Water mediated reactions: TiO₂ and ZnO nanoparticle catalyzed multi component domino reaction in the synthesis of tetrahydroacridinediones, acridindiones, xanthenones and xanthenes

Abstract

Eco-accommodation of TiO₂ nanorods in the four component Domino reaction for the framing of 9-(2-oxo-1,2-dihydroquinolin-3-yl)-10-phenyl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones 4 from 1,3-cyclohexanedione and/or dimedone 1, 2-chloro-3-formylquinoline 2 and anilines 3 in water at 90 °C are accounted for. The present methodology offers a domino reaction strategy, high yield, simple operation, recyclability and is eco-friendly. In addition, a productive, highly chemoselective ZnO catalyzed, water mediated, microwave aided synthesis of functionalized xanthenes and xanthenones 7 and acridinediones 8 in excellent yields is reported through an environmentally benevolent strategy.

---

Introduction

1,8-Acridinediones and their derivatives are adaptable intermediates with potential pharmaceutical action against cardiovascular ailments, hypertension, Alzheimer's disease, and cancer, and are utilized as laser fluorescent dyes, photo-sensitizers with photo physical and electrochemical properties.^1–10 Many strategies have been developed, including catalytic systems, for instance, ceric ammonium nitrate,^11,12 microwave irradiation,¹³ Zn(OAc)₂·7H₂O,¹⁴ CeCl₃·7H₂O,¹⁵ silica bonded S-sulfonic acid,¹⁶ solvent free methanesulfonic acid catalysed,^17,18 In(OTf),¹⁹ p-dodecylbenzenesulfonic acid in an aqueous medium,^20,21 ionic liquids, such as 1-n-butyl-3-methylimidazolium bromide ([bmim]Br),^22,23 Amberlyst-15,^24,25 ammonium chloride,^26,27 P₂O₅,²⁸ [B(C₆F₅)₃],²⁹ and L-proline,³⁰ as well as others along these lines.^31–39 All the techniques delineated above, incorporate the synthesis of symmetrical acridinediones whilst there are few reports known on unsymmetrical acridinediones^40–42 and they experience from one or more distinctive downsides including low yield, longer reaction time, multistep methodology, side products, perilous organic solvents and extravagant catalysts, and are troublesome in the recuperation and reusability of the catalyst. Consequently, there is a need of a gainful strategy, which is a pragmatic, cheap, faster, operationally straightforward and high yielding procedure. Titanium dioxide (TiO₂) of meso-, micro- and nanomaterial nature have been found to have remarkable electronic and optical properties,^43–45 therefore, various endeavors have been made for their synthesis due to their high surface area and uniform pore size, which find enormous applications in photocatalysis,⁴⁶ solar cells,⁴⁷ lithium-ion batteries,⁴⁸ sensors⁴⁹ and catalyst supports, as well as in numerous fields.⁵⁰ In continuation of our research that engages in synthetic strategies for assorted biologically imperative motifs utilizing heterogeneous catalysts,^51–72 we have utilized TiO₂ in a one-pot, four component tandem–cascade reaction towards the synthesis of acridine-1,8-dione under ambient conditions. As of late, we have demonstrated, a domino synthesis of 9-(quinolin-2(1H)-one)-xanthene-1,8(5H,9H)-dione derivatives in an aqueous medium whilst, the present work exhibits the four component, one pot reaction (Scheme 1 and 2). The hydrolysis of the chloro functionality in the reactant to an oxo-functionality under the applied reaction conditions is well discussed in our previous work.

Scheme 1 Synthesis of 9-(2-oxo-1,2-dihydroquinolin-3-yl) acridine-1,8-diones 4.

Scheme 2 Plausible mechanism for the formation of acridine-1,8-dione.

In addition, the synthesis of xanthene and acridine derivatives have attracted chemists' enthusiasm due to their broad variety of biological and pharmaceutical properties, for instance, antiviral,⁷³ antibacterial⁷⁴ and anti-inflammatory activities.⁷⁵ Further, these compounds have been utilized as dyes,⁷⁶ in laser technology⁷⁷ and in pH-sensitive fluorescent materials for the visualization of biomolecular assemblies.⁷⁸ Basically, it is noteworthy that dibenzoxanthenes derivatives have been utilized as sensitizers as a part of photodynamic therapy.⁷⁹ Acridine-1,8-diones containing a 1,4-dihydropyridine parent core has potential pharmacological action, for instance, against malaria,⁸⁰ cancer⁸¹ and leishmania.⁸²

The synthesis of xanthenes and acridine derivatives have been enhanced in the presence of an acidic catalyst, for instance, sulfamic acid,⁸³ Amberlyst-15,⁸⁴ AcOH–H₂SO₄,⁸⁵ p-TSA⁸⁶ and silica sulfuric acid.⁸⁷ There are similar reports incorporating TBAHSO₄ in aqueous dioxane,⁸⁸ wet cyanuric chloride,⁸⁹ TiO₂–SO₄²⁻,⁹⁰ polyaniline p-toluenesulfonate,⁹¹ PPA–SiO₂,⁹² NaHSO₄–SiO₂,⁹³ Fe³⁺–montmorillonite,⁹⁴ 1-methylimidazolium trifluoroacetate,⁹⁵ quaternary ammonium alkyl sulfonate,⁹⁶ polytungstozincate acid,⁹⁷ cellulose-sulfuric acid,⁹⁸ microwave irradiation,^99,100 ionic liquid,^101,102 LiBr, ZrOCl₂·8H₂O,¹⁰³ proline,¹⁰⁴ silica-bonded S-sulfonic acid,¹⁰⁵ ceric ammonium nitrate,¹⁰⁶ methanesulfonic acid¹⁰⁷ and in aqueous media.^108–110

