Author Topic: Replacement of the Hg/Al amalgam reductions?  (Read 10035 times)

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Aurelius

  • Guest
Replacement of the Hg/Al amalgam reductions?
« on: May 09, 2003, 05:29:00 AM »
In a time long, long ago, Piglet posted on 2/2/99 that P2P could be reductively aminated with Ni(NO3)2, Zn and NaOH to yield Amphetamine.  Does anybody have a reference for this (particular) reaction?  (Zinc/Nickel couple)

Rhodium

  • Guest
Very similar to Urushibara-Ni
« Reply #1 on: May 11, 2003, 09:08:00 PM »

Post 270027

(Rhodium: "Zn/NiCl2 reduction of oxime/nitro/nitriles/ketone", Chemistry Discourse)


https://www.thevespiary.org/rhodium/Rhodium/chemistry/urushibara.html



And here we have a few articles on the subject, courtesy of Lugh:

https://www.thevespiary.org/rhodium/Rhodium/djvu/znnicouple.djvu


(Djvu reader plugin at

http://www.lizardtech.com/download

)

Aurelius

  • Guest
WOW!
« Reply #2 on: May 13, 2003, 11:43:00 PM »
How did I manage to miss such a wonderful thread!!  that stuff is as versatile as it comes.  Thanks Rhodium.

moo

  • Guest
Reduction of phenylacetonitriles w/ Zn/Ni couple
« Reply #3 on: May 26, 2003, 04:33:00 PM »
This patent might need a translation. 8)  Oh and Lili, I found a bug in the patent tag too! ;D

Reduction or hydrogenation by the use of a zinc-nickel couple.

Patent FR56321

CA 52:61361

Abstract

The Zn-Ni couple is prepd. by dissolving 7 parts NiSO4 in H2O 70 parts, adding Zn powder 70 parts, and stirring for 15 min. Dehalogenation and reduction processes are claimed.  2-Bromo-4,5-diethoxyphenylacetic acid 50 parts dissolved in 50% KOH 200 parts and H2O 400 parts is added to the Zn-Ni couple while the temp. is maintained at 50-60°C, and the mixt. is kept 48 hr. with stirring. Filtration, acidification, and purification gives 80% 4,5-diethoxyphenylacetic acid, mp. 81-82°C.  A suspension of 2-bromo-4,5-diethoxyphenylacetonitrile 10 parts in alcohol 4, H2O 60, and 50% KOH 20 parts is added with stirring to a Zn-Ni couple prepd. from Zn powder 120 parts and NiSO4 6 parts while the temp. is maintained at 50°C.  Two more identical portions of the suspension are added at 15-min. intervals. After 6 hrs. at 55°C, the mixt. is filtered, the alcohol distd., and the amine, purified by formation of the sulfate, obtained in 70-72% yield, bp15 160°C.


wareami

  • Guest
FR 56321
« Reply #4 on: May 26, 2003, 06:18:00 PM »
moo:
There isn't a bug in the patent tag. You must put a space between the FR...US...etc...and the numbers.

Patent FR56321


Poly Voo Francias??? ;D
Peace of the reaction

Have FUN-Bee SAFE



moo

  • Guest
Corrected... First I teach you, now you teach...
« Reply #5 on: May 26, 2003, 11:59:00 PM »
Corrected... First I teach you, now you teach me. ;D


gabd

  • Guest
Patent FR971429
« Reply #6 on: May 28, 2003, 05:10:00 AM »
This comes from patent

Patent FR971429

. The
patent FR56321 was an addition to this one.

Exemple 1 Transformation of ketones to their corresponding amines

The present invention allow us to obtain amines by reduction of ketones in the presence of excess ammonia.
Starting with cyclohexanone we obtain cyclohexylamine in the following manner:

5 parts nickel sulphate is dissolved cold in 80 parts NH3 20%. Fifteen parts cyclohexanone are added, stirred and the dissolution is helped by adding 20 parts 95% ethanol. The addition of 10 part of Zn powder signals the start of the reaction. Two more 10 parts of Zn powder are added  successively. After a few hours, the solution is centrifuged and by proper treatment, we recover 70-72% cyclohexylamine.
In the same manner we obtain isopropylamine from acetone, isobutylamine from methylethylketone, etc.

