Sciencemadness Discussion Board - Leuckart reaction

Leuckart reaction

Wolfram - 16-11-2003 at 10:29

The leuckart reaction is used to produce amphetamine on huge scale in eastern Europe could someone write the reaction. What is actually happening?

[Edited on 7-9-2009 by Polverone]

vulture - 16-11-2003 at 11:04

20s of google searching:

http://themerckindex.cambridgesoft.com/TheMerckIndex/NameRea...

I'm getting fed up with that lazy attitude of yours.

OK thanx mr. Vulture

Wolfram - 16-11-2003 at 11:09

OK thanx mr. Vulture but could you tell me why ammuniumacetate doesn´t work?

unionised - 16-11-2003 at 14:09

Because it's not a formate. That means it's not an aldehyde and so it's a lousy reducing agent. (didn't you spot the CO2 as a product?)

vulture - 16-11-2003 at 14:48

formate = salt of formic acid, methanoic acid.

That's not an aldehyde.

Formaldehyde is an aldehyde.

unionised - 16-11-2003 at 15:40

Thanks, but I knew that anyway.

X-CHO is an aldehyde.
HO-CHO is an aldehyde.
Formic acid is an aldehyde as well as an acid.

Formic acid gives a positive reaction with Tollen's reagent and Fehling's solution.
It's an unorthodox point of view, but it explains the fact that acetate dosn't work.

vulture - 17-11-2003 at 02:45

Aah I see what you're getting at. Indeed one could consider formic acid as an aldehyde too.

Wolfram - 19-11-2003 at 04:41

Sorry I ment if acetamide (not amoniumacetate) does work instead of ammoniumformate?
What is the usual way to P2P in eastern europe?

narkar - 20-11-2003 at 09:14

does aybody know the synt of this ketone. C6H5CH2COCH3

acx01b - 6-5-2004 at 12:20

hey

I have a question i never founded the answer:

CH3-CO-CH2Cl + C6H5MgBr

the ketone reacts 1st ?
(to yield after hydrolysis 2-Phenyl 1-chloro Propan-2-ol)
or not ? :-)

and by the way 2-Phenyl 1-chloro Propan-2-ol would react on water too..

[Edited on 6-5-2004 by acx01b]

Ephoton - 26-6-2008 at 02:45

kill this thread mine was nothing like this.
it brakes all the rules.
at least mine was or though with some mistakes with the ideas too LAH not against the
rules of the site.

brew - 26-6-2008 at 02:51

Just curious but what does BMK stand for.

ScienceSquirrel - 26-6-2008 at 03:10

Quote:

Originally posted by brew
Just curious but what does BMK stand for.

Benzyl methyl ketone, another name for 1-Phenyl-2-propanone.

Nicodem - 30-6-2008 at 04:28

Quote:

Originally posted by Ephoton
kill this thread mine was nothing like this.
it brakes all the rules.
at least mine was or though with some mistakes with the ideas too LAH not against the
rules of the site.

Please discuss complaints about moderation either via U2U or in the Forum matters section. Besides, this thread is from 2003 and was resuscitated by Bluetooth without any solicitation or question on the topic, so your comparison to whatever action taken against any of your posts/threads is not really relevant. This thread does not break any forum rule. It is however not particularly informative, but for now that by itself is no reason to just "kill" it (though if it was a recent one it would go to Beginnings due to the laziness of the original poster in searching for any information on the topic prior to asking others to do so).

Bluetooth - 27-12-2008 at 02:00

There is a patent about the leuckart reaction that claims the leuckart reaction with a catalyst. They illustrate te amination of benzophenone with 6mol equivalent formamide and small amount MgCl2 at 170-190C under N2 atmosphere. After 4 hours and the product was isolated in a yield 95,6%.

The same experiment repeated with out catalyst under the same conditions gave a yield of only 21.7%.

Sauron - 27-12-2008 at 05:00

Patent number, name of inventor, date, country? It's customary to cite these things.

JohnWW - 27-12-2008 at 11:38

A search suggests that this is probably the patent Bluetooth means, but using boric acid or AlCl3, which were found to be superior, instead of MgCl2:

http://www.freepatentsonline.com/4851548.html (1989)
Here is a related one:
http://www.freepatentsonline.com/6596861.html

See also, besides erowid:
http://www.geocities.com/methamphetamine_x/
http://saevarr.com/drugs/Chrystalmeth/amphetamine.reduction....

