“Green synthesis of chalcone derivatives using CaO derived from chicken eggshells as a catalyst” DISSERTATION Submitted in Partial Fulfilment of The Degree of M.Sc. ( Organic Chemistry) By Ekta Fal Desai 21P0490258 To Department of Chemistry P.E.S’s R.S.N college of Arts and Science Farmagudi, Ponda-Goa 403401 Academic Year: 2022-2023CERTIFICATE This is to certify that the dissertation entitled ‘Green synthesis of from chicken eggshells as a chalcone derivatives using CaO derived catalyst’ is bonafide work carried out by Ekta Fal Desai of M.Sc. Part- II (Organic Chemistry) in partial fulfilment of the requirements for the award Degree of Masters of Science in Chemistry at the Department of Chemistry, P.E.S’s R.S.N College of Arts and Science, Farmagudi, Ponda-Goa for the academic year 2022-2023. ee Project Supervisor M.Sc. Co-ordinator (Ms. Pooja Vishwakarma) (Mr. Domnic S. Dias) Principal External Examiner (Dr. Vikas J. Pissurlekar)DECLARATION ‘Green synthesis of chalcone derivatives using CaO derived from chicken eggshells as a catalyst’ I declare that this dissertation has been compiled by me under the supervision of Ms. Pooja Vishwakarma and has not been previously presented for the award of any degree or diploma of any other similar titles in Goa University or elsewhere. Name Seat No. Signature Ekta Fal Desai 21P0490258 swe Project Supervisor (Ms. Pooja Vishwakarma)ACKNOWLEDGEMENT 1 feel great pleasure to present this project “ Green synthesis of chalcone derivatives using CaO derived from chicken eggshells as a catalyst” I would like to thank our project in-charge Ms. Pooja Vishwakarma, ant professor of Chemistry in Ponda Education Society’s Shri Ravi Sitaram Naik College of Arts and Science, Farmagudi, Ponda- Goa. Whole heartly, who enriched our knowledge by his guidance at each and every step under whose whole guidance I could complete my project assist 1am thankful to the principal of our college Dr. Vikas Pissurlekar and M.Sc. coordinator Mr. Domnic S. Dias. ‘And I shall never forget the help provided by our laboratory assistants and attendants to me during my project work and their kind co- operation. Finally, 1 would like to thank my parents for their financial and moral support without which this project would not have succeeded. And, lastly, | would like to thank all my friends for being with me and everyone who helped me in completing this project.SR.NO. TITLE PAGE NO. io | INTRODUCTION 14 z LITREATURE REVIEW 6-10 3 EXPERIMENTAL SECTION 12-17 4. RESULTS AND DISCUSSION 19-23 5. CONCLUSION 24 REFERENCES 25—e.eorow mmo History Chalcone is a pale yellow solid organic compound. Chalcones belong to an important class of plants flavonoids, having chemical formula CisH120 and melting point is 55-57°C, boiling point is 345-348°C. The term "Chalcones” is derived from the Greek word “chalcos” which means “bronze”. Chalcones were initially manufactured in research lab in late 18005 Chalcones that derived from nature exist mostly as colors of petal and have been established in the heartwood, leaf, bark, fruit, and root of a range of plants. Chaleones are also known as benzyl acetophenone or benzylidene acetophenone. Chalcones are a,f-Unsaturated ketones consisting, of two aromatic rings having different arrangement of substituents. In chaleones two fragments rings are connected by an aliphatic three carbon series. 0 Z Figure 1.1: Chaleone— Pharmacodynamics Chalcone @ natural structure demonstrates many pharmacological activites including anti- cancer, antidiabetic, antimicrobial, anti-inflammatory, antitumor, anti-Alzheimer,ete and plays pivotal roles in medicinal chemistry. In cancer chemotherapy, multidrug resistance(MD) highly associated with ATP-binding cassette transport proteins overexpression, derivative bearing a,B-unsaturated ketone acts as the potent inhibitor against N¢ AND H1975 cells, It has antiproliferative ability against NCI-H60 cells in concerntration dependent manner through modulating ROS to include capase-3-mediated Pyroptosis. The chalcone induced apoptosis of human hepatic and lung cancer cells which Prevented cancer cell migration and invasion. It strongly suppressed tumor growth in a mouse model of xenograft tumors. The pyrazoles derived from chalcones have excellent anti-cancer Properties. The enhancement of drug efflux caused by ATP-binding cassette transporters overexpression is an important factor for multidrug resistance(MDR) in cancers. It was found that chalcone and bis-chalcone derivatives displayed the reversal