SELECTED EXAMPLES OF OUR RESEARCH

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1 SELECTED EXAMPLES OF OUR RESEARCH Title: Water-Mediated One-pot Three-Component Synthesis of Hydrazinyl-Thiazoles Catalyzed by Copper Oxide Nanoparticles Dispersed on Titanium Dioxide Support: A Green Catalytic Process Abstract: The present work describes the catalytic activity of copper oxide nanoparticles dispersed on titanium dioxide in water for one-pot synthesis of a library of hydrazinyl-thiazoles via a three-component reaction of various aldehydes/ketones with thiosemicarbazide and different phenacyl bromides. The structure of the synthesized compound, (E)-4-(4-bromophenyl)-2-(2-(4-methoxybenzylidene) hydrazinyl)thiazole is confirmed by single crystal X-ray diffraction studies. The catalyst prepared by a molten-salt method is characterized by XRD, FESEM with EDS, TEM with EDS, XPS, AES and ESR spectroscopy. The noteworthy advantages of this method include its broad substrate scope, clean reaction profile, short reaction times and high yields at low catalyst loading. Further, the product does not require any chromatographic purification and the method has the potential for large-scale applications in pharmaceutical industries. In addition, the developed catalyst can be recovered and reused for 5 times without significant loss of activity. Mechanistic studies suggest that the reaction begins with the activation of the carbonyl group of both aldehyde/ketone and phenacyl bromide by copper oxide nanoparticles supported on titanium dioxide in water. These studies reveal that the reaction proceeds via the formation of thiosemicarbazone intermediate. Publication: G. Trivikram Reddy, G. Kumar, N. C. Gangi Reddy*, Adv. Syn. Catal., 2018, 360,

2 Title: Zinc oxide-catalyzed Solvent-Free Mechanochemical Route for C-S Bond Construction: A Sustainable Process Abstract: A simple, robust, and solvent-free mechanochemical method has been achieved for the construction of C S bonds by using a nucleophilic substitution (SN2 mechanism) reaction between various thiols (heterocyclic thiols, alkane dithiols, and aromatic thiols) and phenacyl/benzyl/alkyl bromides in the presence of ZnO. This method has many advantages, such as its ease of operation, wide substrate scope, clean reaction profile, short reaction times, scalability, cost-effectiveness, and high product yields without the need for chromatographic purification. The catalyst can be recovered and reused for up to five cycles without significant loss of activity. Hence, the established synthetic route is an alternative to existing procedures for C S bond formation. Furthermore, the prepared synthetic precursors are suitable for further functional group transformations to develop new chemical entities of potential pharmacological interest. Publication: P. Md. Khaja Mohinuddin, N. C. Gangi Reddy*, Eur. J. Org. Chem., 2017, 8, Title: Design And Synthesis of Novel 16-Membered Macrocyclic Z-Di(Aryl/Naphthyl)-Dioxa- Dithia-Diaza Cyclohexadeca-Dienes And Evaluation Of Theiranti-Cancer Activities Abstract: A series of new 16-membered small macrocyclic compounds, (2Z,11Z)-3,11-di(aryl/naphthyl)- 1,13-dioxa- 5,9-dithia-2,12-diazacyclohexadeca-2,11-dienes were designed and developed by a simple and practical synthetic route from readily available substrates using simple organic transformations. Evaluation of in vitro anti-tumor activities on human triple negative breast cancer cells MDAMB-231 cell lines reveal that the newly synthesized macrocycles are promising anti-tumor compounds as evidenced from inhibition of cell migration and proliferation, upregulation of anti-tumor genes p53, MDA7 and

3 TRAIL. The anti-proliferative effect of macrocycles is specific to cancer cells but no cytotoxic effect on normal breast epithelial cells has been observed (MCF10A). The developed synthetic route is free from metals, protecting groups and air-free techniques. Publication: Mohan Reddy Bodireddy, Ranjeet Singh Mahla, P. Md. Khaja Mohinuddin, G. Trivikram Reddy, D. Vijaya Raghava Prasad, Himanshu Kumar, N. C. Gangi Reddy*, RSC Advances, 2016, 6, Title: Synthesis of alkynyl/alkenyl-substituted pyridine derivatives via heterocyclization and Pdmediated Sonogashira/Heck coupling process in one-pot: A new MCR strategy Abstract: A new class of 2-amino-4-(3/2-(alkynyl)/3-(alkenyl)phenyl)-6-phenylnicotinonitriles (6, 7 & 9) has been synthesized with good to excellent isolated yields by the multi-component reaction (MCR) of bromobenzaldehyde (1), malononitrile (2), acetophenone (3), NH 4 OAc (4) and a series of terminal alkynes(5)/alkenes(8) in presence of pyrrolidine and Pd-catalyst in a mixture of H 2 O-DME (1:4 ratio) under reflux conditions in a single step. The Heck-type coupling with terminal olefins takes place stereoselectively with exclusive formation of E-isomers. This new MCR strategy opens new avenues in the development of i) diversity-oriented new cyano pyridines that are useful for further 'FG' transformations and ii) new chemical entities other than the present reported molecules.

