Synthesis, characterization and thermal decomposition of ethyl-2’-amino-5’-cyano-6’-(1H-indole-3yl)-2-oxospiro[indoline-3,4’-pyran]-3’-carboxylate under non‐isothermal condition in nitrogen atmosphere European Journal of Chemistry 10 (1) (2019) 72-81 European Journal of Chemistry View Journal Online View Article Online Synthesis, characterization and thermal decomposition of ethyl-2’-amino-5’- cyano-6’-(1H-indole-3yl)-2-oxospiro[indoline-3,4’-pyran]-3’-carboxylate under non-isothermal condition in nitrogen atmosphere Ganesan Nalini 1,*, Natesan Jayachandramani 2, Radhakrishnan Suresh 3, Prakasam Thirumurugan 4, Venugopal Thanikachalam 5, Govindasamy Manikandan 5 and Dharmalingam Sankari 1 1 Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603203, India nalini7680@gmail.com (G.N.), sankari.biotech09@gmail.com (D.S.) 2 Department of Chemistry, Pachaiyappa’s College, Chennai, 600030, India njmani53@gmail.com (N.J.) 3 Department of Chemistry, Presidency College, Chennai, 600005, India sureshradhakrishnan7680@gmail.com (R.S.) 4 Department of Chemistry, New York University, Abu Dhabi, United Arab Emirates ptm.org@gmail.com (P.T.) 5 Department of Chemistry, Annamalai University, Annamalainagar, 608002, India profvt.chemau@gmail.com (V.T.), phdmani@gmail.com (G.M.) * Corresponding author at: Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603203, India. Tel: +91.44.27417777 Fax: +91.44.27453903 e-mail: nalini7680@gmail.com (G.Nalini). 10.5155/eurjchem.10.1.72-81.1812 Received: 03 November 2018 Received in revised form: 09 January 2019 Accepted: 30 January 2019 Published online: 31 March 2019 Printed: 31 March 2019 A new compound, spiro-oxindole derivative compound namely ethyl-2ʹ-amino-5ʹ-cyano-6ʹ- (1H-indole-3yl)-2-oxospiro[indoline-3,4ʹ-pyran]-3ʹ-carboxylate (EACIOIPC) has been synthesized and characterized by microanalysis, FT-IR, mass spectrum and NMR (1H and 13C) techniques. The thermal decomposition of the compound was studied by thermogravimetric analysis under dynamic nitrogen atmosphere at different heating rates of 10, 15, 20 and 30 K/min. The kinetic parameters were calculated using model-free (Friedman’s, Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO) methods) and model-fitting (Coats and Redfern (CR)) methods. The decomposition process of EACIOIPC followed a single step mechanism as evidenced from the data. Existence of compensation effect is noticed for the decomposition of EACIOIPC. Invariant kinetic parameters are consistent with the average values obtained by Friedman and KAS in conversional methods. Model fitting IKP methods Spiro-oxindole Model free methods Thermal decomposition Thermodynamic parameters Cite this: Eur. J. Chem. 2019, 10(1), 72-81 Journal website: www.eurjchem.com 1. Introduction The spiro-oxindole framework is an important structural organization and the core structure of a variety of medicinal agents and natural products [1,2]. The spiro-oxindole deriva- tives have been described with different biological activities, such as anti-tumor [3], anti-inflammatory, analgesic, antimic- robial, anti-HIV, antimalarial activity and as antipyretic agents [4]. Compounds such as of 5-[(indol-2-on-3-yl)methyl]-2,2- dimethyl-1,3-dioxane-4,6-diones and spiro-cyclopropylox- indole derivatives have been reported to behave as poliovirus and rhinovirus and potential aldose reductase inhibitors. Spiro-pyrrolidinyloxindoles have been extensively studied as potent inhibitors of p53-MDM2 interaction, finally leading to the identification of MI-888, which could achieve rapid, complete and durable tumor regression in xenograft models of human cancer advanced preclinical research for cancer therapy [5]. Spiro-oxindole systems are of great interest in modern organic, medicinal, and natural product chemistry. This type of framework forms a core structure of many alkaloids with promising pharmacological activity, such as horsfiline, gelsemine, mitraphylline and spirotryprotatins A,B [6]. Novel di-spiro-oxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomet- ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2019 