One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-Onesusing Zinc Ferrite Nanocatalyst and Its Bio Evaluation
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catalysts Article One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-OnesUsing Zinc Ferrite Nanocatalyst and Its Bio Evaluation Tentu Nageswara Rao 1 , Nalla Krishnarao 1, Faheem Ahmed 2,* , Suliman Yousef Alomar 3,*, Fadwa Albalawi 4, Panagal Mani 5, Abdullah Aljaafari 2 , Botsa Parvatamma 6, Nishat Arshi 7 and Shalendra Kumar 2,8 1 Department of Chemistry, Krishna University, Machilipatnam, Andhra Pradesh 521001, India; [email protected] (T.N.R.); [email protected] (N.K.) 2 Department of Physics, College of Science, King Faisal University, Hofuf, Al-Ahsa 31982, Saudi Arabia; [email protected] (A.A.); [email protected] (S.K.) 3 Doping Research Chair, Zoology Dept, College of Science, King Saud University, Riyadh 11451, Saudi Arabia 4 Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] 5 Department of Biotechnology, Annai College of Arts&Science, Kumbakonam, Tamil Nadu 612503, India; [email protected] 6 Department of Organic Chemistry, GayathriP.G Courses, Gotlam, Vizianagaram 530045, India; [email protected] 7 Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Hofuf, Al-Ahsa 31982, Saudi Arabia; [email protected] Citation: Rao, T.N.; Krishnarao, N.; 8 Department of Physics, School of Engineering, University of Petroleum & Energy Studies, Ahmed, F.; Alomar, S.Y.; Albalawi, F.; Dehradun 248007, India Mani, P.; Aljaafari, A.; Parvatamma, * Correspondence: [email protected] (F.A.); [email protected] (S.Y.A.) B.; Arshi, N.; Kumar, S. One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl- Abstract: A simple and highly efficient protocol for the synthesis of derivatives 7, 7-dimethyl-4- 2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H- phenyl-2-thioxo-2, 3, 4, 6, 7, 8-hexahydro-1H-quinazoline-5-one from 5, 5-dimethyl cyclohexane-1, Quinazoline-5-OnesUsing Zinc 3-dione (4a–4h) (dimedone) has been described. The aryl aldehydes were substituted with thiourea Ferrite Nanocatalyst and Its Bio Evaluation. Catalysts 2021, 11, 431. in the presence of synthesized zinc ferrite nanocatalyst, which increased the yield under reflux https://doi.org/10.3390/ through condensation, followed by cyclization to give desired products. The other advantages are catal11040431 that it is eco-friendly and economically affordable for large-scale production. Structural validation and characterization of all the newly synthesized compounds were evaluated by spectral analysis Academic Editors: Maria Manuel (mass spectrometry, proton nuclear magnetic resonance (1HNMR), and Carbon-13 nuclear mag- B. Marques and Ana Sofia Santos netic resonance(13CNMR)spectroscopies. The structure of antibacterial and antifungal assays was performed with the newly synthesized compounds. The antimicrobial activity of title compounds Received: 16 March 2021 possessing electron-withdrawing groups such as (4e–4h) (Cl, Br, and cyano group) exhibited more Accepted: 24 March 2021 active potential than the electron-donating groups, C6H5,4-C6H4, 3-OC2H5-4OH-C6H3, etc., (4a–4d) Published: 27 March 2021 containing moiety. Publisher’s Note: MDPI stays neutral Keywords: dimedone; aryl aldehydes; zinc ferrite; bio evaluation; structural validation; NMR with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Multicomponent reaction (MCR) is the most powerful and efficient technique in modern synthetic organic chemistry. The advantages of these reactions in synthetic or- Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. ganic chemistry are the valuable characteristics such as constructing desired compounds, This article is an open access article straightforward reaction design, atom economy, and the simple purification of target distributed under the terms and products. MCRs with heterocyclic moiety are particularly useful for the construction of conditions of the Creative Commons drug-like molecules [1–3]. In the recent past, the six-membered heterocyclic compounds Attribution (CC BY) license (https:// such as hexahydroquinazolinones in medicinal chemistry and synthetic organic chemistry creativecommons.org/licenses/by/ are of special interest. The main focus on the synthesis of derivatives of 7,7-dimethyl-4- 4.0/). phenyl-2-thioxo-1,2,3,4,6,7,8-hexahydro-1H-quinazoline-5-ones has considerably attracted Catalysts 2021, 11, 431. https://doi.org/10.3390/catal11040431 https://www.mdpi.com/journal/catalysts Catalysts 2021, 11, x FOR PEER REVIEW 2 of 12 Catalysts 2021, 11, 431 2 of 12 of 7,7-dimethyl-4-phenyl-2-thioxo-1,2,3,4,6,7,8-hexahydro-1H-quinazoline-5-ones has considerably attracted attention in recent years due to their potential, antioxidant [4], attentionantifungal, in recentantibacterial, years