4 Publication: Mohan Reddy Bodireddy, N. C. Gangi Reddy*, Sangita D. Kumar, RSC Advances, 2014, 4, Title: Silica gel catalyzed α-bromination of ketones using N-bromosuccinimide: An easy and rapid method Abstract: An easy and rapid method for the α-bromination of ketones using N-bromosuccinimide (NBS) catalyzed by silica gel in methanol under reflux conditions is developed. The expected products are formed in excellent isolated yields within a short period of time (5-20 min). Major advantages of the present procedure include the use of inexpensive and readily available catalyst, the exclusion of pre- and post-chemical treatment of the catalyst employed and the use of methanol as solvent instead of ethers and chlorinated solvents. The present method proved to be more productive for large scale ( 100 gram scale) applications both in chemical and pharmaceutical industries. Publication: Reddy Bodireddy Mohan, N. C. Gangi Reddy*, Mahender Rao, S., Chinese Chemical Letters, 2014, 25,

5 Title: One-pot Three-component synthesis of novel 4-Phenyl-2-[3-(alkynyl /alkenyl/aryl)phenyl]pyrimidine libraries via Michael addition, cyclization and C-C coupling reactions: A new MCR strategy Abstract: We have developed a new MCR strategy for the synthesis of 4- phenyl-2-(3- alkynyl/alkenyl/aryl) phenyl substituted pyrimidines with high yields from enaminone (1), 3- bromobenzimidamide hydrochloride (2) and various alkynes/alkenes/aryl boronicacids via a Michael addition, cyclization, isomerisation, dehydration followed by Sonogashira/Heck/ Suzuki coupling in a single pot. This MCR strategy offers advantage of short reaction time, easy isolation of products, simple construction of substituted pyrimidine moiety and subsequent C-C couplings for structural elaboration of pyrimidine framework in one-pot. Publication: L. Srinivasula Reddy, T. Ram Reddy, N. C. Gangi Reddy*,Reddy Bodireddy Mohan, Y. Lingappa, Synthesis, 2013, 45, Title: Pd-mediated multi-component synthesis of highly functionalized pyridines and consequential C-C coupling using Suzuki reaction in One-pot: Their in-vitro evaluation as potential antibacterial agents Abstract: Pd-mediated construction of pyridine scaffold and subsequent Suzuki-based C C coupling reaction in one pot has been accomplished for the synthesis of 4-biaryl substituted 2-amino-3- cyanopyridines via multi-component reaction. The present multi-component reaction is useful in structural elaboration of pyridine framework and also helpful in design and synthesis of novel and diverse analogs of complex heterocyclic compounds other than present reported molecules. Antibacterial activities of the synthesized compounds were systematically evaluated. The correlation between

6 functional group variation and biological activities of the compounds has been evaluated against human pathogenic gram-positive and gram-negative bacterial strains. Publication: L. Srinivasula Reddy, T. Ram Reddy, N. C. Gangi Reddy*, Reddy Bodireddy Mohan, Y. Lingappa, Journal of Heterocyclic Chemistry, 2014, 51, E103-E113. Title: An efficient green multi-component reaction strategy for the synthesis of highly functionalised pyridines and evaluation of their antibacterial activities Abstract: An efficient MCR using grinding technique for green synthesis of 2-amino-4-aryl-3,5- dicarbonitrile-6-thiopyridines has been developed under solvent free reaction conditions (SFRC) in presence of K 2 CO 3 using aryl aldehyde, malononitrile, and 2-mercaptopyridine at room temperature. The advantages of present protocol include operationally simple, solvent free reaction conditions, excellent isolated yields of desired products, environmentally benign and feasible for large scale applications in pharmaceutical industry. R = H; 4 ' -OMe;3 ' -CN,4 ' -F; 3 ' /4 ' -F; 4 ' -Br; 3 ' -OH; 4 ' -NO 2 ; 3 ',4 ',5 ' -triome X = CH 2, N CHO CN CN 3.77 mmol 2 K 2 CO 3 (1.0 equiv) CN X R CN R1.88 mmol 1 HS N 1.5 mmol 3 R = F, Br, CN, NO 2, OCH 3,OH Grinding, Work up RT NH 2 N 4 S 2-amino-4-aryl/heteroaryl-6- (pyridin-2-yl thio)pyridine-3,5-dicarbonitrile(s) N Publication: L. Srinivasula Reddy, T. Ram Reddy, Reddy Bodireddy Mohan, N. C. Gangi Reddy,* A. Mahesh,Y. Lingappa, Chemical and Pharmaceutical Bulletin, 2013, 61,