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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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14.1 ELECTROPHIL1C SUBSTITUTION
137
Table 14.1
Electrophilic carbocyclic substitution
Entry Substituents Reagents Yield ("/ '«) Ref.
1 1 -Acetyl-6-chloroacetyl Chloroacetyl chloride, A1C13 80 Г41
2 6-Acetyl-1 -benzoyl-2,3-dimethyl Acetyl chloride, A1C13 70 [2]
3 2-(F_thoxycarbonyl)-5- (4-nitrobcn7oyl) 4-Nitrobenzoyl chloride, A1C1, 73 [7]
4 2-(Ethoxycarbonyl)-7- methoxy-3-methyl- 4-propanoyl Propanoyl chloride, A1C13 93 L8J
5 7-Methoxy-4-(methoxy-carbonvl)-1 -phenylsulfonyl П) C1COCOC1, A1C13 (2) McOH 75 Lyj
6 1,4-Diacetyl Acetyl chloridc, A1C13 95 [10]
depends upon a chelation effect. Nitriles are known to have a preference for ort/io-acylation when reaction is carried out on a preformed BCla complex[l 1].
м Юг у lly
T н I14'2)
l-Acetylindoline-2-sulfonic acid, which can readily be obtained from indole by addition of sodium sulfite followed by acetylation, is a useful intermediate for introduction of 5-substitucnts by clcctrophilic substitution[12]. The substituted indoline-2-sulfonic acid can be reconverted to the substituted indole by treatment with base.
Procedures
6-Chloroacetyl-1-(2,2-dimethylpropanoyl)indole[4]
To a suspension of A1C13 (89 g, 0.67 mol) in 1,2-dichloroethane (600 ml) chloroacctyl chloride (56ml, 0.70mol) was added dropwise at 0°C. After the addition was complete the mixture was kept at ambient temperature for 15 min, at which time l-(2,2-dimethylpropanoyl)indole (30 g, 0.15 mol) was added over 3 h. After completion of the addition, the mixture was stirred for 15 min and then poured into ice-cold water. The mixture was extracted with 1,2-dichloroethane. The extract was washed with water (3 x) and aq. 5% NaHC03 (3 x), dried (Na2S04) and concentrated in vacuo. The residue was
138
14 INTRODUCTION OF SUBSTITUENTS ON THE CARBOCYCLIC RING
crystallized to give the product (25 g, 60% yield). Additional product (5.4 g, 13% yield) and a small amount of the 4-chloroacetyl isomer (1.7 g, 4% yield) was obtained by chromatography of the mother liquor.
7-Benzoylindole[ 13]
Acylation
A solution of indoline (120 g, l.Omol) and benzonitrile (124 g, 1.2mol) in toluene (555 ml) was heated to boiling and 90 ml of toluene was distilled off to effect azcotropic drying. In a separate flask BC13 (130 g, 1.1 mol) was added to dry toluene (745 ml) at 5°C. This solution was kept at 5-10°C while the indoline-benzonitrile solution was added over 2.5 h. The temperature was maintained at 5-10°C and A1C13 (147 g, 1.1 mol) was added in portions over 45 min. The reaction mixture was then refluxed for 16 h. The reaction mixture was cooled to 8°C and water (188 ml) was added with continued stirring, resulting in separation of a heavy gum. There was then added 2 N HCl (800 ml) and the reaction mixture was heated to reflux for 2.5 h. During heating, a tan granular precipitate formed. After cooling, it was collected by filtration, washed with water and pressed dry. The damp solid was resuspended in water (1.11) and the suspension made basic with 25% NaOH solution while keeping the temperature below 20°C. Stirring was then continued for 4h. The resulting yellow solid was collected by filtration, washed with water and dried to give 179 g (80%) of 7-benzoylindoline.
Aromatization
7-Benzoylindoline (223 g, l.Omol) was dissolved in CH2C12 (2.23 1) and Mn02 (261 g, 3.0 mol, Diamond-Shamrock grade M) was added. The mixture was heated at reflux and agitated for 18 h. The reaction mixture was filtered and the solid washed with hot CH2C12 (200 ml). Evaporation of the solvent left
7-benzoylindole.
References
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14.2 RING METALLATION
139
9. F. Santanagelo, C. Casagrandc. G. Norcmi and F. Gerii, Synth. Commun. 23, 2717 (1993).
10. A. G. M. Barrett, D. Dauzonnc and Г). J. Williams, J. Chem. Soc., Chem. Commun. 636 (1982).
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13. Y. S. Lo, D. Л. Walsh, W. J. Welstead. Jr, R. P. Mays, E. K. Rose, 1). H. Causey and R. L. Duncan, J. Heterocyci. Chem. 17. 1663 (1980); D. A. Walsh, H. W. Moran, D. A. Shamblee,
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