Thursday, February 09, 2006

Exp 002

Objective: To convert adrenaline to a catechol aldehyde under acid catalysis via refulxing under nitrogen gas in glacial acetic acid and a small amount of sulfuric acid. How this fits into the synthesis of anti-malarials is explained here.
IR of Adrenaline


Prepared a solution of 25.5mg (0.139mmol) adrenaline, 25mL acetic acid, 1.5ml 1M sulfuric acid and placed in a 50mL round bottom flask. Refluxed solution under nitrogen gas. Solution refluxed for approximately 2 hours. Ran TLC plates of the reaction against a standard solution of adrenaline and acetic acid.


TLC plates were run under methylene chloride and under methanol. Those under methanol had rf values of approximately 0.6. Those under methylene chloride had rf values of approximately 0.1.
MS Aldehyde in glacial acetic
MS Aldehyde from extraction


Discussion: The mass spectrum that was done by FAB shows no M+ peak for the catechol aldehyde as discussed here in the Discussion section. There was probably some oxidation of the reaction in taking the samples. The TLC plates show no signs of the aldehyde forming either. Moving on.

Conclusion: We learned from Exp003 that FAB is too harsh a process to give us the M+ and M+2 peaks that we expects. MALD/I may generate better results. Also because there were no fast moving spot on the TLC, as is expected, the product was probably not formed.

1. 11:55) Prepared a new solution(Soln1) of 25.5mg (0.14mmol) of adrenaline, 25mL of glacial acetic acid, and 1.5mL of a 1M sulfuric acid solution. Started reflux of new solution in a 50mL round bottom flask, and a 0.5mL sample was taken to use in an NMR tube in a sit in a temperature bath at 60 degrees Celsius flushed with nitrogen gas. Other than this, no sample was taken for a t=0, however at t=0 the solution appeared clear with no visible amounts of undissolved adrenaline.
N.B.: The NMR tube was kept in the temperature bath for an hour and a half, however because a working NMR was not available in a sufficient amount of time, that portion of the experiment has been scraped.
2. 12:55) A 1mL sample was taken from the refluxing of Soln1. (t=1hr) This sample became tan over time as well as the refluxing Soln1.
3. 13:55) A 1mL sample was taken from the refluxing Soln1 which was now very tan. (t=2hr). The Soln1 was taken off reflux and a loosely fitting stopper was placed on the round bottom flask which was then no longer on nitrogen gas atmosphere.
4. 14:10) A small solution of 1.87mg of adrenaline and 1mL of glacial acetic acid was made in a 3mL vile to use as a standard(Std) for TLC against Soln1 samples t=1hr and t=2hr.
5. 14:22) A TLC was done with the Std and t=1hr in both methanol and methylene chloride. The TLC plates were first spotted with thin capillaries however this produced no visible results even in an iodine chamber so the plates were respoted using a melting point capillary tube. The plates were then reintroduced to their respectable methanol and dichloromethane. The Rf values for the plates in dichloromethane were in the vicinity of 0.1 and those in methanol were in the vicinity of 0.6.

11:00. Prepared a solution of 26.4mg adrenaline and 25mL acetic acid.

11:30. Refluxed under N2 gas. Took a 1mL t=0 sample.

12:30. Took a 1.5mL sample of reaction(13t[1]). Took half a mL of this and extracted with 5mL of water and 0.5mL methylene chloride. Ran two TLC of 13t[1] versus the t=0 sample in 4:1 hexanes methylene chloride in MeOH.

13:30. Took a 1.5mL sample of reaction(13t[2]). Took half a mL of this and extracted with 1mL methylenechloride and 5mL of water. Ran two TLC of
13t[2] versus t=0 in 4:1 hexanes methylene chloride in MeOH.

14:30. Took a 1.5mL sample of reaction(13t[3]). Turned off reflux.


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