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29th January 2012 @ 23:46
[i]*PS = Pictet-Spengler[/i] [b][u]Background[/b][/u] Repeat of procedure for the preparation of KAB8-5 with reduced catalyst loading. [blog]3936[/blog] [b][u]Hazard and Risk Assessment[/b][/u] As for KAB8-5 ([url=http://www.ourexperiment.org/data/files/2630/HRA%20KAB8-5.pdf]here[/url]) [b][u]Previous Related Experiments[/b][/u] [blog]3873[/blog] [blog]3660[/blog] [b][u]Following Experiments[/b][/u] [blog]3936[/blog] [b][u]Procedure[/b][/u] [b]Preparation of stock acid[/b]: A 0.26 M solution of TfOH in toluene was prepared by mixing TfOH (~195 mg, 1.3 mmol) in toluene (5 mL). It was assumed the TfOH contributed negligible volume. [b]KAB8-7[/b]: MNR10-1 (153.9 mg, 0.336 mmol) was dissolved in toluene (32 mL) before the TfOH/toluene mixture (0.39 mL; TfOH = 30 mol%) was added at 12:30 at rt. The mixture was heated to 90 °C. [b]KAB8-8[/b]: The procedure was the same as for KAB8-7. MNR10-1 (94.8 mg, 0.207 mmol), toluene (32 mL), TfOH/toluene (0.12 mL; TfOH = 15 mol%). Added at 12:35 at rt, before heated to 90 °C. Aliquot 1 (50 uL) extracted from both solutions at 12:40 Aliquot 2 (50 uL) extracted from KAB8-7 at 13:20 [data]2653[/data][data]2655[/data] TLCs were eluted with EtOAc/hexane, 4:1, v/v. Stain: KMnO4 KAB8-8 taken off @ 12:50. KAB8-7 taken off @ 13:25. The reaction mixture was quenched with saturated sodium bicarbonate solution (50 mL) and the organic layer removed. The alkaline aqueous fraction was extracted with EtOAc (3 × 30 mL). The organic layers were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give the crude products. Crude KAB8-7: 132.7 mg, 175% - yellowish gum + yellow oil. Crude KAB8-8: 89.4 mg, 118% - yellowish solid gum. [b]Recrystallisation[/b] [b]30/01/12.[/b] The crude products of KAB8-7 and KAB8-8 were dissolved in a minimum of hot EtOAc. Hexane was added dropwise until a white precipitate began to form on contact with the hot, yellow EtOAc solution (~1:1, EtOAc/hexane, v/v). The flasks were sealed then placed in the freezer overnight. [b]31/01/12[/b]. Formation of yellow crystals for both KAB8-7 and KAB8-8. Still stored in freezer. [data]2705[/data][data]2707[/data] [b]01/02/12[/b]. The KAB8-8 and KAB8-7 crystals were washed with hexane and filtered to give small orange crystals. KAB8-7 - 102 mg, 83%. KAB8-8 - 69.2 mg, 91%. [data]2733[/data] [b]02/02/12[/b]. 1H-NMR of the KAB8-8 and KAB8-7 samples confirmed both products as the dimethoxy [i]N[/i]-benzoyl PZQ analogues. TLC of the crystals showed no co-spotting and the spot that was visible under long wave UV (350 nm) was no longer present. TO DO: - TLC crystals against filtrate (see where long wave UV spot ends up). [b][u]Summary and Conclusion[/u][/b] -------------------------------------------------------------- NOTES 30/01/12 - KAB8-8 with the lower catalyst loading probably finished first because of the way I added the acid. The acid solution was added into the MNR10-1/toluene solution with a long needle. The KAB8-7 acid was added to the flask, but not directly into the solution. - The KAB8-8 mixture went to temperature faster; reached temperature in less than 2 min. The KAB8-7 reaction mixture did not reach 90 °C. The reaction was quenched at ~80 °C. NOTES 31/01/12 - KAB8-8 filter paper: 1.0973 g NOTES 01/02/12 - KAB8-7 filter paper 1.1030 g NOTES 02/02/12 - Long wave co-spot was absent. Will TLC filtrate. --------------------------------------------------------------
Attached Files
Scheme KAB8-X
Scheme KAB8-X
TLC of reaction mixtures (1)
TLC of KAB8-7 reaction mixture (2)
KAB8-7 just removed from heat
KAB8-7 crystals on 31/01/12
KAB8-8 crystals on 31/01/12
Left: KAB8-7; Right: KAB8-8