Nitrene pathway

The success of this reaction was ascribed to the solubility of the chlorozinc intermediate, whereas other chloramine-T derivatives (e.g. the sodium salt) are insoluble. An alternative non-nitrene pathway was not eliminated from consideration. On the other hand, no aromatic substitution or addition, characteristic of a free sulphonyl nitrene (see below), took place on treatment of jV,lV-dichloromethanesulphonamides with zinc powder in benzene in the cold or on heating. The only product isolated was that of hydrogen-abstraction, methanesulphonamide 42>, which appears to be more characteristic of the behaviour of a sulphonyl nitrene-metal complex 36,37). Photolysis of iV.iV-dichloromethanesulphonamide, or dichloramine-B, or dichloramine-T in benzene solution led to the formation of some unsubstituted sulphonamide and some chlorobenzene but no product of addition of a nitrene to benzene 19>. 

The 2//-azirine may be optically active and therefore be regarded as a chiral building block for enatioselective synthesis. This opens a wide field of investigation and recently efforts have been made to produce optically pure azirines. Considering the anionic displacement as the main pathway (and not the nitrene pathway), the Neber reaction may be modified to serve as a synthetic tool for the production of optically active 2//-azirine intermediates. 

Aziridines can be prepared directly from double-bond compounds by photolysis or thermolysis of a mixture of the substrate and an azide.812 The reaction has been carried out with R = aryl, cyano, EtOOC, and RS02, as well as other groups. The reaction can take place by at least two pathways. In one, the azide is converted to a nitrene, which adds to the double bond in a manner analogous to that of carbene addition (5-50). In the other pathway a 1,3 dipolar addition (5-46) takes place to give a triazoline (which can be isolated), followed by extrusion of nitrogen (7-46). Evidence for the nitrene pathway is most compelling for... 

The Neber rearrangement of oxime sulfonates has been considered to proceed via a nitrene pathway or an anion pathway. If the latter mechanism is operative, the use of a certain chiral base might result in the discrimination of two enantiotropic a-protons to furnish optically active a-amino ketones. Verification of this hypothesis was provided by realizing the asymmetric Neber rearrangement of simple oxime sulfonate 83,... 

The synthesis of N-sulfonylarsinimines 19 has been accomplished by a non-nitrene pathway involving the treatment of triphenylarsine with BAIB and the... 

The first step of the mechanism is the deprotonation of the O-acylated ketoxime at its a-position, which gives rise to the corresponding enolate. This enolate then can react via two possible pathways 1) a concerted anionic pathway in which the leaving group is directly displaced to give the isolable 2H-azirine or 2) a nitrene pathway that leads to the same 2/-/-azirine intermediate via nitrene Insertion. The nitrene pathway has not been disproved experimentally. 

Fragmenting nitrenes [pathway a, Eq. (80)] for these, dimerization yielding tetrazenes is a rather characteristic side reaction. They can also be captured by traps. 

Clearly, in many cases where the formation of N-nitrenes has been postulated as intermediates, the process really proceeds by an alternate non-nitrene pathway. For example, the mechanism of such an apparently simple reaction as the formation of )V,N -diazoles may be presented as (1) the result of dimerization of two nitrene particles (2) interaction of the (V-nitrene with the starting amine affording a tetrazane followed by its... 

The mechanism of azirine formation has been discussed by L abbe.20 A priori, the three paths shown in Scheme 1 can be considered. From a comparison of the activation parameters27 for vinyl azide decomposition ( a 26-30 kcal/mol, AS - 3 to + 5 eu) with those for aryl azides (Ea 35-39, AS 18) it appears that the nitrene pathway a can be excluded, but a clear choice between paths b and c cannot be made at this time.20... 

An example of the differing thermal and photochemical behavior of 2H-azirines is shown in Scheme 10. The starting material 48 rearranges to a pyrazole 49 thermally by a nitrene pathway photochemically an imidazole (50) is formed, implying the nitrile ylide pathway.53... 

A new simple synthetic route to 2,5-dihydrooxazoles 71 by cycloaddition of allyl azido ethers 70 via triazoUnes was shown by Hassner et al. [37]. Earlier, they demonstrated that cr-azido ethers can be easily prepared from aldehydes using an alcohol, hydrazoic acid and titanium tetracliloride as well as the fact that thermolysis of azido ethers in the absence of a double bond forms imi-dates [35,36]. Using the above mentioned facts, the allyl azido ethers 70 were synthesized in good yields employing an aldehyde, an allyl alcohol and HN3 in a 1 3 9 ratio in presence of a Ti catalyst (Scheme 12). Allyl azido ethers 70, on thermolysis in benzene, proved to be ideal substrates for the formation of 2,5-dihydrooxazoles 71 in 66-90% yield. To show that oxazolines are formed via triazolines and not via an independent nitrene pathway, thermolysis of 70 was followed by NMR in hexadeuteriobenzene at 70 °C. 

