Efficient Antimicrobial Activities of Microwave-assisted Synthesis of Benzisoxazole Derivatives

The present study deals with the synthesis of benzisoxazole derivatives beginning from 5,5-dimethyl cyclohexane-1,3-dione by making use of a microwave reactor. The microwave reactions are effortless, well-organized, clean, swift and financially viable for the synthesis of a huge amount of organic molecules, have offered the drive for many chemists to change from conventional heating methods to microwave-assisted chemistry. In latest years, microwave synthesized organic reaction has appeared as a new device in organic synthesis. The synthesized compounds were for the studie by using IR, NMR, mass spectra and antimicrobial studies also carried out.


INTRODUCTION
Microwave assisted synthesis is an eco-friendly and well-organized synthesis of organic compounds in contrast to the conventional process. In this system, reaction takes place more swiftly, securely and with advanced chemical yields and thus, this method becomes greater to the conventional mode.
Benzisoxazole exhibits a remarkable p r o s p e c t i ve a s a n t i m i c r o b i a l , a n t i c a n c e r, anti-inflammatory actions. In medicinal chemistry as it relates to the broad and general outline of the different benzisoxazole analogs, their application as beginning building blocks of diverse architectures on scales adequate to drive human drug experiments. [1][2][3][4][5] Heterocyclic molecules such as benzisoxazole derivatives, particularly 3-(piperidin-4-yl)-1,2-benzisoxazole have been extensively used as antipsychotic drugs. 6 Atypical antipsychotic drugs which are derived from benzisoxazole. 7 Benzisoxazole derivatives are oxygen, nitrogen holding heterocycles with broad variety of synthetic and pharmaceutical applications, and are renowned for biological activities. The high therapeutic properties of these heterocycles have persuaded the medicinal chemist to synthesize a huge quantity of chemotherapeutic agents. 8 Isoxazole is a vital heterocyclic core, which is broadly used as many pharmacological properties. [9][10][11][12] We herein detail the synthesis of benzisoxazole derivatives from dimedone with the use of microwave irradiation.

MATERIALS AND METHOD
Dimedone, benzaldehyde and hydroxylamine hydrochloride were provided by Sigma-Aldrich (St.Louis, USA). IR spectra were documented in SHIMADZU FT-IR 8400S spectrometer by employing KBr pellets. 1 H NMR (500 MHz) and 13 C NMR (400 MHz) spectra recorded on Brucker spectrometer using CDCl 3 solvent. Microwave (Godrej GMS 17M 07 WHGX). Melting point was recorded in Royal Scientific RSW 138 B.

Synthesis of benzisoxazole derivatives
5,5-dimethylcyclohexane-1,3-dione (0.001 mm) react with hydroxylamine hydrochloride (0.001 mm) and benzaldehyde (0.1 mL) under microwave irradiation at a suitable time ( Table 1). The development of the reaction was monitored on TLC (Scheme 1). Following the completion of reaction, the reaction combination was quenched in distilled water and the precipitate was formed. It were filtered and dried.

IR and NMR spectrum of benzisoxazole derivatives (1-4)
Synthesis of benzisoxazole derivatives (1-4) by utilizing microwave irradiation for suitable time (9 min) afforded remarkable yields with absolute transformation of reactants. The foundation of newly synthesized (1-4) was launched by IR and NMR spectroscopy.

Antimicrobial activities
The preliminary antimicrobial activities of the moieties 1-4 are scrutinized using disc diffusion method. The bacterial strains viz., B. subtilis, E. coli, P. aeruginosa, S. aureus, S. pyogenes are used in this study. Dimethylsulphoxide is used as a control. Streptomycin and Amphotericin B are used as an indication for bacterial and fungal studies correspondingly.
The antibacterial screening studies indicated that the compound having 1, 2, 4 showed outstanding antibacterial against B. subtilis, E. coli, S. pyogenes, but no active against P. aeruginosa and S. aureus. The compound 1 is more active against P. aeruginosa and S. pyogenes (Fig. 1). The results are given in Table 2. The antifungal activity screening studies confirmed that the 1, 2, 4 chloro substituted compound showed outstanding activity against A.flavus, P. chryogenum, F. oxysporum and less active against A. niger, T. veride (Fig. 2). The result is given in Table 3.

CONCLUSION
The depicted synthetic protocol permits for the preparation of a series of benzisoxazole derivatives as new arrangement which can be latently useful in various pharmacological applications. Chief benefits of these original techniques are equipped with effortlessness, high yield in a very tiny reaction time, eco-friendly conditions, very cheap, effortlessly available reagent and simple technique employed.