N-methylisatoic anhydride

In the sjmthesis of evodiamine effected by Asahina and Ohta,i N-methylanthranilic acid was converted by ethyl chloroformate into N-methylisatoic anhydride, which, on treatment with 3- -aminoethylindole, furnished 3-/3-o-methylaminobenzoylaminoethylindole (III), and this with ethyl orthoformate at 175-180° gave dZ-evodiamine, m.p. 278°, convertible by boiling alcoholic hydrogen chloride into Zsoevodiamine, m.p. 147°, as shown above. 

The title compounds were also synthesized from quinazoline precursors through the formation of their 1,4-oxazine rings. N-Methylisatoic anhydride was first condensed with ethanolamine to give N-(2-hydroxyethyl)-2-methylaminobenzamide (580). Cyclization of the latter with ethyl pyruvate gave quinazoline derivatives 581 which, upon hydrolysis and dehydrative cyclization with l-methyl-2-chloropyridinium iodide, afforded the l,4-oxazines[3,4- ]quinazoline (582) (8QJHC1163). 

Hydroxy-l-methyl-3-prenyl-2-quinolones, cf. (22), are key intermediates in the synthesis of quinoline alkaloids, and usually are prepared in one stage from an N-methyl-aniline and diethyl prenylmalonate. Interesting new methods beginning with N-methylisatoic anhydrides, cf. (20), have been explored and briefly repor-... 

Araliopsine (62), which is present in Araliopsis soyauxii (J. Vaquette et al., Phytochem., 1975, 15, 743) and Zanthoxyllum simulans (z. Chang et al., Yaoxuc Xuebao, 1981, 16, 394 C.A., 1982, 97, 20735) has been synthesised by G.M. Coppola (J. heterocyclic Chem.,1983, 1589) by reacting N-methylisatoic anhydride with the lithium enolate (51) and treatment of the intermediate epoxide with acid. 

Quinoline, Isoquinoline, and their Benzo- and Hydro- derivatives 6- and 7- Substituted quinolines have been prepared by reaction of the appropriately substituted anilinobutenoate with the Vilsmeier reagent (Scheme 16).92 Reaction of a N-methylisatoic anhydride (70) with the lithium enolate of an acetophenone gives good yields of 2-aryl-4-quinolones (71). 93... 

Coppola (84JHC913) condensed N-methylisatoic anhydride 254 with the lithium enolate of 2,6,7,8-tetrahydro-2,2-dimethylbenzopyran-5-one 255 to... 

Likewise, chlorination of N-methylisatoic anhydride (LXXIII) affords the carbonimidoyl dichloride LXXIV in 42% yield. The position of the chlorine group in the ring has not been established... 

Dreyer and Brenner 62) isolated two new quinazoline alkaloids from seed husks of Zanthoxylum arborescens. The major compound, C17H16N2O2 exhibits a blue fluorescence on TLC. In the H-nmr spectrum the downfield aromatic quartet at 8 8.12 (J = 7.1 Hz) and a one-proton triplet at 8 7.8 (J = 7 Hz), each further split (J = 1 Hz) suggest the presence of four adjacent aromatic protons on an ortho-substituted benzene ring. The aromatic quartet farthest downfield at 8 8.12 indicates the presence of a / r/-related carbonyl group. Two two-proton multiplets (8 2.93—4.40) are consistent with the presence of a 2-phenylethyl system. Other nmr data, in light of the mass spectrum, suggest the presence of an N-methylanthranilic acid system. These characteristics could be assembled in two different ways, leading to structures (7) (Chart 1) and (31). C-spectroscopy and synthesis from N-methylisatoic anhydride and 2-phenylethylamine finally allowed elucidation of the structure. The synthetic product, l-methyl-3-(2 -phenylethyl)-lH,3H-quinazolin-2,4-dione (7) was identical with the alkaloid. 

Coppola (84JHC1569) condensed Al-methylisatoic anhydride 254 with the lithium enolate of 4,5,6,7-tetrahydrobenzofuran-4-one 356 (R = H) and obtained N-methylfuro[2,3-c]acridin-6-one 361 after dehydrogenation of the resultant 4,5-dihydrofuroacridone 360 (Scheme 70). 

N,N -Dimethylisoindigo (3) was synthesized with a yield of 37% by the reaction of 1-methylisatoic anhydride (2) with diethyl sodiumphosphonate at 140°C [3],... 

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