INTRODUCTION:

Ultrasound is the name given to sound waves with frequencies higher than those to which human ears can respond, i.e. greater than 16kHz and between 7.0 and 0.015 cm with wavelength. This is transmitted by any material that exhibits elastic properties-solid, liquid, or gas¹. In 1917, the first commercial use of ultrasonics appeared with Langevin's echo-sound technique for estimating water depths resulting in the system known as SONAR (sound navigation and ranging). Ultrasound is the name given to sound waves with frequencies higher than those to which human ears can respond, i.e. greater than 16kHz and between 7.0 and 0.015 cm with wavelength². This is transmitted by any material that exhibits elastic properties-solid, liquid, or gas. In 1917, the first commercial use of ultrasonics appeared with Langevin's echo-sound technique for estimating water depths resulting in the system known as SONAR (sound navigation and ranging). The ever-increasing recognition of the need to conserve natural resources through the implementation of environmentally friendly processes and energy use efficiency has driven the actions of society's private and governmental sectors. This new paradigm has strongly impacted economic planning, leading to increased demands by society for products produced in a sustainable manner and to more stringent regulatory policies by governments³. Therefore, while profit was always the major concern in the past, more sustainable production practices are favoured in the current economic context. This has triggered a demand for the development of new, cleaner technologies at both industry and academy⁴. In the area of chemistry and chemical technology, Green Chemistry's 12 principles include a set of specific guidelines for the development of new synthetic methodologies and chemical processes, and the assessment of their environmental impact potential^5-6. As a result, various studies now regularly use nontradicional experimental methodologies in organic chemistry, such as solvent-free reactions, the implementation of alternative activation methods such as microwaves or ultrasound, the replacement of volatile organic solvents by water, ionic liquids, or supercritical CO₂, etc. Research has shown in medicinal chemistry that compounds with biological activity are mostly dependent upon heterocyclic structures. Azoles and their derivatives in particular have attracted growing interest as versatile intermediates for the synthesis of biologically active compounds such as potent antitumors, antibacterial, antiviral, and antioxidants⁷. Azoles are a broad class of 5-membered heterocyclic ring compounds with at least one nitrogen atom in their structure and one heteroatom in it. Because of the broad range of biological activities ascribed to structurally distinct azoles, the construction of this type of molecule has received considerable attention. Fluconazole, itraconazole, voriconazole, and posaconazole are commercially available antifungal agents which contain a nucleus of triazole. Celecoxib is a pyrazole class non steroidal anti-inflammatory and analgesic agent. Isoxazole compounds such as valdecoxib are active COX-2 inhibitors and are used in pain management. Researchers in universities and pharmaceutical industries have given much attention in this context to developing new, energy-saving, cost-effective, environmentally safe technologies for the synthesis of azoles⁸. Using ultrasound to accelerate reactions in this sense has proven to be a particularly effective method for achieving the Green Chemistry goals of minimizing waste and reducing energy requirements (Cintas and Luche, 1999). Ultrasonic irradiation applications are playing an growing role in chemical processes, especially in cases where traditional methods require drastic conditions or prolonged reaction times. Cella and Stefani's excellent review (Cella and Stefani, 2009), which covered the literature available up to about three years ago, clearly demonstrated the importance oftaking advantage of the unique features of ultrasound-assisted reactions to synthesize heterocyclic ring systems⁹. These reports were grouped according to the number of heteroatoms present in the ring (2,3or4) and subdivided by the azole class for each group. Reports were collected in the last segment in which more than one class of azoles is prepared, marked "Miscellaneous"¹⁰.

1. Cavitation:

Ultrasound waves can be transmitted through any material having elastic character. The movement of the sound source is transmitted to the medium particles, which oscillate in the direction of the wave and produce both longitudinal and transverse waves. When the medium molecules vibrate, the average distance between the molecules decreases in the process of compression, and increases during rarefaction. If the average molecular distance reaches the critical molecular distance needed to hold the liquid intact, the liquid breaks down; cavities (cavitation) and bubbles are formed. This process, known as cavitation, refers to the formation of liquid bubbles, and their subsequent dynamic life¹¹. In water, organic solvents, biological fluids, these bubbles can be filled with gas or vapor. Liquid helium, molten metals or other liquids. Bubble collapse results in high temperatures (up to 4700°C) and fluctuations in pressure (1 OPa). To produce reactive molecules, such as free radicals or carbenes, the solvent/reagent vapor experiences fragmentation. These high-energy species at the interface are concentrated and result in intermolecular reactions. If there are involatile solutes, though, they would also gather at the interface and react with the high-energy species. Besides this, the shock wave produced by the collapse of a bubble can affect the reactivity by altering the reactive species solvation¹².

