Khalid Mirza


Jean-Claude Bradley at Drexel University


To convert adrenaline to DOPAL by acid catalysis


A solution of adrenaline (1.0g 5.5mmoles) in 85% phosphoric acid was heated (116-118C) in a round bottom flask (for 1hour ) in a heating mantle then removed from heat and allowed to cool . The solution was stirred for 90 min in distilled water and then saturated with NaCl. It was taken up in ethyl ether, and dried over anhydrous MgSO4.The ether extract was then evaporated to obtain DOPAL (80 mg 0.53mmol, 9.5% yield)
25A: 3, 4-dihydroxyphenylacetaldehyde; C8H8O3; brown oil;1H NMR (external image delta.gif ppm, CDCl3 500Mz) 3.4 (bs, 2H), 3.6 (s, 2H), 9.7 (s,1H), 6.4-6.8 (aromatics, 3H).


1. TLC of 25A in 3:1 MeCl2:MeOHand in 6:1 MeCl2/ MeOH, and stained with CAM Rf- 0.66 in 6:1 MeCl2/ MeOH
2. HNMR of 25A in acetone-d6, and the expansions of the prominent peak regions (one, three, four. five) (500MHz Varian inova). The integration is good enough to not require further purification.


This is the first time that DOPAL was obtained pure (by NMR integration) immediately after extraction into ether. There are 3 factors that may have contributed to this: preheating the phosphoric acid then adding the adrenaline powder, carrying out the reaction under nitrogen and a careful temperature control. It is likely that the main impurity showing up in the H NMR spectra of previous attempts (EXP016, EXP023) is the carboxylic acid (Exp016HNMR, Exp023HNMR), the formation of which the inert atmosphere should have prevented.


DOPAL can be obtained pure in 9.5% yield by heating adrenaline in 85% phosporic acid at 116-118 C for an hour followed by hydrolysis and extraction into ether.



13:18] 15 ml of 85% phosphoric acid was stirred in 3-neck round bottom flask with a thermometer inserted in it. A gentle flow of Nitrogen gas was maintained throughout the heating period over the reaction.
14:08] When the temperature of phosphoric acid stabilized at 118C for about 15 mins, 1g of Adrenaline was added.
15:08] The reaction was heated over a period of 1 hour between 116-118C. The reaction was removed from the heating mantle and let stand at room temperature for 20s.
15:10] The hot solution was poured in 180ml of distilled water and stirred for 90 min.
16:40] Saturated the solution with Sodium Chloride
16:50] Extracted successively with 120-,70-, and 50ml portions of ethyl ether. An emulsion like, layer separated soon after the addition of ether. All ethers layers (emulsion) were accumulated together and 30ml of acetone was added to dissolve the emulsion. Addition of acetone cleared-up the emulsion and gave two distinct layers (bottom layer was discarded as being aqueous).
17:30] The extract was stirred for 10mins with 20mls of phosphate buffer solution (pH 7.0), then saturated the solution with sodium chloride again.
17:50] Separated the ether layer, dried it over anhydrous MgSO4, and filtered through a sintered glass funnel, rotovaped and set on high vacuum for 2 hours.
20:00] Obtained 25A (80mg).
10. TLC of 25A was obtained in 3:1 MeCl2 / MeOH and MeCl2.
11. A HNMR of 25A was also obtained in acetone-d6 and the expansions of the prominent peak regions (one, three, four. five) (500MHz Varian Inova).


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