Experimental and computational energetic study of 1-R-2-phenylindole (R = H, CH3, C2H5)
Introduction
Indole has become widely identified as a “privileged structure” to integrate a large number of compounds with important biological activity [1], [2], [3]. In particular, 2-phenylindole and some alkyl derivatives have been the subject of several studies aiming to evaluate the anticancer activity in human cells [4], [5], [6], while the growth-inhibiting effect of these compounds on the hormone-dependent mammary carcinoma of the rat has determined intense research concerning the synthesis of possibly potent anti-estrogens drugs [7], [8]. These aspects justify the interest on the knowledge of the thermodynamic properties of these compounds, in order to evaluate the respective reactivity.
In this work, the standard (po = 0.1 MPa) molar enthalpies of formation at T = 298.15 K, of the title compounds, in the crystalline phase, were derived from the standard molar energies of combustion measured by static bomb combustion calorimetry. The Knudsen mass-loss effusion technique was used to measure the vapour pressure as a function of temperature for the three compounds studied. The standard molar enthalpies of sublimation of these compounds, at the mean temperature of the experiments temperature range, were obtained by the application of the Clausius–Clapeyron equation to the values of the vapour pressure, determined at different temperatures. The obtained value for each compound was corrected for T = 298.15 K, using an estimated value for the heat capacity differences between the corresponding gas and crystal phases. Standard molar entropies and Gibbs functions of sublimation, at the temperature of 298.15 K, were also calculated. The experimental standard molar enthalpies of formation of the compounds, in the gaseous state, at T = 298.15 K, were thus obtained by combining these two sets of results.
The gas-phase molar enthalpies of formation of 2-phenylindole, 1-methyl-2-phenylindole and 1-ethyl-2-phenylindole were also estimated by combining the respective enthalpies of several working reactions, at T = 298.15 K, computed at the G3(MP2) level of theory, with the experimental enthalpies of formation of the auxiliary molecules used. The good agreement between the experimental values and those obtained by the computational calculations gave us confidence to extend the calculations to the study of 1-ethylindole.
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Compound and purity control
2-Phenylindole and 1-methyl-2-phenylindole were obtained commercially from Aldrich Chemical Co and 1-ethyl-2-phenylindole was obtained from TCI Europe, with certified molar fraction purity greater than 0.99 mass fraction. The 2-phenylindole was purified by recrystallization and the remaining compounds were purified twice by sublimation under reduced pressure. The purity was checked by (gas + liquid) chromatography performed on an Agilent 4890D Gas Chromatography equipped with an HP-5 column,
Combustion calorimetry
Table 2 collects the results of a typical combustion experiment for 2-phenylindole, 1-methyl-2-phenylindole and 1-ethyl-2-phenylindole. The Δm(H2O) is the deviation of the mass of water added to the calorimeter from 2900.0 g (the mass assigned for εcal), and ΔUΣ is the energy correction to the standard state. The remaining quantities are as previously defined [17], [29]. The energy associated to the isothermal bomb process ΔU (IBP), was calculated through:
Discussion
As can be seen from TABLE 9, TABLE 10, TABLE 11, using appropriate reactions, we were able to estimate the enthalpy of formation for the compounds studied with deviations, relative to the experimental value, that are not larger than about 10 kJ · mol−1. The results obtained from working reactions (45) and (55) were considered outliers and consequently not included in the mean value for compounds studied.
A mean value was calculated from the computational estimates: (250.7 ± 2.1) kJ · mol−1 for
Acknowledgments
Thanks are due to Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal and to FEDER for financial support given to Centro de Investigação em Química da Universidade do Porto, (PEst-C/QUI/UI0081/2013), and to Programa Ciência 2008.
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