A new polymorph of 4′-hydroxyvalerophenone revealed by thermoanalytical and X-ray diffraction studies

A new polymorph of 1-(4-hydroxyphenyl)pentan-1-one (4′-hydroxyvalerophenone, HVP) was identified by using differential scanning calorimetry, hot stage microscopy, and X-ray powder diffraction. This novel crystal form (form II) was obtained by crystallization from melt. It has a fusion temperature of Tfus = 324.3 ± 0.2 K and an enthalpy of fusion ΔfusHmo = 18.14±0.18 kJ·mol−1. These values are significantly lower than those observed for the previously known phase (form I, monoclinic, space group P21/c, Tfus = 335.6 ± 0.7 K; ΔfusHmo = 26.67±0.04 kJ·mol−1), which can be prepared by crystallization from ethanol. The results here obtained, therefore, suggest that form I is thermodynamically more stable than the newly identified form II and, furthermore, that the two polymorphs are monotropically related

Kinetics and Mechanism of the Thermal Dehydration of a Robust and Yet Metastable Hemihydrate of 4‑Hydroxynicotinic Acid

Hydrates are the most common type of solvates and certainly the most important ones for industries such as pharmaceuticals which strongly rely on the development, production, and marketing of organic molecular solids. A recent study indicated that, in contrast with thermodynamic predictions, a new hemihydrate of 4-hydroxynicotinic acid (4HNA·0.5H₂O) did not undergo facile spontaneous dehydration at ambient temperature and pressure. The origin of this robustness and the mechanism of dehydration were investigated in this work, through a combined approach which involved kinetic studies by thermogravimetry (TGA), crystal packing analysis based on X-ray diffraction data, and microscopic observations by hot stage microscopy (HSM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The TGA results indicated that the resilience of 4HNA·0.5H₂O to water loss is indeed of kinetic origin, c.f., due to a significant activation energy, <i>E</i>_a, which increased from 85 kJ·mol^–1 to 133 kJ·mol^–1 with the increase in particle size. This <i>E</i>_a range is compatible with the fact that four moderately strong hydrogen bonds (typically 20–30 kJ·mol^–1 each) must be broken to remove water from the crystal lattice. The dehydration kinetics conforms to the Avrami-Erofeev A2 model, which assumes a nucleation and growth mechanism. Support for a nucleation and growth mechanism was also provided by the HSM, SEM, and AFM observations. These observations further suggested that the reaction involves one-dimensional nucleation, which is rarely observed. Finally, a statistical analysis of Arrhenius plots for samples with different particle sizes revealed an isokinetic relationship between the activation parameters. This is consistent with the fact that the dehydration mechanism is independent of the sample particle size

Energetics of the oxidative addition of i2 to [Ir(μ-L)(CO)2]2 (L = StBu, 3,5-Me2pz,7-aza) complexes. X-ray structures of [Ir(μ-StBu)(I)(CO)2]2 and [Ir(μ3,5-Me2pz)(I)(CO)2]2

This work was supported by Junta Nacional de Investigaqo Cientifica e Tecnologica, Portugal (Projects PBIC/C/CEN/1042/92 and STRDA/C/CEN/469/92) and CICYT and Generalitat de Catalunya, Spain (Project QFN92--4311). A Ph.D. grant from JNICT (BD/2270/92-RM)Peer reviewe

Effect of ring substitution on the S-H bond dissociation enthalpies of thiophenols. An experimental and computational study

