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All 102 posts   Subject: Leuckart with 92%+ overall yield   Please login to post   Down

 
    Antoncho
(Official Hive Translator)
04-27-02 19:08
No 302161
      Leuckart with 92%+ overall yield
(Rated as: excellent)
    

This is another work of Zealot, whose name undoubtedly will bee engraved with golden letters into the annals of clandestine chemistrysmile.

The guy spent a very significant effort optimizing this procedure. And - keep this in mind - he did all this w/out even knowing of the Hive's existence! In fact, he 1st visited us about a week ago (says he was intimidated by what he sawsmile)






1) Reductive amidation.

"64 g P2P and 40 g HCOONH4 are placed into a 250 ml flask. (recalculated for 47 g for cyclohexanone used in the literature (not used here)) (1.3 excess - 2 times excess HCOONH4 was used in the original, but that's not needed). The flask is equipped w/a thermometer and a Dean-Stark trap w/a reflux condenser, which  should have a wide inlet beecause NH4-formate partially sublimes during the rxn and tends to plug it - one more reason not to use too much formate. The trap is pre-filled w/water.

The whole point of using such setup is that if you plainly distill it, the reaction will end very quickly, and in the receiver there will form two phases: the lower a NH3 soln, the upper - the amine formyl derivative (FD). If you try to toss it back into the reaction, its temp will fall to 125-135 C and all efforts to heat it higher will bee useless.
So the temp of the reaction is slowly adjusted by gradually removing H2O from the Dean-Stark over 4-6 hours - that leads to a gentle and very even rise of the reaction temperature. When it reaches 160-170 C, you simply close the trap's crane and gently boil it for ~1 h (not 4 hrs, as the original sources say).

On cooling the rxn crystallizes completely.

Analysis shows the yield is quantitative at this stage. Interestingly, if formamide or N-subst'd formamide is used instead of ammonium formate, the yield drops to <70% - DMF giving the ugliest yield of all. "

The procedure above was originally (bee4 he finished his work on the 2nd stage) stated for cyclohexanone, but the author says the identical one was used for P2P, with the results also identical. Actually, he just used cyclohexanone as a cheap P2P substitute for working out the optimized procedure.


2) Hydrolysis of the FD.

...i'll omit some of the preface - he describes several attempts hydrolizing the FD w/various acids and solvt systems, none of which lead to a satisfying yield and/or easiness of the proc. Finally, he decided to try alkaline hydrolysis, which resulted in a very pronounced success, 1st tested on cyclohexanone, then on P2P.

"The FD is obtained as described earlier for cyclohexanone, w/same nearly quantitative yield. The main factor here is purity: the higher it is, the better yield. If you take an impure ketone, you may get as low as 50% yield; so only a slightly yellow transparent oil should bee used.

The FD, which on cooling the rxn from the previous step, turns into a yellowish-white paste, is flooded w/isopropanol , about 100-150mls per 30-40 g FD (i used IPA beecause of its availability to me, but it's probably best to use MeOH - the lower the alcohol, the more alkali concentration can bee achieved w/out separation of the mixtr in layers - thus faster rxn rate, no need for stirring etc.) and 75mls 50% NaOH. The layers separate, and in between there appears a precipitate of the FD. The mixture is refluxed for 1-1,5 hrs, every 15 mins homogenizing the mixtr w/a mag stirrer (yes, no stirrer hotplates in the institute labs in Russia!shocked); an overhead stirrer can bee used, in which case hydrolysis occurs even faster - ~30mins. FD gradually disappears and the alcohol layer assumes a deep reddish-brown color.

Upon the passage of the said time the flask is cooled, which usually precipitates an insignificant (less than 1 g) qtty of unreacted FD; the mixtr is paper-filtered, the filtrate saturated w/NaCl or NaOHand the alcohol layer is separated. solvt is removed and the resulting freebase is steam-distilled. It forms in the receiver as an absolutely colorless oil of rather unpleasant smell.

The yield bee4 steam-distillation - ~95% (23,5 g), after it - ~92% (23 g)




Probably the most important thing about this finding is that substituted rings are much less sensitive to alkaline hydrolysis than to acidic, so it should work just as good on MDP2P et cetera.

BTW, a very similar procedure was found and submitted by Psyloxy 1,5 years ago - see Post 61613 (psyloxy: "Re: Leukard scaleable ?", Methods Discourse). It just seemed to go down unnoticedsmile - or maybee some "smart" people tried it and decided to keep the secret to himselfsmile.

If you want to say something pleasant to Zealot, go ahead - i'll pass it on to himwink, or you can PM him as he registered here this Wednesdaysmile - i dunno if he'll stop by often, though.


Yours as ever,

Antoncho
 
 
 
 
    lugh
(Moderator)
04-27-02 22:52
No 302251
      Microwave     

This is an excellent report of some great labwork by one of our comrades, but


Analysis shows the yield is quantitative at this stage. Interestingly, if formamide or N-subst'd formamide is used instead of ammonium formate, the yield drops to <70%




This analysis cannot be the last word in this matter, since if you read the reference in Post 27945 (Chopper_: "Re: yes to refs", Methods Discourse), you will find that the overall yield for the authors was 80% of phenylethylamine. The newbee who posted that reference claimed that the microwave procedure in Post 27089 (Chopper_: "Re: Ducks need help with Leukart", Methods Discourse) provides yields better than 80% smile

 
 
 
 
    humidbeing
(Can't SWIM)
04-27-02 23:56
No 302272
User Picture 
      leuckart     

Shit, is'nt this the first really significant post about
 a leuckart rxn in about, oh, two years is it?
  This has to be the rxn that has been more down played
than any other on the hive, with all sorts of
controversy.
  Was a first consideration, than was abandoned after
alot of tfse.
  Hats off to your friend Antoncho!

CG I miss you sweety, I really do.
 
 
 
 
    Antibody2
(Rehabilitated)
04-28-02 01:26
No 302311
User Picture 
      sweet!     

i heard no mention of tar anywhere in the write-up and talk about slick work-up. gotta luv simple rxns.

tell zealot, antibody says fucking eh dude!smile
 
 
 
 
    Flinger
(FMAN)
04-28-02 03:38
No 302384
User Picture 
      wanted references
(Rated as: misinforming)
    

Hey Cool I just hapen to have a reference to this reaction in my pocket imagine thatsmile
my notes crib like:   Also of interest
LEUCKART SPECIFICS        activated carbon
ORGANIC SYNTHESIS           from coconut shells
VOLUME #49
            cool 
I was never that scientific about it but using my procedure the amphetamine is ripped up into benzaldehyde wich forms the shif base and that get methylated, best results ussing pink eye drops and Tetra[@R] Parafourmaldehyde, iso-propyl glycerol used to be an inactive, ummm I used pharmucuticial amphetamine peroxide 3% vinagear hcl acid lye getto dean stark trap lots of commercial HEET and Tone and White Gas, calcium cloride, oxcylic acid, sulfacedamide, washing soda, ammonia, baking soda um everything insitu basicially two steps waitting for formaldehyde like layer to seperate out, its pretty obvious where the shit is vs the amine *the tolune-like layer was reduced and added to the clear alcohol layer after the singlet "GRAINS" had been harvested these were intermixed with what had been found upon the water layer evaporate, this pyrolyzed upon pot, um the best yet.  Suden relaxation after hit um almost passed out music and thin zig zags lasted about 5 minutes and "it" was the best I had felt as far as anesetic like effects are concerned.  The important thingy in this is that you can issolate a GRAIN OF AMPHETAMINE or whatever your working with pretty easiily so ya need no scale um salt looks like buckyballs or styrofoam rocks turning a beige color upon desication also shrinking, at first there a little purple looking light blue red aura Cyanide like gas evelution real possible       
 
 
 
 
    Antoncho
(Official Hive Translator)
04-28-02 12:33
No 302544
      A correction     

Lugh and all - i am sorry, it was my mistake - i compiled the procedure from two parts, so the weight of starting ketone and the product amine are not consistent.

Zealot noticed that and asked me to tell you that the yield of amine - 23g - is based on 25g of initially taken P2P.


Antoncho
 
 
 
 
    flipper
(Hive Bee)
04-28-02 16:40
No 302582
User Picture 
      This is a question........     

because of my limited English. What does this exactly mean.

Into a 250 ml flask there is placed 64 g P2P (recalculated - 47 g for cyclohexanone) and 40 g HCOONH4  (1,3 xcess - 2x xcess in the original, but that's unneeded).

What about Cyclohexanone and what is meant with xcess? Sorry. crazy

You've gotta love me.
 
 
 
 
    PolytheneSam
(Master Searcher)
04-28-02 20:32
No 302651
User Picture 
      rewording     

64 g P2P and 40 g HCOONH4 are placed into a 250 ml flask.
(recalculated for 47 g for cyclohexanone used in the literature (not used here))
(1.3 excess - 2 times excess HCOONH4 was used in the original, but that's not needed).

Note cyclohexanone and P2P are both ketones.
https://www.rhodium.ws/archive/leuckart.pdf


http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious
 
 
 
 
    flipper
(Hive Bee)
04-29-02 05:36
No 302878
User Picture 
      Saying Thanks     

Thanks laugh


You've gotta love me.
 
 
 
 
    cesium
(LabChamp)
04-29-02 15:59
No 303011
      Catalysed Leucard     

The temperature and reaction time during first step could be lowered to approx. 125-135°C and 45 minutes by using 0,5 % of nickel catatalyst prepared by anaerobic thermal decomposition of Ni formate. Yield of N-formyl-MDA is almost quantitative, however due to the harsh acid hydrolysis the overall yield was lowered to 63% after workup. This procedure was originaly published in russian Zh. Obs. Kchim around 1964.
 
 
 
 
    Rhodium
(Chief Bee)
04-29-02 18:38
No 303069
User Picture 
      Russian Chemistry     

cesium: Is there any possibility at all that you could look up that reference in detail for us and post?
 
 
 
 
    neuromodulator
(Newbee)
04-29-02 22:25
No 303117
      Correct me if I'm wrong, but it's technically ...     

Correct me if I'm wrong, but it's technically impossible to do a Leuckart reaction with ammonium formate.
 
 
 
 
    Osmium
(Stoni's sexual toy)
04-29-02 22:44
No 303121
User Picture 
      Yes you are wrong. Consider yourself corrected ...     

