Author Topic: another question  (Read 5018 times)

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armageddon

  • Guest
another question
« on: July 11, 2004, 07:50:00 PM »
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


moo

  • Guest
You are mistaking the stereochemistry of the...
« Reply #1 on: July 11, 2004, 08:34:00 PM »
Racemic P2P? Did you miss the stereochem classes? ;)  :P  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.


lugh

  • Guest
Very Good Leuckart Article
« Reply #2 on: July 31, 2004, 06:11:00 AM »
The article requested in

Post 518070

(moo: "Please", Novel Discourse)
and abstracted in

Post 512060 (missing)

(moo: "Nickel catalyzed Leuckart reaction.", Methods Discourse)


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




8)


moo

  • Guest
More on Ni-Leuckart (or should we say CTH?)
« Reply #3 on: July 31, 2004, 08:50:00 AM »
Thank you very much lugh! :)  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. ;)  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. :P



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.


armageddon

  • Guest
rather CTH
« Reply #4 on: July 31, 2004, 11:12:00 AM »
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...  ;) )

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..  :) )

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


armageddon

  • Guest
important question
« Reply #5 on: August 23, 2004, 08:39:00 AM »
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


armageddon

  • Guest
92% are impossible to achieve..
« Reply #6 on: August 28, 2004, 05:26:00 PM »
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 unsucessful 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!!  :( )

...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 à 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 (missing)

(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  :) )



Greetz A


LaBTop

  • Guest
You obviously did not read
« Reply #7 on: November 03, 2004, 04:17:00 AM »
what Antoncho/Zealot explained in the first post of this thread!

Look again at

Post 302161 (missing)

(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.


indole_amine

  • Guest
really
« Reply #8 on: November 03, 2004, 04:31:00 PM »
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...  :P

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


indole_amine

LaBTop

  • Guest
Then he put me really on the wrong leg,
« Reply #9 on: November 03, 2004, 06:55:00 PM »
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 (missing)

(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 (missing)

(moo: "Nickel catalyzed Leuckart reaction.", Methods Discourse)

""It appears that in

Post 326428 (missing)

(zealot: "Äàëüíåéøåå óëó÷øåíèå ðåàêöèè Ëåéêàðòà-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%.""


indole_amine

  • Guest
sorry to be a smartass here, but...
« Reply #10 on: November 04, 2004, 05:10:00 AM »
...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 (missing)

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


And although I doubt that Armageddon used >98% pure ketone from "official sources"  ;) , 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

  • Guest
This is the answer you already got then
« Reply #11 on: November 05, 2004, 01:30:00 AM »

Post 517198 (missing)

(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/


indole_amine

  • Guest
me?
« Reply #12 on: November 05, 2004, 02:55:00 AM »
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!  ;)


indole_amine

LaBTop

  • Guest
Dedicated research
« Reply #13 on: November 05, 2004, 03:24:00 PM »
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/


Smilaxium

  • Guest
More Bullshit ?
« Reply #14 on: November 09, 2004, 03:07:00 PM »
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


indole_amine

  • Guest
acetophenone is not exactly like phenylacetone
« Reply #15 on: November 10, 2004, 05:40:00 AM »
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... ;)


indole_amine