Dibenzoyl tartaric acid

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

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.)... 

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. 

Ryhlewska, U., and Warzajtis, B. Interplay between dipolar, stacking and hydrogen-bond interactions in the crystal structures of unsymmetrically substituted esters, amides and nitriles of (R,R)-0,0 -dibenzoyltartaric acid, Acta Cryst., Sec. B. 2001, B57, 415-427. Isostructuralism in a series of methyl ester/methylamide derivatives of (R,R)-0,0 -dibenzoyl tartaric acid inclusion properties and guest-dependent homeotypism of the crystals of (2R,3R)-0,0 -dibenzoyltartaric acid diamide, Acta Cryst., Sec. B. 2002,B58, 265-271. 

Exploiting the same concept, Reinhoudt and Shinkai were able to obtain another example of enantioenriched chiral double-rosette made of achiral components. In this case achiral calix[4]arene bearing dimelamine moieties with pyridine functionalities were assembled with achiral cyanurate leading to racemic chiral double rosettes. The latter are perfect counterparts for chiral D-dibenzoyl tartaric acid via two-point hydrogen-bonding interactions thus... 

Raw Materials Sourcing. There was relatively little problem in sourcing 5-bromoacetylsalicylamide (in-house) or dibenzoyl-(+)-tartaric acid (large tonnage Italian source). Although RS-l-methyl-3-phenylpropylamine was available at low cost ( 10-12/kg) in tonnage quantities (Germany and Holland) no supplier of the R-amine VIII was known. 

Recently, this method was replaced by a more economical route, in which instead of racemic BINAP, racemic BINAPO (7) (diphenylpho-sphinoxide) was prepared which can be resolved using camphorsulfonic acid or 2,3-0,0-dibenzoyl tartaric acid (Scheme 2, 86JOC629). 

An efficient and large scale resolution of methylphenidate (ritalin hydrochloride)using dibenzoyl-tartaric acid has been described (61). Ritalin is marketed for the treatment of children with attention deficient disorder (ADHD). Methylphenidate has two chiral centers and originally was marketed as a mixture of two racemates, 20% OL-threo (29, 30) and 80%DL-erythro (31, 32) (see Fig. 18.12 for the structures of all four isomers). As introduced previously, the erythro-isomer is defined as the case when the main chain of a molecule (drawn vertically in a Fischer projection)has identical or similar substituents at two adjacent non-identical chiral centers on the same side of the chain, whereas the threo isomer has... 

The ROA spectra of tartaric acid, dimethyl tartrate, 2,3-butanediol and dibenzoyl tartaric acid have been reported and discussed801. One striking feature in all these spectra is a large couplet at about 500 cm -1 that might originate in deformations of the twisted O—C—C—O unit. 

Even more complicated reactions can be used to racemise during a resolution. The amino ketone 102 is needed for the synthesis of the analgesic and useful asymmetric reagent (see chapter 24) DARVON. Classical resolution with dibenzoyl tartaric acid 9 succeeds in crystallising the (+) enantiomer and racemising the mother liquors by reverse Mannich reaction.25... 

The separation problem was solved by esterifying racemic 10 with succinic anhydride. The (R)-ester 145 now has a free carboxylic acid group and can be separated simply by extraction with weak base (NaHC03) without any chromatography. The ester is easily hydrolysed to (5)-(+)-10 which was obtained in 32% overall yield (maximum 50%) and 98.9% ee. They do not say whether they prefer this resolution to the classical version with dibenzoyl tartaric acid but both are good. 

R,3R)-(—)-dibenzoyl tartaric acid and partially resolved by chromatography on d-( + )-lactone. ... 

Blue (a) resolved using (—) dibenzoyl +) tartaric acid, red-brown (fi) green (trans) Brown trans configuration, IR, H NMR... 

Scheme 13 (Bottom of facing page). Synthesis of WIN55,212-2 (65). Reagents and conditions (a) (i) TFAA, DMSO, CH2CI2, -78°C, (ii) EtsN (b) H2, Ra-Ni, EtOAc (c) dibenzoyl tartaric acid, MeOH (d) NaN02, HCl (e) LiAlU, THE (f) 1-naphthoylace-tone, C6H5CH3, H+, reflux (g) AcOH, reflux.

If the racemic compound is reacted with half an equivalent amount of resolving agent, the enantiomeric mixture remained after crystallization can be separated by distillation. Such a method was accomplished at the resolution of N-methyl-phenylisopropylamine (MA) by (R,R)-dibenzoyl-tartaric acid ((R,R)-DBTA). In this case the (S)-MA was distilled off beside of crystalline (R)-MA(R,R)-DBTA salt. 25... 

The preparation of the optical isomers of reticuline has been done by Battersby et al. 109) by resolving 0,0-dibenzyl-( + )-reticuline with 0,0-dibenzoyl tartaric acid and debenzylating by treatment with hydrochloric acid, when the (- -)- and (— )-reticuline hydrochlorides were obtained ([ ]d —73.1° [a]j) 4-75.0° in H2O). 

Dimethylamino - a - methylpropiophenone and dibenzoyl - (—) - tartaric acid monohydrate dissolved in acetone, stirred until crystallization begins and for an additional 18 hrs., the solid collected and washed with acetone, the combined filtrate coned, with repeated collection of additional product ( —)-j -di-methylamino-a-methylpropiophenone acid dibenzoyltartrate (Y 94%) treated with aq. NHg, extracted with ether, dried with anhydrous MgS04, and acidified with dry HCl ( —)-/ -dimelhylamino-a-methylpropiophenone hydrochloride (Y 94%).—Concentration of the filtrate from the resolution causes racemization of the soluble diastereoisomeric salt and affords a nearly quantitative yield of the insoluble salt. Dibenzoyl-( + )-tartaric acid yields the insoluble salt with the ( + )-aminoketone. A. Pohland, L. R. Peters, and H. R. Sullivan, J. Org. Ghem. 28, 2483 (1963) cf. W. Theilacker, P. Braune, and G. G. Strobel, B. 97, 880 (1964). 

Oxysulfenylation and oxyselenenylation of olefins, catalysed by chiral Brpnsted acids, have been reported to produce enantiomerically enriched tetrahydrofurans at <63% ee with dibenzoyl-tartaric acid and its derivatives as catalyst. Enantioselective desymmetrization of thiiranium and seleniranium ions (<50% and <84% ee, respectively) in the presence of chiral binaphthol-derived A(-triflyl phosphoramide as a catalyst has also been demonstrated. ... 

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