Annular prototropy

Annular tautomerism between one or more NH-forms and various CH forms of 1,2-diazepines is possible with the favored species dependent upon the nature and position of substituents (69ACS3125, 70T739). Interestingly, unlike monocyclic azepines and tautomeric 1,2-diazepines, 5H- 1,2-diazepines (47) exist preferentially in their bicyclic diazanorcaradiene form (48) (72JA2770). 

For monocyclic fully unsaturated 1,4-diazepines, the NH-forms are unstable. Azonine (35 X = NH) exists exclusively as NH-tautomer that is due to its IOtt electron aromatic character (70TL825). 

All reactions can be broken down into a succession of individual steps in each of which bonds are broken and/or formed. A chemical bond can be formed (or broken) in three ways. 

The basic principles governing the degree and type of reactivity shown by heteroaromatic compounds are familiar from aliphatic and benzenoid chemistry. Three are very important  

These basic principles give much insight into the reactions of aromatic heterocyclic compounds. 

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Annular prototropie tautomerism of 1,2,3-triazole (v-triazole) and its C-substituted derivatives involves the equilibrium of three possible isomers 24a-24c. In the ease of the parent eompound (R = H), 24a and 24c are degenerate isomers (Seheme 11). 

There are two important types of tautomerism found for small and large rings valence bond tautomerism and (to a somewhat lesser extent) annular prototropy. 

Annular prototropy is not of great importance for small heterocycles. However, it should be mentioned that 1-azirine (2) is much more stable than its antiaromatic 2-isomer (3). By analogy, antiaromaticity is certainly a key factor determing instability of lH-azepines which have never been observed. Thus, demethoxycarbonylation of methyl-3,6-di-r-butylazepine-l-carboxylate (46) by DBU gives a mixture of the corresponding 2H-, 3H-, and 4//-azepines in the approximate ratio 13 56 1 (Scheme 9) (94JCS(P1)1753). The distribution of the azepine isomers is proportional to their relative thermal stabilities as they interconvert via allowed 1,5-hydrogen shifts. 

Annular prototropy in pyrans involves migration of protons between different sites in the ring. The equilibrium situation is depicted in equation (6). The systems in which this... 

The tautomerism of 1,2,4-triazoles (see Chapter 4.01 and (76AHC(S1)i)) may involve one or more of the following possibilities annular prototropy, prototropy involving both the ring and substituents and tautomerism restricted to the substituent. Only the first two of these will be considered. 

Prototropy in triazoles is particularly complex when substituents such as OH, SH and NHR are available to donate protons to annular N. A detailed discussion of all possible sub-cases of this type is beyond the scope of this chapter, but the main aspects of this matter are reviewed in a broad critical context (76ahc(s1)i. p. 388, 4i4, 444) tabulating generalizations and their levels of reliability. The section on reactivity (Section 4.12.3) gives examples of the variability of tautomeric preference in some reactions. 

Isomerizations in which an H-atom changes its position in a heterocyclic system are known as annular tautomerisms. This is a special case of prototropy (prototropic rearrangement) [57]. For isoindole, the position of the equilibrium depends to a large extent on the type of the substituent in the 1- and/or 3-position [58]. The 1-phenyl compound exists in the 2//-form and couples with benzenediazonium chloride in the 3-position. 

This special case of prototropy is known as annular tautomerism (see p 111). In solution, equilibria are established so rapidly that the separate tautomers cannot be isolated. However, their presence can be demonstrated by spectroscopic methods. In this case, e.g. R = CH3, the compound is known as 4(5)-methylimidazole. With certain substituents R, the equilibrium lies predominantly to one side, for instance, in the case of the nitro compound (4-nitroimidazole) or with the methoxy compound (5-methoxy-imidazole). Annular tautomerism has also been demonstrated for 4,5-disubstituted imidazoles ... 

Isomerizations in which an H-atom changes its position in a heterocyclic system are known as annular tautomerisms. This is a special case of prototropy (prototropic rearrangement) [212]. 

This special case of prototropy is known as annular tautomerism (cf p. 152). In solution, equilibria establish so rapidly, that separation and isolation of tautomers of the type 3/4 is not possible their presence, however, can be estabUshed by NMR spectroscopy. The equihbrium position 3/4 depends on the substituent. 

The study of annular lactam-lactim tautomerism in solution was continued by employing reference compounds in which prototropy is blocked. For example, the tautomerism of 2,1,3-benzothiadiazinone S,S-dioxides 47 (Scheme 5.38) was assigned by 3( C)-C4a (113.7ppm) comparing with 5( C)-C4a of the blocked... 

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