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.10.1.72-81.1812 http://dx.doi.org/10.5155/eurjchem.10.1.72-81.1812 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.1.72-81.1812&domain=pdf&date_stamp=2019-03-31 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.1.72-81.1812 mailto:nalini7680@gmail.com mailto:sankari.biotech09@gmail.com mailto:njmani53@gmail.com mailto:sureshradhakrishnan7680@gmail.com mailto:ptm.org@gmail.com mailto:profvt.chemau@gmail.com mailto:phdmani@gmail.com mailto:nalini7680@gmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.1.72-81.1812&domain=pdf&date_stamp=2019-03-31� Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 73 N H O HN H2N CN O EtO2C Figure 1. Structure of ethyl-2ʹ-amino-5ʹ-cyano-6ʹ-(1H-indole-3yl)-2-oxospiro[indoline-3,4ʹ-pyran]-3ʹ-carboxylate. hineylide generated from isatin and sarcosine with the dipolarphile 3-(1H-indole-3-yl)-3-oxo-2-(2-oxoindolin-3-ylide- ne) propanenitrile and also spiro compound of acenapht- henequinone obtained by the same optimized reaction condition [7]. The synthesized compounds were evaluated for their antimicrobial activity and all the compounds showed significant activity. Non-isothermal decomposition kinetics of chitosan [8], chitin [9], cephalosporins [10], procaine and benzocaine [11], theobromine [12], spiro-oxindole derivatives [13-15], parthenium hysterophorus [16], nitroimidazoles [17] and ferrocene [18] were studied in detail and appropriate kinetic models were proposed. In this manuscript, we report the synthesis and charac- terization of ethyl-2ʹ-amino-5ʹ-cyano-6ʹ-(1H-indole-3yl)-2- oxospiro[indoline-3,4ʹ-pyran]-3ʹ-carboxylate (EACIOIPC) (Figure 1) [19] and its thermal decomposition under non- isothermal condition in dynamic nitrogen atmosphere. The thermal decomposition of EACIOIPC spiro-derivative com- pound was studied by using TG/DTG and DTA methods. To our knowledge, the thermodynamic and kinetic data of the thermal decomposition of EACIOIPC have not been reported. In this report, the kinetic and thermodynamic parameters were computed by using model-fitting and model free-methods. 2. Experimental 2.1. Materials Isatin, cyanoethylacetate, 3-cyanoacetyl indole and DMSO- d6 were purchased from Aldrich Chemicals. Acetic anhydride and other reagents were procured from SD Fine Chemicals and were used as received. 2.2. Instrumentations Elemental analyses were performed at Central Leather Research Institute (CLRI), Chennai, India. IR measurements were done as KBr pellets for solids using Perkin Elmer Spectrometer RXI FT-IR. The 1H and 13C NMR spectra were recorded in DMSO-d6 using TMS as internal standard with JEOL ECA-500MHz NMR spectrometer. The mass spectrum was recorded using electrospray ionization method with Thermo Finnigan mass spectrometer. Melting points were determined in capillary tubes and are uncorrected. Analytical TLC was performed on pre-coated plastic sheets of silica gel G/UV-254 of 0.2 mm thickness. The simultaneous TGA curves were obtained with the thermal analysis system model Perkin Elmer TAC7/DX (Thermal Analysis Controller TAC-7). The TG analyses of EACIOIPC were carried out under dynamic nitrogen atmosphere (100 mL/min) in an iron pan with the sample at the heating rates of 10, 15, 20 and 30 K/min from 30 to 850 °C. TGA were recorded at Indian Institute of Technology, Chennai, India. The kinetic parameters Ea and A were calculated using Microsoft Excel Software. The sample temperature, controlled by thermocouple, did not exhibit any systematic deviation from the preset linear temperature program. 2.3. Synthesis of ethyl-2ʹ-amino-5ʹ-cyano-6ʹ-(1H-indole-3yl)- 2-oxospiro[indoline-3,4ʹ-pyran]-3ʹ-carboxylate To a stirred solution of isatin (0.294 g, 2 mmol), cyano ethylacetate (0.122 g, 2 mmol), and 3-cyanoacetyl indole (0.368 g, 2 mmol) in methanol (20 mL), triethyl amine (20 mol %) was added and stirring was continued. On completion, the reaction mixture was poured into crushed ice and the precipitate formed was filtered, dried and purified by column chromatography to afford the pure product. The isolated product was further purified by recrystallization in ethanol and the yield of the product was 90 %. Color: Pale brown solid. Yield: 78%. M.p.: 223-225 °C. Rf: 0.25 (40% AcOEt/Petroleum ether). FT-IR (KBr, ν, cm-1): 3367 (NH2), 3253 (NH), 2985 (C2H5), 2208 (C≡N), 1630 (C=O), 1623 (COO-), 1518 (C6H5), 1142 (C-O-C). 