A number of the title compounds are quite effective against Plasmodium berghei in mice. The most active members of this group are disubstituted and bear CFa groups or a combination of CF3 and halogen at positions 3 and 6.None of the 9-phenanthrenemethanols caused photosensitization in the test animals.Many of these compds are curative at 40 mg/kg and some at 20 mg/kg.

and 5% methanol, v/v). Commercial Raney nickel was purchased from W.R. Grace Co. (no. 30). Silica gel was purchased from EM .5-Hydroxy-6-methoxy-4-methyl-8-nitroquinoline (2). 4-Methyl-5,6-dimethoxy-8-nitroquinoline4 (6.21 g, 25 mmol) was dissolved in EtOH (100 mL) containing concentrated HC1 (4.7 mL). The mixture was heated under reflux for 21 h, cooled to 10 °C, and filtered. The solid was washed with cold (10 °C) EtOH (18 mL), followed by petroleum ether (15 mL), and air-dried to yield 5.41 g (92%) of the title compound, mp 253-257 °C dec.Anal. (CuH10N2O4) C, , N.5-Chloro-6-methoxy-4-methyl-8-nitroquinoline (3). A solution of the above 5-hydroxyquinoline (5.25 g, 0.022 mol) in P0C13 (75 mL) was heated at 80 °C for 2 h. The reaction mixture was poured onto ice and basified with excess NH4OH. The tan solid was filtered to give 5.8 g of crude product. This material was purified via column chromatography over silica gel and eluted with CHC13. The fast-moving yellow band was collected and concentrated to give 3.9 g (69%) of the title compound, mp 167-169 °C. Anal. (CUH9C1N203) C, H, Cl, N.6-Methoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxyjquinoline (4a). To a solution of 3-(trifluoromethyl)phenol (4.1 g) in 2-ethoxyethanol (45 mL) containing KOH (1.37 g) was added the above 5-chloroquinoline (5.7 g, 0.023 mol). The mixture was heated at reflux for 8 h and allowed to cool overnight. The solid was filtered and washed well with cold EtOH to give 5.9 g (69%) of the title compound, mp 206-208 6C. An analytical

Thirty-two 5-alkoxyprimaquines have been synthesized and evaluated as blood schizonticides (Plasmodium berghei, mouse) and tissue schizonticides (Plasmodium cynomolgi, monkey). Several of these compounds were extremely active in both screens. Such a broad spectrum of antimalarial efficacy offers the possibility of a single drug that could cure the various relapsing and nonrelapsing malarias.

Various 5-phenoxy derivatives of primaquine have been prepared which are more active and less toxic than the parent compound in murine and monkey antimalarial screens. An improved method for the phthalimido alkylation of amines is described.

A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered.