Tartaric acid, resolution

Synthesis The analgesic activity of racemorphan is due to the (-) isomer, levorphanol, which is obtained by resolving the racemate with (+)-D-tartaric acid. Resolution can also be carried out on the intermediate 1-(4-Methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydro-isoquinoline 6 prior to N-methylation (Grewe 1946, Schnider and Hellerbach, 1950, Schnider and Griissner, 1951, Ehrhart and Ruschig 1972, Kleemann et al. 1999). 

Know the meaning of diastereomer, meso compound, lactic acid, tartaric acid, resolution. 

Tartaric acid is noteworthy for a) the excellent way in which the majority of its salts Crystallise, and h) the frequent occurrence of salts having mixed cations. Examples of the latter are sodium potassium tartrate (or Rochelle salt), C4H40 NaK, used for the preparation of Fehling s solution (p. 525), sodium ammonium tartrate, C4H OaNaNH4, used by Pasteur for his early optical resolution experiments, and potassium antimonyl tartrate (or Tartar Emetic), C4H404K(Sb0). The latter is prepared by boiling a solution of potassium hydrogen tartrate (or cream of tartar ) with antimony trioxide,... 

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

The separation of a racemic mixture into its enantiomeric components is termed resolution The first resolution that of tartaric acid was carried out by Louis Pasteur m 1848 Tartaric acid IS a byproduct of wine making and is almost always found as its dextrorotatory 2R 3R stereoisomer shown here m a perspective drawing and m a Fischer projection... 

The f-base-d-acW salt no longer can be obtained pure when the solution contains about equal proportions of the salts of d- and f-amines. For this reason, also, an initial resolution of the df-amine with d-tartaric acid is not feasible. 

The present method is adapted from that of Loven. The resolution has been carried out with d-a-bromocamphor-TT-sulfonic acid (f-form) 2.3 with /-and d/-malic acids (d- and /-forms) with /-quinic acid and d-tartaric acid (d- and /-forms) and with d- and /-6,6 -dinitrodiphenic acids (d- and /-forms). Methods employing d-benzyimethylacetyl chloride, d-oxymeth-ylenecamphor, /-quinic acid, and d-camphoric anhydride are of theoretical interest only. The d/-amine is not resolved by the active camphor-lo-sulfonic acids or mandelic acids. ... 

Hoshino and Kobayashi (1933) have also described the resolution of di-eserethole by crystallising the mixed d-hydrogen tartrates from alcohol, when d-eserethole d-hydrogen tartrate [m.p. 173-4°, [a]D ° + 113° (HgO) ] separated first. The base recovered from the mother liquors yielded with 1-tartaric acid, l-ha.se i-hydrogen tartrate (m.p. 173-4°, [ajj, — 113°). The active picrates had m.p. 133-6° and the di-picrate m.p. 132°. 

Pacemic acid, i22, resolution of, 123 Ping-burner, 108 Rotation of ethyl tartrate, 120 tartaric acid, 120... 

Unequivocal syntheses of cis- and mns-(i -decahydroquinoxalincs have been achieved by lithium aluminum hydride reduction of the corresponding cis- and trans-decahydroquinoxaIin-2-ones. The latter compounds were prepared by condensation of chloroacetic acid and cis- and trans-1,2-diaminocyclohexane, respectively. The resolution of frans-dUdecahydroquinoxaline was effected by use of first dibenzoyl-cZ-tartaric acid and then of dibenzoyl- -tartaric acid. "" (C/. p. 215.)... 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

BE 613 545 (American Cyanamid appl. 6.2.1962 USA-prior. 23.1.1962). racemate resolution p/ (+)-2-aminobutanol with tartaric acid ... 

Enantiopure (R)- and (S)-nipecotic acid (Nip) derivatives 64 were obtained following classical resolution of ethyl nipecotate with either enantiomer of tartaric acid and successive recrystallization of the corresponding salts [153, 154, 156] or by resolution of racemic nipecotic acid with enantiomerically pure camphorsul-fonic acid [154]. N-Boc protected pyrrolidine-3-carboxylic acid (PCA) 65 for the synthesis of homo-ohgomers [155] was prepared by GeUman from trans-4-hydroxy-L-prohne according to a known procedure [157]. 