2. Ultrasound Sources:

Ultrasonic irradiation of substances was used with a range of instruments. There are three main designs for specific laboratory use:

a. Ultrasonic bath cleaning

b. Cup horn sonicator

c. Direct ultrasonic horn immersion

The ultrasound source is a piezoelectric material (lead-zirconate-titanate ceramic (PZT) or quartz) that undergoes a high voltage alternating current with an ultrasonic frequency (15 kHz-10MHz). In this electric field, the piezoelectric material expands and contracts, and is connected to the cleaning bath (or amplifying horn) walls and transforms electrical energy into sound energy. In most applications the sonicators run in the range of 20-35 kHz at a fixed frequency. The acoustic field is continuous in cleaning baths while in probes it is in the pulsed form¹³. In the ultrasonic cleaning bath (a liquid (H20) is present to move the ultrasound to the reaction vessel from the generators. The reaction vessel (conical or R B flask) is submerged at a level in the water where the liquid in the flask is just above the water surface. The flask is balanced to the point where cavitation (bubbles) is maximum after a sonication is begun. The water temperature is kept constant by refrigeration. Results obtained by using a cleaning bath are not always reproducible, and the use of sonic probes is therefore favored at times¹⁴.

3. Reactions Accelerated by Ultrasound:

Using ultrasound, several common reactions that are used in synthetic organic chemistry can be performed more effectively. There are also benefits of this. Generally, yield increases, and by-product percentages decrease. Reactions occur quicker, allowing to use lower temperatures. Ultrasound provides alternative reaction mechanisms, leading to the formation of intermediates with high energy. Sonochemistry also allows safe conducting of reactions involving organometallic reagents¹⁵.

4. Sonochemical Boon:

In addition to the types of reactions mentioned above, in the case of enzyme. catalyzed reactions, ultrasound was also used. In non-aqueous solvents, where ultrasound has been used over the past few years, there are a great number of other such reactions. For example, there is extensive analysis of conjugate addition of alkyl groups to a,/3 unsaturated compounds.Sonochemical principles have been reportedly applied in polymer chemistry and coal liquification. Extension of sonochemistry combination with other different approaches, such as photochemistry and electrochemistry, seems exciting. Since it is an emerging area of interest and a recent one, there is much more to be explored in ultrasonics as an significant resource to explore its full potential for discovering new reactions using highly energetic sound waves. The sonochemical boom turns out to be a real boon to synthetic chemistry¹⁶.

5. Ultrasound and its chemical effects:

The discovery of the piezoelectric effect in the 1880s laid the groundwork for the development of modern ultrasonic instruments. Mechanical vibrations are produced by piezoelectric materials in response to an applied alternating electrical potential. Ultrasonic waves are produced if the potentiality is applied at sufficiently high frequency. Cavitation is the phenomenon which is responsible for the beneficial effects of ultrasound on chemical reactions. Ultrasonic waves are propagated by alternating compressions and induced rarefactions in the transmission medium they are traveling through. The liquid molecules are separated during the sound wave's rarefaction cycle, generating bubbles which then collapse in the compression cycle. These rapid and violent implosions produce short-lived regions with local temperatures of approximately 5000°C, pressure of approximately 1000 atm and heating and cooling rates that may exceed 10 billion °C per second. These localized hot spots can be considered as micro reactors in which the mechanical energy of sound becomes a useful chemical source. In addition to producing these hot spots, mechanical effects resulting from the violent collapse can also be generated (Mason andLorimer, 2002). Over 80 years have passed since the effect of ultrasound on reaction rates was first recorded by Richards and Loomis (Richards and Loomis, 1927). However, at the time, little attention was given to this work because it employed a high-frequency system that was not widely available to chemists. Two classical papers, published in 1978 and 1980, provided a major stimulus for the development of modern sonochemistry, according to the Cravotto and Cintas review (Cravottoand Cintas, 2006):

a. The report by Fry and Herr (Fry and Herr, 1978) of the reductive dehalogenation of dibromoketones with mercury dispersed by ultrasound.

b. The work of Luche and Damiano (LucheandDamiano, 1980) on the two main sources of ultrasound in organic synthesis are ultrasonic cleaning baths and ultrasonic immersion probes, which typically operate at frequencies of 40 and 20 kHz, respectively (Mason, 1997). The former are used more commonly in organic synthesis simply because they are less expensive and thus more widely available to chemists, even though the amount of energy transferred to the reaction medium is lower than that of ultrasonic probe systems, which directly deposit the acoustic energy into the reaction medium¹⁷.

