| Aziridine | |
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| IUPAC name | Aziridine |
| Other names | Azacyclopropane, Ethylene imine |
| Identifiers | |
| CAS number | 151-56-4 |
| Properties | |
| Molecular formula | C2H5N |
| Molar mass | 43.07 g mol−1 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references |
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Aziridines are a group of organic compounds sharing the aziridine functional group which is a three membered heterocycle with one amine group and two methylene groups.[1][2] The parent compound of the aziridines is called aziridine (or ethylene imine) with molecular formula C2H5N.
Contents |
The bond angles in aziridine are around 60° which is considerably less than the bond angle of 109.5° found in ordinary hydrocarbons and this results in angle strain just like in the comparable cyclopropane and oxirane molecules. Bonding in this type of compound can be explained by invoking a banana bond model. 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. Increased angle strain in aziridine is also responsible for increased barrier for nitrogen inversion. This barrier is high enough for the isolation of separate invertomers for instance the cis and trans invertomers of N-chloro-2-methylaziridine.
Aziridines can be prepared in organic synthesis in several ways.
An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. Amino alcohols have the same reactivity but it is required to convert the hydroxy group into a good leaving group first. The cyclization of an amino alcohol is called a Wenker synthesis (1935) and that of a haloamine the Gabriel ethylenimine method (1888) [3]
Nitrene addition to alkenes is a well established method for the synthesis of aziridines. Photolysis or thermolysis of azides are a good way to generate nitrenes. Nitrenes can also be prepared in-situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the N-sulfonyloxy precursor.[4]
On thermal treatment or photolysis of triazolines, nitrogen is expelled and an aziridine remains. The required triazoline is generated from reaction of an azide with an alkene in a cycloaddition reaction.
One methods involves the ring-opening reaction of an epoxide with sodium azide followed by organic reduction of the azide with triphenylphosphine accompanied by expulsion of nitrogen gas:[5]
The other method involves the ring-opening reaction of an epoxide with amine followed by ring closing with Mitsunobu reaction.[6]
The Hoch-Campbell ethylenimine synthesis describes aziridine synthesis from reaction of certain oximes with Grignard reagents [7] [8] [9] [10]:
Aziridines are reactive substrates in ring opening reactions with many nucleophiles due to their ring strain. Alcoholysis and aminolysis are basically the reverse reactions of the cyclizations. Effective nucleophiles are also carbon nucleophiles such as organolithium reagent and organocuprates.
One application of a ring-opening reaction in asymmetric synthesis is that with trimethylsilylazide TMSN3 and an asymmetric ligand[11] in scheme 2[12] in an organic synthesis of oseltamivir:
N-unsubstituted aziridines can be opened with olefins in the presence of strong Lewis acid B(C6F5)3. [13] Certain N-substituted azirines with electron withdrawing groups on both carbons form azomethine ylides in an electrocyclic ring opening reaction. These ylides can be trapped with a suitable dipolarophile in a 1,3-dipolar cycloaddition.
The toxicology of any specific aziridine compound will depend on its own structure and activity although sharing the general characteristics of the aziridine group. As an electrophile, aziridines are subject to attack and ring-opening by endogenous nucleophiles such as nitrogenous bases in DNA base pairs, resulting in potential mutagenicity [14] [15][16].
Inhalation and direct contact. It is noted in some reports that even when gloves have been used these have not prevented permeation of aziridine. It is therefore important that users check the breakthrough permeation times for gloves and pay scrupulous attention to avoiding contamination when degloving.
The International Agency for Research on Cancer (IARC) has reviewed aziridine compounds and classified them as possibly carcinogenic to humans (Group 2B). http://monographs.iarc.fr/ENG/Monographs/vol9/volume9.pdf 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.
Irritancy
Irritant effects are caused to mucosal surfaces e.g. eyes, nose, respiratory tract and skin.
Sensitisation
Aziridine rapidly penetrates skin on skin contact.
Skin sensitiser - causing allergic contact dermatitis and urticaria.
Respiratory sensitiser - causing occupational asthma