pHarmacist
(Hive Bee) 12-29-02 08:04 No 393845 |
Indoles from 2-methylnitrobenzenes | Bookmark | ||||||
This might be especially usefull for the prep. of 4-subst indoles that there has been much talk about lately: Procedure A. 6-Benzyloxy-2-nitrotoluene. A stirred mixture of 124.7 g (0.81 mol) of 2-methyl-3-nitrophenol (Note 1), 113.2 g (0.90 mol) of benzyl chloride, 112.2 g (0.81 mol) of anhydrous potassium carbonate, and 800 mL of dimethylformamide (DMF) is heated at 90¡ãC for 3 hr. Most of the DMF is removed on a rotary evaporator (20 mm) and the oily residue is poured into 400 mL of 1 N sodium hydroxide and extracted with ether (3 ¡Á 800 mL). The combined extracts are dried (Na2SO4), filtered, and evaporated to give 203.5 g of yellowish solid. Recrystallization from 1 L of methanol cooled to 0¡ãC affords 177.6 (90%) of 6-benzyloxy-2-nitrotoluene as pale-yellow crystals, mp 61¨C63¡ãC3 (Note 2). B. (E)-6-Benzyloxy-2-nitro-¦Â-pyrrolidinost C. 4-Benzyloxyindole. To a stirred solution of 162.2 g (0.50 mol) of (E)-6-benzyloxy-2-nitro-¦Â-pyrrolidinost http://www.orgsyn.org/orgsyn/orgsyn/prep "Turn on, Tune in and Drop Out" |
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flipper (Hive Bee) 12-29-02 13:15 No 393937 |
indole | Bookmark | ||||||
SWIM had a question. If you use methylaniline (without the nitro group). Can Indole be synthesized in a good yield instead of Nitroindole. Organic Syntheses, CV 8, 493 1. Procedure A. Ethyl N-(2-methyl-3-nitrophenyl)formimidate. A 1-L, one-necked, round-bottomed flask, fitted with a Claisen condenser protected from moisture with a drying tube, is charged with 200 g (1.35 mol) of freshly distilled triethyl orthoformate, 1 g of p-toluenesulfonic acid and 152 g (1 mol) of 2-methyl-3-nitroaniline (Note 1) and (Note 2). The solution is heated to 120°C and all of the ethanol formed is continuously distilled off during ca. 1 hr. Fractional vacuum distillation of the residue gives at 156–158°C/6 mm, the imidate ester, 184 g (88%), as a light-yellow, solidifying oil, mp 57–58°C. B. 4-Nitroindole. To a solution of 22 g (0.15 mol) of diethyl oxalate in 50 mL of dry dimethylformamide in a 200-mL beaker is added, under cooling, 11 g (0.13 mol) of potassium ethoxide with vigorous stirring (Note 3) and (Note 4). The solution is immediately (within a few seconds) poured into a 250-mL flask containing a solution of 20.8 g (0.10 mol) of ethyl N-(2-methyl-3-nitrophenyl)formimidate in 75 mL of dry dimethyl sulfoxide (Note 5). The resulting deep-red solution is stirred for 1 hr at ca. 40°C (Note 6) and (Note 7). The solution is then transferred into a 1-L beaker and water is added under stirring at a rate that gives smooth precipitation of 4-nitroindole. The product is filtered off and dried, giving 16.3 g (ca. 100%) of a brownish-yellow solid, mp 195–201°C [sublimation (subl.)], which is sublimed at 170°C/0.5 mm giving 11.5 g (71%) of yellow crystals, mp 204–205°C (subl.) (Note 8). |
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flipper (Hive Bee) 12-30-02 03:50 No 394141 |
indole | Bookmark | ||||||
Can this be done without the phenyl group so you make just Indole? 1. Procedure In a tall 1-l. beaker is placed an intimate mixture of 53 g. (0.25 mole) of freshly prepared acetophenone phenylhydrazone (Note 1) and 250 g. of powdered anhydrous zinc chloride (Note 2). The beaker is immersed in an oil bath at 170°, and the mixture is stirred vigorously by hand. The mass becomes liquid after 3–4 minutes, and evolution of white fumes begins. The beaker is removed from the bath, and the mixture is stirred for 5 minutes. In order to prevent solidification to a hard mass, 200 g. of clean sand is thoroughly stirred into the reaction mixture. The zinc chloride is dissolved by digesting the mixture overnight on the steam cone with 800 ml. of water and 25 ml. of concentrated hydrochloric acid (sp. gr. about 1.2). The sand and crude 2-phenylindole are removed by filtration, and the solids are boiled with 600 ml. of 95% ethanol. The hot mixture is decolorized with Norit and filtered through a hot 10-cm. Büchner funnel, and the sand and Norit are washed with 75 ml. of hot ethanol. After the combined filtrates are cooled to room temperature, the 2-phenylindole is collected on a 10-cm. Büchner funnel and washed three times with small amounts (15–20 ml.) of cold ethanol. The first crop is quite pure; after drying in a vacuum desiccator over calcium chloride it weighs 30–33 g. and melts at 188–189° (cor.) (Note 3) and (Note 4). A little Norit is added to the combined filtrate and washings, which are then concentrated to a volume of 200 ml. and filtered. The filtrate, on cooling, deposits a second crop of 5–6 g. (Note 5) of impure product, which melts at 186–188°. The total yield of 2-phenylindole is 35–39 g. (72–80%). Organic Syntheses, CV 3, 725 (http://www.orgsyn.org/orgsyn/prep.asp?p |
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