Oxaziridine, protonated

According to a kinetic study which included (56), (56a) and some oxaziridines derived from aliphatic aldehydes, hydrolysis follows exactly first order kinetics in 4M HCIO4. Proton catalysis was observed, and there is a linear correlation with Hammett s Ho function. Since only protonated molecules are hydrolyzed, basicities of oxaziridines ranging from pii A = +0.13 to -1.81 were found from the acidity rate profile. Hydrolysis rates were 1.49X 10 min for (56) and 43.4x 10 min for (56a) (7UCS(B)778). O-Protonation is assumed to occur, followed by polar C—O bond cleavage. The question of the place of protonation is independent of the predominant IV-protonation observed spectroscopically under equilibrium conditions all protonated species are thermodynamically equivalent. 

The investigations of the UV spectra, the rate constants of hydrolysis and additional investigations of deuterium isotope and temperature effects of TV-t-butylbenzaldoxime and 2-J-butyl-3-phenyloxaziridine57 suggest a mechanism which is shown in Scheme 3. If the protonated nitrone is the intermediate in both reactions, the formation from either nitrone or oxaziridine should have no effect on the subsequent behaviour under identical conditions. 

Tables 8 and 9 and Figure 5 show that the rate data for hydrolysis of nitrone are almost identical to that for the hydrolysis of oxaziridine under all conditions of acidity at 24.2 °C. This evidence confirms that the salt of both oxaziridine and nitrone has the same kinetics on addition to water and forms products at a rate greater than that of unprotonated oxaziridine or nitrone. The decreasing rate at higher acidities is due to decreasing water activity in the acid media and is well explained by the Bunnett and Bunnett-Olsen criteria of the mechanism. The presented evidence57 is consistent with the mechanism outlined in Scheme 3, for example, a rapid protonation pre-equilibrium of nitrone (II) and oxaziridine (I) to form a common intermediate (HI) followed by slow nucleophilic attack by water and rapid decomposition to benzaldehyde and t-butylhydroxylamine.

The use of the optically active (camphorylsulphonyl)oxaziridine did not afford enantioselectivity. A possible explanation for this lack of stereocontrol lies in the mechanism proposed (Scheme 56). It involves formation of an a-amino epoxide, its nucleophilic ring opening and either loss of a proton (route a) or hydrolysis (route b) (Scheme 56). 

More recently, Usuki etal. studied, using NMR techniques, the conformation of spirocyclic oxaziridines 3 derived from substituted cyclohexanones <1995JOC8028>. Depending on substitution and on the stereochemistry, these compounds exhibit a substantial upfield shift of the cyclohexyl methylene or methane protons with a 1,3-diaxial relationship to the oxaziridine N-substituent. This effect is ascribed to a conformation that places an aromatic group over the plane of the cyclohexane ring. This conformation has also been observed in the solid state by X-ray crystallography and is further supported by molecular mechanics calculations. 

Treatment of pyridinyl cyclohexene 231 with perfluorinated oxaziridine 80 in TFA afforded dihydroxy product 232 in 72% yield <1998T7831>. The pyridine nitrogen is not oxidized under these conditions because TFA protonates the pyridine nitrogen atom. 

Similar attack of methanol on the presumed oxaziridine intermediate in the photolysis of C,N-diphenylnitrone led to the formation of 2- and 4-methoxyazoben-zenes."" The reaction converting dibenz[b,f] [l,4]oxazepine 60 to 2-(2-hydroxy-phenyl)benzoxazole 62 seems better explained by a nucleophilic substitution on protonated 61 than by the electrophilic process suggested by the authors. ... 

Treatment of C-aryl oxaziridines (e.g., 109) with dilute acid causes C—O bond fission to the corresponding nitrone 108. However, similar treatment of C-alkyl oxaziridines (e.g., 112) leads to the 1,4-dicarbonyl compound (e.g., 113) by N—O bond fission.The mode of ring opening is influenced by the stabilization of the positive charge resulting from initial protonation on oxygen. 

Acid-catalyzed hydrolysis of A-aryloxaziridines may proceed via cleavage of either the C—O or N—O bonds, depending upon the ring substitution pattern. These reactions are usually discussed in terms of initial protonation at the oxaziridine oxygen atom <77JHC1393>. Acid-catalyzed isomerization to nitrones has also been reported <64HC(19)624>. 

Acid hydrolysis of oxaziridines was investigated kinetically and found to be of first order and Ho-dependent. 2-t-Butyl oxaziridines with an alkyl or aryl group in position 3 (16) were studied. The acidity-rate-profile approximated a constant rate given by complete protonation of 16. pK values are between -1-0.13 and —1.81, rate constants of hydrolysis in dilute perchloric acid at 25°C are 43.4 x 10 min (R = p-nitrophenyl) and 1.49 x 10 min (R = phenyl). O-Protonation is assumed to be followed by C—O bond cleavage (16a). In the case of 3-alkyloxaziridines there is considerable competition from O—N bond cleavage. 

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