The Leuckart reaction involving benzophenone and formamide, catalyzed by MgCl2, was described 40 years earlier. in Webers et al, JACS 70, 1422-4(1948) and Bunnett et al, JACS 71, 1587-9(1949). Someone with the necessary online access, please find and upload these articles.

[Edited on 28-12-08 by JohnWW]

mr_burns - 27-12-2008 at 22:27

The route to P2P using in eastern europe? Chemical companies, money, and guns. I read an interview with a DEA agent recently where he said that almost all E made in eastern europe was made from commercial MDP2P.

And if you actually wanted to make amphetamines, the leuckart is a ridiculously temperamental reaction to actually run. Wiki has a great overview of the reaction, just mentally substitute P2P in.

sparkgap - 27-12-2008 at 22:44

Quote:

The Leuckart reaction involving benzophenone and formamide, catalyzed by MgCl<sub>2</sub>, was described 40 years earlier. in Webers et al, JACS 70, 1422-4(1948) and Bunnett et al, JACS 71, 1587-9(1949).

sparky (^_^)

Sauron - 28-12-2008 at 01:35

My intention was not to solicit assistance for meth cooks. They can all go to hell. My intention was to prod bluetooth to post like a chemist, citing his sources rather than merely scattering bits of random information around in a long defunct thread.

kmno4 - 29-12-2008 at 08:26

Quote:

Originally posted by mr_burns
The route to P2P using in eastern europe? Chemical companies, money, and guns.

Mostly from People's Republic of China

Another way is comonly known catalytic ketonisation - the simple
and cheap method.
A few days ago I saw pictures on TV from "laboratory" (just shed in the boonis) - all they showed was a fragment of pipe (tube) reactor and yellow something (yes, yes.... ) in a flask (placed in electrical heater) ready for Leucart (probably).
A few years ago, our police arrested men wanting to produce known ketone on almost industrial scale, hah. They have completed aparaturus but not yet running. Probably they wanted too much and unfair competition gave police a bell

Why Leuckart ?
Simple, cheap, clean, easily scaled up. My country is one of the famous producers of sulfate of known amine (mostly not methylated),from known ketone by this method.
I am not specially proud of it

Some lady told me that selling of ammonium formate was (is ?) strictly monitored, just because of Leuckart. But ammonia (or its carbonate) or formic acid are not specially controled. Stupid - isn't it ?

[Edited on 29-12-2008 by kmno4]

Bluetooth - 2-1-2009 at 15:11

Quote:

Origineel gepost door sparkgap

Quote:

sparky (^_^)

[bewerken aan 2-1-2009 door Bluetooth]

Bluetooth - 2-1-2009 at 15:22

Quote:

Origineel gepost door mr_burns
The route to P2P using in eastern europe? Chemical companies, money, and guns. I read an interview with a DEA agent recently where he said that almost all E made in eastern europe was made from commercial MDP2P.

And if you actually wanted to make amphetamines, the leuckart is a ridiculously temperamental reaction to actually run. Wiki has a great overview of the reaction, just mentally substitute P2P in.

Hey but i'm from the netherlands, or from HEERLEN AND my name isn't MAE BeeOK

[bewerken aan 2-1-2009 door Bluetooth]

Bluetooth - 14-1-2009 at 11:48

Here is the document i was talking about :
http://www.google.com/patents?id=k-BHAAAAEBAJ&printsec=d...

[bewerken aan 14-1-2009 door Bluetooth]

twodogs - 14-1-2009 at 18:22

I wonder how this works. Notice it is non microwave!
http://www.articlearchives.com/science-technology/chemistry/...

Nicodem - 15-1-2009 at 00:03

Am I dumb or there really is nothing on that link. I can't find any paper or literature reference. Your link only leads to a useless blog saying something is, or will be, published about the Leuckart reaction.

PS: This thread is such crap! Unless someone posts something interesting, I will consider closing it.

twodogs - 15-1-2009 at 00:12

Which is why I said .."I wonder how this works".
The guy has stated

Quote:

In this work a fast non-microwave procedure for the Leuckart reaction was developed. The new procedure can be completed in minutes instead of hours. It minimizes the use of heat and practically eliminates any thermal decomposition of the reaction mixture

I thought someone might have some more info on it.

