The chemistry of 2H-3,1-benzoxazine-2,4(1H)dione (isatoic anhydride) 4. Synthesis of 2-imino-3-indolinones

The reaction of isatoic anhydrides with potassium cyanide to form 2-imino-3-indolinones ( 2 ) is described. Acidic hydrolysis of 2 furnishes the corresponding isatins.     

The chemistry of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) 3. One step synthesis of 2,3-dihydro-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones

Reactions of N-haloalkylisatoic anhydrides with amines to produce piperidinobenzamides ( 2 ), pyrrolidinobenzamides ( 4 and 5 ), and 2,3-dihydro-6-methyl-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones ( 10 ) are described. Spectral data are also discussed.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (Isatoic Anhydride). 19. Direct formation of 2-aminobenzyl alcohols from the reduction of N-substituted isatoic anhydrides

Isatoic anhydrides 1 are easily reduced with sodium borohydride to o-(substituted-amino)benzyl alcohols 3 in good yield. Sequential reduction of N-(2-nitrobenzyl)isatoic anhydride ( 5 ) with sodium borohydride followed by catalytic hydrogenation of the nitro group affords the naturally occurring 2-(2′-aminobenzylamino)-benzyl alcohol ( 4 ) in 72% yield.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 22 . An efficient synthesis of leiokinine B

The alkaloid leiokinine B has been synthesized in one step from the reaction of N-methylisatoic anhydride and the enolate derived from 3-ethyl-2-pentanone.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)dione (isatoic anhydride). 7. Reactions with anions of active methylenes to form quinolines

The reaction of isatoic anhydrides with carbanions of various active methylene compounds is described. The isolation of 2-oxo or 4-oxoquinolines is possible by varying the functional groups flanking the methylene carbon.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 18. A short synthesis of swietenidin A

N-Methylisatoic anhydrides react with the lithium enolate of ethyl methoxyacetate at low temperatures to produce intermediates which, when cyclized, afford 4-hydroxy-3-methoxy-2(1H)-quinolinones. By this route, 3-methoxy-N-methylisatoic anhydride ( 8 ) can be converted to the alkaloid swietenidin A (2) in 71% yield.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 9. Synthesis of 2-arylquinoline alkaloids

A one-step synthesis of N-methyl-2-aryl-4-quinolone alkaloids is described. These compounds are readily prepared from the reaction of an N-methylisatoic anhydride with the lithium enolate of an acetophenone. By this method, the reaction of N-methylisatoic anhydride ( 5 ) or 5-methoxy-N-methylisatoic anhydride ( 7 ) with acetophenone produces the alkaloids N-methyl-2-phenyl-4-quinolone ( 1 ) and eduline ( 2 ) in 81% and 70% yield, respectively. An analogous reaction of 5 with 3,4-methylenedioxyacetophenone gives graveoline ( 3 ) in 63% yield whereas 7 and α-methoxyacetophenone affords japonine ( 4 ) in 61% yield.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 12. Synthesis of araliopsine and isoplatydesmine

N-Methylisatoic anhydride reacts with the lithium enolate derived from 3,3-dimethyloxiranepropanoic acid ethyl ester (7) to initially produce the acyclic β-ketoester 8 . Under neutral conditions, 8 spontaneously cyclizes to the alkaloid araliopsine ( 1a ). In the presence of acid, 8 cyclizes to a mixture of 1a and its leanear isomer isoplatydesmine (2a).     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 11. Reaction of N-methylisatoic anhydride with 1-cyanoacetylpiperidine

The reaction of N-methylisatoic anhydride with 1-cyanoacetylpiperidine in the presence of sodium hydride produces a tautomeric mixture of 4a and 4b , with 4b predominating. When heated in xylene, 4 is converted to the piperidine adduct 5 whereas heating in dimethylsulfoxide furnishes 3 . Spectral data for 4 and 5 are also discussed.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)dione (isatoic anhydride). 6. Synthesis of spiro[indoline-2,2′(1′H)quinazolines]

The reaction of isatoic anhydrides with potassium cyanide is described. The stoichiometry of the reactants and reaction times dictate the formation of either 2-imino-3-indolinones or spiro[indoline-2,2′(1′H)quinazolines]. Some spectral data is also discussed.     

The chemistry of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) 5. Synthesis of the [1]benzopyrano[3,2-c]quinoline ring system

The reaction of isatoic anhydrides with the anion derived from ethyl o-fluorobenzoylacetate to furnish [1]benzopyrano-[3,2-c]quinolines is described. An analogous reaction with 3-azaisatoic anhydride furnishes 1b , or with tricyclic anhydride 3 , system 4 is isolated. Spectral data is also discussed.     

2H-3,1-benzoxazine-2,4-(1H)-dione (isatoic anhydride). 15. Reactions with lactone enolates

The reaction of N-methylisatoic anhydride, 1 , with the lithium enolates derived from various butyrolactones or δ-valerolactone produces stable anthranoyl lactone derivatives 4 . Heating these products in toluene results in a cyclization to afford 4-hydroxy-3-(2-hydroxyalkyl)-1-methyl-2(1H)-quinolinones, 8 and 14 , in good yields.     

