Aim and Objective: In recent studies, chemistry of heterocyclic compounds, especially isoxazoles,
has been widely considered by organic chemistry researchers because they have been found in many molecules,
including naturally occurring bioactive compounds, pharmaceuticals, and agrichemicals. Isoxazol-
5(4H)-ones and their derivatives, on the other hand, have significant biological properties can be mentioned as
examples of antibacterial, anti-inflammatory, antifungal, anticancer, analgesic, fungicidal, and insecticidal activities.
Therefore, the development of ecofriendly methods, such as three-component processes, for the synthesis
of isoxazol-5(4H)-ones is highly desirable. This work focus on the one-pot, three-component reaction
(3-CR) of aldehydes, hydroxylamine hydrochloride, and three β-ketoester using catalytic amounts of sulfanilic
acid (SA) aimed at the synthesis of isoxazol-5(4H)-ones. Another aim of this study is to use water as a green
solvent for the above-mentioned 3-CR.
Materials and Methods: Using SA as an efficient organocatalyst, the multicomponent cyclocondensation of
aromatic/hetero-aromatic aldehydes, hydroxylamine hydrochloride, and ethyl acetoacetate/ethyl 4-
chloroacetoacetate/ethyl benzoylacetate has been implemented. The reactions were carried out in water as a
green solvent at room temperature. The corresponding heterocyclic products were separated by simple filtration
and washing with water. Also, the solvent was removed from the filtrate by evaporation to recycle the
Results: It was found that SA act as the catalyst for the synthesis of 4-arylidene-3-substituted isoxazole-5(4H)-
ones via three-component reaction of aromatic/hetero-aromatic aldehydes, hydroxylamine hydrochloride, and
three β-dicarbonyl compounds (ethyl acetoacetate, ethyl 4-chloroacetoacetate, and ethyl benzoylacetate). Optimization
of the catalyst quantity and solvent showed that the highest yield was achieved with 20 mol% of SA
in aqueous media. 4-Arylidene-3-substituted isoxazole-5(4H)-ones have been successfully synthesized in the
presence of SA catalyst.
Conclusion: The SA catalyst could be recovered easily from the filtrate via evaporation of solvent and reused
many times. The present synthetic method is a simple, green, clean, and environmentally friendliness alternative
for synthesizing 4-arylidene-3-substituted isoxazole-5(4H)-ones. Reactions were performed without the
use of heating, microwave and ultrasound irradiations.