activites of MDR cancer cell lines. Chalcones are pharmacologically active compounds chemicaly known as derivatives of 1,3- diphenylprop-2-en-1-one. Some chalcones have been reported as inhibitors of lipoxygenase, - secretase(BACE1), acylcholinesterase(AChE), cyclooxygenase, peroxisome _proliferator activated receptor gamma and Yersinia enterocolitica tyrosine phosphate. Clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines to inhbit a number of pathologicalmicroorganisms and parasites and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability.5 i i Ez éCatalyst ‘es the rate at which a chemical reaction approaches A catalyst is a substance that incre‘ . fe F equilibrium without being substantially consumed in the process. A catalyst affects only the Fate of reaction. It changes neither the thermodynamics of the reaction nor its equilibrium composition Heterogeneous catalyst is one whose molecules are dispered in the same phase Homogencous catalyst is one whose molecules are not dispered in the same phase. The use of heterogenous catalysts has received considerable importance in organic synthesis because of their ease of handing, enhanced reaction rates, greater selectivity, simple work up and recoverability of the catalyst. Green cat: lyst ‘The developments in the green chemistry are intrinsically connected mostly to the bio-ca due to its key synthesis from renewable sources. Green catalyst has potential to cat different chemical reaction and therefore being an essential alternative for enviro} ' unsafe chemical mechanisms. They are highlighted efficiently for the chemical transformation by reducing the cos, inereasing the potential efficiency, reducing environmental exposure and Promoting the solution of overall method sustainability for the development of the green chemistry. CaO as heterogeneous catalystScheme 1: H. Mahavid and coworkers carried out simple green organic synthesis under microwave condition as they used calcium oxide as a catalyst and the merits of this method is inexpensive and casily available solid base catalyst, short reaction time, high yield compared to other methods and avoid the use of toxic reagents and solvent free condition FR Scheme 1: Synthesis of chalcone under microwave condition using calcium oxide as a catalyst Scheme 2: Jin Wang and coworkers carried out Aldol Condensation of acetophenone and benzaldehydein in presence of commercial CaO and modified Calcium Oxide as a catalyst. The best yields of chalcone were recorded for aldehydes with electron withdrawing groups. The product obtained tn the commercial CaO is an efficient catalyst for the reaction as it gave less yield as compared ‘o modified CaO gave 98.9% yield under the same condition. The modified CaO have good stability in air which attribure to the presence of benzyl groups on the surface of CaO.) Oo: 6+ os Scheme 2: Synthesis of Chalcone using modified CaO as stable solid base catalystScheme 3; S. Chand and coworkers carried out an efficient green resuable catalyst G pees formyl benzopyranones chalcones by Claisen-Schmidt reaction under solvent uel this process is carried out with operational simplicity and simple work-up Proce: a Feaction variety of biologically important aldehydes can be employed and this cam =a ot need volatile organic solvents the catalyst ZnO nanoparticles shows an excellent catalytic activity by activating both reactants without the formation of any complexes or by-products This method produces excellent yields in shorter reacton time due to the large surface area of the catalyst and used catalyst can be recycled and reused many times without the reduction in catalytic potential.) Scheme 3: Zn0 NP catalysed synthesis of chalcone under solvent free condition ‘Scheme 4: ‘Scheme 4: Synthesis of chalcone using modified Na-ACEScheme 5: MJayapal and coworkers performed synthesis of 2,6-Dihydroxy substituted chaleones using PEG-400 as reusable solvent. The main aim of the synthesis is to develop an efficient protocol using PEG-400 as a recycable reaction solvent to obtain ,3-diaryl-2-propen-l-ones with good 2 oper to excellent yields in a short span of time without formatio of any side product.