All Notebooks | Help | Support | About
15th June 2012 @ 08:04
Conversion of PMY 48-1 to more polar 2-imino-thiazolidin-4-one arylpyrrole compounds by methylation then condensation with amines.

PMY49-1.png

Reaction start time 17.05
Crude PMY 48-1 (502 mg, 1.51 mmol, 1 equiv.) was dissolved in EtOH (30 mL). N,N-diisopropylethylamine (395 μL, 2.27 mmol, 1.5 equiv.) was added followed by iodomethane (478 μL, 7.55 mmol, 5 equiv.). Reaction was stirred for 64 hours, then concentrated under reduced pressure to an orange solid. TLC shows complete reaction. Solid recrystallised from hot methanol (no washes, iodide salts still present most likely. The batch was dissolved in methanol (55 mL), split in 2 portions. The 2 reactions were treated with Ethanolamine (137 μL, 2.27 mmol, 1.50 equiv. PMY 49-1-A) and morpholine (195 μL, 2.27 mmol, 1.50 equiv. PMY 49-1-B) were added and the reactions heated to reflux. After 24 hours, the reactions were cooled to room temperature and concentrated under reduced pressure. The yellow solids were recrystallised from EtOH/water to obtain yellow powders. Yellow powders (PMY 49-1-A, 31 mg) insoluble in CDCl3 and MeOD. Both batches extracted with DCM (4 × 20 mL). The extracts washed with brine (2 × 30 mL), dried (MgSO4) and concentrated under reduced pressure. PMY 49-1-B, orange foam. PMY 49-1-A orange solid. Triturated with Et2O and transferred to vial using DCM, only partially soluble in DCM. Tedious to handle. Light brown solid.

Both dried under vacuum overnight: PMY 49-1-A (134 mg), PMY 49-1-B (253 mg).

TLC (50% EtOAc/hexane) visualised with UV and KMnO4:
TLC intermediate


NMR:
1H NMR intermediate


Risk and Hazard Assessment:
RA
Attached Files
14th June 2012 @ 00:41
Synthesis of the rhodanine derivative of PMY 2-5 for further elaboration to give variation at the imine of 2-iminothiazolidin-4-one.

PMY48-1.png

Experiment Start Time: 0940 12/06/12
Rhodanine (379 mg, 2.84 mmol, 0.95 equiv.) was dissolved in EtOH (20 mL). Piperidine (443 μL, 4.49 mmol, 1.50 equiv.) was added followed by aldehyde PMY 2-5 (650 mg, 2.99 mmol, 1 equiv.). The brown solution was heated to 60 °C. After 7 hours, TLC shows a only a small amount of SM remaining. Reaction allowed to cool to room temperature. After approx. 16 hours, the mixture was cooled in ice. No precipitate formed. Water was added slowly until the mixture became yellow milky and a sticky gum precipitated out. The mixture was extracted with DCM (3 × 25 mL) and washed with brine then dried (MgSO4) and concentrated under reduced pressure to an orange solid (1.36 g). 1H NMR show new product, a small amount of PMY 2-5, piperidine, ethanol and (potential piperidine salts?).

The crude mixture was dissolved in DCM (60 mL) and washed with 1M HCl (2 × 10 mL), 10% NaHCO3 (2 × 10 mL) where upon the mixture became a milky suspension, water (3 × 20 mL), brine then dried (MgSO4) and concentrated under reduced pressure to a yellow solid.

TLC (20% EtOAc/hexanes) visualised with UV and vanillin:
TLC 7 hours


NMR:
1H NMR crude


Reference:
doi: 10.1016/j.bmcl.2011.09.049
doi: 10.1016/j.bmcl.2007.01.081

Risk and Hazard Assessment:
RA
Attached Files
3rd April 2012 @ 01:19
Synthesis of 4-H near neighbour ZYH 3-1

PMY47-1.png

Reaction Start Time: 10.00 03/04/12
PMY 13-1 (148 mg, 0.77 mmol, 1.0 equiv.) and piperidine (115 μL, 1.16 mmol, 1.5 equiv.) were dissolved in EtOH (10 mL). LMW 4-1 (168 mg, 0.77 mmol, 1.0 equiv.) was added as a solution in EtOH (3 mL) and the reaction heated to 60 °C. The reaction turns to a yellow suspension after approx 45 mins. After 4.5 hours, the reaction was cooled to room temperature then filtered and dried overnight (235 mg, 81% of theory).

