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Novel thiazole route to methamphetamine

Started by Rhodium, October 18, 2003, 09:33:00 AM

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Rhodium

This is an indeed novel route to methamphetamine...

4-methyl-5-phenyl-thiazole + Sodium Ethoxide -> Methamphetamine
Helv.Chim.Acta; 25, 528 (1942)

Patent CH233303




Preparations of 4-methyl-5-phenyl-thiazole

1-bromo-1-phenyl-propan-2-one + formamide -> 4-methyl-5-phenyl-thiazole (Benzene, P2S5, 143-147°C/10mmHg, 45%)
J.Chem.Soc.Perkin Trans.2, 1538-1543 (1981)

4-methyl-thiazole + Benzoyl Peroxide -> 4-methyl-5-phenyl-thiazole
Bull.Soc.Chim.Fr., 3280-3288 (1968)

1-bromo-1-phenyl-propan-2-one + thioformamide -> 4-methyl-5-phenyl-thiazole
Helv.Chim.Acta; 25, 528 (1942)

1-chloro-1-phenyl-propan-2-one -> 2,5-dimethyl-3,6-diphenyl-[1,4]dithiane-2,5-diol (Et2O, MeOH, NaHS, H2S, -20°C)
2,5-dimethyl-3,6-diphenyl-[1,4]dithiane-2,5-diol + CH2O + NH3 => 4-methyl-5-phenyl-2,5-dihydro-thiazole
4-methyl-5-phenyl-2,5-dihydro-thiazole + Sulfur -> 4-methyl-5-phenyl-thiazole
Justus Liebigs Ann. Chem.; 615, 77, 83 (1958)

Bull.Soc.Chim.Fr. 4514 (1967)
Bull.Soc.Chim.Fr. 4521 (1967)
C.R.Hebd.Seances Acad.Sci.Ser.C 262, 687 (1966)
C.R.Hebd.Seances Acad.Sci.Ser.C 264, 336 (1967)
C.R.Hebd.Seances Acad.Sci.Ser.C 265, 744 (1967)
C.R.Hebd.Seances Acad.Sci.Ser.C 266, 822 (1968)

RepVip

What are the chances of getting a copy of these articles in english:
Helv.Chim.Acta; 25, 528 (1942)
Bull.Soc.Chim.Fr., 3280-3288 (1968)
?

EDIT:
Actually, if it's possible just to get a copy of Bull.Soc.Chim.Fr., 3280-3288 (1968) I may know someone who can translate it--though I'm sure she'd be suspicious  ;)

Rhodium

I have never before seen such a well-hidden synthesis of methamphetamine in an article before - it is really hard to spot that they are actually synthesizing it from one of their isoxazolines (check the article yourself).

2-Methylisoxazolin-5-ones. Part I.
F. DeSarlo, L. Fabbrini, G. Renzi

Tetrahedron 22, 2989-2994 (1966)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/meth.2-methylisoxazolin-5-one.pdf)

https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000465430-file_v7uu.gif" title="View this image">

2,3-Dimethyl-4-phenylisoxazolin-5-one (IX)

Ethyl alpha-phenylacetoacetate (0.1 mole) and N-methylhydroxylamine hydrochloride (0.45 mole) in anhydrous pyridine (100 ml) were heated at 100°C for 12 hr. The residue after evaporation of the solvent was washed with ether, then with water, yield 91%; mp 112-113°C (ligroin). In alcohol, as reaction solvent, the yield was 73%.

Hydrogenation of IX

A solution of IX (0.02 moles) in 150 ml anhydrous EtOH* was shaken for 1 day under a 3-4 atm. H2 pressure, with Raney Ni. After the absorption of 0.04 moles H2, the solution was filtered and fractionated to isolate N-Methylamphetamine (XIV); bp 38°C/0.3 torr; 208°C/750 torr. mp of the hydrochloride 129-134°C.

* If 95% EtOH was used instead of anhydrous, the compound only absorbed 1 equivalent of H2 and the product was instead the intermediate imine.


Precursor Synthesis

Ethyl Phenylacetate + Ethyl Acetate -> Ethyl alpha-Phenylacetoacetate
J. Amer. Chem. Soc. 69, 119 (1947)
J. Chem. Soc. 123, 1764 (1923)
Chem. Ber. 63, 1557 (1930)
Chem. Ber. 66, 1512 (1933)

Phenylacetonitrile + Ethyl Acetate -> Phenylacetoacetonitrile

Organic Syntheses, Coll. Vol. 2, p. 487

(http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0487)

Phenylacetoacetonitrile -> Ethyl alpha-Phenylacetoacetate

Organic Syntheses, Coll. Vol. 2, p. 284

(http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0284)

psilocin

nice!
other hydrogenation possibilities?

Rhodium

That is very likely, but it is not in the literature as the 5-isoxazolinone is a pretty uncommon ring system.

WizardX

Also...

P2P from a-Phenylacetoacetonitrile

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0389



This is why benzyl cyanide and phenyl acetic acid is so HIGHLY RESTRICTED.

Rhodium

Reference from

Post 465430

(Rhodium: "Novel thiazole route to methamphetamine", Stimulants)


Strukturchemishe Untersuchungen IV.
Über eine reduzierende Aufspaltung des 5-Phenyl-4-methyl-thiazols

H. P. Schenk and D. Lamparsky

Journal of Chromatography, 204, 391-395 (1981)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/nutmeg.oil.analysis.pdf)

Summary: Sodium metal reduction of 5-Phenyl-4-Methyl-Thiazole to Methamphetamine.