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16th January 2012 @ 05:36
Synthesis of 3-N-acetyl-1-phenylthiourea

reactionscheme20-1.jpg

Experiment start time: 17:10 EST 16/01/2012
Phenylthiourea (3.2 g) was combined with pyridine (20 mL) under a nitrogen atmosphere and acetic anhydride (20 mL) was added by portions over two minutes. The reaction was left stirring overnight. In the morning TLC showed formation of two products and the mixture was poured over ice water (100 mL). The precipitate was filtered off to give a yellow crystalline solid (3.4 g, 89% yield) and TLC showed a single spot corresponding with product. H NMR was quite clean and consistent with the desired product and melting point is 168-170 °C, similar to but below the reported value of 173-174 °C for the product acetylated at the primary amine.

Data summary table:
Yield % Melting point °C 1H NMR 13C NMR19F NMR IR Mass spec
ZYH 20-1 89 173-174Quite clean, consistent (pdf, all NMR .zip) Consistent (pdf)NAYes (pdf, .dx) submitted for APCI


Comparison with literature:
The product is a known compound (CAS: 1132-44-1). C NMR is similar to the reference spectrum but with a different peak at 137.39.

Reference:
Method taken from DOI: 10.1080/03086647708079937

Hazard and risk assessment:
Hazard and risk assessment
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11th January 2012 @ 07:40
Acetylation of para-methyl arylpyrrole near neighbour analogue

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Experiment start time: 5:15 EST 11/01/2012
ZYH 5-1 (50 mg, 0.13 mmol, 1 equiv.) was dissolved partially in toluene (~5 mL) and stirred under a nitrogen atmosphere. Pyridine (~20 μL, 0.25 mmol, 1.9 equiv.) was added, followed by acetic anhydride (~40 μL, 0.4 mmol, 3 equiv.). The mixture was heated to 80 °C and left stirring overnight under nitrogen. In the morning the mixture was evaporated under reduced pressure to give a yellow powder and monitored by H NMR, which showed complete disappearance of starting materials but the presence of some impurities. The powder was dissolved in ethyl acetate and adsorbed onto silica and washed with hexane (~ 150 mL) then washed off the silica with ethyl acetate and concentrated under reduced pressure to return a yellow powder (25 mg, 54%). Some mass was lost and appeared to have been retained on the silica but the product was relatively clean by H NMR.

Data summary table:
Yield % Melting point °C 1H NMR 13C NMR19F NMR IR Mass spec
ZYH 17-1 54 decomposes ~256Impurities (pdf May need resynthesisNAYes (pdf, .dx) Submitted for APCI



Hazard and risk assessment:
Refer to: Acetylation of para-trifluoromethyl near neighbour analogue (ZYH 12-1)
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11th January 2012 @ 07:27
Acetylation of unsubstituted arylpyrrole near neighbour analogue

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Experiment start time: 17:15 EST 11/01/2012
ZYH 3-1 was dissolved partially in toluene (~5 mL) and stirred under a nitrogen atmosphere. Pyridine (~20 μL) was added, followed by acetic anhydride (~40 μL). The mixture was heated to 80 °C and left stirring overnight under nitrogen. The liquid was then evaporated off under reduced pressure to give a yellow powder, which showed disappearance of the starting materials and was fairly clean by proton NMR.

Data summary table:
Yield % Melting point °C 1H NMR 13C NMR19F NMR IR Mass spec
ZYH 16-1 108(!) decompose ~245Not assigned (pdf, all NMR .zip) Not assigned(pdf)NAYes (pdf, .dx) Submitted for APCI


Hazard and risk assessment:
Refer to: Acetylation of para-trifluoromethyl near neighbour analogue (ZYH 12-1)
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11th January 2012 @ 00:09
Acetylation of ZYH 6-1

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Experiment start time: 10:45 EST 11/01/2012
ZYH 6-1 (102 mg, 0.22 mmol, 1 equiv.) was dissolved in toluene (~20 mL) and stirred under a nitrogen atmosphere. Pyridine (~40 μL, 0.5 mmol, 2 equiv.) was added, followed by acetic anhydride (~80 μL, 0.8 mmol, 4 equiv.) and the mixture was refluxed under nitrogen at 80 °C for 7 hours. The liquid was then evaporated off under reduced pressure to give a yellow powder. NMR showed the reaction to be complete but also some unexpected complexity in the spectrum, possibly indicating multiple products, and considerable grease contamination. The product was purified by column chromatography, but the complex spectrum and some grease were still present. The product was analysed by HPLC and found to be mostly pure, with around 0.5 % impurity present.

Yield % Melting point 1H NMR 13C NMR19F NMR IR Mass spec
ZYH 12-2 92 Decomposes ~245Yes (pdf, all NMR .zip) Yes pdfYes (pdf)Yes (pdf, .dx) Submitted for APCI



Hazard and risk assessment:
Refer to: Acetylation of para-trifluoromethyl near neighbour analogue (ZYH 12-1)
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6th December 2011 @ 04:25
Vilsmeier Haack Synthesis of 2,5-dimethyl-1-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrrole-3-carbaldehyde from 1-(3,5-bis(trifluoromethyl)phenyl)-2,5-dimethyl-1H-pyrrole (ZYH 1-1, remainder of pure fraction)

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Experiment start time: 3:20 EST 06/12/11
DMF (2 mL, 26 mmol, 13 equiv.) was stirred under a nitrogen atmosphere in an ice bath. Phosphoryl chloride (0.200 mL, 2.15 mmol, 1.1 equiv.) was added and the reaction stirred for 25 minutes. 1-(3,5-bis(trifluoromethyl)phenyl)-2,5-dimethyl-1H-pyrrole (599.9 mg, 1.95 mmol, 1.00 equiv., ZYH 1-1, pure fraction) was dissolved in DMF (8 mL) and added slowly, then the mixture was removed from the ice after 5 minutes. TLC after 45 min showed the reaction to be complete, and the mixture was poured over ice and the pH adjusted to 7, then left stirring overnight. In the morning, the pH was adjusted to 11 and the mixture cooled on ice for 30 minutes then filtered off, to give a fine, pale brown powder (627 mg, 96% yield). Melting point: 88-89 °C.

Data summary table:
Yield % Melting point 1H NMR 13C NMR19F NMR IR Mass spec
ZYH 4-x 91 85.4-86.8Yes (pdf, all NMR .zip) Consistent (pdf, multiplets)Yes (pdf)Yes (pdf, .dx) Submitted


Comparison with literature:
The product was not found in the literature.

NMR assignment:
1H NMR (CDCl3, 300 MHz): δ = 2.03 (s, 3H), 2.33 (s, 3H), 6.44 (d, J = 0.69 (rotamers), 1H), 7.74 (s, 2H), 8.04 (s, 1H), 9.90 (s, 1H). 13C NMR (CDCl3, 300 MHz): δ = 11.4 (1C), 12.8 (1C), 107.4 (1C), 122.7 (q, J = 273.1, 2C), 122.9 (1C) 123.0 (dq, J = 3.9, 3.8 Hz, 1C), 128.7 (q, J = 3.4 Hz, 2C), 130.6 (1C), 133.6 (q, J = 34.3 Hz, 2C), 138.0 (1C), 138.8 (1C), 185.4 (1C) ppm.

TLC (25% ethyl acetate in hexane), visualised using UV and vanillin:
TLC at 45 min

Spots from left to right: reaction mixture; reaction mix plus starting materials; starting material.

Hazard and risk assessment:
Refer to:
Preparation of 2,5-dimethyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrole-3-carbaldehyde (ZYH 2-1)
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