1H NMR (500 MHz, DMSO-d6, δ, ppm): 0.72 (t, J = 6.9 Hz, 3H, CH3), 3.28 (s, 2H, NH2), 3.70-3.73 (m, 2H, CH2), 6.82-6.84 (m, 1H, Ar-H), 6.94 (t, J = 7.65 Hz, 1H, Ar-H), 7.12- 7.22 (m, 3H, Ar-H), 7.49 (d, J = 8.4 Hz, 1H, Ar-H), 7.95-8.09 (m, 3H, Ar-H), 10.54 (brs, 1H,NH), 12.00 (brs, 1H, NH). 13C NMR (125 MHz, DMSO-d6, δ, ppm): 14.2, 46.3, 61.7, 79.8, 80.4, 102.0, 111.1, 117.3, 119.0, 120.1, 122.1, 124.9, 126.1, 127.8, 129.9, 130.8, 135.5, 141.2, 159.9, 162.2, 167.2, 168.2. MS (EI, m/z): 427.13 [M++H+]. 3. Theoretical background 3.1. Model fitting method There are numerous non-isothermal model-fitting methods, and the most popular one is the Coats and Redfern method [20]. This method has been successfully used for studying the kinetics of dehydration and decomposition of different solid substances [21]. The kinetic parameters can be derived from the modified Coats and Redfern Equation (1), ln ln ∗   α  = − −      β ×       α 2 α α g( ) R 2RT 1 T R T EA E E (1) where g(α) is an integral form of the conversion function (α), the expression of which depends on the kinetic model of the occurring reaction. If the correct g(α) function is used, a plot of ln[g(α)/T2] against 1/T should give a straight line from which the values of the activation energy, Ea and the pre-exponential factor, A can be calculated. 3.2. Model free methods Friedman method [22] is a differential method and is one of the first used iso-conversional methods. This model according to logarithmic form of Equation (3). α exp ( ) t ad f d RT α−      E= A (2) gives 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 74 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 [ ] ,ln ln ( ) T α α α β αα  = −   E A ad f d RT (3) The plots of ln(β.dα/dT) vs 1/T (Equation(3)), at each α value were drawn and from the slope of the plots, we can calculate Ea values. The isoconversional integral method suggested indepen- dently by Flynn and Wall [23] and Ozawa [24], and is based on the Equation (4), 0.0048ln ln 1.0516 ( ) a a g R RT β α    = −       AE E (4) and Kissinger-Akahira-Sunose (KAS) method [25,26], Equation (5) is used. ( )2ln / ln ( ) a aT g R RT   β = − α  AE E (5) The plots of ln(β.dα/dT) vs 1/T (Equation(3)), ln β vs 1/T (Equation (4)) and ln(β/T2) vs 1/T (Equation (5)) has been shown to give the values of apparent activation energies for the decomposition of EACIOIPC at different values of α. According tothese equations, the reaction mechanism and shape of g(α)function do not affect the values of the activation energies ofthe decomposition stages. 3.3. Invariant kinetic parameters method The invariant kinetic parameters are obtained by the method of Lesnikovich and Levchik [27]. The straight lines obtained for the plots of ln Aβ vs Eβ for several constant heating rates should intersect at a point [28] which corresponds to the true values of activation energy and pre-exponential factor and they are named invariant kinetic parameters (Einv, Ainv) which are evaluated using the super correlation relation Equation (6), aβ = ln Ainv – bβ×Einv (6) Plot of aβ vs bβ gives a straight line, the values of Einv and ln Ainv are calculated from the slope and intercept of the plot, respectively. 3.4. Thermodynamic parameters The kinetic parameters, energy of activation (Ea) and pre- exponential factor (A) are obtained from Kissinger single point kinetic method which uses the Equation (7),       +=      β αm α 2 m R ln RT - T ln E AE (7) where Tm is temperature that corresponds to the maximum of dα/dT. This model-free kinetic method can be applied with a reasonable approximation without being limited to n-order kinetics [29], providing a single Ea value for each reaction step. For this reason, it is often defined as a Kissinger single point method. The reaction proceeds under conditions where thermal equilibrium is always maintained, then a