Abstract
Despite unprecedented advances in enantioselective synthesis and separation techniques, large scale production of enantiopure substances, such as required by the pharmaceutical and pesticide industries, is still heavily dependent upon the separation of diastereomers obtained from the enantiomers and an optically active resolving agent. Economy of the process can be much enhanced when only a half-equivalent of the resolving agent is used. Substitution of the other half-equivalent by some achiral compound, as well as separation of the unreacted portion of the substrate from the diastereomer by various physical methods, is discussed. Methods for selecting optimal conditions of resolution and for the purification of partially resolved mixtures are also discussed.
1 Introduction and Historical Background
2 Resolution Methods Using a Half-Equivalent of Resolving Agent
3 Selection of the Optimal Resolving Agent and Solvent
4 Phase Transformations of Diastereomeric Salts or Complexes (Kinetic and Thermodynamic Control)
5 Resolution by Formation of Covalently Bound Diastereomers
6 Racemization of an Unwanted Enantiomer
7 Deracemization
8 Resolution of Conglomerate-Forming Racemates by Induced Crystallization
9 Purification of Partially Resolved Mixtures by Crystallization of Conglomerate-Forming and Racemic-Phase-Forming Compounds
10 Purification of a Partially Resolved Mixture of Racemic-Phase-Forming Enantiomers by Fractional Precipitation
11 Resolution by Supercritical Fluid Extraction or Distillation
12 The Non-Linear Character of the Resolution Processes
Key words
resolution of enantiomers - half-equivalent methods - choice of optimal conditions
References 1 Present-day nomenclature will be used throughout this review.
2a Helmchen G.
Hoffmann RW.
Mulzer J.
Schaumann EG.
Georg Thieme Verlag;
Stuttgart, New York:
1996.
2b Nógrádi M.
VCH;
Weinheim:
1995.
3 Catalog prices, 2004: (R )- 1,1′-binaphthol: ı 44/g; (R )-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP): ı 335/g; (-)-α-pinene: ı 12/g; (+)-α-pinene: ı 13/g; (+)-1,4-bis(diphenylphospino)-1,4-dideoxy-2,3-O -isopropylidene-d -threitol [(+)-DIOP]: ı 118/g; (R ,R )-tartaric acid: ı 46/100 g; (S ,S )-tartaric acid: ı 70/100 g; dibenzoyl-(R ,R )- tartaric acid: ı 81/100 g; (S )-lactic acid: ı 33/kg; (R )-1-phenylethylamine: ı 82/100 mL; (R )-1-phenylethylamine: ı 84/100 g; brucine hydrate: ı 83/100 g; quinine: ı112/100 g.
4 Pasteur L.
C. R. Hebd. Seances Acad. Sci.
1853,
37:
162
5 Pope WJ.
Peachey SJ.
J. Chem. Soc.
1899,
75:
1066
6a Chem. Abstr.
1958 , 54 , 11287
6b Chem. Abstr.
1984 , 79 , 104924
7 Chem. Abstr.
1978 , 96 , 6258
8 Chem. Abstr.
1968 , 71 , 50521
9 Cai D.
Hughes DL.
Verhoeven TR.
Reider PJ. In Organic Syntheses, Vol. 76
Martin SF.
John Wiley & Sons;
New York:
1998.
p.1
10 Brandt J.
Gais H.-J.
Tetrahedron: Asymmetry
1997,
8:
909
11a Chem. Abstr.
1978 , 97 , 38959
11b Fogassy E.
Ács M.
Tóth G.
Simon K.
Láng T.
Ladányi L.
Párkányi L.
J. Mol. Struct.
147,
143
12a Chem. Abstr.
1974 , 85 , 192335
12b Ács M.
Kozma D.
Fogassy E.
Ach. Mod. Chem.
1995,
132:
475
13 Rábay J.
Angew. Chem., Int. Ed. Engl.
1992,
31:
1631
14 Fogassy E.
Ács M.
Szili T.
Simándi B.
Sawinsky J.
Tetrahedron Lett.
1994,
35:
257
15 Simon H.
Ph.D. Dissertation
Technical University, Budapest;
Hungary:
2003.
16 Tanaka K.
Kato M.
Toda F.
Heterocycles
2001,
54:
405
17 Kobayashi Y.
Kodama K.
Saigo K.
Org. Lett.
2004,
6:
2941
18 Kassai Cs.
Ph.D. Dissertation
Technical University, Budapest;
Hungary:
2000.
19 Ács M.
Mravik A.
Fogassy E.
Böcskei Zs.
Chirality
1994,
6:
314
20a Kozma D.
CRC Press;
London:
2002.
20b Faigl F.
Kozma D. In Enantiomer Separation: Fundamentals and Practical Methods
Toda F.
Kluwer Academic Press;
Dordrecht:
2004.
21 Kozsda KE.
Keserž Gy.
Böcskei Zs.
Szilágyi J.
Simon K.
Bertók B.
Fogassy E.
J. Chem. Soc., Perkin Trans. 2
2000,
149
22a Chem. Abstr.
1995 , 124 , 117097
22b Chem. Abstr.
2001 , 139 , 90595
23 Bálint J.
Egri G.
Kiss V.
Gajáry A.
Juvancz Z.
Fogassy E.
Tetrahedron: Asymmetry
2001,
12:
3435
24 Sakai K.
Sakurai R.
Hirayama N.
Tetrahedron: Asymmetry
2004,
15:
1073
25 Sakai K.
Sakurai R.
Yuzawa A.
Hirayama N.
