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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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z
Z = АгБОг; R =H; R' =C2H5 Z = CN; R = CH3; R' Si(CH3)3
An Organic Syntheses preparation of 4-nitroindole may involve a related reaction. The condensation occurs in the presence of diethyl oxalate which may function by condensation at the methyl group. If this is the ease, it must subsequently be lost by deacylation[17].
Procedures
2-(tert-Butyl)indole[2]
A stirred solution of omethylpivalanilide (50 mmol) in dry THF (100 ml) was maintained at 15°C under a nitrogen atmosphere. A 1.5 M solution of n-butyllithium in hexane (3 equiv.) was added dropwise. The solution was then maintained at room temperature for 16 h. The solution was cooled in an ice-bath and treated with 2 N HC1 (60 ml). The organic layer was separated and the aqueous layer was further extracted with benzene. The combined layers were dried (MgS04). The product was obtained in 87% yield and recrystallized from ether-cyclohexane.
2-(4-Phenylbutyl)indole[ 14]
4-Phenylbutanoyl chloride (0.8 g, 4.9 mmol) was added dropwise to a stirred solution of o-aminobenzyltriphenylphosphonium chloride hydrochloride (1.6 g,
30
3 CATEGORY Ib CYCLIZATIONS
3.6 mmol) in DMF (3 ml) and pyridine (1ml). The mixture was stirred overnight and then concentrated in vacuo. The residue was dissolved in CHC13 and washed with 1 N HC1 (2 x 10ml) and brine (10ml) and dried over Na2S04. The solution was filtered and evaporated. The residue was triturated with ether (20 ml) to yield 1.8 g (90%) of the intermediate acylated phos-phonium salt. A mixture of this material (4.5 g, 7.98 mmol) and KO-J-Bu (1.0 g, 8.9 mmol) was refluxed in toluene (50 ml) for 30 min. The cooled solution was filtered and then concentrated. The residue was purified by elution through silica gel with CH2C12. The yield was 1.55 g (78%).
References
1. C. F. H. Allen and J. Van Allan, Org. Synth. Coll. Vol. Ill 597 (1955).
2. W. J. Houlihan, V. A. Parrino and Y. Dike, J. Org. Chem. 46, 4511 (1981).
3. J. A. Turner, J. Org. Chem. 48. 3401 (1983).
4. W. Fuhrer and H. W. Gschwend, J. Org. Chem. 44. 1133 (1979).
5. M. Arcari, R. Aveta, A. Brandt, L. Cecchetelli, G. B. Corsi and M. Di Retta, Gazz. Chim. Ital. 121. 499 (1991).
6. J. Bergman, E. Koch and B. Pelcman, Tetrahedron 51, 5631 (1995).
7. R. L. Augustine, A. J. Gustavsen, S. F. Wanat, 1. C. Pattison, K. S. Houghton and G. Koletar,
J. Org. Chem. 38, 3004 (1973).
H. G. Spadoni, B. Stankov, A. Duranti, G. Biella, V. Lucini, A. Salvatori and F. Fraschini, J. Med.
Chem. 36, 4069 (1993).
9. R. E. Lyle and L. Skarlos, J. Chem. Soc., Chem. Commun. 644 (1966).
10. J. P. Li, K. A. Newlander and T. O. Yellin, Synthesis 73 (1988).
11. M. Le Corre, A. Hercouet and H. Le Baron, J. Chem. Soc., Chem. Commun. 14 (1981).
12- С. M. Eitel and U. Pindur. Synthesis 364 (1989).
13. L. Capuano, A. Ahlhetm and H. Hartmann, Chem. Ber. 119, 2069 (1986).
14. N. Prasitpan, J- N. Patel, P. Z. De Croos, B. L. Stockwell, P. Manavalan, L. Kar, М. E. Johnson and B. L. Currie, J. Heterocycl. Chem. 29, 335 (1992).
15. K. Wojciechowski and M. Makosza, Synthesis 651 (1986).
16. E. О. M. Orlemans, A. H. Schreuder, P. G. M. Conti, W. Verboorn and D. N. Reinhoudt, Tetrahedron 43, 3H17 (19H7).
17. J. Bergman and P. Sand, Org. Synth. 65, 146 (1987).
3.2 INDOLES FROM o-ACYLANILINE DERIVATIVES
Retrosynthetic path b in Scheme 3.1 corresponds to reversal of the electrophilic and nudeophilic components with respect to the Madelung synthesis and identifies o-acyl-JV-alkylanilines as potential indole precursors. The known examples require an aryl or EW group on the iV-alkyl substituent and these substituents are presumably required to facilitate deprotonation in the condensation. The preparation of these starting materials usually involves N-alkyla-tion of an o-acylaniline. Table 3.3 gives some examples of this synthesis.
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References
1. C. D. Jones and I-. Suarez, J. Org. Chem. 37, 3622 (1972).
2. К Andersen. J. Pcrrcgaard. J. Amt, J. B. Nielsen and M. Begtrup, J. Med. Chem. 35, 4823
(1992).
3. H. Grcutcr and H. Schmid. Helv. Chim. Ada, 57, 281 (1974).
4. M. Oklobdzija, M. Japelj and T. Fajdiga. J. Heterocyd. Chem. 9, 161 (1972).
3.3 INDOLES FROM o,A/-DIACYLANILINES
Retrosynthetic path d (Scheme 3.1) has recently been realized as an effective synthesis of 2,3-disubstituted indoles using low-valent titanium reagents to effect the reductive cyclization. Several aryl- and methyl-substituted compounds were prepared by using Ti-graphitc prepared from K-graphite and TiCl3[l,2]. An improved methodology which avoids the preparation of K-graphite was subsequently developed[3]. This procedure uses zinc powder to effect in situ reduction of TiCl3.
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