Title:Choline Chloride/Glycerol Promoted Synthesis of 3,3-Disubstituted Indol- 2-ones
Volume: 8
Issue: 2
Author(s): Ling Xu, Wei-Hong Zhang, Zhen-Shui Cui and Zhan-Hui Zhang*
Affiliation:
- Hebei Key Laboratory of Organic Functional Molecules, National Demonstration Center for Experimental Chemistry Education, College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024,China
Keywords:
Choline chloride/glycerol, 3, 3-disubstituted indol-2-ones, green chemistry, isatin, natural deep eutectic solvent, microwave
irradiation.
Abstract:
Objective: 3,3-Disubstituted indol-2-one derivatives have wider applications in pharmaceuticals
and they are key intermediates for the synthesis of many kinds of drug candidates. The development
of an efficient and practical method to prepare this class of compound is highly desirable
from both environmental and economical points of views.
Methods: In order to establish an effective synthetic method for preparing 3,3-disubstituted indol-
2-one derivatives, the bis-condensation reaction of isatin and 1H-indene-1,3(2H)-dione was selected
as a model reaction. A variety of natural deep eutectic solvents (NADESs) were prepared
and used for this reaction. The generality and limitation of the established method were also investigated.
Results: It was found that model reaction can be carried out in natural deep eutectic solvent
(NADES) based on choline chloride (ChCl) at 80°C under microwave irradiation. This protocol
with a broad substrate applicability afforded various 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-
1,3(2H)-dione) derivatives in high yields.
Conclusion: A simple and efficient procedure has been developed for synthesis of 2,2'-(2-oxoindoline-
3,3-diyl)bis(1H-indene-1,3(2H)-dione), spiro[indoline-3,7'-pyrano[5,6-c:5,6-c']dichromene]-
2,6',8'-trione, and spiro[indoline-3,9'-xanthene]trione via bis-condensation between isatin with 1,3-
indandione, 4-hydroxycoumarin or 1,3-cyclohexanedione in natural deep eutectic solvent
(NADES) based on choline chloride (ChCl) and glycerol (Gl) under microwave irradiation. The
salient features of this protocol are avoidance of any additive/catalyst and toxic organic solvent,
clean reaction profiles, non-chromatographic purification procedure, and high to excellent yield.
Furthermore, the use of NADES as green reaction medium reduces burden on environment and
makes the present method environmentally sustainable.