Formation of Six-membered Nitrogen Heterocycles

Piperidines are obtained from 5-amino-5-deoxy sugars by cycliza-tion with C-l their preparation therefore follows the general methods of preparation of such amino sugars. The 5-O-p-tolylsulfonyl- or 5-0-(methylsulfonyl)-pentoses constitute excellent starting-materials, as these sulfonyloxy groups can be replaced by azide, and the azides can be reduced to the 5-amino derivatives, which are capable of cyclization.240-251 The formation of piperidine 178 from 5-O-p-tolyI-sulfonyl-L-arabinose diethyl dithioacetal240 (176) and 177, and of 181 from benzyl 2,3-0-isopropylidene-5-0-(methylsulfonyl)-a-D-lyxofuranoside250 (179) and 180, are examples of this reaction sequence. 

A similar series of reactions was performed on a 6-azido-6-deoxy-2-ketose.246,252 In most of the foregoing syntheses, the piperidine formed is accompanied by the tautomeric furanose. The tautomers can, however, be separated without occurrence of equilibration (which can be induced by changing the pH of the medium). For the ketose derivative 183, the equilibrium mixture includes246 compound 184 and a dehydration product (182). The conformation and anomeric effect in these piperidines have been studied by n.m.r. spectroscopy,253 and their fragmentation pathways have been determined by mass spectrometry.254 

Piperidones of two types have been prepared from saccharide derivatives. Those of one type are lactams, exemplified by 187, obtained by oxidizing255 5-azido-5-deoxy-2,3-0-isopropyidene-/3-D-ribo-furanose (185) to 186, reducing the lactone 186 to the amine, and cyclizing this to 187. The other type comprises the 4-piperidones such as 189 this is obtained256 by oxidizing methyl a-D-arabinopyrano-side (188) with periodate, and treating the product with methylamine and 3-oxopentanedioic acid the bicyclic compound obtained from the a-glycoside differs from that from the /3 anomer. 

A similar condensation has been reported that involves the reaction of the glycosulose monohydrazone 206 with 4,5-diamino-2-phenyl-1,2,3-triazole311 to give 207. 

An oxazine has been obtained320 by oxygen participation between 

---