Dihydropyridine Cascade

International Journal of Materials Science ISSN 0973-4589 Volume 13, Number 3 (2018), pp. 189-204 © Research India Publications http://www.ripublication.com

A Hantzsch condensation reaction / Dihydropyridine Cascade Synthesis on Zeolite substrate Adya Jain*, Shikha Singh, Kautily Rao Tiwari, Neeraj Kumar and Radha Tomar S. O. S in Chemistry, Jiwaji University, Gwalior, M.P., 474011, India.

Graphical Abstract:

Fig 1: Graphical Abstract Abstract Competence of Nanoporous Modified Zeolite-Beta has been observed at various parameters (i.e. different solvent, temperature, catalyst concentration and time interval) on the yield of different derivatives. Synthesis of 9, 10Diarylacridine-1, 8-dione was carried out by single-pot Hantzsch condensation

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reaction, which includes three component reactants i.e. aldehyde, amine and 5, 5-Dimethyl-1, 3- cyclohexanedione (dimedone). Expeditious with excellent Yield of synthesized drug intermediates from Cr2O3-H-β was found to be 88.75% in ethanol at 90ºC. The synthesized zeolites sample were characterized by the help of Fourier transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), BET Surface Area and Porosity and Scanning electron microscopy (SEM) while the synthesis of drug derivatives were confirmed by Fourier transform infrared spectroscopy (FTIR), 1H-Nuclear Magnetic Resonance Spectroscopy (1H-NMR) and Liquid chromatographyMass spectrometer (LC-MS). Keywords: Zeolite Beta, Hantzsch condensation, 9, 10-Diarylacridine-1, 8dione 1. INTRODUCTION Dihydropyridine (DHP) derivatives (i.e. Acridinediones, Quinolines) displays wide array of biological activities such as vasodilator, anti-atherosclerotic, antitumor, antidiabetic [1] calcium β-blockers, antihypertensive activity, α1a-antagonists and heart defibrillation. Acridine derivatives possess number of biological activities i.e. antitumor [2], cytotoxic, anticancer [3], antimicrobial, anti multidrug resistant, fungicidal, antibacterial activity, antiglucoma [4], mutagenic properties etc. Dihydopyridine molecules are synthesized by one pot multicomponent condensation reaction i.e. Hantzsch Condensation Reaction which is a catalytic driven reaction. In the absence of catalyst, the obtained yield percentage is unsatisfactorily in lower amount and the reaction completes in long duration. O

R

1

O

O

Ar

O

OEt N H

CH3 H3C

CH3

N

CH3

N H

CH3

R

Dihydropyridine

Acridine-1,8-diones

Quinazoline

Fig 2: Structures representing Parent Nucleus Molecule and Drug Derivatives A number of different derivates of Acridinedione and Quinolines has been synthesized by different methods in the presence of different catalysts and solvents such as alumina (neutral or basic) as mineral solid supports using DMF as solvent [5], p-dodecylbenezenesulfonic acid (DBSA) as a Bronsted acid-surfactant-combined catalyst [6], Amberlyst-15 in CH3CN [7], 1-butyl-3-methyl-imidazolium tetrafluoroborate ([bmim][BF4]) [8], tris(pentafluorophenyl) borane [B(C6F5)3] [9], Lproline [10], sodium 1-dodecanesulfonate (SDS) [11], Brønsted acidic imidazolium salts containing perfluoroalkyl tails [12] Hf(NPf2)4 [13], nano-Fe3O4 [14], Crossdehydrogenative regioselective Csp3–Csp2 coupling of enamino-ketones [15],

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191

[Bmim]ClO4 [16], aluminium dodecyl sulfate trihydrate [Al(DS)3].3H2O a Lewis acid-surfactant-combined catalyst[17], magnetite (Fe3O4)/chitosan as a magnetically recyclable heterogeneous nanocatalyst[18], P2O5 [19], ionic liquid triethylamine hydrogen sulphate [Et3N]+ [HSO4]- [20], monodisperse platinum nanoparticles supported with reduced graphene oxide[21] etc. Modified/Simple Zeolite are not used as catalyst for Hantzsch condensation reaction till date. 

