Synthesis of Pyrazole Compounds by Using Sonication Method

A simple method for the synthesis of pyrazoles derivatives carried out by cyclization of cyanide with hydrazine hydrate by using sonication method. All the prepared compounds were characterized by 1H, 13C NMR and IR Spectroscopy.

A literature survey reveals that several reported methods for the synthesis of Pyrazole unit generally synthesized i.e using the 3 component coupling reaction of aldehydes, 1,3-dicarbonyls, and diazo compounds, as well as tosyl hydrazones, rhodium-catalyzed addition-cyclization of hydrazines with alkynes 21 cyclic enol triflates and an elaborated set of diazoacetates 22 hydrazones and β-protonation/nucleophilic addition/aromatization sequence. 23 A copper-mediated cyclization, trifluoromethylation, and detosylation. 24 Potassium 1,1,3,3-tetranitropropane treated readily with various (hetero)arylamines. 25 other methods with metals, Lewis acids, or bases were also reported. 26−30 But, those techniques have their benefit whilst a number of these are the problem by the limitation of long time response, individual situations and lower yields. for this reason, the improvement of a brand new technique for the synthesis of Pyrazole derivatives might be fairly applicable.
From the last three decades, ultrasound utility has been utilized in natural product synthesis 31 Which has an overwhelming interest because it gives chemists tremendously simple and less expensive techniques for chemical activation. 32 similarly, this method is also recognized to accelerate the rate of a chemical response, and at the same time increases the reaction yield. 33  laboratory result confirmed that pyrazole derivatives could be readily prepared from the beginning materials of carboxylic acid derivatives beneath ultrasound probe irradiation in neat circumstance as mentioned in this paper (Scheme 1).

Methodology
General Procedure for the synthesis of pyrazole derivative in our research, we developed novel, simple, efficient, and rapid method for synthesis of pyrazole derivative by using carboxylic acid as starting material. First the carboxylic acid is converted into ester using methanol and con. sulphuric acid reflux under nitrogen atmosphere for 16 hours. In the second step acetonitrile in toluene mixed with a solution of NaH under nitrogen atmosphere and stirred for 30 min was added methyl ester and reflux reaction mixture for 17 h to give oxonitrile. In the third step the oxonitrile in acetic acid and hydrazine hydrate undergo cyclization reaction to got final products pyrazole in sonication for 1-2 hours. In this method, we used different halogen aromatic substituted carboxylic acid, nicotinic acid, and acetic acid but we observed the percentage of final products.
To study the generality of this method type of examples had been illustrated for the synthesis pyrazole and outcomes are summarized. The reaction is well matched for various substituents inclusive of CH 3 , I, NO 2 , CN, and F. This approach is also powerful for the heteroaromatic carboxylic acid which shapes their corresponding pyrazole derivatives in 55-67% of yields. The formation of the desired product becomes confirmed by using 1 H NMR, 13 C NMR and IR.

ExPERIMENTAL
Melting points had been determined in an open capillary tube and are uncorrected. IR spectra have been recorded in KBr on a Perkin-Elmer spectrometer. 1 H-NMR and 13 C spectra have been recorded on a Gemini 400 MHz tool in DMSO as solvent and TMS as an inner fashionable. The purity of products was checked by thin-layer chromatography (TLC) on silica gel.

Synthesis of ester 1(a-J)
To a stirred solution of substituted acid (1.0 eq.) in methanol (10 mL) turned into delivered con.H 2 SO 4 (cat.) at 0-5°C below N 2 environment. The resultant became heated at reflux temperature for 16 hours. The reaction turned into monitored through TLC (mobile phase:-20% ethyl acetate: hexane). Upon entire conversion reaction aggregate became distilled out, obtained crude was poured into ice water, extracted with ethyl acetate (3 x 25 mL), blended natural layer changed into washed with sat. bicarbonate answer, dried over Na 2 SO 4 , distilled out organic layer underneath reduced pressure to get methyl ester intermediate (Yield :68-81%).

Synthesis of 3-oxonitril 2(a-J)
In a smooth and dry a 100 mL round bottom flask was taken acetonitrile (5.0 eq.) in toluene (10 mL), cool to 0-5°C, in that solution NaH (55%, 2.5 eq.) became introduced lot wise below N 2 atmosphere and stirred for 30 min, then an answer of substituted methyl ester intermediate in toluene (5.0 mL). Reaction combination becomes heated at reflux temperature for 17 hours. Response become monitored via TLC ( 30% ethyl acetate: hexane). Upon entire conversion reaction mixture was poured into ice water slowly, extracted with ethyl acetate (3 x 25 mL), layer changed into dried over Na 2 SO 4 , distilled out organic layer under reduced vacuum to get 3-oxonitrile intermediate (Yield:80-93 %).

Synthesis of 3-oxonitrile 3(a-J)
To a stirred of 3-oxonitrile (1.0eq.) in acetic acid (5mL), hydrazine hydrate (2.0 eq.). Reaction combination becomes sonicated for 1-2 hours. The reaction became monitored with the aid of TLC (cellular section:-50% ethyl acetate: hexane). Upon complete conversion become poured into water, basify the use of 20% NaOH solution, extracted with ethyl acetate (3 x 30 mL), mixed natural layer became dried over Na 2 SO 4 , distilled out organic layer beneath reduced pressure. obtained crude turned into purified with the aid of column chromatography the usage of ethyl acetate: hexane as an eluent to get substituted three-amino pyrazole intermediate (Yield:55-67%).
The Formation of all preferred Products has been Purified through the usage of column chromatography & confirmed by 1 H & 13 C NMR.

CONCLUSION
We defined a successful approach such as an efficient and handy inexperienced synthesis, for pyrazole derivatives using a sonication technique. The approach offers several advantages increasing the yield of products, the usage of the inexpensive starting fabric, and an easy experimental workup technique that makes it a beneficial process for the synthesis of pyrazole derivatives.

ACKNOwLEDGMENT
We're grateful to the Department of Chemistry of MSP Mandal's Shri Shivaji college Parbhani major Dr. B. U. Jadhav for imparting the laboratory facility. Also thanks to my college Principal Dr. Omprakash Jadhav Sir for Supporting & Enhancing me for doing research.