The majority of the reported procedures have downsides, including low product yields, delayed reaction, lavish reagents or catalysts and the use of dangerous organic solvents. Henceforth, there is an exceptional interest for the advancement of an environmentally benign technique towards the synthesis of xanthenes and acridine derivatives. It must be noted that the aqua-mediated reactions have received a lot of consideration on account of their environmental safety¹¹¹ with the use of universal solvents and reusable heterogeneous catalysts, an influential green chemical approach ensuing negligible pollution and waste material, which could have major industrial applications.¹¹² As of late, bulk zinc oxide has been employed as a heterogeneous catalyst for distinctive organic transformations.¹¹³ The latest literature survey uncovers that nano ZnO¹¹⁴ as a heterogeneous catalyst, has received an impressive amount of consideration because it is inexpensive, non-toxic and has environmental preferences i.e., minimum execution time, low corrosion, waste minimization, recycling of the catalyst, and easy transport and disposal of the catalyst. Different ZnO nanostructures have been prepared, including nanoflower, nanorods and nanowhiskers,^115–125 using the thermal treatment of Zn(OH)₄²⁻ or Zn(NH₃)₄²⁻ precursor in an aqueous solvent utilizing structure directing agents or solvothermal processing.^126–128 Consequently, to our great advantage on heterocycles,^51–62 is represented as a water intervened, eco-accommodating microwave irradiated, flower shaped ZnO catalyzed synthesis of xanthene and acridine derivatives (Scheme 3 and 4).

Scheme 3 General scheme for the synthesis of 2-substituted xanthenediones and acridindiones.

Scheme 4 Mechanism.

Results and discussion

In this paper, we concentrated on the application of TiO₂ nanorods towards the synthesis of the titled compounds (Scheme 1). The present methodology stresses the clean, safe, exceptional yield, shoddy strategy and the reusability of the heterogeneous catalysts. In this study, titania nanorods were successfully acquired using a sol–gel process, employing a titanium(IV) tetraisopropoxide (Ti[OCH(CH₃)₂]₄; TIP) precursor in ethanol. As-procured mesoporous titania was calcined at 600 °C to give the thermally stable anatase crystallites. X-ray diffraction studies demonstrated their crystalline nature with peaks lying at 2θ = 25.28° (101), 2θ = 37.94° (004), 2θ = 47.82° (200), 2θ = 54.39° (105) and 2θ = 62.45° (204) and the diffraction information were in good agreement with JCPDS files # 21-1272. Scanning electron microscopy exhibits the crystalline, anatase and titanium dioxide nanorods (TiO₂) morphology (Fig. 1). The TEM images demonstrated well crystalline TiO₂ NPs of sizes ranging from 10–20 nm (Fig. 2). The XPS spectrum of Ti 2p shows doublet peaks corresponding to the binding energy of Ti 2p_1/2 and Ti 2p_3/2 at 464.9 eV and 458.9 eV, respectively. The peak of O 1s was centred at 530.8 eV, which is ascribed to O atoms bound to titanium (Ti⁴⁺–O). The splitting data (spin–orbital doublet splitting) between the Ti 2p_1/2 and Ti 2p_3/2 core levels was 6.0 eV indicating a normal state of Ti⁴⁺ in the anatase TiO₂.

Fig. 1 XRD spectrum and SEM images of nano TiO₂.

Fig. 2 TEM and XPS spectra of nano TiO₂.

Previously, symmetrical acridindiones were obtained through one pot, four component reactions comprising of arylaldehydes, anilines and diketones or by three component reactions involving the arylaldehyde, diketone and enamines. The above reactions include either catalytic-systems or those without a solvent/catalyst. With this information in hand, the four component reaction of 2-chloro-3-formylquinolines, diketones and amines were endeavored to accomplish the unreported acridindiones using TiO₂ nanorods (Scheme 1). At first, a mixture of 1,3-cyclohexanedione 1a, 2-chloro-3-formylquinoline 2a and aniline 3a in a 2 : 1 : 1 molar ratio in ethanol was refluxed in the presence of and without various metal oxides, including ZnO, SnO₂, CuO, NiO and TiO₂. Interestingly, amongst the explored oxides using TiO₂ in the reaction offered the product 4a with a noteworthy yield of 50% (Scheme 1, Table 1 and entries 1–7). It ought to be noted that SnO₂, CuO and NiO neglects to offer the desired acridone-1,8-dione compound after prolonged reaction times. However, they gave the xanthenediones. The reaction product 4a was affirmed by an additional NH proton peak and N–C=O carbon peak at δ 12.59 in the proton and carbon NMR spectra, respectively, and by the IR and HRMS data. With this perception, to accomplish the streamlined conditions, a variety of solvents, nano TiO₂ catalyst and catalyst loading were investigated. Fittingly, amongst the different tested solvents (Table 1 and entries 8–12), water was found to be the best and cheapest, and offered a high yield of products. Correspondingly, the nano TiO₂ catalyst with a loading of 1 mol% was the best under the improved conditions (Table 1, entry 10) among the different catalyst loadings of 1–10 mol% (Table 1, entry 10 and 11). The reusability of nano TiO₂ reveals that the catalyst is capable of four sequential cycle runs without any noteworthy product loss. The reusable catalysts did not show any noteworthy change in its morphology and size as affirmed by their SEM and TEM analysis. The nano TiO₂ assumes a catalytic role in water at 90 °C, accelerating the reaction rate and increasing the product yield.

