Investigating Differences and Similarities between Betaxolol Polymorphs

Betaxolol belongs to the class of β1-adrenergic blocking agent. Several polymorphs of racemic betaxolol have been reported in the literature, but only one of them (BE_I) had the crystal structure determined from single-crystal X-ray diffraction. Here, we present a new crystalline phase of betaxolol (BE_IV). Its solid-state structure has been obtained from single-crystal X-ray diffraction data. The molecular and crystal arrangements of betaxolol in BE_IV have been further investigated by molecular modelling, by Cambridge Structural Database (CSD) surveys and by Hirshfeld surface analysis. A comparison with the solid-state structure of BE_I have been carried out. In the two polymorphs the 2-hydroxy-3-(isopropylamino)-propoxy chain, which is common to other β-blocker drugs, adopts a different conformation. In addition, the rotational isomer found in BE_IV is different with respect to the four already observed in the solid-state structure of analogous compounds. In both the polymorphs, the most significant interaction is due to the H-bonds involving the OH group as donor and the NH as acceptor, while the interaction where OH works as acceptor (NH acts as donor) is definitely less important. The resulting H-bond patterns are however different: Alternate R2,2(10) a > a (OH donors) and R2,2(10) b > b (OH acceptors) in BE_I vs. alternate R4,4 (8) a > b > a > b (OH donors) and R2,2 (10) b > b (OH acceptor) in BE_IV.

Infrared Study of Phosphorous Oxychloride and Organophosphorus Compounds Containing the P(=O)Cl2 Group in Dilute Solvent Systems

The present study has shown that some normal vibrations shift to lower frequency while others shift to higher frequency as the mole % of the solvent system increases. The vP=O mode for compounds containing the P(=O)Cl2 group shifts to lower frequency with increase in the mole % CHCl3/CCl4. The P=O group is believed to be complexed with the solvent system. Both the vasym.PCl2 and vsym.PCl2 modes shift to higher frequency as the mole % CHCl3/CCl4 increases. The application of IR and different solvent systems aids in assigning rotational isomer band pairs.

An investigation of the rotational isomers of N-acetyl-2,2-dimethyloxazolidine and related compounds by nuclear magnetic resonance spectroscopy and molecular mechanics

The 15 2,2-dimethyloxazolidines described here were found to exist in solution predominantly as a single rotational isomer, unlike N-acetyloxazolidine (1), N-acetyl-2-methyloxazolidine (2), N-acetyl-2-(n-octyl)oxazolidine (3), and other known 2-substituted N-acyloxazolidines. Using 13C NMR spectroscopy, activation energies for interconversion of the E (minor) and Z (major) rotational isomers of 1–3 were determined from coalescence temperature measurements in pyridine-d5. A sample of N-acetyl-2,2-dimethyloxazolidine (4) was isolated for comparison. The rotational isomer of 4 was found by two-dimensional nuclear Overhauser effect spectroscopy (NOESY) to possess the Z (or trans) stereochemistry. Molecular mechanics (MMX) calculations on the E and Z isomers of 1–4 helped to account for these findings. The conformation of the energy-minimized structures resembled a C-5 envelope. Samples of N-aroyl-2,2-dimethyloxazolidines (5a–5n) were isolated and the rotational isomers were assigned the Z stereochemistry by NOESY and 13C NMR experiments. Most of these 2,2-dimethyloxazolidines were ineffective in a bioassay for mosquito repellent activity. Keywords: N-acyloxazolidines, N-aroyloxazolidines, NMR spectroscopy, rotational isomerism, molecular mechanics.