酒石酸拆分

PLEASE SCROLL DOWN FOR ARTICLE This article was downloaded by: [Huazhong University of Science and Technology] On: 26 May 2010 Access details: Access Details: [subscription number 918088208] Publisher Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37- 41 Mortimer Street, London W1T 3JH, UK Organic Preparations and Procedures International Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t902189982 TARTARIC ACID AND ITS O-ACYL DERIVATIVES. PART 2. APPLICATION OF TARTARIC ACID AND OF O-ACYL TARTARIC ACIDS AND ANHYDRIDES. RESOLUTION OF RACEMATES Ludwik Synoradzkia; Urszula Bernaśa; Pawel Ruśkowskia a Laboratory of Technological Processes, Faculty of Chemistry, Warsaw University of Technology, Warsaw, POLAND To cite this Article Synoradzki, Ludwik , Bernaś, Urszula and Ruśkowski, Pawel(2008) 'TARTARIC ACID AND ITS O- ACYL DERIVATIVES. PART 2. APPLICATION OF TARTARIC ACID AND OF O-ACYL TARTARIC ACIDS AND ANHYDRIDES. RESOLUTION OF RACEMATES', Organic Preparations and Procedures International, 40: 2, 163 — 200 To link to this Article: DOI: 10.1080/00304940809458084 URL: http://dx.doi.org/10.1080/00304940809458084 Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. ORGANIC PREPARATIONS AND PROCEDURES INT., 40 (2). 163-200 (2008) TARTARIC ACID AND ITS 0-ACYL DERIVATIVES . PART 2 . APPLICATION OF TARTARIC ACID AND OF 0-ACYL TARTARIC ACIDS AND ANHYDRIDES . RESOLUTION OF RACEMATES Ludwik Synoradzki. * Urszula Bema5 and Pawd RuSkowski Laboratory of Technological Processes. Faculty of Chemistry Warsaw University of Technology Noakowskiego 3 Street. 00-664 Warsaw. POWVD e-mail: Ludwik.Synoradzki@ch pw .ed up1 INTRODUCTION ...................................................................................................................... 165 I . RESOLVING AGENT ........................................................................................................... 167 1 . Resolution via Diastereomeric Salt Formation ................................................................... 167 a) Resolved Compounds ..................................................................................................... 168 b) Resolving Agent .............................................................................................................. 17 1 c) Resolution by Formation and Fractional Crystallization of Diastereomeric Salts ...... 173 e) Alternative Methods of Separation of Diastereomeric Salts ......................................... 179 d) Selection of the Resolution Optimal Parameters ........................................................... 175 f) Industrial Aspect ............................................................................................................. 1 80 2 . Resolution via Diastereomeric Complex Formation .......................................................... 181 a) Resolved Compounds ..................................................................................................... 182 b) Resolving Agent .............................................................................................................. 184 c) Techniques of Resolution via Complex Formation ........................................................ 186 3 . Resolution via Diastereomeric Compound Formation ....................................................... 186 I1 . DERIVATIZATING AGENT ............................................................................................. 187 I . Derivatization of Alcohols .................................................................................................. 188 2 . Derivatization of Amines .................................................................................................... 188 111 . CHIRAL MATERIAL FOR CHROMATOGRAPHY ................................................... 188 1 . Chiral Additive .................................................................................................................... 189 a) impregnated Silica Plates .............................................................................................. 189 b) Chiral Mobile Phase Additives ...................................................................................... 189 c) Chiral Stationary Phases ................................................................................................ 