The Scientific World Journal

Volume 2014 (2014), Article ID 427195, 10 pages

http://dx.doi.org/10.1155/2014/427195

Research Article

Nano-ZnO Catalyzed Multicomponent One-Pot Synthesis of Novel Spiro(indoline-pyranodioxine) Derivatives

Harshita Sachdeva, Rekha Saroj, and Diksha Dwivedi

Department of Chemistry, Faculty of Engineering and Technology, Mody Institute of Technology and Science, Lakshmangarh, Sikar, Rajasthan 332311, India

Received 24 August 2013; Accepted 18 November 2013; Published 5 February 2014

Academic Editors: E. Gomez-Bengoa, G. B. Shul’pin, and A. Silva

Copyright © 2014 Harshita Sachdeva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A simple catalytic protocol for the synthesis of novel spiro[indoline-pyranodioxine] derivatives has been developed using ZnO nanoparticle as an efficient, green, and reusable catalyst. The derivatives are obtained in moderate to excellent yield by one-pot three-component reaction of an isatin, malononitrile/ethylcyanoacetate, and 2,2-dimethyl-1,3-dioxane-4,6-dione in absolute ethanol under conventional heating and microwave irradiation. The catalyst was recovered by filtration from the reaction mixture and reused during five consecutive runs without any apparent loss of activity for the same reaction. The mild reaction conditions and recyclability of the catalyst make it environmentally benign synthetic procedure.

1. Introduction

Heterocyclic chemistry is one of the most complex and intriguing branches of organic chemistry and heterocyclic compounds constitute the largest and most varied family of organic compounds. Among heterocyclic compounds, indole derivatives exhibit a number of biological activities [1–8], for example, antimicrobial, anticonvulsant, antineoplastic, antiviral, antihypertensive, anti-inflammatory, and enzymatic inhibition activities dopaminergic agonist and so forth. In addition to substituted and condensed heterocycles, spiroindoles, with C-3 as spiro atom, have received considerable interest due to their strong biological activities [9–11].

Further, Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-diones) is useful in building block for peptide modification [12], synthesis of pseudopeptides [13], and antimicrobial and antitumoral natural products [14]. Similarly, alkylated Meldrum’s acid has been encountered in the synthesis of dehydro-ar-juvabione [15], indane subunit containing paraquinonic acid ethyl ester, and deliquinone natural products [16]. Thus, 2,2-dimethyl-1,3-dioxane-4,6-diones efficiently serves in the synthesis of versatile intermediates and for the synthesis of pharmacologically active molecules.

The recent literature survey reveals that nano-ZnO as heterogeneous catalyst has received considerable attention because of its ecofriendly nature and has been explored as a powerful catalyst for several organic transformations [17–22]. To the best of our knowledge, there is no report available in the literature regarding the reaction of 1H-indol-2,3-diones and activated methylene reagent (malononitrile/ethylcyanoacetate) with 2,2-dimethyl-1,3-dioxane-4,6-diones.

Hence, prompted by these observations and in continuation to our interest in organic synthesis by different methods with the use of nanocatalyst [23], we report an easy and rapid catalytic application of ZnO nanoparticles for one-pot synthesis of spiroindole derivatives incorporating pyranodioxine by the reaction of 1H-indole-2,3-dione, malononitrile/ethylcyanoacetate, and Meldrum’s acid in absolute ethanol under microwave irradiation and conventional heating (Scheme 1). The overall process involves the Knoevenagel condensation of Meldrum’s acid with 1H-indole-2,3-dione followed by “in situ” Michael addition of malononitrile/ethyl cyanoacetate in single operation to give spiro(indole-pyranodioxine) derivatives similar to the earlier reports [24, 25] of the formation of spiroindoles in the reaction of 3-carboethoxycyanomethylene-2H-indol-2-ones with cyclic ketones under classical conditions (Scheme 1). The process described here offers rapid facile one-pot synthesis of spiroindole derivatives using easily recyclable ZnO nanoparticles. This process is cost effective and hence ecofriendly as it is one-pot synthesis with easy workup and does not require harsh reagents. The process developed by us requires less quantity of catalyst (30 mg) for carrying out the catalytic reaction, thus decreasing the amount of effluent to considerable level.