Table 1 Optimization of the one pot, four component reaction^a

S. no	Catalyst (mol%)	Solvent	Time (h)	Yield^b (%)
a Cyclohexanedione (2 mmol), 2-chloro-3-formylquinoline (1 mmol), aniline (1 mmol), 5 mL of an appropriate solvent.b 1,8-Xanthenediones.c 50, 54, 49, 47 and 56% for MeOH, EtOH, iPrOH, nBuOH and water, respectively.d 56, 58 and 62% for 5, 8 and 10 mol%, respectively.e 76, 83, 79 and 77% for MeOH, EtOH, iPrOH and nBuOH, respectively.f 89, 90 and 92% for 5, 8 and 10 mol%, respectively.g 89, 86, 83 and 83% for cycles 1–4, respectively.
1	Nil	Ethanol	3	30
2	Nil	Nil	6	Trace
3	ZnO	Ethanol	12	32^b
4	SnO2	Ethanol	12	43^b
5	CuO	Ethanol	12	42^b
6	NiO	Ethanol	12	33^b
7	Bulk TiO2	Nil	6	35
8	Bulk TiO2 (1)	Water	6	56^c
9	Bulk TiO2 (5–10)	Water	6	62^d
10	Nano TiO2 (1)	Water	1.5	89^e
11	Nano TiO2 (5–10)	Water	1.5	92^f
12	Nano TiO2 (1)	Water	1.5	89^g

---

With these generally upgraded results in hand, the scope of reaction was examined utilizing unsubstituted 2-chloro-3-formylquinoline and those containing a methyl substituent at different positions, substituted anilines and dimedone or 1,3-cyclohexanedione. The advancement of the reactions was checked by thin layer chromatography and by the disappearance of the aldehyde starting materials. The isolated yields are summarized in Table 2. All the incorporated compounds were well characterized by various spectroscopic methods such as FTIR, ¹H NMR and ¹³C NMR spectroscopy and HRMS. A conceivable mechanism for the domino synthesis of 3,4,6,7-tetrahydro-9-(1,2-dihydro-2-oxoquinolin-3-yl)-10-phenylacridine-1,8(2H,5H,9H,10H)-dione is portrayed in Scheme 2. Initially, 2-chloro-3-formylquinoline gets hydrolyzed to 2-oxo-3-formylquinoline, which then reacts with 1,3-cyclohexanedione to give an intermediate 1i that further reacts with a second molecule of 1,3-cyclohexanedione to form a diketone intermediate 3i. The diketone then condenses with the anilines with the elimination of water to give the desired acridone-1,8-dione product 4b.

Table 2 Synthesis of acridine-1,8-diones^a

a 2-Chloro-3-formylquinoline (1 mmol), cyclohexane-1,3-dione or dimedone (2 mmol), aniline (1 mmol), 1 mol% nano TiO2, 5 mL of water, reflux.

---

The ZnO required for the present study is adequately prepared from a zinc acetate precursor and sodium hydroxide as a precipitating agent using a sol–gel strategy. Typically, 21.94 g of zinc acetate dihydrate was dissolved in 100 mL (0.149 M) doubly distilled water in a flat bottomed flask under steady magnetic stirring conditions and homogenized for 30 minutes, NaOH 3.33 M (30 mL) was then added dropwise to the flask. The colloidal milky solution formed was stirred for an hour and a while later setup in a water bath maintained at 65 °C for an hour, then cooled and centrifuged at 4000 rpm. It must be noted that the basic pH of the reaction mixture was found to be 12.5 and at a pH of 11.9 the flower-shaped ZNP was formed. The white precipitate obtained was washed with doubly distilled water, and then with methanol, and dried at room temperature for 24 h. The procured powder was calcined at 500 °C for 2 h. The chemical reactions included are as follows (see Fig. 3).

Fig. 3 Chemical reaction for Nano ZnO formation.

The morphology and microstructure of flower-like ZnO nanostructure have been depicted by X-ray diffraction (XRD) and scanning electron microscopy (SEM) (Fig. 4). The crystalline structure and the nanosize are adjusted with the XRD pattern. The sharp diffraction peaks at 2θ = 32.009° (100), 34.4746° (002), 36.3087° (101), 47.6093° (102), 56.6418° (110) and 62.8936° (103) demonstrate the incredible crystallinity of the ZnO NPs. The high intensity of the (100) peak at 32 demonstrates the development of ZnO NPs along the direction of crystallization. The ZnO NPs crystallite size was calculated using the Debye–Scherrer equation:

D = kλ/β cos θ

utilizing the highest astounding peak (101), where k = proportionality constant = 0.9; λ = X-ray wavelength Cu-Kα = 1.54178 Å; β = full width at half maxima; and θ = Braggs' angle in degrees. FTIR spectroscopy of the flower-like ZnO nanostructures was analyzed to recognize its structure and quality. The spectra revealed bands at 505 cm⁻¹ identifying with the Zn–O stretching vibration and a broad absorption at 3200–3600 cm⁻¹ demonstrating the hydroxyl mode of vibration on the surface of the ZnO samples.

Fig. 4 XRD and SEM images of nano ZnO.

The morphology and size of the ZnO particles were recognized from the SEM images, which show abundant flower-shaped bundles of ZnO NPs with long and pointed rods and the SEM patterns concur well with the XRD results. The lengths of the flower-shaped ZnO nanostructures are in the range of 0.8–2 mm with the petal widths changing from the tip to the premise. The TEM images showed well crystalline ZnO, nanostructures in the range 70–100 nm (Fig. 5).

Fig. 5 TEM and XPS spectra of nano ZnO. (a) TEM image, inset shows SAED, (b) XPS survey sweep of ZnO nanoparticles, (c) high resolution XPS of Zn 2p level and (d) high resolution XPS of oxygen 1s level.

The XPS survey sweep of the ZnO nanoparticles exhibit the peaks credited to the elements Zn, O and C, and the HRXPS of O 1s and Zn 2p core level (Fig. 5). The XPS spectra show their corresponding binding energies. The peak centered at 530.2 eV is related to the O₂ ions encompassed by the Zn atoms. The other nearby peak located at 531.1 eV is identified with the OH groups ingested onto the surface of the ZnO nanoparticles. The Zn 2p core-level of ZnO NPs reveals two peaks at around 1043.7 and 1020.7 eV identified with Zn 2p_1/2 and Zn 2p_3/2, respectively. The ratio of Zn/O is marginally lower than unity affirming pure ZnO as accommodated by the XRD results.

