Function of Nanocatalyst in Chemistry of Organic Compounds Revolution : An Overview

Heterocyclicmotif is an important scaffoldwhich has both industrial andpharmaceutical applications.Thesemotifs can be prepared using wide variety of reaction conditions such as the use of expensive catalyst, toxic solvent, harsh reaction condition like the use of base, high temperature, andmultistep reaction. Although variousmethods are involved, the chemistry arena is now shifted towards the greener way of synthesis. Nanocatalyst constitutes an important role in the green synthesis. This is because the activity of the catalyst resides in the exposed portion of the particles. By decreasing the size of the catalyst, advantages such as more surface area would be exposed to the reactant, only negligible amount would be required to give the significant result and selectivity could be achieved, thereby, eliminating the undesired products. The current review enlists the various types of nanocatalyst involved in the heterocyclic ring formation and also some other important functionalization over the ring.


Introduction
The new era of chemistry is shifting towards the path of innovative techniques which mainly concentrates on environmental aspects [1,2].Each and every component of the reaction is investigated on the basis of ecofriendly concepts such as use of nonhazardous solvent (water) and solventfree synthesis or inexpensive catalyst, without affecting the yield and quality of the reaction.Synthesis of heterocyclic core constitutes the important portion of organic synthesis because it has wide variety of pharmacological actions [3][4][5][6].Various methods have been adopted for the synthesis which includes the use of catalyst [7,8], ultrasound irradiation [9][10][11], and microwave irradiation [12,13].Although these methods have their own advantages, it also possesses certain disadvantages like expensive instruments, inaccessible materials, nonrecyclable and non-selectivity, and so forth.To overcome these, the role of nanocatalyst holds its application [14].Nanoscience is the cram of phenomenon on a nanometer range.Atoms are a few tenths of a nanometer in diameter, and molecules are typically a few nanometers in size.The smallest structures humans have been made have dimensions of a few nanometers and the smallest structures we will ever make will have the dimensions of a few nanometers.This is because as soon as a few atoms are placed next to each other, the resulting structure is a few nanometers in size.Chemistry is the study of molecules and their reactions with each other.Since molecules typically have dimensions of a few nanometers, almost all of nanoscience can be reduced to chemistry.Chemistry research in nanotechnology concerns carbon nanotubes, self-assembly, C 60 molecules, and structures built using DNA.Sometimes the chemical description of a nanostructure is insufficient to describe its function.Owing to the hasty progress of nanoscience and nanotechnology, the primeval colloid science is given a new life.Because of their great differences from single molecules and bulk materials, nanoscale materials, including colloids, have attracted much attention since the last decade, especially  in the field of catalysis.Over the several past decades, catalysts and catalytic reactions have attracted considerable attention with the aim of finding meaningful applications in the pharmaceutical and fine chemical industries.The nanocatalysts are highly selective, reactive, and stable; thereby it supersedes the conventional catalyst.Nanoparticles with a diameter of less than 10 nm have generated intense interest over the past decade due to their high potential applications in areas such as sensors, nanoscale electronics, catalysis, and optics.The catalytic activity of nanoparticles is affected by size; therefore, the relative ratio of surface atom types changes dramatically with varying particle size.In many cases, the activity increases as the particle size decreases due to favorable changes in the electronic properties of surface atoms, which are located mainly on edges and corners in small particles.On the other hand, the reactivity and selectivity of metal nanocatalysts also depend strongly on the different crystallographic planes present on the nanoparticles and which can be achieved by controlling the morphology of these nanoparticles.Size and surface of the nanocatalyst play a major role because it is the reason for its selectivity and reactivity.Also, in some cases the enhancement by doping and surface chemical modifications would be done to increase its performance [15].Nanocatalyst is not only used in organic transformation but also it has various applications [16,17].These nanocatalysts can be prepared by various methods such as thermal decomposition, microarc oxidation irradiation, chemical vapor synthesis, nonsono and sonoelectrooxidation, sol-gel technique, chemical precipitation, photochemical method, hydrothermal method, antisolvent precipitation, glow discharge plasma electrolysis, wet-chemical method, microwave irradiation, and sonochemical method [16][17][18][19][20][21].The size and nature of nanocatalyst varies on the type of method used for preparation [22][23][24][25][26][27].
Based on the requirement, the method of preparation can be selected.In this paper, we will review recent examples of nanoparticles used in organic transformation such as quinoxaline, naphthoxazinones, coumarins, 1,2,3-triazoles, acridine, pyrazole, and isoquinolinones.(Figure 1).The heart and soul of this paper is Section 2.23, where we cover miscellaneous functionalization on heterocycles; this is a challenge for nanocatalyst researchers to engage.

