Thermochemical study of 1-, 3- and 4-piperidinecarboxamide derivatives
Introduction
Piperidine ring systems are a commonest structural sub-unit in natural compounds and are of great interest in pharmaceutical industry. They exhibit a wide range of biological activities and so, the applicability of piperidine derivatives as raw-material and intermediates for medicines or drugs has been object of great interest. As examples of the applications of piperidinecarboxamides, in medicine, they are referred as inhibitors against aggregation of human platelets [1] and anti-HIV-1 activity [2]. Piperidinecarboxamides are also involved in computational and NMR spectroscopy studies to identify ligand-binding sites of macromolecules, namely proteins [3]. Jurkiewicz-Herbich et al. had studied the adsorption of nipecotamide (3-piperidinecarboxamide) from aqueous solutions in mercury electrodes [4], in order to investigate the factors that govern the adsorption of molecules from aqueous solutions, upon the type of interface and the structure of the solutions, to elucidate the adsorption mechanisms and structure details of the adsorption layer. That molecule has been chosen for this investigation as the model typical nitrogen heterocycle in which all the bonds in the ring are saturated.
As a part of our extensive work on the thermochemistry of nitrogen heterocyclic compounds, we have recently been interested on the derivatives of piperidine [5], [6], [7], [8], [9].
The number of compounds with carboxamide substituents for which thermochemical data are available is very scarce, and so, this work is also a contribution for the knowledge of the thermochemical properties of the carboxamide type of compounds.
This paper presents the thermochemical study of 1-, 3-, and 4-piperidinecarboxamide, reporting their standard (p° = 0.1 MPa) molar enthalpies of formation in the crystalline state derived from the standard molar enthalpy of combustion determined by static bomb calorimetry and their standard molar enthalpies of sublimation measured by Calvet microcalorimetry. From these two thermochemical parameters, the standard molar enthalpies of formation in the gaseous phase, of the three compounds, at T = 298.15 K, have been derived.
Section snippets
Compounds
The piperidinecarboxamide derivatives studied, 1-piperidinecarboxamide, [CAS 2158-03-4], 3-piperidinecarboxamide, [CAS 4138-26-5], and 4-piperidinecarboxamide [CAS 39546-32-2] were all supplied by Aldrich Chemical with initial purity of 99%, 95%, and 97%, respectively. These three compounds were purified by repeated vacuum sublimation and the final purity of the compounds was determined by the recovering the carbon dioxide produced in the combustion experiments and also checked by d.s.c. and
Experimental results
Table 1 lists detailed results for a typical combustion experiment of each compound, where Δm(H2O) is the deviation of the mass of water added to the calorimeter from 3119.6 g and ΔU(IBP) is the energy change for the isothermal combustion reaction under bomb conditions, withand the remaining quantities are as previously defined [24], the corrections to the standard state, ΔUΣ, and the massic energies of combustion, Δcu°, were calculated by the
Discussion
The number of compounds with carboxamide substituents for which thermochemical data is available is too scarce to allow a long discussion about the effect of the carboxamide group into the piperidine ring, and so, in the present state of knowledge only a limited discussion is possible.
Taking into account the value of the standard molar enthalpy of formation of gaseous piperidine, measured by Good [27], (piperidine, g) = −47.15 ± 0.63 kJ mol−1, the enthalpic increments for the introduction of
Acknowledgements
Thanks are due to Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal and to FEDER for financial support to Centro de Investigação em Química, University of Porto. J.I.T.A.C. thanks FCT and the European Social Fund (ESF) under the 3rd Community Support Framework (CSF) for the award of a Ph.D. research grant (BD/5364/2001).
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