A patent procedure for formation of compounds 19 from simple tartaric acid derivatives has appeared <06USP047129> and various new routes to chiral dioxolanones include synthesis of dioxolan-2-ones either by transition metal-mediated asymmetric synthesis <06T1864> or enzyme-mediated kinetic resolution <06H(68)1329> and a new synthesis of the chiral dioxolan-4-ones 21 from lactic or mandelic acid involving initial formation of intermediates 20 with trimethyl orthoformate in cyclohexane followed by reaction with pivalaldehyde <06S3915>. 

TAPA, see (+)- and (-)-a-(2,4,5,7-Tetranitro-9-fluorenylideneami-nooxy)propionic acid Tartaric acid, in resolution of a-phenylethylamine, 49, 93... 

Some other methods of resolution include the use of /-malic acid [(+)-form], /- and d/-malic acids [(+)- and (—)-forms], /-malic acid and d-tartaric acids [(+)- and (—)-forms], d-a-bro-mocamphor-TT-sulfonic acid [(—)-form], /-quinic and d-tartaric acids [(+)- and (—)-forms], 2,3,4,6-tetraacetyl-D-glucose [(+)-form], " and barium (—)-bornyl sulfate [(+)- and (—)-forms]."... 

The bases generally employed in such resolutions have been natural alkaloids, such as strychnine, brucine, and ephedrine. These alkaloids are more complex than the general case shown in the figure, in that they contain several chiral centres (ephedrine is shown in Section 3.4.4). Tartaric acid (see Section 3.4.5) has been used as an optically active acid to separate racemic bases. Of course, not all materials contain acidic or basic groups that would lend themselves to this type of resolution. There are ways of introducing such groups, however, and a rather neat one is shown here. 

It is noteworthy that a safer and more efficient synthesis of catalysts 15 and 16 was recently developed involving a classical resolution of racemic 15 and 16 using commercially available tartaric acids [101],... 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

An efficient and simple kinetic resolution of the racemic Betti base 387 was achieved via its reaction with acetone in the presence of L-(- -)-tartaric acid. When a suspension of racemic 387 in acetone was treated with L-(- -)-tartaric acid, the (A)-enantiomer formed a crystalline L-tartrate salt 389 this was filtered off, and the (iJ)-enantiomer could be isolated as a naphth[l,2-< ]oxazine derivative 388 from the filtrate (Equation 41). Both enantiomers were obtained in excellent yields and ee s. The enantioseparation is presumed to take place via a kinetically controlled N,0-deketalization of the (3)-naphth[l,2-< ]oxazine derivative <2005JOC8617>. An improved method for the enantioseparation of 387 was developed by the reaction of the ring-chain tautomeric l,3-diphenyl-3,4-dihydro-2//-naphth[2,l-< ][l,3]oxazine (41 X, Y = H) and L-(-f)-tartaric acid, yielding the crystalline 389 in 85% yield <2007SL488>. 

Shortly after the first announcement of optical resolution of ( )-cyclooctene, Moscowitz and Mislow 13) published a communication in which, on the basis of their MO calculation/they assigned the (S)-configuration to the (—)-enantiomer. Eventually, this conclusion was proved wrong 14,15) and the opposite configuration was assigned when the absolute configuration of (—)-( )-cyclooctene was shown to be directly correlated with that of (+)-tartaric acid 16a,b). 

Salts have been prepared with optically active camphor sulphonic acids. These also are yellow crystalline bodies, but no resolution of the base has been effected. d-Camphoric acid, d-tartaric acid, and d-nitro-camphor compounds were also prepared, and again no resolution was effected. Hence it is concluded that the hydroxo- and nitroso-groups are probably in the 1-, 0-, or trans-position. 

The resolution of the salts was accomplished by means of sodium d-eamphor nitronate or by the action of chloride with tartaric acid. In each case the 1-salt separated first, leaving the d-salt in solution in the mother-liquor. 

The first described synthesis of the enantiomeric cetirizine employed resolution of a ( )-chlorobenzhydrylainine as the salt with tartaric acid. Later, an asymmetric synthesis was reported by the Corey group in 1996 (Scheme 7). The pivotal step involved a chiral oxazaborolidine (CBS)-catalyzed reduction of an unsymmetrical chlorobenzophenone with a Tt-chromium tricarbonyl group serving as an effective... 

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