At first, when a reaction between aryl aldehyde 5a, diketone, 1 and beta naphthol 6a in an equimolar ratio is completed without a catalyst in ethanol under reflux conditions for 6 h, the reaction continued to offer a low yield of the desired xanthenone product 7a (Table 3, entry 1). Subsequently, the reaction in the presence of a catalytic amount (5 mol%) of metal oxide, including SnO₂, CuO, TiO₂ and ZnO was investigated in ethanol under reflux conditions for 6 h. Amongst the tested metal oxides, ZnO was found to be the best catalyst with a 77% yield of product and TiO₂ the second best with a 56% yield (Table 3, entries 6 and 4). Supported by these results, a variety of catalysts (from bulk to nanomaterials), catalyst loading, heating strategies (for instance, conventional heating and microwave irradiation using a synthetic microwave oven) were investigated. The results revealed that the ZnO NPs were the best catalyst amongst the different bulk and nanomaterial catalysts (Table 3, entry 5 and 7).

Table 3 Optimization of the reaction conditions^a

Sl. no.	Catalyst	Yield^b (%)
		7a
a Reaction conditions: arylaldehyde (1 mmol), cyclohexane-1,3-dione (1 mmol), 2-naphthol (1 mmol), 5 mol% (unless otherwise stated) of appropriate catalyst in water (unless otherwise stated) at 700 W (unless otherwise stated) and microwave irradiated.b Isolated yield.
1	No catalyst	Trace
2	SnO2 (bulk)	12
3	CuO (bulk)	30
4	TiO2 (bulk)	56
5	TiO2 (nano)	60
6	ZnO (bulk)	77
7	ZnO nano (5)	80
8	ZnO nano (10)	85
9	ZnO nano (15)	88
10	ZnO nano (20)	86
11	ZnO nano (ethanol)	70
12	ZnO nano (methanol)	72
13	ZnO nano (n-butanol)	62
14	ZnO nano (isopropanol)	65
15	ZnO nano (100 W)	45
16	ZnO nano (200 W)	56
17	ZnO nano (400 W)	63
18	ZnO nano (600 W)	77

---

An enhanced catalyst loading of 5 mol% from the 0, 5, 10, 15, 20 mol% investigated (Table 3, entry 7–10) and water was found to be the best solvent amongst methanol, ethanol, butanol, and isopropanol investigated for the progression of the reaction and better yields (Table 3, entry 11–14). Microwave irradiation at 700 W for 5 min was the best amongst those tested (100, 200, 400, 600 and 700 W) and offered the desired product in a phenomenal yield (Table 3, entry 15–18). The reusability of nano ZnO reveals that the separated catalyst (from the reaction mixture by dissolving the organic products) was capable of four sequential cycle runs without any noteworthy product and catalyst efficiency loss. The reusable catalyst did not show any noteworthy change in its morphology and size as affirmed by their SEM and TEM analysis. Having the streamlined result in hand, we then examined the scope of the reaction with distinctive aldehydes to give the desired products 7a–f in good yield (Table 4). Subsequently, the isomeric xanthenone product was targeted utilizing alpha naphthol under the optimized reaction conditions to give the desired product 7g in excellent yield (Scheme 3). In any case, it must be noted that without the diketone, aldehydes can productively react with two equivalents of beta-naphthol under the optimized conditions to give the symmetrical xanthenes 7h and 7i (Scheme 3). Further, the scope of the reaction was explored by utilizing the above optimized conditions, including benzaldehyde, diketone and aniline in a 1 : 2 : 1 ratio in attempt to give the desired product 8a. The distinctive aldehydes have turned out to be productive for the desired products 8a–f in excellent yield (Table 5). Correspondingly, the reaction between aldehydes, diketone and ammonium acetate in a ratio of 1 : 2 : 1 was expected to give the product 8f–j. The quinoline aldehydes and napthylamines, when attempted under above optimized condition neglected to offer a pure and quantitative yield of the expected product as outlined. Alternate approaches to attain the same are currently being investigated in our research.

Table 4 Synthesis of xanthenones and xanthenes 7^a

a Reaction conditions: arylaldehyde (1 mmol), cyclohexane-1,3-dione (1 mmol), 2-naphthol (1 mmol), 5 mol% of nano ZnO catalyst in water at 700 W and microwave irradiation.

---

Table 5 Synthesis of acridindiones 8^a

a Reaction conditions: arylaldehyde (1 mmol), cyclohexane-1,3-dione (1 mmol), ammonium acetate or aniline (1.2 mmol), 5 mol% of nano ZnO catalyst in water at 700 W and microwave irradiation.

---

A conceivable mechanism for the domino synthesis of 9-(quinolin-2(1H)-one)-xanthene-1,8(5H,9H)-dione is given in Scheme 4. At the outset, 2-aryl aldehyde and the cyclohexanedione get activated by the ZnO NPs. Subsequently, the first molecule of 1,3-cyclohexanedione condenses with the aldehydes to form the related alkylidene intermediate. Further, the active methylene group of a second 1,3-cyclohexanedione molecule reacts with intermediate through a Michael addition reaction to give another intermediate. The intermediate formation steps are facilitated by the ZnO NPs, which further experience an intra-molecular cyclodehydration in the presence of aniline to furnish the desired acridindione product 8b.

Similarly, the alkylidene derivative structured in the first step experiences a condensation reaction with the naphthol molecule to form an intermediate, which further experiences an intramolecular cyclodehydration to give the desired benzoaxanthenone 7f. The steps are facilitated by the ZnO NPs.

