posted 08-17-98 05:35 PM         

The variety of reductive amination reagents astounds me sometimes. Yes, everybody knows about the alkali-something-or-other-boro-aluminum-give-your-home-address-to-the-DEA-why-don'tcha-hydride type of reagents. We've all read about people using H2 gas and any number of different Ni-Pd-Pt catalysts. And aluminum amalgam is just so "80's" (not to mention all that embarrasing Al(OH)3 crap you have to filter.) So what is a hip, fashion-conscious chemist to do?

As we all know, the true underground style has always been the "retro-cook". Looking back to what was the height of chemical fashion in years past we can get some hot ideas for this Autumn's most sporty cooks.

Zinc

Yes, we've all discussed zinc amalgam as an impossible-to-fuck-up reaction when it comes to the reduction of nitrostyrenes, and it's been seen around town as a reagent for other things too. But now it turns out its a fine reducing reagent as well:

C.R.Hebd.Seqances.Acad.Sci 213, 1941, 304
Synthesis 11, 1991, 1043-1045

This saucy little tip was brought to you by The House of Drone #342 -- the home of underground high-fashion.

posted 08-17-98 05:36 PM         

The House of Drone #342 takes on reductive amination via Fe powder (in a strictly hypothetical, academic sense.)

posted 08-18-98 04:07 AM         

Piglet :)

posted 08-18-98 05:16 AM         

I am really into NH2OH at the moment & I think that if you want to make MDA or such then this is the thing to look @.

I must say, though, that I feel (sadly) that Fe might well just reduce the oxime to the ketone. I think it will reduce hydroxyl amines to amines, though...

Oximes are stable & water soluable (i think) so let's all pray to the kinetic god than a electrolysis analogous to the nitroalkenes will work. (can someone post details of that ?)

posted 08-18-98 10:38 AM         

D342: I read some more about reductions of -NO2 and =NOH groups. Here is what I read:

NO2: H2/Pt or LiAlH4 or Zn/H+.
some cases: Zn + NH4Cl -> NHOH.
(hydroxyl amine without sodium cyanoborohydride!)
Zn/NaOH/CH3OH ?

=N-OH: H2/cat is slow, LiAlH4, Li;Na , Sn,
Zn/H+ (but we knew that already ), H2/Ni

posted 08-18-98 10:54 AM         

The other journal wasn't in the library.

A Simple Method for Preparation of Secondary Aromatic Amines

A simple and efficient method for the preparation of secondary N-alkylarylamines
via reductive amination of ketones with primary aromatic amines using activated
zinc/acetic acid is described. It requires only equimolar amounts of the
starting compounds and affords good yields of the corresponding amines
(50-90 %). It is not applicable to aldehydes nor aliphatic amines.

A large number of methods have been developed to transform a carbonyl
moiety to the corresponding amine. Some of the more commonly used procedures
involve reduction of carbonyl derivatives, such as imines, enamines, or
oximes, 15 either catalytically or with metal hydrides. Alternatively,
a carbonyl compound/amine mixture can often be reduced directly to the
corresponding secondary or tertiary amine, utilizing catalytic hydrogenation,
formic acid (Leucart-Wallace reaction) or certain metal hydrides. 
In the latter instance sodium cyanoborohydride  appears to be the
most convenlent reagent due to wide applicability. However, most of the
aforementioned procedures require elevated pressure or expensive and toxic
reagents. Few aldehydes and acetone have been reductively aminated albeit
in low yields with the simpler and inexpensive zinc amalgam and hydrochloric
acid, but to our knowledge, it has not been generally applied to carbonyl
compounds. It can also effect hydrolysis of various functional groups and
decarboxylate B-keto esters. An intramolecular reductive amination
of keto anilines to tetrahydroquinolines has been effected by zinc, and
37 % hydrobromic acid in acetic acid.

We have found that various ketones and B-keto esters can be reductively
aminated with primary aromatic amines, in good yields utilizing activated
zinc dust and acetic acid. It is more applicable than zinc/hydrochloric
acid, gives better yields, and it is particularly well suited for preparation
of B-arylamino esters. The reaction proceeds rapidly, being complete
in 1-4 hours, at 60-70'C and requires only stoichiometric amounts of the
reagents. In some instances, where shorter reaction times were used, the
intermediate imines could be isolated (IR band at 1650 cm-1), thus providing
the general mechanism as shown in the Scheme. Temperature control was found
to be important since zinc reacts rapidly with acetic acid at elevated
temperatures.

Yields were dependent upon the structure of both the ketone and amine.
More sterically hindered ketones give lower yields, probably because of
slower intermediate imine formation. For example, cyclohexanone gave N-cyclohexylaniline
(2i) in 90% yield, while cycloheptanone afforded only 50% of N-cycloheptylaniline
(2j). Similar differences in reactivity were noted between methyl ethyl
ketone and diethyl ketone. On the other hand, B-keto esters furnished
excellent yields (80-85 %) of the corresponding B-N-phenylaniino
esters. Some conformationally rigid ketones, like tropinone failed to react
at all, and only acetanilide ensued. Aldehydes gave a mixture of secondary
and tertiary amines, as did a-keto esters. Attempted condensation
of aniline with succinic dialdehyde (prepared by acid hydrolysis of 2,5-dimethoxytetrahydrofuran)
gave mainly N-phenylpyrrole while glutaric dialdehyde gave only a tar.

