The dutch resolution variant of the classical resolution of racemates by formation of diastereomeric salts: Family behaviour in nucleation inhibition

Chemistry - A European Journal

Volumn 11, Issue 19, 2005, Pages 5619-5624

  Dalmolen, Jan ^a   Tiemersma Wegman, Theodora D ^a   Nieuwenhuijzen, José W ^b   Van Der Sluis, Marcel ^b   Van Echten, Erik ^b   Vries, Ton R ^b   Kaptein, Bernard ^c   Broxterman, Quirinius B ^c   Kellogg, Richard M ^b  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b Syncom BV   (Netherlands)

^c DSM Pharmaceutical Products   (Netherlands)

Author keywords

Chiral resolution; Chirality; Crystal growth; Diastereo selectivity; Enantioselectivity

Indexed keywords

CARBOXYLIC ACIDS; CRYSTAL GROWTH; NUCLEATION; SALTS; TURBIDITY;

CHIRAL RESOLUTION; CHIRALITY; DIASTEREO-SELECTIVITY; ENANTIOSELECTIVITY;

ORGANIC COMPOUNDS;

INORGANIC SALT;

ARTICLE; CHEMISTRY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOISOMERISM;

MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; SALTS; STEREOISOMERISM;

EID: 25444495914     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200500440     Document Type: Article

References (25)

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3. There is a possible relationship to "tailor-made additives": a) L. Addadi, Z. Berkovitch-Yellin, N. Domb, E. Gati, M. Lahav, L. Leiserowitz, Nature 1982, 290, 21-26;
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8. Calculations support the formation of solid solutions of (roughly isomorphous) diastereomeric salts: a) C. Gervais, R. F. P. Grimbergen, I. Markovits, G. J. A. Ariaans, B. Kaptein, A. Bruggink, Q. B. Broxterman, J. Am. Chem. Soc. 2004, 126, 655-662;
9. see also: b) B. Kaptein, H. Elsenberg, R. F. P. Grimbergen, Q. B. Broxterman, L. Hulshof, K. L. Pouwer, T. R. Vries, Tetrahedron: Asymmetry 2000, 11, 1343-1351;
10. c) This conclusion is an extrapolation from turbidity measurements taken by necessity at different concentrations for the pure diastereomers; a more exact explanation can be derived from the ternary phase diagram discussed in ref. [3a].
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13. Details of an efficient HPLC method to allow rapid and accurate analysis are given in the Supporting Information.
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15. All these compounds were available by means of procedures described in ref. [5].
16. A 1:1:1 mixture of enantiopure 2a, 37 and 42, the latter two of which appear to be nucleation inhibitors (Table 2) has been used in the past (ref. [1]) as a family of resolving agents ("PE-III mix").
17. The preparation of these materials by means of a Leuckart reaction and subsequent easy isolation is described in the Supporting Information.
18. Catalysts: a) R. G. Konsler, J. Karl, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120, 10780-10781;
19. bis-urea gelators: b) J. Brinksma, B. L. Feringa, R. M. Kellogg, R. Vreeker, J. van Esch, Langmuir 2000, 16, 9249-9255; amide-containing Gemini surfactants:
20. c) M. Johnsson, J. B. F. N. Engberts, J. Phys. Org. Chem. 2004, 17, 934-944.
21. 2O (20:1). On addition of additive, the crystallised material contained the (R)-2a/(S)-46 in excess.
22. 2O (20:1). On addition of additive, the crystallised material contained the (R)-2a/(R)-47 in excess.
23. 2O (5:2). On addition of additive, the crystallised material contained the (R)-2a/(R)-D-48 in excess.
24. The "habit modifier" (R,R)-bis(α-methylbenzyl)amine [K. Sakai, Y. Maekawa, K. Saigo, M. Sukegawa, H. Murakami, H. Nohira, Bull. Chem. Soc. Jpn. 1992, 65, 1747-1750], the secondary amine analog of 1-phenylethylamine 2 a, was only modestly effective and raised the S-factor for the resolution of 1 to 0.26 and that of 46 to 0.41; these results were not sufficient to encourage further investigation.
25. From turbidity measurements performed to date, we have observed that "Dutch Resolution inhibitors" have the greatest effect on the more soluble diastereomeric salt. However, not every inhibitor has been subjected to turbidity measurements.