Isosafrole From Piperonal
—This will work just as well in converting benzaldehyde to pro-penylbenzene as it will in converting piperonal. This is like the millionth method Strike has pulled from the reference 19. This was the most street-applicable article Strike has ever come across, but the greatest thing about this article's recipes is that THEY WORK! Strike means to say they work big time! A lot of this has to do, no doubt, with the fact that the most accomplished amphetamine chemists co-authored the work: Drs. Shulgin and Nichols.
This method is merely an application of the Grignard reaction but is a lot less troublesome because it uses really common chemicals. This method can be done as it was done in the reference where a phenylbutene was made using a bromopropane ( bromo-propane and bromoethane are cheap to purchase or can be made
from propanol or ethanol). These phenylbutenes will produce a perfectly respectable amphetamine that make an excellent substitute for X, but for confusion's sake Strike is going to describe the isosafrole synthesis as well.
The apparatus to use is the same as fig. 15. 52g of 1-bromopropane for the phenylbutene or 46g bromoethane for isosafrole or propenylbenzene is placed in the separatory funnel. In the flask is stirring a solution of I4g Mg turnings and 50mL anhydrous ether and the bromine compound is dripped into the flask over a 20 minute period of time then the solution stirred for an extra 10 minutes. Next, a solution of 50g piperonal (or 35g benzal-dehyde) and 200mL anhydrous ether is placed in the separatory funnel and added drop wise to the Grignard reagent over 30 minutes time. The reaction mix is then refluxed for 8 hours, hydro-lyzed by the addition of 75 mL ice cold saturated ammonium chloride solution and vacuum filtered to remove the crud. The etherial filtrate is washed with ice cold 1.5N HCI solution, dried through Na2S04 and the ether removed by distillation to afford a residue of 62g of crude alcohol intermediate (almost 96% yield!).
The alcohol intermediate happens to be the exact kind of intermediate that was produced by the Grignard reagent reaction with propanal to produce isosafrole back-a-ways in the big chapter. So what the chemist does is apply the 1g of KHS04 to that crude alcohol intermediate and process it just as was done before to give isosafrole ,or propenylbenzene or 3,4-methylenedioxyphenyl -1-butene or phenylbutene (yield=91%!). This is a great little procedure.
Continue reading here: Crystallization
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