Aziridine

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File:Aziridine.png
Aziridine parent compound
File:Aziridine3d.png
3D Spacefill of Aziridine

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 (CAS 151-56-4).

Structure

The bond angles in aziridine are around 60° which is considerably shorter 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.

Synthesis

Aziridines can be prepared in organic synthesis in several ways.

Cyclization of haloamines and amino alcohols

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

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]

Triazoline decomposition

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.

From epoxides

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]

Reactions

Nucleophilic ring opening

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[6] in scheme 2[7] in an organic synthesis of oseltamivir:

Other

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.

References

  1. Heterocyclic chemistry T.L. Gilchrist ISBN 0-582-01421-2
  2. Epoxides and aziridines - A mini review Albert Padwaa and S. Shaun Murphreeb Arkivoc (JC-1522R) pp 6-33 Online article
  3. http://www.drugfuture.com/OrganicNameReactions/ONR153.htm
  4. Addition reactions of ethoxycarbonylnitrene and ethoxycarbonylnitrenium ion to allylic ethers M. Antonietta Loreto, Lucio Pellacani, Paolo A. Tardella, and Elena Toniato Tetrahedron Letters, Volume 25, Issue 38 , 1984, Pages 4271-4274 Abstract
  5. Readily Available Unprotected Amino Aldehydes Ryan Hili and Andrei K. Yudin J. Am. Chem. Soc.; 2006; 128(46) pp 14772 - 14773; (Communication) doi:10.1021/ja065898s
  6. De Novo Synthesis of Tamiflu via a Catalytic Asymmetric Ring-Opening of meso-Aziridines with TMSN3 Yuhei Fukuta, Tsuyoshi Mita, Nobuhisa Fukuda, Motomu Kanai, and Masakatsu Shibasaki J. Am. Chem. Soc.; 2006; 128(19) pp 6312 - 6313; Abstract
  7. The catalyst is based on yttrium with three isopropyloxy substituents, the ligand is a phosphine oxide (Ph = phenyl). with 91% enantiomeric excess (ee)

de:Ethylenimin fi:Etyleeni-imiini


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