135:
83:. The derivatives which are then separated by conventional crystallization, and converted back to the enantiomers by removal of the resolving agent. The process can be laborious and depends on the divergent solubilities of the diastereomers, which is difficult to predict. Often the less soluble diastereomer is targeted and the other is discarded or
452:
Yoshito Fujima; Masaya
Ikunaka; Toru Inoue; Jun Matsumoto (2006). "Synthesis of (S)-3-(N-Methylamino)-1-(2-thienyl)propan-1-ol: Revisiting Eli Lilly's Resolution-Racemization-Recycle Synthesis of Duloxetine for Its Robust Processes".
351:
Kuhn, Reinhard.; Erni, Fritz.; Bereuter, Thomas.; Haeusler, Johannes. (1992-11-15). "Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis".
280:
and concentrated. Two millimeter-sized d- and l-crystals are added and after stirring for 125 hours at 40 °C two large d- and l-crystals are recovered in 50% yield.
826:
269:
with a d-crystal on one side of the reactor and a l-crystal on the opposite side, crystals of opposite handedness will form on the opposite sides of the reactor.
831:
167:. The alcohol (S)-enantiomer forms an insoluble diastereomeric salt with the mandelic acid and can be filtered from the solution. Simple deprotonation with
57:
resolution to obtain enantiomerically pure compounds has the disadvantage of necessarily discarding at least half of the starting racemic mixture.
632:
692:
292:
112:
171:
liberates free (S)-alcohol. In the meanwhile the (R)-alcohol remains in solution unaffected and is recycled back to the racemic mixture by
502:
394:
328:
287:
of one of the enantiomers. For example, seed crystals of (â)-hydrobenzoin induce crystallization of this enantiomer from an
685:
616:
87:
for reuse. It is common to test several resolving agents. Typical derivatization involves salt formation between an
864:
217:, a base that forms diastereomeric salts with chiral acids. Many related chiral amines have been demonstrated.
849:
678:
859:
304:
384:
202:
95:. Simple deprotonation then yields back the pure enantiomer. Examples of chiral derivatizing agents are
702:
821:
196:
75:
69:
The most common method for chiral resolution involves conversion of the racemic mixture to a pair of
926:
747:
455:
410:
481:
F. P. Dwyer; F. L. Garvan (1960). "Resolution of cis -Dinitrobis(ethylenediamine)cobalt Ion".
885:
799:
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266:
895:
880:
731:
208:
58:
8:
793:
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146:
854:
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434:
214:
307:
the stationary phase is made chiral with similar resolving agents as described above.
648:
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134:
124:
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890:
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Another form of direct crystallization is preferential crystallization also called
254:
168:
39:
900:
788:
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277:
262:
92:
27:
494:
70:
920:
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108:
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96:
430:
228:
905:
778:
721:
258:
84:
606:
380:
222:
660:
646:
Harold E. Zaugg (1955). "A Mechanical
Resolution of dl-Methadone Base".
545:
Mohacsi, E.; Leimgruber, W. (1976). "(S)-(â)-α-(1-Naphthyl)ethylamine".
365:
773:
242:
128:
35:
467:
273:
238:
54:
321:
Chirotechnology: industrial synthesis of optically active compounds
250:
157:
288:
153:
143:
100:
31:
386:
Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure
205:, an anion, that forms diastereomeric salts with chiral cations.
16:
Separation of a sample of a chiral compound into its enantiomers
389:(6th ed.), New York: Wiley-Interscience, p. 173-179,
272:
Spontaneous resolution has also been demonstrated with racemic
61:
of one of the enantiomers is one means of avoiding this waste.
378:
88:
211:, an acid that forms diastereomeric salts with chiral amines
276:. In a typical setup 50 grams dl-methadone is dissolved in
43:
700:
123:
One modern-day method of chiral resolution is used in the
64:
253:
crystals. These experiments underpinned his discovery of
229:
Spontaneous resolution and related specialized techniques
350:
518:
A. W. Ingersoll (1937). "D- and l-α-Phenylethylamine".
480:
580:)-(â)-1,1'-Binaphthyl-2,2'-diyl Hydrogen Phosphate".
489:. Inorganic Syntheses. Vol. 6. p. 195-197.
225:
consists of many widely available resolving agents.
607:Jean Jacques, André Collet, Samuel H Wilen (1981).
832:Ultravioletâvisible spectroscopy of stereoisomers
572:Jacques, J.; Fouquey, C. (1989). "Enantiomeriic (
544:
408:
918:
160:to which solution is added optically active (S)-
645:
517:
298:
38:. It is an important tool in the production of
571:
686:
257:. In 1882 he went on to demonstrate that by
631:: CS1 maint: multiple names: authors list (
693:
679:
190:
249:to separate left-handed and right-handed
46:. Another term with the same meaning is
609:Enantiomers, racemates, and resolutions
315:
103:. The method was introduced (again) by
65:Crystallization of diastereomeric salts
919:
487:âDinitrobis(ethylenediamine)cobalt Ion
674:
179:in toluene. This process is known as
245:crystals. This phenomenon allowed
13:
310:
133:
73:derivatives by reacting them with
14:
938:
827:NMR spectroscopy of stereoisomers
865:Diastereomeric recrystallization
639:
185:Resolution-Racemization-Recycle
600:
565:
538:
511:
474:
445:
402:
372:
344:
1:
337:
152:is dissolved in a mixture of
118:
107:in 1853 by resolving racemic
860:Chiral column chromatography
411:"Resolution of chiral drugs"
305:chiral column chromatography
299:Chiral column chromatography
7:
241:crystallize as mixtures of
203:Antimony potassium tartrate
183:in which the R's stand for
10:
943:
822:Chiral derivatizing agents
703:enantioselective synthesis
495:10.1002/9780470132371.ch62
409:William H. Porter (1991).