6. Oxadiazole derivatives:

Azoles containing polyhaloalkyl groups are of considerable interest due to their potential herbicidal, fungicidal, insecticidal, analgesic, antipyretic, and anti-inflammatory properties. In addition, 1,2,4-oxadiazoles are reported to posses various types of biological activities (Elguero et al., 2002). Very recently, the rapid preparation of 1,2,4-oxadiazoles (121) under ultrasound irradiation was reported (Bretanha et al., 2011). The products were obtained with short reaction times (15 minutes) and in excellent yields (84-98%)¹⁸. (Scheme-I)

7. Thiazole derivatives:

In 2009, Noei and Khosropour (NoeiandKhosropour, 2009) reported a high yield, green protocol for the synthesis of 2,4-diarylthiazole derivatives via the reaction of arylthioamideswith ┙-bromoacetophenones under ultrasonic irradiation in the ionic liquid [bmim]BF4¹⁹. (Scheme-II)

Among the natural products containing a 1,3-thiazole ring, thiamine (aneurine, vitamin B1) is of great importance (Eicherand Hauptmann, 2003). Several 2-(N-arylamino)-4-arylthiazoles were prepared by the reaction of ┙-bromoacetophenoneswith N-aryl substituted thioureas, as in the classical Hantzsch synthesis, but using ultrasonic irradiation (Gupta et al., 2010). This further confirmed that thiazoleheterocycles can be conveniently synthesized in good yields (88-97%) by the application of sonochemistry. The insecticidal activity of these 1,3-thiazoles was evaluated²⁰.(Scheme-III)

Recently, we reported an ultrasound-based procedure for the synthesis of pyrazolyl substituted thiazoles by the cyclization reaction between thiocarbamoyl-pyrazoles and ┙-bromoacetophenone (96) (Venzke et al., 2011). The reactions occurred in only 15minutes in ethanol at room temperature, affording the pure products in 47-93% yields by simple filtration of the reaction mixture²¹.(Scheme-IV)

Recently, Mamaghani and co-workers described a sonochemical method for the preparation of iminothiazolidinones (Mamaghani et al., 2011). Thioureas were generated in situ and treated with a mixture of a suitable aldehyde, chloroform and 1,8diazabicyclo [5.4.0] undec-7-ene (DBU) in dimethyl ether (DME) under an inert atmosphere. Subsequent addition of aqueous NaOH at and sonication furnished the products in 75-91% yields. A 1:1 mixture of regioisomers was observed when Ncyclohexyl-N’-ethylthiourea was employed. However, a regiosselective reaction took place with other substituents in the thiourea. The target molecules were obtained in better yields and much shorter reaction times using ultrasound than with conventional methodology²².(Scheme-V)

CONCLUSION:

Several convenient synthetic methodologies promoted by ultrasound for preparing the title class of compounds have been established. The key benefits of using ultrasound in azole synthesis are obvious as compared to traditional methodologies, i.e. shortened reaction times and increased yields. Most of the papers covered by the analysis used as energy sources basic ultrasonic cleaning baths. While these low-potency sources of ultrasonic radiation are typically less effective than immersion sonication probes, requiring longer reaction times, cleaning baths in chemistry laboratories are fairly inexpensive and commonly available.

REFERENCES:

1. Shelke, S.; Mhaske, G.; Gadakh, S. and Gill, C. Green synthesis and biological evaluation of some novel azoles as antimicrobial agents. Bioorg Med Chem Let. 2010; 20: 7200-7204.

2. Ahirrao, P. Recent developments in antitubercular drugs. Mini Rev. Med. Chem. 2008; 8: 1441–1451.

3. Migliori, G.B.; DeLaco, G.; Besozzi, G.; Centis, R.; Cirillo, D.M. First tuberculosis cases in Italy resistant to all tested drugs. Euro Surveill. 2007; 12: 3194.

4. Diacon, A.H.; Donald, P.R.; Pym, A.; Grobusch, M.; Patientia, R.F.; Mahanyele, R.; Bantubani, N.; Narasimooloo, R.; De Marez, T.; van Heeswijk, R.. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: Long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob. Agents Chemother. 2012; 56: 3271–3276.

5. Yadav A, Mohite S, Design, Synthesis and Characterization of Some Novel benzamide derivatives and it’s Pharmacological Screening. 2020. Int J Sci Res Sci Technol. 7(2): 68-74.

6. Yadav A, Mohite S, Magdum C, Synthesis, Characterization and Biological Evaluation of Some Novel 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents, Int J Sci Res Sci Technol. March-April-2020; 7 (2): 275-282.

7. Rajput M. D, Yadav A. R, Mohite S.K, Synthesis, Characterization of Benzimidazole Derivatives as Potent Antimicrobial Agents. 2020. Int. J. Pharm. 17(4): 279-285.

