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2nd July 2010 @ 08:40
NMR-monitored experiments - testing various intermediates of PZQ (derivatives) with a strong achiral Bronstedt-acid as pretests for chiral derivatives of the catalyst [data=size:500x200]285[/data] [data=size:500x150]287[/data] [b]Hazard and Risk Assessment:[/b] Reaction Class: 2 Hazards: T Toxic, X Irritant, C Corrosive Risk rating: U = Unlikely Start time: 6:15 PM 02/07/2010 End time: 4:00 PM 08/07/2010 [b]General Procedure:[/b] Each of the compound [b]MW7, [url=]MW29-4[/url], [url=]MW14[/url], [url=]MW40-1[/url][/b] (75.0 µmol) shown in Table1 was solved in CDCl3 (~0.5 mL) in a NMR tube and [url=][b]MW39-2[/b][/url] (1.8 mg, 4.0 µmol, 5 mol%) was added. - after 3 days at r.t no conversion was monitored (by 1H NMR) - heated to 60°C for further 3 days -> no conversion of the starting material [b]MW41-1A – MW41-4A[/b] -> addition of MeSO3H (5.2 µL of a 5% solution in CDCl3, 384 µg, 4.0 µmol, 5 mol%) as a Broensted-acidic co-catalyst [reaction index A] -> reference experiments: MeSO3H (5.2 µL of a 5% solution in CDCl3, 384 µg, 4.0 µmol, 5 mol%). [reaction index B] [data=size:500x150]350[/data] Start time: 5:30 PM 08/07/2010 End time: 4:00 PM 12/07/2010 After 16.5 h at r.t. - no conversion monitored by NMR -> heated to 60°C for 3 d [b]Results:[/b] [b]MW41-1A/MW41-1B[/b] and [b]MW41-3A/MW41-3B:[/b] No conversion of the starting material monitored [b]MW41-2A/MW41-2B[/b] About 50% conversion in both trials, no significant difference to the reference experiment [b]MW41-4A/MW41-4B[/b] Nearly complete conversion of the starting material, but the reference experiment showed a better consumption! [b]Summary:[/b] The BINOL-N-triflyl phosphoramide catalyst [url=][b]MW39-1[/b][/url] showed no activity (for 5 mol% catalyst loading) for an acid-catalysed Pictet-Spengler reaction of the tested compounds. An additional strong Broenstedt-acid MeSO3H, intended as a co-catalyst, didn’t influence the catalytic activity of the phosphoramide [url=][b]MW39-1[/b][/url]. The conversion of [url=][b]MW29-4[/b][/url] and [url=][b]MW40-1[/b][/url] (experiments [b]MW41-2A/MW41-2B[/b] and [b]MW41-4A/MW41-4B[/b]) was caused by the added MeSO3H, but only the N-cyclohexanoyl-protected amines showed a consumption of the starting material, the free amines [b]MW7[/b] and [url=][b]MW14[/b][/url].
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