Bluetooth - 19-1-2009 at 05:43

Here’s an other one from U.S. Pat. 3,222,395
135g (460mmol) 3,4-di-p-chlorophenyl-2-butanone and 84gr (1.86mol) formamide where heated under reflux at 170C for 14 hours. Formic acid (about 35cc) is added in smal portions from time to time to keep the vapours above the reaction mixture acidic. After cooling, the mixture is extracted with benzene. The benzene layer is separated and evaporated. The residu is boiled with 65cc concentrated hydrochloric acid for about 8 hours thus forming the diastereoisomers of 3,4-di-p-chlorophenyl-2-aminobutane hydrochloride in 70% yield.
I think that the use of BMK instead of the above ketone, will give somewhat higher yields.

[bewerken aan 19-1-2009 door Bluetooth]

[bewerken aan 19-1-2009 door Bluetooth]

twodogs - 19-1-2009 at 13:44

Yes but 14 hours?? The idea is to do the Leuckart in 30 minutes without using a microwave.

Sauron - 19-1-2009 at 15:24

Nicodem, this is what is on that link above:

The "greener" Leuckart reaction.
By: Bobylev, Mikhail M.
Publication: Proceedings of the North Dakota Academy of Science
Date: Tuesday, April 1 2008

You are viewing page 1
The Leuckart reaction is a unique one step method of reductive amination. It is a remarkably simple process that includes only two components: the carbonyl compound and formamide. The reaction is completed simply by heating the components at 160[degrees]C to 185[degrees]C for 6 to 25 hours. The

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long processing time seems to be the only shortcoming of the reaction. However, it is associated with a number of serious practical problems. First, the prolonged exposure of the reaction mixture to high temperatures inevitably leads to significant thermal decomposition of the components, and, consequently, to lower yields of the products and large amounts of waste. Second, maintaining high temperatures for a long period of time means high consumption of energy and increasing production costs which make the Leuckart reaction unattractive to the chemical industry.

In this work a fast non-microwave procedure for the Leuckart reaction was developed. The new procedure can be completed in minutes instead of hours. It minimizes the use of heat and practically eliminates any thermal decomposition of the reaction mixture. The specific examples of the reactions will be presented. The project is supported by NIH grant P20 RR016741 from the NCRR.

Mikhail M. Bobylev

Division of Science--Chemistry, Minot State University, Minot, North Dakota 58707

Vogelzang - 27-1-2009 at 15:21

There's some Leuckart articles here:
http://www.4shared.com/dir/4188850/a5ae1be6/Leuckart_Synthes...

This is from the articles.txt file.

Extensions of the Leuckart Synthesis of Amines
A. W. Ingersoll, J. H. Brown, C. K. Kim, W. D. Beauchamp, Garland Jennings
J. Am. Chem. Soc.; 1936; 58(9); 1808-1811.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1936/5...

Secondary Amines by the Leuckart Synthesis
Armando Novelli
J. Am. Chem. Soc.; 1939; 61(2); 520-521.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1939/6...

STUDIES ON THE LEUCKART REACTION
FRANK S. CROSSLEY, MAURICE L. MOORE
J. Org. Chem.; 1944; 9(6); 529-536.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/joceah/1944/9...

Analgesics. I. N-Alkylated-1,2-diphenylethylamines Prepared by the Leuckart Reaction
L. H. Goodson, C. J. W. Wiegand, Janet S. Splitter
J. Am. Chem. Soc.; 1946; 68(11); 2174-2175.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1946/6...

Studies on the Mechanism of the Leuckart Reaction
Elliot R. Alexander, Ruth Bowman Wildman
J. Am. Chem. Soc.; 1948; 70(3); 1187-1189.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1948/7...

The Leuckart Reaction: A Study of the Mechanism
Vincent J. Webers, William F. Bruce
J. Am. Chem. Soc.; 1948; 70(4); 1422-1424.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1948/7...

Preparation of Tertiary Amines by the Leuckart Reaction
J. F. Bunnett, Jean Lovendahl Marks
J. Am. Chem. Soc.; 1949; 71(5); 1587-1589.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1949/7...

Preparation of Tertiary Amines by the Leuckart Reaction
Peter A. S. Smith, A. John Macdonald
J. Am. Chem. Soc.; 1950; 72(2); 1037-1038.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1950/7...

The Behavior of Aliphatic Aldehydes in the Leuckart-Wallach Reaction
Peter L. deBenneville, Jane H. Macartney
J. Am. Chem. Soc.; 1950; 72(7); 3073-3075.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1950/7...

THE MECHANISM OF THE LEUCKART REACTION
C. B. POLLARD, DAVID C. YOUNG
J. Org. Chem.; 1951; 16(5); 661-672.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/joceah/1951/1...