dueantitumor to their, potential,and antitubercular antioxidant activity [4], antifungal, [5]with wide antibacterial, applica- antitumor,tions, including and antitubercular anticonvulsant, activity sedative, [5] with tranquilizer, wide applications, analgesic including [6,7], antimicrobial, anticonvulsant, an- sedative,esthetic [8], tranquilizer, anticancer analgesic [9], antihypertensi [6,7], antimicrobial,ve [10], anti anesthetic-inflammatory [8], anticancer [11], diuretic [9], antihy- [12], pertensiveand muscle [10 relaxant], anti-inflammatory properties [13]. [11 The], diuretic various [12 organic], and muscle transformation relaxant propertiesreactions were [13]. Theemployed various by organic the use transformation of trimethylsilyl reactions chloridewere [14]. employedThere are few by thereports use offor trimethylsi- the synthe- lylsis chlorideof octa [14hydro]. There quinazolinone are few reports derivatives for the synthesisusing catalysts of octa such hydro as quinazolinone concentrated derivativesH2SO4[15], usingNafion catalysts-H [16], suchNH4VO as concentrated3[17], silica-sulfuric H2SO4 acid[15], [18] Nafion-H, and also [16], in NH ionic4VO liquids3 [17], silica-sulfuric[HMIM] H2SO acid4 in [ 18presence], and also of TMSCl in ionic [19], liquids [BMIM]Br [HMIM]-[BMIM]BF H2SO4 in presence4[20], andZrOCl of TMSCl2.8H [192O], [BMIM]Br-[BMIM]BF[21]. This article tends4 [to20 report], and ZrOClthe synthesis2. 8H2O[ of21 7,]. 7 This-dimethyl article-4 tends-phenyl to- report2-thioxo the-2, synthe- 3, 4, 6, sis7, of8 7,-hexahydro 7-dimethyl-4-phenyl-2-thioxo-2,-1H-quinazolin-5-ones 3, 4,using 6, 7, 8-hexahydro-1H-quinazolin-5-ones nanocatalyst. Lanthanum doped using nanocatalyst.Ni0.6Zn0.2Fe2- LanthanumXLaXO4 (x=0.075) doped Ni0.6Zn0.2Fe2-XLaXO4ferrite was developed by (x =Amol 0.075) et ferrite al. This was ferrite developed has a byspinal Amol cubic et al. structure This ferrite and hasa lattice a spinal constant cubic of structure 8.486. The and Ferro a lattice-spinal constant sample of was 8.486. used The as Ferro-spinala magnetically sample recoverable was used heterogeneous as a magnetically catalyst recoverable [22]. Triethanolamine heterogeneous has catalysta significant [22]. Triethanolamineimpact on the morphology has a significant of nano impact-ZnO on catalyst. the morphology For the synthesis of nano-ZnO of coumarin catalyst. Forderiva- the synthesistives, we ofdeveloped coumarin an derivatives, efficient, wesimple, developed and environmentally an efficient, simple, friendly and environmentallysynthetic meth- friendlyodology synthetic [23]. Catalytic methodology reactions [23 ].ensure Catalytic high reactions regio- ensureand stereoselectivity high regio- and of stereoselec- chemical tivitytransformations. of chemical In transformations. recent years, several In recent novel years, catalytic several systems novel were catalytic developed systems for were the developedselective formation for the selective of carbon formation–heteroatom of carbon–heteroatom and carbon–carbon and carbon–carbon bonds [24]. The bonds use [24 of]. Thegreen use nanocatalyst of green nanocatalyst for the synthesis for the synthesisof various of heterocycles various heterocycles has advantages has advantages such as short such asreaction short reactiontime, high time, yield, high inexpensive yield, inexpensive chemical chemical usage, usage, easy easywork work-up-up procedure, procedure, and andspecific specific reaction reaction [25]. [25 The]. The Michael Michael addition addition reaction reaction and and cyclodehydration cyclodehydration,, followed byby dimedonedimedone withwith various various substituted substituted aryl aryl aldehydes aldehydes and and thioureain thiourea thein the presence presence of nanocata- of nano- lystgivecatalystgive 7,7-dimethyl-4-phenyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-ones, 7,7-dimethyl-4-phenyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5- wereones, performedwere performed (Scheme (Scheme1).1). A pilot A reactionpilot reaction using substitutedusing substituted aryl aldehyde aryl aldehyde (1), dimedone (1), dim- (2),edone and (2) thiourea, and thiourea (3) in the(3) presencein the presence of nanocatalyst of nanocatalyst and the and structure the structure and antagonistic and antago- propertiesnistic properties of the synthesizedof the synthesized compounds compounds were also were studied, also studied in addition, in addition to studying to stu thedy- furthering the developmentfurther development of derivatives. of derivatives. SchemeScheme 1.1. SynthesisofSynthesisof 7,7, 7-dimethyl-4-phenyl-2-thioxo-2,7-dimethyl-4-phenyl-2-thioxo-2, 3,4,6,7, 3,4,6,7, 8-hexahydro-1H-quinazolin-5-ones using8-hexahydro zinc ferrite.-1H-quinazolin-5-ones using