Six-Membered Rings Containing Two Hetero Atoms Fused to One Benzene Ring

SIX-MEMBERED RINGS CONTAINING TWO HETERO ATOMS FUSED TO ONE BENZENE RING 

A miscellany of medicinal agents are based on heterocyclic systems that contain two hetero atoms. Unlike their counterparts unfused to an aromatic ring, these drugs do not show any unifying biologic activity. It is therefore likely that in most cases the 

Reaction of pyroc techol with epichlorohydrin in the presence of base affords the benzodioxan derivative, 136, (The reaction may well involve initial displacement of halogen by phenoxide followed by opening of the oxirane by the anion from the second phenolic group.) Treatment of the alcohol with thio-nyl chloride gives the corresponding chloro compound (137). Displacement of halogen by means of diethylamine affords piper-oxan (138), a compound with a-sympathetic blocking activity. 

Esterification of 136 with p-toluenesulfonyl chloride leads to the tosylate (139). Displacement of the ester with guanidine affords guanoxane (140). This drug, not surprisingly, shows peripheral sympathetic blocking activity and is therefore used in control of hypertension. 

The phthalazine ring system has yielded a pair of quite effective antihypertensive agents. Both these drugs are believed to act as vasodilators they would owe much of their effectiveness to the consequent decrease in resistance to blood flow in the periphery. Condensation of the half-aldehyde corresponding 

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