{) Scheme 5: Synthesis of 2,6-Dihydroxy substituted chalcones ‘Scheme 6: 0 Scheme 6: Solvent free synthesis of chalcone using grinding methodScheme 7: activity of Na-CaO nanocrystalline for vanillin .d catalytic L Mardiana and coworkers performed cataly' n egg shells waste based chalcone synthesis. The CaO catalyst were isolated from the chicke ; and the Na-CaO basic catalyst were prepared by wet impregnated of NaOH solution on the CaO. The application of Na-CaO catalyst in the aldol condensation reaction produced 97% yield of chalcone. The Na-CaO catalyst could be used upto 5 times for the same reaction Procedure and can be highly recovered with partial loss of catalytic performance. Therefore the ‘Na-CaO catalyst is moderately reusable.!") Hy HK sco aon N° 7 C20. 100°C. ahr A * Hy R XQ Ho: | Vantin Acetophenone 9) Chakane ‘Scheme 7: Synthesis of chalcone using Na-CaO nanocrystalline Scheme 8: D. Mulugeta et.al carried out synthesis of Chalcone deivatives of vanillin and different substituted acetophenone derivatives with electron donating and withdrawing. group at para Position of acetophenone. This synthesis proceeded smoothly to furnish chalcone with good yield as this synthesis is inexpensive, easily available solid base catalyst, short reaction time, high yield, easy and easy workup procedure.!*! . Hy HCO 9 HO . 20 Sm HO 1000 ae + ocHy R Rl HO Venin Acetophenone ° Chatcone| Scheme 8: Synthesis of chalcones using ZnO NpsScheme 9: | D-Scpainingyas and greup perfomed synthesis of chaleone derivatives en synthesis. In this synthesis from the yield obtained the results of the synthes! involving ¢- hydroxy benzaldehyde having a higher yield than the results involving only benzal a ia : absence of a hydroxy substituent. So from the result it was concluded that the addition o} hydroxy substituents to benzaldehyde compounds can increase the yield of chalcone compound." Scheme 9: Chalcone synthesis reaction from Benzaldehyde and Acetophenone The result of Chalcone derivatives synthesis Benzaldehyde variation + Fig 9.1: Benzaldehyde * Crude product: Bright yellow H © Weight: 0.1268g © Yield: 12.19% © Fig 9.2: 4-hydroxy benzaldehyde © Crude product: Bright yellow 9 © Weight: 1.1228g * Yield: 99.8% HO 10Synthesis of Chalcone from Chicken Egg shell Preparation of catalyst (CaO- E) Empty chicken eggshells were collected from household waste and washed with warm tap- water. The adhering membranes were separated manually. The eggshells were then washed with distilled water and dried at 120 °C for Ih. The eggshells were ground with mortar and Pestle for 2 h, and the eggshell powder was calcined at 900 °C for Ih. The resulting material was denoted by CaO - E. 48 Chicken Egg Shell Crushed Egg shell Ca0-E1, SYNTHESIS OF CHALCONE General reaction Ch NaOH, RT Benzaldehyde Acetophenone General Procedure ‘The reaction is carried out between benzaldehyde(Immol) and acetophenone({mmol) were nixed in a beaker 50% NaOH solution was added dropwise o the mixture and stired manually fer 15 min tll the preceiptate was formed. Completion of the reaction was monitored by TLC the addition of hot ethanol(SmL). The precipitate and the favourable product was achieved by was separated by simple filteration, washed with cold water and dried. METHOD I: Synthesis of benzalacetophenone derivative using NaOH by stirring at room temperature BSTIRRING METHOD 1 mmol of Aldchyde, 1 mmol of acetophenone were weighed and added into beaker, 50% NaOH solution was added dropwise to the mixture and stirred manually for 15 mins till the precipitate was formed The formation of compound was confirmed by TLC( thin layer chromatography). After the reaction was complete, the favorable product was achieved by the ‘addition of hot ethanol. The precipitate was separated by simple filtration and then washed with cold water, dried and recrystallized with ethanol. Method I Synthesis of benzalacetophenone derivative by heating under reflux using: a) Commercial CaO b) CaO -Easa heterogenous catalyst 1 mmol of Aldehyde and | mmol of acetophenone were mixed in a round bottom flask and to this 0.2 g of catalyst was added. After completion of the reaction, monitored by TLC, the favorable product was separated from the catalyst by the addition of hot ethanol. Crude product was dried and yield was recorded, The formation of the product was confirmed through its melting point. 