plot of T ln 2 m       β vs mT 1 gives a straight line with a slope equal to –Ea/R. Based on the values of activation energy and pre- exponential factor for the decomposition stage, the values of ∆S≠, ∆H≠ and ∆G≠ for the formation of activated complex from the reactant were calculated based on the following Equations (8-10) [30-32], B h ln e k p S R T ≠∆ = χ A (8) Since a pH RT≠∆ = −E (9) pG H T S≠ ≠ ≠∆ = ∆ − ∆ (10) 4. Results and discussion 4.1. Non-isothermal TGA The thermograms of pure EACIOIPC recorded in a dynamic nitrogen atmosphere at different heating rates of 10, 15, 20 and 30 K/min are presented in Figure 2. They show two distinct endothermic peaks due to melting and decomposition. The thermal decomposition process of EACIOIPC in three stages is observed from the TGA curves. The decomposition process for first stage starts at 483 K and ends at 563 K with the mass loss of 47.0%. The second stage decomposition starts at 653 K and ends at 773 K with the mass loss of 10.09%. The third stage of decomposition starts at 773 K and ends at 1113 K with the mass loss of 17.38%. 4.2. Model-free analysis The non-isothermal decomposition kinetics of EACIOIPC is first analyzed by model-free methods viz., Friedman, Kissinger- Akahira-Sunose and Flynn-Wall-Ozawa. Tables 1-3 show the variation of apparent activation energy Ea, as a function of extent of conversion α, for the decomposition of EACIOIPC. Ea value increases slightly in the conversion range of 0.12 ≤ α ≤ 0.98 for all the stages. It was pointed out [33] that when Ea changes with α, the Friedman and KAS iso- conversional methods lead to close values of Ea for all the stages. The applied iso-conversional methods do not suggest a direct way for evaluating either the pre-exponential factor (A) or the analytical form of the reaction model f(α), for the investigated decomposition process of EACIOIPC. For the first stage decomposition of EACIOIPC, the values of energy of activation corresponding to the different values of α for the decomposition process obtained by Friedman, KAS and FWO methods are listed in T (Figure 3). It is seen that Ea value depends upon the extent of conversion α. The average value of Ea is 245.59±0.85 kJ/mol (KAS method). From Figure 3, it is evident that the values of activation energy obtained by Friedman and FWO methods (245.01±0.16 kJ/mol, Friedman; 240.94±0.43 kJ/mol, FWO) are slightly lesser than that of KAS method. For stage II the variation of Ea with α for the decompo- sition is shown in Figure 4. The average value of Ea is 283.21±0.16 kJ/mol (Friedman method). From Table 2, it is evident that the Friedman method activation energy is higher than the values of activation energy obtained by KAS (Ea = 275.58±0.28 kJ/mol) and FWO (Ea = 270.96±0.08 kJ/mol) methods. For stage III, the values of apparent activation energies obtained by Friedman and KAS methods are higher than that of FWO method. The average values of Ea in the range 0.12 ≤ α ≤ 0.98 were 629.45±0.60 kJ/mol (Friedman), 620.30±0.51 kJ/mol (KAS), and 604.26±0.55 kJ/mol (FWO), (Figure 5). Form Table 3, it is evident that the Friedman method and KAS methods gave higher values of activation energy than the FWO method. From the average values of Ea for each stage, the rate of decomposition is found to depend upon the nature of the intermediate formed during the decomposition. The third stage is slower than the other stages of decomposition. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 75 Figure 2. TG and DTG curves of EACIOIPC at (a) 10, (b) 15, (c) 20 and (d) 30 K/min heating rates in oxygen atmosphere. The higher value of activation energy for Stage III than the other stages indicates that the intermediate compounds are thermally more stable and hence the decomposition process is slow. 4.3. Model-fitting analysis After carrying out model-free analysis, model-fitting can be done in the conversion region where apparent activation energy is approximately constant where a single model may fit. The non-isothermal kinetic data of EACIOIPC at 0.12 ≤ α ≤ 0.98 where model-free analysis indicates approximately constant activation energy, were then fitted in to each of the 15 models listed in Tables 1 for Stages 1, 2, and 3, respectively. As shown in Tables 2-4, for the applied method, Arrhenius parameters (Ea, ln A) for decomposition process, exhibit strong dependence on the reaction model chosen. 