Scheme 1

2. Results and Discussion

The reaction of 1H-indole-2,3-dione (1), malononitrile/ethylcyanoacetate (2), and 2,2-dimethyl-1,3-dioxane-4,6-diones (3) was examined in the presence of catalytic amount (30 mg) of ZnO nanoparticle under microwave irradiation and conventional heating to give novel 7′-amino--dimethyl-2,4′-dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile/carboxyethylester (4a–f)/(5a–f) (Scheme 1) (Table 1).

Table 1: Experimental data of  7′-amino-2′2′-dimethyl-2,4′dioxo-1,2-dihydrospiroindoline-3,5′-pyrano2,3-d-1′,3′dioxine-6′-carbonitrile (4a–f)/carboxyethylester (5a–f) under microwave irradiation (Method A) and conventional heating (Method B).

Entry
X
Method A (MW)a
Method B
M.P. (°C)

Yield
Time
Yield
Time

(%)
(min.)
(%)
(hrs.)

4a

87
9
62
10
294

4b

85
10
65
11
299

4c

83
10
64
10
305

4d

86
9
63
10
315

4e

81
11
68
9
302

4f

88
9
66
8
318

5a

84
8
65
8
296

5b

85
9
65
9
317

5c

85
9
65
9
325

5d

82
9
68
10
312

5e

84
11
70
9
290

5f

86
10
71
9
319

Reaction conditions: Meldrum’s acid (1.0 mmol), isatin (1.0 mmol), malononitrile/ethylcyanoacetate (1.0 mmol), absolute ethanol (15 mL), and catalyst (30 mg). aReaction under microwave irradiation was carried out at 420 watts.

To obtain the optimal conditions, the synthesis of 4a and 5a was used as a model reaction. A mixture of 1, 2, and 3 in the presence of ZnO nanoparticles (30 mg) was either refluxed for 10 hrs or irradiated inside microwave oven for 9 min resulting in the formation of 4a in 62 or 87% yield, respectively (Table 2).

Table 2: Comparison of catalytic activity of ZnO nanoparticles in the synthesis of compounds 4a and 5a by conventional heating and microwave irradiation method (MW).

Entry
Conditions
Type of catalysts
Reaction time 

(hrs/min.)
Yield 

(%)

4a 

MW 

MW 

No catalyst 

ZnO 

No catalyst 

ZnO
35 min.

9 min.

25 hrs 

10 hrs
traces 

87 

traces 

62

5a 

MW 

MW 

No catalyst 

ZnO 

No catalyst 

ZnO
28 min.

10 min.

25 hrs 

10 hrs
traces 

84 

traces 

65

Amount of Reactants: Meldrum acid (1.0 mmol), isatin (1.0 mmol), and malononitrile/ethylcyanoacetate

(1.0 mmol); reaction under microwave irradiation was carried out at 420 watts.

In order to confirm the effective involvement of ZnO nanoparticle during this transformation, a control experiment was conducted in the absence of ZnO nanoparticle for 4a, the reaction did not proceed, and the substrate remained unchanged even after 35 minutes of microwave irradiation and 25 hrs of conventional heating (Table 2), while good results were obtained in the presence of ZnO nanoparticles. After some preliminary experiments, we found that a mixture of 1H-indole-2,3-dione, malononitrile, and 2,2-dimethyl-1,3-dioxane-4,6-diones in the presence of ZnO nanoparticle afforded products in 87% yield under microwave irradiation (Table 1).

Encouraged by these results, we have extended this reaction to variously substituted 1H-indole-2,3-diones under similar conditions to furnish the respective spiro(indole-pyranodioxine) derivatives in excellent yields (81–88%) using ZnO nanoparticle as a catalyst under microwave irradiation (Table 1).

