Here’s a patent (US 5,041,669) that explicitly describes reduction of an alpha-oximinoketone to an amine w/Pd/C, namely, p-hydroxyacetophenone to tyramine. There’s a trick to it – H2SO4 is used to dehydrate in situ the aminoalcohol that is otherwise produced by this reduction. The overall yield is 64% from p-OH-acetophenone.
It should bee noted that they use DMF for nitrosation, whereas in Rhodium’s example MeOH is used. Why? They don’t explain – if MeOH could bee used it’d bee both cheaper & simpler.
The patent also mentions that Ni catalyst may bee used – for us, the poor ones (won’t it react w/10% H2SO4 in AcOH?). I wonder if activated Urushibara Ni will work well… They say activated Raney Ni reduces acetophenone some 17 times faster than ordinary R. Ni… – see the thread & the patent for details (US 3,997,478).
To a 3-neck 2 L flask is added 2.2 moles of dry HCl to 1000 ml of dry dimethyl formamide (DMF). To the flask is then added 272 grams (2 moles) of p-hydroxyacetophenone all at once. Then, 296 ml grams (2.2 moles) of 90% tertiary butyl nitrite is added very slowly so as to maintain the reaction medium temperature at about 40.degree. C., which takes about 2 hours, after which the reaction medium is stirred for an additional 3 hours while maintaining the temperature at about 40.degree.-45.degree. C. The contents of the flask are then poured into one liter of ice and extracted three times with 200 ml of ethyl acetate. About 200 ml of the crude, dry ethyl acetate solution is then added with 10.5 grams of 5% palladium/carbon catalyst to a reaction medium solution made by combining 350 ml glacial acetic acid and 35 ml of concentrated sulfuric acid. The reaction mixture is then placed in one liter autoclave reactor and degassed 3 times with nitrogen gas, then 3 times with hydrogen gas, after which the reactor is pressurized to 100 psig with hydrogen gas and the reaction is monitored over a period of 7 hours. The reaction mixture from the reactor is then filtered to recover the catalyst, and the filtrate is concentrated to recover Tyramine.H.sub.2 SO.sub.4 in 64% yield.
With that said, Antoncho wants to ask a couple more Q’s from “those skilled in the art” – he knows he’s too curious, yes, yes, his curiosity has killed more than one cat
– that’s fine, he knows how to cook’em…
1. Pray tell me, when preparing acetophenone, why should one bother himself w/AlCl3 and AcOCl? Why not use AcOH/polyphosphoric acid instead (see
http://www.erowid.org/library/books_online/pihkal/pihkal061.shtml
for a gen. procedure). I also refer everyone interested to
https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cb-new.txt
, where Assholium claims he always had 85-90% yields in this rxn.
This way demethylation won’t represent a problem so one can start w/p-diMeObenzene, making things much easier for a kitchen chemist. And polyphosphoric acid, i believe, may bee had by removing water from H3PO4 in vacuum.
2. It is known that =O can bee reduced to –H w/Clemmensen “under vigorous conditions” – my txtbook says. What are those vigorous conditions? Is there a chance that Clemmensen red’n might work? Perhaps 1st doing it at RT so as not to cleave the iminic double bond and them finishing it at an elevated temp?
3. Can anyone post a detailed proc. for making polyphosphoric (temp, time, pressure?) Does anyone know of any other catalysts for these condensations?
Any input will bee greatly appreciated.
Antoncho
