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2 CATEGORY la CYCLIZATIONS
Reductive cyclization of o,(3-dinitrostyrenes
Entry Substituents Reductant Yield (%) Ref.
i 4-Chloro Fe 85 
2 4-Acetyloxy-5-benzyloxy Fe/Si02 64 
3 4,7-b's-Benzyloxy Fe 63 
4 4,7-Dimethoxy NaBiyPd-C 67 
5 5,6-Diacetoxy Hj/Pt-C 70 
6 5,6-Dihydroxy H2/Pd-C 50 
7 5-Methoxy-6-benzyloxy Fe,/Si02 91 
8 5,6-Methylenedioxy NH^HC0;/Pd-C 82 
9 5,6,7-Trimethyl H2/Pd-C 43 
10 5,6-feis-(Benzyloxy)- 4.7-dimethyl Fe/Si02 90 
11 5,6-Dimethoxy-7-iodo- 2-methyl Fe 47 
clear yellow solution was poured slowly into a mixture of 132 ml of conc. HC1 and 198 ml of water. The addition product was obtained as a solid (72 g, 51%). The nitroalcohol (20 g) was added to a suspension of finely powdered anhydrous NaOAc (prepared by fusion and grinding) in acetic acid (90 ml). The mixture was refluxed for 5 min and after cooling it was poured into 600 ml of cold water. The product was obtained as an oil which solidified on standing at room temperature. The nitrostyrene was collcctcd by filtration (17.6 g, 95%) and could be recrystallized from ethanol.
3,4-/7i.s-(Benzyloxy)-2,5-dimethylbenzaldchydc (50 mmol) and nitromethane (150 mmol) and dry NH4OAc (150 mmol) were dissolved in acetic acid (150ml) and heated at reflux for 1.5 h. The reaction mixture was cooled and poured into water (11). The product was collected by filtration, dissolved in CH2C12, washed with NaHC03, dried over Na2S04 and passed through silica gel using CH2C12 for elution. The product (12.5 g, 64%) was purified by recrystallization from benzene-hexane. A solution of the /^-nitrostyrene (3.89 g, 10 mmol) in dry acetic acid (40 ml) was heated to 60-65 С and Cu(N03)2-3H20 was added in small portions over 30 min. The mixture was kept at 60-65°C for 1.25 h, coolcd to room temperature and poured into water (400 ml). The product was collected as a solid and washed thoroughly with water. The dinitrostyrene was collected by filtration, dissolved in CH2C12, washed with NaHC03, dried over Na2S04 and passed through silica gel using CH2C12 for elution. The product was recrystallized from benzene-cyclohexanc and then ethanol (2.1 g, 48% yield).
2.3 CONDENSATION OF o-AM INOBENZYL ALDEHYDES AND KETONES
4.5-few-(Benzyloxy)-3,6-dimethyl-2,p-dinitrostyrene (4 mmol), 70-270 mesh silica gel (10 g), acetic acid (24 ml) and electrolytic iron powder (4g, 71 mmol) were dispersed in toluene (40 ml) and refluxed under nitrogen for 1 h. The mixture was cooled and then filtered. The solid was washed thoroughly with CH2C12. The combined filtrate and washings were washed successively with aq. NaHSOj, water and aq. NaHC03. After drying over Na2S04, the solution was evaporated in vacuo, and eluted through silica with CH2Cl2-hexane. The solvent was evaporated and the residue recrystallized from benzenecyclohexane to give 5,6-b/.s-(benzyloxy)-4,7-dimcthylindolc (1.28 g) in 90% yield.
The o,p-dinitrostyrene (1 mmol) and ammonium formate (10 mmol) were dissolved in methanol and 10% Pd/C (5% by wt) was added. The mixture was refluxed under nitrogen for 1 h. Formic acid (0.44 ml) was added and reflux was continued for 0.5-1 h until the completion of the reaction (tic). The solution was filtered through Celite, evaporated in vacuo and eluted through silica gel with CH2C12.
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9. H.-J. Knolker and K. Hartmann. Synlett 755 (1993).
10. B. P. Murphy, J. Org. Chem. 50. 5873 (1985).
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2.3 GENERATION AND CYCLIZATIVE CONDENSATION OF o-AMINOBENZYL ALDEHYDES AND KETONES
Both o-aminobenzyl aldehydes and ketones rapidly cyclize and undergo dehydration to indoles. The generation of these carbonyl compounds therefore represents a quite reliable route to indoles. The complication is that while there
2 < Ml (iOin la CYCLIZATIONS
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arc numerous potential means of constructing the intermediates, none is entirely general. As a result, the specific synthetic route must be designed for the target compound within the context of the broad approach. Scheme 2.2 illustrates some of the approaches that have been used. A closely related group of reactions in which the intermediate benzyl carbonyl compound is not isolated will be described in Chapter 6.