Tetrahedron: Asymmetry
2003,
14:
3713
26 Sakai K.
Sakurai R.
Nohira H.
Tanaka R.
Hirayama N.
Tetrahedron: Asymmetry
2004,
15:
3495
27 Schanz HJ.
Linseis MA.
Gilheany DG.
Tetrahedron: Asymmetry
2003,
14:
2767
28 Sakai K.
Sakurai R.
Yuzawa A.
Kobayashi Y.
Saigo K.
Tetrahedron: Asymmetry
2003,
14:
1631
29a Fogassy E.
Lopata A.
Faigl F.
Ács M.
Darvas F.
Tőke L.
Tetrahedron Lett.
1980,
21:
647
29b Fogassy E.
Faigl F.
Ács M.
Grofcsik A.
J. Chem. Res., Synop.
1981,
11:
346 ; J. Chem. Res., Miniprint
1981 , 11 , 3981
29c Fogassy E.
Faigl F.
Ács M.
Tetrahedron
1985,
41:
2837
30 Kozma D.
Pokol G.
Ács M.
J. Chem. Soc., Perkin Trans. 2
1992,
435
31 Fogassy E.
Kozma D.
Tetrahedron Lett.
1995,
36:
5069
32 Bálint J.
Egri G.
Vass G.
Schindler J.
Gajáry A.
Friesz A.
Fogassy E.
Tetrahedron: Asymmetry
2000,
11:
809
33 Chem. Abstr.
1984 , 104 , 168835
34 Gizur T.
Péter I.
Harsányi K.
Fogassy E.
Tetrahedron: Asymmetry
1996,
7:
1589
35 Kaptein B.
Elsenberg H.
Grimbergen RFP.
Broxterman QB.
Hulshof LA.
Vries T.
Tetrahedron: Asymmetry
2000,
11:
1343
36 Vries T.
Wynberg H.
van Echten E.
Kock J.
ten Hoeve W.
Kellogg RM.
Broxterman QB.
Minnard A.
Kaptein B.
van der Sluis S.
Hulshof LA.
Angew. Chem. Int. Ed.
1998,
37:
2349
37 Kellogg RM.
Nieuwenhuijzen WJ.
Pouwer K.
Vries T.
Broxterman QB.
Grimbergen RFP.
Kaptein B.
La Crois RM.
de Wever E.
Zwaagstra K.
van der Laan A.
Synthesis
2003,
1626
38 Liu A.
Mok KF.
Leung PH.
Chem. Commun.
1997,
2397
39 Mravik A.
Chem. Eur. J.
1998,
4:
1621
40 Várkonyi SE.
Takács K.
Hermecz I.
J. Heterocycl. Chem.
1997,
34:
1064
41 Robinson DEJE.
Bull SD.
Tetrahedron: Asymmetry
2003,
14:
1407
42 Eames I.
Angew. Chem. Int. Ed.
2000,
39:
885
43 Chem. Abstr.
1984 , 102 , 61849
44 Tsunoda T.
Kaku H.
Nagaku M.
Okuyama E.
Tetrahedron Lett.
1997,
38:
7759
45 Jacques J.
Collet A.
Wilen SH.
Wiley;
New York:
1981.
46 Eliel EL.
Wilen SH.
Wiley;
New York:
1994.
47 Pasteur L.
Ann. Chim. Phys.
1848,
24:
442
48 Mravik A.
Lepp Zs.
Fogassy E.
Tetrahedron: Asymmetry
1996,
718:
2387
49a Pincock RE.
Wilson KR.
J. Am. Chem. Soc.
1971,
93:
1291
49b Kondepudi DK.
Laudadio J.
Asakura K.
J. Am. Chem. Soc.
1999,
121:
1448
50a Chem. Abstr.
1978 , 97 , 6331
50b Fogassy E.
Ács M.
Tóth G.
Simon K.
Láng T.
Ladányi L.
Párkányi L.
J. Mol. Struct.
1986,
147:
143
51 Dolchi C.
Fumagalli L.
Moroni B.
Pallavicini M.
Valoti E.
Tetrahedron: Asymmetry
2003,
14:
3779
52 Tamura R.
Fujimoto D.
Lepp Z.
Misaki K.
Miura H.
Takahasi H.
Ushio T.
Nakai T.
Hirotsu K.
J. Am. Chem. Soc.
2002,
124:
13139
53a Chem. Abstr.
1979 , 99 , 22300
53b Ács M.
Pokol Gy.
Faigl F.
Fogassy E.
J. Therm. Anal.
1988,
33:
1241
54 Ács M.
Fogassy E.
Faigl F.
Tomor K.
Simon K.
Marsó K.
Mol. Cryst. Liq. Cryst.
1988,
156:
193
55 Simon H.
Kassai Cs.
Madarász Z.
Fogassy E.
Kozma D.
Chirality
2001,
13:
29
56 Noyori R.
J. Am. Chem. Soc.
1995,
117:
2675
57 Girard C.
Kagan HB.
Angew. Chem. Int. Ed.
1998,
37:
2922 ; Angew. Chem. 1998 , 110 , 3088
58 Kozma D.
Fogassy E.
Mol. Cryst. Liq. Cryst.
1996,
276:
25
59 Markovits I.
Egri G.
Fogassy E.
Chirality
2002,
14:
674
60a Kozma D.
Madarász Z.
Ács M.
Fogassy E.
Chirality
1995,
7:
381
60b Kozma D.
Simon H.
Kassai Cs.
Madarász Z.
Fogassy E.
Chirality
2001,
13:
29