Variation of the amino component also demonstrated steric influence,
i.e., o-toluldine gave a substantially lower yield than p-toluidine in
reactions with cyclohexanone. Aliphatic amines failed to give the desired
product, although they formed the corresponding imines under the reaction
conditions. Apparently, these imines do not undergo reduction with zinc/acetic
acid.

Workup of the reaction mixture includes removal of the acetic acid under
reduced pressure, and treatment of the residue with excess ammonia. The
latter complexes the zinc(II) ions and prevents precipitation of a gelatinous
zinc hydroxide unlike other bases such as sodium hydroxide and sodium carbonate.
This greatly improves the isolation procedure and affords far better yields.

Activated Zn dust was prepared with 5 % HCl. Aniline, o- and p-toluidine
were purified by reduced pressure distillation from Zn/HCl before use.
Methyl 2-oxocyclohexanecarboxylate was prepared according to a literature
procedure. Reagent quality solvents were used without further purification,
and other reagents were used as supplied, by Aldrich Chemical Co. and Fluka
Chemical Co. Melting points were taken with a Met-Temp apparatus and are
uncorrected. Microanalyses were obtained with Pregl elemental analyzer,
IR spectra with a Perkin-Elmer FT IR 1725 X spectrometer, H-NMR spectra
and 13 C-NMR spectra with Varian FT-80 A spectrometer at 80 MHz and 20
MHz, respectively. In the case of B-keto esters, glacial AcOH was used
instead of 90 % AcOH.

N-Cyclobexalaniline (2i); Typical Procedure:

posted 08-18-98 12:01 PM         

piglet and fan of shulgin,

Have no fear; the ref's I gave do not involve the use of Hg compounds. I too feel a little guilty about working with Hg, but this is a "guiltless synthesis". Just zinc and acetic acid and a little something special.

As for your oximes, I'll look into it. People around here seem more preoccupied with Schiff bases, and so I gave the people what they wanted. I want my chemical style to be an expression of "shabby chic"; something you can use around the house...or for a hot night on the town. Elegant, yet somehow "cheap".

quirks,

Yes, the article you dug up is for anilines, but the method works for other things too. Resonance and all the other quantum shennanigans associated with aromatic structures plays NO SIGNIFICANT PART in the mechanism of the reactions listed, and the other article cited gives examples of what I mean. One reason you probobly had a hard time finding it was the fact that I unfortunately misspelled the title. The full title was:

"Comptes rendus des seances de l'Academie des sciences."

i.e. - there shouldn't have been a "q" in there. This is a saucy Parisian little Journal, peppered oh-so lightly with chem nuggets to die for. I'll pick up a copy for The Hive.

Push it! Work it! Touch it! Yes! Feel it, now let the reagents "move you"! Okay now, gimme sexy! Oh, now let's see some magic! Yes! Oh, do behave!

posted 08-18-98 12:59 PM         

BUT while looking for zinc stuff in a great older book ("reductions" micheal smith) it lists for NO2->NH3:

(Fe/Hcl EtOH reflux) organic synthesis collective, vol 2, pg160

(Fe/HOAc 100'C) chemsitry review 32, 373 (1943) and quarterly review (london) 1, 358 (1947)

(Zn-aq. CaCl2) j.am.chem.soc. #80, 6244 (1958)

posted 08-19-98 03:38 PM         

Could you please post a copy of the article you listed? Unfortunately, I can't find a copy of this at my library. I know this article sites examples of aliphatic amines forming Schiff bases and their subsequent reduction by means of the use of zinc.

quirks,

How did they rationalize this? The second article I listed (according to Beilstein) describes exaclty what the other article stated didn't happen. I can see it happening, but I cannot see why it wouldn't. Mechanisticly, why would anilines be reduced, but aliphatic amines not?

posted 08-19-98 03:41 PM         

Could you please post a copy of the article you listed? Unfortunately, I can't find a copy of this at my library. I know this article sites examples of aliphatic amines forming Schiff bases and their subsequent reduction by means of the use of zinc.

quirks,

How did they rationalize this? The second article I listed (according to Beilstein) describes exaclty what the other article stated didn't happen. I can see it happening, but I cannot see why it wouldn't. Mechanisticly, why would anilines be reduced, but aliphatic amines not?

posted 09-02-98 07:28 AM         

OP did the ole zinc reduction, its yields were at best 50%...the tin was adapted straight out of Vogels, and worked better than thought....

posted 09-02-98 07:54 PM         

Very interesting, and very impressive. However, what exactly are you reporting being reduced? No real need to get into messy details, but what exactly are the orange crystals, nitrostyrenes? The yields sound great, but it soulds like they could be made even better if a little more tin were used.

posted 09-03-98 12:56 PM         

What is that article from? Where did you get it, and what exactly was the structure of the thing reduced? I have to ask, because you lost me on that "primary group" thing?

To put it bluntly, of the numerous reductions we discuss here, what sort of clandestine applications might this have?