1-Azabicyclo butanes, reaction with

Synthesis and chemistry of substituted l-azabicyclo[1.1.0]butanes 97SL1029. Synthesis of aziridines via stereoselective reactions with imines 99PAC1033. 

Marchand and co-workers reported a synthetic route to TNAZ (18) involving a novel electrophilic addition of NO+ NO2 across the highly strained C(3)-N bond of 3-(bromomethyl)-l-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium hydroxide under reduced pressure. The product of this reaction, A-nitroso-3-bromomethyl-3-nitroazetidine (22), is formed in 10% yield but is also accompanied by A-nitroso-3-bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the ferf-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both processes achieved in one pot with an alkaline solution of sodium nitrite, potassium ferricyanide and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large scale manufacture. 

Funke has observed an interesting reaction of l-azabicyclo[ 1.1.01-butane derivative (115) with DMAD in which an azetidine derivative (117) is formed, presumably through the intermediate 116 [Eq. (19)]. 

A convenient, one-pot, two-step synthesis of l-azabicyclo[1.1.0]butane (5, R = H) from f -chlorosuccinimide is reported and its application to the synthesis of 133-tnnitroazetidine (TNAZ) is discussed <98SC3949>. Another novel and efficient synthesis of 1-aza-bicyclo[1.1.0]butane (5, R = H) and its derivatives is from 23-dibromopropylamine. The bicyclic 5 (R = H) is also useful in the synthesis of the pendant group of a ip-methylcarbapenem antibiotic <99TL3761>. The reaction of 5 (R = Et and Ph) with tosyl chloride and tosyl azide are described <98T15127,99H131>. 

The reaction of 3-substituted 1,2-diphenylcyclopropenes with 4-phenyl-4//-l,2,4-triazole-3,5-dione gave urazoles, possibly via the formation of a spiro[2-azabicyclo[1.1.0]butane-2,T-l,2,4-triazole] and subsequent ring opening. 

Synthesis of l-azabicyclo[1.1.0]butane, which contains both a four-membered and two three-membered nitrogen-containing rings ( ), follows the general route described above. As one would anticipate, ringopening reactions, one of which is illustrated, lead to products with an azetidine unit, rather than an aziridine unit. 

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