Book 7x10 - Template - version_15

Polymers Research Journal Volume 10, Number 4

ISSN: 1935-2530 © Nova Science Publishers, Inc.

A NOVEL POLYINDOLE - TIO2 NANOCOMPOSITE FOR THE SYNTHESIS OF PHARMACEUTICALLY IMPORTANT 6- METHYL 4- PHENYL CARBONYL-1, 2, 3,4 TETRAHYDROPYRIMIDINE-2-ONE DERIVATIVES UNDER SOLVENT-FREE CONDITIONS Kalpana N. Handore1, Sanjay V. Bhavsar1, Amit Horne1, P. K. Chhattise1, Sudam Pandule1, S. B. Sharma2, Suresh Shisodia3, Vishwas B. Gaikwad4, and Vasant V. Chabukswar1, 1

Nowrosjee Wadia College, Chemistry Department, Joag Path Pune, University of Pune, India 2 Modern Education Society’s College of Engineering, Pune, India 3 Department of Chemistry, Material and Chemical Engineering, “Giulio Natta,” Politecnico diMilano, Italy 4 B.C.U.D, University of Pune, Pune India

ABSTRACT A Polyindole-TiO2 nanocomposite has been synthesized by chemical oxidative polymerization method. Polyindole -TiO2 nano composite characterized by using various analytical techniques viz FTIR, SEM, XRD. Synthesized nano composite used as a novel catalyst for dihydropyrimidinone synthesis under ultra sound condition. The advantages of this method are mild reaction conditions, shorter time, and excellent yields, with high purity of DHPM’s by low loading of catalyst. Polyindole-TiO2 is a stable, recyclable, mild, cheaper catalyst and can be used several times without loss of activity; it reduces the side reaction which occurs with other protonated acid media. Dihydropyrimidinones were characterized by Mass and NMR spectroscopy.

Keywords: Polyindole -TiO2, XRD, SEM, Dihydropyrimidinones, ultra sound condition

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[email protected]

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Kalpana N. Handore, Sanjay V. Bhavsar, Amit Horne et al.

INTRODUCTION The Biginelli reaction is one of the most important multi-component reactions for the synthesis of dihydropyrimidinones. Dihydropyrimidinone are known to exhibit a wide range of biological activities such as antiviral, antitumour, antibacterial, and anti-inflammatory properties [1]. In addition, these compounds have emerged as potential calcium channel blockers, antihypertensive, α1a–adrenergic antagonists and neuropeptide antagonists [2-4]. Therefore preparation of heterocyclic nucleus has gained great importance in organic synthesis [5-7]. While the biological interest of DHPM exploded the Biginelli reaction has been the subject of high synthetic activity [8]. The classical Biginelli reaction requires long reaction times and often suffers from low yields of products in case of substituted aromatic and aliphatic aldehydes [9-10]. Multi-step synthesis produces somewhat higher yields but lacks the simplicity of original one-pot Biginelli protocol, hence the Biginelli reaction continues to attract the attention of organic chemists interested in finding milder and more efficient procedures for the synthesis of dihydropyrimidinone [11-13]. The disadvantages of poor yield, long reaction time, expensiveness, complexity, and sometimes ineffectiveness associated with most of these catalysts demands development of more efficient and greener approach involving low cost, easily available, easy to handle, efficient and recyclable catalysts [14]. Recently, the application of TiO2 [15] as catalyst for the synthesis of dihydropyrimidinones has been reported. However TiO2 has some limitations i.e., long reaction time and non-recyclability and difficulty in separation. Such draw backs could be obviated by using polymer supported catalyst i.e., polyindole -TiO2 nanocomposites. The present paper report synthesis of Polyindole-TiO2 nanocomposites and its application as a recyclable and potential catalyst for solvent free synthesis of dihydropirimidones through single-pot multicomponent strategy (Scheme-1) using sonicator bath.

Scheme 1. Synthesis of TiO2 nanoparticles.

Scheme 2. Preparation of Polyindole – TiO2 nanocomposite.

Scheme 3. Synthesis of dihydropyrimidinones using Polyindole -TiO2 catalyst.

A Novel Polyindole - TiO2 Nanocomposite for the Synthesis …

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EXPERIMENTAL Material and Methods Indole and methanol was purchased from Merck and indole recrystallized from methanol. Anhydrous ammonium per sulphate from Sigma Aldrich, TiCl4 Loba Chemi, India. Ultrasonicator of the technical specifications is as Electric supply: 230 V, Ultrasonic frequency: 33 KHz, Ultrasonic power: 100 Watts. Reactions were monitored by thin layer chromatography (TLC) on Merck’s silica gel plates (60 F254), visualizing with ultraviolet light. Column chromatography was performed on silica gel (60 - 120 mesh) using distilled hexane and ethyl acetate.

