Cyclic and Acyclic Azaperoxides

in this promising and intriguing field of chemistry, in the present review, we attempted to give a critical account of the achievements of both foreign and Russian researchers engaged in the synthesis and studies of the properties of three-, four-, five-, six-, and eight-membered cyclic and acyclic amino-peroxides with the goal of integrating published results. Three-Membered Aza-Peroxides The simplest cyclic peroxide derivatives are composed of a 3-membered ring consisting of one nitrogen and two oxygen atoms. These dioxaziridine rings can be formed both from nitro compounds [RN (O) O] and from nitroso O-oxides (RNOO) (Scheme 1). Dioxaziridines 1 (aza-dioxiranes) have not been isolated in a pure state, but have been identified as unstable intermediates in solutions in 2-methyltetrahydrofuran at 77 K [2] or acetonitrile at 298 K [3]. Abstract The review integrates and systematically describes the data on the synthesis of three-, four-, five-, six-, and eight-membered cyclic and acyclic amino-peroxides.


Introduction
The enhanced interest in organic peroxide compounds is caused by their broad scope of applications, first of all, in chemical and pharmaceutical industry and in laboratory practice. A real breakthrough in the synthesis of peroxide compounds was made after the discovery of the antimalarial activity of peroxides, which is utilized in highly efficient medicinal drugs (artemisinin, artesunate, artemether, dihydroartemisinin). The advances in the peroxide chemistry and pharmacology stimulated the research related to the synthesis of heteroatom-containing peroxides. Out of heteroatomcontaining peroxides, attention of researchers is focused on aminoperoxides. This enhanced interest in aza-peroxides is attributable to the fact that many natural compounds (verruculogen, dioxetanone) and antimalarial agents (RKA182 and OZ439) contain aza-peroxy moieties in the molecules. The extensive biological activity of nitrogen-containing peroxides promoted active research on the development of synthetic routes to new classes of acyclic and cyclic amino-peroxides.
It is noteworthy that a compound containing both a nitrogen atom and a peroxide group in the molecule was first mentioned in the world literature back 1900 [1]. Despite more than a 100year history, amino-peroxides remain poorly studied because of Dioxaziridines are unstable at room temperature. Most often, they are detected by UV spectroscopy. The key methods used to generate dioxaziridines are photooxidation of aryl azides and О-substituted diazeniumdiolates according to Scheme 1. The main representatives of dioxaziridines and methods for their generation are summarized in Table 1.
1,2-Dioxetanes 2 without nitrogen atom in the ring are among the most readily accessible four-membered peroxide heterocycles, which are synthesized by treatment of alkenes with singlet oxygen [11,12]. Adamantyl-and alkoxy-substituted 1,2-dioxetanes are most stable, whereas other derivatives easily decompose to carbonyl compounds [13]. A similar decomposition pathway should be expected for 1,2,3-dioxazetidines 3, which are generated upon the reaction of singlet oxygen with imines [14,15]. This reaction was first studied in relation to treatment of benzophenone oxime with singlet oxygen to give the oximate anion and О-methyl ether 4 (Scheme 2) [16].
However, C=N containing compounds are not always able to be converted by this photooxidation mechanism. The photooxidation of acyclic ketoximes, aromatic aldoximes and ketoximes, and α-oximino ketones yields the corresponding aldehydes resulting from the competing oxidation of the С=С bond [17]. Amidoximes behave in a similar way, but in this case, the anionic species react with oxygen to give nitriles and amides (via intermediate acyclic peroxide derivatives) rather than 1,2,3-dioxazetidines [18]. Another reaction pathway to the intermediate formation of 1,2,3-dioxazetidine 5 involves, instead of singlet oxygen, UV-induced photooxidation of N-methoxy-4-methoxyphenyl-4'-methylphenylmethanimine in the presence of 9,10-dicyanoanthracene as a photosensitizer (Scheme 3) [19,20]. The 1,2,3-dioxazetidine 5 thus formed decomposes to give diaryl ketone and methyl nitrite with photoisomerization of the C=N double bond [19]. owing to the reaction of singlet oxygen with imidazole or histidine [22], which involves the step of endoperoxide formation [23,24].

Membered Aza-Peroxides
The ozonation and photooxidation of appropriate unsaturated compounds are the major methods for the preparation of the

Scheme 29:
The formation of the nitrone-incorporated cyclic peroxides.