Application of Nanoparticles in Organic Synthesis
2.1.Synthesis of Quinoxaline Analogues.Quinoxaline is an important chemical entity which has interesting biological properties such as trypanocidal property [28], antimycobacterial agent [29], and cytotoxic agent [30].The synthesis of quinoxalines (Scheme 1) was carried out by oxidative coupling of 1,2-diamines, 2.1.1 and 1,2-dicarbonyl compounds, 2.1.2using gold nanoparticles supported on nanoparticulated ceria (Au/CeO) or hydrotalcite (Au/HT) as catalysts and air as an oxidant.The use of nanoparticles led to the mild reaction conditions such as base-free reactions, using mild temperature and air as an oxidant.The catalyst could be reused only with a little loss in activity [31].The use of inexpensive and recyclable SiO 2 which has highly reactive -OH group on its surface has its application in the synthesis of quinoxaline, and it produces high yield in less reaction time.
Because of its reusable nature, it supersedes the other catalyst [32].Quinoxalines can also be synthesized by advantageous nano-BF 3 ⋅SiO 2 and nano-TiO 2 catalyst systems.The reaction was carried out at varied temperatures and different moles of reactants to optimize the reaction condition and concluded that solvent-free conditions at room temperature could be the optimal one.In addition, the report concluded that the reaction time could be reduced by performing the reaction under sonication [33].In nano-TiO 2 system, the same authors carried out the synthesis in the presence of nano-TiO 2 and compared with bulk TiO 2 and other applied catalysts.The satisfactory results were obtained in solvent-free condition at room temperature using 12 mol % as a catalyst [34].Lü and coworkers synthesized quinoxalines using magnetic Fe 3 O 4 nanoparticles.The result shows that the reaction could be performed well in water using 10% Fe 3 O 4 nanoparticles as catalyst at room temperature, and the catalyst can be recovered easily by using external magnet and reused with consistent activity [35].Polyaniline/SiO 2 nanocomposite material was prepared and it was used as a catalyst for the synthesis of quinoxalines.They reported that 10% catalyst was found to be optimal for the reactant transformation, and the catalyst activity was found to be consistent even after three runs [36].
Another popular method to synthesize quinoxalines is by using TiO 2 nanoparticles as a catalyst.The optimal protocol system was found out by using dichloroethane as an efficient solvent with 2.5 mol % catalyst to give the highest yield.Also o-phenylenediamine with electron-withdrawing group gave the higher rates and yield than the electron-donating groups [37].The quantitative yield of quinoxaline was obtained in 10 minutes by using acetonitrile solvent system, 10 mol % of Ninanoparticles as catalyst at 25 ∘ C stirred under N 2 atmosphere [38].Bardajee and coworkers prepared SBA-15 supported on Pd (II) Schiff-base complex nanocatalyst for the synthesis of 2, 3-disubstituted quinoxalines derivatives [39].

Synthesis of Pyrazole Analogues.
Pyrazole is an important novelty which has reported insecticidal [40], antimalarial [41], anti-inflammatory, and antimicrobial [42]  produced satisfactory result, the ease of recoverability and reusability of (-Fe 2 O 3 )-MCM-41 made it to prefer this catalyst for the pyrazole analogue synthesis [44].