Yes you are wrong. Consider yourself corrected wink

I'm not fat just horizontally disproportionate.
 
 
 
 
    neuromodulator
(Newbee)
05-01-02 22:14
No 303934
      au contraire     

Ammonium formate is a salt which is completely dissociated into ammonium ions and formate ions while in solution.  Since the nitrogen moiety and the formate moiety are not even a member of the same molecule, then why on earth are you going to need to hydrolyze them with an acid or base in the next step to get the amine?  This sounds like a nice way to make an imine to me.  Even if he did end up making some crack, no Leuckart reaction has taken place. 

Thank you, drive thru.
 
 
 
 
    Rhodium
(Chief Bee)
05-01-02 22:25
No 303940
User Picture 
      Wrong again Neuromodulator     

At first the imine forms from the ketone and the ammonium ion (along with water), then formic acid adds across the imine bond, forming the N-formylamine (which need to be hydrolyzed).
 
 
 
 
    neuromodulator
(Newbee)
05-02-02 03:26
No 304043
      If that's the case, then why don't people mix ...     

If that's the case, then why don't people mix MDP2P and methylamine and formic acid together to make MDMA?

Also, if someone had answered my query with a reasonable answer in a polite fashion instead of being a smart-ass in the first place, then you would have kept me from being wrong again.  If you don't wish for me to contribute any longer, then I will be glad to leave your discussion board.
 
 
 
 
    Rhodium
(Chief Bee)
05-02-02 03:50
No 304051
User Picture 
      reductive leuckartation     

That could probably work too, but if one already has methylamine and MDP2P, noone would be so stupid as to make the formylamide from the imine, when there are so many other reductive amination routes/reagents avaliable for direct reduction to the amine.
 
 
 
 
    PolytheneSam
(Master Searcher)
11-20-02 23:15
No 381681
User Picture 
      Here's an example with ammonium formate.     

Here's an example with ammonium formate.
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0503

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious
 
 
 
 
    flipper
(Hive Bee)
11-23-02 13:05
No 382564
      A little question     

If this method is used on MDP2P it forms MDA, isn't it. But what have to be used to make MDMA????????????
 
 
 
 
    lugh
(Moderator)
11-23-02 13:14
No 382568
      Salts     

One would use methylammonium formate smile
 
 
 
 
    PolytheneSam
(Master Searcher)
11-23-02 15:36
No 382593
User Picture 
      See also Post 240004 Post 240031     

See also Post 240004 (PolytheneSam: "Re: Benzedrine method", Stimulants) Post 240031 (Rhodium: "Re: Benzedrine method", Stimulants)

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious
 
 
 
 
    dennispeck
(Stranger)
12-19-02 13:04
No 390788
      Are there any (other) methods using this ...     

Are there any (other) methods using this synthesis to achieve higher yields ??
 
 
 
 
    Rhodium
(Chief Bee)
12-19-02 19:39
No 390844
User Picture 
      What was the question again?     

What was the question again?
 
 
 
 
    dennispeck
(Stranger)
12-23-02 12:49
No 391977
      Am curious if it is possible to get better ...     

Am curious if it is possible to get better yields,and if yes,how?
 
 
 
 
    Rhodium
(Chief Bee)
12-25-02 23:48
No 392830
User Picture 
      92% isn't good enough for you?     

92% isn't good enough for you?
 
 
 
 
    drifter
(Stranger)
01-16-03 13:24
No 398679
      What happens if I use Zinc as a catalyst ?     

What happens if I use Zinc as a catalyst?
 
 
 
 
    Barium
(Hive Addict)
01-16-03 13:48
No 398685
      Zinc as a catalyst for the Leukart reaction.     

Zinc as a catalyst for the Leukart reaction? What part in this reaction would zinc catalyze? I don´t think I´ve ever seen zinc as a catalyst, but I´ve often seen it as a reducing agent.

Catalytic hydrogenation freak
 
 
 
 
    drifter
(Stranger)
01-16-03 15:02
No 398702
      Excuse me...,what would Zinc do as a reducing...     

Excuse me...,what would Zinc do as a reducing agent?
 
 
 
 
    Antoncho
(Official Hive Translator)
01-16-03 15:14
No 398706
      An improvement     

Actually Zealot provided an improved version of this, using Raney Ni. If anyone's interested i'll translate it.



Antoncho
 
 
 
 
    drifter
(Stranger)
01-17-03 12:57
No 399022
      Absolutely,am always interested in improved...     

Absolutely,am always interested in improved versions
 
 
 
 
    brownhornet
(Stranger)
01-19-03 08:58
No 399624
      Fractionating column used instead of Dean Stark ?     

Rhodium, SWIB was wondering since the boiling points of h20 BP 100C(which the bee likes to separate from our leuky) ammonium formate BP 180C, and mdp2p BP 250C+ , could bee used to remove  H20 from our RXN using a fractionating column instead Dean Stark.  Thought about running the H20 vapour column just to the stillhead arm, hopefully leaving behind the higher boiling reactants.  She was planning on bring the RXN temp up real SLOW creating the most gentle reflux over a long time (maybe days??).
Please comment, she nailed a 90%+ boro reduction but thought makin ammonium formate by xcess of formic acid over ammonium carbonate would bee faster.
[i][/yellow] bees gives the world luvs wink
 
 
 
 
    Rhodium
(Chief Bee)
01-19-03 09:16
No 399631
User Picture 
      We aren't using expensive equipment to show off     

The point of using a dean-stark trap in this reaction is not simply to distill off the water, because if it was, a distillation setup had been used instead. Do you know how a dean-stark works? The point of using it here is that we can control the reaction temperature very carefully by adjusting how much water is being removed from the reaction mixture and how much is allowed to return. Without it, no water is being returned, and the temperature in the flask rises too high for good yields.

Dean-Stark trap (with reccommended isolation of the glass tube)
 
 
 
 
    brownhornet
(Stranger)
01-19-03 15:31
No 399700
      Dean Stark + Leukey= 92%!!!!     

Thnx Rhodium,was only trying to make rxn work with what i had (no dean stark). i go get one now.
My understanding is that the reactants climb thru dean stark and h20 condenses at condenser and falls into the trap.
Only h20 travels out of flask to the condenser under reflx and the slow removal of it over a longer period of time ensures a even rise in temp. Rhodium could you clarify mechanism of how dean stark works for SWIB?
 
 
 
 
    Rhodium
(Chief Bee)
01-19-03 21:09
No 399748
User Picture 
      How a dean-stark trap works
(Rated as: good read)
    



By carefully controlling how much water is tapped off, the amount of water present in the system can be very finely adjusted, and with that also the reaction temperature.
 
 
 
 
    abolt
(Stranger)
01-21-03 03:59
No 400069
      leuckart with 92% + overall yield     

swim has A.R. grade Formamide, but as the yields are lower for this chem. could he synth. Ammonium Formate by adding H2O to his Formamide
 
 
 
 
    Rhodium
(Chief Bee)
01-21-03 04:15
No 400071
User Picture 
      No, formamide will not revert to ammonium...     

No, formamide will not revert to ammonium formate just like that.
 
 
 
 
    abolt
(Stranger)
01-21-03 04:31
No 400076
      Thanks Rhodium     

I'll give this a try with my Formamide and report back what i find out.
 
 
 
 
    dr_ruthenium
(Hive Bee)
01-26-03 17:31
No 401624
      SWIDR recently witnessed a Leuckart with about     

SWIDR recently witnessed a Leuckart with about 33% yield.  Yeah, this isn't high, but when done with 1 mole ketone results in 60g MDA.  Formamide/Ammonium formate was prepared by neutralizing 90% formic with 3% ammonia and evaporating down.  Equal weight of ketone:formamide (mole ratio of 1:3-4) was used along with a couple ml's of acetic acid for kicks.  Heated at 150 C for 30 hours (slight evolution of CO2 was still evident.  Washed with dH2O x1, to rid of xs formamide.  Hydrolyzed with 15% HCl (should try alcoholic/aqueous NaOH) for 2 hours.  Washed with DCM.  Basified with NaOH.  Extracted with DCM.  Distilled at 150-155 C.  Bioassay with 200mg oil disolved in lemon juice (i.e. MDA citrate) was ++++ for 9 hours.  More like LSD than MDMA.  Maybe bioassay with 100mg in future?

TRISMUS!!!
 
 
 
 
    drifter
(Stranger)
02-05-03 10:26
No 404678
      What do I get when I replace the ammonium...     

What do I get when I replace the ammonium formate for N-methyl ammonium chloride?
 
 
 
 
    Rhodium
(Chief Bee)
02-05-03 19:50
No 404783
User Picture 
      The N-methylimine of the ketone.     

The N-methylimine of the ketone. The reduction to the N-methylamine won't happen without using the methylammonium formate (or N-methylformamide).
 
 
 
 
    drifter
(Stranger)
02-06-03 17:18
No 405144
      Okee...but would I get MDMA when I use ...     

Mmm,let me rephrase would I get MDMA when I use n-methyl ammonium chloride instead of MDA when using ammonium formate?
 
 
 
 
    hypo
(Hive Addict)
02-06-03 17:47
No 405153
      no     

you need n-methylformamide.

and btw: "n-methyl ammonium chloride" is usually called methylamine hydrochloride (methylamine.HCl, MeNH2.HCl)
 
 
 
 
    drifter
(Stranger)
03-23-03 11:22
No 420406
      Looking for clues...     

I'm fairly new at this game and looking for some help.Performed the first step as described(twice) however no crystals after cooling down,please explain or describe the even rise of the reaction temperature,I am working with a Dean-Stark but have a rough time trying to get it to work as described.
Where lies the clue in this matter?
Thanks.
 
 
 
 
    SPISSHAK
(Hive Addict)
03-30-03 22:14
No 422591
      differing mechanisms between these two methods     

So lets summarize the diiferences between action of an amide on a ketone and action of an ammonium formate salt on a ketone.
I would speculate that in the first example the amide forms an imido compound by condensation reaction, this gets reduced by the conjugated formate ion to CO2, saturated amide, And free amine (the reason why this reaction kicks off such a nasty odor.
in the second reaction disassociated amine or ammonium ion codenses on the ketone then the formate ion adds across the double bond.
Making the second stage of this an addition reaction and the second stage of the first reaction a reduction.
This is correct no?
 
 
 
 
    Rhodium
(Chief Bee)
03-30-03 22:18
No 422592
User Picture 
      http://www.rhodium.ws/pdf/leuckart.pdf     

https://www.rhodium.ws/pdf/leuckart.pdf
 
 
 
 
    fathornet
(Stranger)
04-02-03 18:03
No 423355
      no crystalization, what went wrong????     

Can somebody help? swif made her ammonium formate by using a slight excess of 85% formic over ammonium carbonate which produced fizzin and foam, after things had settled, she vac filtered. Is this correct in making ammonium formate, can this white crystaline product be tested ie, melting point???
anyways assumming this was done correctly she performs leukey with a dean stark trap. Brought up temp slow so sublimation (white crystaline product) in reflux condenser is kept managable.  So she slowly removes h20 from the dean stark over the course of hours recommended by antonocho.  She lets it cool and no crystalization???
anyways procedes with an acid hydrolysis but this honey just dont taste the same as a formamide leukey.
Did she fukup the ammonium formate reaction??
what can she do?
Can someone please post a sucessfull ammonium formate leukey with details??
I'm beginning to think high yeild leukeys are myth.
 
 
 
 
    SPISSHAK
(Hive Addict)
04-03-03 07:36
No 423524
      pullesse be a little more terse and specific     

we chemists like details not generalizations.
Can we hear a little more coherent detail about your attempt?
Like times, temps, molar proportions, concentrations etc?
and yes I hear pyrimidines are prevalent in this synth using methylenedioxylphenylacetone as a precusor.
a useful alternative would be the use of the formate in a CTH utilizing Pd/C 10% Barium would know about this.
 
 
 
 
    fathornet
(Stranger)
04-04-03 06:37
No 423807
      no paste crystalization, wtf????     

anyhowz swif used a reflux setup with dean stark trap to reflux 64g mdp2p and 40g ammonium formate (made by neutralizing ammonium carbonate with slight excess of 85% formic acid) Over 5hrs h20 was removed until temp hit 170C and left there for 1hr. She then let it cool and waited and
waited and waited. NO paste, No crystalization.
She tastes to find it different than if formamide had been
used instead up to this point.  No Taste of correct formyl derivative as compared to formamide leukey. 
beginning to think ammonium formate was not synthed correctly.
Which is the best way of making ammonium formate?
1) neutralizing ammonium hydoxide solution with formic acid then distilln to 160C
or
2) neutralizing ammonium carbonate with a slight excess of formic acid then vac filtering crystals and use as  slightly moist 

Why does this reaction get a trophy, when it doesn't even appear on Rhodiums site.  Are other bees too lazy to try this and want the details handed to them on a silver platter??? Where would the hive bee today with this sort of thinking. I'll tell you, NO WHERE!!!!  It frustrates me to see such slow progress (i'm very impatient u see). 
Well I'll tell you I'm very determimed anyhow. When I first saw antnocho's post I ordered the ammonium carb pronto to try this, not afraid to attempt something i beleive has some real merit to.  Bees in nature work collectively in nature but this hive seems have some lazy asses, YA KNOW WHO YA IS. 
But I like to thank some real researchers and pioneers here as well YA KNOW WHO YA IS TOO.
It really annoys me that some bees spend more energy flaming rather than contributing to our cause. 
REMEMBER WE ARE ALL ON THE SAME SIDE RIGHT????
enuff of my rant

Reaction madmad
 
 
 
 
    Rhodium
(Chief Bee)
04-04-03 13:12
No 423860
User Picture 
      Reason     

The reason this excellent Leuckart variation isn't on my page yet is only due to lack of time on my part to edit it together to form a publishable document. Right now there are still a few spelling errors in the writeup and the layout is pretty sketchy... It will end up on my page in time.
 
 
 
 
    drifter
(Stranger)
04-05-03 13:20
No 424072
      Step 2     

Are there any other ways/methods to perform step 2(hydrolysis of the FD)??
 
 
 
 
    drifter
(Stranger)
04-05-03 20:58
No 424154
      Still looking for clues     

I'll try and give a summarized explanation of what swim has been doing for the past week.
Performed the Leucky using a Dean Stark while using P2P,swim used 98% Ammonium Formate which is fairly easy to obtain where swim lives.A gentle and even rise was not the problem but didn't succeed to reach 160C several times! Even after three hours temperature failed to climb higher than 150C/155C.Furthermore no paste and no crystalazation.
Could this have something to do with the impurity if the ketone?
Swim got his hands on some MDP2P and performed step one again,NOW temperature climbed very easy to 160C. and went up as high as 185C.Temperature dropped to 184 and left it there to boil for 1 hour.Swim understands bp's are different for P2P and MDP2P but is curious as to what the proper procedure is : is temperature traject the same for both ketone's ? Or is the higher temperature an obvious and therefor necesarry cause when using MDP2P?
Performed step 2 using MeOH and a aquous NaoH soln.instead of refluxing used a magnetic stirrer hotplate and got soln close to bp.
The result was a dark(black)soln. where seperation of the layers was very difficult to detect.
 
 
 
 
    Rhodium
(Chief Bee)
04-05-03 23:27
No 424178
User Picture 
      What kind of heat source did you use, are you...     

What kind of heat source did you use, are you sure it is powerful enough to heat the amount of liquid you used to 160°C?
 
 
 
 
    drifter
(Stranger)
04-06-03 11:54
No 424298
      Yes,swim has access to all professional lab...     

Yes,swim has access to all professional lab equipment,and did succeed to bring temperatures up as described in Antoncho's post but not on all occasions.
When using MDP2P instead of P2P temperatures when up no problem over the given course of time(4-6 Hrs.) and rised all the way to 185C.
 
 
 
 
    dennispeck
(Stranger)
04-06-03 12:04
No 424300
      Am also curious,like fathornet,if there is...     

Am also curious,like fathornet,if there is anybody who managed to get 92%+ yield using this kind of reaction...
 
 
 
 
    fathornet
(Stranger)
04-06-03 18:56
No 424356
      0% Ammonium formate leukey     

swif got 0% yeild of mda but some inactive free base when reaction was carried to completion even though the formyl derivative tastes nothing like formamide leukey.
the final clear fluid was about 15-20% mass of starting ketone and after tasting realized this was not even contaminated with any taste of mda  mad
 
 
 
 
    Antoncho
(Official Hive Translator)
04-07-03 10:17
No 424514
      Darn it...     

i'll talk to Zeally about that.



Antoncho
 
 
 
 
    fathornet
(Stranger)
04-15-03 19:15
No 427023
      Zeally where art thou????     

Antoncho; Whats happenin with Zealot.  Can he back his claim of a 92% with more details.  swif tried the procedure as described but didn't get crystalization at the formyl derivative step as indicated.  I'm certain this procedure needs more details and feedback from other bees to get it to fly.
Come on bees please throw in your reports of attempts on this promising leukey.
what i need is the synth of ammonium formate using ammonium carbonate/formic acid for bees that cant get Ammonium formate.
are some bees hibernating, well wake up. wink
 
 
 
 
    dennispeck
04-16-03 07:56
      Hear hear...
(Rated as: insignificant)
    
 
 
 
    fathornet
04-16-03 18:33
      secrets???????
(Rated as: insignificant)
    
 
 
 
    Antoncho
(Official Hive Translator)
04-17-03 09:06
No 427535
      I sent him a PM...     

Hopefully, he answers it soon (he hasn't been around for some time now).



Antoncho
 
 
 
 
    drifter
07-17-03 09:42
      Anybody.....
(Rated as: insignificant)
    
 
 
 
    flipper
(Hive Bee)
10-25-03 08:37
No 466655
      Well then     

This means that the 92% yiels Leuckard is a Myth or it's just shit. Or isn't it? mad
Drifter maybe you can do some CTH reaction with that Ammonium Formate.
 
 
 
 
    UncleFester
(Popular Author)
06-07-04 19:49
No 512037
      nickel formate details...???     

Back in the '70's, I did a few runs with phenylacetone and formamide and got nothing except the dreaded red tar. It wasn't until I started making N-methylformamide that I saw good results. These experiments were done using 98% formamide, both alone and in combination with added formic acid.
I was told by someone "in the know" that 99% formamide was what was needed to get that reaction to go. That substance was unavailable to me, so I tried distilling the formamide under roughly 20 torr vacuum, and also tried gassing some dry ammonia into the distilled formamide. All these efforts were a waste of time. Beyond that, distilling formamide is no easy task as it is thick and bumps a lot and distills very slowly.
I would like more info on the use of nickel formate in this reaction. I checked Chem Abstracts for the time period in question under both nickel formate and Leuckart Reaction and came up with zilch...
 
 
 
 
    moo
(Hive Bee)
06-07-04 21:34
No 512060
      Nickel catalyzed Leuckart reaction.
(Rated as: good read)
    

It appears that in Post 326428 (zealot: "Дальнейшее улучшение реакции Лейкарта-zealot’a", Russian HyperLab) is a procedure for nickel catalyzed Leuckart reaction but the catalyst isn't Raney nickel. The catalyst is prepared by thermal decomposition of nickel formate, using a test tube and a gas flame, and is referred to as pyrophoric nickel. I guess this one from Zealot isn't translated to english yet.

Couln't find anything about using nickel formate in Leuckart, but there is a ref. about Raney nickel.