Taking everything into account, an efficient one-pot, four component synthesis of 3,4,6,7-tetrahydro-9-(1,2-dihydro-2-oxoquinolin-3-yl)-10-phenylacridine-1,8-(2H,5H,9H,10H)-dione derivatives was achieved utilizing a TiO₂ nanorods catalyst. The present method offers selectivity to obtain 9-(2-oxo-1,2-dihydroquinolin-3-yl)-10-phenyl-3,4,6,7-tetrahydro acridine-1,8-(2H,5H,9H,10H)-diones product in high yield using a simple technique under gentle conditions with a reusable catalytic system.

Moreover, a proficient one-pot synthesis of xanthenes and acridine derivatives was achieved utilizing a nanocrystalline ZnO catalyst in water by MWI. The present technique offers high return, a simple strategy, mellow conditions and a reusable catalyst. The reaction conversion was good to excellent for all the analogs employed with good isolated yields.

General procedure for the synthesis of acridine-1,8-diones (4)

In a typical experimental procedure, a mixture of 2-chloro-3-formylquinoline (1.0 mmol), 1,3-cyclohexanedione (2.0 mmol), anilines (1.0 mmol) and distilled water (5.0 mL) was placed in a 50 mL reaction vial in the presence of nano TiO₂ (1 mol%) and heated to 90 °C. Advancement of the reaction was observed by thin layer chromatography. After completion, the reaction mixture was filtered to remove the any catalyst, washed with water. The acquired compound was pure enough for further analysis.

Preparation of xanthenones and xanthenes (7)

Preparation of 7a is described as a typical procedure.

A mixture of prydine-2-carboxaldehyde (1 mmol), cyclohexane-1,3-dione (1 mmol), 2-naphthol (1 mmol), 5 mol% of ZnO NPs in water was microwave irradiated at 700 W (using a synthetic microwave oven). After irradiation for 5 min, the reaction was extracted three times with ethyl acetate leaving behind the catalyst (separated by filtration). The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate. After the removal of the solvent under reduced pressure, the residue was purified by column chromatography (hexane : AcOEt 30 : 1) on silica gel to obtain the desired xanthenone as a colorless solid.

A similar procedure was used to prepare 7b–i. However, in the case of xanthenes 7h and 7i, cyclohexane-1,3-dione was not utilized.

Preparation of acridinones (8)

Preparation of 8a is described as a typical procedure.

A mixture of 4-chlorobenzaldehyde (1 mmol), cyclohexane-1,3-dione (1 mmol), aniline (1 mmol) and 5 mol% of ZnO NPs catalyst in water was microwave irradiated at 700 W (using a synthetic microwave oven). After irradiations for 5 min, the reaction was extracted three times with ethyl acetate leaving behind the catalyst (separated by filtration). The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (hexane : AcOEt 30 : 1) on silica gel to give the desired xanthenone as a colorless solid. A comparative procedure was used to prepare 8b–e. However, in the case of xanthenes 8f–j, ammonium acetate was utilized in the place of aniline.

Acknowledgements

The authors wish to express their gratitude to the VIT University Vellore for Major research initiative support and facilities, and SIF-VIT for their support of NMR, GCMS and IR facilities, Sathyabama University, India for SEM facilities and KBSI, Busan Center, South Korea for Mass, TEM and XPS facilities. This work was supported by the Grant no. R0001026 from the Ministry of Trade, Industry & Energy and Busan Metropolitan City, Korea. The authors also acknowledge grants from KBSI, no. C34920, P0E013.

