Author Topic: (pseudo)Ephedrine to Meth w/ Raney-Nickel  (Read 5999 times)

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Rhodium

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(pseudo)Ephedrine to Meth w/ Raney-Nickel
« on: December 26, 2002, 10:23:00 PM »
General procedure for Raney Ni catalyzed hydrogenolysis of aromatic alcohols

Applied Catalysis A: General 219, 281–289 (2001)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ephedrine-rani-1.pdf)

1-Phenylethanol (2g) was added to a mixture of Raney nickel (5g) in 2-propanol (30 ml). While open to the atmosphere, the reaction mixture was vigorously stirred and refluxed (water-cooled condenser attached to flask) for 15 minutes. Isolation of the product involved decanting the 2-propanol solution, washing the Raney nickel with 2-propanol (3×10 ml), filtering the combined 2-propanol layers through celite, and evaporation of the 2-propanol and acetone to give ethylbenzene in 98% yield.

The yield is substantially the same with 1-Phenylethanol, 1-Phenylbutanol, 2,2-Dimethyl-1-phenyl-1-propanol and several other more or less sterically hindered alcohols, and both Raney Nickel and Raney Cobalt can be used as catalyst. The reaction is fast, clean, and uses simple isopropanol (IPA, 2-propanol) as the sole reducing agent (it turns into acetone) in conjunction with the catalyst. It is reasonable to believe that this reaction may work with Urushibara Nickel, and that (pseudo)ephedrine can be used as substrate to give methamphetamine.


Raney Ni catalyzed hydrogenolysis of (pseudo)Ephedrine amide to Methamphetamine amide

J. Org. Chem. 63, 7795-7804 (1998)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ephedrine-rani-2.pdf)

To a mechanically stirred suspension of Raney Ni (wet, prepared from 200 g of aluminum-nickel alloy, Raney type Ni-Al 50:50) in ethanol (700 mL) was added 4 (29.55 g, 0.125 mol), and the mixture was heated to reflux for 2 h. After cooling to room temperature the mixture was filtered through Celite. Concentration, flash chromatography (hexane/ethyl acetate, 2:1) on silica gel (218g), and distillation (88°C/0.35 mmHg) gave 5 as a colorless liquid (23.80 g, 86%).

This is almost as close as it gets. In the article the authors describe that they did not have the proper licenses to synthesize methamphetamine, so they used very similar derivatives of ephedrine and pseudoephedrine (the ethoxycarbonyl amide) and reduced them to the ethoxycarbonyl amide of methamphetamine as the first step towards their target compound (which is completely unrelated). The yields for the ephedrine and pseudoephedrine amides were 86% and 81%, respectively, simply by refluxing them with freshly prepared Raney Nickel (Fieser & Fieser Vol. 1, p 729) in ethanol for two hours. Again, Urushibara Nickel might just work, and there is no glaring obstacle against using plain (pseudo)ephedrine instead of the corresponding amides, but this has not yet been tried in practice, and has been left as an exercise to the reader. Now you have something to do next year too, the Hive staff and elderbees always do their best to prevent you from getting bored...  ;)

Kudos to Foxy2 for finding these articles in the first place, and Happy New Year - whereever you are...  :)

Organikum

  • Guest
not only the Vatikan...
« Reply #1 on: December 27, 2002, 01:25:00 AM »
has hidden archives.....

We will see if it holds what it promises. I have no problem looking like an idiot if something like this comes over in exchange. If it works it may help the methheads to calm down from the annie & RP madness and they can lean back and watch the MDMA cooks getting more greedy every day.....

ORG

now or never

Barium

  • Guest
Mmmm
« Reply #2 on: December 28, 2002, 12:46:00 PM »
What is pretty darn interesting is that the authors used EtOH as the hydrogen source in the second hydrogenolysis described. I like that  :)

Organikum

  • Guest
Very straight forward, I don´t buy it.
« Reply #3 on: December 28, 2002, 06:13:00 PM »
´thatThe first article looks serious and on the point. The second article is IMHO regarding the hydrogenolysis of a benzylalcohol plain BS - just a filler in the lengthy deadly boring synth it describes.(Or a lil´ joke? "´hey I bet no ass sees this as no ass reads it?") Dunno. 2-propanol as hydrogen donor may be possible also I postulate that most hydrogen comes from the nickel which is charged like a hydride   and gets recharged (partly) by the IPA (thats CTH I believe) but this working with ethylalcohol? No thus I don´t buy as this fact would have become obvious long before by some exploding laboratories. I also doubt that this works with urushibara nickel because I think the sponge-like structure of rayney is very important here.

