Phenanthrene methanol

The best example of the class of phenanthrene-methanols is halofantrine (66, Halfan [36167-63-2]) a dmg that is effective against chloroquine-resistant malaria and is now being evaluated in Africa. It produces temporary gastrointestinal disturbances. 

Halofantrine 1 Phenanthrene methanol Treatment of P falciparum infections... 

Halofantrine hydrochloride, a phenanthrene-methanol, is effective against erythrocytic (but not other) stages of all four human malaria species. Oral absorption is variable and is enhanced with food. Because of toxicity concerns, it should not be taken with meals. Plasma levels peak 16 hours after dosing, and the half-life is about 4 days. Excretion is mainly in the feces. The mechanism of action of halofantrine is unknown. The drug is not available in the USA (although it has been approved by the FDA), but it is widely available in malaria-endemic countries. 

Halofantrine1 Phenanthrene methanol Treatment of infections with some chloroquine-resistant P falciparum... 

Halofantrine is a phenanthrene-methanol derivative of an aminoalcohol, active against multidrug-resistant Plasmodium falciparum malaria. Halofantrine was known during World War II but was little used at that time. It is slowly and incompletely absorbed with peak concentrations 3.5-6 hours after dosing. Its absorption in its original formulation was unpredictable (SEDA-13, 820). 

The synthesis of new quinoline methanols,13,14 phenanthrene methanols,15,16 and naphthalene methanols continued, aimed at finding compounds of high activity and low phototoxicity. Against Plasmodium berghei in mice, II was active at 2.5 mg/kg and phototoxic at 100 mg/kg III was the most active of the benzoquinolines but its phototoxicity was not determined. Among the phenanthrene methanols, IV was active at 20 mg/kg and V at 1.25 mg/kg. The naphthalene methanol VI was curative against P. berghei in mice at 10 mg/kg. Phototoxicity appeared to be absent from the series. 

The diastereomers of phenanthrene methanols and quinoline methanols showed striking differences in antimalarial activity,18 postulated to relate to the distance between oxygen and the nonaromatic nitrogen atoms. No exciting new structures were described but activity was found in (4-oxo-2-oxazolin-2-yl)piperazinesl9 and 1,2,4-triazines.20... 

A choice of salts can also expand the formulation options for a material. The antimalarial agent a-(2-piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrene-methanol hydrochloride (Fig. 9) exhibited poor solubility, was delivered as an oral formulation, and required a single dosing of 750 mg (13). Seven salts and the free base were evaluated. The lactate salt was found to be 200 times as soluble as the hydrochloride salt (Table 3). This enhanced solubility would make it possible to reduce the oral dose to achieve the same therapeutic response as well as develop a parenteral formulation for the treatment of malaria. However, the case of lidocaine hydrochloride (Fig. 14) demonstrates that a compound limited to parenteral and topical formulations can be expanded to oral administration by changing to a salt form with acceptable physical properties (16). The hydrochloride salt was hygroscopic, difficult to prepare, and hard to handle. Six salts were evaluated for salt formation, solubility, and hygroscopicity. Other salts, such as phosphate, exhibited properties acceptable for dry pharmaceutical dosage forms. 

Halofantrine, a synthetic phenanthrene-methanol, is a recently introduced antimalarial drug which is a blood schizonticide. The drug is effective against chloroquine-resistant P. falciparum but has been associated with cardiotoxicity, so it must be used with caution (76). 

Refluxing of benzo[l,2,4]triazine-3-thione 86 with epichlorohydrin in the presence of triethylamine in methanol for 14 h resulted in the formation of 3,4-dihydro-2H,97/-l-thia-4a,9,10-triaza-phenanthren-3-ol 87 <2003PS797> (Equation 7). 

