Microwave and Ultrasound Activated Synthesis of 3-(1,3-Diphenyl-1H- Pyrazole-4-Carbonyl)-2-Substituted-4H-Chromen-4-one and Compared with Conventional Method

Introduction: Pyrazoles and chromones represent an important class of heterocyclic scaffolds with extensive applications in medicinal chemistry. A wide range of synthetic methodol-ogies for the construction of these frameworks has been reported in the literature. Among these, microwave- and ultrasound-assisted irradiation techniques have attracted considerable attention for their ability to significantly reduce reaction times and, in many cases, enhance reaction efficiency and yield. materials and methods: 2. MATERIALS AND METHODS All the reagents are research grade and solvents were of analytical grade. The reagents and solvents were used without further purification. RAGA’s scientific microwave system with 700 w power, 31 lit. capacity and 2450 Hz. frequency were used for synthesis. Merck, precoated silica gel 60 F254 (Aluminum sheets) plates were used for analytical TLC.The melting points of synthesized compounds were determined by open capillary method and uncorrected. The IR spectra for some selected compounds were scanned on Perkin-Elmer FT spectrometer 1420 in KBr disc. The 1H NMR spectra of newly synthesized compounds were scanned on Bruckervarian 300 MHz spectrometer using DMSO-d6 as a solvent using TMS as an internal standard. The mass spectra for some selected synthesized compounds were recorded on EI-Shimadzu GC-MS spectrometer. Objective: The primary objective of this work is to synthesize chromone–pyrazole derivatives using ultrasound- and microwave-assisted methodologies. In the present study, the synthesis of five de-rivatives of 3-(1,3-diphenyl-1H-pyrazole-4-carbonyl)-2-methyl-4H-chromen-4-one and five deriv-atives of 3-(1,3-diphenyl-1H-pyrazole-4-carbonyl)-2-ethyl-4H-chromen-4-one is reported. results: The traditional method was used for synthesis of 3-(1,3-diphenyl-1H-pyrazole-4-carbonyl)-2-substituted-4H-chromen-4-one by acid catalysed cyclization of β –diketoneusing hazardous/toxic reagents like phosphorous oxychloride, pyridine and strong base KOH [36]. The required to get desired compound is almost 2 to 3 hrs by conventional heating. In present work 3-(1,3-Diphenyl-1H-pyrazol-4-carbonyl)-2-methyl chromone-4-ones and 3-(1,3-diphenyl-1H-pyrazol-4-carbonyl)-2-ethyl chromone-4-ones are synthesized by the reaction of 1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(2-hydroxyphenyl)-propane-1,3-diones with acetic anhydride and propanoic anhydride under the influence of microwave by using K2CO3 as a green solid support and pyridine in ultrasonic irradiation in quantitative yields (Scheme-1). 3-(1,3-Diphenyl-1H-Pyrazole-4-Carbonyl)-2-Substituted-4H-Chromen-4-one The similar compounds were synthesized and characterization data were compared with data reported in previous investigation [36]. The melting points of synthesized compounds were recorded and compared with previous reported data. The melting points are match with reported data and are in the range of 180-232 0C. The required for synthesis of desired compounds is about 30 min by ultrasound method and about 5-6 min by microwave irradiation method. This is very less as compared with conventional method. All the synthesized products were obtained with excellent yields and which is higher than the conventional method. The synthesized compounds 2a-e by ultrasound and microwave irradiation method are listed in Table-1 with their physico-chemical analytical data. While compounds 3a-e were synthesized by ultrasound and microwave irradiation method are listed in Table-2 with their physico-chemical analytical data. Method: Five derivatives of 3-(1,3-diphenyl-1H-pyrazole-4-carbonyl)-2-methyl-4H-chromen-4-one were prepared by treating 1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(2-hydroxyphenyl)propane-1,3-dione with acetic anhydride. Similarly, five derivatives of 3-(1,3-diphenyl-1H-pyrazole-4-car-bonyl)-2-ethyl-4H-chromen-4-one were synthesized by reacting the same precursor with propanoic anhydride. Microwave-assisted reactions were carried out using potassium carbonate as a green solid support, whereas pyridine was employed in the ultrasound-assisted protocol. discussion: The IR spectra of some selected compounds were taken using KBr pallet and shows characteristic absorption bands for two carbonyl groups. The bands observedin the range 1635-1645 cm-1 for chromone carbonyl and the band in the range 1648-1655 cm-1 for carbony near the pyrazole ring. In addition to this, the IR spectrum shows absorption band in the range 3050-3060 cm-1 for =C-H stretching frequency. The C=N shows two absorption band around 1600-1610 cm-1 and 1555-1565 cm-1. The IR spectrum also shows characteristic absorption band for C-Cl in the range 680-760 cm-1 and C-Br in the range 630- 675cm-1. The 1H NMR spectra of synthesized compounds were taken in the solvent DMSO-d6 using TMS as internal standard. The 1H NMR spectra study shows proton signals at 2.36-2.43 δppm due to aromatic methyl groups. A spectrum also shows signals at 2.60 -2.80 δppm doublet for aromatic –CH2 and singlet in the range 1.2-1.3 δppm for methyl group. The proton signal at 7.20-8.50 δppm is due to aromatic proton shows multiplate. The pyrazole proton appears around 9.21-9.88 δppm and which shows singlet. Results: The chromone–pyrazole derivatives were successfully synthesized and characterized. The structures of the synthesized compounds were confirmed by melting point determination (in agreement with reported values), TLC, and spectroscopic analyses, including IR, 1H NMR, and mass spectrom-etry. The results obtained were also compared with those from conventional thermal methods. Discussion: The comparison with conventional thermal methods indicates the effectiveness of the proposed approach. The microwave- and ultrasound-assisted procedures offer significant advantages, including the elimination of hazardous or toxic reagents such as phosphorus oxychloride, pyridine, and strong bases like KOH, thereby making the process more environmentally friendly and safer. Conclusion: The microwave- and ultrasound-mediated protocols provide clean, efficient, and su-perior alternatives to traditional thermal methods for the synthesis of the target chromone–pyrazole derivatives. Microwave irradiation enabled completion of the reactions in approximately 6 min, which is significantly faster than the ultrasound-assisted method, which required about 30 min. All target compounds were isolated in excellent yields, exceeding those obtained under conventional heating conditions. Notably, ultrasound-assisted reactions afforded slightly higher yields than mi-crowave-assisted reactions.