(Official Hive Translator)
11-11-03 10:48
No 470154
(Rated as: excellent)
Hi!
This is a story of a girl named Lucky
Just kidding
This is a story of a young and clever hallucination whose name is SWIM
Once upon a time SWIM decided he needed some cyclohexylamine. I'll omit the reason why. He just thought it'd bee nice to synth some, of its own interest.
So he dreamt up some nice cyclohexanone oxime and set his imaginary PC to look for the best method of reducing it to the amine - of all the countless methods known to The Hive.
Much to his surprize, very soon he stumbled upon this document:Post 435995 (gabd: "Patent FR971429", Chemistry Discourse). His surprize grew even more when he realized that it was completely overlooked! Not a single response on the subject has been submitted and the discussion in that thread quickly diverted to smth else.
He then thought: 'Fuck! Of all things, why bother making an oxime when it seems possible to convert a ketone directly to its corresponding amine in good yield?' So, although the oxime was sitting happily in the freezer, he decided to venture upon this route for the sake of satisfying his research cravings.
So here's what this fictional character has fictionally done (i hope you forgive me this long preface
:In a 250 mls flask there was placed:
- 13g Ni(NH4)2(SO4)2*6H2O (33mmole, Mr=395) (the reason SWIM used this particular salt was that the jar w/it was closer to his reach than the one with ordinary NiSO4. Beesides, SWIM just loves its really nice turqois color
)- 80mls of household ammonia (the mixture turns divinely purplish-blue and the salt readily dissolves)
- 15mls cyclohexanone
- 20mls 95% EtOH
After that, the mixtr was subjected to a vigorous mech stirring and thence there was added 10g zinc dust (dark-grey in color). Naturally, the room beegan to stink of ammonia since SWIM's stirrer is of non-hermetic type
.An ice bath was kept nearby, but the rxn appeared to bee not very exotermic, the highest the temp ever climbed was about 40° C.
After ~1,5hrs the temp fell to ambient and further 10g Zn was added. Another 10g was added after 1,5hrs more.
After 4,5hrs of total stirring the mixtr represented a rather thick dark-grey goo, all Zn was consumed at that point (no H2 evolution). Smell of the starting product was completely gone, as far as SWIM could judge, another smell - fragrant smell of cyclohexanol - was also apparent.
It was put overnight in the fridge (it was too late for the work-up) and the next day:
- diluted w/conc NaOH and some aqua to make it xtractable, total volume ~400mls (SWIM didn't manage to get it all to dissolve, but it isn't really needed)
- xtracted 3x~50mls toluene
- washed with a little dilute alkali, then - 20mls brine
- toluene back-xtracted with 30x20x10 dil. sulfuric acid
- aq. phase made basic w/conc NaOH (amine layer immediately forming at the top)
- xtracted w/3x40mls DCM
- NP phase washed with 2x30mls brine and dried w/Na2SO4
- DCM removed on waterbath at 80-50 C, care being taken not to evaporate significant qtty of the rather volatile product
- Remaining liquid was chilled and the leftover DCM was removed as thoroughly as possible using a car vac cleaner with a tube attached to it
The result was a clear oil with a very slight yellow coloration, which amounted to 15mls
An 1,5mls aliquot was dissolved in dil. H2SO4 in a plastic syringe, and the product was found to contain about 25-30% non-polar liquid (the leftover toluene and some DCM).
Which gives us a total yield of 70%, exactly as stated in the patent
The oxime is still sitting in the freezer
SWIM wonders what to use it for nowNow - some discussion.
Obviously, this route is perfectly suitable for OTC production of simple amines - such as isopropyl- and isobutyl - both acetone and MEK are mentioned in the French patent as tested substrates. Those are usable for many a purpose - e.g., Henry condensation catalysts.
What is more important, i really see no obstacle to this reaction in case of the more interesting ketones
I would really appreciate if some adventurous bee with some P2P or MDP2P on his/her hands would give it a shot ASAP (as SWIM ain't gonna do that).
And of course, the BIG advantages of this reaction is the fact that it is very simple to perform and absolutely non-toxic: no mercury, no hydroxylamine.
Yours As Ever,
Antoncho
(Chief Bee)
11-11-03 11:32
No 470160
absolutely non-toxic
I'd like to disagree on that point. Nickel salts are highly allergenic and also pretty toxic, although not in the same league as mercury salts.
(Hive Bee)
11-11-03 12:29
No 470180
Am I turning blind? I was reading the same thread last week and even then managed to miss that example. Nice find!
