Oxaziridines

The synthesis of oxaziridines from Schiff bases and peracids, as reported by Krimm, ° Emmons, and Horner and Jurgens, is still the most popular procedure for their preparation [Eq. (1)]. 

Kinetic investigations failed to distinguish between a one-step reaction of the olefin epoxidation type and a two-step reaction through an adduct such as 4. The formation of Z,E isomeric mixtures of oxaziridines from sterically definite Schiff bases supports the two-step mechanism. 

In certain cases, hydrogen peroxide alone is sufficient to prepare oxaziridines. The hydroxyoxaziridine 6 was obtained (70% yield) from 5 with hydrogen peroxide in dilute sulfuric acid at 60°C.  

There are apparently no limitations in the structure of the Schiff base. Oxaziridines were prepared from cyclic azomethines in the steroid field Schiff bases with benzazepine structures were converted into oxaziridines, first by Metlesics and Sternbach, later by other groups.The preparation of oxaziridines from imino ethers has been described in recent papers,e.g., the preparation of 7 and 8. 

Configurational stability became evident from the preparative results, when both diastereomeric oxaziridines with E-Z isomerism and optically active oxaziridines were prepared. 

Schmitz, Dreiringe mit zwei Heteroatomen, Oxaziridine, Diaziridine, cyclische Diazoverbindungen. Springer-Verlag, Berlin and New York, 1967. 

Schmitz, Trechtschlcnnye Zikly s Dvumja Geteroatomami. MIR, Moscow, 1970. 

6 Photochemistry of Three-membered Ring Heterocycles N. R. Bertonniere and G. W. Griffin, Org. Photochem. 105 (1973). 

7 Diaziridines and Oxaziridines D. J. Matland, Saturated Heterocycl. Chem. (Chem. Soc., Spec. Period. Rep.) 3, 1-91 (1975). 

An improved synthesis of 2-sulphonyloxaziridines has been reported.Oxidation of (356 R = Ph, R = 3-NO2 R = Ph, R = 4-NO2 R = Me, R2 = H or R = PhCH2, R = H) by 3-CIC6H4CO3H in the presence of a phase-transfer catalyst gives (357) (80-90%). These compounds epoxidize alkenes in good yield and with retention of stereochemistry thus trans-stilbene with (356 R = Ph, R = 4-NO2) gave the fraws-stilbene oxide (95%).  

The photochemical electrocyclic reaction of CH2N=0 to form oxaziridine has been explored on the basis of the potential-energy surfaces that are obtained by MINDO/3 Cl calculations.  

The reactions of oxaziridines with nucleophilic reagents have been 

In the presence of CsF, carbonyl difluoride combines with the oxaziridine (13.16) to form a high yield of CF3N(0Cp3)C(0)F [1834]. The result indicates that the [CF3O] nucleophile, generated from the reaction of CsF with COF, attacks the nitrogen atom, and this is confirmed, in a separate experiment, in which the salt Cs[OCF3] was employed in the reaction. 

Theoretical ab initio SCF investigations have been reported for the photochemical transformations of oxaziridine into a nitrone, into an amide, or into methanal plus nitrene.  

The cyanonitrones (358 R = H, Me, or Ph) isomerize to the oxaziridines (359) on irradiation in benzene.Prolonged irradiation, however, converts (358) or (359) into (360). A similar reaction of nitrones (361 R = H, R = Me or Pr ) gave (362) on treatment with FeS04, this eliminated the Bu group to yield pyrrolidinones (363).  

spectra of (364 R = Me, Et, Pr, Bu , or PhCH2) in EtOH and in iso-octane have been reported.The chiroptical properties of the oxaziridine chromophore were generally characterized by a positive pattern at 190—350 nm. The notable exception to this was a clear negative Cotton effect for (364 R = Pr ). The seemingly anomalous behaviour of this compound was interpreted in terms of the possible existence of solvation equilibria and conformational rotamers about the N—CHMe2 bond. The relatively new technique of Liquid-Crystal-Induced Circular Dichroism (LCICD) has been used in the 

Slanina and Z, R. Grabowski, Collect. Czech. Chem. Commun., 1979, 44, 3441. 

The reactions of ( )-(371) with lithium amide bases, e.g. LiNEt2 in THF, give rise to two products after protonation i.e., (372) (major) and (373). ° It has been concluded that the reduction product (372) arose primarily by a route involving electron transfer from the base to (371). The amide product was formed in a competing isomerization reaction involving simultaneous deprotonation and ring-opening to the anion of (373). 

The oxidation of N-alkyl or N-aryl aldimines or ketimines with f-amyl hydroperoxide in the presence of either M0CI5 or Mo(CO)6 leads to oxaziridine formation, equation (137) [184]. In benzene solution the reaction proceeds rapidly and yields are high (80-95%). The catalytic procedure is considerably more convenient than conventional methods of oxaziridine preparation. 

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The mechanism of this reaction involves an activation of the ammonia and hydrogen peroxide because these compounds do not themselves react (118—121). It appears that acetamide functions as an oxygen transfer agent, possibly as the iminoperacetic acid (41) which then oxidizes the transient Schiff base formed between MEK and ammonia (40) to give the oxaziridine (42), with regeneration of acetamide ... 

