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The reaction of allyl chloride (7), at -40 °C to -20 °C, with in situ generated phenylsulfenyl chloride (6) affords exclusively the anti-Markovnikov product 1,3-dichloro-2-(phenylthio)propane (8) in 85-90% yield. Oxidation of 8 with 1 equiv of MCPBA to sulfoxide 9 followed by DBU-catalyzed dehydrochlorination yields 3-chloro-2-(phenylsulfinyl)-l-propene (Id) (70%). Treatment of 8 with 2 equiv of MCPBA yields sulfone 10 which is similarly dehydrochlorinated to 3-chloro-2-(phenylsulfonyl)-l-propene (le) (81%). The reaction of pyrrolidine enamines of cyclic ketones with Id and 1.1 equiv of triethylamine in Me2SO at 95-100 °C affords moderate yields of bicyclic keto thioenol ethers, formed via an , '-annelation-Pummérer reaction sequence, together with noncyclized, 2-(phenylsulfinyl)allylated ketone. Similar reactions with le provide good yields of bicyclic keto sulfones as approximate 1:1 mixtures of endo and exo isomers, which may be equilibrated to mixtures containing predominantly the exo compounds by treatment with methanolic sodium methoxide.

A series of substituted 2,2'-bi-1H-imidazoles and related analogues was synthesized and evaluated for inotropic activity. Structure-activity relationship studies based on a nonclassical bioisosteric approach indicated the necessity of a cyano group on one of the imidazole rings to obtain the desired pharmacological profile. 4(5)-Cyano-2,2'-bi-1H-imidazole (15a) was the most potent inotropic agent in the series. It produced a 25% increase in left ventricular dP/dt at 0.16 mg/kg iv (ED25% = 0.16 mg/kg) and increased left ventricular contractile force 60% at 1 mg/kg iv in anesthetized dogs. Compound 15a is a good inhibitor of type IV cyclic nucleotide phosphodiesterase isolated from dog heart having a potency similar to that of amrinone. Neither 5'-cyano-2,4'-bi-1H-imidazole (44) nor 4-cyano-2,4'-bi-1H-imidazole (48) demonstrated inotropic activity. In addition, the two possible 1,1'-dimethylcyano-2,2'-bi-1H-imidazoles (24 and 25) were inactive, indicating that an acidic NH as well as a cyano group are essential for inotropic activity.

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