Not to forget the insane substrate to nickel ratios, 1 to 10 seems favorable following WizardX whose earlier posted hydrogenolysis of ephedrine with nickel  is much the same. Interesting is that the reference WizardX names uses Ni and Pd hydride not rayney.

So could one of those skilled in the art have some mercy on thy worthless methheads and post an easy Nickelhydride OTC synth? Pleaze?

The idea of Tengo to use NiMH in a electrosynth wasn´t bad at all - he just never tried it in realworld.
Might doping the nickel with some noble metal be the way to go?

Just my 2 cents
ORG




Tengo

  • Guest
Organikum: I understand that christmas is a...
« Reply #4 on: December 29, 2002, 03:29:00 AM »

Organikum

  • Guest
Tengo, I asked already ...
« Reply #5 on: December 29, 2002, 05:41:00 AM »
and I did it here:

Post 392797 (missing)

(Organikum: ""it works" is not enough...", Stimulants)

your answer:

Post 393007 (missing)

(Tengo: "What could possibly be mentioned about the ...", Stimulants)


What could possibly be mentioned about the reaction, except that it bubbles H2 from the cathode, and that the silver anode turns black and white, due to the formation of Ag2O and AgCl.


(complete description of the reaction)

You can do in a sentence for what those chemists need pages over pages in journals and write whole books. And on a brandnew item also. Not disclosing how you came to the idea, no references.

You didn´t do the reaction except in your dreams perhaps but you strongly believe that it works (whats possible) and now someone shall try it for you, do all the fucking little work and tuning here and there until it works, but you can tell: "I did it before!"

My christmas was ok, thanks for thinking on me  :P
ORG




Tengo

  • Guest
Organikum: You are wrong about me.
« Reply #6 on: December 29, 2002, 08:18:00 AM »
Organikum: You are wrong about me.

Organikum

  • Guest
nickel doped zeolithe?
« Reply #7 on: December 30, 2002, 04:19:00 AM »
The immense amount of nickel needed makes me think that this isn´t a surface reaction as with Pd/Pt but a reaction occuring by trapping the benzylalcohol in a nickel structure (sponge). This leads me to the question if a basic nickel doped zeolithe might be usable.

anyone knows or can point me?
ORG


PolytheneSam

  • Guest
How about this?
« Reply #8 on: December 30, 2002, 04:51:00 AM »

http://www.geocities.com/dritte123/Nipat.html



Patent US3431220

Nickel is mentioned in column 4 lines 21-22.



foxy2

  • Guest
hehehe
« Reply #9 on: January 11, 2003, 11:40:00 PM »
Thanks for the mention Rhodium.
:)

PrimoPyro
Remember when you asked me about this, well here it is.
foxy

SPISSHAK

  • Guest
What about Pd/C 10%?
« Reply #10 on: June 26, 2003, 07:27:00 PM »
I agree that ethanol as a cth donor looks like bullshit, but swim has a good qauntity of degussa Pd/C and wants to know if you could substitute Pd/C as in the IPA CTH of benzylic alcohols?
Anyone.
I'll try it and let you know I just don't want to waste good catalyst If I can avoid it.

java

  • Guest
RE:General procedure for Raney Ni catalyzed hydro.
« Reply #11 on: June 26, 2003, 10:50:00 PM »
I'm thinking phenylalanol alcohol reduction to an alkane with this method , hence would the catalyst react with the amine group? Although there are manyways to reduce the primary alcohol to the CH3, some methods are cleaner than others, I found Zinc+ HCl to be messy  once the OH was halogenated and the low yields , and the silane seems a bit involved with some hard to get solvents. Ideally I would like to treat the alcohol in acid and make an alkene then hydrogenate with a Pd catalyst but I'm not sure of the action with the amine group and the H2SO4 environment.......java


SPISSHAK

  • Guest
no I'm aware of acid promoted
« Reply #12 on: June 27, 2003, 05:20:00 AM »
Palladium catalyzed reductions of benzylic alcohols, my question is this, would 10% Pd/C be a viable substitute in the reaction the Rhodium proposed, or are the catalyst's mechanics different?

Lucid_Dreamer

  • Guest
Isolation
« Reply #13 on: July 04, 2003, 08:08:00 AM »
What is the importance of filtering through celite and flash chromotagraphy in the second one, if someone were to try this out what would be an easier work-up/isolation method? If the Ni catalyst stay in tact the whole time wouldn't ot be that much easier to seperate and work-up?


