Acridine 9- chloro

The unstable dibenz[c,/][l,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous Af-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

Unstable dibenz[c,/ [l,2]oxazepines (73 R = CN, Cl) are major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (71) in benzene. No oxaziridine tautomer (72) was detectable by UV spectroscopy. 

Acridine Syntheses and Reactions. Part VI. A new dehalogenation of 9-chloro-acridine and its derivatives. Further acridine ionization constants and ultraviolet spectra. 

Chloroacridine is readily hydrolyzed in neutral and acid solutions hence it must not be exposed to the air after removal of the phosphorus oxychloride and before treatment with ammonia. I f the drying is carried out at a higher temperature, loss results through sublimation. Care should be taken to keep 9-chloro-acridine from entering the eyes, as it is distinctly irritating. 

Cyano- and 10-chloro-acridine A-oxides yield 1,2-oxazepines on photolysis in benzene (Scheme 237). When the 10-substituent is methyl the unstable 1,2-oxazepine undergoes electrocyclization to a benzisoxazoline (320). Secondary photoproducts may be formed by direct irradiation of N- oxides or by rearrangement of the primary photoproduct. 

Improved Syntheses of Acridines. Part V. The Dechlorination of 5-chloro-acridines and a new Synthesis of Acridine. 

Q lllllflCrillC [Atebrine, 3-chloro-9(4-diethylamino-l-methyl)butylamino-7-methoxy)acridine] dihydrochloride. [69-05-6] M 472.9, m 248-250 (dec), pK -6.49 (aq H2SO4), pKj 7.73 (ring NH ), pKj 10.18 (Et2N). Cryst from H2O (sol 2.8% at room temp) as yellow crystals. Slightly sol in MeOH and EtOH. Antimalarial, antiprotozoal and intercalates DNA. [Wolfe Antibiot 3 (Springer-Verlag) 203 1975.]... 

Acridine and compounds Aniline and compounds Benzanthrone and compounds Benzidine and compounds Chloro compounds... 

Of greater versatility is an extension of Albert and Royer s acridine synthesis. The first successful use of this in the quinazoline series was for the removal of the chlorine atom in 2-chloro-4-phenylquin-azoline, although it had been used previously to prepare 8-nitro-6-methoxyquinazoline in very poor yield. The 4-chloroquinazoline is converted to its 4-(A -toluene-p-sulfonylhydrazino) quinazoline hydrochloride derivative which is decomposed with alkali in aqueous ethylene glycol at lOO C (Scheme 13). The yields are high (60-70%) when R is Me, Cl, OMe but low when R is NO2, and in the latter case it is preferable to use dilute sodium carbonate as the base. This reaction is unsatisfactory if the unsubstituted pyrimidine ring is unstable towards alkali, as in 1,3,8-triazanaphthalene where the pyrimi-... 

Quinolynes are generated and behave analogously to pyridynes. The reaction of 3-bromo-4-chloro- and 3-bromo-2-chloro-quinoline with lithium amalgam in the presence of furan gives phenanthridine (83, 9% yield) and acridine (85, 0.1% yield), respectively, via 3,4-... 

An acridine with a radically different substitution pattern, interestingly, still exhibits antimalarial activity. Condensation of acetone with diphenylamine in the presence of strong acid affords the partly reduced acridine, 20. Alkylation with 3-chloro-dimethylaminopropane (via the sodium salt of 20) affords dimethacrine (21). ... 

Pyridazines continued to play a central role in the construction of new biologically active compounds. 2,7-Dihydro-3//-pyridazino 5,4,3-17 acridin-3-ones were synthesized as cytotoxic agents <05BMC1969> and 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2//-... 

Although chlorination, bromination and iodination of thiophenes by polyhalide salts require forcing conditions with the addition of zinc chloride [52], halogenation of acridine and acridone has been recorded to yield both 3-halo and 3,7-dihalo derivatives under relatively mild reaction conditions [53], However, whereas chloro-, bromo- and iodo-compounds are readily obtained from acridone, acridine only forms the bromo derivatives, as it produces stable complexes with the dichloroiodate and tetrachloroiodate salts [53]. 

Quinacrine Quinacrine, 6-chloro-9-(4-diethylamino-l-methylbntylamino)-2-methoxy-acridine (37.1.4.3), is synthesized from 6,9-dichloro-2-methoxyacridine (37.1.4.2) and aforementioned 4-diethylamino-l-methylbutylamine (37.1.1.2). The 6,9-dichloro-2-methoxyacridine (37.1.4.2) necessary for the synthesis is made in two stages. The initial reaction of 2,4-dichlorobenzoic acid and p-anizidine in the presence of copper dnst and potassium carbonate gives 2-(4-methoxyanilino)-4-chlorobenzoic acid (37.1.4.1), which upon reaction with phosphorus oxychloride turns into the necessary 6,9-dichloro-2-methoxyacridine (37.1.4.2) [33-38]. 

Beak has measured the UV spectra of 2- (0.4) and 4-hydroxypyridine (<0.1), 6-chloro-2-hydroxypyridine (0.05), 2- (<0.1) and 4-mercaptopyridine (<0.1) and acridin-5-one (>10) (73JA1700, 76JA171). A heated cell was employed with vacuum jacketed windows, over the temperature range 120-140 °C. It was thus demonstrated that these compounds exist predominantly in the form named above (the figure in brackets after each name gives the value of Kt = [NH]/[OH], or [NH]/[SH]), using the methylated compounds as model chromophores. 

Many acridines and benzacridines have been synthesized by the Bernthsen reaction (l884LA(224)l) in which a diphenylamine is heated with a carboxylic acid and zinc chloride, with or without aluminum chloride. The reaction has been reviewed (73HC(9)141), and will be outlined here. The yields are not generally high one of the better examples is the synthesis of 2-chloro-9-methylacridine (312) (63BCJ1477). In the synthesis of the... 

Oxidation of 5//-dibenz[6,/]azepines by Fremy s salt has been examined closely. At pH 7.5 the quinonoid dibenz[6,/]azepin-2-one is produced together with acridine-9-aldehyde (74CRV101). 3-Chloro-10,11 -dihydro-5//-dibenz[6,/]azepine yields a mixture of the quinoneimines (174 R=C1) and (175) which with sodium dithionite reduce to the corresponding chlorohydroxydihydrodibenzazepines (76JHC269). 

---