Heterocyclics azirines

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

The participation of a single double bond of a heterocycle is found in additions of small and large rings azirines (Section 5.04.3.3) and thietes (Section 5.14.3.11) furnish examples. Azepines and nonaromatic heteronins react in this mode, especially with electron deficient dienes (Scheme 16 Section 5.16.3.8.1). 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

A particularly interesting system where nitrogen is lost cheletropically after formation of the initial [4 + 2] cycloadduct involves the thermal reaction of azirines with tetrazines (82) (74CC45, 74TL2303, 74CC782, 75JHC183). A variety of heterocyclic products are produced depending on the structure of the azirine and tetrazine used and the reaction conditions. 

In contrast to the well-defined photochemical behavior of 1-azirines the thermal reactions of these compounds have been studied less thoroughly (68TL3499). The products formed on photolysis of azirines can best be rationalized in terms of an equilibration of the heterocyclic ring with a transient vinylnitrene. Thus, products formed from the thermolysis of azirines are generally consistent with C—N cleavage. For example, the vinylnitrene generated from the thermolysis of azirine (149) can be trapped with phosphines (72CCS6S). 

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). 

The protonated azirine system has also been utilized for the synthesis of heterocyclic compounds (67JA44S6). Thus, treatment of (199) with anhydrous perchloric acid and acetone or acetonitrile gave the oxazolinium perchlorate (207) and the imidazolinium perchlorate (209), respectively. The mechanism of these reactions involves 1,3-bond cleavage of the protonated azirine and reaction with the carbonyl group (or nitrile) to produce a resonance-stabilized carbonium-oxonium ion (or carbonium-nitrilium ion), followed by attack of the nitrogen unshared pair jf electrons to complete the cyclization. 

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... 

NMR, 3, 542 oxidation, 3, 546 phosphorescence, 3, 543 photoelectron spectra, 3, 542 photolysis, 3, 549 reactions, 3, 543-555 with alkenes, 3, 50 with alkynes, 3, 50 with IH-azepines, 3, 552 with azirines, 3, 554 with cyclobutadiene, 3, 551 with cyclopropenes, 3, 550 with dimethylbicyclopropenyl, 3, 551 with heterocyclic transition metal complexes, 7, 28 29... 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

R] Deyrup, 1. A. In Small Ring Heterocycles, Part 1, Aziridines, Azirines, Thiiranes, Thiirenes Hassner, A., ed. John Wiley Sons New York, 1983, Chapter 1, ppl-214. 

It is known that unsaturated three-membered nitrogen heterocycles display tautomerism involving nonaromatic and antiaromatic (i.e., Air systems) forms. In all cases, the nonantiaromatic tautomer is the most stable 1-azirine la and 1-diazirine 2a. Nonetheless, antiaromatic tautomers are known, for instance, triazirines 3. 

Bis(trifluoromethyl)-substituted 1,3-heterodienes are a rich source of heterocycles through cycloadditions, for example, with ketenes (86CZ83) and azirines [89JFC(42)51] to give dioxazines and triazepines, respectively. 

Azirines are the most strained three-membered aza-heterocycles. Remarkably, these highly strained types of molecules occur in nature, namely azirino-mycin 14 and dysidazirine 15 (Fig. 1). 

Independent work by Schmid93 and by Padwa94 on the photochemistry of 2H-azirines has shown that irradiation of such systems leads in the first instance to the formation of nitrile ylids (nitrilium betaines). Subsequent 1,3-addition to a variety of dipolarophiles affords five-membered heterocycles. These additions take place in a stereospecific and regioselective manner thus, irradiation of the diphenyl-2f/-azirine 117 in the presence of dimethyl maleate leads to the formation of the two isomeric 1-pyrrolines... 

I.3.4.2.2. Nonaromatic Unsaturated Heterocycles Reactions of aromatic nitrile oxides with 1-azirines are followed by the ring opening of the latter to give 4-benzamidoisoxazoles 145 (314). The structure of 145 (R = 4-C1C6H4, Ar = Ar7 = Ph) was established by single-crystal X-ray analysis. A mechanism for the formation of 145 has been proposed, (see Scheme 1.29). 

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 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... 

Heimgartner and co-workers conducted a detailed mechanistic investigation of the reaction of [ NJlabeled 2,2-dimethyl-3-(dimethylamino)-27/-azirine 332 with NH-acidic heterocycles (Scheme 6.71). Based on these studies the authors proved that ring opening of 188a with 332 afforded the imidazolone 336 in which... 

Reactions related to cyclopropanation can also be carried out with (phosphino) (silyl)carbenes (I). For example, benzaldehyde reacts with la at 0 °C leading to the corresponding epoxide, again as only one diastereomer. Even more striking are the reactions with benzonitrile and tert-butylphosphaalkyne that lead initially to azirine and phosphirene. Both three-membered heterocycles subsequently undergo ring expansion reactions affording azaphosphete and diphosphete, respectively (Scheme 8.18). This reaction is a new route for the synthesis of heterocyclobutadienes, and this demontrates the usefulness of (phosphino)(silyl)carbenes (I) for the synthesis of novel species. 

Methyl I-azirine-3-acrylates 318 (R1 = H) have recently been reported to yield five-membered heterocycles, e.g., triazoles 320 (35% yield) or imidazoles 322 (62% yield), by reaction with hydrazine and formamidine (91JOC7) (Scheme 70). The mechanism postulated by the authors to account for the formation of 320 and 322 implies initial addition of the... 

Azirine derivatives 318 were shown in the same article to be precursors of triazines 324 (30-35% yield) and pyrimidines 326 (30% yield) upon treatment in DMSO with guanidine and formamidine, respectively (Scheme 71). A similar pathway to that outlined above is also invoked to explain these results thus, intermediate 323 would yield 324 by electro-cyclic ring closure, whereas 326 would be formed by heterocyclization of 325 and loss of ammonia (91JOC7). 

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