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Indoles - Sundberg R.J.

Sundberg R.J. Indoles - Academic press, 1996. - 95 p.
ISBN 0-12-676945-1
Download (direct link): indoles1996.djvu
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Thionyl chloride (11.5 g, 96.4 mmol) was added to 2-nitrophenylacetic acid (8.72 g, 48.2 mmol) and the suspension was warmed to 50°C and stirred until gas evolution was complete. The resulting solution was concentrated in vacuo and the residue dissolved in CH2C12 (30 ml). This solution was added dropwise to a stirred solution of Meldrum’s acid (6.94 g. 48.2 mmol) in CH2C12 (200 ml) under nitrogen at 0°C. The solution was stirred at 0CC for 1 h after the addition was complete and then kept at room temperature for an additional hour. The reaction solution was then worked up by successively washing with dil. HC1, water and brine and dried (MgSOJ. The dried solution was concentrated in vacuo and abs. ethanol (200 ml) was added to the residue. The mixture was
(2.10)
18
2 CATEGORY la CYCLIZATIONS
heated at reflux until gas evolution ceased. The ethanol was removed in vacuo and the residue triturated with a little ethanol and refrigerated overnight. The product solidified and was recrystallized from ethanol to give the product as a biege powder (10.28 g, 85%).
Ethyl indole-2-acetate[3]
Ethyl 4-(2-nitrophcnyl)acetoacetate prepared as above (2.68 g, 10.7 mmol) was dissolved in acetone (30 ml) and placed in a separatory funnel. Aqueous NH4OAc (288 ml, 4 M) was added, followed by aq. TiCl3 (77 ml, 15% w/v). The mixture was shaken for 7 min. The resulting dark green solution was extracted with ether (4 x 100 ml) and the combined ether layers washed with water and brine. The solution was dried (MgS04) and concentrated in vacuo. The residue was purified by chromatography using CH2C12 for elution and gave the product (1.63 g) in 75% yield.
4-Chloroindole[ 10]
2-Chloro-6-nitrotoluene (25g, 146mmol) and 40% PhCH2N+(CH3)3OH“ in methanol (Triton B, 1.8 ml), paraformaldehyde (60 mmol) and DMSO (60 ml) were mixed and stirred at 90°C for 2h. The product was obtained by distillation (92% yield on basis of paraformaldehyde). The 2-(6-chloro-2-nitrophenyl)ethanol (10.2 g) was reduced by addition as a solution in ethanol (10ml) to a suspension of zinc powder (42g) and CaCl2 (4.2g) in 3:1 ethanol-water (200 ml). The mixture was heated at reflux for 8 h. The product was obtained in 45% yield by extraction with ether. The 2-(6-chloro-2-aminophenyl)ethanol (7 mmol) was added to a mixture of RuCl2(PPh3)2 (2mol%)in toluene under an argon atmosphere in a flask equipped with a gas burette. The mixture became homogeneous after being stirred for about 5 min and was then heated to 120°C in a preheated oil bath and kept at reflux for 6 h. The product was obtained in 92% yield.
6-Bromooxindole[26]
A. 4-Bromo-2-nitropyruvic acid
Diethyl oxalate (29.2 g, 0.20mol) and 4-bromo-2-nitrotoluene (21.6 g, O.lOmol) were added to a cooled solution of sodium cthoxide prepared from sodium (4.6 g, 0.20 mol) and ethanol (90 ml). The mixture was stirred overnight and then refluxed for 10 min. Water (30 ml) was added and the solution refluxed for 2 h to effect hydrolysis of the pyruvate ester. The solution was coolcd and conccntrated in vacuo. The precipitate was washed with ether and dried. The salt was dissolved in water (300 ml) and acidified with conc. HC1. The precipitate was collected, washed with water, dried and recrystallizcd from hexane-EtOAc to give 15.2 g of product.
2.3 CONDENSATION OF o-AMlNOBENZYL ALDEHYDES AND KETONES
19
B. 4-Bromo-2-nitrophenylacetic acid
The pyruvic acid (28.8 g, 0.10 mol) was dissolved in 1 NNaOH (300 ml) and stirred at OX. Л solution of 30% H2Oz (11.3 ml, 0.10 mol) was added dropwise. The solution was stirred for 1 h at 5ЭС and then acidified with dil. HC1. The precipitate was collected by filtration, washed with water, dried and recrystallized from hcxanc-EtOAc to yield 22.2 g (85% yield) of the product.
C. 6-Bromooxindole
4-Bromo-2-nitrophenylacetic acid (26 g, O.lOmol) was dissolved in a mixture of 50% H2S04 (400 ml) and ethanol (600 ml) and heated to 90°C. Over a period of 1 h, zinc dust (26.2 g, 0.40 mol) was added slowly and then heating was continued for 2 h. The excess ethanol was removed by distillation. The solution was cooled and filtered. The filtrate was extracted with EtOAc. The filtered product and extract were combined, washed with 5% NaCOa and brine and then dried (MgS04). The solvent was removed in vacuo and the residue recrystallized from methanol to give 20.5 g (97% yield) of the oxindole.
6-Benzoyloxindole[22]
A. Diethyl 2-(4-benzoyl-2-nitrophenyl)propanedioate
Sodium hydride (9.3 g, 0.22 mol) was washed with petroleum ether and DMSO (200 ml) was added and the mixture was heated to 100°C. A solution of diethyl malonate (35.2 g, 0.22 mol) in DMSO (50 ml) was then added and stirred for 10 min to give a clear solution. A solution of 4-bromo-3-nitrobenzophenone (30.6g, O.lOmol) in DMSO (100ml) was added and the resulting dark solution kept at 100°C for 1 h. The solution was poured into water (3 1) and extracted (2x) with ether. The extract was washed with water, dried (Na2S04) and concentrated in vacuo to give an oil which crystallized. The solid was recrystallized from isopropyl alcohol to give 35.4 g (92% yield) of the product.
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