An Antimalarial alkaloid from hydrangea. XV. Synthesis of 5-, 6-, 7-, and 8-derivatives with no identical substituents was written by Ablondi, Frank;Gordon, Samuel;Morton, John II;Williams, J. H.. And the article was included in Journal of Organic Chemistry in 1952.Application In Synthesis of 4,7-Dimethylindoline-2,3-dione The following contents are mentioned in the article:
To study the effect of substituents in the C6H6 ring on the antimalarial activity and chemotherapeutic index of the DL-form of the hydrangea alkaloid, a series of derivatives with 2 identical substituents in the benzene ring are synthesized by converting, according to Marvel and Hiers (C.A. 20, 193), the appropriate R2C6H3NH2 into the R2C6H3NHCOCH:NOH (I) (Table F) which, on ring closure with 86% H2SO4, give the corresponding isatins (II) (Table G). Oxidation of II with alk. peroxide gives the disubstituted o-H2NC6H4CO2H (III) (Table H) which, on fusion with HCONH2 (see preceding abstract), give the corresponding disubstituted 4(3H)-qainazolones (IV) (Table I). Condensation of 1-carbethoxy-2-(3-bromoacetonyl)-3-methoxypiperidine with the appropriate IV gives the disubstituted 3-[2-oxo-3-(1-carbethoxy-3-methoxy-2-piperidyl)propyl]-4(3H)-quinazolones (V) which, hydrolyzed with 6 N HCl, give the corresponding 3-[2-oxo-3 – (3-methoxy-2-piperidyl)propyl]-4(3H)-quinazolones (VI). Demethylation of VI then gives the corresponding 3-hydroxy-2-piperidyl derivatives (VII) (VIa, R = H). The IV, V, VI, and VII are listed in Table I. Cyclization of 55 g. 3,4-Me.2C6H3NHCOCH:NOH with 292 cc. 96% H2SO4 and 29 cc. H2O, solution of the isatin mixture in 1.2 l. H2O and 310 cc. 10% NaOH, dropwise addition of 12 N HCl to the filtered solution until turbid, and then addition of 4-cc. portions of acid and separation of the precipitate after each addition give 12.6 g. crude 4,5-dimethylisatin. The 4th addition gives no precipitate and strong acidification of the mother liquor gives 23.3 g. 5,6-dimethylisatin. Treating 21.5 g. 4-chloroisatin 4 h. at 50° in 440 cc. AcOH with 20 cc. SO2Cl2 and a crystal of iodine gives 60% 4,5-dichloroisatin. In the same way 6-chloroisatin gives 5,6-dichloroisatin. Adding 16.2 g. NaNO2 in small portions to 25 g. 3,5,2-Me2(H2N)C6H2NO2 in 70 cc. 6 N HCl at 0-5° with stirring and adding the diazonium solution to 35.6 g. NaCN and 34.5 g. NiCl2.H2O in 230 cc. H2O with warming on a steam bath 45 min. give 79% 3,5,2-Me2(NC)C6H2NO2, m. 125-8° which (18.7 g.), heated with 50 cc. 80% H2SO4 5 h. on a steam bath and poured onto ice, gives 52% 4,6,2-Me2(O2N)C6H2CONH2; Table F. Disubstituted α-isonitrosoacetanilides (I); Reaction time, Yield, M.p.,;R2, (min.), %, °C.; 3,4-Di-Me, 2, 84, 179-80a; 2,5-Di-Me, 5, 33, 151-3; 2,4-Di-Me, 8, 55, 158-9; 2,3-Di-Me, 3, 64, 131-2; 2,5-Di-Cl, 15, 22, 166-8; 3,5-Di-Br, 15, 11, 197-200; 3,4-(CH2)4–, 120, 87, 147-50; (a) Decomposition Table G., Disubstituted isatins (II); Yield, M.p., R2, Color, %, °C.; 4,5-Di-Me, red, 25, 225-6; 4,7-Di-Me, orange, 75, 260-4; 5,6-Di-Me, red, 46, 214-15; 5,7-Di-Me, orange, 91, 228-31; 6,7-Di-Me, orange, 57, 230-2; 4,5-Di-Cl, red, 60, 243-5; 4,7-Di-Cl, 99, 239-41; 5,6-Di-Cl, orange-red, 68, 264-8a; 4,6-Di-Br, orange, 88, 254-6; 4,5-(CH2)4–, orange, 32, 188-90a; 5,6-(CH2)4–, orange, 17, 176-85a; (a) Decomposition; Table H. Disubstituted anthranilic acids; Yield, M.p.a,; R2, %, °C.; 5,6-Di-Me, 65, 140-1; 4,6-Di-Me, 91, 160-1; 3,6-Di-Me, 58, 111-13; 4,5-Di-Me, 81, 213-14; 3,5-Di-Me, 65, 188-9; 3,4-Di-Me, 69, 184-6; 5,6-Di-Cl, 59, 165-7; 3,6-Di-Cl, 59, 148-50; 4,5-Di-Cl, 99, 208; 3,5-Di-Cl, 39, 230-1; 4,6-Di-Br, 73, 170-1; 5,6-(CH2)4–, 62, 114; 4,5-(CH2)4–, 86, 171-3; (a) Decomposition (VIII), m. 169-71°. Reduction of 12.9 g. VIII in 100 cc. Methyl Cellosolve 20 min. with 1 g. Pd-charcoal at 2-3 atm. H gives 91% 4,6,2-Me2(H2N)C6H2CONH2, m. 160-1°. Adding 25 cc. SO2Cl2, over a period of 15 min. to 20 g. o-H2NC6H4CO2H in 500 cc. AcOH at 40°, stirring the mixture 2 h., and extracting the precipitate with 15% HCl on a steam bath give 39% 3,5,2-Cl2(H2N)C6H2CO2H, m.230-1°. This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6Application In Synthesis of 4,7-Dimethylindoline-2,3-dione).
4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Application In Synthesis of 4,7-Dimethylindoline-2,3-dione
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles