Natural Science Forum / Chemistry / Organic Synthesis / July 2003

Why not try some other sorts of acids, then, e.g. mandelic (or
derivatives thereof), Mosher's, camphorsulphonic..

I assume that the Jacobsen route is fairly optimised however, what sorts
of problems are you encountering?

Stephan

What kind of nightmare? What base did you use to displace the salt?

R-NH2.HO2C-R' + NaOH --> R-NH2 + NaO2C-R' + H2O

PH Z

Why is free-basing so difficult?  Just dissolve the tartrate in water, add
NaOH, extract the free amine with ether, strip down.  Keep under N2 as much
as possible, because chelating diamines are frequently rather sensitive to
CO2.  I don't know if DACH is a solid or liquid, but if you're lucky, the
free amine will be a crystalline solid and you can collect from the basic
water just by filtration.

   Eric Lucas

1. Diaminocyclohexane is very unpleasant to work with: Highly
hygroscopic, (melts on moist air) and vigorously absorbs CO2 from air.

2. Resolution through mono(+)tartrate is in Org.Syn.: here is a free
reference

http://orgsyn.org/orgsyn/prep.asp?rxntypeid=276&prep=V75P0001

(The free base isolation is not done there - they basify and use it in
situ, but you may find a reference there)

I would suspend the tartarate in anhydrous (99+) non-denaturated EtOH,
add exactly 2 equivalents of powdered sodium methoxide, reflux for 30
min under nitrogen, cool, if there is precipitate remove it by quick
filtration through a large medium-porosity sintered glass frit (and
wash with extra anh. EtOH, concentarte on rotavap and then on highvac.
Take the solidified residue and distill it on Kugelrohr shortpath
apparatus. (careful, do not cool with dry ice to avoid CO2
absorbtion). If the distilled material is not pure enough, re-distill.

Store in tight glass bottle with teflon-lined cap.

These polar amines are not easy to get pure and anhydrous - expect to
spend one day on getting the freebase from salt.

Good luck on your chemistry.

You can write an e-mail to E. Jacobsen - I guess he will be glad to
answer if you write him a nice letter and add your FAX number there,
so that he can send over the prep.
His phone is 617-496-3688, FAX 617-496-1880. Don't postdoc for him -
He sux dik.

Eric N. Jacobsen, Dept. Of Chemistry, Harvard, 12 Oxford St.,
Cambridge, MA 02138

Seems to me like a bit of an unnecessary hammer...

Even more of an unnecessary hammer (although doing it under N2 is the key in
any case)

Now that really does sound like a nightmare.  I would do it a much easier
way.  Working entirely under a N2 atmosphere, dissolve the tartrate in water
(presparged with N2).  Add excess KOH, extract with ether (again, sparged to
remove CO2), dry the ether layer over solid KOH pellets, decant and strip.
The key is to do *everything* under a dry N2 atmosphere, as Muhammar
correctly points out the difficulties of handling diamines.

Unbelievably unprofessional and inappropriate comment!  I've known Eric
pretty well for about 20 years, and he certainly doesn't deserve that.  I
sure hope you aren't looking for a job in chemistry anytime soon....

   Eric Lucas

By the way by what reaction do you get trans-1,2-diaminocyclohexane?
I have the wild dream to make 1,2,3,4,5,6 hexaaminocylohexane but I
would like to pass via another way than via hydrogenation of TATNB
(triamino,trinitrobenzene)...so your synthetical approach might give me
new ideas...except if it has to remain secret, please answer me.

PH Z

LOUIS wrote:

Work under nitrogen or argon.

Uncle Al hates to state the obvious, but... you *are* saturating the
solution with salt before extracting the diamine, right?  If NaCl or
Na2SO4 doesn't improve things much, try magnesium sulfate (Epsom salt)
or calcium chloride (note exotherm on hydration.  Use fine powder).
You want to avoid hard Lewis acid cations that like diamine chelation,
so Group II cations are kinda iffy.  Small scale diddling before you
commit.

Tartrate salts precipitate.  Dump them out and go for the diamine
recovery in concentrated salt.

Isolate the solid tartrate salt diamine, add two equivalents of solid
sodium methoxide (or sodium hydride or sodum amide if you have big
brass cajones).  Immediately close, pump down, then mix while
pot-to-pot pumping the liberated diamine into a Dry Ice or liquid
ntrogen cooled pot under high vac.  Uncle Al made (volatile)
1,1,1,3,3,3-hexafluoroacetylacetone as an undergrad.  The isolated
product is the water hydrate.  One powders the hydrate, dumps it into
an excess of P2O5, and pumps the off gas into a big liquid
nitrogen-cooled round bottom.  It is a race between liberating the
product and having it to go Hell with more P2O5.  Big exotherm.  The
adjective "vigorous" was slathered everywhere.

Liquid-liquid extraction (ether, toluene, cyclohexane) suffers from
water carry-over.  Can you azeotrope the diamine dry from
toluene/water extract?  Your prdouct has a vapor pressure of about 15
torr at 90 C.  Drying over P2O5 is probably not the most clever thing
to do.

Use a liquid/liquid continuous extractor.  If you can get 37% out with
6 extractions, a continuous extractor will get every bit out after
running overnight.  They are amazingly effective.  No organic chemist
should be without one.

As others have pointed out, this diamine is probably going to avidly
soak up CO2.  If you choose to do a continuous extraction, run it
under a nitrogen or argon blanket.

Steve Turner

Real address contains worldnet instead of spamnet

I think that following what you write, the partition coefficient is arround 7%
(DCM/water).
But this must be improved by increasing basicity (pH) , so use NaOH saturated
solution.... it will drop the diamine more out of the water since its non
protonated (molecular) form vs salt form will be favourised.
OK density will increase and DCM will decantate less easily, also it must be
unstable in NaOH conditions (hydrolyse)...so better use diethyl ether (wich is even
more easy to rotavaporate, stable towards bases, and much less dense than water).
Make several extractions too.

Good luck!

PH Z

LOUIS <Louisphz@SKYNET.be> wrote in message news:<beunqi$e5g@panther.Gsu.EDU>...

Not secret, but not much use either...I buy in racemic trans diamine
(Aldrich) and then resolve it (or try to - thanks to all for the
suggestions!).

Sorry I couldn't be more help.

Uncle Al <UncleAl0@hate.spam.net> wrote:

I would advise against using any group II salts.  They WILL complex
with amines (monoamines, diamines, primary, secondary, tertiary, it
doesn't matter) and you will likely get a mess.

I have not had a problem with this.  I normally use dichloromethane,
which is not very hydrophilic to begin with, and the trace of water
that appears in the extract azeotropes when the dichloromethane is
distilled off.  Sodium sulfate is good for drying extracts containing
amines.  It's slower than mag sulfate, but does not complex the
product.

Steve Turner

Real address contains worldnet instead of spamnet

I would be very surprised if the intrinsic partition coefficient is that
low.  Are you taking pains to exclude CO2 during the extraction?
1,2-Diamines react with CO2 surprisingly rapidly.  I'd bet you're only
recovering 37 % because the rest is turning into the carbamic acid
zwitterion.

   Eric Lucas

"James B" <boydell@soton.ac.uk> wrote in message
news:beumi5$c6n@panther.Gsu.EDU...

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