Racemic Resolution of Praziquantel and Praziquanamine

 

Reaction performed on 01/03/10 carried over from Lab notebook

Synonyms: (-)-2,3-Dibenzoyl-L-tartaric acid, (-)-O,O′-Dibenzoyl-L-tartaric acid, L-Tartaric acid 2,3-dibenzoate





Start time: 1:00 PM 01/03/2010
End time: 4:00 PM 01/03/2010

Procedure:
A mixture L-(+)-tartaric acid (4.50 g, 30 mmol) and benzoyl chloride (14.8 g, 12.2 mL, 105 mmol) was heated to 130°C for 3 h. After which time a pale brown solid was formed and the mixture was cooled to room temperature. The pale brown solid was washed with cold Et2O and recrystallized from toluene affording 7.50 g (22.0 mmol, 73%) of colorless fine crystalline solid.

Analytical Data:
m.p. 183-184°C (decomposion). [lit: 185° (for (-)-dibenzoyl-D-taratric acid) check Scifinder]
1H NMR (CDCl3, 200 MHz): δ = 6.00 (s, 2 H), 7.46-7.54 (m, 4 H), 7.64-7.71 (m, 2 H), 8.06-8.11 (m, 4 H). 13C NMR (CDCl3, 50.3 MHz):  = 72.9 (2 C), 127.2 (2 C), 128.2 (4 C), 130.4 (4 C), 134.7 (2 C), 163.5 (2 C), 165.5 (2 C). C18H14O8 (358.3).
1H NMR (CDMSO-d6, 200 MHz): Data: 1H NMR MW10-1 in DMSO update data
Anhydride C18H12O7 (M.W. 340.3).

-> it's the Anhydride!
See:
Synthesis of (+)-Dibenzoyl-D-tartaric acid (MW10-5)
Synthesis of (+)-Dibenzoyl-D-tartaric acid - alternative route (MW10-6)
Scale-up: Synthesis of (-)-Dibenzoyl-L-tartaric acid (MW10-7)


product is sparingly soluble in EtOH!?
[α]20D = -122° (c=0.5, EtOH) [lit. 118.51°, c=4.90; EtOH )
[α]20D = -106° (c=1, EtOH)
[α]20D = -108° (c=0.5, EtOH)

Hydrolysis of the anhydride:
The anhydride (4.51 g, 13.3 mmol) was dissolved in a mixture of acetone (30 mL) and water (3 mL) and heated to reflux for 2 h. After which time, water (20 mL) was added and the acetone was evaporated by heating the the solution. Anothertime water (20 mL) was added but no occured (seprartion of a liquid layer). The mixture was evaporated under reduced pressure and when the remaining acetone was removed a colorless solid precipitated. The mixture was cooled to 0° and the solid was filtered off.
Yield: 5.68 g wet crude (-)-O,O′-Dibenzoyl-L-tartaric acid
- for (-)-O,O′-Dibenzoyl-L-tartaric acid (M.W. 358.3): 15.9 mmol (119%)
- for (-)-O,O′-Dibenzoyl-L-tartaric acid*H2O (M.W. 376.3): 15.1 mmol (113%)

The colorless solid (4.02 g) was dissolved in a refluxing mixture of iPrOH and hexane (20 mL, 1:2) and cooled to room temperature. The precipitate was filtered off and rinsed with a cold mixture of iPrOH and hexane.

Yield: 4.22 g colorless crystalline solid dried on air and afterwards in high vac

Analytical data:
m.p. 99-102°C. (lit. 95–98°C)
1H NMR: Data: 1H NMR MW10-1-30 after recrystallisation.pdf: ~ 2 molecules of i-PrOH in the lattice (?)
IR (neat): nu = 3465 cm-1, 2975, 1730, 1237, 1098, 938, 706.Data: MW10-1-30 acid.pdf -> no OH-peak for i-PrOH
[α]D20 = -85.0° (c=1, EtOH). ([α]D20 = 119.4° (c=1.055, MeOH))
C24H30O10 (478.5 g/mol): calc. C 60.24%, H 6.32%; found: C 60.27%, H 6.33%
-> dibenzoyltartaric acid * 2 i-PrOH

-> Problem: varying/inconsistent data for melting points, optical rotation and IR: what's the molecular weight??? DTA* H2O, DTA*i-PrOH, or DTA*2 i-PrOH?
-> elemental analysis (determined!)

References:
[1] “The Reduction of Various Sugar Acids to Glycitols with Lithium Aluminum Hydride”, R. K. Ness, H. G. Fletcher and C. S. Hudson, J. Am. Chem Soc. 1951, 73, 10, 4759-4761.

[2] “Relative Stereoselectivity of the Reactions of (2R,3R)- and (2R,3S)-Dibenzoyloxysuccinic Anhydrides with Chiral Amines and Alcohols”, K. H. Bell, Aust. J. Chem. 1987, 40, 399-404. doi:10.1071/CH9870399.