194:
111:with optically active (+)-
76:chiral derivatizing agents
873:
840:
809:
761:
709:
285:resolution by entrainment
233:Via the process known as
197:Chiral derivatizing agent
748:Supramolecular chirality
594:10.15227/orgsyn.067.0001
559:10.15227/orgsyn.055.0080
532:10.15227/orgsyn.017.0080
323:. New York, NY: Dekker.
267:sodium ammonium tartrate
251:sodium ammonium tartrate
142:In one of its steps the
431:10.1351/pac199163081119
319:, Roger Arthur (1993).
191:Common resolving agents
81:chiral resolving agents
24:enantiomeric resolution
456:Org. Process Res. Dev.
235:spontaneous resolution
139:
30:for the separation of
886:Chiral pool synthesis
800:Diastereomeric excess
137:
42:compounds, including
896:Asymmetric catalysis
881:Asymmetric induction
354:Analytical Chemistry
209:Camphorsulfonic acid
59:Asymmetric synthesis
794:Enantiomeric excess
661:10.1021/ja01615a084
379:Smith, Michael B.;
366:10.1021/ac00046a026
34:mixture into their
891:Chiral auxiliaries
855:Kinetic resolution
753:Inherent chirality
738:-symmetric ligands
215:1-Phenylethylamine
140:
48:optical resolution
26:, is a process in
914:
913:
850:Recrystallization
842:Chiral resolution
649:J. Am. Chem. Soc.
520:Organic Syntheses
504:978-0-470-13237-1
468:10.1021/op060118l
396:978-0-471-72091-1
360:(22): 2815â2820.
330:978-0-8247-9143-8
177:hydrochloric acid
125:organic synthesis
20:Chiral resolution
934:
817:Optical rotation
762:Chiral molecules
727:Planar chirality
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425:(8): 1119â1122.
419:Pure Appl. Chem.
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291:solution of (±)-
255:optical activity
169:sodium hydroxide
79:, also known as
40:optically active
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927:Stereochemistry
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901:Organocatalysis
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789:Racemic mixture
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743:Axial chirality
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710:Chirality types
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311:Further reading
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278:petroleum ether
237:, 5-10% of all
231:
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93:carboxylic acid
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28:stereochemistry
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12:
11:
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483:Resolution of
473:
462:(5): 905â913.
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263:supersaturated
230:
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195:Main article:
192:
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99:and the amine
71:diastereomeric
66:
63:
15:
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3:
2:
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784:Meso compound
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618:0-471-08058-6
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247:Louis Pasteur
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210:
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204:
201:
200:
198:
188:
186:
182:
181:RRR synthesis
178:
174:
173:epimerization
170:
166:
163:
162:mandelic acid
159:
155:
151:
148:
145:
138:RRR synthesis
136:
132:
130:
126:
116:
114:
110:
109:tartaric acid
106:
105:Louis Pasteur
102:
98:
97:tartaric acid
94:
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62:
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45:
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37:
33:
29:
25:
21:
906:Biocatalysis
841:
779:Diastereomer
769:Stereoisomer
732:
722:Stereocenter
701:Concepts in
655:(10): 2910.
652:
647:
641:
608:
602:
585:
581:
577:
576:)-(+)- and (
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385:
381:March, Jerry
374:
357:
353:
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293:hydrobenzoin
284:
282:
271:
265:solution of
234:
232:
220:
184:
180:
164:
149:
141:
127:of the drug
122:
113:cinchotoxine
80:
74:
68:
52:
47:
23:
19:
18:
243:enantiopure
223:chiral pool
53:The use of
36:enantiomers
774:Enantiomer
582:Org. Synth
547:Org. Synth
338:References
129:duloxetine
119:Case study
874:Reactions
717:Chirality
627:cite book
611:. Wiley.
274:methadone
239:racemates
85:racemized
921:Category
810:Analysis
439:35860450
383:(2007),
158:methanol
317:Sheldon
289:ethanol
259:seeding
154:toluene
147:alcohol
144:racemic
101:brucine
32:racemic
615:
553:: 80.
526:: 80.
501:
437:
393:
327:
91:and a
55:chiral
588:: 1.
435:S2CID
414:(PDF)
175:with
89:amine
44:drugs
22:, or
802:(de)
796:(ee)
633:link
613:ISBN
499:ISBN
391:ISBN
325:ISBN
221:The
156:and
657:doi
590:doi
555:doi
528:doi
491:doi
485:cis
464:doi
427:doi
362:doi
303:In
923::
653:77
629:}}
625:{{
586:67
584:.
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460:10
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358:64
356:.
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261:a
187:.
131::
115:.
50:.
736:2
733:C
694:e
687:t
680:v
663:.
659::
635:)
621:.
596:.
592::
578:R
574:S
561:.
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368:.
364::
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165:3
150:1
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