Synthesis of N-Arylhomophthalimides and Benzannelated
Isoquinolinones.Isoquinolinones are reported to cause allosteric modulation of metabotropic glutamate receptor 2 [51], and also it has JNK inhibitory action [52].An emerald procedure was developed utilizing an efficient catalyst; that is, ZnO nanoparticles mediated the synthesis of Narylhomophthalimides and benzannelated isoquinolinones.Krishnakumar and coworkers synthesized flower-shaped ZnO nanoparticles and used them in the reaction between homophthalic acid, 2.4.1, and substituted anilines, benzyl amine, for the ecofriendly synthesis of N-arylhomophthalimide 2.4.2, and benzannelated isoquinolinones, 2.4.3 (Scheme 6).They carried out the reaction using various catalysts, solvents, and different concentration of the catalyst.Nano ZnO at a concentration of 5% mol in the toluene system was found to be effective [53].The ZnO nanoparticles exhibit admirable catalytic action, and the proposed methodology was capable of providing the desired products in good yield and purity.The possible mechanism for the formation of this product is illustrated in Figure 2.
2.5.2, benzyl bromide, 2.5.3, and sodium azide, 2.5.1, under click reaction condition to give triazole derivatives.These derivatives of natural products having wide variety of application were obtained in high yield using copper nanoparticles [57].CuI supported on poly(4-vinylpyridine) [P 4 VPy-CuI] acts as a heterogenous catalyst for the synthesis of triazoles.Using the optimized ratio of 1 : 1 : 1.1 of phenacyl bromide, 2.5.4,phenyl acetylene, 2.5.5 and sodium azide, 2.5.1, 0.1 g of P 4 VPy-CuI and water, required triazoles were obtained after refluxing.Also, this catalyst can be reused up to 8 runs without losing its efficiency [58].Metalloanthraquinone complex, an important catalyst for the synthesis of 1,4-disubstituted 1,2,3-triazole, was prepared, and various reaction conditions were studied.Various metal  ligands complexes were tested, but only copper was found to be catalytically active due to the richness of electron on metal.Water was found to be an effective solvent, and also the amount of water is also an important criterion.The optimum amount of water required was found to be 5 mL for the reaction between styrene oxide, 2.5.6, sodium azide, 2.5.1 and phenyl acetylene, 2.5.5 [59].Another environment friendly synthesis of triazoles was the cyclisation reaction between three components benzyl bromide 2.5.3, sodium azide 2.5.1, and phenyl acetylene 2.5.5 in the presence of magnetically separable CuFe 2 O 4 nanoparticles, water at 70 ∘ C. The catalyst can be separated easily and reused effectively [60].In an alternative method, various copper salts [CuI, CuSO 4 , CuCl 2 , Cu (NO 3 ) 2 , Cu 2 --CD complex] were used for the synthesis of 1,2,3-triazoles of phenyl boronic acid from coupling of aryl boronic acids, 2.5.7, sodium azide, 2.5.1 and phenyl acetylene, 2.5.5.Among these cooper catalyst Cu 2 --CD complex gave excellent yield of 1,2,3-triazole, 2.5.8 without adding any additives [61].

Synthesis of Coumarins.
Coumarins are attractive molecule in chemistry with anti-inflammatory activity [62], antioxidant and lipoxygenase inhibitory activity [63], and antifungal activity [64].Coumarin has been used as an aroma enhancer in pipe tobaccos and alcoholic drinks although in general it is banned as a flavorant food additive, due to concerns about coumarin's hepatotoxicity in animal models.
The synthesis of coumarins and its analogues has attracted extensive thought from organic and medicinal chemists for many years as a large number of natural products contains this heterocyclic nucleus.Moreover, coumarins have various pharmacological activities (Figure 3).Knoevenagel condensation is one of the widely used reactions for the synthesis of coumarins (Scheme 8).Since it involves the use of acids and bases, an alternative approach for carrying out the condensation is essential.The reaction between ohydroxy benzaldehyde, 2.6.1, and 1,3-dicarbonyl compounds, 2.6.2, is an effective reaction for the formation of coumarins, 2.6.3.ZnO nanoparticles were found to be an effective alternative in 10% mol concentration.Increase or decrease in the concentration of the ZnO extends the time taken for the reaction with fewer yields [65].