Catalysts and mechanism of the Leuckart reaction.
Kost, A. N.; Grandberg, I. I.
Zhurnal Obshchei Khimii, 25, 1432-7 (1955).
CAN 50:23865  ISSN 0044-460X
 
Abstract
Alk. catalysts in the presence of Raney Ni accelerate the Leuckart reaction and direct the reaction to the formation of predominant formation of secondary amines.  It was shown that the Leuckart reaction goes through the step of dissocn. of HCONH2, and the 1st product is not the amine but its formyl deriv.  Improved techniques for formation of amines are described below.  To 450 g. mixt. contg. 6 moles HCONH2 and 2.5 moles HCO2H [prepd. by passing NH3 into 85% HCO2H or addn. of (NH4)2CO3 to the acid, followed by distn. to bath temp. 150 Deg; the residue was heated until the pot temp. rose to 175-80 Deg, when the mixt. was distd. in vacuo to yield HCONH2], was added 1 g. Raney Ni, the mixt. heated to 120 Deg and treated over 1.5 hrs., with continuous distn., with 150 g. cyclohexanone; after 1.5 hrs. further heating the mixt. was treated with 300 ml. 50% NaOH, decanted, and the ppt. treated with hot H2O; the sepd. oil was taken up in Et2O and distd., yielding 98% formylcydohexylamine, b19 153-4 Deg, b751 268-74 Deg, m. 27 Deg, nD17 1.4892, d17 1.0123.  To 100 g. formate-formamide mixt. was added 100 g. 85% HCO2H and 0.5 g. Raney Ni, followed at reflux over 1.5 hrs. by 48 g. cyclohexanone; after 2.5 hrs. at 115 Deg, evapn. with 500 ml. concd. HCl, treatment with KOH and distn. there was obtained 85.2% cyclohexylamine, isolated as the HCl salt, m. 207 Deg.  CO(NH2)2 (30 g.), 29.4 g. cyclohexanone, 20 g. 85% HCO2H, and 0.5 g. Raney Ni heated 3 hrs. to 110 Deg while 20 g. HCO2H was being added, gave 84.8% dicyclohexylamine, b19 137-9 Deg (HCl salt, m. 335 Deg).  To a refluxing mixt. of 18.5 g. HCONH2, 47.7 g. Ac2O, and 0.5 g. Raney Ni was added over 20 min. 9.9 g. cyclohexylamine, heated 40 min. and treated with NaOH yielding 74% acetylcyclohexylamine, m. 102-3 Deg; no formylcyclohexylamine was detected.  If Ac2O is omitted, the formyl deriv. formed in 32% yield.  This with Na under Et2O gave a powdery Na enolate of the formylcyclohexylamine, which with EtI gave 22.8% ethyl-cyclohexylamine, b761 163-5 Deg (picrate, m. 132 Deg), after the sapon. of the intermediate formyl deriv. with 5% NaOH at reflux.  In the Leuckart reaction the addn. of the ketone component to the hot HCONH2 tends to raise the yield of the primary amine.  If HCONH2-HCO2H is added to excess ketone, the secondary amine is mainly formed but part of the ketone is unreacted.  Addn. of Ni facilitates the reaction by accelerated decompn. of HCO2H and decline of acidity of the medium.  In a basic soln. (pyridine, NH3, Na or urea salts) the reaction goes very energetically.  Excess acid almost prevents the formation of secondary amine.  Also in J. Gen. Chem. U.S.S.R. 25, 1377-81(1955)(Engl. translation).

fear fear hate hate
 
 
 
 
    Rhodium
(Chief Bee)
06-08-04 17:22
No 512217
User Picture 
      Leuckart article for reference
(Rated as: good read)
    

Secondary Amines by the Leuckart Synthesis
Armando Novelli
J. Am. Chem. Soc. 61, 520-521 (1939) (https://www.rhodium.ws/chemistry/leuckart.2nd-amines.html)

Summary
A new method of obtaining secondary amines, based on the Leuckart synthesis, is described. It has been applied to the preparation of several old and new amines.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    ning
(acetaminophanatic)
06-09-04 01:28
No 512270
User Picture 
      Is it really a leuckart with Ni?     

I respectfully submit that the reaction is likely not a leuckart anymore when nickel is added, and instead becomes a CTH reaction. Probably stereochemistry or isotopic studies would support this. AFAIK leuckart reaction is a free-radical reaction, and works best when carried out in glass, rather than metal, containers, because some metal ions catalyze the useless breakdown of formic acid into H2 and CO2. With a hydrogenation catalyst to recieve and transfer this hydrogen, it is no problem. But I think it has to be considered a different reaction.

"...Now that's as close as a chemical, a drug, can get to being a good woman"
 
 
 
 
    moo
(Hive Bee)
06-09-04 05:24
No 512306
      That's what I've been thinking too. :-)     

Regarding the CTH analogy, that's what I've been thinking too.smile

fear fear hate hate
 
 
 
 
    synthon
(Stranger)
06-09-04 06:20
No 512315
      Leuckart mechanism     

AFAIK leuckart reaction is a free-radical reaction...

Interesting. Do you have any reference for that statement? Here is the Leuckart as I remember it:

mechanism_Leuckart.gif

I don't remeber reading anything about involvement of radicals in a Leuckart.... or a "Leucky". smile
 
 
 
 
    Rhodium
(Chief Bee)
06-11-04 01:36
No 512672
User Picture 
      Leuckart Reaction Mechanism
(Rated as: excellent)
    

Taken from Synthetic Reductions in Clandestine Amphetamine and Methamphetamine Laboratories - A Review (https://www.rhodium.ws/chemistry/amphetamine.reduction.html)

"The mechanism of the Leuckart reaction has been studied65,71-72 and shown to be a free radical process initiated by formic acid."

#65:
Studies on the Leuckart reaction
F.S. Crossley and M.L. Moore
J. Org. Chem. 9, 529-536 (1944) (https://www.rhodium.ws/pdf/leuckart.amph.1944.pdf)

#71
Studies on the mechanism of the Leuckart reaction
E.R. Alexander and R.B. Wildman
J. Am. Chem. Soc. 70, 1187-1189 (1948) (https://www.rhodium.ws/pdf/leuckart.rxn-mech.study.pdf)

#72
The mechanism of the Leuckart-Wallach reaction and of the reduction of Schiff bases by formic acid.
A. Lukasiewicz
Tetrahedron, 19, 1789-1799 (1963) (https://www.rhodium.ws/pdf/leuckart.rxn.mechanism.pdf)

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    armageddon
(Hive Bee)
07-03-04 02:17
No 517101
      92% is no myth     

As I read through this wonderful thread, I realize some bees doubted Zealots results, because they didn't manage to get it to work as described...

...but in conversations with my buddy SWIA, he once told me that he had tried the described procedure on 6.3ml P2P, using a water/toluene solvent system and lab grade ammonium formate (if I remember correctly). The reason for the additional solvent was the small amount of starting material, and with water/toluene he was able to heat slowly at the beginning, although using a 500ml-flask/heating mantle...smile

Anyway, when the water had been removed via dean-stark, SWIA distilled away the toluene (still using the trap smile), refilled the trap with water to the top and during the next 4 hours slowly removed the water in increments of 4-5 drops a time. Temp. climbed to 180°C, where it was held for 1h. On cooling, nothing solidified..

NaOH/EtOH hydrolysis was allowed for 2 hours, then NaOH(s) and toluene was added and the organic layer separated,  washed with aequ.NaOH/brine and dried. After removing the toluene/ethanol (again using dean-stark as it was still set up laugh), SWIA dissolved the remaining oil in 20%HCl, washed 5x with CHCl2 (which removed lots of red tar/gunk), basified, xtracted w/toluene 2x, removed solvent using aspirator vacuum and heating, and finally dissolved the remainder in anhydr. EtOH and titrated to pH 6.9 with alcoholic H2SO4...

...yield of sulfate salt: 49% of theory...
(with bad technique/sloppy workup/mechanical loss of maybe 10% of product, due to big glassware used)

And I would say, this clearly shows that 92% yields ARE possible (at least when done right, and with a good amount of starting material to minimize losses). Please don't doubt it.

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    Rhodium
(Chief Bee)
07-03-04 02:52
No 517110
User Picture 
      defying logic     

And I would say, this clearly shows that 92% yields ARE possible

Huh? Your trial does not indicate anything whatsoever, besides sloppy lab technique...

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    OcoteaCymbarum
(Hive Bee)
07-03-04 03:19
No 517114
      AS anyone taken a look at this article     

This seems pretty interesting.
Tetrahedron letters, Vol 37, no 45 , 8177-8180, 1996

They claim close to 97% yield using microwave technology. Someone chould try this.
Using 3 equivalents of formic acid and formamide for every mol ketone, with around 30 minute reaction time.
 
 
 
 
    Rhodium
(Chief Bee)
07-03-04 07:55
No 517141
User Picture 
      MW Leuckart     

Most of it has been posted here: Post 108529 (dormouse: "Son of Leuckart arises to battle the evil Narc hordes.  -Cherrie Baby", Novel Discourse)

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    armageddon
(Hive Bee)
07-03-04 15:12
No 517180
      I just thought..     

Huh? Your trial does not indicate anything whatsoever, besides sloppy lab technique...

Firstly, it wasn't "my trial" but SWIAs trial, and I already mentioned explicitly that I did't post because being proud about exceptionally high yields - I posted just because I wanted to show other bees that Zealots variation isn't bogus..

Secondly, I thought that a standard leuckart (p2p, ammonia, formic acid, heat to 190°C for hours) would give much inferior yields (like 20-30%) - and SWIA got better yields (~45%) ALTHOUGH having much water present (and despite his sloppy technique), i.e. the only difference was the slow temp. adjustment with a dean-stark.
So I concluded that even higher yields are possible when Zealots procedure is followed exactly.

Sorry if I'm wrong.

Considering "my bad lab technique": If SWIAs glassware held back approximately 1g of product (considering he used big 500ml glassware/29-joints, this is realistic), he got in fact 65% yield...

Anyway Rhod, If you think I can't contribute to this thread with useful info, I'll simply let it be!?

A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    Rhodium
(Chief Bee)
07-03-04 17:51
No 517198
User Picture 
      Quality control of provided data points     

So I concluded that even higher yields are possible when Zealots procedure is followed exactly. Sorry if I'm wrong.

The only conclusion which can be drawn from your experiment is that with your technique and setup, a yield of 49% is possible (assuming the product is pure, etc.). I am not questioning the findings you posted (or Zealot's writeup for that matter), only that it is an unreasonable leap of faith to use a 49% yield gotten with suboptimal lab technique to claim that 92% yield would be the result of better technique.

Considering "my bad lab technique": If SWIAs glassware held back approximately 1g of product (considering he used big 500ml glassware/29-joints, this is realistic), he got in fact 65% yield...

If an attainable reaction yield is to be proven in an experiment it is imperative that the glassware fits the reaction size, so if a 500 mL NS 29 setup is all you got, you need to scale up the reaction accordingly. Not only will your measured yield consistently be lower than the actual value, it will also be very imprecise with such a small batch size. You have no idea of knowing if you isolated 98% of an actual yield of 50% or if you isolated 53% of an actual yield of 92% (both these percentages corresponds to the claimed yield of 49%). Without knowing if your mechanical losses were 2% or 47%, the claimed yield has an exceptionally large error margin.