Compounds were also synthesized under conventional heating using ZnO nanoparticle but yield of the product was found to be low (62–71%) as compared to that obtained under microwave irradiation. The synthesis of compound 4a was carried out by refluxing for 10 hrs resulting in 62% yield, while under microwave irradiation, reaction took 9 min with 87% yield of the product. It showed that microwave irradiation was found to have a beneficial effect on the synthesis of spiro(indole-pyranodioxine) derivatives (Table 2).

On optimizing the amount of catalyst, we found that 30 mg of ZnO nanoparticles could effectively catalyze the reaction for the synthesis of desired product. With the inclusion of 10 mg and 20 mg, reaction took longer time. Using more than 30 mg has less effect on the yield and time of the reaction. Therefore, 30 mg of ZnO nanoparticles was sufficient to push the reaction forward, and further increasing of the amount of ZnO nanoparticles did not increase the yields (Table 3).

Table 3: Optimization of the ZnO nanoparticle catalyzed model reaction for synthesis of 7′-amino-2′2′-dimethyl-2,4′-dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile (4a).

Entry
Catalyst (mg)
Yield (%)

1
No catalyst
—

2
10
80

3
15
81

4
20
83

5
25
86

6
30
89

Amount of Reactants: Meldrum acid (1.0 mmol), isatin (1.0 mmol), malononitrile (1.0 mmol), and absolute ethanol (15 mL).

Reusability is one of the most important properties of this catalyst. To study the recyclability of the catalyst, the ZnO nanoparticles were used for the same reaction repeatedly and the change in their catalytic activity was studied. The relation between the number of cycles of the reaction and the catalytic activity in terms of yield of product is presented in Figure 1. The catalyst recovered by filtration from the reaction mixture after dilution with ethyl acetate was reused as such for subsequent experiments under similar conditions. The catalyst retained optimum activity till five cycles after which drop in yield was observed (Figure 1).

Figure 1: Recyclability of ZnO nanoparticles for the synthesis of 7′-amino--dimethyl-2,4′dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][]dioxine]-6′-carbonitrile (4a).

A conceivable mechanism for the formation of the product would be as follows. The ZnO nanoparticle facilitate the Knoevenagel type coupling through Lewis acid sites (Zn⁺²) coordinated to the oxygen of carbonyl groups. On the other hand, ZnO nanoparticles can activate methylene compounds so that deprotonation of the C–H bond occurs in the presence of Lewis basic sites (O⁻²). As a result, the formation of spiroindole derivatives proceeds by activation of reactants through both Lewis acids and basic sites of ZnO nanoparticles.

3. Experimental

3.1. General

Reagents and solvents were obtained from commercial sources and used without further purification. Melting points were determined on a Toshniwal apparatus. The spectral analyses of synthesized compounds have been carried out at SAIF, Punjab University, Chandigarh. Purity of all compounds was checked by TLC using “G” coated glass plates and benzene : ethyl acetate (8 : 2) as eluent. IR spectra were recorded in KBr on a Perkin Elmer Infrared RXI FTIR spectrophotometer (Figure 3) and ¹HNMR spectra were recorded on Bruker Avance II 400 NMR spectrometer using DMSO-d₆ and CDCl₃ as solvent and tetramethylsilane (TMS) as internal reference standard. The obtained products were identified from their spectral (¹HNMR, ¹³C NMR, and IR) data. The microwave-assisted reactions were carried out in a Catalysts Systems Scientific Multimode MW oven attached with a magnetic stirrer and reflux condenser, operating at 700 W generating 2450 MHz frequency.

3.2. General Procedure for the Synthesis of ZnO Nanoparticle

Nanoparticles were synthesized by the literature method [26]. Zinc acetate dihydrate, sodium hydroxide, CTAB, and the other reagents used were all analytical grade (from Shanghai Chemical Corp.) without further purification and reactions were carried out in air. In a typical synthesis, zinc acetate dihydrate, CTAB, and sodium hydroxide were mixed (molar ratio 1 : 0.4 : 3) and ground together in an agate mortar for 50 min at room temperature (25°C). The reaction started readily during the mixing process, accompanied by the release of heat. The mixture was washed with distilled water in an ultrasonic bath. Finally, the product was dried in air at 60°C for 2 hrs.

