Nano Nickel-Cobalt Ferrite Catalyzed One Pot Synthesis of 14-Aryl-14 H-dibenzo [ a , j ] xanthenes and 12-Aryl-8 , 9 , 10 , 12-tetrahydrobenzo [ a ] xanthene-11-one Derivatives RAGHU

A simple, green and multi component, one pot synthesis of 14-Aryl-14H-dibenzo[a, j]xanthene derivatives by condensation of aryl aldehydes with 2-naphthol using magnetically separable and recyclable heterogeneous catalyst nano nickel cobalt ferrite (Ni0.5Co0.5Fe2O4), has been described. In addition, a one-pot three component condensation of aryl aldehydes, 2-naphthol and dimedone has been developed to furnish 12-Aryl-8, 9, 10, 12-tetrahydrobenzo[a]xanthene-11-one derivatives in good to excellent yields under the same reaction conditions. The main advantage of this method is the nano catalyst can be reused up to five reaction cycles without losing the catalytic activity.


INTRODUCTION
One-pot, Multi Component Reactions (MCRs) are having momentous meaning due to formulation of mono product with elevated yields by the blending of two or more components in a one step process 1 , 2 .The advantages of MCR's are atom economy, less time consuming, easy purification process and avoid protection -deprotection steps.Therefore, the design and development of efficient and green MCRs focussed on a target molecule is one of the most important challenges in organic synthesis in both medicinally and industrially.
Xanthenes and benzoxanthenes are an important class of oxygen heterocycles 3 .Xanthenes and benzoxanthenes are important intermediates in organic synthesis due to their wide range of biological and pharmaceutical activities such as antiviral 4 , antibacterial 5 and anti-inflammatory activities 6 .These compounds are also being utilized as antagonists for the paralyzing action of zoxazolamine 7 , in photodynamic therapy 8 , as leuco-dyes in laser technology 9 and as P H -sensitive fluorescent material for visualization of biomolecules 10 .
Many synthetic strategies has been developed for synthesis of xanthenes and benzoxanthenes because of their pharmacological and biological activities such as cyclo-acylation of carbamates 11 , trapping of benzynes by phenol 12 , cyclocondensation between 2-hydroxy aromatic aldehydes and 2-tetralone 13 , cyclodehydrations 14 and cyclization of polycyclic aryltriflate esters 15 .Recently the synthesis of benzoxanthenes has been achieved by the condensation of aromatic aldehydes with 2-naphthol by cyclodehydration in the presence of various catalysts such as amberlyst-15 16 , sulfamic acid 17 , molecular iodine 18 , Al(HSO 4 ) 3
The methods which are specified above are having its own advantages and merits, however many of these methods are unsatisfactory as they involve the use of halogenated solvents, unsatisfactory yields, catalyst loadings up to 30 mol%, prolonged reaction time and tedious experimental procedures.All of these disadvantages make further improvements for the synthesis of such molecules essential.Therefore, it is necessary to develop the alternate methods for the synthesis of 14-Aryl-14H-dibenzo [a, j] xanthenes and 12-Aryl-8, 9, 10, 12-tetrahydrobenzo[a]xanthene-11-one derivatives.The synthesis mechanism should involve simple in process, efficient, eco friendly with high yields with novel catalysts.
Recently, nanomaterial-based catalysts as prominent heterogeneous catalysts are widely used in order to accelerate catalytic processes, particularly because they are accompanied with the principle of the green chemistry.The greener generation of nanoparticles and their eco-friendly applications in catalysis via magnetically recoverable and recyclable nano-catalysts for a variety of oxidation, reduction, and condensation reactions [37][38][39][40] , has made an incredible impact on the development of sustainable pathways.Magnetically recyclable nano catalysts and their use in benign media is an ideal merge for the development of sustainable methodologies in organic synthesis.
Therefore, in order to accomplish the novel, high yielding and eco-friendly synthetic process, minimizing the by-products, with minimum number of separate reaction steps, improving the yields, our research work was extended by the application of nano catalysts in MCRs, we wish to report a clean and environmentally friendly approach to the synthesis of 14-Aryl-14H-dibenzo[a, j]xanthenes and tetrahydrobenzo[a]xanthen-11-ones via multicomponent reaction of aldehydes, 2-naphthol and dimedone in the presence of nickel cobalt ferrite nanoparticles.
Due to the effective activity of magnetically separable nickel cobalt ferrite nano particles have the advantages of recyclability, easy work-up and clean reaction profiles apart from the lack of necessity ligands and in minimizing the organic waste generation when compared to the conventational catalytic systems.In this, we report 14-Aryl-14H-dibenzo[a, j]xanthenes and 12-Aryl-tetrahydrobenzo[a]xanthen-11-ones using magnetically separable and recyclable nano nickel cobalt ferrite as heterogeneous catalyst.The synthesised derivatives were characterised by IR, H 1 -NMR and Mass spectral data.