Synthesis of TiO2 Nanoparticles TiO2 nanoparticles were synthesized by drop wise addition of titanium tetrachloride (TiCl4) in ethanol and water (1:1) under nitrogen atmosphere. The reaction mixture was irradiated for 30 min under ultrasound and stirred for further 2 hour at room temperature until a yellow colored solution of TiO2 nanoparticles obtained. The obtained nano particles was then filtered and dried in an oven at 80oC and calcined at 350°C for one hour in a furnace.

Preparation of Polyindole –TiO2 Nanocomposite Polymerization reaction was carried out in a two neck round bottomed ﬂask containing monomer indole (0. 01 mol) and methanol (10 mL) under nitrogen atmosphere. To this solution, TiO2 nanoparticles (0.01mol) were added. The polymerization reaction was allowed to proceed for one hour. The oxidizing agent, ammonium per sulphate (0.01mol) was dissolved separately in10 mL de-ionized water and was added drop wise at a rate of approximately 1 mL/min in the monomer solution containing TiO2 nano particles with constant stirring at 0-5°C. After complete addition of oxidizing agent, the polymerisation was kept in sonicator bath for 2 hours. The greenish black precipitate of the polymer was isolated by ﬁltration and washed with distilled water until the washing liquid became completely colorless. Finally, the polyindole - TiO2 nano composite was vacuum dried for overnight. The polyindole - TiO2 composite were characterized by FTIR, XRD, and SEM.

Synthesis of Dihydropyrimidinone A mixture of β dicarbonyl compound (1mmol), aldehydes (1 mmol), urea (1.2 mmol) and catalyst (polyindole -TiO2) 0.015 gm was added to the reaction vessel and reaction was performed in sonicator. Reactions were monitored by TLC. Product was separated from the reaction by stirring in water to remove excess of urea and then filtered and washed with water and recrystallized from ethanol.

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Spectral Data of Synthesized Compounds 4a) 6- methyl 4- phenyl carbonyl-1, 2, 3, 4 tetrahydropyrimidine-2-ones HNMR (CDCl3, 400MHz): δ 8.11(s, 1H, -NH), 5.87(s, 1H, -NH), 7.26 -7.30 (m, 5H, C6H5), 5.39 (s, 1H, -C4H), 4.06 (q, J = 6.88 Hz, 2H, -OCH2CH3), 1.1 (t, J = 6.88 Hz, 3HOCH2CH3), 2.4(s- CH3). 1

MS: m/e = 261(M+1), 260 (M+) (283-23). IR (KBr) (cm-1): 3242cm-1(-NH stretching), 3115 cm-1 (-CONH), 1726 cm-1 (-CO ester), 1647cm-1(-CONH), 1600, 1419, 1311, 1091, 783 cm-1.

Characterization UV-Visible absorption spectra of Polyindole –TiO2 nanocomposite was taken in m-cresol solvent were recorded by using double beam spectrophotometer (Perkin-Elmer). The polyindole- TiO2 solutions were prepared by dissolving 5 mg in 100 mL of m-cresol. FTIR measurements were recorded in a Perkin-Elmer 1600A spectrometer (frequency range 400- 4000 cm−1). The X-ray diffraction pattern were recorded using a Bruker axs D-8 Advance X-ray diffractometer (CuKα radiation source, λ = 1.542A◦). The spectra were recorded in the range of 2θ = 0˚ to 80˚and scanning was performed at a rate of 2◦ min−1. Scanning electron microscope (SEM) was conducted on a JEOL-JSM-6360A analytical scanning microscope. Diffraction patterns TiO2 powders were compared with reference to JCPDS database.

RESULT AND DISCUSSION UV Analysis UV-Vis absorption spectra of TiO2 nanoparticles shown in Figure 1. The spectrum reveals a characteristic sharp absorption peak at wavelength 365 nm indicates TiO2.

