GRAHAM Diazirine Synthesis

An extension of the Graham method of diazirine synthesis has enabled the first synthesis of 3-carboalkoxy-3-halodiazirines (e.g., 76) <2004JOC7359>. Conversion of the amidines 74a and 74b into the corresponding N,N,N -trichloroamidines 75a and 75b was achieved through successive chlorination steps reductive dechlorination with bromide or chloride gave the diazirines 76a and 76b (Scheme 26). 

Graham recently reported a second synthesis of diazirine [Eq, (57)]. The yield reached 62%. 

Diazirines are popular precursors for the formation of carbenes and a review of their synthesis and use has addressed the Graham reaction, the diazirine exchange reaction, and radical-initiated exchange in addition to mechanistic details of the diazirine exchange.1... 

Considering the synthesis of 3-halodiazine, Graham proposed that the valence isomerization of the intermediate W-substituted 3H, l//-aziri-di-1//-diazirine to C-halosubstituted 3//-diazirine occurs either through a diazirinium ion (pathway a), or by a SN2 process (pathway b). Realization of any of these pathways could explain the formation of a mixture of 3-halodiazirine <65JA4396>. Later it was shown that in this reaction isolable chlorodiazirines, initially formed under the reaction conditions, are transformed into 3-chlorodiazirines <80CB2040>. Padwa and Eastman found two... 

The general methods of synthesis of diaziridines and diazirines were worked out by Schmitz (Equation (12)) <84CHEC-i(7)i95> and Graham (Equation (13)) <65JA4396> at the beginning of the study of these classes of compounds. 

Synthesis of diazirine. Graham devised a simple method by which it is possible to prepare pure diazirine, a colorless gas, b.p. —14°. The starting material, r-butyl-azoraethine (b.p. 65°), is the product of condensation of /-butylamine with formalde-... 

In 1960, however, Paulsen and, in the following years, Schmitz and Ohme (1961 a-c), and Graham (1962) achieved the first synthesis of diazirine. As Scheme (5-14) shows, they used methods that are completely independent of diazomethane. With ammonia and hydroxylamine-O-sulfonic acid (or NH2CI with an oxidant such as tert-h xiy hypochlorite, -C4H90C1), formaldehyde (for mono-and disubstituted diazirines other aldehydes and ketones, respectively) forms diaziridine (5.61, originally called an isohydrazone), which is then dehydrogenated to diazirine with silver oxide or bichromate (5-14). 

Graham (1962) described a direct one-step synthesis of diazirine by the reaction of difluoroamine (HNF2) with er butyl- or octyl azomethine (H2C=N —R) in CCI4 solution in a vacuum system. A yield of 62<7o was reported without any further information on mechanistic details. It seems that dealkylation and defluorination take place in the transient l-alkyl-2-fluoro-diaziridine (5.62, 5-15). 

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