There are conflicting reports on the origin of the effect of Y substituents on the S-H bond dissociation enthalpies (BDEs) in 4-Y-substituted thiophenols, 4-YC\u2086H\u2084S-H. The differences in S-H BDEs, [4-YC\u2086H\u2084S-H] - [C\u2086H\u2085S-H], are known as the total (de)stabilization enthalpies, TSEs, where TSE = RSE - MSE, i.e., the radical (de)stabilization enthalpy minus the molecule (de)stabilization enthalpy. The effects of 4-Y substituents on the S-H BDEs in thiophenols and on the S-C BDEs in phenyl thioethers are expected to be almost identical. Some S-C TSEs were therefore derived from the rates of homolyses of a few 4-Y-substituted phenyl benzyl sulfides, 4-YC\u2086H\u2084S-CH\u2082C\u2086H\u2085, in the hydrogen donor solvent 9,10-dihydroanthracene. These TSEs were found to be -3.6 \ub1 0.5 (Y = NH\u2082), -1.8 \ub1 0.5 (CH\u2083O), 0 (H), and 0.7 \ub1 0.5 (CN) kcal mol\u207b\ub9. The MSEs of 4-YC\u2086H\u2084SCH\u2082C\u2086H\u2085 have also been derived from the results of combustion calorimetry, Calvet-drop calorimetry, and computational chemistry (B3LYP/6-311+G(d,p)). The MSEs of these thioethers were -0.6 \ub1 1.1 (NH\u2082), -0.4 \ub1 1.1 (CH\u2082O), 0 (H), -0.3 \ub1 1.3 (CN), and -0.8 \ub1 1.5 (COCH\u2082) kcal mol\u207b\ub9. Although all the enthalpic data are rather small, it is concluded that the TSEs in 4-YC\u2086H\u2084SH are largely governed by the RSEs, a somewhat surprising conclusion in view of the experimental fact that the unpaired electron in C\u2086H\u2085S c5 is mainly localized on the S. The TSEs, RSEs, and MSEs have also been computed for a much larger series of 4-YC\u2086H\u2084SH and 4-YC\u2086H\u2084SCH\u2083 compounds by using a B3P86 methology and have further confirmed that the S-H/S-CH\u2083 TSEs are dominated by the RSEs. Good linear correlations were obtained for TSE = \u3c1\u207a\u3c3p\u207a(Y), with \u3c1\u207a (kcal mol\u207b\ub9) = 3.5 (S-H) and 3.9 (S-CH\u2083). It is also concluded that the SH substituent is a rather strong electron donor with a \u3c3p\u207a(SH) of -0.60, and that the literature value of -0.03 is in error. In addition, the SH rotational barriers in 4-YC\u2086H\u2084SH have been computed and it has been found that for strong electron donating (ED) Ys, such as NH\u2082, the lowest energy conformer has the S-H bond oriented perpendicular to the aromatic ring plane. In this orientation the SH becomes an electron withdrawing (EW) group. Thus, although the OH group in phenols is always in-plane and ED irrespective of the nature of the 4-Y substituent, in thiophenols the SH switches from being an ED group with EW and weak ED 4-Ys, to being an EW group for strong ED 4-Ys.Peer reviewed: YesNRC publication: Ye

Extraction Optimization and Structural and Thermal Characterization of the Antimicrobial Abietane 7α-Acetoxy-6β-hydroxyroyleanone

The abietane 7α-acetoxy-6β-hydroxyroyleanone (AHR), obtained from plant extracts, is an attractive lead for drug development, given its known antimicrobial properties. Two basic requirements to establish any compound as a new drug are the development of a convenient extraction process and the characterization of its structural and thermal properties. In this work seven different methods were tested to optimize the extraction of AHR from <i>Plectranthus grandidentatus</i>. Supercritical fluid extraction (SFE) proved to be the method of choice, delivering an amount of AHR (57.351 μg·mg^–1) approximately six times higher than the second best method (maceration in acetone; 9.77 μg·mg^–1). Single crystal X-ray diffraction analysis of the ARH molecular and crystal structure carried out at 167 ± 2 K and 296 ± 2 K showed only a single phase, here dubbed form III (orthorhombic space group <i>P</i>2₁2₁2), at those temperatures. The presence of two other polymorphs above room temperature was, however, evidenced by differential scanning calorimetry (DSC). The three forms are enantiotropically related, with the form III → form II and form II → form I transitions occurring at 333.5 ± 1.6 K and 352.0 ± 1.6 K, respectively. The fact that the transitions are reversible suggests that polymorphism is not likely to be an issue in the development pharmaceutical formulations based on ARH. DSC experiments also showed that the compound decomposes on melting at 500.8 ± 0.8 K. Melting should therefore be avoided if, for example, strategies to improve solubility based on the production of glassy materials or solid dispersions are considered

Polymorphic Phase Transition in 4′-Hydroxyacetophenone: Equilibrium Temperature, Kinetic Barrier, and the Relative Stability of <i>Z</i>′ = 1 and <i>Z</i>′ = 2 Forms

Particularly relevant in the context of polymorphism is understanding how structural, thermodynamic, and kinetic factors dictate the stability domains of polymorphs, their tendency to interconvert through phase transitions, or their possibility to exist in metastable states. These three aspects were investigated here for two 4′-hydroxyacetophenone (HAP) polymorphs, differing in crystal system, space group, and number and conformation of molecules in the asymmetric unit. The results led to a Δ_f<i>G</i>_m°-<i>T</i> phase diagram highlighting the enantiotropic nature of the system and the fact that the <i>Z</i>′ = 1 polymorph is not necessarily more stable than its <i>Z</i>′ = 2 counterpart. It was also shown that the form II → form I transition is entropy driven and is likely to occur through a nucleation and growth mechanism, which does not involve intermediate phases, and is characterized by a high activation energy. Finally, although it has been noted that conflicts between hydrogen bond formation and close packing are usually behind exceptions from the hypothesis of <i>Z</i>′ = 1 forms being more stable than their higher <i>Z</i>′ analogues, in this case, the HAP polymorph with stronger hydrogen bonds (<i>Z</i>′ = 2) is also the one with higher density