Heat capacity and decomposition of rimantadine hydrochloride
Introduction
An important branch of the chemical industry is specialty chemicals manufacturing (synthetic dyes, drugs, chemical additives, insecticides, etc.). A noticeable interest in this field is directed to adamantane derivatives, whose chemistry has been intensively studied since the middle of the 20th century [1,2]. Compounds from this class have already found numerous applications due to the diversity of their properties: e.g., as medicines, lubricants, and additives. To date, hundreds of adamantane derivatives have already been studied for pharmacological activity. Some of them are being used as drugs, such as rimantadine, amantadine, memantine, and gludantane [[3], [4], [5], [6]]. However, insufficient thermodynamic property knowledge for these compounds inhibits development of effective, environmentally friendly technologies for their production and limits the possibility of effective property prediction for this class.
This paper is a continuation of a series of publications on condensed-phase thermodynamic properties of adamantane derivatives [[7], [8], [9], [10], [11], [12], [13], [14]]. Rimantadine hydrochloride (C12H22NCl, 1-(1-adamantyl)ethanamine hydrochloride, CAS registry number 1501-84-4, Fig. 1a), which is produced as a racemic mixture, was selected in this study due to its current use as an antiviral drug [3] and its potential use as an antiparkinsonian medication [15,16]. Rimantadine hydrochloride is structurally similar to another compound (amantadine hydrochloride – Fig. 1b) recently studied by us [7]. This similarity allows tracing patterns in changing thermodynamic properties with structural modifications. Besides the crystallographic density of 1.13 g·cm−3 obtained by single-crystal X-ray diffraction analysis at 291 K (tetragonal space group P42bc with the lattice cell parameters of a = 1.83774 nm, c = 0.75049 nm, and Z = 8) [17], no relevant property data were found for this compound in the literature.
Section snippets
Sample preparation
Two samples of rimantadine hydrochloride (racemic mixture) were used in this work (Table 1). One sample used for heat-capacity experiments in an adiabatic calorimeter and in a Knudsen-effusion apparatus was supplied by RUE “Belmedpreparaty” (Minsk, Belarus). The initial mass-fraction purity was not less than 0.99 according to a certified analysis carried out by the manufacturer. The sample was additionally exposed to vacuum at T = 293 K and p = 0.4 kPa for 2 h in order to remove volatile
Computations
The rimantadine molecule has two symmetric tops, methyl and adamantyl, and an asymmetric NH2 top. Optimization of geometries and calculation of vibrational frequencies and rotational potentials were performed using B3LYP hybrid density functional with the def2-TZVP basis set and D3(BJ) correction [[22], [23], [24], [25]]. Parameters of the symmetric tops were found for the most stable conformer formed by rotation of the NH2 top. The rotational barriers and energies of the NH2 conformers were
Thermodynamic properties of crystalline rimantadine hydrochloride
Experimental molar heat capacities of crystalline rimantadine hydrochloride measured in the adiabatic calorimeter and the differential scanning calorimeter described in Section 2.2 are shown in Fig. 2 and are summarized in Tables S1 and S2 of the Supporting Information, respectively. For comparison, Fig. 2 also includes the heat capacity of amantadine hydrochloride measured previously [7].
The data for rimantadine hydrochloride from both calorimeters are in excellent agreement: within 0.6 %
Conclusions
Condensed-phase heat capacity of crystalline rimantadine hydrochloride in a wide temperature range was measured. Decomposition of the compound was shown to be complex (at least two concurrent processes), with a simple decomposition into gaseous amine and hydrogen chloride prevailing at lower temperatures. Identification of the nature of the high-temperature decomposition requires additional study. The complexity of the decomposition did not allow determination of equilibrium partial pressures
CRediT authorship contribution statement
Ala Bazyleva: Investigation, Data curation, Writing - original draft. Eugene Paulechka: Data curation, Writing - review & editing. Dzmitry H. Zaitsau: Investigation. Andrey V. Blokhin: Investigation. Gennady J. Kabo: Conceptualization, Supervision.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
DHZ acknowledges the financial support from Deutsche Forschungsgemeinschaft (DFG), Germany, grant ZA 872/3-1, 407078203.
Trade names are provided only to specify procedures adequately and do not imply endorsement by the National Institute of Standards and Technology. Similar products by other manufacturers may be found to work as well or better.
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