Diaziridines synthesis

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

A novel principle of diaziridine synthesis was found in nitrogen extrusion from tetrazolines (275). Af-Aryldiaziridines (276) almost unaccessible by older procedures thus become available (74CL185). 

The reactions of chloramine are not generally successful with N-chloroalkylamines. Therefore it was surprising that the diaziridine synthesis occurred smoothly from aliphatic Schiff s bases and V-chloro-alkylamines [Eq. (33), Table VII]. As can be seen from examples... 

The majority of diaziridine syntheses proceed by intramolecular electrophilic amination in a geminal compound 84/ ° an aminallike °° compound from an amine, a carbonyl compound, and an electrophilic aminating agent like chloramine or hydroxylamine-O-sulfonic acid. The different ways of diaziridine synthesis differ mainly in the timing of the build-up of this geminal intermediate 84, from which the diaziridine 85 is isolated. 

In the steroids diaziridine formation occurs most successfully in the sterically unhindered 3-position, less favorably in the 2-position, in which formation of an aminal-like intermediate is hindered by 1,3-diaxial interaction with a methyl group. In the sterically most hindered 17-position, diaziridine synthesis may be effected by formation of a Schiff base with cyclohexylamine, thus eliminating water before introduction of the aminating... 

The general pattern of diaziridine synthesis is probably also followed by three-membered ring formation from perfluorinated aminals " as well as by a diaziridine synthesis from hydrazoic acid." In the course of the difluorodiazirine synthesis of Mitsch," perfluoromethylenediamine 96 is defluorinated by ferrocene. 

A photochemical diaziridine synthesis, analogous to the photoisomerization of nitrones, was worked out at suitable azomethine imines. By the action of sunlight, 104 is isomerized to the unstable diaziridine 105 in nearly 80% yield. 

A further photochemical diaziridine synthesis starts from tetrazolines like 109, which on irradiation lose nitrogen. In particular, the almost unknown A-aryldiaziridines became accessible by this procedure. ... 

The formation of optically active 115 demonstrates that the chiral leaving group takes part in the rate-determining step of the diaziridine synthesis, which is an argument against a nitrene intermediate. 

With regard to the simple diaziridine synthesis under large-scale conditions from ketone, ammonia, and chlorine, - some patents claim a direct preparation of hydrazine products by reaction of diaziridines with suitable reagents. For example, hydrazine dicarboxylic acid diamide is obtained directly from 3-ethyl-3-methyldiaziridine and urea in acidic so-lution. The reaction conditions, however (some hours at 70°-80°C), point to acid hydrolysis prior to reaction with urea. 

Besides the dehydrogenation agents silver oxide and bichromate, described in the first papers on diazirine synthesis, there has been application of bromine, iodine, and t-butyl hypochlorite. Chloramine, which is used as aminating agent in diaziridine synthesis, may act as a dehydrogenating agent when applied in excess, e.g., in reactions of simple aliphatic ketones or steroid ketones. ... 

Diaziridine synthesis from chloramine, ammonia and (excess) aldehyde. In the presence of excess aldehyde formation of bicyclic triazolidines takes place (see 1st edition). 

---