Synthesis of 7′-Amino-2′2′-dimethyl-2, 4′dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d]-[1′,3′]dioxine]-6′-carbonitrile/carboxyethylester (4a–f)/(5a–f) (see Scheme 2). Compounds 4a–f and 5a–f were prepared by two different methods.

Scheme 2

Method A: Microwave Irradiation Method. An equimolar mixture of 1H-indole-2,3-dione (1) (1 mmole), malononitrile/ethylcynoacetate (1 mmole) (2), and 2,2-dimethyl-1,3-dioxane-4,6-diones (1 mmole) (3) taken in absolute ethanol (15 mL) in presence of ZnO nanoparticle (30 mg) was charged into a glass microwave vessel and refluxed inside a microwave oven at 420 watts for 9-10 min. Progress of the reaction was monitored by TLC. After completion of reaction, the reaction mixture was cooled to room temperature and solidified within an hour. The resulting solidified mixture was diluted with ethyl acetate (5 mL) and the catalyst was separated. The filtrate was evaporated on rota-evaporator to give a solid, which was dried and recrystallized from ethyl acetate.

Method B: Conventional Heating Method. An equimolar mixture of 1H-indole-2,3-dione (1) (1 mmole), malononitrile/ethylcynoacetate (2) (1 mmole), and 2,2-dimethyl-1,3-dioxane-4,6-diones (3) (1 mmole) taken in absolute ethanol (15 mL) in presence of ZnO nanoparticle (30 mg) was refluxed for 10-11 hrs Progress of the reaction was monitored by TLC. After completion of reaction, the reaction mixture was cooled to room temperature and solidified within an hour. The resulting solidified mixture was diluted with ethyl acetate (5 mL) and the catalyst was separated. The filtrate was evaporated on rota-evaporator to give a solid, which was dried and recrystallized from ethyl acetate.

All the synthesized compounds were identified by their melting point, IR, ¹HNMR, ¹³CNMR, and mass spectral studies.

The spectroscopic characterization data of (4a–f/5a–f) are given below.

4a  7′-Amino-2′2′-dimethyl-2,4′-dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3400 (NH₂), 3265 (NH), 3059 (aromatic C–H str), 2984 (aliphatic C–H str), 2204 (CN), 1727 (NH–C=O), 1620 (O=C–O), 1188.46 (C–O–C); ¹HNMR ( ppm): 10.93 (s, 1H, NH indole), 7.89 (s, 2H, NH₂), 6.88–8.22 (m, 4H, Ar–H), 1.48 (s, 3H, CH₃), 1.90 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃); Anal. Calcd. for C₁₇H₁₃N₃O₅: C, 60.1, H, 3.8, N, 12.3. Found: C, 60.01, H, 3.85, N, 12.37; MS: [M]⁺ at 339.

4b  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-chloro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3410 (NH₂), 3260 (NH), 3053 (aromatic C–H str), 2980 (aliphatic C–H str), 2202 (CN), 1720 (NH–C=O), 1622 (O=C–O), 1180 (C–O–C); ¹HNMR ( ppm): 10.84 (s, 1H, NH indole), 7.78 (s, 2H, NH₂), 6.82–8.20 (m, 3H, Ar–H), 1.42 (s, 3H, CH₃), 1.94 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃); Anal. Calcd. for C₁₇H₁₂ClN₃O₅: C, 54.63, H, 3.24, N, 11.24. Found: C, 54.80, H, 3.26, N, 11.26; MS: [M]⁺ at m/z 373.74.

