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29th February 2012 @ 05:24
Conclusion: Ethyl β-(carbethoxymethylthio)propionate was synthesised with an 84.5% yield.

This experiment, adapted from Brown et al. (1946), is an upscaled version of JRC 4-1.

1751.png

Experiment start time: 3:55 pm, 29/02/2012: Ethyl mercaptoacetate (2.19 mL, 18.22 mmol, 1 equiv.) and piperdine (0.1 mL, 1 mmol, 0.05 equiv.) were stirred under a dry nitrogenous atmosphere whilst ethyl acrylate (1.94 mL, 18.21 mmol, 1 equiv.) was added dropwise over 2 hr. The reaction was left overnight, and was monitored via TLC 19 hr later, as shown below.

TLC +19hr (10% ethyl acetate/hexane, visualised with UV and anisaldehyde):
JRC4-2(11am).png


Reaction had not gone to completion, as it had in JRC 4-1, so additional ethyl acrylate was added dropwise over 0.5 hr (total ethyl acrylate: 2.14 mL, 20.08 mmol, 1.1 equiv.) alongside additional piperidine (2 drops). TLC 6 hr later showed reaction had gone to completion.

TLC +25 hr (10% ethyl acetate/hexane, visualised with UV and anisaldehyde:
JRC4-2(5pm).JPG


1H-NMR was consistent with JRC 5-1. Ethyl β-(carbethoxymethylthio)propionate (3.395 g, 15.4 mmol) was recovered in 84.5% yield.

H1NMR:
JRC4-2.zip
JRC4-2.pdf


Risk Assessment
As in JRC 4-1

Linked Posts:
Synthesis of ethyl β-(carbethoxymethylthio)propionate (JRC 4-1) - JRC 4-1

References:
Brown, G. B.; Baker, B. R.; Bernstein, S.; Safir, S. R., BIOTIN. II. 3,4-trans-DIAMINOTHIOPHANE. The Journal of Organic Chemistry 1947, 12 (1), 155-159.
Linked Posts
Attached Files
27th February 2012 @ 04:45
This procedure, adapted from Duus (1981), is summarised below diagramatically.

2003.png

Experiment start time: 3:43 PM, 27/02/2012:
JRC 5-1 (1.19 g, 6.83 mmol, 1 equiv.) was dissolved in methanol (6 mL) and added to a pre-cooled solution of 25% sodium methoxide in methanol (1.4 mL, 5.36 mmol, 0.95 equiv.) dropwise over 2 hr at 0°C. TLC at 5:45 pm showed no reaction as of yet (TLC was difficult to read, presumably due to low concentrations)

TLC: 5PM 28/2/2012 in 10% ethyl acetate/hexane, visualised with UV/anisaldehyde
JRC5-2(5PM).JPG


TLC the following day showed nothing moving in the RM column, and various materials in the SM column.

TLC: 1PM 28/2/2012 in 10% ethyl acetate/hexane, visualised with UV/anisaldehyde
JRC5-2(1PM).JPG


Reaction was stopped at 1:30 PM and mixture was poured onto 12 g glacial acetic acid/ice, before being extracted twice with DCM (10 mL). The combined organic layers were washed twice with sodium hydrogen carbonate (10 mL) and twice with water (10 mL) before being dried with anhydrous magnesium sulfate. Solvent was removed under reduced pressure to yield 0.285 g of product. H1NMR was inconclusive.

1H-NMR:
1.zip
JRC52.pdf


The product was placed under high vacuum to dry overnight, before another H1NMR was run. Again, this was inconclusive.

1H-NMR:
1.zip
JRC5-2dried.pdf


Risk Assessment (paper copy signed):
JRC 5-1 RA (2).pdf


Linked Posts:
Synthesis of 2-Ethoxycarbonylthiolan-3-one (JRC 5-1) - JRC 5-1

References:
F, Duus., A study of the tautomerism of 2- and 4-ethoxycarbonylthiolan-3-ones implicating stereochemical effects of ring-substitution. Tetrahedron 1981, 37 (15), 2633-2640.
Linked Posts
Attached Files
22nd February 2012 @ 04:44
This procedure, adapted from Duus (1981), is summarised below diagramatically.