Some commercial drugs of 1, 4 Dihydropyridine

Calcium Channel Blocker

Dihydropyridines

Second Generation

First Generation

Nifedipine Short half life [< 3 hrs]

Third Generation

Amlodipine Very long [> 30 hrs]

Nicardipine Felodipine Isradipine Long half life [< 14 hrs]

O

Cl

O

+

N

+

N O

O O

H3C O

O

O H3C

N H

CH3

Nifadipine(1)

O

Cl

-

CH3

O

O

H3C O

O H3C

-

N H

Felodipine(2)

CH3

CH3

O

H3C O

O H3C

N H

CH3

CH3

Nitrendipine(3)

Fig. 3: Structure of Nifadipine(1), Felodipine(2) and Nitrendipine(3)

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Zeolites are nanoporous crystalline aluminosilicates containing labyrinth of molecular dimensions which can be filled by water or other guest molecules. Zeolites are obtained as natural minerals which can also be artificially engineered. Major applications of Zeolite are adsorption, catalysis and ion-exchange property. Zeolite exclusive advantages includes less or noncorrosive nature, no waste or disposal problem, abundance, low cost, high thermostability, great adaptability to practically all types of catalysis, heterogeneous i.e. easily separable from reaction mixture, great acid strength, easier scale up for continuous processes, etc. Hence, we decided to work on zeolite as catalyst for the synthesis of 1,4-Dihyropyridine drug molecules. The use of catalyst greatly enhances the yield percentage and purity of drug molecules therefore fulfills the needs of huge demands for pharmaceutical medicines. Zeolite Beta is one of the large pore and high synthetic silicate zeolite thus attribute higher catalytic activity, higher hydrophobicity, high cation concentration and acidic strength. Therefore we had chosen this zeolite as catalyst due to its remarkable properties. Zeolite Beta consists of an intergrowth of two distinct structures termed Polymorphs A and B (hybrid of tetragonal and monoclinic structure). [22] The polymorphs grow as two-dimensional sheets and the sheets randomly alternate between the two. Both polymorphs have a three dimensional network of 12-ring pores. Material formula of zeolite β is Na0.92 K0.62 (TEA)7.6 [Al4.53Si59.47O128] with Si/Al ratio of 13.1. The BEA framework topology attracts much attention because of the large available micropore volume, large-pore channel system and the presence of active sites in different concentrations that are useful in a number of acid-catalyzed reactions e.g., dewaxing, hydroisomerization, hydrocracking, alkane and aromatic alkylation, disproportionation and other organic synthesis processes [23,24]. Therefore we had chosen this zeolite for the synthesis of pharmaceutical drug molecules because of unique exceptional properties.ad chosen this zeolite To best of our knowledge, these novel drug intermediates are first time synthesized by using Cr2O3-H-β zeolite as nanoporous catalyst.

Fig 4: Polymorph combination for the formation of Zeolite Beta


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2. EXPERIMENTAL 2.1 Synthesis of Zeolite and its derivatives 2.1.1. Synthesis of Zeolite Beta In a 250 ml round bottomed flask, 29.7 ml distilled water, 44.8 ml Tetramethyl ammonium hydroxide (template), 0.265 g NaCl, 0.72 g KCl and 14.77 g silica gel was added to it. Then 10 ml distilled water, 0.165 g NaOH and 0.895 g sodium aluminate solution was mixed to the above solution (Scheme 1). This mixture was stirred for 10 min and a thick gel was obtained. This thick gel was kept in autoclave at 135ºC for 18 h. Thereafter obtained mixture was centrifuged, washed and filtered by double distilled water (pH=12). Finally precipitate was dried in oven for an overnight at 77ºC. 2.1.2 Conversion of Na-form zeolites to H-form zeolites In a 250 ml round bottomed flask, 9 g of zeolite (Na form), 7.230 g NH4Cl and 13.80 ml distilled water mixed with 0.1M HCl solution to reach pH=4. This reaction mixture was stirred for 30 min at 60ºC. Thereafter obtained material was washed and filtered by double distilled water. Finally precipitate was dried in oven at 60ºC for 24 h. Further the powdered mixture was calcinated at 200ºC for 60 min (Scheme 2). 2.1.3 Synthesis of Cr2O3-zeolites beta In a 250 ml round bottomed flask, 1.5 g zeolite and 20 ml of 1M Anhydrous Sr(NO 3)2 were mixed and stirred for 5 h. During stirring 50 ml of 0.2 M KMnO4 solution was added suddenly. Thereafter the reaction mixture was washed with double distilled water and dried in oven at 100ºC for more than overnight. Finally the powdered form was calcinated at 550ºC for 4h (Scheme 3).

