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17th August 2011 @ 00:29
Product obtained in 10% yield. === Synthesis of the core pyrrole of [url=http://www.chemspider.com/Chemical-Structure.1769782.html]TCMDC-123794[/url] and [url=http://www.chemspider.com/Chemical-Structure.1817204.html]TCMDC-123812[/url] from the GSK Tres Cantos antimalarial dataset listed in [url=https://www.ebi.ac.uk/chemblntd]ChEMBLdb NTD database[/url] Condensation of 4-fluoroaniline and 2,5-hexanedione to form 1-(4-fluorophenyl)-2,5-dimethyl-1[i]H[/i]-pyrrole. [b]Experiment start time 16.10 EST 17/08/2011[/b] 4-fluoroaniline (94.7 μL, 1 mmol, 1 equiv.) and [url=http://en.wikipedia.org/wiki/Hexane-2,5-dione]2,5-hexanedione[/url] (117.3 μL, 1 mmol, 1 equiv.) were dissolved in ethanol (50% aqueous, 1 mL) in a microwave tube and heated in a CEM Discover microwave. Target temperature 160 °C for 20 minutes (5 minute ramp time). Measured 96 °C, 50 psi. Reaction shows new product by TLC and baseline starting materials. Reaction mixture diluted with water (10 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were then washed with 1M HCl (5 mL), dried (MgSO4) and concentrated under reduced pressure to obtain a brown oil. The oil was purified by chromatography on base (NEt3) washed silica (1% NEt3/petrol) to obtain a thick colourless oil (18 mg, 10%) that turned blue on standing (10 minutes). No mass ions consistant with SM or products were observed by ESI (11.38 EST 18/08/2011). 1H NMR consistant with product and literature[url=http://dx.doi.org/10.1002/cmdc.200600026]1[/url] [b]TLC (10% EtOAc/petrol) visualised by UV and vanillin:[/b] Column TLC: [b]Analytical Data[/b] 1H (200 MHz, CDCl3, TMS) 7.24-7.10 (4H, m), 5.90 (2H, s), 2.02 (6H, s). [b]1H NMR Spectra[/b] [data]24[/data] [b]References:[/b] [list=1] [*] Manetti, F.; Magnani, M.; Castagnolo, D.; Passalacqua, L.; Botta, M.; Corelli, F.; Saddi, M.; Deidda, D; De Logu, A. [i]ChemMedChem[/i], [b]2006[/b], [i]1[/i], 973–989. doi: [url=http://dx.doi.org/10.1002/cmdc.200600026]10.1002/cmdc.200600026[/url] [/list] [b]Hazard and Risk Assessment:[/b] [data]6[/data]
Attached Files
PY111
PY111.png
Risk Assessment
TLC
column TLC
PY11.pdf
Comments
Re: Paal-Knorr Synthesis of 1-aryl-2,5-dimethyl Pyrrole Core (PMY 1-1) by Matthew Todd
18th August 2011 @ 06:20
Crude 1H might indicate if getting any product at all if you can see those pyrrole methyls?