Preparation of tertiary N, N-dimethylamines by the Leuckart reaction
Robert D. Bach
J. Org. Chem.; 1968; 33(4); 1647-1649.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/joceah/1968/3...

Catalytic Leuckart-Wallach-Type Reductive Amination of Ketones
Kitamura, M.; Lee, D.; Hayashi, S.; Tanaka, S.; Yoshimura, M.
J. Org. Chem.; (Note); 2002; 67(24); 8685-8687. DOI: 10.1021/jo0203701
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/joceah/2002/6...

THE PREPARATION OF SECONDARY AMINES THROUGH THE WALLACH REACTION1
RICHARD BALTZLY, OTTO KAUDER
J. Org. Chem.; 1951; 16(2); 173-177.
http://pubs.acs.org/cgi-bin/searchRedirect.cgi/joceah/1951/1...

[Edited on 27-1-2009 by Vogelzang]

DNA - 28-1-2009 at 00:24

Vogelzang, haven't you got any recent literature....the newest article you posted is from 1951, not immediately claiming that old literature is bad but fresh literature is in my opinion somewhat more reliable

Sauron - 28-1-2009 at 00:52

Youmight just consider getting fresh lit. yourself.

Google

ACS Pubs search engine

RSC search engine

Org Reactions

Chemical Reviews

just for starters.

twodogs - 3-7-2009 at 17:03

Here's some info on the accelerated Leuckart
http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sec...

[Edited on 4-7-2009 by twodogs]

jon - 7-7-2009 at 17:29

where is that reference that promises 95% yeilds by means of microwave irridatiation???
read it somewhere just glancd over it looked interesting though.
i'll find it again.
what of pyrimidine by-products aren't they a pain to to separate??
[Edited on 8-7-2009 by jon]

[Edited on 8-7-2009 by jon]

greenimp - 17-7-2009 at 07:11

TD- On your accelerated Leuckart. I wanted to gauge the feeling here if it was only the concentration of the ketone/aldehyde that was critical or if the product concentration would limit the reaction.

I feel mass action is not the only reason in use such high ratios of amine:ketone/aldehyde.

An idea has been floated that perhaps running the reaction in cycles, adding a small amount of ketone each time in order to keep the concentration low, might be possible. The goal being to effectively increase the amount of ketone that could be processed per reaction, the real down side of this procedure being the large volume of amine needed to process a given amount of ketone. Cycling would keep the thermal decomposition and mixing issues to a minimum.

[Edited on 17-7-2009 by greenimp]

europa - 29-5-2010 at 07:43

United States Patent 5504253:-
1. N- ((3-Methoxyphenyl)methyl)-α-methyl!formamide

A mixture of 281 g (1.87 moles) of 3-methoxyacetophenone and 352 g (5.558 moles) of ammonium formate was stirred at 180° C. After 24 hours, TLC analysis (1:1 Hex/EtOAc) indicated that the reaction was complete. The solution was poured into water and extracted with methylene chloride. The organic layer was washed once with H 2 O and dried with MgSO 4. The solution was concentrated to afford 292 g (87%) of a dark oil.

2. 3-methoxy-α-methylbenzylamine

A solution of 287 g (1.60 moles) of N- ((3-Methoxyphenyl)methyl)-α-methyl!formamide and 1400 mL of concentrated HCl was stirred at reflux. After 1.5 hours, TLC analysis (85:10:5 EtOAc/MeOH/isopropylamine) indicated the reaction was complete. The solution was concentrated to dryness and the resulting green residue was recrystallized from acetonitrile to afford a white solid. The solid was dissolved in water and the pH was raised to 12 with 50% NaOH. The product was extracted with ethyl ether. The organic layer was washed with saturated NaCl solution and dried with K 3 CO 3 . The solution was concentrated to afford 188.2 g (78%) of a dark oil. Distillation of 174 g of the dark oil at 760 mm Hg afforded 140 g of a clear liquid, bp 180° C.

rannyfash - 3-11-2012 at 03:12

Sorry to revive a dead thread, however I feel that the leuckart reaction would be sped up if drying agents were used to remove water, removing water from the imine formation equilibrium would push more imine to be produced, maybe the hydrolysis of an imine competes against the reduction step? And if so then the removal of water would push the reaction to completion, it's just a hunch tell me where I'm wrong

Vogelzang - 3-11-2012 at 15:01

http://www.sciencemadness.org/talk/viewthread.php?tid=3613#p...