Proposed synthesis of Safrole from PhenolIf anyone gets really bored here is a nice little project to undertake. I am mainly posting it to show just how easy it
could be to avoid the commercial sources of precursors, if neccessary or simply as just a prudent step. I hope that at the very least this might inspire some more thought as to precursor synthesis from availiable materials.
Phenol is used in making plywood, construction, automotive and appliance industry. It is also used in the production in the manufacture of nylon and epoxy resins. Other uses of phenol include a disinfectant, slime-killing agent, and in some medicines.
Phenol to SalicylaldehydeEquip a 1 liter 3 necked flask with an efficient reflux conderser, a mechanical stirrer, and a thermometer; the bulb of which is within 2 cm of the bottom of the flask. Place a warm solution of 80 grams of sodium hydroxide in 80 ml. of water in the flask, add a solution of 25 grams of phenol in 25 ml. of water, and stir.
Adjust the temperature inside the flask to 60-65*C (by warming on a water bath or by cooling, as neccessary); do not allow the crystalline sodium phenoxide to separate out. Introduce 60 grams of chloroform in 3 portions at intervals of 15 minutes, by means of a dropping funnel fitted into the top of the condenser with a grooved cork. Maintain the temperature of the well-stirred mixture at 65-70*C during the addition by immersing the flask in hot or cold water as may be required. Finally heat on a boiling water bath for 1 hour to complete the reaction. Remove the excess chloroform from the alkaline solution by steam distillation. Allow to cool, acidify the orange-colored liquid cautiously with dilute sulphuric acid, and again steam distill the almost colorless liquid until no more oily drops are collected. Set aside the residue in the flask for the isolation of p-hydroxybenzaldehyde.
Extract the distillate at once with ether, and remove most of the ether from the extract on a water bath. Transfer the residue, which contains phenol as well as salicylaldehyde, to a seperatory funnel or small stoppered bottle, add about twice the volume of saturated sodium bisulfite solution, and shake vigorously (preferably mechanically) for about a half hour, and allow to stand for 1 hour. Fliter the past of bisulfite compound at the pump, wash it with a little alcohol, and finally with a little ether to remove the phenol. Decompose the bisulphite compound by warming in a round bottom flask on a water bath with dilute sulfuric acid, allow to cool, extract the salicylaldehyde with ether, and dry the extract with anydrous manesium sulphate. Remove the ether and distill the residue from an air bath. Collect the salicylaldehyde ( colorless ) at 195-197*C. The yeild is 12 grams ( from 25 grams of phenol not too shabby )
It can be purified either by formation of the bisulfite compound or by adding to a large excess of a luke-warm solution of copper acetate (previously saturated near the boiling point), shake well, and allow to stand several hours in ice. Filter, wash the precipitate thoroughly first with alcohol and then with ether. Decompose the solid with dilute sulfuric (10%) acid, extract the aldehyde with ether, dry the ether, and distill. The yeild from a good commercial sample may be as high as 80% ( but of course mechanical loss will vary with purification )
VOGEL IV, 122
Salicylaldehyde to CatecholConversion in 91% yeilds to the hydroxyphenol product, catechol, via the Dakin reaction with sodium percarbonate.
Sodium Percarbonate: A Convenient Reagent for the Dakin Reaction
Tetrahedron Letters 33(7) (1992) 865-866
G W Kabalka, N K Reddy, C NarayanaPost 377353
(GC_MS: "Sodium percarbonate and the Dakin reaction", Novel Discourse)
Catechol to 1,2-methylenedioxybenzeneTet Lett 3489-3490 (1975) and J. Chem. Soc. Section C, 1202-1204 (1969)1,2-methylenedioxybenzene to 4-Bromo-1,2-methylenedioxybenzeneJ. Org. Chem. 23, 908-910 (1958) and J. Liebigs Annalen der Chemie, 689, 156-162 (1965)4-Bromo-1,2-methylenedioxybenzene to SafroleBull. Soc. chim. France, 1892-1895 (1964)
(
https://www.thevespiary.org/rhodium/Rhodium/pdf/benzodioxole.deriviatives.pdf)
https://www.thevespiary.org/rhodium/Rhodium/chemistry/safrole.html
This is for those of you who are just plain bored but could easily turn out to be a viable source if you are willing to do the legwork. In any case I thought this route might be interesting and no promises (as I have quite a few little projects already) but I will probably give it a shot if I have time in the future between other things.
In any case it amuses me that potential (although perhaps not viable) MDMA precursors can be found in everyday things like rotting wood, or cigarette smoke. The war will never be lost. Precursors are everywhere!
Pr(+)tium
