High Regioselectivity in Polar Additions to 1,6‐Diazacyclodeca‐3,8‐diynes

The reactions of 1,6‐dialkyl‐1,6‐diazacyclodeca‐3,8‐diynes ( 9, a = CH 3 , b = C 2 H 5 , c = i ‐C 3 H 7 ) with HCl, H 2 O and CH 3 OH have been investigated. The reaction of 9c with HCl selectively gives N,N′ ‐diisopropyl‐4‐chloro‐1,2,3,5,6,7‐hexahydro‐2,6‐naphthyridine ( 13c ) in quantitative yield. Investigation of this reaction at different temperatures allows the activation parameters for the process to be derived (Δ H ≠ = 24 ± 1 kcal · mol −1 , Δ S ≠ = – 9 ± 2 cal · mol −1 · K −1 ). The regioselective reaction of 9c with methanol affords a quantitative yield of N,N′ ‐diisopropyl‐4‐methoxy‐1,2,3,4,5,6,7‐hexahydro‐2,6‐naphthyridine ( 29c ). Addition of water to 9a in the presence of H 2 SO 4 gives N,N ‐dimethyl‐7‐oxo‐1,2,3,4,5,6,7,8‐octahydro‐2,6‐naphthyridine ( 28a ) in low yields (15%). If the addition of water is carried out in the presence of Hg 2+ , the yield of 28a is increased considerably. The mechanisms of all three reactions are discussed and those involving electrophilic addition (Ad E 2) are favored.