Aziridines

Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine (-NR-) and two methylene bridges (-CR2-). The parent compound is aziridine (or ethylene imine), with molecular formula C2H4NH. Several drugs feature aziridine rings, including mitomycin C, porfiromycin, and azinomycin B (carzinophilin). The bond angles in aziridine are approximately 60°, considerably less than the normal hydrocarbon bond angle of 109.5°, which results in angle strain as in the comparable cyclopropane and ethylene oxide molecules. A banana bond model explains bonding in such compounds. Aziridine is less basic than acyclic aliphatic amines, with a pKa of 7.9 for the conjugate acid, due to increased s character of the nitrogen free electron pair. Angle strain in aziridine also increases the barrier to nitrogen inversion. This barrier height permits the isolation of separate invertomers, for example the cis and trans invertomers of N-chloro-2-methylaziridine. Several routes have been developed for the syntheses of aziridines (aziridination). An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. The parent aziridine is produced industrially from aminoethanol via two related routes. The Nippon Shokubai process requires an oxide catalyst and high temperatures to effect the dehydration. In the Wenker synthesis, the aminoethanol is converted to the sulfate ester, which undergoes base-induced sulfate elimination. Nitrene addition to alkenes is a well-established method for the synthesis of aziridines. Photolysis or thermolysis of organic azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides, or the ethoxycarbonylnitrene from the N-sulfonyloxy precursor. Thermolysis or photolysis of triazolines expels nitrogen, producing an aziridine.