Novel route to Cathinone

[foxy2]

Propiophenone -> ISONITROSOPROPIOPHENONE (1,2-Propanedione, 1-phenyl-, 2-oxime)

http://www.orgsyn.org/orgsyn/prep.asp?prep=CV2P0363

Then reduce the oxime and you have Cathinone, if you can selectively reduce the oxime while not also reduceing the ketone.  Or if you reduce it all, you have Amphetamine.

You can also use butyl nitrite in the synth.
Butyl nitrite preparation.

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0108

Here is a similar transformation in which butyl nitrite is used.

http://www.orgsyn.org/orgsyn/prep.asp?prep=CV3P0191

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[foxy2]

Here is a synthesis of propiophenone, which is then converted to methcathinone (ephedrone) and then to racemic ephedrine.  This is another alternative to the above synthesis.

Synthetic ephedrine from propionic acid. 
Fel'dman, I. Kh.; Bel'tsova, N. N.; Ginesina, A. A.
Zh. Priklad. Khim.  (1962),  35(6),  1364-7.

Stirring 37 g. EtCO2H, 40 ml. dry C6H6, and 29 g. PCl3 1 hr. at 55-62°, cooling to 30°, and removing H3PO4 gave a soln. of EtCOCl.  Adding this soln. to 85 g. dry C6H6 and 65 g. anhyd. AlCl3 over 3 hrs. at 35-45°, heating 2 hrs. at 45-50°, cooling to 30°, pouring into 300 g. ice and 50 g. coned. HCl, sepg. the C6H6 layer, adding 20% Na2CO3 till alk. to litmus, distg, with steam, drying the C6h6 layer of the distillate over CaCL2, distg. C6H6, and distg. residue at 103-5°/10 ram. yielded PhCOEt (I).(propiophenone) 

Adding dropwise 67.5 g. Br to 56.5 g. I in 130 ml. C6H6 at 30°, blowing out HBr formed with air while stirring, adding 30 ml. H2O, neutralizing with 20% Na2CO3, adding 56.5 g. MeNH2.HCl in 55 H2O, adding over 10 rain. 67.5 g. NaOH in 80 ml. H2O at 50-60°, raising the temp. to 70°, cooling to room temp., blowing out with the air unreacted MeNH2, sepg. the C6H6 layer, extg. the H2O layer with C6H6, washing combined C6H6 soln. with H2O, mixing with N HCl, evapg. in vacuo to sirupy consistency, stirring with Me2CO, heating to boiling in Me2CO, cooling, filtering, washing with Me2CO, and drying yielded 70-74 % (based on I) ephedrone-HCl (II), m. 175-9°.

Adding 14.2 g. NaOH in 135 ml. EtOH to 62 g. II in 300 ml. EtOH at 5-10°, filtering, washing pptd.  NaCl with EtOH, reducing filtrate and wash EtOH with H over Raney Ni at room temp. and attn. pressure, cooling to 5-10°, filtering, acidifying the filtrate with HCl, filtering, evapg, in vacuo at 45° yielded 64% dl-ephedrine-HCl m. 187-90° (EtOH), and 19% pseudoephedrine-HCl.  
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[foxy2]

This has to bee one of the easiest synths, if you can make your L-PAC.

3-Imidazoline. III. Intramolecular oxidation-reductions.
Kirchner, Gerhard.   
Ann.  (1959),  628  92-5.     
CAN 55:144117    AN 1961:144117

cf. CA 54, 3389g. 
(-)-Phenylacetylcarbinol (15 g.), 9.8 g. cyclohexanone, and 15 cc. concd. NH3 was stirred 5 hrs., the mixt. extd. with Et2O, and the ext. dried and distd. to give 10-11 g. (-)-4-methyl-2,2-pentamethylene-5-phenyl-D3-oxazoline (I), b. 120°/0.3 mm., n20D 1.5370, [a]20D -192.7° (96% EtOH).

a-Aminopropiophenone (Norephedron)(Cathinone). 
I (5 g.) was heated under reflux for 15 min. with H2O-free HCl-satd. iso-PrOH, 0.3 cc. H2O was added, and heating continued to give 3.7 g. Norephedron hydrochloride, m. 182°. 
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Antoncho]

Foxy, buddy, in all my frankness i must say that the nitrosation procedure has been known for quite some time. It was first brought up by Assholium - as a way to 2C-B: acetophenone by condensation p-DMB w/ AcOH in polyposphoric - (BTW, see PiHKAL, there's such a procedure w/propionic acid, i believe) followed by nitrosation and 1-step reduction to 2C-H (Assholium suggested 4 bar hydrogenation on Pd/C - i guess i know one person who could try this for us   ) Unfortunately, this last step is kinda dubious (esp-lly w/out pressure, which would bee highly desirable) - although i once posted a such proc. (AcOH/H2SO4)

Sheesh, i'm resembling fMan, proally  - in a great hurry.


Now. The 2nd procedure you posted absolutely fucken ROCKS. I saved it to my disk immediately.

Rhodium, if you ever decide (have time and courage, i should've said) to review all the old interesting stuff that you forgot to add to your page, ask me - i will bee of help  

Also i wonder if there is a way to selectively reduce oxime to amine, not affecting ketogroup... Any thoughts?

Antoncho

[Rhodium]

Yes, sodium dithionite reduces oximes but not ketones. I have posted references for that.

There is no real problem choosing what methods from my "not done yet" directory on my hard drive which are worth publishing - they all are. They are just not compiled, organized and converted to HTML yet... And I never use any HTML editors, they write worse code than I do, and I don't have complete control over what it writes either.

