Dibenzoyltartaric acid

In 1996, Fu et al. reported the S3mthesis of the planar chiral heterocycles 64, formally DMAP fused with a ferrocene core [82]. While the original synthesis provided racemic 64a in only 2% overall yield requiring a subsequent resolution by preparative HPLC on a chiral stationary phase, a recently improved synthesis furnished the racemic complexes 64 in 32-40% yield over seven steps. A subsequent resolution with di-p-toluoyltartaric or dibenzoyltartaric acid gave access to the enantiomers with >99% ee (28 14% yield for each isomer in this step) [83]. 

Analysis of Amines, Hydroxylamines, Amino Acids and Peptides via 0,0-Dibenzoyltartaric Acid Imides... 

Table 11. 1 H-NMR Analysis of Amines. Amino Acids, Esters, Peptides and Hydroxylamines via (/ ./ )-0,0 -Dibenzoyltartaric Acid Imides (5, CDC13)50...

To a refluxing solution of racemic 2,2, 6,6 -tetramethoxy-bis[di(3,5-dimethylphe-nyl)phosphinoyl]-3,3 -bipyridine [( )-6, 4.09, 5.1 mmoL] in 30mL CHCI3, a solution of (—)-2,3-(9,(9 -dibenzoyltartaric acid monohydrate [l-(—)-DBT, 1.90g, 5.1 mmol] in 50mL ethyl acetate was added slowly. The mixture was stirred under reflux for 30 min and then allowed to stand at room temperature overnight. 

Resolution of 3-aminopyrrolidine is reported in the hterature using diben-zoyltartaric acid via a 2 1 salt. We found that the (R)-enantiomer of the IN-Boc protected racemate could be crystallized in 32% yield and 99.5% ee from ethanol in a single crystallization with 0.25 mol equivalents of (R,R)-dibenzoyltartaric acid (Scheme 13.9). Other solvents tested gave poorer results. 

Screening several amine racemization catalysts, we found that the SCRAM and the Shvo catalyst would both racemize the (S)-enantiomer at temperatures above 11() G. Interestingly, no dimeric products were found. The best racemization conditions were found to be using toluene or TBME at 150°C in a pressure vessel with 1 mol% SCRAM or 5 mol% Shvo catalyst over 24 h, providing quantitative conversion. In the presence of (R, R)-dibenzoyltartaric acid the racemization slowed, possibly because of unfavorable coordination of the alkylammonium substrate or acid quenching of the iridium hydride catalyst intermediate. 

Synthesis (Pohland, 1953 1955 1963 janssen and Karel (Janssen)1956 Sullivan et al., 1963) In the Grignard reaction of 3-dimethylamino-2-methyl-1-phenyl-propan-lone with benzylmagnesium chloride 4-dimethylamino-3-methyl-1,2-diphenyl-butan-2-ol is formed. The preferred product is the a-diastereomer(75 % a-form, 15 % p-form). The a-form crystallizes and the diastereomeric p-form remains in solution, because of its better solubility. Racemic resolution to obtain the analgetically (+) enantiomer can be achieved on the pure a-Grignard product via fractional crystallization of the salts with D-camphorsulfonic acid. Alternatively the resolution can be achieved by treating the racemic mannich product 3-dimethylamino-2-methyl-1-phenyl-propan-1-one with (-)-dibenzoyltartaric acid in acetone as solvent. 

The chiral ligand BINAP was originally prepared from 2,2 -binaphthol and resolved by complexation with an optically active Pd complex [ 10]. A new method starting from 2-naphthol was developed (Scheme 3.2) [11], In this method optical resolution was achieved at the stage of BINAP dioxide (BINAPO) by using inexpensive optically active acids such as camphorsul-fonic acid and dibenzoyltartaric acid. 

Key words optical resolution, diastereoisomeric complexes, 0,0 -dibenzoyltartaric acid, hydroxycarboxylic acid esters, hydroxycarboxylic acids, chiral phosphine oxides, racemic alcohols. 