There is a scattered body of data in the literature on ordinary photochemical reactions in the pyrimidine and quinazoline series in most cases the mechanisms are unclear. For example, UV irradiation of 4-aminopyrimidine-5-carbonitrile (109 R=H) in methanolic hydrogen chloride gives the 2,6-dimethyl derivative (109 R = Me) in good yield the 5-aminomethyl analogue is made similarly (68T5861). Another random example is the irradiation of 4,6-diphenylpyrimidine 1-oxide in methanol to give 2-methoxy-4,6-diphenyl-pyrimidine, probably by addition of methanol to an intermediate oxaziridine (110) followed by dehydration (76JCS(P1)1202). 

For oxaziridines the N-inversion barrier is considerably higher than that for similar aziridines. Af-Alkyl-3,3-dialkyloxaziridines are resolvable and absolute configurations have been determined (Section 5.08.2.3.1). 

The introduction of a second heteroatom (other than sulfur) does not change drastically the absorption characteristics of small heterocycles. Oxaziridine and diaziridine are still transparent to light of wavelengths above 220 nm (Section 5.08.2.3.2). 

In the oxaziridines (1) ring positions 1, 2 and 3 are attributed to oxygen, nitrogen and carbon respectively. The latter almost always is in the oxidation state of a carbonyl compound and only in rare cases that of a carboxylic acid. Oxaziridinones are not known. The nitrogen can be substituted by aryl, alkyl, H or acyl the substituent causes large differences in chemical behavior. Fused derivatives (4), accessible from cyclic starting materials (Section 5.08.4.1), do not differ from monocyclic oxaziridines. 

Whereas oxaziridine and diaziridine were partial subjects of comprehensive theoretical studies on cyclic compounds (73MI50800), diazirine and some of its simple derivatives were the special target of quantum chemical investigations. Since diazirine, the lowest molecular weight heterocycle, has only five atoms and is of high symmetry, there was a chance for ab initio calculations, which followed some semiempirical studies. 

There were also several calculations of geometrical parameters, dipole moment and energy of oxaziridine 71MI50800). Since the parent compound of oxaziridines is unknown, comparison of calculated and experimental values is still lacking. 

X-ray analysis of an optically active oxaziridine substituted at nitrogen with the 1-phenylethyl group of known configuration led to the absolute configuration (+)-(2R,3R)-2-(5-l-phenylethyl)-3-(p-bromophenyl)oxaziridine of the dextrorotatory compound as expected, C-aryl and A-alkyl groups were trans to each other (79MI50800). 

S.08.2.3.1 NMR investigations on oxaziridines and diaziridines, configurational stability at nitrogen... 

An E-Z discrimination between isomeric oxaziridines (27) was made by NMR data (69JCS(C)2650). The methyl groups of the isopropyl side chains in the compounds (27) are nonequivalent due to the neighboring carbon and nitrogen centres of asymmetry and possibly due to restricted rotation around the exocyclic C—N bond in the case of the Z isomer. The chemical shift of a methyl group in (Z)-(27) appears at extraordinarily high field, an effect probably due to the anisotropic effect of the p-nitrophenyl group in the isomer believed to be Z. 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

Nitrogen chirality may also be produced by the action of an achiral peroxyacid on a Schiff base containing a chiral amine (75JOC3878). In this case the oxaziridine contains a configurationally known centre of chirality relative to this, absolute configurations of the centres of chirality at nitrogen and carbon, and thus the complete absolute configuration of the molecule, can be determined (see Section 5.08.2.2). 

NMR spectra of oxaziridine enantiomers may be different from each other in chiral media. In the presence of chiral arylperfluoroalkylcarbinols, shift differences of up to 0.35 p.p.m. are observed, which may be used for discrimination of enantiomers (77JOC3217). 

NMR investigations in the diaziridine field also led to the problem of inversion stability at nitrogen. Further investigations paralleled those of oxaziridines NMR investigation in solution (67CB1178) was followed by preparative separation of invertomers and finally preparation of optically active individuals. 

The inversion barrier between (28a) and (28c) is 114kJmoF , the invertomers having the same free energy by chance. NMR data of oxaziridine carbon and substituent groups of the ring for compounds (29) and (30), taken from the above publications, are as shown. 

Simple oxaziridines and diaziridines do not absorb in the near UV. Lack of absorption was one argument to distinguish between true three-membered ring structures and unsaturated open chain isomers like nitrones or hydrazones. 

An investigation of acylaziridines was carried out by comparison of IR, NMR and MS data and included some 1,2-dibenzoylaziridines as well as 2-p-nitrobenzoyl-3-phenyl-oxaziridine (68IZV1530). Amide conjugation in acylated nitrogen-containing three-membered rings is weaker than in open chain acid amides. 

The IR spectra of oxaziridines often show a band between 1430 and 1470 cm , which is assumed to be due to C—H bending (57JA5739). 

In the discussion of some mass spectra of nitrones (41), intermediate isomerization to oxaziridines was concluded from the occurrence of aldehyde fragments. 

S.08.3.1.1. Reactions of oxaziridines with conservation of the three-membered ring... 

There are only few reactions known introducing substituents to the H-bearing nitrogen of oxaziridines. (V-Alkylation of l-oxa-2-azaspiro[2.5]octane (3,3-pentamethylene-oxaziridine 52) with r-butyl chloride to give (53) was carried out for structure proof of (52). This reaction is of no preparative importance, since N-alkylated oxaziridines are easily obtained by ring synthesis. 

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