Aziridinium mechanism

Recent development of regio- and stereoselective aminohalogenation reaction of alkenes, particularly, aziridinium mechanism of the reaction 07EJO2745. 

These findings can be interpreted in terms of a normal ring-opening mechanism of intermediate 325 with proton transfer favored by protic solvent, whilst in aprotic solvent cycloreversion of the unstable aziridinium grouping in 325 followed by ring expansion prevails. Likewise, 2,3-disubstituted aziridines follow this reaction pattern, while N-substituted aziridines do not225. ... 

That the metabolism of melphalan occurs by the same reaction mechanism as that of mechlorethamine has been demonstrated in in vitro studies [65]. Under physiological conditions of temperature and pH, formation of the first and second aziridinium intermediates en route to the bis(hydroxyethyl) metabolite occurred with rate constants of ca. 0.017 and 0.041 min-1, respectively. After 60 min, ca. 2/3 of the drug had been converted to the monohydroxy and dihydroxy products in comparable amounts. In the presence of a phosphate buffer, competition between hydrolysis and phosphatolysis was seen, such that at completion of the reaction (4 h) the two major products were the dihydroxy and the hydroxy/phosphate metabolites, with the dihydroxy derivative produced in small amounts. Similar hydrolytic dehalogena-tion has also been observed for ifosfamide in acidic aqueous solution [69]. 

Phenyl azide was also found to react with alkenes in TFA (Scheme 11). The reaction was assumed to go via an aziridinium ion generated from attack of the alkene on the nitrenium ion because of the overall /rans-addition to the alkene noted in product 29. An alternative Sn2 mechanism was disfavored because phenyl azide decomposes at 21 °C in 50 vol% cyclohexene/TFA with an almost identical first-order rate constant as in 50vol% benzene/TFA even though cyclohexene is a considerably stronger nucleophile than benzene. ... 

Several studies on the reactions and preparation of aziridines have been published. The ring opening of 2-substituted aziridines, accomplished by first converting them into aziridinium salts by reaction with a benzyl bromide and then attack of the bromide counter ion, gave only one bromide in a regio- and stereo-specific reaction.43 Since attack by the bromide ion of the aziridinium salt only occurred at the most substituted carbon with an inversion of stereochemistry, it was concluded the reaction occurred by an SN2 mechanism. This was supported by calculations at the MPWBlK/6-31+G(d) level of theory for reactions featuring two solvating acetonitrile molecules embedded in an acetonitrile matrix. 

The aminochlorination of methylenecyclopropanes and vinylidenecyclopropanes has been explored with use of FeCT (20 mol%) as a Fewis acid catalyst in acetonitrile under convenient mild conditions. The aziridinium-based mechanism, accounting for... 

The Willgerodt Reaction allows the synthesis of amides from aryl ketones under the influence of a secondary amine and a thiating agent. The mechanism involves the formation of an enamine which undergoes thiation, and the carbonyl group migrates to the end of the chain via a cascade of thio-substituted iminium-aziridinium rearrangements. 

In a second example, the Norton group has presented evidence that the reduction of phenyl substituted aziridinium cations to the corresponding amines by Cp Ru (dppf)H proceeds via a similar mechanism [34] that is shown in Scheme 13. 

The amine product plays a critical role, as it deprotonates the H2 complex 18 to regenerate the catalytically active 17. This also prevents side reactions based on nucleophilic ring opening of the aziridinium cations by the amine products. Alkyl substituted aziridinium cations react via a classical SN2-mechanism. 

Chloroxymorphamine (/3-COA), 191 (R = Me), on the other hand, produced irreversible agonist responses(307) also, presumably by an alkylating mechanism. Alkylation probably occurs from attack by a receptor nucleophilic group upon a mediating aziridinium ion. The mutagenic nature of compounds capable of generating aziridinium ions is likely to render compounds of this sort unacceptable for human therapy. 

Dialkyl diazenedicarboxylates do not undergo efficient cycloaddition with vinyl ethers. For example the [2 -I- 2] adduct was obtained in low yield from the cyclopropane-fused dihydropy-ran 11 even at high temperature28. From the same substrate the [2 + 2] cycloadduct with 4-phenyl-3//-1,2,4-triazole-3,5(4//)-dione was obtained quantitatively even at low temperature through a polar mechanism involving an aziridinium imide as the intermediate28. 

Copper triflate has been found to promote the [3+2] cycloaddition of iV-tosylaziridines with nitriles <2006TL5399>. Ghorai has found that aziridine 149 and a substituted benzonitrile were dissolved and added to a suspension of copper triflate, resulting in the formation of good yield of the imidazoline 150. The mechanism proposed involves the addition of the nitrogen atom of the nitrile to the presumed copper aziridinium ion formed with the triflate catalyst. Subsequently, the iV-Ts moiety attacks the electrophilic carbon of the nitrilium ion to form the imidazoline. 

Treatment of some mesylated N,N-diallylamino sugars with triethylamine tnhydrofluoride results in the fluorination and regioselective transfer of the nitro gen atom to give, after platinum-catalyzed reductive deallylation, 2,3-amino-fluorodeoxysugars A mechanism involving aziridinium ions has been proposed [44] (equation 32)... 

An alternative mechanism for the formation of the substitution products 333 entails the intermediacy of an aziridinium ion (334). Curiously, reaction of these allyl halides (291,... 

Although the formation of phthalidylisoquinolines presumably proceeds via the aziridinium salt by route B in Scheme 14, the mechanism shown in Scheme 16 is also a possibility. 

Aminomercuration leads to substituted organomercurials 5.5, which also suffer demercuration with sodium borohydride, preferentially under PTC conditions [BEl, EB4] (Figure 5.5). The mechanism proposed for this reduction in protic solvents is an ionic one, implying the intermediate formation of aziridinium salt [L3]. This method has been applied to the synthesis of cyclic amines from a,P-ethyienic precursors 5.6 [EB4] (Figure 5.5). When the reduction in run in alcohol or water, mixtures of five- and six-membered cyclic amines are obtained from each precursor 5.6 (n = 1 or 2). 

Enamines may serve as precursors as well (Eqs. 85195 and 8674). The latter reaction is of interest for the formation of rearrangement product 48, which apparently has not been followed up as a means of preparing a-amino aldehydes. A mechanism involving an aziridinium intermediate has been proposed.74... 

Scheme 19.11 Phenoxybenzamine s (35) irreversible interaction with its targeted biological surface, namely that for treating pheochromacytoma. Note that while this is analogous to the mechanism of the nitrogen mustards displayed in Scheme 19.10, in this case the rate of formation of the aziridinium species has been attenuated by the steric features of the N-benzyl group. This feature, in turn, allows 35 to first associate with its target biological surface (A). Once bound at this intended destination, formation of an aziridinium does occur (B) and this is rapidly followed by a reaction with an endogenous nucleophile located within this immediate locale (C). Ultimately, this biological surface is selectively shut down (D).

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