Fig. 16. CEC separation of naphthalene (1), fluorene (2), phenanthrene (3), anthracene (4), pyrene (5),triphenylene (6),andbenzo(a)pyrene (7) using capillary filled with CIO alkyl substituted polyallylamine. (Reprinted with permission from [86]. Copyright 1997 Elsevier). Conditions capillary 50 pm i.d., 48 cm total length, 33 cm active length, field strength 400 V/cm, carrier concentration 20 mg/ml, mobile phase 60 40 methanol-20 mmol/1 borate buffer pH=9.3...

One of the interesting molecules that has been studied in considerable detail is nor-bomadiene (80). Much of this interest has been associated with the interactions between the double bonds of the system. Thus irradiation affords quadricyclane (81). This area of study will be discussed later in this chapter. The radical cation 82 can also be formed from both norbomadiene and quadricyclane by irradiation in acetonitrile/methanol solution with the DCB/phenanthrene sensitizer system. Several products (Scheme 2) are formed in low yield and it should be noted that there is little difference in the yields of products obtained from either starting material. However, it is evident that attack by methanol occurs from the exo face32. 

Phenanthrene (5.0 mg/L) in a methanol-water solution (2 3 v/v) was subjected to a high pressure mercury lamp or sunlight. Based on a rate constant of 6.53 x 10 Vmin, the corresponding half-life is 1.78 h (Wang et al., 1991). 

AI3-00040, see Cyclohexanol AI3-00041, see Cyclohexanone AI3-00045, see Diacetone alcohol AI3-00046, see Isophorone AI3-00050, see 1,4-Dichlorobenzene AI3-00052, see Trichloroethylene AI3-00053, see 1,2-Dichlorobenzene AI3-00054, see Acrylonitrile AI3-00072, see Hydroquinone AI3-00075, see p-Chloro-rrr-cresol AI3-00078, see 2,4-Dichlorophenol AI3-00085, see 1-Naphthylamine AI3-00100, see Nitroethane AI3-00105, see Anthracene AI3-00109, see 2-Nitropropane AI3-00111, see Nitromethane AI3-00118, see ferf-Butylbenzene AI3-00119, see Butylbenzene AI3-00121, see sec-Butylbenzene AI3-00124, see 4-Aminobiphenyl AI3-00128, see Acenaphthene AI3-00134, see Pentachlorophenol AI3-00137, see 2-Methylphenol AI3-00140, see Benzidine AI3-00142, see 2,4,6-Trichlorophenol AI3-00150, see 4-Methylphenol AI3-00154, see 4,6-Dinitro-o-cresol AI3-00262, see Dimethyl phthalate AI3-00278, see Naphthalene AI3-00283, see Di-rj-butyl phthalate AI3-00327, see Acetonitrile AI3-00329, see Diethyl phthalate AI3-00399, see Tributyl phosphate AI3-00404, see Ethyl acetate AI3-00405, see 1-Butanol AI3-00406, see Butyl acetate AI3-00407, see Ethyl formate AI3-00408, see Methyl formate AI3-00409, see Methanol AI3-00520, see Tri-ocresyl phosphate AI3-00576, see Isoamyl acetate AI3-00633, see Hexachloroethane AI3-00635, see 4-Nitrobiphenyl AI3-00698, see IV-Nitrosodiphenylamine AI3-00710, see p-Phenylenediamine AI3-00749, see Phenyl ether AI3-00790, see Phenanthrene AI3-00808, see Benzene AI3-00867, see Chrysene AI3-00987, see Thiram AI3-01021, see 4-Chlorophenyl phenyl ether AI3-01055, see 1.4-Dioxane AI3-01171, see Furfuryl alcohol AI3-01229, see 4-Methyl-2-pentanone AI3-01230, see 2-Heptanone AI3-01231, see Morpholine AI3-01236, see 2-Ethoxyethanol AI3-01238, see Acetone AI3-01239, see Nitrobenzene AI3-01240, see I idine AI3-01256, see Decahydronaphthalene AI3-01288, see ferf-Butyl alcohol AI3-01445, see Bis(2-chloroethoxy)methane AI3-01501, see 2,4-Toluene diisocyanate AI3-01506, see p,p -DDT AI3-01535, see 2,4-Dinitrophenol AI3-01537, see 2-Chloronaphthalene... 

