Synthesis of lysergic acid. I. Derivatives of indole was written by Barltrop, J. A.;Taylor, D. A. H.. And the article was included in Journal of the Chemical Society in 1954.Category: indole-building-block This article mentions the following:
As a model for the synthesis of lysergic acid, 2-methyl-3(2-oxocyclohexylidenemethyl)indole (I), prepared by condensing 2-methylindole (II) with formylcyclohexanone (III), was reduced to 2-methyl-3-(2-oxocyclohexylmethyl)indole (IV) and cyclized in small yield to a tetracyclic system (V), 4,6,6a,7,8,9-or 4,6,7,8,9,10-hexahydro-5-methyldibenz[cd,f] isoindole. An alternative, involving the cyclization of 4-bromo-3(2-oxocyclohexylmethyl)indole by an intramol. Grignard reaction, failed since the essential intermediate, 4-bromoindole (VI), could not be prepared II (9.5 g.) and 20 g. III in EtOH refluxed 2 h. gave 10 g. I, yellow prisms, m. 126° (from EtOH); dinitrophenylhydrazone, orange needles, m. 234°. I (0.67 g.) in EtOH hydrogenated at room temperature and pressure over Pd-C 1 h. gave IV, a colorless oil; picrate, m. 135° (from C6H6); semicarbazone, plates, m. 199-200° (decomposition). Indole (2 g.) and 4 g. III refluxed 2 h. in EtOH also gave 3-(2-oxocyclohexylidenemethyl)indole, needles, m. 232°. 2-Phenylindole and III in EtOH gave a blue substance, m. 200°, which is apparently of complex structure. IV (1 g.) was stirred 2 min. at 130° in 4 g. P2O5 and 3 cc. sirupy H3PO4, the insoluble residue dissolved in MeOH, the solution brought to pH 6, 2 g. Girard’s reagent “P” added, and the solution refluxed 20 min. The residue yielded the picrate of V, red needles, m. 144°. When 9.3 g. IV in 50 cc. PhMe was refluxed 1 h. with P2O5 no ketone fraction could be isolated. 2,6-Br(O2N)C6H3Me (VII) (1 kg. crude), recrystallized, yielded 400 g. pure VII, m. 42°, and 500 g. 4,2-Br(O2N)C6H3Me (VIII), m. 47°. VII (216 g.) and 143 g. (CO2Et)2, refluxed 45 min. with NaOEt in EtOH give 119 g. 2,6-Br(O2N)C6H3CH2COCO2H (IX), m. 117° (from C6H6); semicarbazone, m. 216°. From the steam distillate was recovered 115 g. VII. Similarly VIII gave 40% 4,2-Br(O2N)C6H3CH2COCO2H (X), needles, m. 144°, and 51% unchanged VIII. IX (28 g.) reduced in a refluxing solution of 150 g. FeSO4.7H2O and 60 cc. NH4OH in 600 cc. H2O 5 min. gave 18 g. 4-bromo-2-indolecarboxylic acid (XI), m. 266° (from EtOH). IX (28 g.) and 45 cc. 10% NaOH in 100 cc. H2O treated during 1 h. with 53 g. Na2S2O4, and the solution acidified with HCl and heated 2 h. gives 22 g. XI. Similarly X gave the 6-Br isomer of XI, needles, m. 223° (from aqueous EtOH). VII (21.6 g.) suspended in 50 cc. EtOH, hydrogenated with Raney Ni at room temperature and 3 atm. pressure, gave 17 g. 6,2-Br(H2N)C6H3Me (XII), b16 130°. XII (9.3 g.) heated overnight in 20 cc. anhydrous HCO2H gave 10 g. N-formyl derivative, (XIII), leaflets, m. 116°. 4,2-Br(HCONH)C6H3Me, needles, m. 137°, was similarly prepared from VIII. XIII (16 g.) added to 2.9 g. K in 100 cc. tert-BuOH, the alc. distilled, and the residue heated 0.5 h. to 270° did not form any VI. 6,2-Br(AcNH)C6H3Me (34 g.) warmed under N with 14 g. NaNH2 until evolution of NH3 ceased, then heated 15 min. at 240°, did not afford 4-bromo-2-methylindole. Me 2-bromocinnamate (11.4 g.) in concentrated H2SO4 treated during 0.5 h. at 0° with 3.5 g. HNO3 (d. 1.48) in 10 cc. H2SO4 gave 13.7 g. crude product which, triturated with MeOH, yielded 9.5 g. Me 2-bromo-5-nitrocinnamate (XIV), yellow needles, m. 169° (from MeOH). XIV (6 g.) suspended in 50% H2SO4 and refluxed a few min. with a saturated solution of 7 g. KMnO4 gave 2.4 g. 2,5-Br(O2N)C6H3Me, needles, m. 178° (from aqueous EtOH). In the experiment, the researchers used many compounds, for example, 4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2Category: indole-building-block).
4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Category: indole-building-block
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