Scheme 1, 2 and 3: Synthesis and Modification of Zeolite

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2.2 Synthesis of 1,8-Acridinedione derivatives (3,3,6,6-Tetramethyl-3,4,6,7,9,10hexahydro-1,8-acridinedione) In ethanol (solvent), Primary amine (1 mmol) was added to the mixture of 5, 5dimethyl-1,3-cyclohexanedione (dimedone) (2 mmol), an aromatic aldehyde (1 mmol) and zeolite (0.1 g) at 90 °C (Fig. 5). Reaction completion was realized by Thin Layer Chromatography. The reaction mixture was filtered and the product was obtained as filtrate, collected and dried at room temperature. The purification of solid residue was performed by recrystallizing from ethanol to obtain pure 1, 8-dioxodecahydroacridine derivative form. The synthesized compound was characterized by the help of FTIR, LC-MS and 1H-NMR. 𝐀𝐜𝐭𝐮𝐚𝐥 𝐲𝐢𝐞𝐥𝐝 (𝐠)

𝐏𝐫𝐨𝐝𝐮𝐜𝐭 𝐲𝐢𝐞𝐥𝐝 (%) = 𝐓𝐡𝐞𝐨𝐫𝐢𝐭𝐢𝐜𝐚𝐥 𝐲𝐢𝐞𝐥𝐝 (𝐠) × 𝟏𝟎𝟎% O

O

R

O

+

H3C

RCHO

+

1

R NH2

Refluxing Water

90 °C, 15-20min.

O

CH3 H3C

N

CH3

H3C

R

CH3

1

Fig 5: One Pot Hantzsch Condensation Reaction Table 1: Synthesis of Different derivatives of 1, 8-Acridinedione: S.No. 1.

Benzaldehyde (R) O

Amine (R’)

Product O

O

Cl Cl

Cl

Yield (%) 86.29

Cl

H2N

CH3 H3C

CH3

N

CH3

Cl Cl

2.

OH

H2N

O

O

90.23 O

CH3

Cl

H3C

CH3

N

HO Cl

CH3

A Hantzsch condensation reaction / Dihydropyridine Cascade Synthesis on Zeolite substrate O

3.

OH

H2N

89.88

O

O

CH3

Cl

H3C

Cl

HO

N

CH3

CH3

Cl

Cl

O

4.

195

H2N

O

+

O

-

88.49

N

O

O

CH3 H3C

+

O

-

N

CH3

O

O

5.

N

CH3

Cl

H2N

84.82

O

O

CH3 H3C

Cl

Cl

N

CH3

CH3

Cl

O

Ar

O

O

O ArCHO

H3C H3C

aldol H3C O

O

Ar

O Michael

H3C

O

O

O

NH2

O O

Ar

Ar

O

O

O

N

O HN

Ar O

Ar

O

O O -H2O N

N HO

Scheme 2: Plausible mechanism for the formation of 1, 8-Acridinedione

Adya Jain et al

196 3.1 Result and Discussion [I]