190 2 . Templating Agent ................................................................................................................ 193 6 2008 by Organic Preparations and Procedures Inc . 163 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 SYNORADZKI. BERNAS AND RUSKOWSKI IV . SUMMARY .......................................................................................................................... 193 REFERENCES ........................................................................................................................... 194 164 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 TARTARIC ACID AND ITS 0-ACYL DERIVATIVES. PART 2 TARTARIC ACID AND ITS 0-ACYL DERIVATIVES. PART 2. APPLICATION OF TARTARIC ACID AND OF 0-ACYL TARTARIC ACIDS AND ANHYDRIDES. RESOLUTION OF RACEMATES Ludwik Synoradzki," Urszula Bema5 and Pawel Ruhkowski Laboratory of Technological Processes, Faculty of Chemistry Warsaw University of Technology Noakowskiego 3 Street, 00-664 Warsaw, POLAND e-mail: Ludwik.Synoradzki@ ch .pw .edu p l INTRODUCTION The history and popularity of tartaric acid (1) and its application (Fig. I) started 150 years ago with Pasteur's discovery of L and D enantiomers of 1 and of their optical activity. Toward the end of the 19" century, Pasteur successfully resolved tartaric acid into its enan- tiomers by manual separation of enantiomorphous tartaric acid ammonium salts and by selective crystallization of tartaric acid salt formed in the reaction of the racemate with the chiral base cinchonicine. The latter method was in fact the first resolution via diastereomeric salt formation. These innovative experiments were a cornerstone in stereochemistry in general as they intro- duced tartaric acid into the chemistry of chiral compounds. From this time on, tartaric acid has become popular and attractive molecule, which is still being used in all the field of asymmetric chemistry allowing one to prepare individual enantiomers on different ways. Thus, tartaric acid 1 (Fig. 2a) and its acyl derivatives 2 and 3 (Fig. 2b) play an impor- tant role as building blocks in the synthesis from the chiral pool. They have been successfully used in the asymmetric synthesis as chiral auxiliaries or as chiral ligands applied in numerous catalysts. Compounds 1-3 also find application in chromatography as additives or templates in the formation of chiral materials and as a derivatizating agent in the sample functionalization. Despite those various uses of 1-3, their utillization as resolving agents is the major application. Since the monograph of Gawronski and Gawronska covers the literature concerning the use of tartaric acid in synthesis up to 1997,'" we decided to write this review to illustrate new examples and the continued interest in novel applications. In view of the large amount of publications and 165 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 SYNORADZKI, BERNAS AND RUSKOWSKI Resolving Resolution via diastereomers agent [Yp Derivafizating Analysis , * - C h i d - . material L Kinetic resolution L Preferential crystallization Chiral builin block Chiral auxiliary Biocatalysis C h i d ligand Chemocataly sis Routes to Enantiopure Compounds with Highlighted Possibilities of Application of Tartaric Derivatives depicted in gray Fig. 1 of patents showing the use of tartaric acid derivatives over the last decade, this review describes only the applications of 1-3 in the resolution of racemates since 1998; other applications will be described in the next review. 0 Ho$; Ho/j$H OH HO\\" HO 0 0 L- 1 D-1 Tartaric Acids (1) Fig. 2a RC02+0H OH R = a) Me b) e) t-Bu 0 L Most Commonly used Diacyltartaric Acids (2) and Anhydrides (3) Fig. 2b 166 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 TARTARIC ACID AND ITS 0-ACYL DERIVATIVES. PART 2 I. RESOLVING AGENT Following the US FDA policy statements (1992) which allow marketing of new chiral drugs only in enantiomerically pure forms, there has been a growing interest in the isolation of enantiomers? Resolution of racemates via diastereomeric intermediates is still the major method, applicable also on the industrial ~cale.3.~ It is based on the derivatization of racemic mixture and the subsequent separation of the resulting diastereomeric derivatives. The isolation of the diastereomers can be achieved because, contrary to enantiomers, they differ in physical and chemical properties. Therefore resolution may be accomplished via conventional achiral methods, such as distillation? and most often crystallization, as well as by other physical manip- ulations such as supercritical fluid extraction for example.