Aziridines

Functional group made of a carbon carbon nitrogen heterocycle
the parent compound

In organic chemistry, aziridines are organic compounds containing the aziridine functional group (chemical structure |(R\s)4C2N\sR), 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.

Aziridines are obtained by treating a mono , di , tri or tetra substituted alkene (olefin) with 2,4 Dinitrophenoxyamin in the presence of rhodium catalysts. \mathrm{Alkene} + \mathrm{DPH} >[{}\atop\ce{Rh2(CO2R)4}] \mathrm{Aziridine}

For instance, Ph Aziridine Me can be synthesized by this method and then converted by ring opening reaction to (D) and (L) amphetamine (the two active ingredients in Adderall).

The De Kimpe aziridine synthesis allows for the generation of aziridines by reacting an α chloroimine with a nucleophile, such as hydride, cyanide, or a Grignard reagent.

2 azido alcohols can be converted into aziridines with the use of trialkyl phosphines such as trimethylphosphine or tributylphosphine.

Lewis acids, such as B(, can induce decomposition of the ring to a carbocation and linear azanide, which then attack unsaturated moieties in tandem. Oxidation to the N oxide instead induces nitroso compound extrusion, leaving an olefin.

As electrophiles, aziridines are subject to attack and ring opening by endogenous nucleophiles such as nitrogenous bases in DNA base pairs, resulting in potential mutagenicity. The International Agency for Research on Cancer (IARC) classifies aziridine compounds as possibly carcinogenic to humans (IARC Group 2B). In making the overall evaluation, the IARC Working Group took into consideration that aziridine is a direct acting alkylating agent, which is mutagenic in a wide range of test systems and forms DNA adducts that are promutagenic. The features that are responsible for their mutagenicity are relevant to their beneficial medicinal properties.