Exemple 2  Transformations of nitrocetones into their corresponding aminoalcools

Solution 1
Nickel sulphate 80 parts
Water 600 parts

Solution 2
Isonitrosoacetophenone 200 part
Regular NH3                 2670 parts
KOH 35%                      120 parts

Shake solution 1 then add in one shot, 600 parts Zinc powder. 15 to 30 minutes later, start adding solution 2 keeping the temperature below 60-70 celsius. The addition should take 2-3 hours. The solution is left stirring for a few more hours. The solution is centrifuged to separate the zinc precipitate. The precipitate is washed several times with 250 parts distilled water. The washes are added to the solution separated by centrifugation as above. Potassium carbonate is added in sufficient quantity to extract the base just formed. After washing the extracted base, it can be reacted with sulphuric acid in the usual conditions to yield the sulphate salt. The yield starting with 200 parts of nitroketones is around 90% of theoric following the reaction
C6H5COCNOH-CH2     + 6H+   =    C6H5COHCNH2CH2

Exemple 4 Transformation of oximes into primary amines

It is quite normal that oximes give their corresponding amines since nitro containing molecules are regularly transformed into amines. This way we obtain B-phenylethylamine from the oxime of acetophenone. The oximes of phenylacetone and benzylacetone give respectively with yields of 85-88%, the phenylisopropylamine and benzylisopropylamine.

Example 6 Reduction of a nitrile function to its primary amine

Diverse nitriles are reduced to their corresponding amine by the zinc/nickel couple by the addition of 4 hydrogen atoms. This way, benzyl cyanide gives phenyl ethylamine

Summary

The present invention has for goals:

1.   A reduction or hydrogenation of organic compounds in aqueous or hydroalcoolic solvent, thas consists essentially in doing the reaction with the metallic couple Zinc/Nickel
2.   An execution mode for this invention, that consists in preparing the Zinc-Nickel couple using nickel sulphate at a maximum concentration of 5% of the hydrated salt and of metallic zinc, and to effectuate the reduction at temperatures under around 50 Celsius
3.   Application range from transformation of ketones in amines, nitroketones in aminoalcools, of ethylenic derivatives into saturated compounds, oximes into primary amines, of carboxylated aldehyde or ketone into alcool, and of nitriles into primary amines.

I translated the important parts. If anybody feel that some parts may be missing in the above translation, its just that they dont give more details. Remember this patent was applied for in the 1940's so a lot must have been learned about this system since then.

Aurelius

  • Guest
Reduction
« Reply #7 on: May 29, 2003, 09:55:00 AM »
Has anybody thought to use cinnamaldehyde in the Zn/Ni couple?  It reduces both C=C and aldehyde functionalities.  The product would (presumably) be 3-phenylpropanol, just a step or three away from P2P.  All OTC.

gabd

  • Guest
My experience being limited
« Reply #8 on: May 29, 2003, 04:11:00 PM »
I was curious how you would transform the alcool function(on carbon 3) to the ketone(on carbon 2)?
Any ideas?

Aurelius

  • Guest
Read more
« Reply #9 on: May 29, 2003, 10:09:00 PM »
Go to Rhodium's site.  You'll find an article on dehydration of alcohols with KHSO4 to give the alkene. The alkene formed is allylbenzene.  This can be isomerized just like safrole.  The product formed in propenylbenzene.  This can be oxidized in several ways (performic acid) to P2P.

FloridaAlchemist

  • Guest
Perhaps KHSO4 can be replaced with NaHSO4.
« Reply #10 on: May 30, 2003, 04:04:00 AM »
Perhaps KHSO4 can be replaced with NaHSO4. The NaHSO4 is a very common OTC item.

gabd

  • Guest
Its a primary carbon
« Reply #11 on: May 30, 2003, 04:36:00 AM »
The mecanisms has to go through a carbocation which you wont get for this particular compound. Primary carbocations are highly unstable and almost dont exist. I highly doubt this would work. What do you think?

Aurelius

  • Guest
Primary Carbon
« Reply #12 on: May 30, 2003, 05:27:00 AM »
Which reaction are you referring to?  The reduction or the dehydration?  The reductions have both been proven as given in the Zn/Ni couple thread:

Post 270027

(Rhodium: "Zn/NiCl2 reduction of oxime/nitro/nitriles/ketone", Chemistry Discourse)


1) alpha,beta-Unsaturated acids (reduction to the saturated acid).

"Malic, crotonic, oleic, and cinnamic acid have been respectively transformed in succinic, butyric, stearic and phenylpropionic acids"

This shows that the alkenyl would be reduced to an alkane. 

