Reactions of N- and C-alkenylanilines: VIII. Synthesis of functionalized cycloalka[b]indoles from o-(cycloalk-2-en-1-yl)anilines

SHORT COMMUNICATIONSHalocyclization of o-allylanilines is fairly frequently used to obtain dihydroindole [1] and tetrahydroquinoline structures [2]. We made an attempt to perform bromocyclization of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate (II) which was obtained in turn from 2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylic acid synthesized previously [3]. However, the only isolated product was methyl 8-allyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate (III). The observed unusual bromination may be rationalized assuming intermediate formation of stable bridged bromonium ion which acts as brominating agent in electrophilic substitution process. Methyl 1-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate (I).A solution of 1 g (5 mmol) of methyl 2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate in 15 ml of allyl bromide was heated for 10 h on a water bath. The solvent was removed from the solid residue by decanting, the residue was dissolved in water, and the solution was made alkaline by adding a 10% solution of sodium hydroxide to pH >10 and extracted with chloroform. The organic phase was separated, dried over anhydrous sodium sulfate, and evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel using petroleum ether-ethyl acetate (25 : 1). Yield 0.82 g (82%), colorless oily substance, R f 0.54 (benzene-ethyl acetate, 8 : 1). IR spectrum, ν, cm -1 : 2854-3074 (CH 2 ), 1731 (C=O), 1643 (C=C). 1 H NMR spectrum (DMSO-d 6 ), δ, ppm: 1.05 d (3H, Me, J = 6.6 Hz), 2.11 t (2H, 3-H, J = 6.6 Hz), 3.45 q (1H, 2-H, J = 5.9 Hz), 3.65 s (3H, OMe), 3.77-3.87 m (2H, NCH 2 ), 3.91-4.01 m (1H, 4-H), 5.01-5.20 m (2H, =CH 2 ), 5.77-5.91 m (1H, CH), 6.48-6.57 m (2H, 6-H, 8-H), 6.86 d (1H, 5-H, J = 7.3 Hz), 7.00 t (1H, 7-H, J = 7.0 Hz). Mass spectrum, m/z (I rel , %): 245 (47) [M] + , 230 (60), 186 (30), 170 (100), 144 (45), 130 (70). Found, %: C 73.53; H 7.97; N 5.73. C 15 H 19 NO 2 . Calculated, %: C 73.44; H 7.81; N 5.71. M 245.32.Methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate (II). A solution of 0.85 g (3.5 mmol) of compound I and 0.98 g (7 mmol, 0.87 ml) of boron trifluoride-diethyl ether complex in 15 ml of o-xylene was heated for 30 min at 130°C under argon. The mixture was cooled, 25 ml of a 10% solution of sodium hydroxide was added, and the mixture was treated with chloroform. The organic phase was separated, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The product was isolated by column chromatography on silica gel using petroleum ether-ethyl acetate (25 : 1) as eluent. Yield 0.77 g (91%), colorless oily substance, R f 0.49 (benzene-ethyl acetate, 8 : 1). IR spectrum, ν, cm -1 : 3402 (

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Unusual bromination of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate

et al. 2011

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ChemInform Abstract: Reactions of N‐ and C‐Alkenylanilines. Part 8. Synthesis of Functionalized Cycloalka[b]indoles from o‐(Cycloalk‐2‐en‐1‐yl)anilines.

Гатауллин¹,

Likhacheva²,

Suponitskii³

et al. 2008

ChemInform

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Fused pyrrole derivatives R 0160 Reactions of N-and C-Alkenylanilines. Part 8. Synthesis of Functionalized Cycloalka[b]indoles from o-(Cycloalk-2-en-1-yl)anilines. -1,2-Functionalized hexahydrocarbazoles and 2,3-disubstituted perhydrocyclopenta[b]indoles are synthesized using the halocyclization of cycloalkenylanilines as the key step. -(GATAULLIN, R. R.; LIKHACHEVA, N. A.; SUPONITSKII, K. Y.; ABDRAKHMANOV, I. B.; Russ.

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Synthesis of (1′S,2R,3R)‐ and (1′S,2R,3S)‐N‐arylsulfonyl‐2‐(1′‐halogenethyl)‐3‐methylindolines and their selective toxicity against SH‐SY5Y cell line

Гатауллин

Zileeva

Maksimova

et al. 2020

Journal of Heterocyclic Chem

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N‐tosyl‐2‐ and N‐tosyl‐4‐halogen‐substituted derivatives of 2‐(1‐methylbut‐2‐en‐1‐yl)aniline were synthesized and their molecular iodine‐mediated cyclization was investigated. The cyclization upon interaction of N‐tosyl‐6‐methyl‐2‐(1‐methylbut‐2‐en‐1‐yl)aniline with molecular iodine in methyl tert‐butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N‐bromosucinimide in dichloromethane. Synthesized (2R*,3R*)‐ and (2R*,3S*)‐N‐arylsulfonyl‐2‐(1‐halogenoethyl)‐3‐methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH‐SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)‐N‐arylsulfonyl‐7‐bromo‐2‐(1‐halogenoethyl)‐3‐methylindoline cis‐4a, stereoisomeric (2R*,3R*)‐trans‐4h and (2R*,3S*)‐N‐tosyl‐7‐chloro‐2‐(1‐halogenoethyl)‐3‐methylindoline cis‐4h demonstrated selective toxicity against SH‐SY5Y cell line (IC50 ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.

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Reactions of N- and C-alkenylanilines: VIII. Synthesis of functionalized cycloalka[b]indoles from o-(cycloalk-2-en-1-yl)anilines

Cited by 13 publications

References 15 publications

Unusual bromination of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate

Unusual bromination of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate

ChemInform Abstract: Reactions of N‐ and C‐Alkenylanilines. Part 8. Synthesis of Functionalized Cycloalka[b]indoles from o‐(Cycloalk‐2‐en‐1‐yl)anilines.

Synthesis of (1′S,2R,3R)‐ and (1′S,2R,3S)‐N‐arylsulfonyl‐2‐(1′‐halogenethyl)‐3‐methylindolines and their selective toxicity against SH‐SY5Y cell line

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Reactions of N- and C-alkenylanilines: VIII. Synthesis of functionalized cycloalka[b]indoles from o-(cycloalk-2-en-1-yl)anilines

Cited by 13 publications

References 15 publications

Unusual bromination of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate

Unusual bromination of methyl 8-allyl-2-methyl-1,2,3,4-tetrahydroquinoline-4-carboxylate

ChemInform Abstract: Reactions of N‐ and C‐Alkenylanilines. Part 8. Synthesis of Functionalized Cycloalka[b]indoles from o‐(Cycloalk‐2‐en‐1‐yl)anilines.

Synthesis of (1′S*,2R*,3R*)‐ and (1′S*,2R*,3S*)‐N‐arylsulfonyl‐2‐(1′‐halogenethyl)‐3‐methylindolines and their selective toxicity against SH‐SY5Y cell line

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Synthesis of (1′S,2R,3R)‐ and (1′S,2R,3S)‐N‐arylsulfonyl‐2‐(1′‐halogenethyl)‐3‐methylindolines and their selective toxicity against SH‐SY5Y cell line