: a versatile building block in organic synthesis

: Aqueous phase synthesis of
organic compounds is environmentally friendly, safe, non-toxic, clean, green
and inexpensive 1-3. Many important transformations can be carried out in
water 1-3. Multicomponent reactions in water is the best method for the
synthesis of a variety of organic compounds
under eco friendly conditions 4,5. Use of water decreases the risk associated
with organic solvents
and also maintains a healthy laboratory atmosphere for the workers. Thus, water
as a reaction media is attractive from both the economical and environmental point
of view 6. Isoxazole derivatives have served as a versatile building block in
organic synthesis 7. Isoxazol-5-one derivatives have attracted increasing
interest because of their significant pharmaceutical and therapeutic
properties, such as hypoglycaemic, immunosuppressive, anti-inflammatory, and
anti-bacterial activities 8-11. In addition, isoxazole core is a structural
element in many commercial pharmaceuticals 12-15.

The
present work was carried out using conventional method to synthesize
4-3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-ylmethylene-3-methyl-4H-isoxaol-5-ones. At first step,
ethyl acetoacetate reacts with hydroxylamine hydrochloride to afford oxime, and
further ring closure occurs to form product 3-methyl-4H-isoxazol-5-one. And then, the Knoevenagel reactions between
3-methyl-4H-isoxazol-5-one and
3-(substituted phenyl)-1-phenyl-1H-
pyrazole 4-carbaldehydes produces final product.

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In
recent years, some new methods such as solid state grinding 16, solid state
heating 16 and multicomponent reactions 17,18 have been reported, with
variable yields of condensation compounds in solution or under solvent-free
conditions. Recently, synthesis of these compounds was reported to be carried
out using ultrasound irradiation 19. A study on effect of solvent and mole
percent of sodium benzoate as catalyst was also reported earlier 20.

In
present study, the conventional method of aqueous phase stirring was adopted
for the synthesis of 3-methyl-4H-isoxazol-5-one.
The second step i.e. Knoevenagel reaction was carried out in situ by adding appropriate pyrazole-4-carbaldehyde derivative
along with a catalyst. Knoevenagel reaction was carried out without catalyst
and also by using sodium benzoate as catalyst, separately. Second step was also
carried out as room temperature stirring only.

Present
work reports the antibacterial and antifungal study of all synthesized products
along with crystal structure of five compounds.
Some compounds were found to have activity comparable to ampicillin against E. coli and one compound was found to
have activity comparable to S. pyogenus.
This is the first known report of crystal structure of this class of molecules.