4.4. Invariant kinetics parameters analysis Criado and Morales [34] reported that almost any α=α(T) or (dα/dt) (T) experimental curve may be correctly described by several conversion functions. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 76 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 Table 1. Algebraic expressions of f(α) and g(α) for the reaction models considered in the present work. S. No. Symbol Reaction Model Differential form a f(α) = (1/k)(dα/dt) Integral form a g(α) = kt Nucleation models 1 P2 Power law 3α (2/3) α (1/3) 2 P3 Power law 2α (1/2) α (1/2) 3 P4 Power law 2/3α -1/2 α (3/2) Reaction-order models 4 F1 First-order (Mampel) (1−α) −ln(1−α) 5 F2 Second-order (1−α)2 (1−α)–1−1 6 F3 Third-order (1−α)3 0.5[(1−α)–2−1] Diffusion models 7 D1 1-D Diffusion 1/2α–1 α2 8 D2 2-D Diffusion [−ln(1−α)]–1 [(1−α)ln(1−α)]+α 9 D3 3-D Diffusion-Jandereqn. 2(1−α)2/3[1−(1−α)1/3] –1 [1−(1−α)1/3]2 10 D4 Ginstling-Brounshtein 3/2[(1−α)–1/3−1] (1−2α/3)−(1−α)2/3 11 A2 Avrami-Erofe’ev 2(1−α)[−ln(1−α)]1/2 [−ln(1−α)]1/2 12 A3 Avrami-Erofe’ev 3(1−α)[−ln(1−α)]2/3 [−ln(1−α)]1/3 13 A4 Avrami-Erofe’ev 4(1−α)[−ln(1−α)]3/4 [−ln(1−α)]1/4 Geometrical contraction models 14 R2 Phase-boundary controlled reaction (contracting volume i.e., bidimensional shape) 2(1−α)1/2 [1−(1−α)1/2] 15 R3 Phase-boundary controlled reaction (contracting volume i.e., tridimensional shape) 3(1−α)2/3 [1−(1−α)1/3] Table 2. Arrhenius parameters for non-isothermal decomposition of compound EACIOIPC (Stage I) at various heating heats. Kinetic model β = 10 K/min β = 15 K/min β = 20 K/min β = 30 K/min Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r P2 2.71 -3.86 -0.891 2.71 -3.47 -0.893 2.62 -3.25 -0.887 2.60 -2.87 -0.886 P3 -0.71 - 0.648 -0.72 - 0.658 -0.79 - 0.692 -0.82 - 0.707 P4 -2.41 - 0.973 -2.43 - 0.974 -2.49 - 0.976 -2.53 - 0.977 F1 22.64 3.46 -0.934 22.71 3.85 -0.935 22.53 4.04 -0.934 22.57 4.41 -0.934 F2 36.02 7.87 -0.895 36.14 8.27 -0.896 35.89 8.42 -0.895 35.97 8.77 -0.895 F3 52.58 13.10 -0.867 52.77 13.50 -0.868 52.43 13.61 -0.867 52.57 13.95 -0.867 D1 40.86 14.87 -0.987 40.98 15.27 -0.987 40.78 15.44 -0.987 40.90 15.81 -0.987 D2 38.79 6.59 -0.974 38.90 6.99 -0.975 38.65 7.14 -0.974 38.74 7.49 -0.974 D3 45.56 7.27 -0.962 45.70 7.67 -0.962 45.41 7.80 -0.962 45.52 8.14 -0.962 D4 41.02 5.82 -0.970 41.14 6.21 -0.971 40.88 6.35 -0.970 40.98 6.70 -0.970 A2 7.56 -1.38 -0.874 7.57 -0.99 -0.876 7.46 -0.76 -0.873 7.46 -0.39 -0.873 A3 2.52 -3.73 -0.680 2.52 -3.34 -0.682 2.43 -3.12 -0.670 2.41 -2.75 -0.667 A4 0.01 -9.79 -0.006 0.00 -10.30 -0.002 -0.07 - 0.036 -0.10 - 0.050 R2 17.35 0.92 -0.955 17.39 1.31 -0.956 17.24 1.52 -0.955 17.27 1.88 -0.955 R3 15.85 0.65 -0.961 15.89 1.05 -0.962 15.74 1.26 -0.962 15.76 1.63 -0.961 Figure 3. Ea versus α plot for the decomposition of EACIOIPC under non-isothermal condition (Stage I). The use of an integral or differential model-fitting method leads to different values of the activation parameters. Although obtained with high accuracy the values change with different heating rates and among conversion functions. Lesnikovich and Levchik [27,28] suggested that corre- lating these values by the apparent compensation effect, ln A = aβ + bβ Ea, one obtains the compensation effect parameters aβ and bβ, which strongly depend on the heating rates (β) as well as on the considered set of conversion functions. The straight lines of ln A vs Ea for four constant heating rates should intersect at a point (iso-parametric point) which corresponds to the true values of the activation energy and pre-exponential factor. These were named as invariant kinetic parameters. The invariant kinetic parameters method was applied to the data calculated for the heating rates of 10, 15, 20 and 30 K/min. The evaluation of the kinetic parameters was perfor- med using Coats-Redfern method. For these kinetic models in the range 0.12 ≤ α ≤ 0.98 for EACIOIPC for all the stages, the straight lines corresponding to Coats-Redfern method is characterized by correlation coefficient values close to unity. