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20th October 2010 @ 01:05
Synthesis of a chiral acid as a potential resolving agent for Praziquanamine following a patent procedure for the Synthesis of (-)-Di-p-anisoyl-L-tartaric acid (MW46-1)

See also:
Synthesis of (+)-Dibenzoyl-D-tartaric acid - alternative route (MW10-6)
Synthesis of (-)-Dibenzoyl-L-tartaric acid (MW10-1-30) and previous experiments MW10-2-32, MW10-3-33, MW10-4-37 (lab notebook #1)

Scheme MW10-5


Table MW10-5.JPG


Hazard and Risk Assessment:
HRAF MW10.pdf


Start time: 5:15 PM 06/10/2010
End time: 10:00 AM 08/09/2010

Procedure: [1]
A mixture of D-(-)-tartaric acid (6.0 g, 40.0 mmol) and FeCl3 (130 mg, 800 µmol, 0.02 eq.) in xylene (20 mL) was heated to 95°C and benzoyl chloride (11.3 g, 80.0 mmol, 9.3 mL, 2.0 eq.) was added dropwise over a period of 1.0 h. After stirring for additional 1 h at the same temperature thionyl chloride (5.71 g, 48.0 mmol, 3.49 mL, 1.2 eq.) was added over a period of 1h and the mixture was stirred for another 1 h. The mixture was heated to 110° for 2 h and then cooled down to room temperature while stirring for 11 h.
The ice cooled reaction mixture was filtered off and the brown precipitate was washed with cold toluene and hexane obtaining the tartaric acid anhydride as a pale grey solid.

- remain from the mother liquor: 590 mg benzoic acid -> remaining starting material, reaction not completed
- no NMR possible: impurities of iron (paramagnetic)

Hydrolysis of the anyhdride:
Test reaction with 1 g anhydride: Data: 1H NMR 10-5 test.pdf

3.80 g (10.6 mmol) of a pale green solid, solvent impurities (Et2O), no benzoic acid
1H NMR: Data: 1H NMR 10-5 hydrolysis of the anhydride.pdf

IR (neat): nu = 3065 cm-1, 1719, 1239, 1178, 1092, 704. Data: IR MW10-5.pdf:
-data matches with IR spectrum from AIST database (search for CAS # 2743-38-6)
[α]D20 = -104° (c=1, EtOH)

Recrystallization
Recrystallized from DCM/i-PrOH: residue was dissolved in a minimum of hot DCM and stored in the fridge for 1 d. The obtained spicular crystals were filtered off and washed with cold DCM.
yield: 320 mg, remain: 1.48 g oil -> lots of remaining substanz in the mother liquor, slow crystallization - useful as seed crystals...
-drying crystals over 2 days

m.p. = 97-99°C [lit: XX]
1H NMR:Data: 1H NMR 10-5 recryrstallized from i-PrOH DCM.pdf: remaining i-PrOH in the crystal (2 molecules)
-> (+)-Dibenzoyl-D-tartaric acid * 2 i-PrOH: M.W. = 478.5 g/mol

Recrystallization from:
- i-PrOH/CHCl3 (1:1, 216 mg in 0.4 mL): fridge/seed crystals- no crystallization
- i-PrOH/CHCl3 (1:10, 215 mg in 2 mL): fridge/seed crystals- no crystallization
- i-PrOH/hexane (1:1, 226 mg in 1.2 mL): fridge, then seed crystal from previous crystals -> crystallization!!!

Yield: 185 mg (82%)
-> test for optimizing solvent/conditions
1H NMR: Data: 1H NMR 10-5 recryrstallized from i-PrOH hexane.pdf: 2 molecules of i-PrOH in the crystal

Recrystallization from i-PrOH/hexane 1:2 (~ 1.5 g in 20 mL solvent)
Yield: 964 mg colorless - pale brown crystalline solid
remain in mother liquor: 483 mg pale brown solid

See alternative procedure to (+)-Dibenzoyl-D-tartaric acid (MW10-6)

Analytical data:
m.p. 97-100°C.
[α]D20 = +84.5° (c=1, EtOH).
MS (ESI (-)) m/z (%): 357 (100) [M-H]-.
HRMS (ESI (-)) Calcd. for [ C18H13O8]-: 357.0616, found: 357.0616.
HRMS (ESI (+)) Calcd. for [C18H14O8+Na]+: 381.0581, found: 381.0579.

References:
[1] "Process for preparation of chiral tartaric acid derivatives" Z. Zhou, Y. Hu, Yu; X. Sun, Y. Guo, H. Yao, H. Chen, Faming Zhuanli Shenqing Gongkai Shuomingshu (2008), CN 101239913 A 20080813, Language: Chinese.

[2] "Novel processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol", W. Laux, G. Guillamot, F. Laskovics, C.-H. King, J. Hitt, S. Stolz-Dunn, I. Tomlinson and J. N. Koek, U.S. Pat. Appl. Publ. (2005), US 20050261341 A1 20051124.
Attached Files
Scheme MW10-5
Table MW10-5.JPG
HRAF MW10.pdf
1H NMR 10-5 test.pdf
1H NMR 10-5 hydrolysis of the anhydride.pdf
IR MW10-5.pdf
1H NMR 10-5 recryrstallized from i-PrOH DCM.pdf
1H NMR 10-5 recryrstallized from i-PrOH hexane.pdf