H-Azirine

Phenyl- 2/f-azirine 3-Phenyl-2 H-azirine 2,3,4,5,6,7,8 a-Octa-hydroquinoline ... 

Synonyms Aminoethylene Azacyclopropane Aziran Azirane Aziridin Aziridine 1H-Azirine, dihydro- Dihydroazirene Dihydro-1 H-azirine Dimethyleneimine Dimethylenimine El Ethirydine Ethylenimine Ethylimine Empirical C2HSN... 

By means oforganocatalytic methods, it is also possible to synthesize 2 H-azirines, which are the smallest heterocycle containing a C=N in a three-membered ring, and which occur in some natural products. For this purpose, the Neber reaction of several P-ketoxime sulfonates 16 catalyzed by thiourea 17 was carried out, giving the corresponding 2H-azirines 18 with good results (Scheme 27.6) [17]. This reaction was applied as a key step in the synthesis of the antipode of natural dysidazir-ine, which was achieved in five steps with 75% yield and 93% ee. 

A comparison between aziridine 4, as a model of nonaromatic structure, l//-azirine lb, l//-diazirine 2b, and triazirine 3 using 6-31G /MP3 calculations leads to the following values for the N-H inversion barriers 4, 86.2 (experimental value 80 kJ mol ) lb, 190.4 2b, 160.2 and 3, 246 kJ mol [89JCC468].Tlie difference in inversion barrier values between lb and 2b was attributed to a decrease in the antiaromaticity of the latter. Tire antiaromaticity of lb was examined subsequently by the same authors [89JST(201)17]. 

Diels-Alder cycloaddition of 2/f-azirines 23 with cyclopentadienones provides 3//-azepines 25 in excellent yields by electrocyclic ring opening, with concomitant loss of carbon monoxide, of the initially formed, nonisolable cycloadducts 24, followed by a [1,5]-H shift in the resulting 2//-azepines.31 108... 

The 3//-azepines obtained by cycloaddition of azirines to cyclopentadienones (see Section 3.1.1.1.2.) are thought to arise from the initially formed 2/7-azepines by [1,5]-H suprafacial sigmatropic shifts.31-108 In contrast, 1/Z-azepine 9 results from the thermal rearrangement of the nonisolable 2//-azepine-2-carboxylate 8.13 Presumably, the 1 //-azepine is stabilized, relative to the 3//-isomer, by intramolecular hydrogen bonding between the NH and the adjacent ester group. 

Aminobenzylamine (1, R1 = H) reacts with benzil in refluxing acetic acid for 24 hours to give the yellow 2,3-diphenyl-5//-l,4-benzodiazepine (2) in 47% yield, but the reaction is not general. However, 2-chloro-2//-azirines function as diketone equivalents, yielding the benzodiazepines 3, when treated with equivalent amounts of the diamines 1 in pyridine at 20 C. Further details were not reported.192... 

A refluxing solution of 3-phenyl-2//-azirine (0.468 g, 4 mmol) in toluene (10 mL) was treated with 3,6-diphcnyl-l,2.4.5-tetrazine (0.702 g, 3 mmol) in toluene (10 mL) and the solution was boiled under reflux for 22 h. On cooling, the mixture deposited an orange precipitate, which was filtered off and washed with pentane. Further product was obtained from the mother liquor by chromatography (silica gel). The combined solids were recrystallized (benzene/pentane) to give the product yield 0.664 g (68%) orange plates mp 210 C. 

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. ... 

The second type is examplified in the condensation of 1,2-benzenediamine with dimethyl 3-bromo-3//-azirine-2,3-dicarboxylate to give dimethyl 2,3-quinoxaline-dicarboxylate (347) (Me2NCHO, 20°C, ultrasound, 2 h 69%) analogs were made likewise. 

Interestingly, both invertomers of the obtained M-chloroaziridines 16 were clearly observable in the H-NMR spectrum and they could even be separated by chromatography. The dehydrochlorination was investigated with a variety of bases however, the resulting yields were disappointingly low. Only for R = Ph, a yield of 39% of azirine 17 was obtained using DBU as the base, in all other cases the yields were lower [22]. Davis et al. [23] successfully applied the -elimination of the sulfinyl group in chiral non-racemic N-sulfinylaziridines (Scheme 9), whereby the eliminated sulfenate was trapped by an excess of methyl iodide, which facilitated the isolation of the desired product (18). 

