Chitosan decorated copper nanoparticles as efficient catalyst for one-pot multicomponent green synthesis of novel quinoline derivatives

Chitosan decorated copper nanoparticles catalysts (CSCuNPs) were synthesized via reduction methods utilizing green protocol. The catalytic performance of CSCuNPs were tested for one-pot multicomponent reaction (MCR) using four reactant components: aromatic aldehydes, dimedone, ammonium acetate and ethylcyanoacetate under ultrasonic irradiation. The best catalyst (Cu-CS-NPs) that provided good conversion reaction yield and high turnover frequency (TOF) utilizing a facile and fast ultrasonic process was characterized using FTIR, TGA, XRD, TEM and XPS techniques. Generalization of the scope of the proposed catalytic process was studied using different aldehydes and excellent products yields and high TOF in even shorter reaction time (5 min.) was attained. Recyclability performance of the catalyst over five times re-use without detectable loss in product yield was recorded. The current method is green process utilizing environmentally benign catalyst and considered to be promising sustainable protocol for the synthesis of fine chemicals.

The use of nanoparticles (NPs) in catalysis is considered to be one of the most significant principles of green chemistry that is owing to a number of different reasons; the reaction time is short, diminishes generation of hazardous materials, economically visible as high yields produced with low cost [15].
nanoparticles have been widely used as the catalyst support in organic transformation [16].Our previous achievements in the synthesis of different organic synthons of important biological activities utilizing different nanosized solid heterogeneous catalysts under green protocol [17][18][19][20][21][22] revealed that exploring efficient, sustainable and green catalyst is crucial to achieve green sustainable perspectives.
To attain our goal, natural bio-polymer supported heterogeneous nano-catalysts that have been utilized in recent years [23,24], was selected to be a catalyst support.One of the promising catalyst's support candidate is chitosan, which is produced by the N-deacetylation of chitin.It is considered to be the second most abundant natural polymer after cellulose [25].Chitosan a chemically stable, non-toxic is an excellent candidate to be used as a support for copper and other transition metals due to its insolubility in organic solvents and the presence of functionalize amino groups in the structure [26][27][28].
Nanoparticles have a special characteristic to aggregate and will clump together to form larger particles, thus nanoparticles lose their large surface area and other benefits [29].Chitosan as a polymer-based stabilizes the nanoparticles to prevent their aggregation via coordination with metal nanoparticles through chelation mechanism, makes it a perfect support for metal nanoparticles [30].
Gold, silver and transition metals nanoparticles such as palladium are available for the development of hybrid catalyst complexes and they can also be used in chemical transformation whereas a new glyoxal cross-linked chitosan Schiff base was prepared as a support material for palladium catalyzed Suzuki cross coupling reactions [31,32].In addition, chitosan was used as support of copper nanoparticles as catalyst for the C-S coupling of thiophenol with aryl halides [33].The synthesis of Cu nanoparticles using chitosan as both reducing and capping agent was reported elsewhere [34,35].This single step method is considered to be cost-effective, convenient and echo-friendly relative to other method of preparation [34].
In the present work, chitosan decorated copper nanoparticles catalysts were synthesized through green methods [34,35] and its application as an efficient catalyst in multicomponent reaction to the synthesis of novel quinolone derivatives under ultrasonic irradiation were extensively studied.The Cu-CS-NPs catalyst is a promising efficient sustainable green catalyst for the synthesis of quinolone derivatives in satisfactory yield in short reaction time under ultrasonication conditions.In order to find out suitable Cu-CS NPs catalyst for the synthesis of quinoline derivatives via fourcomponent one-pot reaction of P-Chlorobenzaldehyde, dimedone, ethyl cyanoacetate and ammonium acetate as the model reaction under ultrasound irradiation and its behavior was studied on the presence two kind of Cu-CS NPs catalyst.Firstly, has been studied the catalytic activity of model reaction via four weights from Cu-CS NPs. then has been tested the catalytic activity of the model reaction also with using four weights from Cu-CS NPs /TPP on the same conditions.the weights of catalysts were as follows (0.05,0.1,0.15,0.2).The results clearly showed that the best result was obtained at (Cu-Cs NPs 0.1 g) provides high yield product Fig. 6.The ultrasonic irradiation method has been chosen based on the advantages of this method, which is to shorten the time and also the slightly high product yield.Therefore, a variety of quinolines derivatives were also synthesized via this method by using the best catalyst (Cu-CS NPs 0.1 g).After finding the best reaction condition, the reactions were carried out with various aldehydes under similar conditions.Catalyst provides an efficient synthesis of a new quinoline derivatives with several advantage involve high productivity, in short reaction time (Table1).

Catalytic Test
Scheme 1: Synthesis protocol of quinolone derivatives.As shown in table 1 the products were isolated in excellent yields.In addition, the reaction provides a new product with high TOF.Therefore, the catalyst plays crucial role in the success of the reaction in terms of rate and yields of polyhydroquinoline derivatives.Basically, catalytic activity of nanoparticles is related by size the particle so the surface of atom types changes with varying particle size.Moreover, the activity increases with decrease in particles size.On the other hand, the surface area of active species is increased.as well as spread the CuNPs on chitosan surface prevents the aggregation Cu NPs.Cu NPs appeared clearly in the TEM image (see characterization section).Many catalysts have been used for one pot-catalytic synthesis of organic precursors utilizing nanocrystalline and nanoparticle catalysts such as ClO4/Zr-MCM-41 nanoparticles [36], Fe3O4@B-MCM-41 [37], and ZnO nanoparticles [38].All of these catalysts showed pronounced catalytic activity due to their nanosized and large surface area features.In contrary to that the produced % yield of products especially after re-use of catalysts for four time was not sufficient relative to our proposed catalyst in the present work.In order to study the sustainability of the present efficient catalyst towards four components one-pot catalytic synthesis of novel quinoline derivatives under ultrasound irradiation, the re-use test was carried out and the results are given in the following section.

