Molecular energetics of pyrrolecarbonitriles and derivatives: A combined calorimetric and computational study

Abstract

In this work, calorimetric measurements were carried out, in order to determine the standard (p^o = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, ${\mathrm{\Delta }}_{\text{f}}{H}_{\text{m}}^{\text{o}}(\text{g})$, at T = 298.15 K, of 2-pyrrolecarbonitrile and 1,5-dimethyl-2-pyrrolecarbonitrile. These data were calculated from the standard molar enthalpies of formation, in the condensed phase, ${\mathrm{\Delta }}_{\text{f}}{H}_{\text{m}}^{\text{o}}(\text{cr,l})$, at T = 298.15 K, derived from static bomb combustion calorimetry measurements, and from the standard molar enthalpies of phase transition, ${\mathrm{\Delta }}_{\text{cr,l}}^{\text{g}}{H}_{\text{m}}^{\text{o}}$, at T = 298.15 K, obtained by high temperature Calvet microcalorimetry. The gas-phase enthalpies of formation were also calculated from high level ab initio molecular orbital calculations, at the G3(MP2)//B3LYP level, and a very good agreement between experimental and computational values was obtained, giving us support to estimate the gas-phase enthalpies of formation of 3-pyrrolecarbonitrile and 1,5-dimethyl-3-pyrrolecarbonitrile. Moreover, the molecular structure of the four molecules was established and the structural parameters were determined at the B3LYP/6-31G(d) level of theory.

Introduction

Pyrrole derivatives represent a class of compounds of great importance in heterocyclic chemistry. They constitute the structural feature of many biologically important molecules, which include the hemoglobin, chlorophyll, porphyrins, corrins, vitamin B₁₂ and the bile pigments [1], [2], [3], [4].During the last years, we have directed our attention towards the understanding of the molecular and energetic properties of this kind of compounds, their stability and reactivity, as well as their energetics-structure relationships, by studying the thermochemical and thermophysical properties of pyrrole derivatives [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], both experimental and computationally, owing to its role as building blocks of the naturally-occurring porphyrins, the tetrapyrrolic “pigments of life”, and due to the relevance of the molecule and its derivatives in the synthesis of organic polymers [15], [16], [17], dyes [18], [19], agrochemicals [20] or other organic compounds [21], [22], [23], [24], [25].

As a continuation of the systematic work that we have been carrying out, the present study is focused on the molecular energetics of pyrrolecarbonitriles and derivatives. The 2-pyrrolecarbonitrile derivatives are key compounds in the synthesis porphobilinogen, the main building block used in the biosynthesis of the “pigments of life” [26], [27], [28]. The tetrapyrrolic compounds have been applied in photodynamic therapy for the treatment of cancer [29], [30]. The 2-pyrrolecarbonitrile finds application in organometallic chemistry [31] and it is present in tobacco and tobacco smoke [32], [33]. The 3-pyrrolecarbonitrile moiety was found to impart antibacterial activity; it is presented in compounds with antibacterial activity in vitro against Gram-positive and Gram-negative pathogens and that are effective in vivo against S. aureus and S. pneumoniae [34]. Fensome and collaborators [35] synthesized a compound in which pyrrolecarbonitriles moieties are presented; these compounds demonstrated potent activity on progesterone receptor antagonist, that can be potential contraceptive agents.

In this paper, the experimental and computational standard (p^o = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of 2-pyrrolecarbonitrile and 1,5-dimethyl-2-pyrrolecarbonitrile, whose structural formulas are depicted in figure 1, are reported. These values were derived from the standard molar enthalpies of formation, in the condensed phase, obtained by static bomb combustion calorimetry and from their standard molar enthalpies of phase transition, determined by high temperature Calvet microcalorimetry.

High-level ab initio molecular orbital calculations, at the G3(MP2)//B3LYP level, were performed and the estimated gas-phase enthalpies of formation of 2-pyrrolecarbonitrile and 1,5-dimethyl-2-pyrrolecarbonitrile were obtained. These calculations were further extended to the 3-pyrrolecarbonitrile and 1,5-dimethyl-3-pyrrolecarbonitrile that were not studied experimentally. The molecular structures of the four molecules were also established.