Hatano, K., Takeda, T., and Saito, R. Optical resolution of trans-b QyQ Q> 2.2.l]heptane-2,3-diamine chiral recognation in the crystal of its complex with (2R,3R)-0,0 -dibenzoyltartaric acid, J. Chem. Soc. Perkin Trans 2.1994,579-584. 

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. 

Mravik, A., Bocskei, Zs., Katona, Z., Markovits, I., and Fogassy, E. Coordination-mediated optical resolution of carboxylic acids with 0,0 -dibenzoyltartaric acid, Angew. Chem. Int. Ed. Engl. 1996, 36, 1534-1536. 

Mravik, A., Bocskei, Zs., Simon, K., Elekes, F., and Izsaki, Z. Chiral recognition of alcohols in the crystal lasttice of simple metal complexes of 0,0 -dibenzoyltartaric acid enantiocomplementarity and simultaneous resolution, Chem. Eur. J. 1998, 4, 1621-1627. 

D-Dibenzoyltartaric acid (D-DBTA) (32.2 g, 90 mmol, 1.0 eq) is added to a hot solution of racemic 4-benzyl albuterol (29.6 g, 90 mmol, 1.0 eq) in 180 mL of anhydrous denatured ethanol (type 3A, denatured with 5 vol % 2-propanol). The resulting solution is refluxed for 15 min and cooled to room temperature over 40 min and seeded with 99% ee (R)-4-benzyl albuterol D-DBTA salt. The mixture is cooled to 5°-10°C and stirred for 1 hour. The white solid is collected by filtration and dried at 40°C and 28 inches of Hg for 1 hour to give (R)-4-benzyl albuterol D-DBTA salt (31.8 g, 50% yield, 83.6% ee). 

To ()-5 -methoxylaudanosine (46.4 g) in methanol (240 mL) was added (-)-dibenzoyltartaric acid monohydrate (45.2 g). The mixture was heated to boiling, cooled at 5°C for 16 h and the (S)-(-)-5 -methoxylaudanosinium dibenzoyltartrate salt (35.6 g, 80%) was filtered and discarded. The mother liquors were made basic with concentrated aqueous NaOH and evaporated under vacuum. The solid residue was partitioned between H20 and diethyl ether. The ether phase was dried and evaporated to an oil (24.9 g). To the oil in methanol (128 mL) was added (+)-dibenzoyltartaric acid monohydrate (26.6 g). The mixture was heated to boiling and cooled at 5°C for 16 h. Crystals were collected and recrystallized from methanol until a constant specific rotation of [a]D20= + 17.7° (1% EtOH) had been achieved. The yield of (R)-(+)-5 -methoxylaudanosinium dibenzoyltartrate as white crystals was 29.4 g (66%). A portion of the salt (15.0 g) in methanol (200 mL) was made basic with concentrated aqueous NaOH. The mixture was evaporated under vacuum and the residue was partitioned between H20 and diethyl ether. The combined ether layers were dried and evaporated under vacuum to yield 7.2 g (92%) of (R)-(-)-5 -methoxylaudanosine as an oil. 

Pipecoloxylidide hydrochloride (1.0 kg), acetone (3.75 L), and water (0.85 L) were charged. NaOH (aq) was added to pH>ll. The phases, thus formed, were separated and the organic phase was diluted with water (1.4 L). L-(-)-Dibenzoyltartaric acid (0.67 kg), dissolved in acetone (3.75 L), was added. 

Aminoquinuclidine S-( —)-l-Phenylethyl isocyanate R-1-(1-Napthyl)ethyl isocyanate RR-( + )-O,0-Dibenzoyltartaric acid SS-( — )-0,0-Dibenzoyltartaric acid 189... 

The resolution of 3-phenylFischer s base itself would make available the chiral base for the preparation of not only indolinospiropyrans, but also for cyanine, merocyanine, and styryl dyes. Several attempts to effect this resolution using the camphorsulfonic, bromocamphorsulfonic, and dibenzoyltartaric acids in lower alcohols, 1,2,-dimethoxyethane and tetrahydrofuran, were unsuccessful in giving a clean resolution. Perseverance and luck are of prime importance. 

Optical Resolution of Mannich Bases by (-)- or (+)-Dibenzoyltartaric Acid... 

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