Notes and references

1. H. Sarkarzadeh, R. Miri, O. Firuzi, M. Amini, N. Razzaghi-Asl, N. Edraki and A. Shafiee, Arch. Pharmacal Res., 2013, 36, 436.
2. M. G. Gündüz, F. İşli, A. El-Khouly, Ş. Yıldırım, G. S. Öztürk Fincan, R. Şimşek, C. Şafak, Y. Sarıoğlu, S. Öztürk Yıldırım and R. J. Butcher, Eur. J. Med. Chem., 2014, 75, 258.
3. A. Jamalian, R. Miri, O. Firuzi, M. Amini, A. Moosavi-Movahedi and A. Shafieea, J. Iran. Chem. Soc., 2011, 8, 983.
4. M. Kawase, A. Shah, H. Gaveriya, N. Motohashi, H. Sakagami, A. Varga and J. Molnár, Bioorg. Med. Chem., 2002, 10, 1051.
5. B. Rethy, H. J. Ohmann, R. Minorics, A. Varga, I. Ocsovszki, J. Molnar, K. Juhasz, G. Falkay and I. Zupko, Anticancer Res., 2008, 28, 2737.
6. P. Shanmugasundaram, K. J. Prabahar and V. T. Ramakrishnan, J. Heterocycl. Chem., 1993, 30, 1003.
7. N. Srividya, P. Ramamurthy, P. Shanmugasundaram and V. T. Ramakrishnan, J. Org. Chem., 1996, 61, 5083.
8. V. Thiagarajan, P. Ramamurthy, D. Thirumalai and V. T. Ramakrishnan, Org. Lett., 2005, 7, 657.
9. P. Shanmugasundaram, P. Murugan, V. T. Ramakrishnan, N. Srividya and P. Ramamurthy, Heteroat. Chem., 1996, 7, 17.
10. H. Timpe, S. Ulrich, C. Decker and J. Fouassier, Macromolecules, 1993, 26, 4560.
11. M. Kidwai and D. Bhatnagar, Chem. Pap., 2010, 64, 825.
12. S. Tu, Y. Gao, C. Miao, T. Li, X. Zhang, S. Zhu, F. Fang and D. Shi, Synth. Commun., 2004, 34, 1289.
13. A. A. Abdelhamid, S. Mohamed, A. Maharramov, A. Khalilov and M. Allahverdiev, J. Saudi Chem. Soc., 2014, 18, 474.
14. S. Balalaie, F. Chadegani, F. Darviche and H. R. Bijanzadeh, Chin. J. Chem., 2009, 27, 1953.
15. X. Fan, Y. Li, X. Zhang, G. Qu and J. Wang, Heteroat. Chem., 2007, 18, 786.
16. Q. H. To, Y. R. Lee and S. H. Kim, Bull. Korean Chem. Soc., 2012, 33, 1170.
17. S. Rostamizadeh, A. Amirahmadi, N. Shadjou and A. M. Amani, J. Heterocycl. Chem., 2012, 49, 111.
18. K. Niknam, F. Panahi, D. Saberi and M. Mohagheghnejad, J. Heterocycl. Chem., 2010, 47, 292.
19. X. Fan, X. Hu, X. Zhang and J. Wang, Can. J. Chem., 2005, 83, 16.
20. T. S. Jin, J. S. Zhang, T. T. Guo, A. Q. Wang and T. S. Li, Synthesis, 2004, 12, 2001.
21. A. Davoodnia, A. Khojastehnezhad and N. Tavakoli-Hoseini, Bull. Korean Chem. Soc., 2011, 32, 2243.
22. D. Q. Shi, S. Ni and N. F. Y. Fang-Yang, J. Heterocycl. Chem., 2008, 45, 653.
23. W. Shen, L. M. Wang, H. Tian, J. Tang and J. Yu, J. Fluorine Chem., 2009, 130, 522.
24. B. Das, P. Thirupathi, I. Mahender, V. S. Reddy and Y. K. Rao, J. Mol. Catal. A: Chem., 2006, 247, 233.
25. A. Nakhi, P. Srinivas, M. S. Rahman, R. Kishore, G. Seerapu, K. Lalith Kumar, D. Haldar, M. Rao and M. Pal, Bioorg. Med. Chem. Lett., 2013, 23, 1828.
26. X. Wang, D. Shi, D. Zhang, Y. Wang and S. Tu, Chin. J. Org. Chem., 2004, 24, 430.
27. M. Kidwai and D. Bhatnagar, Tetrahedron Lett., 2010, 51, 2700.
28. K. Venkatesan, S. S. Pujari and K. V. Srinivasan, Synth. Commun., 2008, 39, 228.
29. D. J. Parks and W. E. Piers, J. Am. Chem. Soc., 1996, 118, 9440.
30. H. Wang, L. Li, W. Lin, P. Xu, Z. Huang and D. Shi, Org. Lett., 2012, 14, 4598.
31. M. Alvala, S. Bhatnagar, A. Ravi, V. U. Jeankumar, T. H. Manjashetty, P. Yogeeswari and D. Sriram, Bioorg. Med. Chem. Lett., 2012, 22, 3256.
32. D. Patil, D. Chandam, A. Mulik, P. Patil, S. Jagadale, R. Kant, V. Gupta and M. Deshmukh, Catal. Lett., 2014, 144, 949.
33. J. J. Xia and K. H. Zhang, Molecules, 2012, 17, 5339.
34. P. Xiao, F. Dumur, M. A. Tehfe, B. Graff, D. Gigmes, J. P. Fouassier and J. Lalevée, Macromol. Chem. Phys., 2013, 214, 2276.
35. R. Velu, V. Ramakrishnan and P. Ramamurthy, J. Photochem. Photobiol., A, 2011, 217, 313.
36. G. Periyasami, R. Rajesh, N. Arumugam, R. Raghunathan, S. Ganesan and P. Maruthamuthu, J. Mater. Chem. A, 2013, 1, 14666.
37. P. Xiao, F. Dumur, M. A. Tehfe, B. Graff, D. Gigmes, J. P. Fouassier and J. Lalevée, Polymer, 2013, 54, 3458.
38. C. O. Okoro, M. A. Ogunwale and T. Siddiquee, Appl. Sci., 2012, 2, 368.
39. S. K. Singh and K. N. Singh, J. Heterocycl. Chem., 2011, 48, 69.
40. F. Shirini, S. S. Beigbaghlou, S. V. Atghia and S. A. R. Mousazadeh, Dyes Pigm., 2013, 97, 19.
41. S. Abdolmohammadi, Chin. Chem. Lett., 2013, 24, 318.