Synthesis of Biscoumarins.
Transition metal nanoparticles have gained tremendous importance due to their interesting electrical, optical, magnetic, chemical properties, and especially catalytic properties, which cannot be achieved by their bulk counterparts.Recently, there has been growing interest in using nickel nanoparticles in organic synthesis owing to their easy preparation, potent catalytic activity, possible process ability, and high stability.Heterocyclic systems are common structural motifs in many biologically active substances and natural products and therefore warrant the design of newer and efficient protocols for their synthesis.In view of this biscoumarins is an important molecule which possesses anticoagulant activity (Scheme 9) [66].When the same reaction was carried out without PEG-400, the yield was only 30%.Due to various drawbacks of results with the solvents such as DMSO, acetonitrile, ethanol, THF, and ethylene glycol, the ideal solvent for the synthesis of naphthoxazinones was found to be PEG-400.Not does only it act as a solvent, but also it provides stability to Cu nanoparticles [69].

Synthesis of Benzo[b]
Furans.Furan ring possesses some important activity such as cytotoxic activity [84] and antibacterial activity [85].An ecofriendly multicomponent synthesis of benzo[b]furans (Scheme 16) was carried by the condensation reaction between salicylaldehyde, 2.12.1, morpholine, 2.12.2, and phenyl acetylene 2.12.3, using copper iodide nanoparticles as a specific catalyst.The reaction was standardized with various aldehydes, amines, and acetylenes.
The result concluded that salicylaldehyde with electron-withdrawing groups, aromatic alkynes and aliphatic amines, gave the desired benzo[b]furans [86].

Synthesis of Imidazoles.
Imidazoles are present in various pharmacologically active compounds which act as antituberculosis agent [93] and antibacterial agent [94].They were synthesized as either-trisubstituted or -tetrasubstituted imidazoles by using various reaction conditions such as ultrasonic irradiation [95], TBAB catalyst [96], and HClO 4 -SiO 2 catalyst [97].Imidazoles (Scheme 20) can also be obtained by multicomponent reaction using benzil, 2.16.1, aldehydes, 2.16.2, andamines, 2.16.3, in the presence of metal nanoparticles as a catalyst.TiCl 4 supported on silica was used as a mild solid Lewis acid for the synthesis of triphenylimidazoles.This catalyst system can be prepared, handled, and stored without any special precautions by maintaining its efficiency.They carried out the reaction under solvent-free condition at 110 ∘ C for 30 minutes [98].The solvent-free synthesis of imidazoles was explored with sulfonic acid functionalized SBA-15 as a catalyst.It was found that aliphatic aldehyde gave moderate yield and the aromatic aldehyde with electron-withdrawing and electron-donating groups gave excellent yield in the presence of catalyst and it could be recovered by continuous washing with dilute acid, water, and acetone [99]  was utilized for the efficient synthesis of substituted imidazoles under ultrasound irradiation.Because of the decrease in size of the crystal magnesium aluminate, a defect was produced in the coordination of constituent atoms which increases the reactivity of the catalyst, and thereby it leads to cyclocondensation reaction for the formation of imidazoles [100].The synthesis of imidazole was carried out using clay and zeolite and also with nanocrystalline-sulfated zirconia catalyst in the presence of ethanol at room temperature.The optimization of the reaction condition was performed and found that the yield was increased up to 93% by the SZ catalyst [101].The Bronsted acid nanoreactor, MCM-41-SO 3 H, was involved in the solvent-free synthesis of trisubstituted and tetrasubstituted imidazoles.In this experiment, it was found out that the solvents have no role on the synthesis of imidazoles.The modified action of the nanoreactor increased its efficiency and resulted in higher yield and good reusability [102].An efficient catalyst, magnetic Fe 3 O 4 nanoparticles, can also be used for the synthesis of imidazole derivatives.Magnetic Fe 3 O 4 nanocatalyst and temperature (80 ∘ C) play a crucial role in this reaction under solvent-free condition and gave a maximum yield of up to 96% [103].Rostamizadeh and coworkers developed a toxic-free solvent reaction for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetra-substituted imidazoles using nanosized MCM-41-SO 3 H as a catalyst [88].
2.17.Synthesis of Pyrimidine Carbonitriles.The three-component reaction involving aldehydes, 2.17.1, malononitrile, 2.17.2, and amidines, 2.17.3, in the synthesis of 4amino-5-pyrimidinecarbonitriles, 2.17.4,(Scheme 21) was catalyzed using CuO microspheres.CuO microspheres are made by granulation of nanoparticles using immobilizationcalcination method [104].Even though the surface area of microspheres is lesser than nanoparticles, they are larger than bulkier substances.The main purpose of microspheres is to avoid the physical instability of nanoparticles such as agglomeration.The polar solvents such as THF, CH 3 CN, and CH 3 CH 2 OH gave fewer yields than water in the synthesis of 4-Amino-5-pyrimidinecarbonitriles.4-amino-5pyrimidinecarbonitriles can also be synthesized using ZnO  nanoparticles.Being insoluble in water and other organic solvents it can be easily recovered from the reaction mixture immediately after the reaction [105].the desired product.Ag-Pd alloy nanoparticles supported on carbon, a comparison of the activity of Ag-Pd/C catalyst with that of palladium-based nanocatalystscore-shell Ag@Pd/C and Pd/C were studied.At 125 ∘ C, all the catalyst produced more-or less-same yield whereas at 90 ∘ C Ag-Pd/C catalyst superseded the other two catalysts in yield.This was explained due to the transfer of charge from lesselectronegative Ag metal to more electronegative Pd [107].An alternative method to synthesize quinoline derivatives such as imidazo [  ].This support is more water soluble than the other inorganic supports.Thereby, the reactions in aqueous solution will be catalyzed effectively.The reaction between 2-iodoanilines, 2.22.1, and phenyl acetylene, 2.22.2, in the presence of 3%-Pd/MIL-101 will lead to the formation of indole, 2.22.3,(Scheme 32).In addition, the substituents on the ring will have an effect on the current reaction medium [116].

