Download PDF
Synthesis 2002(1): 0104-0110
DOI: 10.1055/s-2002-19299
PAPER
© Georg Thieme Verlag Stuttgart · New York

New Diastereoselective Synthesis of 3-Alkylidene-1-methyloxindoles

Pilar López-Alvarado, Carmen Avendaño*
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(91)3941822; e-Mail: avendano@eucmax.sim.ucm.es;
Further Information

Publication History

Received 12 June 2001
Publication Date:
04 August 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

Addition of alkyl or aryl α-substituted acetophenones to N-methylisatin in basic media gives diastereomeric mixtures of the corresponding α-substituted 3-benzoylmethyl-3-hydroxy-1-methyloxindole in good yields. Under anhydrous conditions (concentrated sulfuric acid at 0 °C) these adducts eliminate benzoic acid, instead of water, to give pure (E)-3-alkylidene derivatives in quantitative yield. Applying the same treatment to the α-unsubstituted analogue, dehydration took place to give pure (Z)-3-benzoylmethylen-1-methyloxindole.

Key words

indoles - addition reactions - eliminations - rearrangements - isatinylidenes

    References

  • 1a Sato A, Asao T, Hagiwara Y, Kitade M, and Yamazaki Y. inventors; PCT Int. Appl. WO  9726242 A1..  ; Chem. Abstr. 1997, 127, 161696
  • 1b Sato A, Asao T, Hagiwara Y, Kitade M, and Yamazaki Y. inventors; PCT Int. Appl. WO  9725986A1.  ; Chem. Abstr. 1997, 127, 190643
  • 2a Tacconi G. Maggi LD. Righetti P. Desimoni G. Azzolina O. Ghislandi V. J. Chem. Soc., Perkin Trans. 2  1976,  150 
    CrossrefGoogle Scholar
  • 2b Sumpter WE. Miller FM. Heterocyclic Compounds with Indole and Carbazole Systems   Interscience; New York: 1954. 
    CrossrefGoogle Scholar
  • 3a Wahl A. Livovschi V. Bull. Soc. Chim. Fr.  1938,  5:  653 
    Google Scholar
  • 3b Anthony WC. J. Org. Chem.  1966,  31:  77 
    Google Scholar
  • 4 Lathourakis GE. Litinas KE. J. Chem. Soc., Perkin Trans. 1  1996,  491 
    CrossrefGoogle Scholar
  • 5a Pietra S. Tacconi G. Il Farmaco  1958,  13:  893 
    Google Scholar
  • 5b Tacconi G. Gamba A. Marinone F. Desimoni G. Tetrahedron  1971,  27:  561 
    Google Scholar
  • 5c Tacconi G. Marinone F. Gamba A. Desimoni G. Tetrahedron  1972,  28:  1517 
    Google Scholar
  • 5d Fahmy AM. Badr MZA. Mohamed YS. Abdel-Latif FF. J. Heterocycl. Chem.  1984,  22:  1233 
    Google Scholar
  • 5e Faita G. Mella M. Righetti PP. Tacconi G. Tetrahedron  1994,  50:  10955 
    Google Scholar
  • 5f Kozminykh EN. Berezina ES. Kozminykh VO. Zh. Obshch. Khim.  1996,  66:  1128 ; Chem. Abstr. 1996, 126, 7942
    Google Scholar
  • 6 Lindwall HG. Maclennan JS. J. Am. Chem. Soc.  1932,  54:  4739 
    CrossrefGoogle Scholar
  • In the case of compounds 9, 11, and 15 we observed slight variations in the positions of the NMe, C(2)=O and C(3)NMR signals, which may be a new example of the known concentration dependence of NMR data that has been found in other indole derivatives. For other examples, see:
  • 7a Jardine RV. Brown RK. Can. J. Chem.  1963,  41:  2067 
    Google Scholar
  • 7b Reinecke MG. Johnson HW. Sebastian JF. J. Am. Chem. Soc.  1969,  91:  3817 
    Google Scholar
  • 7c Avendaño C. De Diego C. Elguero J. Bull. Soc. Chim. Belg.  1989,  98:  73 
    Google Scholar
  • For other acid-catalyzed dehydrations of 3-hydroxy analogues, see:
  • 10a Autrey RL. Tahk FC. Tetrahedron  1967,  23:  901 
    CrossrefGoogle Scholar
  • 10b Beccalli EM. Marchesini A. Pilati T. J. Chem. Soc., Perkin Trans. 1  1994,  579 
    CrossrefGoogle Scholar
8

Compound (Z)-3 has been obtained in Ref.5e by isomerization of (E)-3 in the presence of AlCl3.

9

Both isomers are clearly distinguished by the chemical shift of their H(3α)-protons.

11

A mutual NOE between H-4 and (3α)-methyl protons characterized the Z-isomer.