Fio. 12. Graph illustrating the dependence of the logarithm of retention factor for aromatic hydrocarbons on the carbon load of octadecyl silica bonded phases prepared from Par-tisil with octadecyhrichlorosilane. Mobile phase methanol-water (70 30) eluitest A, benzene A, naphthalene , phenanthrene , anthracene O, pyrene. Reprinted with permission from Herndon t al. (70). 

To obtain a true k in MEEKC, it is important to trace the migration of the pseudostationary phase accurately. Sudan III, timepidium bromide, and quine, which have generally been used as tracers for micelles in MEKC, could not be employed as tracers for microemulsions consisting of sodium dodecylsulfate salt (SDS) or cetyltrimethylammonium bromide (CTAB), n-butanol and heptane (12). An iteration method based on a linear relationship between log k and the carbon number for alkylbenzenes (13) seems to provide a reasonable value of the migration time of the microemulsions. Dodecylbenzene shows a migration time larger than the value calculated by the iteration method and those of other hydrophobic compounds, such as phenanthrene, fluoranthrene, and Sudan III (Table 1). Methanol and ethanol were used as tracers for the aqueous phase. 

The present method is based on the earlier described ozonolysis of phenanthrene in methanol. The reduction of the peroxidic reaction mixture with trimethyl phosphite to give diphenaldehyde, isolated as the di- -nitrophenylhydrazone, in quantitative yield has been described recently.10 The disadvantage of this method is that the dialdehyde cannot be isolated in the free state in high yield. Diphenaldehyde has also been obtained by sodium... 

A. 3,8-Dimethoxy-4,5,6,7-dibenzo-l,2-dioxacyclooctane. Theozo-nolysis of 10 g. (0.0562 mole) of phenanthrene in dry methanol is carried out as described in the diphenaldehyde preparation (p. 41). The reaction mixture is not reduced, however, but is acidified with 1-3 drops of concentrated hydrochloric acid (Note 1) and allowed to stand at room temperature for an hour and then in the refrigerator for several hours or overnight. Suction filtration yields 11.5-12.5 g. (75-82%) of crystals melting at 178-181°. Trituration with methyl ethyl ketone gives a 90-95% recovery of colorless crystals melting at 180-181° (Note 2). 

The method here described is based on the reported ozonolysis of phenanthrene in methanol, followed by conversion of the initial ozonolysis product to diphenaldehyde (p. 41), diphenalde-hydic acid, methyl diphenaldehydate (Note 6), and diphenic acid (Note 7). Diphenaldehydic acid has previously been made in low yields by oxidative decomposition of the monohydrazide of diphenic acid.3-4 The presently described method is far superior, not only in yield, but also in simplicity. 

Effect of Temperature and Solution Composition on Kioc Illustrative Example 9.4 How Much Does the Presence of 20% Methanol in the "Aqueous Phase Affect the Retardation of Phenanthrene in an Aquifer ... 

To estimate the effect of the methanol on Kid, assume that a is about 1 in Eq. 9-34. Get the of value of phenanthrene from the PAH data summarized in Fig. 5.8 using (see figure caption) ... 

Little attention has so far been paid to studying exchange energy-transfer processes in media so viscous that a steady-state is no longer established. Butler and Pilling [200] specifically sought experimental evidence for time-dependent rate coefficients of the form of eqn. (98). They chose to study triplet phenanthrene in methanol—water mixtures and used cupric chloride as the acceptor since it is readily soluble and a very efficient quencher of triplet phenanthrene. To observe even the t 1/2 dependence of the time-dependent rate coefficient, concentrations [A] > 10-2 are required that is with Re 1 nm and [A] > 10 mmol... 

Estimates of the effective encounter distance, f eff, and diffusion coefficient, D, from quenching of triplet phenanthrene by cupric ions in methanol—water mixtures (Butler and Pilling [200])... 

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