nium chloride couples with 3,8-diamino-5-ethyl-6-phenylphenanthridinium salts to give a mixture of a red diazoamino-(11; R = m-amidino) and a purple aminoazo-compound (V; R = m-amidino), in proportions which vary with the pH of the reaction medium. The diazoamino-compound is formed by reaction of the diazonium salt with the 8-amino-group of the phenanthridinium salt, and the aminoazo-compound by coupling in the ortho-position to either the 3or the 8-amino-group, probably the latter. THE coupling of 9-amidinobenzenediazonium chloride with 3,8-diamino-5-ethyl-6-phenylphenanthridinium chloride (homidium chloride) (I; R = Et, R' = H, X = C1) was first described by Wragg, Washbourn, Brown, and Hill.2 When the reaction was carried out in acetic acid-sodium acetate solution a mixture of two isomers, one red and one purple, was obtained, and these could be separated by fractional crystallisation. They were considered to be different diazoamino-derivatives of homidium chloride because of the method of preparation, and because of the evolution of nitrogen when each was heated with sulphuric acid. Structure (11; R = 9-amidino, X = Cl) was tentatively assigned to the predominant purple isomer and structure (111; R = 9-amidino) to the red isomer. Considerable differences in the infrared spectra of the two compounds rendered the existence of stable tautomers unlikely.Similar results were obtained by coupling m-amidinobenzenediazonium chloride with homidium chloride, the mixed isomers being given the name metamidium chloride. The high trypanocidal activity of metamidium ~h l o r i d e , ~~~ due largely to its red component, isometarnidi~m,~'~ prompted the present studies aimed at elucidating the structures of
1961] Berg. 404 1 786. A Xearch jor New Trypanocides. Part VI? Amidinophen yldiaxoamino-quinolinium and -quinazolinium Xalts. By S. S. BERG.mand p-Amidinobenzenediazonium chlorides couple with 4,6-diaminoquinolinium and 4,6-diaminoquinazolinium salts to give stable diazoaminocompounds which have significant trypanocidal and babesicidal activity. THE high trypanocidal activity of isometamidium [I ; R = m-C(:NH)*NH,] and its positional isomer [I; R = $-C(:NH)*NH,] has been described by Wragg et ale1 and by Berg2 These compounds were prepared by coupling of the appropriate amidinobenzenediazonium chloride with 3,8-diamino-5-ethyl-6-phenylphenanthridinium chloride. Jensch had earlier reported the condensation of mor p-amidinobenzenediazonium chloride with m-or 9-aminobenzamidine to give the corresponding diazoamino-compounds, which were active against trypanosoma and babesia infections. One of these compounds was the drug " Berenil." In view of the activity of the heterocyclic compounds described by Wragg et aZ.l and Berg2 and since 4,6-diamino-quinolines (11) and -quinazolines (111) are formally related to m-aminobenzamidine, it was decided to prepare analogous diazoamino-compounds by coupling their quaternary salts with mand p-amidobenzenediazonium chlorides.The quaternary salts (IV) used in these investigations were mentioned in various Patent Specifications which claimed a series of pyrimidinium salts related to Antrycide. Although the preparations of the intermediate quinolinium salts were described, no details were given of the synthesis of the corresponding quinazolinium salts.The basic intermediates required for the preparation of the 4,6-diaminoquinazolinium salts were 4-amino-6-nitroquinazoline (Va) and 4-amino-2-methyl-6-nitroquinazoline (Vb) .The preparation of the chloro-nitro-derivative (Vd) from 2-methyl-6-nitro-4-quinazolone (VIb) and phosphorus pentachloride was only accomplished in poor yield. The thiol (Ve), however, was obtained in good yield by the reaction of the quinazolone (VIb) with phosphorus pentasulphide in xylene. Methylation of the thiol (Ve) in aqueous sodium hydroxide gave the methyl derivative (Vf), which was fused with ammonium acetate to give the amine (Vb). Passage of a slow stream of methylamine through a solution of the S-methyl compound (Vf) in dimethylformamide at 140" gave the 4-methylamino-derivative (Vg) . The 4-ethylamino-and 4-dimethylamino-homologues were prepared similarly.Morley and Simpson failed to quaternise 4-amino-6-nitroquinazoline (Va) by prolonged *
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