Just don't take my comments personally, I just want to raise this issue as a way of telling you and others how to improve the quality of the data you provide other members with. The better the quality of your data, the higher becomes your credibility and the things you post becomes more useful to others.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    armageddon
(Hive Bee)
07-03-04 18:18
No 517204
      ok     

OK I see. Think SWIA will try it again with apropriately sized glassware/bigger amounts - at least I'm sure he will do if I tell him about your "quality control"...wink

(there is no followup post verifying Zealots procedure, think this needs to be fixed smile)

(BTW even with bigger reactions, SWIAs glassware almost ALWAYS holds back ~1ml of substance - at least from his experience - but I understand how you are sceptical about the percentages isolated..)

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    cublium
(Hive Bee)
07-03-04 19:45
No 517220
      People are making amphetamine in Europe with...     

People are making amphetamine in Europe with Leuckart method(do you know any other widely used method for amphetamine manufacture?) so yields must good enough for clandestine manufacture.I've heard from quite reliable source that some people,who have messed with Leuckart few years,developing it and so one,get about 16 kgs of amphetamine sulfate from 20 kgs of P2P.
 
 
 
 
    armageddon
(Hive Bee)
07-04-04 16:36
No 517401
      big scale production     

cublium: High pressure hydrogenation over RaNi or Pd/Pt catalysts with ammonia/methylamine in huge stainless steel pressure tanks? (more state-of-the-art than oldschool leuckart - but with the given procedure the leuckart becomes comparable again, seen yieldwise)

Oh, and I just "discovered" that the use of a dean-stark isn't that new, quote:
"The distilled ketone, if any, is separated from time to time and returned to the reaction mixture. Alternatively, when rather volatile ketones are used, the reaction may be run in a flask fitted with a simple automatic separator so arranged as to return the (upper) ketone layer and discharge the aequous layer."

..taken from https://www.rhodium.ws/pdf/leuckart.amine.synthesis.extensions.pdf  (the authors used acid hydrolysis, though)

(antoncho, this is NOT the original article you mention, isn't it?)

Greetz A

"my OTC idea involves several liters lsyergic acid, plutonium and 2 tons of wheat starch."
 
 
 
 
    Shane_Warne
(Hive Bee)
07-04-04 23:12
No 517478
      armageddon, in: Post 508257 You mention an 80%     

armageddon, in: Post 508257 (armageddon: "CTH а la Sunlight - revisited", Methods Discourse)

You mention an 80% molar yield from an attempt using ammonium formate, Pd/C, but with no pressurised apparatus.

Or isn't that technically a leuckart and hense not what's being discussed here?
 
 
 
 
    Rhodium
(Chief Bee)
07-05-04 00:43
No 517492
User Picture 
      Catalytic Transfer Hydrogenation     

The Pd/C-catalyzed reductive amination is a Catalytic Transfer Hydrogenation (of an in situ formed ketimine) and is not classified as a Leuckart reaction, as it uses a palladium catalyst.
The Leuckart reaction always produces an N-formyl-amine, which has to be hydrolyzed before the amine can bee isolated.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    Shane_Warne
(Hive Bee)
07-05-04 13:12
No 517553
      understood     

Thanks for the explaination.
Is it common for an N-formyl-amine impurity to bee found in a Pd/C CTH, and likewise, for a ketimine impurity to bee found in Leuckart reactions?

(Because it uses mostly the same reactants obviously.)
 
 
 
 
    armageddon
(Hive Bee)
07-08-04 00:00
No 518055
      maybe, but nothing to bother with     

Maybe there are formyl derivatives formed during CTH rxns, but only in traces (if any). You don't have to bother with hydrolysis (unless you want to clean you catalyst) and still get good yields. But in a Leuckart rxn, the product is mainly formylamph. (in this case it is amph at least), which has to be hydrolyzed (preferably with alcoholic NaOH) before you can proceed with purification (A/B or steam dist.)
Ketimines are no impurities found in Leuckart reactions AFAIK - they form with a finely divided Pd/C catalyst (in fact they even form complex compounds with the Pd/C, and this complex formation enables their reduction). But besides from having the same sources for hydrogen and ammonia, these reactions have nothing in common - CTH proceeds in an aequous solvent at room temp over several days and needs a catalyst, and the Leuckart is heated to >180° while gradually removing water formed in the rxn over a period of a few hours, and "only" needs fine adjustment of the heating and dean-stark (and hydrolysis of an intermediate amine) and gives slighly less pure products...

Hope this answers your questions..

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    Rhodium
(Chief Bee)
07-08-04 08:52
No 518137
User Picture 
      Ketone + Ammonia -> Ketimine + Water     

Ketimines are no impurities found in Leuckart reactions AFAIK - they form with a finely divided Pd/C catalyst (in fact they even form complex compounds with the Pd/C, and this complex formation enables their reduction).

??? - Ketimines are condensation products between ketones and ammonia, and they form spontaneously in solution without any need for Pd/C.

Ketone + Ammonia -> Ketimine + Water

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    armageddon
(Hive Bee)
07-08-04 18:31
No 518197
      in said CTH, the ketimine forms but...     

in said CTH, the ketimine forms but isn't reduced directly - instead the formate ion bonds to the catalyst surface and the catalyst/formate complex  attacks the hemiaminal, therefore it needs more time to do so (at least https://www.rhodium.ws/pdf/redamin.cth-pd.pdf suggests it as rxn mechanism).

Of course the ketimine forms whenever ketones and amines meet (in anhydrous conditions preferably), but in this special case, the intermediate is a hemiaminal which bonds to a Pd-formate-complex and is subsequently reduced.

Quote: "Further evidence which supports the 'hemiaminal pathway' is the behaviour of scondary amines under our experimental conditions. Hydrogenolysis of the aminal intermediate is the commonly accepted pathway in the reductive amination of secondary amines, due to the fact that conversion to the unstable iminium species is unlikely. The good reactivity of secondary amines (see table 2) in our conditions, strongly disfavouring the iminium formation because of the basic medium, is in agreement with the hypothesised hydrogenolytic pathway." (they mean their 'hemiaminal pathway' rather than leuckart-like ketimine reduction)

So the impurities in CTHs and Leuckarts are not the same, and ketimine impurities are only likely to be found if a leuckart isn't hydrolized right (or is run with too little formic acid) - and if a CTH rxn isn't given enough time and isn't run with sufficient amount of catalyst, ketimine impurities could also be present. But in case of a CTH, this is very unlikely... (it is more likely that due to the workup, all ketimine will turn back into ammonium ions and ketone, which in turn can happen to condense with the product to give P2P-amphetamine imine, a soon as workup conditions shift to anhydrous...)

(sorry for my confusion Rhod)

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    Shane_Warne
(Hive Bee)
07-09-04 07:32
No 518348
      Thank you.     

armageddon, thanks for all that. You answered my queries, combined with Rhodiums responses regarding products in general.

I just wasn't certain as to whether one should use a combination of work-ups when dealing with these reactions.

Thank you.
 
 
 
 
    armageddon
(Hive Bee)
07-10-04 16:52
No 518564
      rxn time - slightly longer or perfect?     

Antoncho: do you know if Zealot has experimented with prolonged reaction times (probably yes) and do you know if slower heating over a longer time period might be good? Or would that be inferior, seen yieldwise?

I'm asking because I had the idea of adding a few drops of toluene to rxn - it would allow for a VERY slow and even temp. rise, as the toluene vapors would fill the flask and they would be only removed very slowly/continuously, thus temp. would rise even slower than with a dean-stark alone.

But I guess Zealot spent a good effort on optimizing everything, so rxn time is perfect w/o toluene, right?
(just wanted to be sure)

Greetz A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    armageddon
(Hive Bee)
07-12-04 02:50
No 518796
      another question     

I have a question about chirality/optical rotation. in some other thread I stated the following:

"oxime reductions result usually in more potent product, as the syn/anti ratio of the intermediate oxime is 9:1 or something like that. In most cases, this means a more potent phenylisopropylamine - not with 3,4-methylenedioxy compounds, but in most other cases"

 - first question: can anybee confirm this? Or did I write bogus?

 - next question: Assume that said oxime is hydrolyzed back to P2P (e.g. ketone purification via oxime): what is the rotation of the P2P? Or is it again racemic?

 - last question: if said P2P is reductively aminated w/NH4COOH àla Leuckart: is the end product (after hydrolysis) THEN racemic? I would guess so?

THX A

"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
 
 
 
 
    moo
(Hive Bee)
07-12-04 03:34
No 518807
      You are mistaking the stereochemistry of the...     

