3.4 - Reactivity of Five-membered Rings with Two or More Heteroatoms

Abstract

This chapter deals with the reactivity of five-membered heterocyclic compounds, including those with two or more than one heteroatom (either nitrogen, sulfur, or oxygen) in the ring, including neutral azoles, azolium salts, azole anions, azolinones, azolinethiones, azolinimines, N-Oxides, N-imides, and N-ylides of azoles. The chemistry of five-membered aromatic rings with two or more heteroatoms shows similarities to both that of the five- and six-membered aromatic rings containing one heteroatom. Thus, electrophilic reagents attack lone electron pairs on multiply bonded nitrogen atoms of azoles (cf. pyridine), but they do not commonly attack electron pairs on heterocyclic nitrogen atoms in NR groups or on heterocyclic oxygen or sulfur atoms (cf. pyrrole, furan, thiophene). Azolium systems show essentially no reactivity towards electrophilic attack at ring carbon atoms. Even if an azolium ion contains additional unquaternized pyridine-like nitrogen, this nitrogen is hardly basic/nucleophilic in character. By contrast, azolium cations show a high reactivity toward nucleophiles and bases: at ring carbon atoms, at the hydrogen of ring CH and NH groups, and even at ring sulfur atoms. In all azoliums, oxolyliums, and thiolyliums, the positive charge facilitates attack by nucleophilic reagents at ring carbon atoms or to the charged heteroatom. Hydroxide, alkoxide, sulfide, cyanide and borohydride ions, certain carbanions, amines, and organometallic compounds react under mild conditions, usually at a position to the quaternary center, to give initial nonaromatic adducts which can be isolated in certain cases but undergo further reactions including oxidation (e.g., the formation of cyanine dyes), ring opening with subsequent alternative closure (e.g., the reactions of oxazoliums with amines), and ring opening without subsequent closure (e.g., the reactions of oxazoliums with hydroxide ion).