Small ring nitrogen heterocycles

Nitrogen can be incorporated in the macroring by inclusion of a small-ring nitrogen heterocycle such as pyridine or pyrimidine. Three approaches should be noted. If the pyridyl unit is incorporated as a 2,6-bis(methyleneoxy)pyridine derived from lutidine, the precursor will normally be a lutidine dihalide or diol. In the case of sulfur, the diol would be a dithiol. If the pyridyl unit is to be attached by 2,6-aminomethyl groups, amide formation followed by reduction is a possibility. In the event that the heterocycle will be attached directly to a macroring heteroatom, nucleophilic aromatic substitution may be useful. 

Azides are important for the synthesis of two classes of small ring nitrogen heterocycles 2H-azirines and aziridines. The synthetic methods fall into two broad categories (1) those in which organic azides are the direct precursors and (2) those in which azides are used to provide intermediates that are then converted into heterocycles. We aimed to provide examples of both types. Routes that lead to 2//-azirines and those that lead to aziridines are described in Sections 6.2 and 6.3. Azides have been used less frequently for the preparation of other small nitrogen heterocycles but some examples are given in Sections 6.4 and 6.5. 

Monocyclic aziridines and 2//-azirines have found broad application in the synthesis of complex natural products. The facility with which these small ring nitrogen-containing compounds can be converted to important pharmaceutical products under mild conditions with wide functional group compatibility makes these molecules quite useful for heterocyclic chemistry. 

The a-metalation of azoles (aromatic nitrogen-containing five-mem-bered rings) is a much more facile process than that for the analogous saturated systems, and a small number of heterocycles containing free NH groups can undergo some direct lithiation, despite the ionization of the... 

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