Wenker aziridine synthesis

Aziridine synthesis via treatment of a -amino alcohol with sulfuric acid to give P-aminoethyl sulfuric acid, which is subsequently treated with base. 

Dermer, O. C. Ham, G. E. Ethyleneimine and Other Aziridines, Academic Press New York, 1969. (Review). 

Deyrup, J. A. In Small Ring Heterocycles, Part 1, Hassner, A., ed. Wiley-Interscience New York, 1983, 1-214. (Review). 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

In 1935, Wenker first prepared P-aminoethyl sulfate ester (4, a solid) from thermal dehydration of monoethanolamine acid sulfate at 250°C according to Gabriel s procedure. Subsequently, the mixture of 4 and 40% NaOH aqueous solution was distilled. Further fractional distillation of the distillate in the presence of KOH and then Na at 55-56 C led to pure aziridine in 26.5% yield. 

The mechanism for the Wenker aziridine synthesis is very straightforward. As depicted by conversion 2— 3, the transformation is a simple case of intramolecular Sn2 displacement process, in which the sulfate ester is the leaving group. 

Due to the convenience of the Wenker aziridine formation from P-aminoethyl sulfate ester (4) and base, many improvements ensued. Leighton et al. improved the yield of the first step for the formation of sulfate ester 4. First of all, both ethanolamine and 95% sulfuric acid were diluted with half of their weight of water and then slowly mixed together at 0 C. Finally, by keeping the temperature below 145 C, sulfate ester 4 was obtained in 90-95% yield. 

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As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

Graham reaction—additive oxidation Hoch-Campbell aziridine synthesis Payne rearrangement Wenker synthesis Aziridine synthesis... 

Water-solubilization 16, 501 Wenker aziridine ring synthesis 17, 537 Wessely-Moser rearrangement... 

Ethylenimines from 2-aminoalcohols via 2-aminosulfuric acid monoesters Wenker aziridine ring synthesis... 

The procedure reported here, which is that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via 8-iodo carbamates).356 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7-9... 

Wenker synthesis is a typical method for synthesis of aziridines in which 2-amino alcohols from natural or synthetic amino acids are cyclized by base. The synthesis of N-tosylaziridines 7 was accomplished by base-mediated cyclization of bis-tosylafes 6 of 2-amino alcohols 5 in water and dichloromethane in equal amounts (Scheme 1). The products were obtained in reasonable yields [23]. In a further improved procedure, the 2-amino alcohols are first converted into their hydrogen sulfates using chlorosulfonic acid and then cyclized by aqueous sodium hydroxide or sodium carbonate to corresponding aziridines (Scheme 2) [24],... 

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