Rhodium

  • Guest
Skip the column, keep the rest
« Reply #14 on: July 04, 2003, 06:09:00 PM »
Filtering through Celite is to remove the catalyst (it would just clog an ordinary filter), but careful vacuum distillation and recrystallization of the HCl salt is enough for purification, the flash column can be skipped.

Rhodium

  • Guest
More References on Raney-Ni/2-Propanol CTH
« Reply #15 on: March 12, 2004, 10:44:00 PM »
Related to

Post 393077

(Rhodium: "(pseudo)Ephedrine to Meth w/ Raney-Nickel", Stimulants)


Deiodination of Iodolactones by Transfer Hydrogenolysis Using Raney Nickel and 2-Propanol
Robert C. Mebane, Kimberly D. Grimes, Summer R. Jenkins, Jonathan D. Deardorff, and Benjamin H. Gross
Synthetic Communications, 32(13), 2049–2054 (2002)

Abstract
Raney nickel in refluxing 2-propanol is an effective catalytic system for reducing iodolactones into their corresponding lactones.

Iodolactonization of suitable unsaturated carboxylic acids followed by reductive deiodination constitutes an important synthesis of lactones.[1] This synthetic methodology has been widely utilized in natural product synthesis[2] and in the synthesis of complex organic molecules.[3] A number of different reagents have been used in iodolactonizations and have been thoroughly summarized by Simonot and Rousseau.[4] Two of the more common methods[5] for deiodination are metal catalyzed hydrogenolysis with

molecular hydrogen[6] and radical cleavage with tri-n-butyl tin hydride.[7] Although tri-n-butyl tin hydride is an effective reducing agent, there are toxicological and ecological concerns regarding its use as clearly described by Chatgilialoglu.[8] In addition, products are often contaminated with trace organotin compounds which are difficult to remove.[9] A disadvantage to the metal catalyzed hydrogenolysis procedure is the special handling precautions which must be exercised when using molecular hydrogen. In this report we describe an attractive alternative to deiodination of iodolactones which is based on catalytic transfer hydrogenolysis using Raney nickel and 2-propanol as the hydrogen donor. Raney nickel is widely recognized as a versatile catalyst for e.ecting reductive transformations of organic compounds.[10] Less well known and utilized is Raney nickel’s ability to catalyze reductions using hydrogen donors, such as 2-propanol, instead of molecular hydrogen.[11] Although the literature is somewhat sparse, Raney nickel catalyzed transfer hydrogenations utilizing 2-propanol have been reported for the reduction of ole.ns,[12] ketones,[12–14] phenols,[12] aromatic nitro compounds,[15,16] and certain aromatic hydrocarbons.[12,17] The experimental procedure for the catalytic transfer hydrogenolysis of iodolactones is simple and straightforward and a.ords lactones in good yields. The overall reaction is described in Figure 1 and a summary of our results is presented in Table 1. Iodolactones previously described in the literature were used in this study.[18] The yields reported in Table 1 are isolated yields and represent the average of at least two reactions. Yields as determined by glc were essentially quantitative. The low isolated yield observed for lactone 10 may result from our inability to remove the lactone from the catalyst surface due to a strong adsorptive interaction between the phenyl group in 10 and the nickel surface.[19] Isolation of lactone 7 was hindered by its volatility.

The optimal substrate to catalyst ratio found for the hydrogenolysis of iodolactones was 1:10 by weight. This high catalyst loading is necessary because of the poisoning effect of the HI that is generated in the reaction. The need for higher catalyst ratios when cleaving C–X bonds with Raney nickel and molecular hydrogen is well documented.[20,21] The catalyst load could be reduced with the addition of at least one equivalent of base such as KOH, NaHCO3, Et3N, or pyridine or with the use of ammonium formate[22] as the hydrogen donor. Good yields of lactones were obtained with the inclusion of base; however, in all cases minor amounts (5–20%) of ring-opening products were also obtained. Although a high catalyst load was necessary in our deiodination reactions, we did find that the Raney nickel catalyst could be reused repeatedly (at least 6x) after a simple regeneration step consisting of re.uxing the catalyst in 2-propanol containing KOH (0.12 g/1 g catalyst used) for 15 min followed by rinsing the catalyst with cold 2-propanol (3x). In conclusion, catalytic transfer hydrogenolysis with Raney nickel and 2-propanol is an effective method for the conversion of iodolactones into lactones. Furthermore, this environmentally-friendly and inexpensive method is an attractive alternative to catalytic hydrogenolysis with molecular hydrogen and the widely used procedure which employs tri-n-butyl tin hydride.