The chemistry of 2H-1,3-benzoxazine-2,4-(1H)dione (isatoic anhydride). 8. A one step synthesis of the quinindoline ring system and related compounds

The reaction between N-substituted isatoic anhydrides and the carbanion generated from 3-methylthio-oxindole to produce the quinindoline ring skeleton is discussed. Analogous reactions of azaisatoic anhydride 6 and tricyclic anhydride 8 produces the 4-aza analog 7 and pentacycle 9 . Some spectral data is also described.     

Chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 16. Facile construction of the furacridone ring system

The synthesis of the furacridone ring skeleton was accomplished in one step by the reaction of N-methylisatoic anhydride ( 7 ) with the lithium enolate derived from 6,7-dihydro-4(5H)-benzofuranone ( 10 ). Aromatization of the C ring with DDQ furnished 5-dehydroxyfuracridone ( 6 ).     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 10. Reactions with ester enolates. Synthesis of 4-hydroxy-1-methyl-3-prenyl-2(1H)-quinolinones,Crucial intermediates in the synthesis of quinoline alkaloids

N-Methylisatoic anhydride reacts with the lithium enolates of esters to produce β-ketoesters 4 in nearly quantitative yield. Thermal cyclization of these relatively unstable intermediates afford the corresponding 3-substituted-4-hydroxy-1-methyl-2(1H)-quinolinones (5) in good yields. The reaction of the lithium enolate of 5-methyl-4-hexenoic acid ethyl ester ( 14 ) with various nuclear substituted isatoic anhydrides gives 4-hydroxyl-methyl-3-prenyl-2(1H)-quinolinones 8, 9 , and 18 which are highly desirable intermediates in the synthesis of a variety of quinoline alkaloids. Treatment of 18 with DDQ furnishes oricine in 73% yield.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 21. a mild process for the preparation of 10-alkyl-9-acridanones and it's application to the synthesis of acridone alkaloids

10-Substituted-9-acridanones are readily prepared by the reaction of the corresponding isatoic anhydride with the lithium enolate of 2-cyclohexen-1-one. The initially formed product, the 1,2-dihydroacridone need not be purified but can be aromatized directly with DDQ to the desired acridone. This methodology is applicable to the synthesis of acridone natural products. Two alkaloids, 1,2,3-trimethoxy-10-methylacridone ( 9 ) and evoxanthine ( 10 ), were prepared from 4,5,6-trimethoxy-N-methylisatoic anhydride and 6-methoxy-4,5-methyl-enedioxy-N-methylisatoic anhydride respectively. In these trioxygenated systems, palladium-on-charcoal must be used to aromatize the penultimate intermediate.     

Reactions of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) with anions of 1,4-dihydro-5H-pyrazol-5-ones: Synthesis of pyrazolo[5,1-b]quinazolin-9-ones

Reactions of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) (1) with anions of 1,4-dihydro-5H-pyrazol-5-ones (2) gave pyrazolo[5,1-6]quinazolin-9-ones (3) via the nucleophilic attack of the anion 2b rather than 2a. However, in the case of 5-methoxyisatoic anhydride ( 10c) , both products 3e and 11c were obtained. A new synthetic method of preparation of 5-(alkylthio)-2-aminobenzoic acids (18) was described. These acids (18) were used to synthesize a series of substituted pyrazolo[5,1-b]quinazolin-9-ones (3) .     

Synthesis of partially saturated N-substituted 4H-3,1-benzothiazine-2(1H)-thiones

Summary Acid-catalyzed reaction of 2-arylidenecyclohexanones1 with N-substituted dithiocarbamic acids2 gave open-chain addition products3 and4. Dehydration of3 and4 afforded only one of the three possible isomeric N-substituted 4H-3,1-benzothiazine-2(1H)-thiones5 and6.

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Synthese von partiell gesättigten N-substituierten 4H-3,1-Benzothiazin-2-(1H)-thionen

Zusammenfassung Die säurekatalysierte Reaktion von 2-Arylidencyclohexanonen1 mit N-substituierten Dithiocarbaminsäure2 ergab die offenkettigen Additionsprodukte3 und4. Die Dehydratation von3 und4 führte ausschließlich zu einem der drei möglichen N-substituierten 4H-3,1-Benzothiazin-2(1H)-thion-Isomeren5 und6.

     

The chemistry of 2h-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 17 Synthesis of 2-alkyl-4-quinolone alkaloids via a one-step reaction of N-methylisatoic anhydride with methyl ketone enolates

Lithium enolates derived from aliphatic methyl ketones react with N-methylisatoic anhydride (5) at ?78° to give 2-alkyl-4-quinolone alkaloids 7 in a single step. The method was used to synthesize both double bond isomers of 1-methyl-2-(8-tridecenyl-4(1H)-quinolinone (8) thereby showing that the alkaloid evocarpine possesses the Z-olefin stereochemistry 8a. Reduction of 8a provided the alkaloid dihydroevocarpine (16). Compound 16 was also directly prepared from the reaction of 5 with the lithium enolate of 2-pentadecanone.