FTIR Spectra FTIR spectra of TiO2 nano particles are represented in Figure 2. The broad adsorption band at 3405 cm-1 is due to stretching vibration of O-H bond and peak at 1630 cm-1 indicates O-Ti-O bond in TiO2 nanoparticles. FTIR spectra of polyindole - TiO2 shows broad band at ~3400 cm-1 indicates presence of -NH bonds (Figure 2). The band at 1573 cm-1 is due to stretching and deformation vibrations of -NH bond indicates nitrogen of indole is not the polymerisation site. The sharp band at 742 cm-1 indicates that the benzene ring is not affected during polymerization of indole. Peak at 1454 cm-1 and 1610 cm-1 corresponds to stretching mode of benzene ring, reveals that benzene ring was not the polymerization site. This suggests that polymerization took place at 2 and 3 position of indole.


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Figure 1: U.V. of TiO2 nanoparticles

Figure 1 U.V. of TiO2 nanoparticles.

Figure 1: U.V. of TiO2 nanoparticles

Figure 2. FTIR of nano polyindole -TiO2. Figure 2: FTIR of TiO nano TiO -TiO2 2 and 2 and polyindole

XRD Analysis

Figure 2: FTIR of nano TiO2 and polyindole -TiO2

XRD pattern of TiO2 and polyindole -TiO2 nanocomposite was shown in Figure 3.a) and b). Figure 3a shows XRD pattern of TiO2 nano particles. The diffraction pattern of TiO2 matches well with literature and are in good agreement with the standard spectrum (JCPDS no. 88-1175 and 84-1286). In XRD sharp peaks at 25° and 48° indicates TiO2 present in anatase phase and crystalline in nature. The XRD analysis shows the major reflections between 25 to 70o (2Ө values) which indicate TiO2 nanoparticles on average size of 60-80 nm. XRD pattern of polyindole -TiO2 nanocomposite in Figure 4 reveals strong diffraction peaks at 25°, 48° indicating TiO2 present in nanocomposite in anatase form.

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Figure 3. a) XRD pattern of nanoTiO2 particles.

Figure 3. b) XRD pattern of polyindole -TiO2 nanocomposite.

SEM Analysis The surface morphology of TiO2 and polyindole -TiO2 nanocomposites were analyzed by SEM and represented in Figure 4 a) and b) respectively. TiO2 nano particles are highly agglomerated with spherical morphology to form a cluster as observed in SEM micrograph. Figure 4.a). While Polyindole particles are aggregate to form the clusters in which TiO2 nano particles are distributed with approximately size of 60-80 nm. This acts as a soft template by


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forming spheres. SEM results reveal that the nanostructure TiO2 particles uniformly distributed embedded within the Polyindole matrix.

Figure 4. a) SEM of TiO2.

Figure 4. b) SEM of Polyindole -TiO2.

Catalytic Activity Literature survey revealed that there is no report on the application of polyindole - TiO2 nanocomposite as catalyst for dihydropyrimidinones synthesis. To evaluate the catalytic effect we used various catalysts with model reaction of EAA with benzaldehyde and urea under sonochemical condition. It can be seen from results that Polyindole –TiO2 nanocomposite shows the best catalytic activity (Table 1, Entry 4). While conventional heating requires7-8 hours. Which was supported by FTIR Figure 5. FTIR of Polyindole-TiO2 freshly prepared and after the fifth run shows the same peaks indicates Stability of Polyindole –TiO2 nanocomposite.

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Figure 5. FTIR of Polyindole-TiO2 before and after the reaction.

Table 1. Synthesis of 5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4 dihydropyrimidin-2(1H)one (4a) under ultrasound conditions Entry 1 2 3 4 5

Catalysta

Timeb

Yieldc

Polyindole Polyaniline Polyindole -ZnO Polyindole -TiO2 TiO2

(min) 25 40 35 28 60

(%) 92% 90% 92% 95% 65%

6 ZnO 56 70% Catalysts: polyaniline ,polyindole, polyindole-ZnO and Polyindole-TiO2 synthesized and used. Temperature of sonicator bath is 45oC. b Time for completion of reaction. c Yields refer to isolated pure products. a

Concentration of Catalyst The effect of catalyst concentration on yield was evaluated for the model reaction of Benzaldehyde, Urea and Ethyl Acetoacetate. In The First Stage Reaction Was Carried Out In absence of catalyst which resulted into insignificant yield of product. (Table 2, Entry 1). When amount of catalyst was increased from 0.01 to 0.015 gm it was found that the reaction proceeded in quantitative yield. (Table 2, Entry 3).