‘.* Depending on the type of bonds formed between resolving agent and enantiomer, resolution can be achieved via diastereomeric salts (ionic), diastereomeric compounds (covalent) or diastereomeric complexes (hydrogen bond). The specific diacidic structure of 1 and 2 enables convenient formation of diastereomeric salts, in contrast to anhydrides 3 which are utilized in the preparation of diastereomeric esters and amides. The unique three-dimensional arrangement of 1 and 2 has also been used in the forma- tion of diastereomeric host-guest type complexes. The advantages provided by the structure of 1- 3 coupled with their high purity, stability and availability, make them the most widely used resolving agents. The application of other acidic resolving agents such as L-aspartic, L-glutamic, malic, mandelic, N-(p-toluenesulfony1)glutamic and quinic acids has been described in a CRC Handbook edited by Kozma? 1. Resolution via Diastereomeric Salt Formation Generally, the formation of ionic bonds between the basic racemic mixture and acid 1 or 2 proceeds readily and quantitatively. Isolation of individual enantiomer from the resulting intermediate salts is also generally rapid and efficient. This makes resolution via diastereomeric salt formation with 1 and 2 an attractive route to obtain enantiomerically pure compounds. The structure and stoichiometry of diastereomeric salts of amines and diacids such as 1 and 2 has been investigated.”-13 There are a ~ i d i c ’ ~ . ’ ~ and n e ~ t r a l ’ ~ . ’ ~ salts, depending on the number of amine equivalents bonded to the diacid (one or two for monoamines, respectively). Unfortunately, sometimes the mixed enantiomer neutral salts may also be formed, when 1 or 2 are combined with both enantiomers of an amine, leading to significant decreases in ee. The type of diastereomeric salt formed (1 : 1 or 1 :2) has a considerable influence on the efficiency of reso- lution and may sometimes be controlled by the molar ratio of resolving agent used.12 There are examples when ee of the desired enantiomer decreaseszn or increases*’ when an acidic diastere- omeric salt is formed. This is the consequence of different solubilities of appropriate acidic and neutral diastereomeric salt pairs, which may be even reversed (resolution of 4 with D-2c).12 167 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 SYNORADZKI, BERNAS AND RUSKOWSKI a) Resolved Compounds Acids 1 and 2 have been employed for the resolution of numerous compounds, including primary (Fig. 3) , secondary (Fig. 4) and tertiary (Fig. 5) monoamines. T O H 4 5 6 Ph A NH2 NH2 7 8 Fig. 3 9 Some of these amines are very simple linear or cyclic molecules. Others have more complicated structures, possessing various functional groups or condensed rings. Resolution of dimethoxyisoquinoline derivatives (23, 24) (Fig. 4) as well as two aminooxiranes derivatives COOEt n/ I n/ "J 'OH J HN COOMe 11 12 l A 15 -. 10 13 Fig. 4 23 (26,27) (Fig. 5) was achieved. Among tertiary amines resolved by acids 1 and 2, the preparation of the enantiopure alkaloids such as narwedine 33 has been also reported (Fig. 5)F0 It appears that better resolution can be achieved, when the chiral center is close to the amine function, which forms an ionic bond with the carboxylic group of 1 or 2. Acids 1 and 2 are used to resolve racemates of polyamines, amines that are sterically crowded and bearing fused heterocyclic rings. Resolution of common diamines (35) as well as 168 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 TARTARIC ACID AND ITS 0-ACYL DERIVATIVES. PART 2 N' % I 25 Ph Ph x N 7 P h 30 A 5" Q 29 CN ("I 26 O l h 0 27 9, 28 F OMe 31 &o" \ \ / / o&N, \ g N OH 34 I Me0 33 3 32a X =-N 32b X =-NHz Fig. 5 more complicated tricyclic ethano Troger's base (39) or benzodiazepines (36, 37) was achieved with excellent results (Fig. 6). Tartaric acid (1) may be utilized for the efficient resolution of racemic a-amino acids. It is achieved by crystallization-induced asymmetric transformation (also named 2"d order asym- metric transformation) (Scheme 1): This strategy combines selective crystallization of less soluble diastereomeric salt with continuous racemization of its antipode in solution. The racem- ization is