4c  7′-Amino-2′2′-dimethyl-2,4′-dioxo-7-chloro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3402 (NH₂), 3256 (NH), 3039 (aromatic C–H str), 2977 (aliphatic C–H str), 2210 (CN), 1732 (NH–C=O), 1610 (O=C–O), 1175 (C–O–C); ¹HNMR ( ppm): 10.78 (s, 1H, NH indole), 7.76 (s, 2H, NH₂), 6.84–8.26 (m, 3H, Ar–H), 1.46 (s, 3H, CH₃), 1.92 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃); Anal. Calcd. for C₁₇H₁₂ClN₃O₅: C, 54.63, H, 3.24, N, 11.24. Found: C, 54.79, H, 3.27, N, 11.26; MS: [M]⁺ at m/z 373.74.

4d  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-bromo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3400 (NH₂), 3280 (NH), 3050 (aromatic C–H str), 2974 (aliphatic C–H str), 2200 (CN), 1722 (NH–C=O), 1618 (O=C–O), 1180 (C–O–C); ¹HNMR ( ppm): 10.74 (s, 1H, NH indole), 7.72 (s, 2H, NH₂), 6.87–8.26 (m, 3H, Ar–H), 1.40 (s, 3H, CH₃), 1.98 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃); Anal. Calcd. for C₁₇H₁₂BrN₃O₅: C, 48.82, H, 2.89, N, 10.05. Found: C, 48.65, H, 2.91, N, 10.07; MS: [M]⁺ at m/z 418.

4e  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-nitro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3400 (NH₂), 3265 (NH), 3059 (aromatic C–H str), 2984 (aliphatic C–H str), 2204 (CN), 1727 (NH–C=O), 1620 (O=C–O), 1188.46 (C–O–C); ¹HNMR ( ppm): 10.78 (s, 1H, NH indole), 7.71 (s, 2H, NH₂), 6.83–8.28 (m, 3H, Ar–H), 1.48 (s, 3H, CH₃), 1.90 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃); Anal. Calcd. for C₁₇H₁₂N₄O₇: C, 53.13, H, 3.15, N, 14.58. Found: C, 53.30, H, 3.17, N, 14.59; MS: [M]⁺ at m/z 384.

4f  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-methyl-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carbonitrile. IR (cm⁻¹): 3405 (NH₂), 3261 (NH), 3048 (aromatic C–H str), 2981 (aliphatic C–H str), 2206 (CN), 1724 (NH–C=O), 1618 (O=C–O), 1178 (C–O–C); ¹HNMR ( ppm): 10.81 (s, 1H, NH indole), 7.75 (s, 2H, NH₂), 6.81–8.20 (m, 3H, Ar–H), 2.35 (s, 3H, CH₃) 1.40 (s, 3H, CH₃), 1.98 (s, 3H, CH₃); ¹³CNMR ( ppm): 166.4 (C=O), 159.4 (C–NH₂), 124.0–141.6 (aromatic carbons), 117.1 (C≡N), 110.1 (O–C–O), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 25.1 (CH₃); Anal. Calcd. for C₁₈H₁₅N₃O₅: C, 61.19, H, 4.28, N, 11.89. Found: C, 61.40, H, 4.30, N, 11.87; MS: [M]⁺ at m/z 353.

5a  7′-Amino-2′2′-dimethyl-2,4′-dioxo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3402 (NH₂), 3298 (NH), 3059 (aromatic C–H str), 2984 (aliphatic C–H str), 1727 (NH–C=O), 1620 (O=C–O), 1184 (C–O–C); ¹HNMR () 10.97 (s, 1H, NH indole), 8.15 (s, 2H, NH₂), 6.92–7.46 (m, 4H, Ar–H), 4.44 (q, 2H, CH₂), 1.35 (t, 3H, CH₃), 1.18 (s, 3H, CH₃), 1.14 (s, 3H, CH₃); ¹³CNMR () 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–142.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₁₉H₁₈N₂O₇: C, 59.07, H, 4.70, N, 7.25. Found: C, 59.25, H, 4.68, N, 7.26; MS: [M]⁺ at m/z 386.

