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3rd July 2011 @ 08:00
Synthesis of nitro substituted tartaric acid resolving agent.
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See also:
Alternative synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-4-1)
Synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-3-1)
Synthesis of di-p-toluoyl-D-tartaric acid (CS-2-1)
Synthesis of (+)-Di-p-anisoyl-D-tartaric acid (MW46-2)

Procedure
A mixture of (L)-(+)-tartaric acid (1 g, 7 mmol, 1 eq.), sulphuric acid (0.05 mL), 4-nitrobenzoyl chloride (4.6 g, 25 mmol, approx. 3 eq.) and toluene (1 mL) was heated at 130oC for a period of 2.5 hrs (Note 1.). Toluene (3 mL) and H2O (0.2 mL) were added to the solution before being refluxed for 30 min. Solution was cooled, filtered and washed with toluene yielding a white and brown solid (Note 2.), di-4-nitrobenzoyl tartaric acid (crude yield; 3.6 g).

Purification:
Resulting crude product was dissolved in hot EtOH (ca 5 mL). Solution was then cooled, filtered and washed with cold EtOH (2 x 1 mL). Purifcation procedures were repeated twice more to yield the pure nitro substituted tartaric acid derivative as a light, brown crystalline solid (Note 3.)(0.2 g, 6%, m.p. 72-74.8o)(Note 4.). Additional product was recrystallized from filtrates with EtOH/Hexane (2:1) yielding additional product (0.8 g, 27%, m.p. 72-75o)(0.88g, 29%).

Notes:
(1) Brown, mushroom-like solid with tar-like consistency formed in solution; most likely the product.

(2) Crude product procured an artificial chocolate/coffee fragrance.

(3) Crystallized product was flakey and extremely light. Identified through a visual resemblance to tuna flesh.

(4) Majority of product crystallised in the filtrate from purification steps. Hesitation to concentrate and retrieve it was due to dangers of the byproducts of reaction found similarly in filtrate. Poor efficiency of recrystallisation could be due to a good solubility of product in solvent used; EtOH.
Attached Files
30th June 2011 @ 04:03
resolution reagent.png


See also:
Alternative synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-4-1)
Synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-3-1)
Synthesis of di-p-toluoyl-D-tartaric acid (CS-2-1)
Synthesis of (+)-Di-p-anisoyl-D-tartaric acid (MW46-2)

Procedure:

[1] A mixture of (L)-(+)-tartaric acid (1.00 g, 7 mmol 1 eq), sulfuric acid (ca 0.05 mL) and 2-bromobenzoyl chloride (2.75 ml, 21 mmol, 3 eq) in toluene (1 mL) was heated at 110 oC for 2.5 h. Toluene (3 mL) and water (ca 0.2 mL) were added to the mixture and heated for 30 min.

[2] The mixture was cooled to room temperature, filtered* and washed with cold toluene to give pale yellow solid. The solid was then recrystalized from hot EtOH and no precipitation was observed (Note 1).

[3] White crystals formed after the filtrate* was stood overnight. The mixture was filtered to give 2-bromobenzoic acid as white fluffy fine crystals (0.4 g, 29.9%, m.p. 148-150 oC, lit. 144-147 oC).

[4] The resulting mixture from [2] was evaporated under reduced pressure to give sticky yellow solid. Solvent EtOH:hexane mixture (1:1, 1:2, 1:3) and isopropanol:hexane (1:2) were all tried to recrystallise O,O'-di-2-bromobenzoyl-(L)-tartaric acid.

Notes:

(1) O,O'-di-2-bromobenzoyl-(L)-tartaric acid and 2-bromobenzoic acid have very different solubilities.
Attached Files
6th June 2011 @ 07:22
kb.pzq.1005.png


See also:
Synthesis of O,O'-di-4-bromobenzoyl-(L)-tartaric acid (KB-PZQ-1003)
Synthesis of (-)-Dibenzoyl-L-tartaric acid (MW10-1-30)
Synthesis of (+)-Dibenzoyl-D-tartaric acid (MW10-5)

Procedure:
A mixture of (L)-(+)-tartaric acid (10.00 g, 70 mmol, 1 eq), sulfuric acid (0.5 mL) and benzoyl chloride (24.6 mL, 210 mmol, 3 eq) in toluene (10 mL) was heated at 130 oC for 2h. The resulting mixture was diluted with toluene (30 mL) and water (2 mL) and refluxed for 30 min. The mixture was then cooled to room temperature and concentrated in vacuo.