42. Y. Wan, X. X. Zhang, C. Wang, L. L. Zhao, L. F. Chen, G. X. Liu, S. Y. Huang, S. N. Yue, W. L. Zhang and H. Wu, Tetrahedron, 2013, 69, 3947.
43. F. Rashedian, D. Saberi and K. Niknam, J. Chin. Chem. Soc., 2010, 57, 998.
44. H. J. Lin, T. S. Yang, C. S. Hsi, M. C. Wang and K. C. Lee, Ceram. Int., 2014, 40, 10633.
45. H. X. Zhu and J. M. Liu, Comput. Mater. Sci., 2014, 85, 164.
46. G. Wu, S. K. Zheng, P. Wu, J. Su and L. Liu, Solid State Commun., 2013, 163, 7.
47. N. Miranda-García, S. Suárez, M. I. Maldonado, S. Malato and B. Sánchez, Catal. Today, 2014, 230, 27.
48. B. Atomsa Gonfa, H. Zhao, J. Li, J. Qiu, M. Saidani, S. Zhang, R. Izquierdo, N. Wu, M. A. El Khakani and D. Ma, Sol. Energy Mater. Sol. Cells, 2014, 124, 67.
49. J. Wang, L. Shen, H. Li, X. Wang, P. Nie, B. Ding, G. Xu, H. Dou and X. Zhang, Electrochim. Acta, 2014, 133, 209.
50. S. Singh, H. Kaur, V. N. Singh, K. Jain and T. D. Senguttuvan, Sens. Actuators, B, 2012, 171–172, 899.
51. K. Prabakaran, F. N. Khan, J. S. Jin and P. Manivel, Res. Chem. Intermed., 2012, 38, 429.
52. K. Prabakaran, M. Gund, T. K. Kim, E. D. Jeong, C. Y. Oh, F. R. N. Khan and J. S. Jin, Chem. Pap., 2011, 65, 707.
53. V. Krishnakumar, K. B. K. Mandal and F. R. Khan, Res. Chem. Intermed., 2012, 38, 1881.
54. S. M. Roopan, T. Maiyalagan and F. Nawaz Khan, Can. J. Chem., 2008, 86, 1019.
55. S. S. Tajudeen and F. Nawaz Khan, Synth. Commun., 2007, 37, 3649.
56. K. Prabakaran and F. Nawaz Khan, Phosphorus, Sulfur Silicon Relat. Elem., 2010, 185, 825.
57. M. Gund, F. R. N. Khan, A. Khanna and V. Krishnakumar, Eur. J. Pharm. Sci., 2013, 49, 227.
58. F. Nawaz Khan, P. Manivel, K. Prabakaran, J. S. Jin, E. D. Jeong, H. G. Kim and T. Maiyalagan, Res. Chem. Intermed., 2012, 38, 571.
59. K. Prabakaran, P. Manivel and F. Nawaz Khan, Tetrahedron Lett., 2010, 51, 4340.
60. K. Prabakaran, F. Nawaz Khan and J. S. Jin, Tetrahedron Lett., 2011, 52, 2566.
61. K. Prabakaran, F. Nawaz Khan and J. S. Jin, Res. Chem. Intermed., 2012, 38, 615.
62. V. Krishnakumar, F. Nawaz Khan, B. K. Mandal and E. D. Jeong, Tetrahedron Lett., 2014, 55, 3717.
63. N. T. Patil, F. Nawaz Khan and Y. Yamamoto, Tetrahedron Lett., 2004, 45, 8497.
64. Y. Isogai, F. Nawaz Khan and N. Asao, Tetrahedron, 2009, 65, 9575.
65. R. Subashini and F. R. Nawaz Khan, Monatsh. Chem., 2012, 143, 485.
66. S. M. Roopan and F. R. Nawaz Khan, Med. Chem. Res., 2011, 20, 732.
67. P. Manivel, K. Prabakaran, V. Krishnakumar, F. Nawaz Khan and T. Maiyalagan, Ind. Eng. Chem. Res., 2014, 53, 7866.
68. M. Gund, F. R. Nawaz Khan, A. Khanna and V. Krishnakumar, Eur. J. Pharm. Sci., 2013, 49, 227.
69. K. R. Ethiraj, A. Jesil Mathew and F. Nawaz Khan, Chem. Biol. Drug Des., 2013, 82, 732.
70. K. R. Ethiraj, J. M. Aranjani and F. Nawaz Khan, Med. Chem. Res., 2013, 22, 5408.
71. K. Prabakaran, F.-R. Nawaz Khan, J. S. Jin, E. D. Jeong and P. Manivel, Chem. Pap., 2011, 65, 883.
72. S. M. Roopan, F. R. Nawaz Khan and B. K. Mandal, Tetrahedron Lett., 2010, 51, 2309.
73. J. P. Poupelin, G. Saint-Rut, O. Foussard-Blanpin, G. Narcisse, G. Uchida-Ernouf and R. Lacroix, Eur. J. Med. Chem., 1978, 13, 67.
74. (a) R. M. Ion, Prog. Catal., 1997, 2, 55; (b) R. M. Ion, D. Frackowiak, A. Planner and K. Wiktorowicz, Acta Biochim. Pol., 1998, 45, 833.
75. S. M. Menchen, S. C. Benson, J. Y. L. Lam, W. Zhen, D. Sun, B. B. Rosenblum, S. H. Khan and M. Taing, Chem. Abstr., 2003, 139, p5427fUS Pat., US6583168, 2003.
76. O. Sirkeeioglu, N. Talinli and A. Akar, J. Chem. Res., Synop., 1995, 502.
77. C. G. Knight and T. Stephens, Biochem. J., 1989, 258, 683.
78. A. R. Khosropour, M. M. Khodaei and H. Moghannian, Synlett, 2005, 955.
79. D. W. Knight and P. B. Little, J. Chem. Soc., Perkin Trans. 1, 2001, 1, 1771.
80. S. Girault, P. Grellier, A. Berecibar, L. Maes, E. Mouray, P. Lemiere, M. Debreu, E. Davioud-Charvet and C. Sergheraet, J. Med. Chem., 2000, 43, 2646.
81. S. A. Gamega, J. A. Spicer, G. J. Atwell, G. J. Finlay, B. C. Bagu-ley and W. A. Deny, J. Med. Chem., 1999, 42, 2383.
82. D. G. Carole, D. M. Michel, C. Julien, D. Florence, N. Anna, J. Séverine, D. Gérard, T. D. Pierre and G. Jean-Pierre, Bioorg. Med. Chem., 2005, 13, 5560.
