The Leukart Reaction

Vitriodor · Tue Mar 29, 2005 5:54 am

I have heard lots of negative talk about the Leuckart reaction for the synthesis of deoxy (nor)ephedrine from P2P. It is supposed to be messy and gives low yields. But what yields can be expected ? I remeber a thread by one of the former Russian Hive bees which claimed a yield of 90%. Has this been verified by other bees?

Vit

IndoleAmine · Dreamreader Deluxe

...is crap. Also the russian variation with dean-stark/NH4COOH.

Verified as being most definately hypothetical or based on "raw product" not on amnt. of salt.

Got 30% yield at best, IIRC. Lots of tar.

May I cite Strike: "it is possible to get 10g of product from 40g ketone with this method - but its also possible that you get only 10g from 400g of ketone with the same method".....

Not to shit on Mr.Leuckarts head though: for acetophenone and other substrates, it works amazingly well - just not with phenylacetone.....

i_a

Lief · Wed Mar 30, 2005 5:12 am

IndoleAmine · Dreamreader Deluxe

With pleasure - if you tell me where to look them up.... Very Happy

i_a

Lief · Thu Mar 31, 2005 4:45 am

Lief · Thu Mar 31, 2005 4:50 am

Lief · Thu Mar 31, 2005 5:03 am

Lief · Thu Mar 31, 2005 6:09 am

madbrat · Thu Mar 31, 2005 11:51 pm

In russian post mentioned by IndoleAmine (the nick of Russian Bee was zealot) the yield of vacuum distilled amphetamine base was claimed 92%. The one difference between traditional Leukart and this one was applying of base hydrolysis instead of acid, because this step is crucial in yield decreasing (if you take pure distilled ketone - white or slightly coloured - N-formyl-derivative is obtained in almost quantative yield). If smb. interesting about details I could translate it for you.

IndoleAmine · Dreamreader Deluxe

Yes, and he used a dean-stark trap to regulate the rxn temp. by adjusting the water content....

(do you know how much "ultra-pure, distilled ketone" and ACS ammonium formate were used up finding out how crappy the leuckart can be? Yes sure, almost colorless formamide intermediate - but low yield of this intermediate as well as of product. Oxime reduction with EtOH/Na gives 2x as much in SWIAs experience)

Vitriodor · Fri Apr 01, 2005 4:53 am

Madbrat is right! After three Leuckart reactions and six GC/MS runs Mr. bizzy Bee convinced me that refluxing the right ketone with formamide/formic acid quantitatively forms N-formyl deoxy norephedrine. Only small amounts of unreacted ketone were detected (up to 5-10%). Surprisingly, a small amount of the end-product was present as well. Somehow hydrolysis already occured ?

After boiling the N-formyl with 40% sulphuric acid analyses have shown that a number of (partially unknown) by-products are formed. Bizzy bee is going to work on the second step to reduce these. Suggested improvements: more dilute acid, lower "boiling" temperatures, shorter reaction times.

Vit

IndoleAmine · Dreamreader Deluxe

We're talking about a leuckart variation using ammonium formate, not formamide/formic acid - at least Zealot/Antoncho used NH4COOH, and this gives 40% yield at most, confirmed without analytical equipment.

Why do you leuckart guys never claim your yield of purified salt, expressed in molar percent with respect to the starting material ketone? Like is common?

("almost quantitative yield of intermediate XY at a certain point somewhere in between start and finish" doesn't mean the procedure does give good yields of purified end product, BTW)

How much of the "right ketone" do you guys want me to waste further for the leuckart, 100ml, 200ml....?

And I just want to remark that the new twist Zealot mentioned as being supposedly responsible for his high yields was NaOH hydrolysis, not acid hydrolysis.

Remember: leuckart with NH4COOH followed by aequous NaOH hydrolysis yields 40% at most, and I never claimed anything else.

But of course you're welcome to develop new, higher-yielding variations at every time.

i_a

Lief · Mon Apr 04, 2005 8:02 am

IndoleAmine · Dreamreader Deluxe