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The Hive => Stimulants => Topic started by: Rhodium on October 18, 2003, 09:33:00 AM

Title: Novel thiazole route to methamphetamine
Post by: Rhodium on October 18, 2003, 09:33:00 AM
This is an indeed novel route to methamphetamine...

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

Patent CH233303 (http://l2.espacenet.com/dips/viewer?PN=CH233303&CY=gb&LG=en&DB=EPD)




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)
Title: Articles
Post by: RepVip on October 20, 2003, 11:21:00 AM
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  ;)
Title: Methamphetamine via 2-Methylisoxazolin-5-one
Post by: Rhodium on November 25, 2003, 01:00:00 AM
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/pdf/meth.2-methylisoxazolin-5-one.pdf)

(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000465430-file_v7uu.gif)

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)

(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)

(http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0284)
Title: wow
Post by: psilocin on November 25, 2003, 01:35:00 AM
nice!
other hydrogenation possibilities?
Title: That's left as an exercise for the reader
Post by: Rhodium on November 25, 2003, 02:18:00 AM
That is very likely, but it is not in the literature as the 5-isoxazolinone is a pretty uncommon ring system.
Title: Also...
Post by: WizardX on November 25, 2003, 07:34:00 PM
Also...

P2P from a-Phenylacetoacetonitrile

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



This is why benzyl cyanide and phenyl acetic acid is so HIGHLY RESTRICTED.
Title: 5-Phenyl-4-Methyl-Thiazole to Methamphetamine
Post by: Rhodium on March 17, 2004, 12:50:00 PM
Reference from

Post 465430 (https://www.thevespiary.org/talk/index.php?topic=7893.msg46543000#msg46543000)

(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)

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

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