Conclusions
This review is the first attempt to compile the literature on the subject of nanomaterials application in organic synthesis.It should be noted that a correct and update citation and literature survey is very important for researchers to find relevant information, pioneer ideas, and progress of any subject.On the other hand, published data using nanomaterials indicate a wide synthetic potential of the described catalysts and a great interest of researchers in this field.The use of green nanocatalyst for the synthesis of various heterocycles has advantages such as short reaction time, high yield, inexpensive chemicals usage, easy work-up procedure, and very specific reaction [2].The use of nanocatalyst can also be applied on the synthesis of various heterocycles which  are very difficult to prepare by conventional methods.Also more and transition metals can be checked for its catalytic activity and surface modifications of the existing catalyst can also be performed.In most of the reactions the spent catalyst can be easily separated from the reaction mixture, also it can be reused without noticeable change in its catalytic activity.A wide range of original procedures for synthesizing various classes of organic compounds, including organic functional group transformation, have been developed on the basis of nanoparticles.We assume that the present review article may be bringing a basis to advance information to this very important subject and to encourage active researchers in this field for the synthesis of organic compounds using nanoparticles.

Figure 1 :
Figure 1: Application of nanoparticles in organic synthesis.

.19.15 and
(Scheme 25)in the presence of water and microwave irradiation was carried out in an ecofriendly way.These derivatives can be synthesized from arylaldehyde,

.19.18, under
[111]rent catalysts (TiO 2 , SiO 2 , Al 2 O 3 , ZnO, MgO, CuO bulk and nano-CuO) in solvent-free condition at 60 ∘ C, and nano-CuO was found superior to all the other catalysts[110].So et al. explored that AuNPs/SiO 2 + O 2 as an efficient catalyst system for the synthesis of polyheterocyclic compounds containing nitrogen, 2.19.21 (Scheme 27) from aniline, 2.19.13, and aldehyde, 2.19.6.They performed the mechanistic studies of quinolines and reported that the reaction does not follow the radical pathway, and the yield was very less in the presence of silica alone.Therefore, AuNPs/SiO 2 + O 2 protocol is the optimal one for the quinoline synthesis[111].Ferrite magnetic Scheme 30: CuO-mediated various benzoheterocycle synthesis, 2.20.3.