Protium (Hive Bee)
11-13-02 00:53
No 379220
      Synthesis of Safrole from Phenol  Bookmark   



Proposed synthesis of Safrole from Phenol

If 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 Salicylaldehyde

Equip 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 Catechol

Conversion 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 Narayana


Post 377353 (GC_MS: "Sodium percarbonate and the Dakin reaction", Novel Discourse)



Catechol to 1,2-methylenedioxybenzene
Tet Lett 3489-3490 (1975) and J. Chem. Soc. Section C, 1202-1204 (1969)

1,2-methylenedioxybenzene to 4-Bromo-1,2-methylenedioxybenzene
J. Org. Chem. 23, 908-910 (1958) and J. Liebigs Annalen der Chemie, 689, 156-162 (1965)

4-Bromo-1,2-methylenedioxybenzene to Safrole
Bull. Soc. chim. France, 1892-1895 (1964) (../rhodium/pdf /benzodioxole.deriviatives.pdf)

../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! 

smilelaughwinkcooltonguecoolwinklaughsmile


Pr(+)tium
 
 
 
 
    ChambeRed
(Hive Bee)
11-13-02 01:34
No 379229
      This is an area I am very interested in.  Bookmark   

This is an area I am very interested in.I doubt catechol will be hard to obtain in my lifetime so i'm more interested in the various process beyond that but the farther back one has the ability to start the more options they havesmile.We all have more projects that we'd like to complete than we realistically can but these routes need work,not to mention it's just good chemical family funcool.

Bee's don't die,we just multiply.
 
 
 
 
    Protium
(Hive Bee)
11-13-02 08:32
No 379301
      Just for amusement  Bookmark   

Precursor sources will always be availiable that are much more convienient, it is just one of those synths that made me smile.

This was posted for those who walk around all day with that uncontrollable grin all day because of the secrets that they carry, constantly laughing on the inside with the knowledge that it can be done, and walking around each day musing at everything around them as synthetic precursors.

I was particularly interested in this due to the building of the methylenedioxy bridge, and after studying the mechanics I am surprised that I had never realized it could be done this easily.  It was not until GC_MS posted about this "Dakin" reaction that it came to me, and after some study I have realized some very nice synthetic options, and this is but an obvious one.

Here is to those of us who walk around all day with that secretive smile smile

Pr(+)tium
 
 
 
 
    Rhodium
(Chief Bee)
11-13-02 09:40
No 379309
      The MD-bridge can be even easier than so - reflux ...  Bookmark   

The MD-bridge can be even easier than so - reflux catechol and a base with DCM, dilute with water, extract and distill or steam distill.
 
 
 
 
    ChambeRed
(Hive Bee)
11-13-02 09:56
No 379316
      No need for DMSO chief?,that would be nice.  Bookmark   

No need for DMSO chief?,that would be nice.

Bee's don't die,we just multiply.
 
 
 
 
    Rhodium
(Chief Bee)
11-13-02 09:58
No 379317
      errata  Bookmark   

Oops, I left out the fact that you need a aprotic non-polar solvent, like DMSO. If you want to use water, a PTC is reccommended.

However, the reaction should work in acetone, but I don't know if that's been tested yet.
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
11-15-02 09:55
No 380035
      PTC methylenation recommended  Bookmark   

The PTC methylenation is a very easy and high-yielding reaction. I've performed several runs with 3-methylcatechol and dihalomethane (adogen 464 as catalyst). With DCM I got almost zero yield, but with bromochloromethane (bp abt. 68C) and dibromomethane (bp abt. 100C) it worked really good, yield in both cases approx. 80% of theory. Maybe with DCM is prolonged refuxing under pressure necessary, normal refluxing for 2-3 hours gave almost zero yield. Steam distillation is not necessary, just extract the product from the cooled reaction mixture with low-boiling petroleum ether, remove with a hot water bath the solvent and finally fractional vacuum distillation. An additional wash with dilute NaOH is recommended to remove traces of phenolic impurities.
 
 
 
 
    GC_MS
(Hive Bee)
11-15-02 10:03
No 380037
      diiodomethane  Bookmark   

My old German texts mostly apply CH2I2. I never tried it before, since I can't get it cheap. Dibromomethane is much cheaper and yields aren't that bad at all. At least, for the m-hydroxyphenol I tried almost a year ago wink.

Ave Hive, synthetisandi te salutant!
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
11-15-02 10:14
No 380042
      Dijodomethane = catalyst poison  Bookmark   

At present time I haven't the article at hand, but form memory they say that you can NOT use CH2I2 because it is a PTC poison. It is also MUCH more expensive than bromochloromethane or dibromomethane. Why waste money? I prefer 80% yield with cheap precursors instead maybe a few percent more with expensive reagents.
 
 
 
 
    GC_MS
(Hive Bee)
11-15-02 10:39
No 380051
      CH2I2  Bookmark   

The OLD texts (1920s) I'm referring to don't use any PTC catalyst.

Ave Hive, synthetisandi te salutant!
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
11-15-02 12:01
No 380067
      Logical  Bookmark   

I just want to point out that you can not use it with PTC. If you work without PTC under anhydrous conditions, however, CH2I2 is advantageous. DCM and DBM gave poor yields in this case.