series a low ANRORC activity. Comparison of both series of reactivities is, however, a delicate matter, mainly because the yields obtained for the amino compounds in the 1,2,4-triazine series are much lower than those obtained in the pyrimidine series, because of the occurrence of many side reactions, such as ring contraction, dehalogenation, ring transformations, and degenerate ring transformations... 

A. Degenerate Ring Transformations Involving the Replacement of the Nitrogen of the Azaheterocycle by Nitrogen of a Reagent... 

An interesting application showing the general usefulness of the Zincke degenerate ring transformation is the immobilization of proteins to... 

An interesting series of degenerate ring transformation has been found when the A-alkyl-3-R-pyridinium salts (5, R = NO2, SO2CH3, CONH2, CF3, CN) react with liquid ammonia at room temperature (73JOC1949 ... 

Degenerate ring transformations have also been observed in reactions of 6-ethoxy-4-oxopyrimidinium salts (25, R = H, CH3, C6H5) with liquid ammonia (77RTC68). Besides open-chain compounds, 2-R-l-ethyl-4-(ethylamino)pyrimidin-6(l//)-one is formed. The presence of the ethyl-... 

A very interesting case of a degenerate ring transformation has been observed when the mesitylenesulfonate (MS )(30) reacts with N-double-labeled anhydrous hydrazine for a short period of time. When after the reaction starting material is recovered, the compound shows a considerable enrichment of the label, i.e., the formation of 30 (83JHC415) ... 

This degenerate ring transformation is generally applicable, since with different aryl substituents at positions 1, 4, and 6, aryl-substituted pyrimidine A -oxides are indeed formed. In a very similar reaction, 4,6-... 

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