Racemic P2P? Did you miss the stereochem classes?winktongue You are mistaking the stereochemistry of the oxime group with the stereochemistry of the asymmetric carbon of amphetamine molecule - they are two different things (you wrote bogus). The chiral center of the alpha carbon isn't present in P2P or its oxime. It is formed during the reduction of the imine/oxime/schiff base of P2P and unless the method used is stereoselective, which Leuckart isn't, the product is going to be racemic. Discussion about oximes in a Leuckart thread is quite off-topic, btw.

fear fear hate hate
 
 
 
 
    lugh
(Moderator)
07-31-04 13:11
No 522924
      Very Good Leuckart Article
(Rated as: good read)
    

The article requested in Post 518070 (moo: "Raney Ni catalyzed Leuckart reaction", Novel Discourse) and abstracted in Post 512060 (moo: "Nickel catalyzed Leuckart reaction.", Methods Discourse)

J. Gen. Chem. U.S.S.R. 25, 1377-81(1955)(Engl. translation)




cool

Chemistry is our Covalent Bond
 
 
 
 
    moo
(Hive Addict)
07-31-04 15:50
No 522942
      More on Ni-Leuckart (or should we say CTH?)
(Rated as: excellent)
    

Thank you very much lugh!smile That article really made my day. It also made me notice there were a few references on the subject that I had missed completely! They might not be so good as the one above, but I'll include them for the sake of completeness.wink The first one actually uses the very same catalyst Zealot uses in his procedure. Urushibara nickel might work too by the way. Dedicated to Uncle Fester praising the Leuckart reaction while calling Soviet scientists lying commies.tongue



Reaction of formamide with carbonyl compounds in the presence of nickel catalyst.
Kost, A. N.; Terent'ev, A. P.; Shvekhgeimer, G. A.
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, , 150-60 (1951).
CAN 45:60003  ISSN 0002-3353

Abstract
The reaction of HCO2NH2 with carbonyl compds. is accelerated by the presence of hydrogenation catalysts (Ni, Co, Pt, Pd, etc.), and the limit of active temp. is lowered by 20-80 Deg.  Particularly effective are such substances in reactions of naphthenic compds.  The use of catalysts improves the yield of primary amines.  The results indicate that the mechanism of the reaction is such the H2O-removing substances have little bearing on it and the true mechanism may proceed by addn. of HOCNH2 to R2CO in the sense of addn. of the HOC and NH2 (or NR2) fragments across the CO link of the carbonyl; the resulting R2C(NH2 or NR2)OCHO then decomp. into CO2 and the amine R2CHNH2 (or NR2).  The above mentioned catalysts give 2-5% better yields of RNH2 at 110-30 Deg in comparison with the 180 Deg required without a catalyst.  The Ni catalyst was prepd. by treating Ni carbonate with excess HCO2H 10-12 hrs. at room temp., filtering the Ni formate, and thermally decompg. the requisite amt. just before use after moistening with a little HCO2H; the decompn. was done by an ordinary burner.  Typical reactions with HCO2NH2 (I) (from the reaction of 82% HCO2H with (NH4)2CO3, followed by concn.) follow.  Heating 60 g. I, 1 g. Ni catalyst, and 24.5 g. MeEtCO 60 hrs. at 90 Deg and 6 hrs. at 160 Deg, then hydrolysis by boiling 2 hrs. with 100 ml. concd. HCl, gave 51.5% 2-aminobutane, b758 61-3 Deg; picrate, m. 137-8 Deg.  Similarly 60 g. I and 30 g. MePrCO with 1 g. Ni gave 43.5% 2-aminopentane, b750 88-91 Deg; HCl salt, m. 168 Deg (from EtOH).  To 60 g. I and 1 g. Ni in a Claisen flask heated to 130 Deg was slowly (0.5 hr.) added 25 g. EtPrCO and the mixt. heated 7 hrs. at 125-30 Deg with recycling of the distd. ketone, yielding 32.8% 3-aminohexane, b751 118-22 Deg; HCl salt, m. 225 Deg.  Similarly MeAmCO gave 55.1% 2-aminoheptane, b756 140-3 Deg; HCl salt, m. 133 Deg; heating at 120-5 Deg 4 hrs. gave a 49% yield.  Similarly Pr2CO after 8 hrs. at 140 Deg gave 63.8% 4-aminoheptane, b753 138-41 Deg; HCl salt, m. 240-1 Deg (from EtOH); at 130-5 Deg the yield is 64.4%, when the proportion of the ketone is higher.  I (75 g.) and 48 g. MeCOC6H13 gave in 2 hrs. at 155-60 Deg 59.4% 2-amino.ovrddot.octane, b752 164-7 Deg; HCl salt, m. 83.5 Deg (from EtOH).  Heating 120 g. I, 2 g. Ni, and 34.2 g. iso-Pr8CO to 100-10 Deg, when reaction starts, and gradually heating to 150 Deg over 8 hrs. gave, after 6 hrs.' hydrolysis by hot HCl, 61.5% 3-amino-2,4-dimethylpentane, b756 124-6 Deg.  Repetition with 90 g. I and 27 g. iso-Pr2CO, 6 hrs. at 120-30 Deg with 4 hrs.' hydrolysis, gave 45.9% above amine and 5.9 g. 3-formamido-2,4-dimethylpentane, b754 240 Deg, b9 128-30 Deg, n20D 1.4569.  Heating 60 g. I with 30 g. AcCMe3 and 1 g. Ni 10 hrs. at 105-10 Deg and hydrolysis 2 hrs. with concd. HCl gave 73.4% 3-amino-2,2-dimethylbutane, b756 101-3 Deg; HCl salt, sublimes at 245 Deg; a lesser excess of I and shorter hydrolysis period (1 hr.) gave 65% of the above amine and 18.7% 3-formamido-2,2-dimethylbutane, b756 232-5 Deg, b6 107.5 Deg, n20D 1.4506; if the heating period is 10 hrs. at 160-70 Deg and the hydrolysis 5 hrs., 50 g. I and 23 g. ketone give only a trace of the above amine, the main product (44% yield) being the formyl deriv., b11-12 120-5 Deg, n20D 1.4532, d204 0.9243, and a substance, b. above 250 Deg, whose structure is unknown.  Addn. of 29.4 g. cyclohexanone to 90 g. I and 1 g. Ni preheated to 130 Deg and heating 30-5 min. at 130-5 Deg, followed by boiling 10-15 min. with concd. HCl, gave 55.2% cyclohexylamine, b750 132-4 Deg [HCl salt, m. 206 Deg (from EtOH)], and 26% dicyclohexylamine, b14 122-5 Deg [HCl salt, m. 338 Deg (from EtOH)].  I (60 g.) and 29.4 g. ketone gave, after 1 hr. at 120 Deg and 10-min. hydrolysis, 53% RNH2 and 3% R2NH; heating 15 min. to 150 Deg gives complete reaction and a 25% yield of RNH2.  Reaction with 2-methylcyclohexanone at 160-75 Deg (10-15 min.) with 0.5-hr. hydrolysis gave 51% 2-methylcyclohexylamine, b758 150-50.5 Deg [picrate, m. 77.5 Deg; HCl salt, m. 268 Deg (from EtOH)]; some 15.6% bis(2-methylcyclohexyl)amine, R2NH, b12 135-7 Deg (HCl salt, m. 281 Deg), also forms along with some formyl deriv. of the primary amine.  Similarly 3-methylcyclohexanone gave 44% 3-methylcyclohexylamine, b750 150-1 Deg (HCl salt, m. 174 Deg), and 19.6% bis(3-methylcyclohexyl)amine, b7 127.5-8.5 Deg, b12 132-5 Deg, b750 168-70 Deg, n20D 1.4783, d204 0.8967; 90 g. I and 52 g. ketone gave after 70 min. at 100-5 Deg and 2 hrs.' hydrolysis 26% primary and 44% secondary amine.  Reaction of 90 g. I, 1.5 g. Ni, and 60 g. AcPh 1.5 hrs. at 130-40 Deg, followed by diln. with H2O, extn. with Et2O, and hydrolysis of the ext. by hot concd. HCl (2 hrs.), gave 67.5% PhCHMeNH2, b756 185-8 Deg; HCl salt, m. 158 Deg.  PhCOEt gave in 3 hrs. at 150 Deg, followed by 6 hrs.' hydrolysis, 64.1% PhCHEtNH2, b758 203-5 Deg (HCl salt, m. 187 Deg); an excess of the ketone after 1 hr. at 150-60 Deg with 10 hrs.' hydrolysis gives 68%.  Reaction of EtNHCHO (from 50 g. EtNH2), 46 g. cyclohexanone, and 1 g. Ni gave in 1.5 hrs. at 130-40 Deg, 23.3% ethylcyclohexylamine, b764 163-6 Deg (HCl salt, m. 182 Deg; phenylureide, m. 124-5 Deg); in addn. some 53.3% N-ethyldicyclohexylamine, b5 114.5-15.0 Deg, b748 246-50 Deg, n20D 1.4838, was formed.  Reaction without catalyst (7 hrs. at 160-80 Deg) gave 33% tertiary amine and no secondary amine.  PhNHCHO (from 90 g. PhNH2) with 2 g. Ni and 29.4 g. cyclohexanone after 1 hr. at 110-20 Deg, with 2 hrs.' hydrolysis by concd. HCl, gave 51% N-cyclohexylaniline, b9 139-41 Deg, b10 140 Deg, n20D 1.5659 [HCl salt, m. 227 Deg; picrate, m. 164 Deg (from MeOH)]; heating 1 hr. at 100-10 Deg gave 54% yield; without catalyst, 46% is obtained in 7 hrs. at 180-90 Deg.  Usually, lower reaction temps. and shorter reaction times require shorter hydrolysis periods (brief heating suffices), while reaction time of over 1 hr. usually requires more drastic hydrolysis because of the considerable amts. of formyl deriv. formed.


Synthesis of amines by the method of Leuckart.
Kost, A. N..
Nauchnye Doklady Vysshei Shkoly, Khimiya i Khimicheskaya Tekhnologiya, (No. 1), 125-9. (1958).
CAN 53:16978  ISSN 0470-469X