Experimental
Sigma Aldrich has been selected as vendor for sourcing the chemicals.All chemicals were purchased, which is having the purity not less than 99.9%.Analytical Thin Layer Chromatography (TLC) was carried out by using silica gel 60 F254 precoated plates.Visualization was accomplished with UV lamp.All the products were characterized by their IR, H 1 NMR and Mass spectra. 1 H NMR was recorded on 300 MHz in CDCl 3 /DMSO, and the chemical shifts were reported in parts per million (ppm, ä) downfield from the Tetramethyl silane (TMS).and 0).In this Ni 0.5 Co 0.5 Fe 2 O 4 (x=0.5)has been chosen for the study and was synthesised by a chemical solgel co-precipitation method.In order to prepare Ni 0.5 Co 0.5 Fe 2 O 4 nanoparticles, 0.05 moles of nickel nitrate, 0.05 moles of cobalt nitrate and 2 moles of iron nitrate are dissolved separately in a little amount of deionised water and then citric acid solution was prepared stoichiometric proportions.These two solutions were added in a 1:1 molar ratio and P H adjusted to 7 by the addition of ammonia and ethylene glycol is added.The aqueous mixture was heated to 60 0 C, it was converted to gel and then temperature increased to 200 0 C finally to get powder.That powder was calcined to 600 0 C and then characterised with XRD and SEM.

General experimental procedure for synthesis of 14-Aryl-14H-dibenzo[a, j]xanthenes
Aromatic aldehyde (2 mmol) and 2-naphthol (4 mmol) and nano nickel cobalt ferrite (Ni 0.5 Co 0.5 Fe 2 O 4 , 20 mol %) catalyst were taken in a round bottomed flask and the contents are dissolved in 5 mL of ethanol.Then the reaction mixture stirred for 20 min at reflux temperature (scheme-1).The progress of the reaction was monitored by TLC (n-hexane: ethyl acetate 4:1).After completion of the reaction the catalyst was separated by using an external strong Neodymium35 magnet.Then 10 mL of ethanol Then the reaction mixture stirred for 30 min at reflux temperature (scheme-2).The progress of the reaction was monitored by TLC (n-hexane: ethyl acetate 4:1).After completion of the reaction the catalyst was separated by using an external strong Neodymium35 magnet.Then 10 mL of ethanol was added to the reaction mixture and removal of solvent by rota vapor.After, the dried product was recrystallized from hot ethanol for several times to get the corresponding pure product tetrahydrobenzo [a]  xanthene-11-one derivatives in excellent yields.The products were confirmed by IR, H 1 NMR, and Mass spectras.