"Formaldehyde, salicylaldehyde and vanillin has been reduced to methanol, salicylalcohol and vanillic alcohol. Salicylaldehyde forms an insoluble complex with nickel in ammoniacal solutions (4), its reduction has been furnished in the presence of potassium carbonate. The beta-keto-substituted phenylpyruvic and benzoylpropionic acid has been transformed to phenylacetic acid and gamma-phenylbutyrolactone respectively"

This shows the reduction of the aldehyde to an alcohol. 

https://www.thevespiary.org/rhodium/Rhodium/chemistry/propiopropen.html


Post 211259

(Scooby_Doo: "Re: Phenylpropanol Dehydration", Chemistry Discourse)

These show the procedure for the dehydration of an alcohol with KHSO4

Post 345222

(Ritter: "dehydration reaction", Chemistry Discourse)

This is the dehydration with p-tosic acid.

In any case, we have formed allylbenzene as the major product with perhaps a little propenylbenzene. 

The remaining allylbenzene can be separated by distillation (don't really even have to separate the two) and then isomerization can be performed by the many ways discussed here and at Rhodium's site.

The oxidation from propenylbenzene to P2P is also well-covered.

(there are even methods that go from allylbenzene to P2P through the epoxide - and maybe others)

gabd

  • Guest
After reading the posts
« Reply #13 on: May 30, 2003, 07:32:00 PM »
Talking about the dehydration reaction:

I'm still not convinced. If someone can explain me the mecanism, then I will agree. From the posts I've read(your links) it doesnt seems that easy to do. As anyone done it with good success? No offense to Ritter or any other experienced bees.

If its not trough a primary carbocation, then how?

And if through a primary carbocation, since when are these stable? The energy barrier to create a  primary carbocation is really high and they to most purposes dont exist

Any ideas?

moo

  • Guest
How about a rearrangement to a secondary ...
« Reply #14 on: May 30, 2003, 08:12:00 PM »
How about a rearrangement to a secondary carbocation, which is more stable? This rises a question: could the secondary carbocation rearrange further to a benzylic secondary carbocation, which would make propenylbenzene a side product of the reaction, maybe in amounts worth isolating.


Aurelius

  • Guest
Idea
« Reply #15 on: May 31, 2003, 09:06:00 PM »
The basic idea behind this whole scheme is that I don't know anybody (relative to location) who can't get cinnaldehyde (cinnamon oil) in gallon quantities for a very cheap price.  Which means that if possible, and I think it is, that this is an excellent way to precursors. Perhaps more study into the the hydration reaction is called for in this case.

Ziqquratu

  • Guest
The textbooks say...
« Reply #16 on: June 01, 2003, 03:07:00 AM »
gabd, just had a quick flick through the trusty o-chem textbook, and it seems, as I suspected, that primary alcohols can be dehydrated (the book suggests 170oC and 95%H2SO4, but as we all know textbooks arent the last word in what actually works in a practical setting... What it does say, however, is that while secondary and tertiary alcohols go via an E1 mechanism(and hence carbocation intermediate), primary alcohols go via E2 (no carbocation formed).  So dehydration should be possible under some conditions, anyway.

Aurelius

  • Guest
Ziqquratu
« Reply #17 on: June 01, 2003, 03:52:00 AM »
After looking in the books, you're right.  Also, ZnCl2/HCl can be used to chlorinate the substrate for elimination.  Or the tosylate can be made (easier, better yields, and better leaving group) but the tosylchloride may need to be purchased.  (it can be made from tosic acid.

Post 398337

(Aurelius: "Compilation of Acid Reagents", Chemistry Discourse)
)
tosyl chloride

Post 311175

(foxy2: "Acid Chloride Synthesis", Chemistry Discourse)

Post 383271

(Aurelius: "Cyanuric chloride: -COOH to -COCl/COOR/CONR2", Novel Discourse)

https://www.thevespiary.org/rhodium/Rhodium/pdf/trichloroisocyanuric.pdf




and apparently, the last document (the pdf) shows that coversion from the alcohol to the chloride is possible using the reagent discussed in that document. 

Basically, I still see no reason (although there may be one or two more steps involved) that this isn't a completely OTC and potentially cheap (this part may change) method to precursors.

hypo

  • Guest
...
« Reply #18 on: June 02, 2003, 07:22:00 PM »
> This patent might need a translation.

nope, it paraphrases exactly the abstract you posted.
(well, except for the Zn/Ni-couple generation  :P )

Aurelius

  • Guest
Dehydration
« Reply #19 on: December 13, 2003, 07:13:00 AM »
Dehydration is debatable, but elimination of the tosylate isn't that hard. 

Post 436456

(Aurelius: "Primary Carbon", Chemistry Discourse)


this gets us to the alcohol

Post 476352 (missing)

(Rhodium: "TsOH/CoCl2: Tosylation of alcohols", Novel Discourse)


gets us the tosylate

simple elimination of the tosylate with base ought to do the trick to get the alkene.