Large rings tautomerism

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

Large-ring Complexes. Variable-temperature n.m.r. studies of the l(l f),2-diazepine complex (40 = R = H) reveal the fluxional/tautomeric rearrangement shown... 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

A selection of agonists is shown. 4-Methylhistamine (4.140) is selective for the Hj receptor, whereas the 2-methyl derivative (4.141) is a weak but usable Hj agonist. The fact that the 2-pyridyl (4.142) and 2-thiazolyl rings (4.143) also lend Hj activity to histamine derivatives shows that tautomerism is not an issue in Hj activity. Large alkyl... 

Ring-chain tautomerism294 (as in sugars) consists largely of cyclic analogs of the previous examples. There are many other highly specialized cases of proton-shift tautomerism. 

All known examples of ring-chain tautomerism can be conveniently divided into two large groups (i) those without direct involvement of any substituent in the heterocyclic ring and (ii) isomerizations with participation of certain substituents. 

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