Aziridinyl compounds

The action of nitrous acid on the benzodiazepine A -oxide 38 gives the nitrosoamino derivative 39,234 which reacts with alcohols, ethanethiol and various amino compounds, such as hydrazines and guanidine, by replacement of the methyl(nitroso)amino group.235 Reaction with aziridine affords the aziridinyl compound 40f or the 2-(aziridin-l-yl)ethylainino derivative 40g, depending on the conditions. 

Use Intermediate and monomer for fuel-oil and lubricant refining, ion exchange, protective coatings, pharmaceuticals, adhesives, polymer stabilizers, surfactants. Alkyl-substituted forms, called alkyl aziranes, are used as intermediates and for microbial control aziridinyl compounds are also used as polymers and intermediates. 

Although the direct application of isocyanates proved to be impractical, their reaction products have been in commercial use as water repellents. Octadecyl isocyanate was reacted with ethylenimine to yield an aziridinyl compound [32-34] ... 

The reaction with cellulose is accompanied by polymerization of the aziridinyl compound. The durability of water repellency to laundering was improved by coapplying a di(azirinyl) compound, such as... 

The antitumor activity displayed by the mitosanes and many synthetic aziridines stems from their ability to act as alkylating agents which chemically modify (crosslink) DNA. For this reason, a large number have been screened for antitumor activity, the mechanism of which has been the subject of considerable research effort <75CJC289l). An excellent account of the broad spectrum of biological properties of a multitude of compounds containing the aziridinyl moiety has been published [Pg.93]

It is extremely important that the interaction of quinones with XO (Reaction (3)) is reversible that can lead to receiving erroneous results at the measurement of superoxide production by SOD-inhibitable cytochrome c reduction [28,29] (see also Chapter 27). Lusthof et al. [30] demonstrated that 2,5-bis(l-aziridinyl)-l,4-benzoquinones are directly reduced by XO. Interestingly at quinone concentrations greater than 25pmol I 1, quinones entirely suppressed one-electron reduction of dioxygen, and cytochrome c was completely reduced by the semiquinones formed. It is well known that cytochrome c and lucigenin are effective superoxide scavengers and due to that, these compounds are widely used in the quantitative assays of superoxide detection. Nonetheless, under certain experimental conditions they can be directly reduced by XO [31]. 

The highly potent compound MH3, a semi-rigid -substituted aziridinyl-steroid was chosen as template (Fig. 9.3). 

Tsunoda et al. (73BCJ3499) have reported a novel reverse Smiles rearrangement of N,N- bis-(l,3,5-triazinyl)-2-aminophenols (Scheme 25). 2,4,6-Tris(l-aziridinyl)-l,3,5-triazine is rearranged by acid into the tetracyclic compound (40 equation 16) (55JA5922). 

The reaction of phosgene [75-44-5] or thiophosgene [463-71-8] with ethyleneimine yields either a bisaziridine compound (l,l -carhonylhisaziridine [1192-75-2] on l,T-thiocarbonylhisaziridine [13163-23-0]) or a 2-chloroethyliso(thio)cyanate, depending on the reaction conditions. The former can he isomerized by catalysis with triiodide to give l-aziridinyl-2-oxazoline [19587-77-0] or l-aziridinyl-2-thiazoline [17205 18-0] (173—177). 

V-acylaziridine-2-imides to oxazoline-4-imides, followed by hydrolysis of these latter compounds, has been used586 to afford chiral / -hydroxy-a-amino acid precursors. It has been suggested587 that the observed thermal rearrangement of c/.s-aziridinyl ketone tosylhydrazones (449) to 5-alkylamino-3,5-diphenyl-l-tosyl-2-pyrazolines (450) is... 

Fused aziridines are interesting compounds owing to the fact that the strained three-membered ring can easily open and cause dipolar cycloaddition reactions as well as their photochromic properties. Therefore, most of this chapter covers the chemical and photochemical properties of bi- and tricyclic aziridines. Some properties of aziridinyl ketones are also reviewed, in particular, reactions leading to aziridinyl anils. 