See also:
Synthesis of phenyliminothiazolidinone-substituted arylpyrrole (ZYH 3-1)
Vilsmeier Haack Synthesis of 2,5-dimethyl-1-phenyl-1H-pyrrole-3-carbaldehyde (LMW 4-1)
Preparation of 2-phenyliminothiazolidin-4-one (PMY 13-1)

Risk and Hazard Assessment:
See: Synthesis of phenyliminothiazolidinone-substituted arylpyrrole (ZYH 3-1)
Linked Posts
This post is linked by:
Attached Files
9th March 2012 @ 03:22
Testing reactivity of Michael-acceptor of ZYH 6-2 (PMY 41-1) using benzylthiol at 40 °C (close to biological temperatures).

PMY41-1.png

Reaction Start Time: 14.20 09/03/12
ZYH 6-2 (20 mg, 0.05 mmol, 1 equiv.) was stirred in DCM (10 mL). Benzylthiol (27 μL, 0.23 mmol, 5 equiv.) was added and the reaction heated to 40 °C. After 68 hours, solvent had evaporated. A sample of the mixture showed starting materials only by 1H NMR. No peaks consistent with expected product. K2CO3 (approx 0.1 g) was added. After 1 hour, the reaction is a solution with solid base. Stirred at room temperature for approx 20 hours. 1H NMR shows change but no obvious expected product peaks. TLC consistent with SM and some minor products. ESI mass spec. shows only SM. But no mass consistent with benzylthiol adducts.

NMR:
1H NMR 68 hours


Mass Spec:
ESI mass spec


Risk and Hazard Assessment:
Risk Assessment
Attached Files
29th February 2012 @ 03:37
Synthesis of (Z)-2-((4-fluorophenyl)imino)thiazolidin-4-one (PMY 40-1) from rhodanine, ethyl bromoacetate and 4-fluoroaniline. Reference contains an error between text and experimental, therefore also present in SciFinder. Literature experimental procedure omits alkylation of sulphur, prior to subsitution by the aniline.

PMY40-2.png

Reaction Start Time: 14:10 29/02/12
Rhodanine (500 mg, 3.75 mmol, 1 equiv.) was stirred in IPA (5 mL). Does not dissolve on brief heating. Triethylamine (0.58 mL, 4.13 mmol, 1.1 equiv.) was added and the mixture heated to 60 °C. After 5 minutes, the reaction was an orange solution. Reaction was cooled slightly and ethyl bromoacetate (0.46 mL, 4.12 mmol, 1.1 equiv.) added, reaction turns red and a precipitate forms (<5 mins). Reaction was heated to 80 °C. After 1 hours 20 mins, rhodanine consumed. 4-fluoroaniline (0.39 mL, 4.12 mmol, 1.1 equiv) was added portionwise to the hot reaction. After 2 hours, reaction was allowed to cool. After a further 16 hours, the reaction was a thick brown slurry. TLC shows reaction complete. IPA (10 mL) added and stirred for 5 minutes to thin the slurry, then filtered to obtain a brown/grey powder. Recrystallised from hot IPA/water to obtain dark tan needles (0.85 g, 107% of theory). Poorly soluble in CDCl3 but 1H NMR appears to show CH2 and 4 × aryl-H. Requires DMSO NMR.

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 1 hour 20
TLC stage 2, 1 hour
TLC stage 2, 18 hours

Stage 2:left spot is rhodanine for comparison, top spot is intermediate seen in first plate (limiting reagent for stage 2).

NMR:
1H NMR CDCl3


Reference:
doi:10.1016/j.bmc.2010.05.073

Risk and Hazard Assessment:
As for Synthesis of (Z)-2-((4-fluorophenyl)imino)thiazolidin-4-one (PMY 40-1), additional risk of lachromator and toxic ethyl bromoacetate.
Attached Files