Experimental

Raney 2800 nickel was obtained from W.R. Grace Company, Chattanooga Davison. The catalyst was washed prior to use with distilled water (6) and 2-propanol (3) and stored in 2-propanol. 1H NMR spectra were recorded on a Varian Gemini 300 using tetramethylsilane as internal reference. IR spectra were recorded on a Nicolet Impact 410 spectrometer. The IR and NMR spectra of the lactones prepared in this work were identical to the spectra described in the literature.[23–27]

As an illustrative example of the hydrogenolysis procedure, iodolactone 3 (0.50 g, 2.1 mmol) was re.uxed in a magnetically stirred suspension of Raney nickel (5 g) in 2-propanol (30 mL) for 15 min with the condenser open to the atmosphere. After cooling to room temperature the organic layer was decanted from the Raney nickel[28] and the catalyst was washed with 2-propanol (3x10mL). The combined organic layers were .ltered through Celite and the solvent was removed by rotary evaporation and high vacuum to give dihydro-5-ethyl-2(3H)-furanone (9) as an oil in 90% yield.

References

[1] (a) Dowle,M.D.; Davies, D.I. Chem. Soc. Rev. 1979, 8, 171;
(b) Larock, R.C. Comprehensive Organic Transformations: A Guide to Functional Group Preparations; Wiley-VCH: New York, 1999, Chapter 8 and references therein;
(c) Harding, K.E.; Tiner, T.H. In Comprehensive Organic Synthesis; Trost, B.M., Ed.; Pergamon Press: New York, 1991; Vol. 4, p. 363.
[2] For examples:
(a) MacMillan, J.; Taylor, D.A. J. Chem. Soc., Perkin Trans. 1 1985, 837;
(b) Zanoni, G.; Vidari, G. J. Org. Chem. 1995, 60, 5319;
(c) Yamada, S.; Nakayama, K.; Takayama, H. J. Org. Chem. 1982, 47, 4770.
[3] For examples:
(a) Paquette, L.A.; Wyvratt, M.J.; Schallner, O.; Schneider, D.F.; Begley, W.J.; Blankenship, R.M. J. Am. Chem. Soc. 1976, 98, 6744–6745;
(b) Chuang, C.-P.; Hart, D.J. J. Org. Chem. 1983, 48, 1782;
(c) Whitlock, H.W. J. Am. Chem. Soc. 1962, 84, 3412–3413.
[4] (a) Simonot, B.; Rousseau, G. J. Org. Chem. 1993, 58, 4; See also:
(b) Royer, A.C.; Mebane, R.C.; Swa.ord, A.M. Synlett 1993, 899.
[5] Zinc–Copper couple and ammonium chloride in methanol solution has been used to reduce an iodolactone, see ref. 3(a).
[6] (a) Klein, J. J. Am. Chem. Soc. 1959, 81, 3611;
(b) House, H.O.; Carlson, R.G.; Babad, H. J. Org. Chem. 1963, 28, 3359.
[7] (a) House, H.O.; Boots, S.G.; Jones, V.K. J. Org. Chem. 1965, 30, 2519;
(b) Kuivila, H.G. Acc. Chem. Res. 1968, 1, 299.
[8] Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188.
[9] Curran, D.P.; Chang, C.-T. J. Org. Chem. 1989, 54, 3140.
[10] Augustine, R.L. Heterogeneous Catalysis for the Synthetic Chemist; Marcel Dekker: New York, 1996.
[11] (a) Brieger, G.; Nestrick, T. J. Chem. Rev. 1974, 74, 567;
(b) Johnstone, R.A.W.; Wilby, A.H.; Entwistle, I.D. Chem. Rev. 1985, 85, 129.
[12] Andrews, M.J.; Pillai, C.N. Indian J. Chem. 1978, 16B, 465.
[13] Stevovic, L.S.; Soskic, V.; Juranic, I.O. J. Serb. Chem. Soc. 1995, 60, 1071.
[14] Gonikberg, E.M.; le Noble, W.J. J. Org. Chem. 1995, 60, 7751.
[15] Banerjee, A.A.; Mukesh, D. J. Chem. Soc., Chem. Commun. 1988, 1275.
[16] Kuo, E.; Srivastava, S.; Cheung, C.K.; le Noble, W.J. Synth. Commun. 1985, 15, 599.
[17] Srivastava, S.; Minore, J.; Cheung, C.K.; le Noble, W.J. J. Org. Chem. 1985, 50, 394.
[18] Iodolactones were prepared by the method described in ref. 4b.
[19] Reference 10, page 11.
[20] Pattison, J.N.; Degering, E.F. J. Am. Chem. Soc. 1951, 73, 611.
[21] Denton, D.A.;McQuillin, F.J.; Simpson, P.L. J. Chem. Soc. 1964, 5535.
[22] Banik, B.K.; Barakat, K.J.; Wagle, D.R.; Manhas, M.S.; Bose, A.K. J. Org. Chem. 1999, 64, 5740.
[23] The lactones prepared in this work were found to be >95% pure by 1H- and 13C-NMR. No over-reduction products were detected.
[24] Hullot, P.; Cuvigny, T.; Larcheveque, M.; Normant, H. Can. J. Chem. 1977, 55, 266.
[25] Hanazawa, T.; Okamoto, S.; Sato, F. Org. Lett. 2000, 2, 2369.
[26] Burnell, D.J.; Wu, Y.-J. Can. J. Chem. 1990, 68, 804.
[27] Nicolaou, K.C.; Seitz, S.P.; Sipio, W.J.; Blount, J.F. J. Am. Chem. Soc. 1979, 101, 3884.
[28] Raney nickel is paramagnetic and sticks to the magnetic stir bar which facilitates decantation.