Reusability Procedure
The reusability experiments were performed to investigate the stability of Cu-CsNPs under the optimized reaction conditions using 4-chlorobenzaldehyde and dimedone as model substrates.
Typically, after 15 in ultrasound irradiation, Cu-chitosan NPs was filtered and washed 4-6 times with hot ethanol to remove all the unreacted reactants and dried at room temperature for 24 h.The dried Cu-chitosan was used as catalyst in the subsequent runs and the results are summarized in Fig. 2. At the end of recycle tests, Cu-CS NPs catalyst had been five runs.The reusability test showed that promising catalyst could be re-used and regenerated for many times without substantial change in catalytic performance.

FTIR of catalyst
FT-IR spectra of chitosan and copper decorated chitosan nanoparticles (Fig. 3) displayed a broad band for OH and NH stretching of amine groups located at 3250 cm −1 .The existence of band at 1553 cm

SEM-EXD of Cu-Cs NPs catalyst
The morphology of Cu-decorated chitosan sample (CuNPs) described by SEM image (Fig. 5) displayed asymmetrical deposits of chitosan.The nonattendance of copper nanoparticles could be ascribed to the good scattering of copper nanoparticles over chitosan.EDX spectra (Fig. 6) showed copper in addition to carbon, nitrogen and oxygen elements.The atomic % of copper should be complemented by XPS analysis in order to give accurate turnover number of copper relative to the total atomic percentage derived from ICP-AES analysis.

Tentative Mechanism
A tentative mechanism for multicomponent reaction of quinolines derivatives over Cu-Cs NPs has been proposed to occur via three different reaction steps (Scheme 2).Firstly, the well dispersed copper nanoparticles facilitate the electrophilicity of carbonyl group of the aldehyde via reduction of Cu 2+ ions into Cu o , which resulted in ease of attack on the active methylene carbon of ethylcyanoacetate and elimination of water.Secondly, the reaction proceeded via Michael addition assisted by Lewis acidic sites of the catalyst then followed by the last step in ionic mechanism.

Scheme 2:
Proposed mechanism for the synthesis of quinolone derivatives.

Materials
Chitosan (molecular weight 100,000-300,000) (Acros Organics-Belgium).Sodium tripolyphosphate  The synthesis of Cu-chitosan nanoparticles was carried out according to two methods: Firstly: Cuchitosan NPs (Cu-Cs NPs) have been prepared via one-step synthesis green protocol.In a typical method, 0.75 g chitosan dissolving in 100 ml 0.1% acetic acid (in distilled water) then 50 ml of the solution and 25 ml of 0.05 M copper solution were delivered under stirring at 70°C for 9 h till the reaction was completed.the colloid was centrifuged for 10min.to separate particles from suspension then washed with acetone (90%, v/v) and the centrifugation was repeated three times to remove unreacted reagents.The particles were dried under vacuum at the room temperature overnight and stored [34].

Synthesis of Cu-Chitosan Catalyst
Secondly: Cu-chitosan NPs (Cu-Cs NPs /TPP) were prepared based on the ionotropic gelation between chitosan and sodium tripolyphosphate (TTP).Chitosan acted as a reducing/stabilizing agent.TPP was dissolved in water to a concentration of 0.25%.Under magnetic stirring at room temperature, 33 ml of TTP solution was added into 50 ml of chitosan solution 0.75% (in dil.acetic acid 0.1 %) and the mixture was stirred for 15min.Chitosan nanoparticles loaded Cu 2+ were obtained by adding metal ion solutions 16ml 0.05 M into the chitosan nanosuspensions and heated to 70 °C using a water bath, after a blue color appeared, stirring continued for another 90 min.before removing the heater.The resulting solution was cooled to room temperature for characterization [35].
After completion of the reaction (monitored by TLC, petroleum ether: EtOAc, 1:2), the reaction mixture was filtered to separate the catalyst, then cooled at room temperature and the solid product obtained and was filtered off, dried and recrystallized from ethanol.

Measurements and characterization
The reactions were monitored by TLC and all yields refer to isolated products .Melting points were obtained by the Barnstead international 1002 melting point apparatus.IR spectra of the catalyst and products were recorded for the compounds in PerkinElmer spectrum 100 FT-IR spectrophotometer.

Physical and spectroscopic data of product compounds
Ethyl-

Figure 1 .
Figure 1.Catalytic activity of all the investigated catalysts with different masses.

Figure 2 .
Figure 2. Robust feature of Cu-CS A NPs catalyst after five times r-use

Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 8 October 2018 doi:10.20944/preprints201810.0123.v1 30mA
. XPS measurements were carried out in an ultra-high vacuum multi-technique surface analysis system (SPECS GmbH, Germany) operating at a base pressure range of 1010 bar.Catalyst morphology was investigated by means of field emission scanning electron microscopy (FEG-SEM, Quanta FEG450, FEI, the Netherlands) using an ETD Everhart Thornley detector (High Vacuum mode), a solid-state backscattering electron detector (VCD)and EDS detector (XFLASH6-30, Brucker) for elemental analysis.HRTEM samples were prepared by sonication of the suspended powder in ethanol.A single drop of the sonicated suspension was deposit on TEM carbon grid 200 mesh and leaved for total evaporation at room temperature.Then the grid was mounted on a TEM single tilt holder, the residual solvent was removed by plasma cleaning process.The reactions that carried out by U.S irradiation was done using Daihan (Wiseclean, D-40 MHz) ultrasonic bath.Microanalysis was performed by Perkin Elmer elemental analyzer at the Faculty of Science, King Abdul Aziz University.