Methods have been developed for the synthesis of 3-cyano-5,8-ethano-5,6,7,8-tetrahydro-l,5-naphthyridine-2(iH)-thione and 2-allyl-(and 2-cyclohexen-l-yl)thio-1,5-naphthyridines, and their structures have been studied. X-ray diffraction examination has shown that these compounds contain a disordered contact between the free electron pair of the pyridine nitrogen and the ~-bond of the allyl grouping, so that they react stereoselectively with halogens to give thiazolo[3,2-a]-l,5naphthyridinium salts.
We have shown previously [i, 2] that electrophilic quaternization of 2-allyl-(and 2cyclohexen-l-yl)thio-(and seleno)pyridines to give thiazolo-(and selenazolo)[3,2-a]pyridinium salts proceeds stereoselectively as the trans-reaction. It was assumed that the high stereoselectivity of the reaction was favored in the transition state by donor-acceptor interactions between the p-orbital of the pyridine nitrogen, the w-bond of the allyl system, and the positively charged dipole of the halogen molecule.
We now report the preparation of 2-allyl-(and 2-cyclohexen-l-yl)thio-3-cyano-5,8-ethano-5,6,7,8-tetrahydro-l,5-naphthyridine and -3-cyano-2(IH)-quinuclidino[3,2-b]pyridinethione, and discuss the stereochemical features of their quaternization to thiazolo[3,2-a]-l,5-naphthyridinium salts.
Condensation of the sodium salt of 2-formyl-3-quinuclidone (I) with cyanothiacetamide in ethanol in the presence of acetic acid afforded 1,5-naphthyridine-2(iH)-thione (III). The reaction was regioselective, no other reaction products being found, owing to the electrophilicity of the sp2-hybridized carbon atoms in the NaO-~H-----C-C-----O chain in these compounds.