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Phenylalanine to amphetamine or N-methylamphetamine;

Historically

There are two routes that have been previously investigated and are documented on Rhodiums website and I am sure everyone reading this has seen. The first method uses Lithium Aluminium Hydride to reduce  phenylalanine to phenylalaninol. Then proceeds to protect the amine function, with a carbobenzyloxy (Cbz) group. p-Toluenesulfonyl chloride is then used to create the toluenesulfonate ester which when  reduced will remove the hydroxyl group aswell. Reduction with lithium aluminium hydride affords methamphetamine, all steps proceed with retention of configuration so if one started with D-phenylalanine one would end up with the required (S) enantiomer. The second route similarily starts by reducing phenylalanine to phenylalaninol this time using lithium borohydride, then protection of the amine  functionality with a tert-Butyloxycarbonyl(BOC) group forming a carbamate. Iodination of the hydroxyl group proceeds, and reduction of the iodo compound with sodium selectride reduces it to its parent  hydrocarbon. Triflouroacetic acid removes the BOC protection to leave amphetamine. Also this method proceeds with retention of configuration if you started with D-phenylalanine you would end up with the required (S) enantiomer.

Method 1

Method 2

http://www.erowid.org/archive/rhodium/chemistry/amphetamine.phenylalanine.html

Now obviously those are not OTC, and require multi-step synthesis using some nasty chems. I was hoping to investigate some of the newer more relavent methods that are not the same as above. If anyone wants to add anything please feel free.

Phenylacetaldehyde from Phenylalanine

Phenylalanine can be treated with nitrous acid to produce phenyllactic acid, nitrous acid is produced from sodium nitrite and any mineral acid. Phenyllactic acid can then be treated with Lead tetra acetate (made with red lead oxide and glacial acetic acid) and will yield around 58% phenylacetaldehyde.

http://www.journalarchive.jst.go.jp/jnlpdf.php?cdjournal=bcsj1926&cdvol=9&noissue=1&startpage=8&lang=en&from=jnlabstract

Strecker degradation of phenylalanine with sodium hypophosphite should return a better yield of phenylacetaldehyde than the procedure above.  Also alpha methylation of phenylalanine as previously discussed after strecker degradation yields phenylacetone.

http://www.erowid.org/archive/rhodium/chemistry/p2p.strecker.html

With phenylacetaldehyde in hand one would proceed to gas with methylamine to create the schiffs base, which could be dripped into methyl magnesium iodide to produce a modest (40%+) yield of racemic methamphetamine.

Phenylalaninol from phenylalanine

Lithium Aluminium Hydride or Lithium Borohydride have been used in the past but the best option is today is Sodium Borohydride with nickel chloride or molybdenum trioxide to return the amino alcohol in 80%+ yields.

http://journals.tubitak.gov.tr/chem/issues/kim-99-23-2/kim-23-2-2-98058.pdf

From here I have seen much controversy, many loosely thrown accusations of reducing phenylalaninol with Hydroiodic acid to amphetamine. A poster named JustIce from WD was throwing around claims of reducing phenylalaninol to amphetamine with 80% yields using phosphorous acid and iodine with 2x excess at 120*C for 15 hours. He was actually quietly telling members via PM to do it, the results were verified via hp chromatography he said. A highly regarded member also wrote this at science madness, adding to the confusion;

“however the alcohol of phenylalanine, phenylalaninol, has been reduced to the alkane …..that claim I've made …….next!……solo”

To clear this up for good! Javas comments are true but.. Hydroiodic reductions refluxing phenylalaninol at anywhere under 125*C that are under 35 hours in duration WILL produce 1-phenyl-2-amino-3-iodopropane hydroiodide. Hydroiodic acid reductions ARE able to further dehalogenate 1-phenyl-2-amino-3-iodopropane to amphetamine but it will take around  a week at high temps under reflux, or in a sealed bomb that would have to be very hot!!! 58.4% Hydroiodic acid and red phosphorous refluxed at 125*C for 24 hours will produce 1-phenyl-2-amino-3-iodopropane in about 80-85% yield with traces of amphetamine! Decreasing the red-p and increasing the reflux to 35 hours will have no effect except the reaction rate will be decreased one third. So unless an extremely long hot reflux is employed or the use of a sealed bomb at high temps for a prolonged period of time is employed you will be producing 'JustIodo'. Hopefully Java can clear this up and explain what is actually necessary for complete reduction, but be certain that your average HI/I2 reaction wont cut it! (read the patent!) A much safer route would be to halogenate the amino alcohol to 1-phenyl-2-amino-3-iodopropane hydroiodide with an average hydroiodic acid/I2 reflux at about 110*C for seven hours to yield over 80%. Or with 48% hydrobromic acid in a sealed reaction vessel heated to 170*C for five hours to return 49% yield of 1-phenyl-2-amino-3-bromopropane hydrobromide. 

References

Ref for iodo; Ref for phenylalaninol reduction Patent no;3193581

Ref for bromo; Ring Cleavage of 1-Benzenesulfonyl-2-benzylethylenimine with 

Hydrogen Bromide http://pubs.acs.org/doi/abs/10.1021/ja01137a505

Reductive dehalogenation of 1-pheny-2-amino-3-halopropane

Then reductive dehalogenation, is carried out with LAH or raney nickel to yield amphetamine. N-methylation should proceed swiftly at this point!


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