FriendlyFinger (Hive Bee)
05-05-03 05:52
No 431447
      Safrole Isomerising methods  Bookmark   

Hi there, This has to be a mistake right?

Isomerisation of 2 to 7. (Safrole to Isosafrole). To 80.0g(0.49mmol) of 2(safrole) was added 100mL of a 3N solution Of Potassium hydroxide in n-butyl alcohol and the reaction mixture was stirred at room tempreture for 3 h. The mixture was poured into a solution of 12mL concentrated HCl, and 52mL of ice water. After neutralization with additional concentrated HCl, the organic layer was extracted with three 35-mL portions of ethyl acetate. After usual workup, A white oily residue was obtained and distilled to furnish 78.4g (96-98%) of the styrene derivative 7(isosafrole) as a colourless oil. J.Pharm.Sci Vol.81, No.12 1220-1221 1992.

I haven't isomerised yet, but from what I've been reading on the fabulous fucking search engine, the above should read "refluxed for 3 hours" and not "room tempreture for 3 hours"  Am I right?

What about this one from J Braz Chem Soc 11(4), 371-374 (2000) on Rhodium's site.

To 91 mL (100g, 620 mmol) safrole were added 500 mL of a 3M solution of potassium hydroxide in n-butanol and the reaction mixture was stirred under reflux for 3 h. After cooling, the mixture was poured into a solution of 3 mL of concentrated hydrochloric acid and 20 mL of ice water. After neutralization, the organic layer was washed with water and dried with anydrous Na2SO4. After removal of the excess n-butanol, the residue obtained was distilled under reduced pressure giving 9.5 g (95%) of pure isosafrole as a colorless oil, with spectra in agreement with the literature.

That decimal point looks sus!!

They are using 4 times the amount of KOH than the first write up for the same amount of safrole (80g) to get about the same yield. I'm sure they mean 95g not 9.5g. Does the first method work? If so, why would anybody use the second method? 

(Chief Bee)
05-05-03 09:27
No 431485
      Typo  Bookmark   

Here is the original article: J Braz Chem Soc 11(4), 371-374 (2000) (

It does actually say 9.5% but on the other hand they claim 95% yield from 100g of safrole, so it has to be 95g. Scrap that decimal point, I have corrected it in the file at my page.

Where did you find the J Pharm Sci article text? In a post at the Hive?
(Hive Bee)
05-06-03 08:43
No 431687
      Rhodium, it was actually posted by you.  Bookmark   

Rhodium, it was actually posted by you.

Post 385627 (Rhodium: "Isosafrole Physical data", Newbee Forum)

Thanks for the Brazilian reference. I've noticed that on you page this proceedure is scaled 10x, except for the amount of HCl and water.


Be joyful, though you've concided all the facts!
(Chief Bee)
05-07-03 03:00
No 431807
      I'll fix that  Bookmark   

Oops, sorry - I will correct that scaling error.

In the post linked by you, I have not posted any actual text from the J Pharm Sci article, only a single line describing its topic. Is the whole article available somewhere, or parts of it?
(Hive Bee)
05-07-03 04:22
No 431830
      I have a photo copy of the full text.  Bookmark   

I have a photo copy of the full text. I just bought a scanner, so I will post it once I've figured out how to do it properley.