5b  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-chloro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3400 (NH₂), 3292 (NH), 3050 (aromatic C–H str), 2980 (aliphatic C–H str), 1722 (NH–C=O), 1622 (O=C–O), 1182 (C–O–C); ¹HNMR (): 10.90 (s, 1H, NH indole), 8.12 (s, 2H, NH₂), 6.92–7.26 (m, 3H, Ar–H), 4.40 (q, 2H, CH₂), 1.32 (t, 3H, CH₃), 1.12 (s, 3H, CH₃), 1.10 (s, 3H, CH₃); ¹³CNMR (): 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–142.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₁₉H₁₇ ClN₂O₇: C, 54.23, H, 4.07, N, 6.66. Found: C, 54.40, H, 4.05, N, 6.65; MS: [M]⁺ at m/z 420.80.

5c  7′-Amino-2′2′-dimethyl-2,4′-dioxo-7-chloro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3408 (NH₂), 3290 (NH), 3058 (aromatic C–H str), 2984 (aliphatic C–H str), 1728 (NH–C=O), 1624 (O=C–O), 1188 (C–O–C); ¹HNMR (): 10.92 (s, 1H, NH indole), 8.10 (s, 2H, NH₂), 6.90–7.20 (m, 3H, Ar–H), 4.42 (q, 2H, CH₂), 1.30 (t, 3H, CH₃), 1.16 (s, 3H, CH₃), 1.10 (s, 3H, CH₃); ¹³CNMR (): 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–140.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₁₉H₁₇ ClN₂O₇: C, 54.23, H, 4.07, N, 6.66. Found: C, 54.42, H, 4.06, N, 6.64; MS: [M]⁺ at m/z 420.80.

5d  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-bromo-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3400 (NH₂), 3260 (NH), 3050 (aromatic C–H str), 2982 (aliphatic C–H str), 1790 (C=O), 1722 (NH–C=O), 1618 (O=C–O), 1130 (C–O–C); ¹HNMR (): 10.74 (s, 1H, N indole), 6.90 (s, 2H, NH₂), 6.87–8.26 (m, 3H, Ar–H), 4.19 (q, 2H, CH₂), 1.98 (s, 3H, CH₃), 1.40 (s, 3H, CH₃), 1.34 (t, 3H, CH₃); ¹³CNMR (): 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–142.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₁₉H₁₇ BrN₂O₇: C, 49.05, H, 3.68, N, 6.02. Found: C, 49.24, H, 3.70, N, 6.04; MS: [M]⁺ at m/z 465.

5e  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-nitro-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3420 (NH₂), 3290 (NH), 3069 (aromatic C–H str), 1732 (NH–C=O), 1620 (O=C–O), 1180 (C–O–C); ¹HNMR (): 10.92 (s, 1H, NH indole), 8.14 (s, 2H, NH₂), 7.2–8.08 (m, 3H, Ar–H), 4.40 (q, 2H, CH₂), 2.78 (s, 1H, NH), 1.38 (t, 3H, CH₃), 1.16 (s, 3H, CH₃), 1.10 (s, 3H, CH₃); ¹³CNMR (): 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–142.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (Spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₁₉H₁₇ N₃O₉: C, 52.90, H, 3.97, N, 9.74. Found: C, 52.71, H, 3.95, N, 9.75; MS: [M]⁺ at m/z 431.