catalyzed by the addition of aldehyde (most often salicyladehyde) in carboxylic acid as a solvent. By this methodology, resolution of racemic histidine,22 h o m o c y ~ t e i n e , ~ ~ phenylalar1ine,2~ phenylglicyne,2s prolineZ6 with 1 and ~ a l i n e ~ ~ (with D-2b) in high yield (>90%) and excellent optical purity (even 100%) was accomplished. This mechanism led to the produc- tion of D-amino acids from natural L enantiomers. Resolution via diastereomeric salt of other compounds such as acid hydrazides and various non-amine phosphonium, arsonium and sulfonium salts with the help of 1 and 2,Ib as well as highly efficient chiral resolution of six-coordinate silicon (IV) complex using 2 was also The resolutions of optically active compounds demonstrated above were most often carried out for two purposes. For example, resolutions of a-phenylethylamine (4)I0J3 and of methamphetamine (11)629~30 with the help of 1 and 2 were used as a tool in basic research. On the other hand, chiral resolutions of numerous compounds utilizing 1 and 2 reveal a practical appli- cation due to the widespread interest in development of single enantiomeric drugs. For example compounds 7,16 8;I 14,2l 31,32 4733 play role as key intermediates in the synthesis of biologically active substances, compounds such as 9,3436, 37,14433s are potentially active and 15,3621,11 25,37 4038 play role as active pharmaceutical ingredients. 169 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 SYNORADZKI, BERNAS AND RUSKOWSKI 37 38 0 HN I ' 48 b 47 OH OH 49 Fig. 6 50 The great importance of applicability of 1 and 2 in the resolutions via diastereomeric salt formation is also emphasized by the large number of patents' informations. During the last decade, some useful optically active pharmaceuticals was successfully resolved (Fig. 7), amlodipine (51) with L-139 and ~ - 2 h , ~ arenolol (52) (with L-~c)?' bupivacaine (53) ( ~ - 1 ) p ephedrine (54) ( ~ - 2 ) : ~ erhambutol(55) (L-1): nefopam (56) ( ~ - 2 h ) ~ ~ and rumipriZ(57) (~-2h).@ It is noteworthy that if the structure of the diastereomeric salt formed is not established (X-Ray crystallography, 'H NMR, IR), it is not certain that the formation of salt actually occurs. This is implied by the fact that amines are as good as alcohols in being able to form supramolec- ular complexes with 1 and 2."5 Therefore it reveals possible that chiral resolutions of some compounds depicted in Figures 3-6 were achieved via the formation of diastereomeric complexes and not of salts. 170 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 TARTARIC ACID AND ITS 0-ACYL DERIVATIVES. PART 2 Solution more soluble (or less stable) diastereorneric salt \ N H3 [ RYcooH NCCRIRP] R-COOH HoYCooH HO"" COO- iH; - Precipitate of less soluble diastereorneric salt Scheme 1 b) Resolving Agent Among tartaric acid derivatives, tartaric acid (l), dibenzoyl- (2b) and di-p-toluoyltar- taric acid (2c) are most frequently used. The results of optical resolutions of previously presented amines (Fig. 3-6) accomplished by these acids are collected in Tables 1-3 respectively. Table 1. Compounds Resolved using L-1 and D-1 Cmpd Resolving Isolated ee Yield Ref. agent isomer (%) @,>. 4 L-1 (-)+)-4 72.1b 33.4b 10 6 L-1 (1S,2S)-6 92 28b 46 7 L-1 (-1-7 >95 41 16 D-1 (+)-7 >95 42b D- 1 (3-9 99 30b 9 L-1 (R)-9 99 34b 34 47 29 L-1 (+)-29 96 32a L-1 (S)-32a 98 40 48 --__ _ _ _ _ (-)-29 97 (R)-32a 75 55 32b L- 1 (S)-32b >99 48b 49 35 L-1 (RP)-35 >99.8 49 17 38 L-1 ~-(-)-38 >99 30-35 50 (SS)-35 >99.8 37 D- 1 ~-(+)-38 >99 46 L-1 (S)-46 >99 7fIb' 51 47 L-1 (R)-47 98.4 4 0 b 33 48 D-1 U0-48 98.6 41 33 a) Overall yield based on racemate; b) Result given for diastereomeric salt; c) Result of enantiomenc enrichment. 171 D o w n lo ad ed B y: [ Hu az ho ng U ni ve rs it y of S ci en ce a nd T ec hn ol og y] A t: 1 1: 41 2 6 Ma y 20 10 SYNORADZKI, BERNAS AND RUSKOWSKI Table 2. Compounds Resolved using L-2b and D-2b Cmpd Resolving Isolated ee Yield Ref. 5 8 11 12 13 14 15 20 24 26 27 36 40 43 45 L-2b ~-2b*H,0 L-2b L-2b L-2b L-2b L-2b D-2b D-2b L-2b ~-2b*H,0 ~-2b*H,0 L-2b D-2b ~-2b*H,0 L-2b D-2b L-2b D-2b (+)-(R3)-8 (-)-11 (9-12 (S)-13 (S)-14 (-)-15 (+)-15 (-HR 31-20 24 (-)-26 (-)-27 (-)-(R)36 (+)-(S)-36 (+)-(R)-40 (-)-(S)-40 (4-43 (-)-43 (-)-45 (4-45 99 97.9 61 298 >99 99.9 99.9 >98 97 >98 96 298 298 99.9 99.9 98 97 __-- ____ 35 ---- ---_ 19 >30 38 40.3 25 67" 23b 47b 24 20 22 27 ---- -