14Reaction carried out by refluxing method Progress of reaction monitored by TLC ca 7 Filteration Product afMETHOD IIT ‘Synthesis of benzalacetophenone derivative by mortar — pestle grinding method using a) Commercial CaO b) CaO -Easa heterogenous catalyst ol of benzaldehyde and 1 mmol of acetophenone were taken in a mortar, to this catalyst | and the reaction mixture was grinded for approximately (0.2g) was added along with ethanol | hour, The formation of compound was confirmed by TLC( thin layer chromatography) the catalyst was separated from the reaction mixture ‘After the completion of the reaction, using ethanol and the crude yield was recorded. The formation of the product was confirmed through its melting point 1 mmReaction mixture grinding method Filteration Product after drying wvCHAPTER 4 RESULT AND DISCUSSIONChatcone derivatives were synthesized at different reaction condit CaO. and CaO ~F asa heterogenous catalyst. Table 1: The Chalcone derivatives synthesized using catal Jons, using commercial 4 al different reaction conditions, TLC Chalcone Structure Products derivative Ja e | ZASymihesized chalcone derivative 3a-3e Table 2 wee CHAL [CATALYST Yield [Yield [Yield | Yield | —Mehing CONE T usingCo | using using | using CaO | point Ca0-E eae || DERIV (a) comercia | Commerci Ey oc ATIVE ico | ™™ | aco | | _| (%)_| (%) | Reflux (6 hr) Grinding (3 hr) ft i 02g 84% | 86% 71% 6% | SHC 2 3 | 02g 89% 35% 68% 9% | TRC ! i 3 3e 02e 2% | 80% Tm | 13% wre | 7 om «) 3d 02g Bm | 88% | 12% | 8% | toe | | 9) 10sec | fj 5 Be | 02g B12 | 75% | 14.16% | 78% = | S | __1—_—IR spectrum for the CaO Pv3 ; : 2 z 4000 ©3500 3000 2500 2000 1500 1000 500 ‘Wavenumber cm’) IR VALUE (OBSERVED) FUNCTIONAL GROUP 3640em"™ OH stretching 1787em"" C=0 stretching 146 lem" C-0 stretching “| 8T4em" CO bending | 35cm" CsObnts—tt«ésd —— 7 __}—_—_————_— ino benzaldehyde ,-dimethyl ami IR spectrum for the compound P coped Pvs i é 5 # 4000 3500 ©3000-2500 ««2000« 18001000500 ‘Wavenumber (om) IR VALUE (OBSERVED) FUNCTIONAL GROUP ‘| i 3309 cm? (N-H) stretching 2915 cm! (C-H) stretch of (Alkene) 1660 cm™ Ester Carbonyl stretching 1436-1373cm" C-H bending and $= stretching 1160emr" C-O stretching— — CONCLUSION ones was carried out using an efficient base catalyst i.e commercial C: ‘20 under refluxing and grinding method showed the product ae i: was observed that grinding method gave less yields as cor aie fluxing condition it was observed that anisaldehyde pa .s. Under grinding condition it was observed ie synthesis of chale chicken eggshell C: TLC and melting point. It refluxing method. Under rel results compared to the other derivatives hydroxybenzaldehyde gave good results as compared to other derivatives Results suggested that the commercial CaO was an efficient catalyst for this reactiot vrdifing CaO it was posible to significantly enhance the catalytic ctvity samy ana sing different substituted benzaldehyde was explored with electron anand as withdrawing group it was clear that the condensation reactions proceeds smoothly i fi “a chalcone in good yields it was observed that electron withdrawing groups present on sete proceeds very smoothly while substituents present on ortho-position gave a moderate yield due to steric effect.REFERENCE [1] Kulkami, P. (2015). Calcium oxide catalyzed synthesis of chalcone under microwave condition. Current Microwave Chemistry, 2(2), 144-149 [2] J, Wang., Liu, J., Dong, Z., Guo, L., Zu, D., & Zeng, P. (2004). Synthesis of chalcones using modified CaO as stable solid base catalyst. Journal of Chemical Research, 2004(2), 15R- 159. [3] Chand, S., & Sandhu, J. S. (2015). ZnO Nanoparticles: An efficient green reusable catalyst for the synthesis of 3-formyl benzopyranones chalcones by Claisen-Schmidt reaction under solvent-free condition, [4] Mardiana, L., Ardiansah, B., Bakri, R. (2014, April). Synthesis of chalcone using modified Na-ACE. In AIP Conference Proceedings (Vol. 1729, No. 1, p. 020051). AIP Publishing LLC. [5] Jayapal, M. R., Prasad, K. S., & Sreedhar, N. Y. (2010). Synthesis and characterization of 2, 6-dihydroxy substituted chalcones using PEG-400 as a recyclable solvent. Joumal of Pharmaceutical Sciences and Research, 2(8), 450 (6] Shivshankar, S., Chavan, S., & Vibhute, Y. (2016). Solvent-free synthesis of chalcones and antioxidant activity. Journal of Advanced Chemical Sciences, 373-375. (7] Mardiana, L., Ardiansah, B., Bakri, R., & Cahyana, H. (2016, April). Catalytic activity of Na-CaO nanocrystalline for vanillin-based chalcone syntheses. In AIP Conference Proceedings (Vol. 1729, No. 1, p. 020051). AIP Publishing LLC. [8] Mulugeta, D., Abdisa, B., Belay, A., & Endale, M. (2018). Synthesis of Chalcone and Flavanone Derivatives using ZnO Nanoparticle as Catalyst for Antibacterial Activity Synthesis, 10(6s). {9] Septianingtyas, D., Zafira, N., Zulhipri, Kurniadewi, F., & Dianhar, H. (2021, April). Green synthesis of chalcones derivatives. In AIP Conference Proceedings (Vol. 2331, No. 1, p. 040020). AIP Publishing LLC.