5f  7′-Amino-2′2′-dimethyl-2,4′-dioxo-5-methyl-1,2-dihydrospiro[indoline-3,5′-pyrano[2,3-d][1′,3′]dioxine]-6′-carboxyethylester. IR (cm⁻¹): 3434 (NH₂), 3298 (NH), 3060 (aromatic C–H str), 1730 (NH–C=O), 1628 (O=C–O), 1188 (C–O–C); ¹HNMR (): 10.90 (s, 1H, NH indole), 8.12 (s, 2H, NH₂), 6.92–7.26 (m, 3H, Ar–H), 4.40 (q, 2H, CH₂), 2.32 (s, 3H, CH₃), 1.32 (t, 3H, CH₃), 1.12 (s, 3H, CH₃), 1.10 (s, 3H, CH₃); ¹³CNMR (): 167.7 (O–C–O), 166.4 (NH–C=O), 166.1 (C=O), 159.2 (C–NH₂), 124.3–142.0 (aromatic carbons), 61.2 (OCH₂), 46.6 (spiro carbon), 26.3 (CH₃), 24.1 (CH₃), 14.1 (CH₃ ester); Anal. Calcd. for C₂₀H₂₀ N₂O₇: C, 60.00, H, 5.03, N, 7.00. Found: C, 60.19, H, 5.05, N, 6.99; MS: [M]⁺ at m/z 400.

3.3. Characterization of the Synthesized ZnO Nanoparticles

The synthesized ZnO nanoparticles were characterized by using X-ray diffraction (XRD), FTIR, UV-VIS spectra, and fluorescence spectroscopy.

3.3.1. XRD Pattern of ZnO Nanoparticles

The nanostructure of ZnO nanoparticle has been studied at room temperature by using X-ray diffraction pattern (Figure 2). The particle size was calculated from X-ray diffraction images of ZnO powders using the Scherrer formula:

where is the average particle size perpendicular to the reflecting planes, is the X-ray wavelength, is the full width at half maximum (FWHM), and is the diffraction angle. The average size of ZnO nanoparticles obtained from the XRD is about 5.1 nm, using the Scherrer formula.

Figure 2: XRD pattern of ZnO nanoparticles.

Figure 3: FTIR of ZnO nanoparticles.

3.3.2. Fourier Transforms Infrared Spectroscopy (FTIR)

The FTIR was acquired in the range of 400–4000 cm⁻¹ (Figure 3). The band between 450–550 cm⁻¹ correlated to metal oxide bond (ZnO). The peaks in the range 1400–1500 cm⁻¹ correspond to CO bonds. The peaks at 1340 cm⁻¹ and 1574 cm⁻¹ correspond to CO and OH bending vibrations, respectively. IR spectra were recorded in KBr on a Perkin Elmer Infrared RXI FTIR spectrophotometer.

3.3.3. U-V Spectroscopy

The U-V spectrum was taken by using Cary 60 UV-VIS, Agilent Technologies. The sample was vigorously mixed through vortex for 10 min. The U-V absorption spectrum of ZnO nanoparticle in methanol gave absorption peak at 275 nm (Figure 4).

Figure 4: U-V spectrum of ZnO nanoparticles.

3.3.4. Fluorescence Spectroscopy

The fluorescence spectrum of nano-ZnO at different molar concentrations in methanol was taken at different excitation wavelength 300–600 nm (Figure 5) (Table 4). All the samples were vigorously mixed through vortex for 10 min. Fluorescence spectrum was recorded by using spectrofluorophotometer model number 5301PC, Shimadzu Cooperation, Kyoto, Japan.

Table 4: Fluorescence data ZnO in methanol at different molar concentrations.

Entry
Molar concentration
ZnO nanoparticle

em (nm)

1

420

2

280

3

395

4

445, 365

5

455

6

400

Figure 5: Fluorescence spectrum of ZnO nanoparticles.

4. Conclusion

We have demonstrated an environ-economic and simple protocol for the synthesis of novel spiroindole derivatives by the one-pot three-component reaction of isatin, malononitrile/ethylcyanoacetate, and Meldrum’s acid with ZnO nanoparticles as a green, effective, and recoverable catalyst. The catalyst can be recycled and reused without apparent loss of activity.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

The authors are thankful to the Dean and to the Head of the Department (Science and Humanities), FET, MITS, for providing necessary research facilities in the department. Financial assistance from FET, MITS, is gratefully acknowledged. They are also thankful to SAIF Punjab University, Chandigarh, for the spectral and elemental analyses.

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