83. B. Rajitha, B. Sunil Kumar, Y. Thirupathi Reddy, P. Narsimha Reddy and N. Sreenivasulu, Tetrahedron Lett., 2005, 46, 8691.
84. S. Ko and C. F. Yao, Tetrahedron Lett., 2006, 47, 8827.
85. R. J. Sarma and J. B. Baruah, Dyes Pigm., 2005, 64, 911.
86. A. R. Khosropour, M. M. Khodaei and H. Moghannian, Synlett, 2005, 955.
87. H. R. Shaterian, M. Ghashang and A. Hassankhani, Dyes Pigm., 2008, 76, 564.
88. H. N. Karade, M. Sathe and M. P. Kaushik, ARKIVOC, 2007, 252.
89. Z. H. Zhang and X. Y. Tao, Aust. J. Chem., 2008, 61, 77.
90. T. S. Jin, J. S. Zhang, A. Q. Wang and T. S. Li, Synth. Commun., 2005, 35, 2339.
91. A. John, P. J. P. Yadav and S. Pataniappan, J. Mol. Catal. A: Chem., 2006, 248, 121.
92. S. Kantevari, R. Bantu and L. Nagarapu, J. Mol. Catal. A: Chem., 2007, 269, 53.
93. (a) B. Das, P. Thirupathi, K. Ravinder Reddy, B. Ravikanth and L. Nagarapu, Catal. Commun., 2007, 8, 535; (b) A. H. Zhang and Y. H. Liu, Catal. Commun., 2008, 9, 1715.
94. G. Song, B. Wang, H. Luo and L. Yang, Catal. Commun., 2007, 8, 673.
95. M. Dabiri, M. Baghbanzadeh and E. Arzroomchilar, Catal. Commun., 2008, 9, 939.
96. D. Fang, K. Gong and Z. L. Liu, Catal. Lett., 2009, 127, 291.
97. M. M. Amini, Y. Fazeli, Z. Yassaec, S. Feizi and A. Bazgir, Open Catal. J., 2009, 2, 40.
98. H. A. Oskooie, L. Tahershamsi, M. M. Heravi and B. Baghernejad, Eur.– J. Chem., 2010, 7, 717.
99. S. K. Singh and K. N. Singh, J. Heterocycl. Chem., 2011, 48, 69.
100. M. Z. Ghodsi, B. Alireza, H. Malihe and M. Somayeh, Arabian J. Chem., 2014, 7, 335.
101. D. Q. Shi, S. N. Ni, F. Yang, J. W. Shi, G. L. Dou, X. Y. Li and X. S. Wang, J. Heterocycl. Chem., 2008, 45, 653.
102. D. Kumar and J. S. Sandhu, Synth. Commun., 2010, 40, 510.
103. (a) B. M. Choudary, M. L. Kantam, K. V. S. Ranganath, K. Mahender and B. Sreedhar, J. Am. Chem. Soc., 2004, 126, 396; (b) H.-Y. Lu, J.-J. Li and Z.-H. Zhang, Appl. Organomet. Chem., 2009, 23, 165.
104. K. Niknam, F. Panahi, D. Saberi and M. Mohagheghnejad, J. Heterocycl. Chem., 2010, 47, 292.
105. M. Kidwai and D. Bhatnagar, Tetrahedron Lett., 2010, 51, 2700.
106. Y. B. Shen and G. W. Wang, ARKIVOC, 2008, xvi, 1.
107. J. J. Xia and K. H. Zhang, Molecules, 2010, 17, 5339.
108. D. Q. Shi, J. W. Shi and H. Yao, Chin. J. Org. Chem., 2009, 29, 239.
109. Z. Safari, Zarnegar and M. Heydarian, Journal of Taibah University for Science, 2013, 7, 17.
110. M. M. Heravi, K. Bakhtiari, V. Zadsirjan, F. F. Bamoharram and O. M. Heravi, Bioorg. Med. Chem. Lett., 2007, 17, 4262.
111. W. Shen, L. M. Wang, H. Tian, J. Tang and J. J. Yu, J. Fluorine Chem., 2009, 130, 522.
112. M. Dabiri, M. Baghbanzadeh and E. Arzroomchilar, Catal. Commun., 2008, 9, 939.
113. L. Rout, T. K. Sen and T. Punniyamurthy, Angew. Chem., Int. Ed., 2007, 46, 5583.
114. F. M. Moghaddam, H. Saeidian, Z. Mirjafary and A. Sadeghi, J. Iran. Chem. Soc., 2009, 6, 317.
115. Z. Chen, Z. Shan, S. Li, C. B. Liang and S. X. Mao, J. Cryst. Growth, 2004, 265, 482.
116. W. I. Park, G. C. Yi, M. Kim and S. J. Pennycook, Adv. Mater., 2002, 14, 1841.
117. C. Bingqiang, C. Weiping, D. Guotao, L. Yue, Z. Qing and Y. Dapeng, Nanotechnology, 2005, 16, 2567.
118. M. H. Huang, Y. Wu, H. Feick, N. Tran, E. Weber and P. Yang, Adv. Mater., 2001, 13, 113.
119. S. W. Kim, S. Fujita, H. K. Park, B. Yang, H. K. Kim and D. H. Yoon, J. Cryst. Growth, 2006, 292, 306.
120. H. Zhang, D. Yang, X. Ma, Y. Ji, J. Xu and D. Que, Nanotechnology, 2004, 15, 622.
121. Q. Xie, Z. Dai, J. Liang, L. Xu, W. Yu and Y. Qian, Solid State Commun., 2005, 136, 304.
122. X. Wang, Y. Ding, C. J. Summers and Z. L. Wang, J. Phys. Chem. B, 2004, 108, 8773.
123. Y. J. Xing, Z. H. Xi, X. D. Zhang, J. H. Song, R. M. Wang, J. Xu, Z. Q. Xue and D. P. Yu, Solid State Commun., 2004, 129, 671.
124. P. Li, Y. Wei, H. Liu and X. Wang, Chem. Commun., 2004, 2856.
125. J. Y. Lao, J. Y. Huang, D. Z. Wang and Z. F. Ren, Nano Lett., 2002, 3, 235.
126. C. Wu, X. Qiao, L. Luo and H. Li, Mater. Res. Bull., 2008, 43, 1883.
127. J. Zhang, L. Sun, J. Yin, H. Su, C. Liao and C. Yan, Chem. Mater., 2002, 14, 4172.
128. A. Pan, R. Yu, S. Xie, Z. Zhang, C. Jin and B. Zou, J. Cryst. Growth, 2005, 282, 165.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra13045f

---