Abstract
The use of Ni and Co catalysts in the Leuckart reaction is studied.  The procedure for the synthesis of a few amines is given.  To 60 g. dry formamide (I) heated to 130 Deg is added 1 g. skeletal Co and then during 1 hr. 35 g. AmCOMe in 35 ml. 85% HCO2H (originally read HCHO but that must be a typo)(II), the mixt. refluxed under a small condenser 4 hrs. (120-40 Deg) (water and a little ketone evap. which neutralized with NaOH are returned to the flask), giving on cooling, hydrolyzing, extg. and distg. 60%, 2-aminoheptane, b752 140-2 Deg, and di(2-heptyl)amine b6 110-1 Deg, n20D 1.4421, d2020 0.8073.  Dry I (75 g.) and 48 g. Me hexyl ketone in 30 ml. 85% II soln. treated as above (130-60 Deg, 3.5 hrs.) in the presence of skeletal Ni yielded 65% 2-amino.ovrddot.octane, b758 165-7 Deg, and 8% di(2-octyl)amine, b7 140-1 Deg, n20D 1.4432, d2020 0.8058.  Dry I (1 part NH4O2CH and 6-7 parts I) (50 g.), 30 g. cyclopentanone (III), and 20 g. 85% II soln. heated to 120 Deg in the presence of 2 g. skeletal Co 4 hrs., cooled, dild. with water, and extd. 6 hrs. with Et2O yielded after fractional distn. 45% dicyclopentylamine, b16 118-20 Deg, 10% formylcyclopentylamine, b10 127-30 Deg, and 8 g. residue, b10 above 180 Deg.  To I, obtained from 139 g. aniline and 86 g. 80% II soln., is added at 120 Deg 1 g. Co and 25 g. cyclopentanone, the mixt. refluxed 4 hrs., decanted from the catalyst with excess 15% HCl, leached, extd. with Et2O, and distd. giving 80% cyclopentylaniline.  I (27 g.), 10 ml. dry II, and 0.5 g. skeletal Ni is heated 0.5 hr. at 130 Deg, 12 g. 3-methylcyclohexen-2-one added dropwise, then 5 ml. II, the mixt. refluxed 2 hrs. more, cooled, 250 ml. 15% HCl added, the soln. boiled 5 hrs., decompd. by NaOH under a layer of C6H6, the aq. layer extd. 6 hrs. with Et2O, and the ext. dried giving 3-methylcyclohexylamine, b750 149-52 Deg.  Urea (60 g.), 58.4 g. cyclohexanone (IV), 35 ml. 85% II, and 1 g. skeletal Ni is refluxed 4 hrs. vigorously, 65 ml. 85% II added dropwise, the mixt. cooled, decanted, evapd. in a porcelain dish with 400 ml. concd. HCl nearly to dryness, the residue leached under reflux with 170-200 ml. 40% KOH, the sepd. layer extd. with Et2O, dried over molten KOH, and distd. yielding 22-30 g. cyclohexylamine and 23-29 g. dicyclohexylamine. To I, obtained by neutralizing 93 g. freshly-distd. aniline with 85% II soln. and subsequent evapn. of the H2O, is added 2 g. Ni and 29.4 g. IV and the mixt. refluxed 1 hr. giving by the usual treatment 43-51% cyclohexylaniline and 36.5% N,N-dicyclohexylaniline.  To 30 g. I and 0.3 g. Ni is added at 130 Deg 18 g. butyrophenone in 10 ml. anhyd. II during 1 hr. while the temp. of the mixt. rises gradually to 150 Deg, the mixt. then heated gradually to 170 Deg 4 hrs., replacing from time to time the evapd. butyrophenone (after neutralizing with NaOH), when reaction ceases 100 ml. 20% HCl added, the soln. refluxed 8 hrs., and treated as usual giving 75% a-phenylbutylamine.  Dry 60 g. I is heated to 100 Deg with 1.5 g. Ni and during 0.5 hr. 40 g. BzH in 46 g. anhyd. II added, after the vigorous boiling of the soln. ceases heated 1 hr. more at 130 Deg, on cooling 200 ml. 10% HCl added, the soln. refluxed 3 hrs., neutralized with 40% KOH, extd. with Et2O, dried, and evapd. yielding 32.2 g. benzylamine, the aq. layer still contg. 3.6 g. (overall yield 88.5%).


Synthesis of substituted benzhydrylamines by Leuckart reaction.
Kalamar, J.; Ryban, B.
Chemicke Zvesti, 20(1), 79-84 (1966).  Journal written in Slovak.
CAN 64:93044  ISSN 0366-6352
 
Abstract
A modified method for the synthesis of benzhydrylamines by the Leuckart reaction from benzophenones, HCO2H, urea, and a small amt. Ni as catalyst gave the following I.HCl (R, R1, m.p.,% yield, and m.p. N-acetyl deriv. given): H, H, 290 Deg, 95, 149 Deg; 2-Cl, H, 235 Deg, 95, --; 3-Cl, H, 230 Deg, 90.3, 124 Deg: 4-Cl, H, 279 Deg, 96, 130-1 Deg; 4-Cl, 4-Cl, 278-9 Deg, 90, --; 2-Br, H, 257-8 Deg, 67.2, 191 Deg; 3-Br, H, 244 Deg, 85, 114 Deg; 4-Br, H, 246 Deg, 85, 152 Deg; 4-Br, 4-Br, 243 Deg, 84, --; 2-OMe, H, 216-17 Deg, 75, --; 4-OMe, H, 229 Deg, 75, 165 Deg; 4-OMe, 4-OMe, 199-200 Deg, 52.6, --; 3-Me, H, 230 Deg, 74.8, 108 Deg; 4-Me, H, 260 Deg, 90, 136 Deg; 4-Me, 4-Me, 243 Deg, 92, 164 Deg; 4-NH2.HCl, H, 290 Deg (decompn.), 60, --. a-Naph- thylphenylmethylamine-HCl m. 292 Deg; N-acetate m. 228 Deg.

fear fear hate hate
 
 
 
 
    armageddon
(Hive Bee)
07-31-04 18:12
No 522949
User Picture 
      rather CTH     

Hi! VEEERY interesting! But maybe these combined CTH/leuckart is just for theoretical argument - in real live, I wouldn't bother with the 2-5% higher yield if the workup would become much more work-intensive (hydrolysis while non-noble metals are present? No THX... wink)

And instead of taking care of a proper leuckart-conform heating AND babysitting a CTH, I would therefore rather choose one of these methods than trying to combine them...

Yields are nearly the same; product purity is better with pure CTH, leuckart rxn is scalable almost indefinately...

(ok when multiple kilo scaleups are on the plan, the few percent higher yield may become of interest.. smile)

But as the leuckart is characterized by being a non-catalyzed reaction using formate ion as the reducing agent for imines, whereas CTH uses different hydrogen donors in conjunction with a H+-transferring catalyst and sometimes involves different intermediates, I would rather say this is DEFINATELY a CTH...

(at least we know that these reductions can both be carried out in same flask simultaneously - competing, but not interfering maybe?)


Greetz A

Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
 
 
 
 
    armageddon
(Hive Bee)
08-23-04 15:39
No 526947
User Picture 
      important question     

One thing that came into my mind: is it essential how the Dean-Stark is operated? While thinking about why SWIA isn't able to achieve high yields with this method, I realized that there are two ways of tapping off:

1. In a way that allows the FD top layer to fall back into rxn flask, i.e. tapping off as much water as is formed, minus the amount of FD that distills too - the FD top layer inside trap stays the same size all the time.

2. Such that the formed FD is continuously removed from the rxn, or better said tapping off same amount like  FD that distills over - the FD layer gets thicker and thicker, while the amount of water in trap decreases constantly.


 - Now which is the right way to do, Zealot (or Antoncho)? My guess would be the second one, as it seems to allow for a smoother temp. control - and after all, this is the purpose behind it, right?

Thanks for your help!

Greetz A

Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
 
 
 
 
    armageddon
(Hive Bee)
08-29-04 00:26
No 528023
User Picture 
      92% are impossible to achieve..     

As long as nobody is able to reproduce the results Antoncho posted (this unfortunately includes SWIA, although he tried it numerous times, with highest purity reagents, exactly same amounts, appropriately sized glassware and the utmost care to do good lab work - 55% yield!), I am tempted to believe the >92% yield are a myth, too.

(sorry to say that Antoncho; I really would've loved to say otherwise, but all facts speak against it! What would be a motivation for writing such a bullshit - the reputation? Can't be - as it doesn't get better by posting exaggerated yields!? Wanting other bees to test out your theory? Then you could've said that, too - there's enough experimental data about [b]unsucessful[b] NH4COOH leuckarts using traps. Or maybe what you wrote is true; then this would bee the right point to give a bit more details about Zealot's work!! frown)

...And please don't come and say that Zealot forgot to separate unreacted ketone from amine product! Because I don't see any comment about their separation; you just mention the steam distillation of crude "product", but did you realize that every unreacted ketone will steam distill, too?? And that the distillate mustn't only be extracted with nonpolar, but also further purified via a/b to get the pure amine? That if this isn't done, a healthy amount of phenylacetone/amphetamine imine forms, as soon as crystallization is attempted and the solvent dried for that purpose?

That would be the only explanation to me about the big differences between Zealots and other bees yield (which you calculate from amount of assumed freebase, not dried hydrochloride or sulfate)!



So to prevent other bees from getting disappointed, and until you maybe decide to give further details so that more experiments can be done - might I suggest the following alternatives:

Post 335851 (Sunlight: "MDA and MDMA from CTH reductive amination", Novel Discourse)

Post 508257 (armageddon: "CTH а la Sunlight - revisited", Methods Discourse)

Post 503533 (Bandil: "Pseudo-"wet"- BH4 amination BH4", Methods Discourse)

Post 461926 (cublium: "NaBH4 is just amazing.", Newbee Forum)

Post 477266 (Lego: "Reduction of oximes with zinc/ammonium formate", Novel Discourse)

Post 258972 (baalchemist: "Baal,Al/Hg/Nitro, & a 55gal drum.....", Methods Discourse)  (now that's a big one smile)



Greetz A

Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
 
 
 
 
    LaBTop
(Daddy)
11-03-04 03:17
No 539328
User Picture 
      You obviously did not read     

what Antoncho/Zealot explained in the first post of this thread!

Look again at Post 302161 (Antoncho: "Leuckart with 92%+ overall yield", Methods Discourse),
and see that you have to remove ALL refluxed water from the Dean Stark trap, while very gently warming up over 4-6 hours untill it reaches 160-170 C, then you simply close the trap's crane and gently boil it for ~1 h (not 4 hrs, as the original sources say).
""On cooling the rxn crystallizes completely"". If you did not see that, you did something wrong.

""Analysis shows the yield is quantitative at this stage.
The procedure above was originally stated for cyclohexanone, but the author says the identical one was used for P2P, with the results also identical.""

Now here's my explanation what you did wrong, you forgot to READ this CLUE:
""The trap is pre-filled with water.""

You stated a few posts before:
""2. Such that the formed FD is continuously removed from the rxn, or better said tapping off same amount like  FD that distills over - the FD layer gets thicker and thicker, while the amount of water in trap decreases constantly.
 - Now which is the right way to do, Zealot (or Antoncho)? My guess would be the second one, as it seems to allow for a smoother temp. control - and after all, this is the purpose behind it, right? ""

NO, the purpose of the Dean-Stark trap in this special occasion is to fill it FIRST to the TOP with water, so that the amine formyl derivative (FD) can only float on top of the water and will thus flow back in the flask directly, and does not add sufficient cooling mass to the flask to cool the reaction to a too low temperature, which will stop the wanted reaction !!! (This has happened in your cases).

