Synthesis of 4-methoxy PCP

Warning: while the final compound is not scheduled, and therefore is legal, one of the intermediates (PCC) is a schedule II controlled substance in the USA. Thus proper licensing would be required to undertake this procedure. Note that replacement of pyrrolidine with piperidine in step 1 of this synthesis would provide a final compound that would almost certainly be as potent as 4-methoxy PCP, and would avoid the use of controlled PCC.

4-methoxy PCP has been previously tested in animals and found to be somewhat less potent than PCP itself. Results in this human volunteer confirm this. A rough estimate would be 70% as potent. This is still significant, considering how potent PCP is.

A possible advantage of this analog is decreased duration of effect. This is because the 4-methoxy group provides a site for metabolism and elimination of the drug. This is a significant point, because the extended action of PCP is a real disadvantage in cases of acute overdosage.

For those that are unfamiliar with the effects of these compounds, the experience is very hard to describe. The most commonly known compound that is directly comparable is ketamine. Ketamine's effects are quite similar to PCP and 4-methoxy PCP, but K. is much less potent.

Be Aware:

These compounds can be quite devilish to bioassay for the uninitiated. Remember that the dissociatives are often powerful deleriants. They can produce effects that are strikingly similar to schizophrenia. This similarity is much closer than that generally seen with the phenethylamine and tryptamine hallucinogens. So if you find that you have suddenly discovered any cosmic keys to the universe, you should probably wait until you come down before acting on them. Also, even after an individual feels that he has returned to baseline consciousness, there are often subtle alterations in thinking patterns that may not be apparent to himself. Physical coordination and ability to think coherently may not totally return for a day or more after dosage. I highly recommend reading the book "The Scientist" by John Lilly for a good discussion of the dangers of repeated use, as well as interesting points about the actual user experience.

A preferred method of administration is to smoke small amounts (several milligrams) of the material on an inert carrier, such as parsley. Since the effects are felt fairly rapidly, it is easy to build up to the desired effects, with little danger of overdosage. Note that very intense synergistic effects are produced with THC. When the desired state of consciousness is produced by inhalation of the PCP analog, a tiny toke of marijuana will produce very profound effects, changing the nature of the experience dramatically (and extremely pleasurably).

I strongly believe that this class of compounds has real potential as adjuncts to psychotherapy, and possibly as antidepressants. They can produce feelings of overwhelming bliss and integration with the universe. I've been told by one person that suffers from depression that their depression is lifted for a period of a week or more following a single dose.

Synthesis of 4-methoxy PCP

Step 1: preparation of piperidine cyclohexane carbonitrile (PCC)

A solution of 6.3g sodium bisulfite in 21 mL of water was cooled in an ice bath. 5.3g (5.03 mL) of cyclohexanone was added with rapid stirring. This resulted in a thick white slurry. A solution of 3.93g if potassium cyanide in 9.48g (8.17 mL of piperidine was added to the slurry. The slurry turned into a two-phase reaction mixture, which was allowed to stir overnight. The next morning, stirring was stopped, and the mixture was cooled on ice. The upper oily phase soon crystallized as beautiful ice-like crystals. These were removed by filtration, washed well with cool water, and dried between paper towels.

Yield: about 5.45g

Step 2: preparation of the Grignard reagent

1.9g (.08 moles) of Magnesium turnings were placed in a round bottom flask, along with a magnetic stirbar and 30 mL of dry ether. In a second flask, a solution of 15.2g (0.08 mol.) of 4-methoxy bromobenzene (i.e. 4-bromo anisole, see Note 1) in 10 mL of ether was prepared. Approximately 9 mL of the bromobenzene solution was added to the flask containing the ether/magnesium. This flask was then gently heated and stirred until the reaction began, as indicated by formation of a cloudy gray precipitate. The remaining ether/bromobenzene solution was added at a rate that allowed for gentle reflux (see Note 2 and Note 3).

Step 3: reaction of PCC and Grignard reagent

A solution of 3.5g (0.02 mol) of the compound from step 1 was dissolved in a small amount of toluene (~10 mL). This solution was then dried over calcium chloride, filtered, and then diluted with an equal amount of anhydrous ether. This was slowly added to the Grignard reagent prepared in step 2, followed by heating and stirring for 2 hours. The reaction mixture was then poured onto a mixture of several grams of ammonium chloride and ice, with stirring. After bubbling stopped, several grams of sodium hydroxide was added and the mixture was shaken in a seperatory funnel. The lower aqueous phase was separated, shaken with fresh ether, and discarded. The combined organic phases were washed 3 times with water, and the water layers discarded. The organic layer was then extracted 3 times with dilute hydrochloric acid. The acid layers were basified with sodium hydroxide and then extracted with ether. The combined ether layers were evaporated to give ~2.5g of a colorless oil (see Note 4). After sitting for 2 days, followed by cooling in a freezer, the oil began to crystallize into awesome colorless crystals.

Notes

1. Goddamn this shit stinks! Its not so bad at first, somewhat of a floral smell. But it won't go away! It just seems to get stronger and stronger. Care must be taken not to spill the tiniest drip, unless you want everything to be covered with its overpowering odor and your neighbors asking pointed questions about your hobbies.
2. Success of step 2 and 3 are dependent of having absolutely dry conditions! A drying tube and a closed addition funnel are helpful, but not absolutely necessary. All of the glassware used in these steps was previously dried in an oven for an hour at 350 degrees F.
3. The actual amount of 4-methoxy bromobenzene needed could be reduced by about half. The amount used here was about a four fold excess, to insure complete reaction under the less-than-ideal conditions in which the synthesis was being carried out. A two-fold excess should be more than sufficient under better laboratory conditions.
4. Ether is extremely flammable, dumbshit! Doing this in the open is asking for trouble! Trying to evaporate the remaining ether after extraction by open evaporation led to a small fire. The only source of ignition was a frying pan heated above the flash point of ether (no spark was needed)! Fortunately the chemist was prepared to smother the fire without disaster. A fire extinguisher was also on hand just in case, but was not needed. Do you really want to be in the situation of trying to control a fire whose smoke contains vapors of a powerful psychoactive drug?