Piperidine:

The main stumbling block for clandestine synthesis of PCP in the US is the aquisition of piperidine. Piperidine is a closely watched chemical and is generally obtained by diversion from wholesale manufacturers. It has little legitimate use outside of pharmaceutical manufacturing. A clean bottle (i.e one that is not watched or traceable) can sell for as much as $1000 a kg on the black market. It can be synthesized by the reduction of pyridine, but it should be noted that pyridine itself is somewhat watched because of its use in methamphetamine synthesis. It also may be obtained by the hydrolyis of piperine, a major constituent of black pepper oil, by hydrolysis with aqueous KOH or by cyclization of 1,5-diaminopentane. Of course, the necessity of piperidine can be eliminated by synthesis of a PCP analog that does not contain the piperidine ring, such as PCPy. The piperidine ring can also be built by alkylation of PCA with 1,5-dibromopentane, as discussed in Scheme V.

 

Methods for reduction of pyridine to piperidine:

1. Electrolysis- a common method of industrial preparation. J.Chem.Soc.; 1950; 679; J.Chim.Phys.Phys.Chim.Biol.; 22; 1925.
2. Sodium metal in ethanol- Chem.Ber.; 17; 1884; 513; Justus Liebigs Ann. Chem.; 247; 1888; 51; Chem.Ber.; 17; 1884; 156; US pat. 1971743.
3. Sodium in NH3 at Temperature -80  -50 C - Chem.Ber.; 57; 1924; 1685.
4. Catalytic hydrogenation with Platinum- Chem.Ber.; 45; 1912; 3592; Chem.Ber.; 49; 1916; 1600; J.Amer.Chem.Soc.; 50; 1928; 2260. J.Appl.Chem.USSR (Engl.Transl.); EN; 58; 1985; 278-281 (Solvent H2O Yield 97.9% temperature 149.9 C).
5. Cat. Hydrogenation with Paladium at 150 C-  Chem.Ber.; 57; 1924; 152.
6. Hydrogenation with Nickel- European Patents 395231; 346222; J.Amer.Chem.Soc.; 56; 1934; 2425, 2427; J.Org.Chem.; 50; 3; 1985; 394-396.
7. Tin in HCl- Chem.Ber.; 14; 1881; 1856.

Cyclohexanone:

Although cyclohexanone is not watched as closely as piperidine, it is well known to be a vital ingredient for PCP manufacture. It is commonly available in bulk in the resins industry, where it is used as a solvent, and is also used in huge quantities in the manufacture of several polymers. It may also be synthesized on a laboratory scale by the oxidation of cyclohexanol.

Procedure: Cautiously add 20 ml of conc. sulfuric acid to 60 g of crushed ice and mix well. Add 20 g of cyclohexanol and place a thermometer in the mixture (temp. should be <30 C). Prepare a solution of 21 g sodium dichromate dihydrate in 10 ml of water. Add about 1 ml of this solution to the reaction flask with vigorous swirling. Add the rest of the dichromate solution with continuous swirling at a rate that keeps the temperature between 25 and 35 C. After the addition is complete, continue stirring until the temperature falls by 1 or 2 degrees. Add about 1 g of solid oxalic acid to destroy any excess dichromate. Rinse the reaction mixture into a 500 ml distillation flask with 100 ml of water, add a boiling stone, and distill the product rapidly. The cyclohexanone will distill as a mixture with water (an azeotrope) at about 95 C. Continue distillation until 60-100 ml of distillate is obtained. Add about 15 g of sodium chloride to the distillate and swirl until most of it has disolved. Transfer the mixture to a seperatory funnel and discard the lower aqueous layer. Dry the upper layer with 1-2 g of potassium carbonate and decant. The cyclohexanone will now be of sufficient purity to use in PCP synthesis, but if further purification is desired, it can be redistilled.