2//-Azirines 5- ones

The conversion of small rings to smaller ones, without loss, is not common. 3-Chloroazetidine isomerizes reversibly to 2-chloromethylaziridine (Section 5.09.2.2.5). Flash vacuum pyrolysis can convert isoxazoles to azirines (Section 5.04.4.3). More common is the isomerization of medium-sized, i.e. five- or six-membered rings, e.g. certain succinimides (Scheme 23) (81JOC27) to azetidinediones, or bicyclic 1,2-dioxetanes to bis-oxiranes (Section 5.05.4.3.2). 

The 1-azirine ring also undergoes a number of reactions in which the heterocycle plays the role of the nucleophile. Although the basicity of the nitrogen atom in the azirine ring is much lower than in simple aliphatic amines, this system can still function as a nucleophilic reagent. One example of this involves the acid-catalyzed hydrolysis of 1-azirines to a-aminoketones (200) which represents a well-established reaction. In fact, in many reactions of 1-azirines where acid catalysis is used, formation of a-aminoketones is difficult to avoid (67JA44S6). 

Preparative routes to aziridines and 1-azirines are derived from cycloelimination processes in which one, and sometimes two, bonds are formed directly to the nitrogen atom (Scheme 1). For aziridines these include the two intramolecular cyclization pathways involving either nucleophilic displacement by the amine nitrogen (or nitrenium anion) on the /3-carbon (route a) or nucleophilic displacement by a /3-carbanionic centre on the amine nitrogen... 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

Oxirene (2) is one of a number of heterocycles in which the CH2 group of cyclopropene has been replaced by a group or element associated with Groups V or VI of the periodic table. Replacement of the CHj group of cyclopropene by an NH group gives l//-azirine... 

By analogy with the formation of3//-azepines by cycloaddition of 2//-azirines withcyclopenta-dienones, l,3-diphenyl-2//-inden-2-one (58) and its dibenzo analog 60 enter into [4 + 2] cycloadditions with 27/-azirines to give 3//-2-benzazepines 59 and phenanthro[9,10-e]azepincs 61, respectively.96... 

Recent examples of this synthesis are of two types. The first involves condensation of the activated phenol, 2-amino-4,6-dinitrophenol (346a) with 2-dimethyl-amino-3,3-dimethyl-3//-azirine (346b) (in MeCN, 0°C- 20°C, A, 24 h) to afford a separable mixture of four products, one of which was 2-dimethylamino-3,3-dimethyl-5,7-dinitro-3,4-dihydroquinoxaline (346c) ( 20% yield) and another its hydrolysis product, 3,3-dimethyl-5,7-dinitro-3,4-dihydro-2(l//)-quinoxalinone (346d) ( 8%) the mechanism of such condensations has been discussed. ... 

Komendantov et al. found that thermal decomposition of methyl diazoacetate in the presence of benzonitrile yielded two products.<73JOU431> One is the expected 2-phenyl-5-methoxyoxazole 4 in about 35% yield and the other product was methyl 3-phenyl-2//-azirine-2-carboxylate 5 in around 1% yield (Scheme 4). 

The palladium-catalyzed trimethylenemethane reaction with tropanones was reported in 1987 by Trost and Seoane and is the first example of a [6 + 3]-cycloaddition.130 Chromium-mediated [6 + 3]-cycloadditions of two types have been described-one in which the chromium complex activates the six-carbon component and one in which the chromium complex activates the three-atom component. An example of the first type involves the reaction of a cycloheptatriene-Cr(CO)3 complex with azirines to give cyclic imines in moderate yields (Scheme 40).131... 

Formation of 2//-azirines by thermal decomposition of vinyl azides has been shown to exhibit small entropy of activation and insensitivity to solvent polarity acyclic vinyl azides decompose more readily than analogous cyclic ones and it is advantageous to have a hydrogen atom cis to the azido group ( -are more reactive than Z-isomers). These results and the linear correlation found for ring-substiment effects on decomposition of a-styryl azides are consistent with a nonconcerted mechanism in which elimination of nitrogen and cyclization into a three-membered ring proceeds synchronously. 

Aromatic cyclic 7r-electron delocalization does indeed stabilize the planar structure with bond equalization (84ZOR897)—the problem is that, in addition to that effect, there may exist some others that may eventually overshadow it. Thus, the foregoing warrants the conclusion that the preference of a planar or nonplanar geometry of heterocycle depends on a number of factors including aromaticity (antiaromaticity), which may not even be the most important. In any case, this factor should not be disregarded if one wishes to obtain a correct overall energy balance. For example, aromaticity is reflected in the values of inversion barriers. Thus, for antiaromatic 2-azirine the nitrogen inversion barrier is, as was mentioned earlier, 37.7 kcal/mol, whereas in the case of its saturated... 

The reaction of 2-amino-2//-azirines (58) with 5-substituted l,3,4-thiadiazol-2(3H)-ones (59) yields dipolar 1 1 adducts as shown in Scheme 8. The reactions were carried out at room temperature in 2-propanol and the percentage yields (in parentheses) were somewhat dependent on the nature of the substituent at C(5) as follows CFj (76), CN (83), MeSO (95), CCI3 (54), MeO (84) and CF3... 

The suggestion that three-membered heterocycles (362) are involved is illustrated by the postulated generation of derivatives of IH-diazirine (315 and 345), thiiren (328), thiazirin (337), and lif-triazirine (358). These three-membered heterocycles belong to the class of 4n-antiaromatic heterocycles their possible role as reaction intermediates is of general interest. There is, however, an interesting difference between the photochemistry of sydnones (Fig. 4) and meso-ionic l,2,4-triazol-3-ones (Fig. 6). In both cases IH- azirines (315 and... 

The synthesis of tetrahydrooxazine 349 from an epoxide was shown in Equation 49. Azirines 350 and 352 have been used in the synthesis of dihydrooxazines. Scheme 39 shows the formation of 2/f-dihydrooxazine 351 <2002JOC66> from 350 and Scheme 40 the formation of 4f/-dihydrooxazin-3-one 353 from 352 <2004RCB1092>. 

In contrast, photolysis followed by y-irradiation of 3-(4-biphenylyl)-2//-azirine 105 resulted in the formation of the nitrile ylide radical anion 111 (57). Two mechanisms were suggested, either the one shown in the scheme, or via the photochemical opening of the azirine radical anion. 

TABLE 7.13. 5-(DIMETHYLAMINO)-3,6-DIHYDROPYRAZIN-2(l//)-ONES FROM REACTION OF 5(2i7)-OXAZOLONES WITH 3-(DIMETHYLAMINO)-2i7-AZIRINES... 

It was also reported " that the reaction of 4,4-disubstituted-2-(trifluoromethyl)-5(4f/)-oxazolones 251 with 2,2-dimethyl-3-(dimethylamino)-2//-azirine afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(l//)-ones 252 (Scheme 7.81). In this case, the reaction only occurs when electron-withdrawing substituents are present at C-2 of the oxazolone. 

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