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 77 Table 3. Arrhenius parameters for non-isothermal decomposition of compound EACIOIPC (Stage II) at various heating rates. Kinetic model β = 10 K/min β = 15 K/min β = 20 K/min β = 30 K/min Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r P2 44.73 7.51 -0.883 46.67 8.32 -0.893 46.59 8.53 -0.894 45.77 8.65 -0.881 P3 26.67 3.23 -0.860 27.95 3.92 -0.872 27.88 4.15 -0.872 27.31 4.35 -0.857 P4 17.69 0.94 -0.830 18.64 1.58 -0.845 18.57 1.82 -0.845 18.13 2.06 -0.827 F1 162.69 34.24 -0.957 168.54 35.76 -0.961 168.35 35.81 -0.962 166.51 35.52 -0.955 F2 255.26 55.11 -0.984 263.80 57.11 -0.987 263.50 57.03 -0.987 261.40 56.53 -0.983 F3 372.08 81.20 -0.994 383.95 83.79 -0.995 383.51 83.56 -0.996 381.15 82.81 -0.993 D1 220.48 53.41 -0.915 228.60 55.37 -0.921 228.47 55.37 -0.922 225.41 54.74 -0.913 D2 241.04 49.93 -0.926 249.99 52.04 -0.933 249.77 52.00 -0.933 246.54 51.28 -0.925 D3 285.91 58.53 -0.945 296.21 60.88 -0.950 295.92 60.77 -0.951 292.52 59.94 -0.943 D4 255.78 51.75 -0.933 265.18 53.94 -0.939 264.93 53.87 -0.940 261.65 53.12 -0.932 A2 76.67 15.13 -0.951 79.57 16.10 -0.957 79.45 16.27 -0.957 78.50 16.31 -0.950 A3 47.93 8.52 -0.945 49.86 9.32 -0.951 49.76 9.52 -0.952 49.10 9.68 -0.943 A4 33.65 5.12 -0.938 35.09 5.83 -0.945 35.00 6.05 -0.946 34.49 6.26 -0.936 R2 127.25 25.46 -0.933 132.05 26.79 -0.939 131.90 26.89 -0.939 130.20 26.69 -0.931 R3 117.42 23.48 -0.923 121.92 24.76 -0.930 121.79 24.87 -0.931 120.13 24.70 -0.921 Table 4. Arrhenius parameters for non-isothermal decomposition of compound EACIOIPC (Stage III) at various heating rates. Kinetic model β = 10 K/min β = 15 K/min β = 20 K/min β = 30 K/min Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r Ea (kJ/mol) ln A r P2 -3.47 - 0.941 -3.55 - 0.942 -3.58 - 0.943 -3.66 - 0.947 P3 -7.07 - 0.995 -7.14 - 0.994 -7.17 - 0.994 -7.25 - 0.995 P4 -8.86 - 0.998 -8.93 - 0.998 -8.96 - 0.998 -9.04 - 0.998 F1 17.51 -1.59 -0.897 17.40 -1.23 -0.896 17.39 -0.96 -0.895 17.32 -0.59 -0.895 F2 31.62 1.40 -0.865 31.48 1.75 -0.864 31.48 2.02 -0.863 31.42 2.38 -0.864 F3 49.09 4.77 -0.843 48.92 5.12 -0.843 48.92 5.38 -0.842 48.89 5.73 -0.843 D1 42.05 9.83 -0.985 41.96 10.20 -0.985 42.00 10.47 -0.985 42.00 10.84 -0.985 D2 34.47 -0.20 -0.966 34.33 0.16 -0.966 34.34 0.43 -0.966 34.27 0.79 -0.966 D3 41.61 -0.27 -0.953 41.46 0.08 -0.952 41.47 0.35 -0.952 41.41 0.70 -0.952 D4 36.83 -1.22 -0.961 36.68 -0.87 -0.961 36.69 -0.60 -0.961 36.63 -0.24 -0.961 A2 1.64 -5.95 -0.380 1.55 -5.62 -0.363 1.52 -5.36 -0.356 1.45 -5.03 -0.344 A3 -3.67 - 0.833 -3.74 - 0.838 -3.77 - 0.839 -3.85 - 0.847 A4 -6.30 - 0.966 -6.38 - 0.967 -6.41 - 0.967 -6.48 - 0.969 R2 11.93 -3.64 -0.914 11.82 -3.27 -0.912 11.81 -3.00 -0.912 11.74 -2.63 -0.912 R3 10.35 -3.78 -0.918 10.24 -3.41 -0.917 10.23 -3.14 -0.916 10.16 -2.77 -0.917 Figure 4. Ea versus α plot for the decomposition of EACIOIPC under non-isothermal condition (Stage II). Figure 5. Ea versus α plot for the decomposition of EACIOIPC under non-isothermal condition (Stage III). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 78 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 Figure 6. Super correlation (compensation effect parameters) plot for the best combination of kinetic models (Stage I). Figure 7. Super correlation (compensation effect parameters) plot for the best combination of kinetic models (Stage II). Figure 8. Super correlation (compensation effect parameters) plot for the best combination of kinetic models (Stage III). For several groups of apparent activation parameters, obtained by different kinetic models, we tried to establish the best correlation (r→1), a better resolution in determining the invariant kinetics parameters and the closet value to the mean iso-conversional activation energies. For Stage I for AKM–{P2;A3}, the plot of ln A vs Ea has the highest correlation coefficient and is a straight line (Figure 6). The invariant