Melting points were determined in open capillaries from melting point instrument. Infrared spectra of the synthesized drug intermediates and zeolites were recorded by “Spectrumto-Perkin Elmer” spectrophotometer in the range of 4000–400 cm-1 by using KBr pellets. X-Ray diffraction spectra were recorded by using “Miniflex 600” Diffractometer. 1H-NMR spectra were determined in DMSO-d6 solvent by the help of JEOL-JNM-ECA Series (Delta V4.3)-400 MHz-FT-NMR. Data for 1H NMR are reported as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet) and coupling constants. BET surface area and porosity of zeolite samples was determines by using Gemini VII 2390 Surface Area Analyzer (Micromeritics). Analytical thin layer chromatography was performed using 0.25 mm silica gel plates (Ethyl Acetate: n-Hexane :: 3:1). 3.1.1 Fourier Transform Infrared Spectroscopy The finger print region of FT-IR determines the formation of zeolite. The absorption peaks between 750-700 cm-1 (i.e. 743.42, 734.91, 726.83, 712.83 and 702.84) corresponds to the symmetric stretching vibration of SiO4 groups. The bands around 635.57, 546.81 and 467 cm-1 relates to bending vibration of SiO4 groups or in the vibration modes of the 4-membered rings of silicate chains. The stretching vibration of SiO4 are shifted towards lower frequency indicating that the presence of the internal Si-O···HO-Si bonds. 25

H-Beta Cr203-H-Beta

% Transmittance

20

15

10

5

0

4000

3500

3000

2500

2000

1500

1000

500

-1

Wavelength (cm )

Fig 6: FT-IR of H-beta and Cr2O3-beta 3.1.2 Scanning Electron Microscope The SEM micrograph of zeolite shows the interconnection of porous structure by agglomerating of nanoparticles of Cr2O3 on H-beta with an average particle size less than 50 μm.


197

Fig 7: SEM micrograph of Zeolite Cr2O3-H- β 3.1.3 X-Ray Diffraction

4000

4000

3000

3000 Intensity (counts)

Intensity (counts)

The X-Ray Diffraction pattern is the fingerprint of the crystalline phase of zeolite. From the diffraction signals, the sharp peaks at 2θ value corresponding to 25.0 for zeolite-H-β and Cr2O3- H-β are clearly observed. Generally sharp peaks determine the crystalline nature of material, but here the broadening of peaks determines the polycrystalline nature of zeolite beta. It is also clearly observed that the X-ray diffraction patterns of H-forms and metal oxide exchanged forms of zeolites are similar to the diffraction patterns of their respective parent zeolites. These observations indicate that zeolite framework has not undergone any significant structural change during the incorporation of metal ion and crystallinity of the zeolite was preserved.

2000

1000

2000

1000

0

0

20

40 2-theta (deg)

60

80

20

40

60

80

2-theta (deg)

Fig 8 and 9: XRD of H-beta and H-beta- Cr2O3 respectively 3.1.4 BET Analysis The BET surface area of H-BETA zeolite was found to be 310.1525 m²/g, Langmuir surface area: 446.6285 m²/g, BJH adsorption cumulative surface area of pores

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between 17.000 A0 and 3000.000 A0 widths: 348.805 m²/g, BJH desorption cumulative surface area of pores between 17.000 A0 and 3000.000 A0 widths: 408.7747 m²/g. The BET surface area of Cr2O3-H-BETA zeolite was found to be 139.4775 m²/g, Langmuir surface area: 202.3463 m²/g, BJH adsorption cumulative surface area of pores between 17.000 A0 and 3000.000 A0 widths: 166.174 m²/g, BJH desorption cumulative surface area of pores between 17.000 A0 and 3000.000 A0 widths: 199.1166 m²/g. 600

1.2

550

1.1

Quantity Adsorbed (cm³/g STP)

dV/dlog(w) Pore Volume (cm³/g·Å)

Cr2O3-H-Beta H-Beta

500 450 400 350 300 250 200 150 100

Cr2O3-H-Beta H-Beta

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2

50

0.1

0

0.0 0

0.0

0.2

0.4

0.6

0.8

200

400

1.0

600

800

1000

Pore Width (Å)

Relative Pressure (P/Po)

Fig 10 and 11: BET analysis representing Relative Pressure v/s Quantity Adsorbed and Pore width v/s Pore volume 3.2 Result and Discussion [II] Table 2, Graph 1: Studying the yield of 9-(4-OH C6H5)-10-(3, 4-Cl2 C6H5)-3, 3, 6, 6Tetramethyl acridine-1, 8-dione [6] from different zeolites derivatives

Different Catalyst

1.

Ethanol

H-β

89.88

2.

Ethanol

Cr2O3-β

85.45

Yield (%)

S.No. Solvent Catalyst Yield (%) 95 90 85 80

89.88 85.45

H-β

Cr2O3-β Zeolite

All reactions were carried out at 90ºC from 30-40 min. with catalyst amount of 0.10 g.