[foxy2]

"Foxy, buddy, in all my frankness i must say that the nitrosation procedure has been known for quite some time."

Antoncho
I can't remember everything that gets posted.  I was messing around over at Org. Syn. and just happened to stumble across that synth and it looked like a simple way to CAT, so I posted it.  The other procedure was only dealing with acetophenone's and when looking at it, even after posting this, it is not obvious to me that it was also applicable to propiophenones.

But alas now I find the little tidbit tucked away.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cb-new.txt

Funny to see Rhodium argueing with assholeium

here is the 2C-B post

Post 171132

(Rhodium: "New ways of making 2C-B", Novel Discourse)

So you are right it was "known".
Oh well, this adds some more info to whats already on Rhodiums site.  
Foxy
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Rhodium]

This is not fair... I'll almost delete that! I didn't know what kind of authority I was talking to back then - in 1998!  

[Osmium]

Yes, that oxime via nitrite synth is old, I've seen it first in a JMC ref where they used it to make the indane analogs of amphetamines.

Acetophenones/propiophenones etc. can be prepared from (substituted) benzenes, the acids and P2O5 or polyphosphoric acid and SiO2. Yields aren't perfect, but this reaction is very cheap and easy to do. I posted this years ago, anyone remembers this?
I'm not fat just horizontally disproportionate.

[Rhodium]

Oh, yes - I archived it on my page:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/acetophenones.html

Antoncho: What is the journal Zh. Priklad. Khim. 35(6), 1364-7 (1962) and is it accesible?

[Antoncho]

It means "Journal of Applied Chemistry". I believe, it isn't particularly rare - in addition, there recently appeared a couple of library enthusiasts at HyperLab (who already got several wanted articles that i just don't have time to trtanslate yet)

I'll ask if it can bee obtained, but if by any chance someone gets it bee4 - tell me.


Antoncho

[Rhodium]

Methcathinone and Designer Analogues: Synthesis, Stereochemical Analysis, and Analytical Properties
Jack DeRuiter, Lisa Hayes, Allen Valaer, F.T. Noggle, and C. Randall Clark

Journal of Chromatographic Science, Vol. 32, 552-564 (1994)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/forensic/methcathinone.analog.analysis.pdf)

Abstract
This paper describes the synthesis, stereochemical analysis, and analytical properties of methcathinone and related compounds. Methcathinone represents a new class of designer street drugs that can be prepared easily from readily available starting materials such as the ephedrines and pseudoephedrines. The oxidation of each individual isomer of ephedrine and pseudoephedrine produces homochiral methcathinone via conservation of configuration. Thus 1R,2S-ephedrine and 1S,2S-pseudoephedrine yield S-methcathinone, and 1S,2R-ephedrine and 1R,2R-pseudoephedrine produce R-methcathinone. The isomers of methcathinone were separated by gas chromatography as the diastereomeric amides following derivatization with S-(-)-N-(trifluoroacetyl)prolyl chloride (TPC). The gas chromatographic-mass spectrometric analysis of methcathinone and designer analogues showed a major chromatographic peak with a mass spectrum characteristic of the parent molecule. However, the major chromatographic peak was accompanied by a secondary, well-resolved peak that yielded a molecular ion 2 mass units less than that of the major peak. Deuterium labeling experiments showed this minor component to arise through the thermal oxidation of the 2,3-carbon-carbon bond of the side chain to yield the 2,3-enamine. Cathinone, methcathinone, dimethcathinone, ethcathinone, and diethylcathinone (diethylpropion) were separated by reversed-phase liquid chromatography using a phenyl bonded stationary phase and an acidic (pH 3) mobile phase. Methcathinone and cathinone do not interfere or cross-react in standard drug abuse screening methods based on analysis by thin-layer chromatography or immunoassay.

[Rhodium]

Radiosynthesis of [³H]methcathinone, an inhibitor of monoamine reuptake transporters
Nicholas V. Cozzi and Arnold E. Ruoho

Journal of Labelled Compounds and Radiopharmaceuticals, 41, 927-933 (1998)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/cathinone.methylation.html)

Abstract
[³H]Methcathinone (2-[³H]methylamino-1-phenylpropan-1-one), an inhibitor of monoamine reuptake transporters, was synthesized by N-methylation of cathinone using [³H]methyl iodide in toluene/methanol. A two-step purification procedure employing preparative silica gel TLC, followed by reverse-phase HPLC, was developed to separate [³H]methcathinone from unreacted starting material and side products. We were able to generate radio- and chemically pure [³H]methcathinone, ready for use in pharmacological experiments, in about eight hours. Overall yield was about 4% based on [³H]methyl iodide.

[Rhodium]

Ephedrone: 2-Methylamino-1-Phenylpropan-1-One (Jeff)
K. Y. Zhingel, W. Dovensky, A. Crossman and A. Allen

Journal of Forensic Sciences 36(3), 915-920 (1991)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/ephedrone.html)
^{(Kudos to Smilaxium for retrieving the original article!)}

Abstract
Ephedrine and pseudoephedrine, commonly used in clandestine laboratories within the United States to synthesize methamphetamine by means of reduction, are utilized within the Union of Soviet Socialist Republics (USSR) in synthetic oxidation with potassium permanganate to form 2-methylamino-1-phenylpropan-1-one. This ketone product of methamphetamine, termed "ephedrone" and "Jeff", is profiled with the use of spot tests, infrared spectrophotometry, mass spectrometry, gas chromatography, ultraviolet spectroscopy; and hydrogen (¹H) and carbon-13 (¹³C) nuclear magnetic resonance spectroscopy.