Chemistry
Initially a model reaction is conducted at room temperature using different solvents and different mol% of catalyst for synthesis of 14-Aryl-14H-dibenzo[a, j]xanthenes and 12-Aryl-8, 9, 10, 12tetrahydrobenzo[a]xanthene-11-one to investigate the feasibility of the reaction.
Benzaldehyde and 2-naphthol were taken in different solvents (CH 2 Cl 2 , CHCl 3 , CH 3 CN, ClCH 2 CH 2 Cl and ethanol), stirred for 5 hrs without catalyst at room temperature.It is observed that very low yield (<10%, Table-1, entry 1-5) of product is obtained even after 5 hrs of stirring.There was a slight increase in yield (10% to 52%, Table-1, entry 6-10), when the reaction mixture is added with 5 mol% nano nickel cobalt ferrite (Ni 0.5 Co 0.5 Fe 2 O 4 ) catalyst even on stirring for just 3 hrs at refluxed temperatures.It was observed that yield 52% obtained was much better in ethanol solvent at the same reaction conditions.On increasing the catalyst to 10 and 15 mol%, there was increase in yield up to  With the optimised conditions in hand, the reaction was performed with different benzaldehydes (scheme 1) to explore the scope and generality of the present protocol and the results of these observations are summarized in Table 2. From the results, Benzaldehyde and other aromatic aldehydes containing electron-withdrawing and electrondonating groups were converted efficiently to the corresponding dibenzoxanthenes in excellent yields.The structures of synthesized dibenzo xanthenes were confirmed by IR, H 1 NMR and Mass spectral analysis.The plausible mechanism for the formation of 14-Aryl-14H-dibenzo[a,j]xanthenes by using nickel cobalt ferrite NPs is shown in figure 1.
On the other hand a model reaction is conducted by using different solvents and different mol% of catalyst for synthesis of 12-aryl-8, 9, 10, 12tetrahydrobenzo[a]xanthene-11-one to investigate the feasibility of the reaction.
Dimedone, benzaldehyde and 2-naphthol were taken in different solvents chloroform (CHCl 3 ), acetonitrile (CH 3 CN), tetrahydrofuran (THF), dichloroethane (ClCH 2 CH 2 Cl) and ethanol stirred for 8 hrs without catalyst at room temperature.It is observed that very low yield (<10%, Table-4, entry 1-5) of product is obtained even after 8 hrs of stirring.There was a slight increase in yield (10% to 55 %, Table-4, entry 6-10), when the reaction mixture is added with 5 mol% nano nickel cobalt ferrite (Ni 0.5 Co 0.5 Fe 2 O 4 ) catalyst even on stirring for just 5 hrs at refluxed temperatures.It was observed that yield 55% obtained was much better in ethanol solvent at the same reaction conditions.On increasing the catalyst to 10 and 15 mol%, there was increase in yield up to 70% and 85% respectively at the 75-78 0 C. Further increasing the catalyst to 20 mol% increased the yield to 96% (Table-4, entry 13) in 30 minutes.All the results are tabulated in Table-4.No change was observed on further enhancing the catalyst mol%.
With the optimised conditions in hand, the reaction was performed with different benzaldehydes (scheme 2) to explore the scope and generality of the present protocol and the results of these observations are summarized in Table 5.From the results, aromatic aldehydes carrying either an electron donating groups or an electron withdrawing groups reacted successfully and gave the products in good to excellent yields.The structures of synthesized tetrahydrobenzo xanthenes were confirmed by IR, H 1 NMR and Mass spectral analysis.The plausible mechanism for the formation of 12-aryl-8, 9, 10, 12-tetrahydrobenzo[a]xanthene-11-one by using nickel cobalt ferrite NPs is shown in figure 2.

Reusability of the catalyst
The reusability of nickel cobalt ferrite NPs is one of the most important advantages of this protocol that makes it useful for practical commercial applications.We have examined the recyclability of nickel cobalt ferrite NPs catalyst for the model reaction.Interestingly, the recovered catalyst could be reused for up to five cycles which is evident from Table 7.The catalyst was separated by using a magnet after completion of the reaction, washed with water followed by chloroform, dried in oven and reused for the next cycle.

CONCLUSION
Based on above conclusion it was concluded that, we have described a novel, efficient, multi-component one pot green synthetic method using nano nickel cobalt ferrite catalyst and ethanol as a solvent.The novelty and synthetic utility of this method is demonstrated in the efficient synthesis of 14-Aryl-14H-dibenzo xanthene and 12-aryl tetrahydrobenzo xanthene-11-one derivatives.The advantages of this method include its simplicity of operation, cleaner reaction, and good to excellent yields.Further, the purification of the product is simple filtration is involved.The catalyst is easily separated by using external magnet and is reusable up to five cycles.

Nickel Cobalt Ferrite catalysed synthesis of 14-Aryl-14Hdibenzo[a,j]xanthene derivatives
Ni 0.5 Co 0.5 Fe 2 O 4 , 20 mol %) catalyst were taken in a round bottomed flask and the contents are dissolved in 5 mL of ethanol.
Table-1, entry 11 and 12).Further increasing the catalyst to 20 mol% increased the yield to 95% (Table-1, entry 13) in 20 minutes.All the results are tabulated in Table 1.No change was observed on further enhancing the catalyst mol%.