2001.png

Reaction start time: 3pm 22/2/2012
A dried reaction vessel under nitrogenous atmosphere was cooled in an ice bath. 2.95 mL (9.11 mmol, 1 equiv.) of 21% wt sodium ethoxide in denatured ethanol and 4 mL 100% ethanol were added to the vessel with stirring before 1.88 g (9.11 mmol, 1 equiv.) of crude JRC 4-1 was added dropwise over 2 hr. Mixture turned from light yellow to orange with addition of JRC 4-1. TLC at 5pm showed some starting material remaining, with several new products formed.

TLC 5pm (22/2/2012) in 10% ethyl acetate/hexane. Visualised with UV/vanillin

JRC 5-1 (5PM 22/2/12)


TLC at 10am the following morning was nearly identical (indicating equilibrium has possibly been reached). Reaction mixture at this time was orange.

TLC 10am (23/2/2012) in 10% ethyl acetate/hexane. Visualised with UV/vanillin

JRC 5-1 (10am 23/2/12)


The mixture was poured onto 6g ice/6g glacial acetic acid (1.04 mol, ~ 12 equiv.) before being extracted with DCM (2 x 10 mL). The organic layer was washed with sodium bicarbonate (3 x 10 mL) with vigorous bubbling, and washed with water (1 x 10 mL) before being dried over MgSO4. DCM was removed under reduced pressure to yield 0.943 g of product as an orange oil. H1NMR revealed the cyclisation did not occur, and that the starting material remained throughout the reaction.

H1NMR:
1.zip
JRC5-1.pdf


Risk Assessment:
5-1riskassessment


Linked posts:
Synthesis of ethyl β-(carbethoxymethylthio)propionate (JRC 4-1)

References:
F, Duus., A study of the tautomerism of 2- and 4-ethoxycarbonylthiolan-3-ones implicating stereochemical effects of ring-substitution. Tetrahedron 1981, 37 (15), 2633-2640.
Linked Posts
Attached Files
21st February 2012 @ 02:15
This procedure, adapted from Brown et al. (1946), details the synthesis of ethyl β-(carbethoxymethylthio)propionate, as shown below diagramatically.

1751.png

Conclusion: Ethyl β-(carbethoxymethylthio)propionate was successfully synthesised from the procedure below, though in an unknown yield (JRC 4-2 was synthesised in an upscaled procedure, giving the same product in 85% yield).

Start time: 2pm 21/2/2012:
Ethyl mercaptoacetate (1 mL, 9.120 mmol, 1 equiv.) and piperidine (0.005 mL, 0.05 mmol, 0.005 equiv.) were mixed under nitrogen. The reaction vessel was cooled in ice water whilst ethyl acrylate (1.01 mL, 9.576 mmol, 1.05 equiv.) was added dropwise over an hour. Upon addition of the ethyl acrylate, the mixture appeared to turn white. TLC at 5:00 pm showed much of the mercaptoacetate consumed. The reaction was left to react overnight.

TLC (5pm): 20% ethyl acetate/hexane visualised with UV/vanillin
JRC4-1(21st@5pm).JPG


The following day TLC showed no ethyl mercaptoacetate remaining and hence the crude reaction mixture was used in JRC 5-1 without further purification (hencem no yield recorded).

TLC (10am): 20% ethyl acetate/hexane visualised with UV/vanillin
JRC4-1(22nd@10am).JPG


1H-NMR revealed that the reaction had taken place as planned.

1H-NMR:
1.zip
JRC4-1.pdf


Risk Assessment: (paper copy signed)
UPDATEhazardform


Linked posts:
Synthesis of 2-Ethoxycarbonylthiolan-3-one (JRC 5-1)
Upscaled synthesis of ethyl β-(carbethoxymethylthio)propionate (JRC 4-2)

References:
Brown, G. B.; Baker, B. R.; Bernstein, S.; Safir, S. R., BIOTIN. II. 3,4-trans-DIAMINOTHIOPHANE. The Journal of Organic Chemistry 1947, 12 (1), 155-159.
Linked Posts
Attached Files