Title:Solvent-Free Synthesis of New 3’H-spiro[indole-3,2’-[1,3]]benzothiazole- 2(1H)-one Derivatives Using Michael Reaction
Volume: 14
Issue: 5
Author(s): Zahra Zare, Gholamhassan Imanzadeh*Zahra Soltanzadeh
Affiliation:
- Department of Chemistry, Faculty of Basic Science, University of Mohaghegh Ardabili 56199-11367, Ardabil,Iran
Keywords:
Acrilic esters, Aza-Michael addition, regioselective, solvent-free, 3’H-Spiro[indole-3, 2’-[1, 3]]benzothiazole-
2(1H)-one, Tetrabutylammonium bromide.
Abstract: Background: Benzothiazole is a heterocyclic compound, weak base and having various biological
activities. This compound and its derivatives are widely found in bioorganic and medicinal chemistry
with application in drug discovery. Spiro[indole-benzothiazoles] are one of analogs of the benzothiazole
and isatin, having biological properties, such as anticancer and antioxidant. (15). The aim of this
manuscript is to develop a green reaction for the synthesis of a new series of benzothiazole compounds
using Michael addition reaction 3’H-spiro[indole-3,2’-[1,3]]benzothiazole-2(1H)-one to α,β-unsaturated
esters under solvent-free conditions.
Methods: 3’H-Spiro[indole-3,2’-[1,3]]benzothiazole-2(1H)-one and different acrylic and fumaric esters
have been used to synthesize new derivatives of 3’H-Spiro[indole-3,2’-[1,3]]benzothiazole-2(1H)-one via
aza-Michael addition amide nitrogen of 3’H-Spiro[indole-3,2’-[1,3]]benzothiazole-2(1H)-one to β-carbon
atom of this α,β-unsaturated esters. These reactions were performed using K2CO3 (for single aza-Michael
addition) and K2CO3 and tetrabutylammonium bromide (for double aza-Michael addition) at room temperature
under solvent-free conditions. The structural assignments of the synthesized compounds were
made on the basis of elemental analysis and spectroscopic data (IR, 1H NMR, 13C NMR and Mass).
Results: The mono and bis-Michael adduct were synthesized using reaction between 3’H-Spiro[indole-
3,2’-[1,3]]benzothiazole-2(1H)-one and different acrylic esters in good to excellent yields (75%-95%).
This reaction was performed in the presence of inorganic base K2CO3 and tetrabutylammonium bromide
(for bis-Michael adduct) at room temperature under solvent-free conditions. Fumaric esters were
unable to react with 3’H-Spiro[indole-3,2’-[1,3]]benzothiazole-2(1H)-one and produced no products.
Conclusion: We developed a regioselective Michael addition reaction for the exclusive synthesis
mono-Michael adduct in the presence of base K2CO3 under solvent-free conditions at room temperature.
We have found that this selectivity disappears in the presence of TBAB under the same conditions. The
present procedure has notable advantages, for example, simple operation procedure, environmentally benign
reaction conditions, inexpensive and availability of the employed base catalyst.