kinetic parameters, Einv = 250.68±0.72 kJ/mol for AKM and ln Ainv = 80.56 are obtained with r = 0.995 (Figure 6). For these groups, the invariant activation energy is high 250.68 kJ/mol compared to Friedman, KAS and FWO methods (245.59±0.85, 245.01±0.16, 240.94±0.43 kJ/mol, respectively). For Stage II, a better resolution in determining the inva- riant kinetic parameters, and the correlation coefficients (Figure 7) show a good agreement of all kinetic models. The efficiency of IKP method is strongly revealed by AKM- {F2;D1;D4} (Figure 7) and even by AKM (all kinetic models) which comprises all the best-fitting function that makes it a more powerful method. The invariant activation energy is 283.21 kJ/mol, which is close to Friedman method. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 79 Figure 9. Determination of A value by plotting (1–α)–1–1 against Ea×p(x)/β×R for the decomposition of EACIOIPC at different heating rates (β) (Stage I). Figure 10. Determination of A value by plotting 0.5[(1-α)-2-1 against Ea×p(x)/β×R for the decomposition of EACIOIPC at different heating rates (β) (Stage II). Figure 11. Determination of A value by plotting 0.5×[(1-α)-2-1] against Ea×p(x)/β×R for the decomposition of EACIOIPC at different heating rates (β) (Stage III). The invariant kinetic parameters are Einv = 277.38 kJ/mol and ln Ainv = 58.76 obtained with r = 0.994. For third stage of AKM-{A2;R2}, the plot of ln A versus Ea has the highest correlation coefficient (r = 0.883) (Figure 8). Depending upon the choice of kinetic models, the compen- sation effect parameters are obtained with different accura- cies, their values and the derived invariant activation para- meters varying substantially. For AKM-{A2;R2}, the invariant kinetic parameters are 673.73 kJ/mol and ln Ainv = 130.68 obtained with r = 0.883. For these groups, the invariant activation energy is high in comparison with Friedman, KAS and FWO methods (629.45±0.60 kJ/mol, Friedman; 620.30±0.51 kJ/mol, KAS; 604.26±0.55 kJ/mol, FWO). 4.5. Determination of kinetic models The most suitable kinetic model for the decomposition process of EACIOIPC is F2. By introducing the derived reaction model g(α) =(1–α)–1–1, the following equation is obtained. ( )–11– –1 α β = α p(x) R AE (11) 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 80 Nalini et al. / European Journal of Chemistry 10 (1) (2019) 72-81 Table 5. Values of kinetic and thermodynamic parameters for the thermal decomposition of EACIOIPC in nitrogen atmosphere. Parameter Stage I Stage II Stage III Ea (kJ/mol) 687.51 223.97 323.49 ln A 17.82 48.80 44.17 ∆G≠ (kJ/mol) 113.91 137.73 224.45 ∆H≠ (kJ/mol) 65.00 219.36 316.23 ∆S≠ (J/K.mol) -108.49 147.41 105.10 r 0.991 0.988 0.993 The plots of 1–α)–1–1 against Ea×p(x)/β×Rat the different heating rates are shown in Figure 9. The activation energy for Stage I, Ea = 245.59 kJ/mol and the frequency factor was found to be 9.699×1034 min-1 (ln A = 80.56). The obtained value of ln A is in good agreement with values obtained by Friedman iso- conversional intercept. The most suitable kinetic model is F3 for stages II and III as confirmed by introducing the derived reaction model g(α) = 0.5 [(1-α)-2 -1], when the following equation is obtained [30]. ( )α β    × = α p(x) R AE–20.5 1– –1 (12) The plots of 0.5×[(1–α)–2–1] against Ea×p(x)/β×R at the different heating rates are shown in Figures 10 and 11. The activation energy Ea = 283.21 kJ/mol and frequency factor for Stage III is 3.304×1025 min-1 (ln A = 58.76) and the activation energy Ea = 629.45 kJ/mol and the frequency factor for Stage IV is 5.670×1056 min-1 (ln A = 130.68) as determined by IKP method. Venkatesan et al., non-isothermal decomposition of 4- ((4-fluoro-3-phenoxy-benzylidene)amino) benzene sulfon- amide under oxygen atmosphere [35] decomposition kinetics model F2, and Manikandan et al., 1,5-bis(4-hydroxy-3-methoxy phenyl)pentan-1,4-diene-3-one compound was decomposed under R2 model [36]. 