This raises a question: how much secondary amine does that method produce? The original patent answers that 90% of the prepared amines was the primary one, that's quite good!
Also, to my recollection nobody has tried the ammonia-activated urushibara nickel catalyst (U-Ni-NH3). As I've understood it, it is supposed to be more active in forming primary amines than acid or base activated urushubara catalysts, and this Zn/Ni-couple reduction has lot in common.
fear fear hate hate
(Official Hive Translator)
11-11-03 18:48
No 470243
Am I turning blind? I was reading the same thread last week and even then managed to miss that example. Nice find!
Thanx, Moo! Actually, i never read the thread at all - that was the time closely after my birthday, which i usually celebrate pretty vigorously
I managed to miss it somehow reading up the Hive afterwardsThis raises a question: how much secondary amine does that method produce?
Shit! Frankly speaking, i didn't even think of this possibility
Whereas i should've. Obviously, even if SWIM's final yield was at least 10% 'diaminous', the overall yield of pure product is <=63%, which doesn't sound that much nice at all
Anyway, i hope that this will come handy for some bees in need of an efficient OTC Henry rxn catalyst. It's way easier than making methylamine, IMHO
Also, to my recollection nobody has tried the ammonia-activated urushibara nickel catalyst (U-Ni-NH3)..., and this Zn/Ni-couple reduction has lot in common.
I would say that this rxn uses exactly U-Ni-NH3, only it's made in situ.
SWIM for some reason thought that SO42- were inhibiting Ni's cat activity, at least in al preps they use the chloride. Is it indeed the case or SWIM's impression was wrong?
Actually, it seems to me that the following modus operandi could bee used to improve the yield and selectivity of this rxn:
To make a sat solution of NH3 in MeOH or some other alcohol ((NH4)2SO4, lye, stirring in icebath), then put in there your ketone. Let sit for 24 hours.
The point is - the formed Na2SO4 will remove water that is produced in imine formation, shifting the equilibrium all the way to the right, much like in preparation of HEtSO4.
The resulting imine solution is then reduced with Zn/Ni - however, one point of concern is if zinc would dissolve in alcoholic NH3 - it will have to form an alkoxide. With aluminium this is performed with some iodine as catalyst and under reflux, here we have a condition when very little side-reaction of the metal with the solvent will take place at RT.
I want to ask everyone:
a) What do you think?
b) Have you ever heard that non-alkylated imines can bee produced from ketones as i described above?
Antoncho
P.S. Rhodium: thanx for the warning!
But i really think that the dangers of nickel and its salts are not that bad at all - otherwise, people wouldn't make money and all sorts of things from itActually, the main potentially possible contact with nickel in this procedure is during the workup -and at this point it is just as dangerous as handling nickels (as in '5 cents')
(Moderator)
11-12-03 02:15
No 470329
b) Have you ever heard that non-alkylated imines can bee produced from ketones as i described above?
Excellent work, but you may bee surprised to find out something very similar to this has been posted before, albeit without nearly as many useful details:
6) Direct reductive amination of ketones to amines in the presence of ammonia.
If the usual reaction mixture is mixed with anhydrous alcohol to increase the solubility of the ketone to be reacted, one obtains with a satisfactory yield, in certain cases, the corresponding primary amine. Cyclohexanone, in particular, furnishes in these conditions 60-70% of primary cyclohexylamine. Phenylacetone and b-naphtanone have been transformed equally in amphetamine and beta-naphtanamine.
Post 270027 (Rhodium: "Zn/NiCl2 reduction of oxime/nitro/nitriles/ketone", Chemistry Discourse)
Chemistry is our Covalent Bond
(Hive Bee)
11-12-03 07:33
No 470399
That piece of information made me dig up the patent in the thread Antoncho refers to, which in turn lead to gabd finding the patent with even more interesting details. It is frustfrating when literature tells you that something has been tried and it has worked but nothing else...
fear fear hate hate
(Newbee)
11-12-03 23:26
No 470554
Do you think that NiCl2 could be used directly in place of your weird ass NH4 SO4 salt?
(Soothsayer)
11-13-03 03:54
No 470581
yes, i saw a ref, a while back on this [zn/ni] system
I've seen alot of crazy shit, over the years,
of course it will work,!,
Get to it!
hm
I went down to the depot of evolution, and ordered the man to supply me enough, to last a lifetime..
(Newbee)
11-13-03 15:01
No 470652
I don't see why NiCl2 wouldn't work, it's just a shame no one has actually tried it yet! The only thing I could think of is sometimes a Cl ligand inhibits catalytic reactions, who knows though without an empirical test!