UncleFester

  • Guest
more examples from the archives
« Reply #16 on: March 14, 2004, 05:14:00 PM »
A very similar set of results can be found in Bull. Chem. Soc. Japan Vol. 43 p.2143-52 (1970) titled Catalytic Hydrogenolysis of Benzyl-type Alcohols and their Derivatives. The constant in all is the use of alcohol as solvent.

Rhodium

  • Guest
Catalytic Hydrogenolysis of Benzyl Alcohols
« Reply #17 on: April 13, 2004, 09:54:00 PM »
Stereochemistry and Mechanism of Catalytic Hydrogenation and Hydrogenolysis: Catalytic Hydrogenolysis of Benzyl-type Alcohols and Their Derivatives
Sekio Mitsui, Shin Imaizumi and Yasuyoshi Esashi

Bulletin of the Chemical Society of Japan 43, 2143-2152 (1970)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/benzyl-oh.cat-hyd.pdf)

Abstract
In order to obtain evidence for the mechanism we proposed of the catalytic hydrogenolysis of benzyl-type alcohols and their methyl ethers, optically active 2-phenyl-2-butanol (Ia), 2-phenyl-2-methoxybutane (IIa), ethyl atrolactate (Ib), and ethyl 2-phenyl-2-methoxypropionate (IIb) were hydrogenolyzed over Raney nickel and Pd(H) catalysts under hydrogen or helium atmosphere in an ethanol solution. In all cases, the hydrogenolysis proceeded stereoselectively with retention of configuration over Raney nickel catalyst but with inversion of configuration over palladium catalyst. A reverse stereoselectivity was observed when the benzyl alcohols (Ia and 2-phenyl-1,2-dihydroxypropane (Ic)) and methyl ethers (IIa) and (IIb) were hydrogenolyzed in the presence or absence of various additives over nickel catalysts. It was also found that the hydrogenolysis of benzyl alcohols always proceeds with retention of configuration over nickel catalyst containing sodium hydroxide. Various binary mixtures of Ia, IIa, Ib and IIb were hydrogenolyzed competitively over Raney nickel and Pd(H) catalysts. The order of relative rates was found to be Ia>Ib>IIa>IIb over Raney nickel, and IIa>Ia>>IIb>Ib over Pd(H) catalyst. The results support our mechanism. The catalytic hydrogenolysis is a competitive reaction of two courses (SNi type and SN2 type reactions), and the stereoselectivity reflects the difference of the free energy levels of the transition states to form pi-benzylic complexes. The free energy levels of the corresponding transition states depend on stereoelectronic factor, affinity of substituents for catalyst metal, catalyst hindrance and electronic effects of substituents. The acetates (IVa) and (IVb) of Ia and IIa were hydrogenolyzed with inversion of configuration over nickel and palladium catalysts, whereas the stereoselectivity of the hydrogenolysis of the benzoate (V) of IIa depended on the kind of catalyst. The results are also explained on the basis of our mechanism.

This article has also been referenced in

Post 368735 (missing)

(WizardX: "Stereochemistry and Mechanism of Catalytic ...", Stimulants)