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17th November 2010 @ 04:18
Testing (-)-dibenzoyl-L-tartaric acid as a resolving agent for the racemic resolution or PZQamine via diastereomeric salt formation to obtain [i]R[/i]-(-)-PZQamine See related experiments: [*] [url=http://www.ourexperiment.org/racres_pzq/1206]Racemic resolution of praziquanamine with (+)-Dibenzoyl-D-tartaric acid (MW49)[/url] [*] [url=http://www.ourexperiment.org/racres_pzq/687]Synthesis of (-)-Dibenzoyl-L-tartaric acid (MW10-1-30)[/url] -> [i]S[/i]-(+)-PZQamine [*] [url=http://www.ourexperiment.org/racres_pzq/1110]Diastereomeric salt resolution of praziquanamine with (-)-di-p-anisoyl-L-tartaric acid obtainig [i]S[/i]-(+)-PZQamine (MW47-3)[/url] [data=size:500x180]667[/data] Start time: 13:45 PM 17/11/2010 End time: 13:45 PM 17/11/2010 [b]Procedure:[/b] [url=http://www.thesynapticleap.org/node/296][i]rac[/i]-Praziquanamine[/url] (101 mg, 500 µmol) and [url=http://www.ourexperiment.org/racres_pzq/687](-)-dibenzoyl-L-tartaric acid* 2 [i]i[/i]-PrOH[/url](239 mg, 0.5 mmol) were dissolved in a various solvents (mixtures) by heating the stirred mixture. - M.W. diastereomeric salt = 560.6 g/mol) [b]MW49-5:[/b] Solvent: EtOH/water 9:1, 3 mL - formation of crystals after 5 min - after 1 h: 185 mg (66%) - salt: [α]D20 = -100° (c = 1, DMSO) [b]MW49-6:[/b] Solvent: EtOH/water 9:1, 4 mL - formation of crystals after 5 min - after 1 h: 159 mg (57%) - salt: [α]D20 = -103° (c = 1, DMSO) [b]MW49-7:[/b] Solvent: EtOH/water 9:1, 5 mL - formation of crystals after 15 min - after 1 h: 128 mg (46%) - salt: [α]D20 = -110° (c = 1, DMSO) - 118 mg recrystallized from EtOH/water (2 mL, 9:1), after 50 min: 90 mg (76%, 32% over-all) [u]Diastereomeric salt:[/u] [α]D20 = -117° (c = 1, DMSO) m.p. = 149-150.5°C [u]PZQamine:[/u] 24 mg [α]D20 = -257° (c = 1.71, DCM) -> 87% ee (calculation error -> c=1 ?) -> crystallization too fast, lower concentration should slow down the crystallization [b][u]Further experiments:[/u][/b] Start time: 6:15 PM 17/11/2010 End time: 7:40 PM 17/11/2010 [b]MW49-8:[/b] Solvent: EtOH/water 9:1, 6 mL (former MW49-6, - 10.4 mg for optical rotation) - after 90 min: 127 mg (45%) [u]Diastereomeric salt:[/u] [α]D20 = -118° (c = 1, DMSO) [not consistent ???] m.p. = 144-145°C [u]PZQamine:[/u] 36 mg [α]D20 = -198° (c = 1, DCM) 67% ee [b]MW49-9:[/b] Solvent: EtOH/water 9:1, 7 mL (former MW49-5, - 12.3 mg for optical rotation) - after 90 min: 72 mg (26%) [u]Diastereomeric salt:[/u] [α]D20 = -115° (c = 1, DMSO) m.p. = 147-148°C [u]PZQamine:[/u] 16 mg [α]D20 = -210° (c = 1, DCM) -> 71% ee [b]Results:[/b] - rising melting point of the diastereomeric salt - deviations of the optical rotation (not consistent) - crystallisation with another solvent / solvent mixture (higher content of water or i-PrOH/water) [b]MW49-10:[/b] Start time: 10:30 PM 24/11/2010 End time: 13:00 PM 24/11/2010 Solvent: EtOH/water 9:1, 5 mL - at first no crystals, stirring -> precipitate - heated again - formation of crystals after 30 min - after 3 h: 155 mg (55%) m.p. = 136-138°-c - salt: [α]D20 = -103° (c = 1, DMSO) [u]2. Crystallization:[/u] Solvent: EtOH/water 2:1, 3 mL Start time: 9:00 PM 24/11/2010 End time: 9:30 PM 24/11/2010 after 1 h: 110 mg (39%) - salt: [α]D20 = -115° (c = 1, DMSO) - PZA: [α]D20 = -246° (c = 0.90, DCM) -> 83% ee [b]MW49-11:[/b] Start time: 10:30 PM 24/11/2010 End time: 11:00 PM 24/11/2010 Solvent: [i]i[/i]-PrOH/water 5:1, 3 mL - crystallization too fast Solvent: [i]i[/i]-PrOH/water 5:1, 4 mL - crystallization after 5 min, after 30 min separated: 172 mg (61%) - salt: m.p. = 135-137°C, [α]D20 = -115° (c = 1, DMSO) [u]2. Crystallization:[/u] Start time: 9:00 PM 24/11/2010 End time: 9:20 PM 24/11/2010 Solvent: [i]i[/i]-PrOH/water 2:1, 3 mL - complete precipitation Solvent: [i]i[/i]-PrOH/water 2:1, 4 mL - after 1 h: yield: 99mg (35%) - salt: [α]D20 = -121° (c = 1, DMSO) [α]D20 = -262° (c = 1.09, DCM) -> 89% ee
Attached Files
Scheme
scheme MW49-5.png