1,2,4-Triazolo [3,4-alphthalazines have been shown to possess antihypertensive'-+, tuberculostatic3, antiinflammatory5, hypotensive6", and cardiovascular' activities. We have previously described the synthesis"", and conformational analysis',", as well as some of the biologicaP" activities and industrial""' applications of 3-(polyhydroxyalkyl)-1,2,4-triazolo [3,4-ulphthalazines. In this paper we describe new routes for the synthesis of these compounds.
RESULTS AND DISCUSSION
We have previously synthesized acyclic 1,2,4-triazolo[3,4-ulphthalazine C-nucleoside analogs by the dehydrogenative cyclization of hydrazones derived from monosaccharides and cyclic amidrazones, namely 1-hydrazinophtalazine~?lo. Some monosaccharide hydrazonesi3 derived from the other cyclic amidrazones such as 2-hydrazinoquinoline, 2-hydrazino4-methylquinoline (2_hydrazinolepidine), 2-hydrazinobenzothiazole, and 2_hydrazinopyridine, however, were resistant to such a dehydrogenative cyclization even under catalytic conditions13. We decided, therefore, to direct our attention to derivatives other than hydrazones which possess better leaving entities than hydrogen. Hydrazides derived from aldonic acids and cyclic amidrazones seemed to us to fulfil this requirement since their dehydrative cyclization is expected to be much more facile than the dehydrogenative cyclization of the hydrazone congeners. In this paper we describe two routes for the synthesis of these hydrazides and their cyclization to the title compounds.
Reaction of l-hydrazino-4-phenyIphthalazine4,'4
(2) with o-glucono-1,5lactone (4) or of 1 -chloro-4-phenylphthalazine'4 (6) with D-gluconic acid hydrazidei4*" (8) gave one and the same product. This product showed C=N and OH absorptions, its 'H-n.m.r. spectrum showed signals of nine aromatic protons in addition to the pentahydroxypentyl chain protons and hydroxyl protons, and it gave a satisfactory analysis * To whom correspondence should be addressed.