4.6. Thermodynamic parameters From the DTG curves, the peak temperatures of EACIOIPC are 450.82, 553.81 and 873.21 K. These peak temperatures are used to evaluate single point kinetic parameters [25]. The obtained values are 687.51, 223.97, 323.49 kJ/mol for Stages I, II and III, respectively. The thermodynamic parameters, ∆S≠, ∆H≠ and ∆G≠ were calculated at the peak temperature Tm in the DTG curves for the corresponding stage [37,38] since the temperature characterizes the higher rate of decomposition. As can be seen from Table 5, the value of ∆S≠ for the decomposition is positive for Stages II and III. It means that the corresponding activated complexes were with lesser degrees of arrangement than the initial state, whereas for the first stage the transition state was more ordered than the initial stage. The positive values of ∆H≠ and ∆G≠ show that they are connected with absorption of heat and are non-spontaneous processes [39]. The obtained Ea values coincide with invariant parameters. 5. Conclusion The compound chosen for the study decomposed in three stages. Activation energies of three stages of obtained compound could be determined from a model-free analysis and model-fitting analysis of TGA data. Since, the activation energy values varied with conversion level, the activation energy values were used to interpret decomposition models for each stages followed by different kinetic models namely F2 for first stage and F3 for second and third stages. The rate of decomposition of third stage is slow due to high energy of activation when compared to Stages I and II. The positive free energy values indicated that the decomposition of studied compound is non-spontaneous process. Acknowledgment The authors thank Dr. Paramasivam Thirumalai Perumal, Organic Chemistry Division, CSIR-Central Leather Research Institute, Chennai for their fruitful suggestions and The Head, Indian Institute of Technology, SAIF, Chennai for TGA/DTG measurements. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID Ganesan Nalini http://orcid.org/0000-0001-6072-1713 Natesan Jayachandramani http://orcid.org/0000-0002-7087-9722 Radhakrishnan Suresh http://orcid.org/0000-0002-9340-317X Prakasam Thirumurugan http://orcid.org/0000-0003-3450-6328 Venugopal Thanikachalam http://orcid.org/0000-0003-1076-6272 Govindasamy Manikandan http://orcid.org/0000-0003-2732-4366 Dharmalingam Sankari http://orcid.org/0000-0002-3553-9626 References [1]. Bhaskar, G.; Arun, Y.; Balachandran, C.; Saikumar, C.; Perumal, P. T. Eur. J. Med. Chem. 2012, 51, 79-91. [2]. Gribble, G. W. J. Chem. Soc. Perkin Trans. I 2000, 1045-1075. [3]. Zhu, S. L.; Ji, S. L.; Su, X. M.; Sun, C.; Liu, Y. Tetrahedron Lett. 2008, 49, 1777-1781. [4]. Farghaly, A. M.; Habib, N. S.; Khalil, M. A.; El-Sayed, O. A. Alexandria. J. Pharm. Sci. 1989, 3, 84-86. [5]. Yu, B.; Yu, D. Q.; Liu, H. M. Eur. J. Med. Chem. 2015, 97, 673-698. [6]. Fuchao, Y.; Huang, R.; Hangchen, N.; Juan, F.; Shengjiao, Y.; Lin, L. Green. Chem. 2013, 15, 453-462. [7]. 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Chemical Data Collections, 2017, 9(10), 67-79. [36]. Manikandan, G.; Rajarajan, G.; Jayabharathi, J.; Thanikachalam, V. Arab. J. Chem. 2011, 9, 570-575. [37]. Ma, H. X.; Yan, B.; Li, Z. N.; Song, J. R.; Hu, R. Z. J. Therm. Anal. Calorim. 2007, 95, 437-444. [38]. Boonchom, B. J. Therm. Anal. Calorim. 2010, 31, 416-429. [39]. Criado, J. M.; Perez-Maqueda, L. A.; Sanchez-Jimenez, P. E. J. Therm. Anal. Calorim. 2005, 82, 671-675. Copyright © 2019 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.72-81.1812 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Materials 2.2. Instrumentations 2.3. Synthesis of ethyl-2ʹ-amino-5ʹ-cyano-6ʹ-(1H-indole-3yl)-2-oxospiro[indoline-3,4ʹ-pyran]-3ʹ-carboxylate 3. Theoretical background 3.1. Model fitting method 3.2. Model free methods 3.3. Invariant kinetic parameters method 3.4. Thermodynamic parameters 4. Results and discussion 4.1. Non-isothermal TGA 4.2. Model-free analysis 4.3. Model-fitting analysis 4.4. Invariant kinetics parameters analysis 4.5. Determination of kinetic models 4.6. Thermodynamic parameters 5. Conclusion Acknowledgment Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField19: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: PrintField29: