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30th January 2012 @ 04:54
[i]*PS = Pictet-Spengler[/i] TO DO: - Write conclusion START: 30/01/12 FINISH: 02/02/12 [b][u]Background[/b][/u] Further reduction of catalyst loading. See procedure for the preparation of KAB8-7 and KAB8-8. [b][u]Hazard and Risk Assessment[/b][/u] As for KAB8-5 ([url=]here[/url]) [b][u]Previous Related Experiments[/b][/u] [blog]3912[/blog] [blog]3873[/blog] [blog]3660[/blog] [b][u]Following Experiments[/b][/u] [blog]4323[/blog] [blog]4376[/blog] [blog]4520[/blog] [blog]4684[/blog] [b][u]Procedure[/b][/u] MNR10-1 (123.8 mg, 0.270 mmol) was dissolved in toluene (33 mL) before the addition of TfOH/toluene* (51.9 uL, 0.25 M, 13.5 umol) at rt. The clear, colourless reaction mixture was reflux heated at 90 °C from 15:35. [data]2665[/data] The reaction progress was monitored by TLC of extracted aliquots (20-50 uL) against the MNR10-1 starting material and the expected product (identical to KAB8-1). The TLCs were eluted with EtOAc/hexane, 4:1, v/v and stained with KMnO4. 30/01/12 15:40 - Aliquot 1 16:00 - Aliquot 2 16:15 - Aliquot 3 16:30 - Aliquot 4 16:45 - Aliquot 5 17:15 - Aliquot 6 18:00 - Aliquot 7 31/01/12 08:45 - Aliquot 8 09:00 - Taken off heat [data]2661[/data][data]2663[/data][data]2667[/data][data]2671[/data] [b]31/01/12[/b]. TLC of the extracted aliquot 8 suggested no change had occurred overnight and the reaction mixture contained the enediamide intermediate, in lower concentration, and the major component, the completely cyclised product (identical to KAB8-1). The reaction mixture was quenched after 22 hours, with saturated sodium bicarbonate solution (50 mL). The organic fraction was separated and the aqueous layer extracted with EtOAc (3 × 30 mL). The organic layers were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB8-9 as a pale yellow oil. The product began crystallising on standing and was put in the freezer overnight to promote crystallisation. [data]2709[/data] [b]02/01/12[/b] The crystals were filtered and washed with hexane to give KAB8-9 as pale orange crystals (92.4 mg, 93%). 1H-NMR confirmed KAB8-9 as the dimethoxy [i]N[/i]-benzoyl PZQ analogue. [data]2961[/data][data]2963[/data] [b][u]Summary and Conclusion[/u][/b] -------------------------------------------------------------- NOTES 30/01/12 - TfOH/toluene solution made up in previous experiment ([url=]here[/url]). - First time seeing a decent amount of the enediamide intermediate with the TfOH reaction. The unknown low Rf spot started to disappear just as the high enediamide spot appeared. - 17:24. The enediamide spot hasn't got less intense over the last 30 minutes. Will leave the reaction overnight. The amount of acid may be low enough that if it the reaction goes to completion overnight, the product won't decompose (too much). NOTES 31/01/12 - Still no apparent change based on TLC. i.e. reaction contains intermediate and product. - After work-up: product stored in freezer. --------------------------------------------------------------
Attached Files
Scheme KAB8-9
TLC of reaction mixture (1)
TLC of reaction mixture (2)
Reaction mixture at 1 hr
TLC of reaction mixture (3)
TLC of reaction mixture (4)
TLC of reaction mixture (4)
Crystals forming
Raw H-NMR KAB8-9