For synthesis of N-substituted aziridinyl ketones, primary amines such as methylamine [11, 12, 13], cyclohexylamine [8, 11, 14, 15, 16, 17] and benzyla-mines [17, 18, 19, 20] are introduced in the reaction instead of ammonia. These reactions can be carried out in different solvents, such as alcohols, benzene, toluene, dimethylformamide, etc. On the basis of this chemistry, aziridinyl ketones containing either one or more three-membered cycles can be synthesized (e.g., compounds 7 and 10 Scheme 1.3). 

Another synthetic method for the preparation of aziridinyl ketones involves the initial modification of unsaturated ketones, with formation of /3-methoxyamino derivatives, followed by treatment with either metal alcoholates [11, 28, 29, 30, 31], or hydroxylamine hydrochloride and then potassium hydroxide [32]. An obvious drawback of this approach is the possibility of obtaining an exclusively unsubstituted nitrogen atom for the aziridinyl ketones. Among the advantages are high yields for these reactions. For example, Jin et al. [31] recorded yields of aziridine 18 of 99%. In other publications the yields of target compounds were reported to be around 90%. 

As already mentioned, besides multistage reactions there are also synthetic methods for obtaining aziridinyl ketones from unsaturated carbonyl compounds without the need for initial modification. Among such methods, the Southwick reaction consisting of the interaction of unsaturated ketones... 

The processes involving the aziridine cycle are very diverse. For instance, reactions of alkylation by alkyl halogenides [63], bromoacetic acid derivatives [29, 30] and acetoxypropene [64], are known. The use of arylboronic acids for synthesis of TV-alkyl derivatives, e.g., compound 45, is described in [63] (Scheme 1.13). The one-step reaction at room temperature of aziridinyl ketones 46 with chloroacetamides 47 and sulfur in the presence of Et3N yields mono-thio-oxamidines 48 [65]. 

Khomutov and Pashkevich [19] have established that the aziridine ring in compound 52 can open, giving rise to aminochlorobutanole 53. N-Chloro derivatives of aziridinyl ketones can be obtained by the reaction of tert-butyl hypochlorite [47] or TV-chlorosuccinimide [61]. The action of N204 on azirinochalcones in the presence of triethylamine leads to chal-cones [71]. 

Reactions characterizing aziridinyl ketones as polyfunctional compounds are also described in the literature. An example is a widely studied [11, 15, 72, 73, 74] reaction of ketones 18 with phenylhydrazine in which the main products are pyrazole derivatives 55. 

An interesting example of heterocyclization involving both the aziridine fragment and the carbonyl group is a reaction of aziridinyl ketones with ammonia and carbonyl compounds, giving rise to 3,5a-dihydro-l//-azireno[l,2-c]imidazoles. This reaction will be considered in more detail in Sects. 1.2 and 1.3. 

It was found later [94] that aziridinyl ketones do not react with aldehydes in the absence of ammonia apparently owing to the strong intramolecular hydrogen bond [96]. Kaluski et al. [94] considered a more probable mechanism where the carbonyl group of the aziridinyl ketone is first attacked by an ammonia molecule, releasing the aziridine imino group, which reacts with the carbonyl compound and subsequently cyclizes into azirenoimidazoles (Scheme 1.22). 

Pashkevich and Khomutov [111] reported the synthesis of aziridines containing polyfluoroalkyl substituents on the aziridine cycle. In the case where RF is CF3, the only reaction product is bis(aziridinyl ketone) 103 (Scheme 1.28). The results also provide information about the reaction mechanism. As well as in [107], it is assumed that the reaction proceeds via the formation of a-bromo-ketones and /5-aminoketones 101 and 102 where the next step is the intramolecular bromine substitution and heterocyclization into quinoxaline 104. But in the case where RF is CF3, the formation of the aziridine cycle is followed by the interaction of the second amino group of the diamine with another molecule of the intermediate 102, leading to compound 103. 

Besides photochromism of aziridinyl anils, possible radiochromic properties are mentioned in the literature [110, 124, 125]. In the opinion of Chebanov et al. [110, 124, 125], the most representative radiochromic compounds are the bi- and tricyclic aziridines containing polyarene fragments. To synthesize polyarene derivatives of aziridinyl anils, a modification of the Suzuki-Miyaura reaction was used (Scheme 1.47). 

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