199

Table 3, Graph 2: Studying the yield of 9-(4-OH C6H5)-10-(3, 4-Cl2 C6H5)-3, 3, 6, 6Tetramethyl acridine-1, 8-dione [6] from different solvents Solvent

Yield (%)

1.

Ethanol

89.88

2.

Acetonitrile

86.60

3.

Chloroform

81.23

4.

1,4-Dioxane

76.91

5.

Toluene

75.35

95 90 85 80 75 70 65

Yield (%)

S.No.

89.88

86.6 81.23 76.91

75.35

Solvents

All reactions were carried out at 90ºC from 30-40 min. with catalyst H-β amount of 0.10 g .

Table 4, Graph 3: Studying the yield of 9-(4-OH C6H5)-10-(3, 4-Cl2 C6H5)-3, 3, 6, 6Tetramethyl acridine-1, 8-dione [6] at different temperature Temperature

Yield (%)

1.

0ºC

31.90

2.

30ºC

53.31

3.

60ºC

64.77

4.

90ºC

89.88

5.

120ºC

47.29

89.88

100 80 Yield(%)

S.No

53.31

60 40

64.77 47.29

31.9

20 0 0ºC

30ºC

60ºC

90ºC

120ºC

Temperature

Table 4, Graph 3: Studying the yield of 9-(4-OH C6H5)-10-(3, 4-Cl2 C6H5)-3, 3, 6, 6Tetramethyl acridine-1, 8-dione [6] at different time 89.88

100

Time

Yield (%)

1.

15 min

34.16

2.

30 min

52.09

3.

45 min

67.41

4.

60 min

89.88

5.

75 min

80.23

80 Yield (%)

S.No.

52.09

60 40

80.23

67.41 34.16

20 0 15 min 30 min 45 min 60 min 75 min Time

Adya Jain et al

200 Spectroscopic data of some synthesized drugs

 9-(4-OH C6H4)-10-(4-Cl C6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione: FTIR (KBr in cm-1) 3883.47, 3055.4, 2999.5, 2850.78, 1718.37, 1488.5, 1517.61, 755.12, 724.33; UV-Vis. λ max – 893.2 nm Absorbance at 0.100 Å; m/z = 476.5 (M+H) +.1H NMR (400 MHz, DMSO-d6): d = 0.74 (s, 6 H, 2 CH3), 0.87 (s, 6 H, 2 CH3), 1.75 (d, J = 17.6 Hz, 2 H, 2 CH), 2.03 (d, J = 16.0 Hz, 2 H, 2 CH), 2.18 (d, J = 16.0 Hz, 2 H, 2 CH), 2.18 (d, J = 17.6 Hz, 2 H, 2 CH), 5.00 (s, 1 H, CH), 7.30 –7.49 (m, 6 H, ArH), 7.68 (d, J = 8.8 Hz, 2 H, ArH), 9.05 (s, 1H, -OH ).  9-(4-OH C6H4)-10-(3, 4-Cl2 C6H3)-3, 3, 6, 6-tetramethyl acridine-1, 8dione: FT-IR (KBr in cm-1) 3471.47, 3184.5, 2949, 2719.14, 1674.64, 1575, 1460, 1575, 825.5 and 753.56; UV-Vis. λ max – 893.5 nm Absorbance at 0.142 Å; m/z = 511 (M+H) +.1H- NMR (400 MHz, DMSO-d6): d = 0.72 (s, 6 H, 2 CH3), 0.89 (s, 6 H, 2 CH3), 1.78 (d, J = 17.6 Hz, 2 H, 2 CH), 2.01 (d, J = 16.0 Hz, 2 H, 2 CH), 2.19 (d, J = 16.0 Hz, 2 H, 2 CH), 2.20 (d, J = 17.6 Hz, 2 H, 2 CH), 5.01 (s, 1 H, CH), 7.30 –7.49 (m, 6 H, ArH), 7.68 (d, J = 8.8 Hz, 2 H, ArH), 9.05 (s, 1H, - OH ).  9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione: FT-IR (KBr -1 in cm ) 3051.84, 2960.17, 2873.28, 1688, 1575.18, 1424.78, 852.7, 762.46; UV-Vis. λ max – 893.5 nm; Absorbance at 0.142 Å; 1H NMR (400 MHz, DMSO-d6): d = 0.72 (s, 6 H, 2 CH3), 0.89 (s, 6 H, 2 CH3), 1.89-2.01 (d, J = 16.0 Hz, 2 H, 2 CH2), 2.42 (d, J = 17.6 Hz, 2 H, CH2), 5.01 (s, 1 H, CH), 7.30 –7.49 (m, 6 H, ArH), 7.68 (d, J = 8.8 Hz, 2 H, ArH).Anal. Calcd for C29H29Cl2NO2: C, 70.44; H, 5.91; N, 2.83. Found: C, 70.28; H, 6.05; N, 2.90.; m/z = 470 (M+H)+ . 9,10-bis-(4-Cl C6H5) Acridine-1,8-dione

