Three different types of chirality‐driven crystallization within the series of uniformly substituted phenyl glycerol ethers

Abstract

Seven chiral arylglycerol ethers 2-R-C(6)H(4)-O-CH(2)CH(OH)CH(2)OH (R = H, Me, Et, Allyl, n-Pr, i-Pr, tert-Bu) were synthesized in racemic and scalemic form. The IR spectra, melting points, and enthalpies of fusion for racemic and scalemic samples of every species were measured, the entropies of enantiomers mixing in the liquid state and Gibbs free energies of a racemic compound formation were derived and binary phase diagrams were reconstructed for the whole family. Solid racemic compounds stabilities were ranked for the four substances. Spontaneous resolution was established for the registered chiral drug mephenesin and its ethyl analogue. Metastable anomalous conglomerate, forming crystals having three independent R* and one independent S* molecules in the unit cell, is formed during solution crystallization of tert-butyl derivative; metastable phase transforms slowly into traditional racemic conglomerate.

From racemic compounds through metastable to stable racemic conglomerates: crystallization features of chiral halogen and cyano monosubstituted phenyl glycerol ethers

“…16 5 Ar H). 13 .08-4.14 (m, 1H, CH), 6.81 (m, 1H, C 6 Ar H), 6.92 (m, 1H, C 2 Ar H), 6.95 (m, 1H, C 4 Ar H), 7.20 (t, J = 8.1 Hz 1H, C 5 Ar H). 13 C NMR spectrum was identical with that cited above for rac-6a.…”

“…In addition, a quantitative measure, which allows ranking the observed properties for all the compounds studied, would be desirable. In our previous papers, this approach was successfully applied to a series of o-halogen, 5 o-alkyl, 6 and o-alkoxysubstituted 7 phenyl glycerol ethers of the general formula 1.…”

Stereoselective Crystallization as a Basis for Single‐Enantiomer Drug Production

“…A third example of the final racemic API, which we were able to resolve by the entrainment procedure, proved to be the muscle relaxant mephenesin 42 i. The binary phase diagram for 42 is typical for a normal conglomerate and it was possible to organize the robust process of resolution by entrainment for racemic mephenesin in water .…”

Crystallographic evidence of side-arm lariat effect in the series of chiral ortho- and para-methoxyphenoxymethyl-15-crown-5 complexes with sodium perchlorate

“…(S)-3-(4-Methoxyphenoxy)propane-1,2-diol, (S)-6 was prepared by analogy with a published procedure [8] from 4-methoxyphenol and (S)-3-chloropropane-1,2-diol (S)-5. Mp 79-81°C (n-hexane/benzene) ½a 20 D ¼ þ7:5 (c 0.6, EtOH); 95% ee [7].…”