Meth by catalytic hydrogenation at atm. pressure

[Rhodium]

I cannot think of any reason this procedure shouldn't work great with (pseudo)ephedrine to give meth... Use the HCl salt, so that the perchlorate is available for protonation of the alcohol, alternatively add an extra equivalent of the perchlorate to form the salt from the freebase (but I don't know if that amounts of perchlorate would be hazardous). In any case, be sure to perform a proper A/B of the product, so as to not isolate or ingest the perchlorate salt of the product.


A High-yielding Catalytic Hydrogenation of benzylic alcohol at atmospherical pressure with 10% Pd/C and catalytic HClO₄

Organic Process Research & Development 7, 585-587 (2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/pd-c.deoxygenation.benzyl-oh.pdf)

Hydrogenolysis of [the benzylic alcohol] in methanol at atmospheric pressure using Pd-on-carbon catalyst gave [the fully reduced hydrocarbon] in nearly quantitative isolated yield. With smaller batches (<50 g) the reduction was typically performed at ambient temperature in ethanol with or without acid catalyst, but on a large scale it was preferably carried out in methanol in the presence of 70% aqueous HClO₄ (ca. 0.03% with regard to solvent) and at 40°C with efficient magnetic stirring. Although acetic acid (up to 10% with regard to solvent) was also found to facilitate the reduction, its removal, for example by distillation or extraction, complicates workup.


meta-Hydroxy-Phenylpropane

A solution of 1-(meta-Hydroxy-Phenyl)-1-propanol (381 g, 2.50 mol) in analytical grade methanol¹ (2.0 L) was added to a pre-hydrogenated suspension of 10% Pd-on-carbon² (28.0 g) and 70% aqueous HClO₄ (0.3 mL) in analytical grade methanol (1.3 L) while stirring, and then the reaction mixture was hydrogenated with vigorous magnetic stirring at 40°C (water bath) from a 20-L gas buret until gas absorption ceased (ca. 60 L during 12 h). The suspension was filtered, and the catalyst was washed with a small amount of methanol and saved for further use. The filtrate was concentrated and the residue distilled in a vacuum. After a small forerun, 320g (94%) of phenol 1 was collected as a colorless oil; bp 93-95°C/2.3 mmHg. Purity (HPLC): 99.5%. Hydrogenation of two additional batches of the starting alcohol using recycled catalyst proceeded smoothly with similar results. The three distilled batches were then combined, giving a total of 995g of product with 98.5% purity.


(1) As a rule, analytical grade methanol (>99.9%) is used at the pilot plant  for the various syntheses. No other grades were tried, but ordinary methanol could also work. As mentioned earlier, laboratory-scale preparations also used 95% ethanol (with added acetic acid) successfully for the reduction. Due to the notoriously higher price of ethanol, its use on a larger scale was abandoned.

(2) In preliminary small-scale experiments reductions using 5% Pd/C from one supplier (Aldrich) were rather slow even in the presence of acetic acid. Note, however, that catalysts on various supports and even with the same support but from different sources can vary in their efficiency. No other types of 5% Pd/C were tested.

[fierceness]

am i reading this correctly? It says it works even without the acid catalyst in batches under 50g and at ambient temperature in EtOH...  so all that is necessary is magnetic stirring and Pd/C for a batch <50g ?

[ragnaroekk]

interpretation .......?

It says that you have to use analytical grade solvents and compounds (thats not labgrade thats more!) and you have to use an highly active catalyst which can´t be made by oneself.

Steric hinderance in the (pseudo)ehedrine molecule might complicate this also.

[java]

Great  find , since I enjoy hydrogenation synthesis , I always look to maximize the use of this great apparatus. The method  reminds me of the one WizardX talked about and explained that it went through esterification with the acetic acid present and the addition of the perchloric acid all in methanol, (it's a waste to use a fine reagent methanol since you are introducing water with the acid),. He too suggestd the Pd./C , regular stuff that is sold, nothing fancy, or PdBariumsulfate .

I think the method will work well for a hydrogenator with 40-60psi as it will increase the hydrogeanation substitution as the acid promoted ester leaves and is replaced by the hydrogen.....java

[ragnaroekk]

reread WizardX´s post here:

Post 359715 (missing)

(WizardX: "Hydrogenation/Reduction of Ephedrine.", Stimulants)

you will see your memory didn´t serve you well in this case.

peace

[java]

Ragnaroekk, you're right ! paraphrased WizardX's method with some inaccuracy, for that I apologize if I mislead someone, but I didn't mean to quote him exactly only that the current thread reaction had some similarities.....thanks for posting the link so the reader can compare the methods and possibly see the stated similaries in some ways.....java