40 35

(%) Transmittance

30 25 20 15 10 5 0 -5 4000

3500

3000

2500

2000

1500

1000

500

-1

Wavenumber(cm )

Fig. 12: FT-IR of 9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione


201

Fig 13: 1H-NMR of 9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione

Inten.(x100) 8.0

470.50

7.0 6.0 5.0 4.0 3.0 2.0 469.5

470.0

470.5

471.0

471.5

472.0

472.5

473.0 m/z

Fig 14: LC-MS of 9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione  9-(4-OH C6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione: FT-IR (KBr in cm-1) 3286.91, 3056.78, 2914.20, 2872.61, 1666.86, 1512.53, 1593.36, 832.62, 805.15; UV-Vis. λ max – 893.5 nm Absorbance at 0.142 Å; m/z = 365 (M+H) +. 1HNMR (400 MHz, DMSO-d6): d = 0.75 (s, 6 H, 2 CH3), 0.88 (s, 6 H, 2 CH3), 1.75-1.99 (d, J = 17.6 Hz, 2 H, 2 CH2), 2.14-2.21 (d, J = 16.0 Hz, 2 H, 2 CH2), 4.85 (s, 1 H, CH), 6.61(m, 2H, ArH), 7.02 (m, 2 H, ArH), 9.02 (s, 1H, NH), 9.25 (s, 1H, OH).

Adya Jain et al

202 70

9(4-OH C6H6)Acridinedione

60

% Transmittance

50

40

30

20

10 4000

3500

3000

2500

2000

1500

1000

500

-1

Wavelength (cm )

Fig 15: FT-IR of 9-(4-OH C6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione

Fig 16: 1H-NMR of 9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione

A Hantzsch condensation reaction / Dihydropyridine Cascade Synthesis on Zeolite substrate Inten.(x100,000) 7.5

203

364.10

5.0 2.5 0.0 100

427.20

121.00 200

300

400

500

600

700

800

900

m/z

Fig 17: LC-MS of 9, 10-Bis (4-ClC6H4)-3, 3, 6, 6-tetramethyl acridine-1, 8-dione 4. CONCLUSION The foremost merits of this work are significant due to its competency, environmentally benevolent methodology, recyclable as well as thermally stable zeolite heterogeneous catalytic applicability. In this study we found that, with escalating electronegativity, ionization energy decreases consequently reactivity increases since it uses less energy to lose electrons. The reactivity order H (2.1) > Cr (1.6) has been confirmed experimentally. The reactivity was found highest in ethanol with H-β at 90ºC for 60 min. i.e. 89.88%. Further the yield of different derivative is affected by the presence of electron withdrawing groups (EWG) and electron donating groups (EDG). Yield of acridine drugs having EWG was found higher than those for having EDG. 5. ACKNOWLEDGEMENT I owe to my mentor for supporting and guiding me to make this work possible and Central Instrumentation Laboratory (CIF), Jiwaji University, Gwalior, M.P. for providing necessary instrument support (FT-IR, XRD, LC-MS). I am also thankful to DRDE, Gwalior for providing BET surface area studies and IIT Delhi for 1H-NMR studies. REFERENCES [1]

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