The formation of product 68 from 67 can readily be explained as depicted in Scheme 50. For R = H, R = Ph, this reaction was also performed with enantiomerically enriched azirine ester in product 68 this chirality was retained [27b, 70]. 

The lipase-catalyzed resolution of (2/ , 35 )-3-methyl-3-phenyl-2-aziridine-methanol ( )-H by using the low-temperature method gave synthetically useful (2/ ,35 )-ll and its acetate (2S, iR)- a with (25 )-selectivity E = 55 at —40°C), while a similar reaction of (2/ , 3f )-3-methyl-3-phenyl-2-aziridinemethanol ( )-12 gave (25,35 )-12 and its acetate (2/ ,3/ )-12a with (2/ )-selectivity E = 73 at —20°C) (Scheme 2). Compound ( )-ll was prepared conveniently via diastereos-elective addition of MeMgBr to t-butyl 3-phenyl-2//-azirine-2-carboxylate, which was successfully prepared by the Neber reaction of oxime tosylate of t-butyl... 

The presence of a 2-substitutent in 3-phenylazirines (17, R —H in Scheme 21) modifies the mode of reaction with molybdenum carbonyl.47 In contrast to pyrazine formation for (17, R =H see Section V,C,2), the alkenyl azirine (18, Scheme 22) is transformed in excellent yield into 2-phenyl-5-carboxy-methylpyrrole. This product probably arises by intramolecular cyclization within an intermediate dienylnitrene intermediate, and related reactions have been devised to synthesize isoxazoles (see Section IV,E,2) and pyrazoles (see Section IV,D,1).47 The molybdenum carbonyl-promoted formation of 2,5-disubstituted pyrroles47 has analogy in uncatalyzed thermal, but not photochemical decomposition of 3-phenyl-2//-azirine 2-acrylate.49... 

P Wipf, H Heimgartner. 2. Synthesis of peptides containing a,a-disubstituted a-amino acids by the azirine/oxazolone method. Helv Chim Acta 73, 13, 1990. 

It was found that the azirine-nitrile ylide isomerization was a completely reversible process. The unlabeled nitrile ylide showed a prominent band at 1926 cm that underwent a 66-cm shift with N substitution. This shift was interpreted as being consistent with an allene-like skeleton (8) rather than the alternative pwpargyl-like stmcture (9). This conclusion was supported by the spectra from the C- and H-labeled variants. Warming the nitrile ylide in a xenon matrix from 12 to 82 K provided no new absorptions suggesting that the allene-like structure may also be adopted in solution. Some absorption spectra for benzonitriho benzylide (DPNY) and some substituted benzonitrilio methylides obtained via pulsed-laser photolysis of azirines are given in Table 7.1 (5). 

Much work has been done since the early 1980s on the detailed investigation of the azirine-nitrile ylide interconversion using pulsed-laser photolysis. Thus the azirines 103 (R =R =Ph, R =H R =Me, R = R =Ph R = p-napthyl, R = Me, R = H), on irradiation in isooctane, gave intense long-hved absorptions (250-400 nm) attributed to the nitrile ylides 104 (44). Quenching studies with electon-deficient alkenes led to the determination of absolute rate constants that were similar to those reported earlier for steady-state trapping experiments. The nitrile ylide-olefin reactions are discussed in more detail in Section 7.3.1. 

Theoretical work on the unsubstituted azirine-nitrile ylide system indicates that the latter is formed directly from the nn excited 5i state of the azirine via an SfSo conical intersection (52). Wavelength-dependent experiments using 3-phenylazirine (103) (R =Ph R, R = H) showed that the nitrile ylide is formed only via n—% ) excitation (248.5 nm) while excitation at 308 nm (ti—ti ) leads to a different transient attributed to a triplet state (5). In the case of 2,3-diphenylazirine, the nn and nn states were found to be nearly degenerate and no wavelength-dependent... 

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