SCHMITZ Diaziridine Synthesis

Modifications of the Schmitz procedure include the use of electrochemical methods <2002RJE1220> and the application of chlorine instead of chloramine for the synthesis of symmetrical diaziridines 6 (Scheme 5) <2006RCB2056>. 

The Schmitz reaction can be unsuccessful in sterically demanding environments in such circumstances, the electrophilic aminating agent reacts faster with ammonia than with hindered ketones <1965JA2665>. Consequently, the synthesis of 2-azi-camphane 64, a compound which is unobtainable under standard conditions <1996TL6647>, was achieved by slow diaziridination of camphor imine hydrochloride 63 (rather than camphor itself) with hydroxylamine-O-sulfonic acid (HOSA)-ammonia, followed by iodine-mediated oxidation (Scheme 22) <2001S379>. 

Some aldehyde-derived diaziridines are unstable and hamper the Schmitz synthesis of the corresponding diazirines <1975J(P2)686>. A one-pot derivative of the standard Schmitz reaction has been developed to circumvent such problems, in which an intermediate diaziridine is stabilized by a trimethylsilyl group <2000TL795>. Treatment of the aldehydes 68a-c with LiHMDS, then HOSA, gave the silicon-stabilized diazirines 69a-c. In situ oxidation with f-butyl hypochlorite generated the diazirines 70a-c in moderate yields (Scheme 24). 

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. 

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). 

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