Preparative resolution of some 5,5‐hydantoin derivatives via formation of diastereoisomeric salts

Abstract

Several preparative resolutions of 5,5-disubstituted hydantoins have been achieved via fractional crystallization of diastereoisomeric salts. The process can be extended by making use of the difference between the variation of solubilities of the hydantoins and their salts with a-methylbenzylamine as a function of the alkalinity of the medium. Optimization for each resolution procedure involves a refinement of the excess amount of base needed. 0 1992 Wiley-Liss, Inc.

Processes To Separate Enantiomers

“…[99,[110][111][112][113][114][115][116][117] Selected applications of preferential crystallization will be presented and discussed in chapter 3.3 below. There, advanced process concepts such as an auto-seeded polythermal process mode, first introduced by Coquerel and coworkers, [118] innovative crystallizer configurations and the extension of applying preferential crystallization to racemic compounds in integrated process schemes will be addressed. With regard to the latter, the ability of tailor-made ("molecularly" designed) additives to selectively inhibit the crystallization of the racemic compound and, accordingly, to support enantioselective crystallization in such systems was studied and reported.…”

Is the optical rotation sign/absolute configuration relationship still a problem? Examples taken from unnatural quaternary aminoacids

“…12,13 Preferential crystallization using the auto seeded programmed polythermic preferential crystallization (AS3PC) method 14 at the hydantoin stage afforded each enantiomer in optically pure form: 15 hydrolysis of hydantoin (þ)-2b in basic conditions afforded the corresponding aminoacid (þ)-a-methyl-a-(p-bromophenyl)glycine 1b with a complete conversion. 16,2 Preparative HPLC of an aliquot allowed us to get rid of any sodium chloride, in order to ensure chemical purity and therefore an accurate measurement of the optical rotation of the aminoacid; apart from the sign of the optical rotation, large discrepancies could also be found in the various optical rotations reported in the literature for a-methyl-a-phenylglycine (Fig.…”

Verfahren zur Enantiomerentrennung

“…[99,[110][111][112][113][114][115][116][117] Ausgewählte Anwendungen der Bevorzugten Kristallisation werden in Abschnitt 3.3 vorgestellt und diskutiert. Insbesondere werden fortgeschrittene Verfahrenskonzepte, wie die von Coquerel und Mitarbeitern eingeführte polytherme Auto-Seeding-Variante, [118] innovative Kristallisatorkonfigurationen und die erweiterte Anwendung der Bevorzugten Kristallisation auf Systeme mit racemischen Verbindungen in integrierten Verfahren betrachtet. Im Hinblick auf Letzteres wurde der Einsatz maßgeschneiderter Additive zur selektiven Hemmung der Kristallisation der racemischen Verbindung und damit der Unterstützung der enantioselektiven Kristallisation untersucht und beschrieben.…”

“…verfolgt werden. [174][175][176] [118] [175] Mit einer mittleren Ausbeute von 4.1 % pro Halbzyklus [175] scheint die durchgeführte Trennung laut Schätzungen von Collet wirtschaftlich attraktiv zu sein. [94] Wie…”