8. Shinde, A. D.; Kale, B. Y.; Shingate, B. B. andShingare, M. S. Synthesis and characterization of 1-benzofuran-2-yl thiadiazoles, triazoles and oxadiazoles by conventional and non-conventional methods. J KorChem Soc. 2010; 54: 582-588.

9. Shinde, A. D.; Sonar, S. S.; Shingate, B. B. and Shingare, M. S. Synthesis and biological screening of novel thiadiazoles, selenadiazoles, and spirocyclicbenzopyran by ultrasonic and microwave irradiation. Phosphorus, Sulfur, and Silicon. 2010; 185: 1594-1603.

10. Silva, F. A. N.; Galluzzi, M. P.; Albuquerque, B.; Pizzuti, L.; Gressler, V.; Rivelli, D. P.; Barros, S. B. M. and Pereira, C. M. P. Ultrasound irradiation promoted largescale preparation in aqueous media and antioxidant activity of azoles. Let Drug Design andDiscov. 2009; 6: 323-326.

11. Tiwari, V.; Parvez, A. and Meshram. J. Benign methodology and improved synthesis of 5-(2-chloroquinolin-3-yl)-3-phenyl-4,5-dihydroisoxazoline using acetic acid aqueous solution under ultrasound irradiation. UltrasonSonochem. 2008; 18: 911-916.

12. Venzke, D.; Flores, A. F. C.; Quina, F. H.; Pizzuti, L. and Pereira, C. M. P. Ultrasound promoted greener synthesis of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4phenylthiazoles. UltrasonSonochem. 2009; 18: 370-374.

13. Yuan, Y.-Q. and Guo, S.-R. TMSCl/Fe (NO3)3-Catalyzed synthesis of 2arylbenzothiazoles and 2-arylbenzimidazoles under ultrasonic irradiation. SynCommun. 2011; 41: 2169-2177.

14. Zang, H.; Su, Q.; Mo, Y.; Cheng, B.-W. and Jun, S. Ionic liquid [emim]OAc under ultrasonic irradiation towards the first synthesis of trisubstitutedimidazoles. UltrasonSonochem. 2010; 17: 749-751.

15. Pizzuti, L.; Martins, P. L. G.; Ribeiro, B. A.; Quina, F. H.; Pinto, E.; Flores, A. F. C.; Venzke, D. and Pereira, C. M. P. Efficient sonochemical synthesis of novel 3,5-diaryl4,5-dihydro-1H-pyrazole-1-carboximidamides. UltrasonSonochem, 2010; 17: 34-37.

16. Pizzuti, L.; Piovesan, L. A.; Flores, A. F. C.; Quina, F. H. and Pereira, C. M. P. Environmentally friendly sonocatalysis promoted preparation of 1-thiocarbamoyl3,5-diaryl-4,5-dihydro-1H-pyrazoles. UltrasonSonochem. 2009; 16: 728-731.

17. Richards, W. T. and Loomis, A. L. The chemical effects of high-frequency sound waves. I. A preliminary survey. Journal of the American Chemical Society. 1927; 49: 30863100.

18. Rodrigues-Santos, C. E. and Echevarria, A. (2011). Convenient syntheses of pyrazolo [3,4b] pyridin-6-ones using either microwave or ultrasound irradiation. Tetrahedron Let. 2010; 52: 336-340.

19. Saleh, T. S. and El-Rahman, T. S. Ultrasound promoted synthesis of substituted pyrazoles and isoxazoles containing sulphone moiety. UltrasonicsSonochemistry, 2009; 16: 237-242.

20. Sant’Anna, G. S.; Machado, P.; Sauzem, P. D.; Rosa, F. A.; Rubin, M. A.; Ferreira, J.; Bonacorso, H. G.; Zanatta, N. and Martins, M. A. P. Ultrasound promoted synthesis of 2-imidazolines in water: a greener approach toward monoamine oxidase inhibitors. Bioorg MedChem Let. 2009; 19: 546-549.

21. Shekouhy, M. and Hasaninejad, A. Ultrasound-promoted catalyst-free one pot four component synthesis of 2H-indazolo [2,1-b] phthalazine-triones in neutral ionic liquid 1-butyl-3-methylimidazolium bromide. UltrasonSonochem. 2010; 19: 307-313.

22. Cravotto, G.; Cintas, P. Power ultrasound in organic synthesis: Moving cavitational chemistry from academia to innovative and large-scale applications. J. Chem. Soc. 2006, 35, 180–196.

Received on 08.07.2020 Modified on 31.07.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(4):308-312.

DOI: 10.5958/0975-4377.2020.00051.8