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Table 2. Optimization of reaction conditions for the synthesis 5-Ethoxycarbonyl-6methyl-4-phenyl-3,4 dihydropyrimidin-2(1H)-one using various concentrations of catalyst under solvent free condition Amount a (gm) 0 0.01 0.015 0.020 0.025 0.030 0.030 0.040

Entry 1 2 3 4 5 6 7 8 a b

Time (min) 30 30 30 30 30 30 30 30

Yield b (%) >20 82 95 88 88 78 76 72

Amount of catalyst. Isolated yield.

Table 3. Influence of the solvent on the yield of model reaction Entry Solvent a Time b Yield c 1 Solvent-Free 30 min 95% 2 MeOH 35min 89% 3 EtOH 32 min 90% 4 Acetonitrile 40 min 86% 5 Xylene 50 min 60% 6 Butanol 60 min 55% 7 DCM 55 min 82% 8 THF 50min 80% 9 CHCl3 45 min 90% 10 DMF 80 min 60% All products were characterized by IR, NMR and mass spectroscopy. a Solvents used for synthesis of 5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4 dihydropyrimidin2(1H)one. Reaction conditions: benzaldehyde (1 mmol), ethylacetoacetate (1 mmol), urea (1.2 mmol) and polyindole - TiO2 (0.015 g), and temperature of sonicator bath 45oC. b Time: for completion of reaction in different solvents. c Isolated yield.

Effect of Solvent Dihydropyrimidinones obtained more efficiently in solvent free condition than in solvent as catalyst and reagents are arranged more tightly when solvent is not used. Therefore in solvent less reaction need short reaction time with quantitative yield of product (Table 3, Entry1). Using these optimized conditions, the reaction of various aromatic aldehydes was explored (Table 3).

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Aromatic aldehydes containing electron donating and electron withdrawing were reacted under the same reaction condition to produce the corresponding DHPM in good yield. Aliphatic aldehyde remain intact under the same reaction conditions (Table 4, entry 5 and 6).Therefore this method useful for chemoselective Biginelli condensation of aromatic aldehydes in the presence of aliphatic aldehydes. It is worth to note that polyindole-TiO2 shows excellent recovery and reusability with high yield of dihydropyrimidinones. The polyindole-TiO2 offers an additional advantage of being separable by simple filtration, washed with water, dried at 60°C temperature and used for the several cycles. Recyclability of the catalyst for the standard reaction conditions at sonicator was investigated for the synthesis of dihydropyrimidinone of benzaldehyde. The yields of the product obtained in the subsequent cycles are found to be in Table No .4. Table 4. Dihydropyrimidone compound synthesized by using polyindole- TiO2 nanocomposite Entry Product Ar-CHO X Time(min) Yield M.P(°C) 1 4a Ph O 28 95 202-205 2 4b 4-MeOC6H4 O 22 92 203-207 3 4c 4-NO2 C6H4 O 50 82 234-236 4 4d C6H5CH = CH O 40 90 230-236 5 4e CH3 O 60 6 4f H O 45 Reaction Conditions: aldehyde (1 mmol), ethylacetoacetate (1 mmol), urea (1.2 mmol), catalyst. Polyindole – TiO2 (in solvent free condition.0.015gm). Temp: Reactions carried out in sonicator bath 45°C. Time: for completion of reaction.

Table 5. Study of reusability of catalyst on the model reaction Reaction cycles a First Second Third Fourth Fifth Sixth Yield b (%) 95 93 90 90 89 86 Reaction conditions: Reaction conditions: benzaldehyde (1 mmol), ethylacetoacetate (1 mmol), urea (1.2 mmol) &Temperature of sonicator bath 45oC. a Reaction cycles: Polyindole- TiO2 catalyst is recovered and reused.

CONCLUSION Polyindole-TiO2 nanocomposite successfully synthesized by insitu by chemical oxidative method. XRD and SEM study reveals there is an intermolecular interaction between the polyindole and TiO2 nanoparticles. The use of polyindole -TiO2 nano composites as an effective catalyst for the clean and rapid cyclocondensation of aromatic, hetro aromatic and acid sensitive aldehydes under ultrasound condition. This novel polymer composite catalyst can practically replace lewis acids in view of the following advantages high catalytic activity under mild reaction conditions, easy separation of the catalyst after reaction, excellent functional group tolerance and low loading of catalyst. The approach of recovery and


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reusability of the catalyst several times without any loss in the yield of the reaction is significant toward environmentally benign procedure.

ACKNOWLEDGMENTS We sincerely acknowledge financial support from UGC, Nowrosjee Wadia College, Pune University Indian Academy of Science and ISRO, Also, we thank to National Chemical Laboratory, Pune for performing analysis.

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