TETRACYCLIC COMPOUNDS FROM CYCLOPENT[b]lNDOLES. SYNTHESIS OF ISOXAZOLO[3',4':5,4]CYCLOPENT[b]INDOLES.

Abstract

Cyclopentan-1 ',2'-dione-1 '-arylhydrazones 3 obtained from the Japp-Klingemann reaction of diazotised aniline derivatives i and 2-hydroxymethylenecyclopentanone 2 on acid catalysed cyclization afforded cyclopent [6]indoles 4. These on mixed aldol condensation with 4-methoxybenzaldehyde followed by reaction with hydroxylamine hydrochloride gave isoxazolo [3',4':5,4]cyclopent[6]indoles 6. IntroductionThe chemistry of Indole alkaloids and related compounds have been studied more extensively during the past few decades owing to their potential applications in diverse pharmacological field'"® In particular they were reported to have antitumour, antibacterial and antifungal activities'^. Based on these facts we proposed to undertake a novel attempt towards the synthesis of cyclopentanone ring fused with indoles, cyclopent[6] indoles 4 from the diazotised anilines I and 2-hydroxymethylenecyclopentanone 2 followed by acid catalysed cyclisation which were used as synthons to derive the titled isoxazolo[3',4':5,4]cyclopent[Z>]indoles 6 through the intermediates, 2benzylidenecyclopent[i]indoles 5 (schemel). Experimental General informationPurification of the crude products was carried out using chromatographic columns. Melting points were determined on a Mettler fp-5 instrument. Infrared spectra of the compounds were recorded in KBr pellets using PERKIN-ELMER model-1600 spectrometer. The 'H-NMR spectra were recorded on AMX-400 spectrometer using tetramethylsilane (TMS) as an internal referance and chemical shifts are reported in parts per million (δ) downfield from the internal standard. The signal multiplicities are represented by s (singlet), d (doublet), b s (broad singlet) and m (multiplet). The microanalytical data are obtained on carlo Erba 1106 Perkin Elmer model 240 CHN analyzer. General procedures. Preparation of 2-hdroxymethyIenecyclopentanone 2Cyclopentanone (1.6 ml, 0.02 mol) was added to a well cooled, vigorously stirred mixture of sodium methoxide (from 5.17 g of sodium in 5 ml of abolute methanol), dryether (4 ml) and ethyl formate (1.8ml, 0.02 mol) in a small portions over a period of 10 minutes. The resulting mixture was stirred continuously for one hour in an ice bath and kept at room temperature . After a period of 24 hours, the yellow solid mass obtained was dissolved by adding ice water and neutralized with concentrated HCl. The oily mass that separated out upon acidification was extracted with ether, washed with brine and cold water and dried over anhydrous sodium sulphate. The residual oil after the removal of solvent by distillation to give 2-hydroxymethylenecyclopentanone 2 as viscous liquid in good quantity (65% yield). Preparation of cyclopentan-r,2'-dione-l'-aryl hydra zones 3_.A mixture consisting of 2-hydroxymethylenecyclopentanone 2 (0.004 mol) and sodium acetate trihydrate (lg) in methanol (6ml) was kept in ice bath. A solution of the respective aniline derivative (0.004 mol) in aqueous hydrochloric Brought to you by | Biblioteca de la Universidad de Sevilla

Stereoselective Formation of Carbon−Carbon Bonds via SN2-Displacement: Synthesis of Substituted Cycloalkyl[b]indoles

“…10b was prepared in 95% yield as a solid from 7b via the general Fischer cyclization procedure. Spectral data matched that for the known compound …”

Synthesis of Heteroarene‐Fused Cyclopentadienes and Related Compounds Suitable for Metallocene Preparation

“…[183] The acid-catalyzed Fischer rearrangement of cyclopentan-1,2-dione monoaryl hydrazones resulted in 1,2-dihydrocyclopenta[b]indol-3(4H)-ones (Scheme 48). [184][185][186][187] Substituted 4-methyl-2,3-dihydrocyclopenta[b]-indol-1(4H)-ones were obtained in average yields by the base-catalyzed cyclization of 1,2-dimethyl-3-(α-bromoacyl)indoles. The same products were obtained using sterically hindered 3-haloacyl-2-methylindole which was unsubstituted on the nitrogen, but the yield was lower (Scheme 49).…”

“…Synthesis of 1,2-dihydrocyclopenta[b]indol-3(4H)ones using the Fischer rearrangement. [184][185][186][187] A catalytic approach to 1,2-dihydrocyclopenta[b] indol-3(4H)-ones and related compounds via an intramolecular Rh-catalyzed alkene hydroacylation was proposed by Stanley et al; [106] the reaction conditions were optimized for the preparation of (S)-1,4-dimethyl-1,2-dihydrocyclopenta[b]indol-3(4H)-one, and a series of 1-alkyl and 1-aryl derivatives was obtained in 65-99% yields. The best results were obtained with the diphosphine ligand presented in Scheme 50A.…”