NOW you know what you did wrong, you read again this, and see what you have to do:
Damn slowly remove refluxed water BIT by little BIT from the Dean-Stark trap, keeping the water level in the trap as high as can bee, thus letting all refluxed FD flow slowly back in the refluxing reactionflask :

""So the temp of the reaction is slowly adjusted by gradually removing H2O from the Dean-Stark over 4-6 hours - that leads to a gentle and very even rise of the reaction temperature. When it reaches 160-170 C, you simply close the trap's crane and gently boil it for ~1 h (not 4 hrs, as the original sources say).""

Please try to understand totally what you read, first, before waisting good precursors. LT/

PS: let this special research GO ON!
PS2: This took 2,5 YEARS to find the obvious problem?
You are all dismissed from class, and have to start in grade 1 again. Shame on you.

WISDOMwillWIN
 
 
 
 
    indole_amine
(Hive Bee)
11-03-04 15:31
No 539444
User Picture 
      really     

I think Armageddon is quite familiar with the use of a Dean-Stark.

He did read the first post, did prefill the trap, and he knew what to do and still got consistently bad yields.

It took him 2.5 minutes to realize that this leuckart variation is bullshit.

Think he won't be taking Leuckart class again... tongue

Please try to understand totally what you read, first - before claiming things like above...


indole_amine
 
 
 
 
    LaBTop
(Daddy)
11-03-04 17:55
No 539466
User Picture 
      Then he put me really on the wrong leg,     

and everyone else, with this remark:
""My guess would be the second one, as it seems to allow for a smoother temp. control - and after all, this is the purpose behind it, right? ""
While the second one is the one he proposed to do like this :
""2. Such that the formed FD is continuously removed from the rxn, or better said tapping off same amount like FD that distills over - the FD layer gets thicker and thicker, while the amount of water in trap decreases constantly.""
And that is NOT the way it should be done. The FD must flow back in the reaction, nearly exactly as is proposed by him in the first one :
""1. In a way that allows the FD top layer to fall back into rxn flask, i.e. tapping off as much water as is formed, minus the amount of FD that distills too - the FD top layer inside trap stays the same size all the time.
I got a PM where it is explained now, that Armageddon used the prefilled-with-water trap and got zilch (btw the word only Uncle Fester used in this thread) :
""You obviously didn't read Armageddons other posts in this thread: he DID prefill the trap with water, and he DID get the clue that it would have to be tapped off slowly so as to just allow the formyl amphetamine to flow back nto the rxn vessel, while gradually tapping off the water as it is formed...
...over the course of 4-6 hours, until 160°C are reached......followed by 1h boiling at that temp. ......got zilch (40% yield, from P2P)....this Leuckart variation is BULLSHIT!!!!!!!!!!!!""

I did read all Armageddons posts several times in this thread, and have not found any indication there, that he prefilled the trap with water first. This is the only time I am told now, in PM.

So lets presume he did that. Then there are numerous other things which could lead to a low yield.
Zealot described the problems which could arise when you start with an impure ketone (P2P f.ex.):
""The FD is obtained as described earlier for cyclohexanone, w/same nearly quantitative yield. The main factor here is purity: the higher it is, the better yield. If you take an impure ketone, you may get as low as 50% yield; so only a slightly yellow transparent oil should bee used"".
This will mean that if one did not obtain the P2P from a trustable official source which indicates a purity above 98%, then one should double or triple distill ones obviously homebrew P2P, untill sufficient purity is obtained.

And there is much more to read in the first post, which could go wrong if not followed exactly.
A 72% yield with a modified Leuckart with P2P can be obtained, no doubt about that, but I personally have never seen higher yields.

But the proposed addition of a nickel catatalys by Cesium in
Post 303011 (cesium: "Catalysed Leucard", Methods Discourse)
""The temperature and reaction time during first step could be lowered to approx. 125-135°C and 45 minutes by using 0,5 % of nickel catatalyst prepared by anaerobic thermal decomposition of Ni formate. Yield of N-formyl-MDA is almost quantitative, however due to the harsh acid hydrolysis the overall yield was lowered to 63% after workup. This procedure was originaly published in russian Zh. Obs. Kchim around 1964.""
sounds damn interesting, and if an alkaline hydrolysis as proposed by Zealot would be adopted, it will have the possibility of heightening the yield in the 90+% ranges.
The preparation of such a nickle catalyst is described in :
Post 512060 (moo: "Nickel catalyzed Leuckart reaction.", Methods Discourse)
""It appears that in
Post 326428 (zealot: "Дальнейшее улучшение реакции Лейкарта-zealot’a", Russian HyperLab)
is a procedure for nickel catalyzed Leuckart reaction but the catalyst isn't Raney nickel. The catalyst is prepared by thermal decomposition of nickel formate, using a test tube and a gas flame, and is referred to as pyrophoric nickel. I guess this one from Zealot isn't translated to english yet.
Couln't find anything about using nickel formate in Leuckart, but there is a ref. about Raney nickel.""

in Moo's same post is this Raney nickle one described in the abstract:
""
Abstract
Alk. catalysts in the presence of Raney Ni accelerate the Leuckart reaction and direct the reaction to the formation of predominant formation of secondary amines.  It was shown that the Leuckart reaction goes through the step of dissocn. of HCONH2, and the 1st product is not the amine but its formyl deriv.  Improved techniques for formation of amines are described below. ""


This technique should be concentrated on, to obtain higher yields as 72%.  LT/

PS: this remark of Nicodem should be looked at also:
""Post 529543 (Shane_Warne: "Sodium ethanoate is the same as sodium acetate", Newbee Forum) +
Post 529389 (Nicodem: "Urea hydrolysis and urea pyrolysis", Newbee Forum)
I think most amides get hydrolysed faster with NaOH than HCl, but urea may be an exception, I don't know. You should bee able to notice the end of hydrolysis by the end of CO2 bubbles formation from the boiling stones if you lower the reflux bellow the boiling point for a moment. Usually this is a clear sign in reaction involving CO2 formation (like the Leuckart or decarboxylisations). If I dare making a guess I would say that 6h of reflux would do, but don't forget you need an excess of conc. HCl since it gets neutralised by the forming ammonia (at least a 20% excess). If you will use the 20% HCl put a somewhat larger excess and reflux for a longer time.""

And this one, about never exposing your ketones to extreme pH values:
Post 338541 (lab_bitch: "The chemistry of ketone polymerization", Chemistry Discourse)
""The moral of the story is NEVER, NEVER, NEVER expose ketone to extreme pH, ESPECIALLY if you plan to heat it up (i.e. distillation).  Simple distilled water and sodium bicarb washes are sufficient. ""
And there is a lot more info in that post which should be taken to heart.

This post is also highly interesting:
Post 61613 (psyloxy: "Re: Leukard scaleable ?", Methods Discourse)
""a variation of the Leuckart, that doesn't even use formic acid and has yields reported as high as 70%.""

WISDOMwillWIN
 
 
 
 
    indole_amine
(Hive Bee)
11-04-04 04:10
No 539585
User Picture 
      sorry to be a smartass here, but...     

...what about this?

"Anyway, when the water had been removed via dean-stark, SWIA distilled away the toluene (still using the trap), refilled the trap with water to the top and during the next 4 hours slowly removed the water in increments of 4-5 drops a time. Temp. climbed to 180°C, where it was held for 1h. On cooling, nothing solidified.."

and

"The reason for the additional solvent was the small amount of starting material"

Post 517101 (armageddon: "92% is no myth", Methods Discourse)

And although I doubt that Armageddon used >98% pure ketone from "official sources" wink, I remember that he distilled his ketone at least twice, and also purified it via oxime recrystallization (or was it bisulfite?) - so the purity should've been quite good...


indole_amine
 
 
 
 
    LaBTop
(Daddy)
11-05-04 00:30
No 539752
User Picture 
      This is the answer you already got then     

Post 517198 (Rhodium: "Quality control of provided data points", Methods Discourse)
And ofcourse the method SWIA used is totally different from the one Zealot proposed.
A really convincing check of the proposed method should be performed with 1 gmol P2P.
And I would like to sea someone try the Raney nickle patent. And report back. LT/

WISDOMwillWIN
 
 
 
 
    indole_amine
(Hive Bee)
11-05-04 01:55
No 539764
User Picture 
      me?     

I think Rhodiums answer was dedicated to Armageddon, not me...

And, by the way:
"although he tried it numerous times, with highest purity reagents, exactly same amounts, appropriately sized glassware and the utmost care to do good lab work - 55% yield!"
Post 528023 (armageddon: "92% are impossible to achieve..", Methods Discourse)


The road is open for new explorers in this field! wink


indole_amine
 
 
 
 
    LaBTop
(Daddy)
11-05-04 14:24
No 539854
User Picture 
      Dedicated research     

is of the utmost importance, and I highly appreciate your remarks, showing us that at least he tried everything he could to obtain the advertized yields. And that's the most important part of this board, those who dare to investigate, and try to copy referenced procedures in a homebrew fashion.

If we all had sophisticated labs to experiment in, we all would move to purely scientific forums or journals.
And this board would die.
Since it is the research of -many- members which will definitely proof that a proposed procedure can not or can be duplicated, we need more input from others to lay this discussion to rest.

I would like to hear from Antoncho, if he could get in contact with Zealot again, for his view on Armageddons results.
And if their ever was a discussion in the russian forum on this subject, and what their verdict was.
LT/

WISDOMwillWIN
 
 
 
 
    Smilaxium
(Newbee)
11-09-04 14:07
No 540639
User Picture 
      More Bullshit ?     

The authors claim to have 80% of analyticaly pure alpha-methylbenzylamine when reacting acetophenone with plain formamide and water for 6 hours at 180 C, followed by an HCL hydrolysis. Would this work for P2P ?

Carlson et. al, Acta Chemica Scandinavia, 1993, 47, 1046-1049

The light at the end of the tunnel is usually a "No Exit" sign.
 
 
 
 
    indole_amine
(Hive Bee)
11-10-04 04:40
No 540744
User Picture 
      acetophenone is not exactly like phenylacetone     

Probably not, acetophenone always gives better yields than P2P. The latter is more prone to polymerization, therefore sodium alkoxide hydrolysis is better than HCl in this case.

But the article seems interesting...

And I too would love to hear if there is/was any discussion of this topic amongst the Hyperlab bees...wink


indole_amine
 
 

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