Purification:
The crude material was recrystallised from i-PrOH/hexane (1:2) to give a white crystalline solid, which was found to be O,O'-dibenzoyl-(L)-tartaric acid, complexed with 2 equivalents of i-PrOH (30 g, 90%).

References:
H. Hajmowicz, J. Wisialski, and L. Synoradzki,Org. Process Res. Dev., 2011, 15 (2), pp 427–434
Attached Files
2nd June 2011 @ 06:06
kb.pzq.1003.png


See also:
Alternative synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-4-1)
Synthesis of di-p-chlorobenzoyl-(L)-tartaric acid (CS-3-1)
Synthesis of di-p-toluoyl-D-tartaric acid (CS-2-1)
Synthesis of (+)-Di-p-anisoyl-D-tartaric acid (MW46-2)

Procedure:
A mixture of (L)-(+)-tartaric acid (1.00 g, 7 mmol 1 eq), sulfuric acid (ca 0.05 mL) and 4-bromobenzoyl chloride (4.59 g, 21 mmol, 3 eq) in toluene (1 mL) was heated at 130 oC for 2h. The resulting mixture was diluted with toluene (3 mL) and water (0.2 mL) and refluxed for 30 min. The mixture was then cooled to room temperature, filtered and the precipitate washed with toluene (5 mL) and water (3 mL) to give a mixture of di-4-bromobenzoyl-L-tartaric acid and 4-bromobenzoic acid (crude yield 4.39 g).

Purification:
The precipitate was dissolved in a minimal amount of hot EtOH (ca 5 mL). The solution was cooled and filtered and the precipitate (4-bromobenzoic acid) washed with cold EtOH (2 x 1 mL). The filtrate was concentrated in vacuo. This was repeated twice more to give the pure tartaric acid derivative (crystallised with 1 eq EtOH) as a white solid (2.90 g, 73%).

Data:
m.p.
104 oC; 13C NMR (500 MHz, CDCl3): 168.89 (C), 168.88 (C), 133.17 (CH), 132.53 (CH), 129.83 (C), 129.37 (C), 73.15 (CH); LRMS (nESI) 516.60 ([M-H]-, 40), 514 ([M-H]-, 100), 512 ([M-H]-, 42), 201 ([Br81C6H5COO]-, 75), 199 ([Br79C6H5COO]-, 75);

References:
H. Hajmowicz, J. Wisialski, and L. Synoradzki,Org. Process Res. Dev., 2011, 15 (2), pp 427–434
Attached Files
13th May 2011 @ 01:19
Testing of (+)-di-p-toluoyl-D-tartaric acid as a possible resolving agent for PZQamine via a diastereomic salt.

Scheme:
cs-5-1.png


See Also (Synthesis of resolving agent):
Synthesis of p-toluoyl chloride (CS-1-1)
Synthesis of di-p-toluoyl-D-tartaric acid (CS-2-1)

See also (Resolution experiments):
Racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-5 to MW49-11)
Scale-up: Racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-12)
Racemic resolution of praziquanamine with (+)-Dibenzoyl-D-tartaric acid (MW49-1 to MW49-4)

Start: 11:30am 13/05/11
Finish:

Procedure: rac-Praziquanamine (101 mg, 500 µmol) and di-p-toluoyl-D-tartaric acid(192 mg, 0.5 mmol) were dissolved in a various solvents (mixture or isopropanol and water (5mL in a 5:1 ratio) by heating the stirred mixture.

Overnight in fridge (5 degrees C) - white precipitate appeared but not crystalline, rather clumpy-white.

Solvent was removed and solid was washed with isopropanol. The salt was liberated with sodium hydroxide (2N, 8 mL), and extracted with dichloromethane (10 mL), then dried over sodium sulfate. The solvent was evaporated leaving a yellowish solid.

Yield: 27.7 mg
Attached Files