Acyl azides can undergo photolytic cleavage and rearrangement upon irradiation at room temperature or below. In that case acyl nitrenes 8 have been identified by trapping reactions and might be reactive intermediates in the photo Curtius rearrangement. However there is also evidence that the formation of isocyanates upon irradiation proceeds by a concerted reaction as in the case of the thermal procedure, and that the acyl nitrenes are formed by an alternative and competing pathway " ... 

The possible routes leading to azides 2 are outlined in Scheme 1. The only pathway which we can exclude the 2=>C=>D=>E=>2 sequence since neither intermediate E nor its possible derivative E could be detected in the reaction mixture. (P-Azido a,P-unsaturated ketones are known to afford isoxazoles via nitrenes derived by loss of nitrogen (refs. 4,10). Azides 2 may form either via intermediate A (Sn + E route) or via allyl bromide-type intermediate B (E -f Sn route), both routes may operate on the basis of experimental results obtained so far. 

Fig. 10. Possible photoactivation pathway of 4 mechanism for nitrene formation and subsequent trapping with dimethylsulfide (DMS) results in C-C bond formation, DMS oxidation, and oxygen evolution.

In remembrance of the isolation of carbene 78 (Section m.C) it seems acceptable that 141, formed from 140 by a [l,2]-migration of the substituent, functions as a second intermediate. Carbene 141 can subsequently fragment into a nitrene 143 and carbon monoxide or open to an isocyanate 144, which alternatively may also be generated from an acid azide via acylnitrene 142. In comparison to calculated reaction pathways 75 78 and 82 81 (Schemes... 

This last example again demonstrates the usefulness of correlating hypersurface calculations as closely as possible to measurement data although methyl and vinyl nitrenes, which by chemical intuition seem to be reasonable intermediates, do not have to occur necessarily along the reaction pathway (36,39), the predictions stimulated an experiment, which otherwise - due to the hazardous starting material (38) - hardly would have been carried out. 

Several lines of inquiry have been explored to address key mechanistic issues in the rhodium-catalyzed C-H insertion of carbamates and sulfamates (Scheme 17.32) [99]. A pathway involving initial condensation between substrate 96 and PhI(OAc)2 to form iminoiodinane 97 was envisioned in the original design of this chemistry. Coordination of 97 to an axial site on the rhodium dimer would promote nitrene formation and the ensuing C-H insertion event Surprisingly, control experiments with PhI(OAc)2 and sulfamate 96 (or analogous carbamates) give no indication for a reaction between these two components. 

Apart from the azirine pathway, a vinylnitrene 526 was postulated as a possible intermediate in the reaction (Scheme 14). The nitrene may be formed by a base-promoted elimination of the leaving group on the nitrogen and gives rise to the 277-azirine by electrocyclization (nitrene insertion) and, in view of current data, this pathway cannot be excluded. 

JCS(P1)1587], In some case, depending on substituents, a concomitant pathway proceeds via extrusion of nitrogen from the azido species 470. In this way, the resulting nitrene 472, and then the rearranged carbodiimide species, would explain the concomitant formation of aminotriazoles 473... 

Nitration opens up another pathway to metabolic activation. Nitro-PAHs are wide-spread environmental pollutants that are mutagenic and carcinogenic. Metabolism of nitro-PAHs could occur via nitro-activation (reduction to hydroxylamine, eventually leading to nitrenes that can bind to nucleotides) and/or by ring oxidation and formation of DEs. ... 

Azolines of type (13) undergo thermal decomposition in an analogous way to that already discussed for azolones (see Section 4.14.5.2) (Scheme 19). Path (i) is followed by those azolines having Z = S and path (ii) by those with Z = O. Path (i) is a typical retro-1,3-dipolar cycloaddition process, via an intermediate nitrile sulfide, while path (ii) might involve an acyl (Y = Z = O) or thioacyl (Y = S, Z = O) nitrene intermediate (136), which in turn rearranges to iso(thio)cyanate. However, no systematic attempts to trap this possible nitrene intermediate seem to have been made, and so a concerted pathway for the fragmantation cannot be ruled out. 

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