external image adrenalinereaction.jpg


Objective

To convert adrenaline to DOPAL by acid catalysis. How this fits into the synthesis of anti-malarials is described here.

Procedure

A solution of adrenaline (0.5 g; 2.75mmol) in 85% phosphoric acid (8 mL) was heated in a 125ml Erlenmeyer flask (for 30 mins) in a glycerol bath then removed from heat and allowed to cool for 30 seconds. The solution was added to distilled water (90mL) and then saturated with NaCl. It was taken up in ethyl ether (60 mL, 35 mL, 40 mL, 25 mL) and dried over anhydrous MgSO4. The ether extract was then evaporated to obtain 100 mg of product that was characterized by TLC and HMR but failed to show an aldehyde peak in 9-10 ppm region.

Results

Characterization of Dopal (24A)

Ran TLC of 24A against adrenaline in 3:1 methylene chloride to methanol (Picture under UV light).

Discussion

NMR of 24A (H-NMR)
-- shows no aldehyde peak at 10.0 ppm
-- this is unexpected since EXP024 is a repeat of step one in EXP023.

Conclusion

Experiment was aborted because there was no aldehyde peak.

Log

2006-08-28

16:00 : Started to heat glycerol bath to 170C.
16:10 : 0.5 g adrenaline and 85% phosphoric acid (8 mL) were added to a 125mL Erlenmeyer flask
16:11 : Adrenaline and phosphoric acid solution was placed in glycerol bath (170C) and stirred.
16:15 : Adrenaline and phosphoric acid solution reaches 120C. The temperature of the solution was maintained between 115-125C by lowering or raising the Erlenmeyer flask in te glycerol bath.
16:45 : The solution was removed from heat and added to 90 mL of distilled water. Solution was then allowed to sit for 1.5 hours.
18:15 : Solution was saturated with NaCl (without filtering).
7. Added 40 mL distilled water to solution and separated with 60 mL ethyl ether. Washed the ether layer by adding 40 mL distilled water and separated with 35 mL ethyl ether. Separated two more times with 40 mL ethyl ether each.
8. Obtained about 25 mL of a semi-solid substance that formed between the ether layer and the bottom layer (from above step). This was separated as best as possible and added to 10 mL acetone, which dissolved it.
9. The sample dissolved in 10 mL acetone (above step) was added to the ether layer collected. The solution was then separated again using 25 mL ethyl ether.
10. Added 10 mL of buffer solution (pH 7.0) and stirred for 10 minutes.\
11. Separate the ether layer out.
12. Solution was saturated with anhydrous magnesium sulfate, stirred for one mintute, and then filtered.
13. Rotovaped the solution.

2006-08-29

14. High vacuum sample to get a crude product, 24A, with a mass of 100 mg.
15. Ran TLC of 24A against adrenaline in 3:1 methylene chloride to methanol.

Tags

Adrenaline InChI=1/C9H13NO3/c1-10-5-9(13)6-2-3-7(11)8(12)4-6/h2-4,9-13H,5H2,1H3
DOPAL InChI=1/C8H8O3/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,4-5,10-11H,3H2