Synthesis of 3,6-diazahomoadamantane

Abstract

Condensation of 1-phenylsulfanylpropan-2-one with 1, 3,6,8-tetraazatricyclo[4.4.1.1 3,8 ]dodecane gave 1-phenylsulfanyl-3,6-diazahomoadamantan-9-one which was reduced to 1-phenylsulfanyl-3,6-diazahomoadamantane, and the latter was subjected to desulfurization over Raney nickel to obtain previously unknown 3,6-diazahomoadamantane. Heating of 9-phenyl-3,6-diazahomoadamantan-9-ols with Raney nickel resulted in reduction of the hydroxy group with formation of 9-phenyl-3,6-diazahomoadamantanes.By condensation of methyl ketones with 1,3,6,8-tetraazatricyclo[4.4.1.1 3,8 ]dodecane [1] and subsequent Wolff-Kishner reduction of the resulting 3,6-diazahomoadamantan-9-ones we obtained a number of 3,6-diazahomoadamantane derivatives substituted at the bridgehead position [2][3][4]. In the present communication we report on the synthesis of 3,6-diazahomoadamantane in a similar way. For this purpose, as initial ketone we used 1-phenylsulfanylpropan-2-one (I); its condensation with 1,3,6,8-tetraazatricyclo-[4.4.1.1 3,8 ]dodecane in propan-2-ol afforded more than 60% of 1-phenylsulfanyl-3,6-diazahomoadamantan-9-one (II) (Scheme 1). δ C 65.63 and 59.45 ppm from four bridging methylene carbon atoms.Ketone II was reduced to 1-phenylsulfanyl-3,6-diazahomoadamantane (V) in two ways: (1) through 1-phenylsulfanyl-3,6-diazahomoadamantan-9-one hydrazone (III) according to Wolff-Kishner and (2) by reduction of 1-phenylsulfanyl-3,6-diazahomoadamantan-9-one p-tolylsulfonylhydrazone (IV) with sodium tetrahydridoborate in acetic acid [5] (Scheme 2). Desulfurization of 1-phenylsulfanyl-3,6-diazahomoadamantane (V) by heating over Raney nickel according to the procedure described in [6,7] gave previously unknown unsubstituted 3,6-diazahomoadamantane (VI) [8] which was isolated as a readily sublimable white crystalline substance with mp 250-251°C.In the 1 H NMR spectrum of diazahomoadamantane VI, the NCH 2 CH 2 N ethylene fragment gave rise to