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Synthesis of Embelin, Rapanone and Related Quinones 71 (see above) was dissolved in benzene and the solution added slowly to an ethereal solution of diazomethane prepared from nitrosomethylurea (7.0 g.) and allowed to stand at 0°for sixteen hours. The solvent, together with the excess diazomethane, were removed under reduced pressure. The crude product (2.1 g.) was used directly in the following procedure.C. , Hydrolysis of 3,4,5-Trimethoxyphenyl Diazomethyl Ketone.-The 3,4,5-trimethoxyphenyl diazomethyl ketone (2.1 g.) (see above) was hydrolyzed by heating at 70°for three hours with aqueous 2% sulfuric acid (100 cc.). The solution, after cooling, was extracted with chloroform, the chloroform solution dried and the solvent removed. The resulting product was recrystallized from ether: yield, 1.5 g.,m.p. 77-78°.Anal. Caled, for CnHi.Os: OCHs, 41.1. Found: OCH3, 40.85.D. Reduction of 3,4,5-Trimethoxyphenyl Hydroxymethyl Ketone.-3,4,5-Trimethoxyphenyl hydroxymethyl ketone (1.0 g.) was dissolved in ethanol (100 cc.) and hydrogenated over copper chromium oxide (0.5 g.) at 150-160°for one hour. The bomb contents were filtered, the filtrate concentrated under reduced pressure and the resulting yellow oil distilled at 220-240°( bath temperature) (0.02 mm.): yield, 0.8 g.

IN connection with our studies of the synthesis of 5-phenyl-l,4-benzodiazepinones,1 we have prepared a series of 2-amin0-2'-fluorobenzophenones.~ These compounds undergo internal nucleophilic exchange to give high yields of the corresponding 9-acridones. In contrast to substituted 2-amino-2'-chlorobenzophenones, which, as we have verified, do not cyclize under these condition^,^ the fluorine is sufficiently activated by the orthocarbonyl group to react readily with the aromatic amine.Both solvent apd catalyst affected the yield and it was determined that NN-dimethylformamide was the preferred solvent. The use of potassium carbonate as a catalyst significantly improved the yields of the 9-acridones in all cases. The catalytic effect of other salts was not investigated. N-Substituted 2-amino-2'-fluorobenzophenones were also easily cyclized by this method, although in NN-dimethylformamide only 2-chloro-9acridone was obtained from the 5-chloro-2'-fluoro-2-toluene-~-sulphonamidobenzophenone. We were, however, able to obtain the desired 2-chloro-lO-toluene-$-sulphonyl-9-acridone directly by using 2-ethoxyethanol as solvent.ExperirnentaZ.-M. p.s were determined microscopically on a hot stage and are corrected. The acridone structure of known compounds not directly compared with authentic samples was confirmed by a comparison of experimental and published ultraviolet ~p e c t r a , ~ and by satisfactory analysis.CjGclization of 2-amino-2'-fluorobenzophenones to 9-acridones. A typical procedure is described. A solution of 2-amino-2'-fluoro-5-nitrobenzophenone (1.0 g., 3.85 mmoles) and potassium carbonate (0-65 g., 4.75 mmoles) in NN-dimethylformamide (20 ml.) was refluxed for 17 hr., cooled, diluted to 100 ml. with water, and filtered. The precipitate was washed successively with water and boiling methanol, and was dried to give 2-nitro-9-acridone (0.8 g., 87%), m. p. >350".

In these methods diphenylacetonitrile is alkylated with 1-methylformamido-2-chloropropane and with the tosyl ester of 1-chloropropanol-2 to give, respectively, 4-methylformamido-2,2-diphenyl-3-methylbutanenitrile (IV) and 4-chloromethyl-2,2-diphenyl-3-methylbutanenitrile (VIII). These nitriles are readily converted into isornethadone.Two new and direct syntheses of isomethadone are described.