Author Topic: PNP's to phenylnitropropanes by cat. hydrogenation  (Read 1747 times)

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  • Guest
PNP's to phenylnitropropanes by cat. hydrogenation
« on: September 26, 2004, 06:22:00 PM »
Finally, after many years, the nut of all nuts has been cracked. Here is a simple way to selectivly reduce the C=C bond in phenylnitropropenes. The catalyst has so far been reused six times without any loss of activity. This makes this method by far the most economical of all the other available methods. The trick is to use neutral conditions. Any traces of acids in the solvent and the result will be simultaneous oxime formation and subsequent carbonyl formation due to hydrolysis. Remember that the catalyst is very likely to contain acidic residues.


A 300 ml hydrogenation reactor containing 100 ml water was charged with 16.3 gram (100 mmol) twice recrystallised phenyl-2-nitropropene crushed to a fine dust and mixed with 320 mg 5% Pd/C (2% w/w of the substrate). The reacor was pressurised to 3 bar with argon and then vented back to atmospheric pressure. This was repeated six times to effectively reduce the oxygen content to a non-dangerous level. Then the reactor was filled with hydrogen to 3 bar and the stirrer started using a stirring rate of 1500 rpm. After a induction period of 2 minutes hydrogen consumption started and continued at the same rate for about 40 minutes. At that point exactly 0.1 mol hydrogen had been consumed and the hydrogen uptake ceased abruptly.

The reactor was ventilated back to atmospheric pressure and was then flushed with argon for 10 seconds. 30 ml DCM was added to the opened reactor, now containing a oil floating on the water surface, the reactor was closed again and stirring started for 30 seconds. This was done to get all the oil from the reactor walls into the DCM-phase. The reactor contents was filtered through a pad of celite to remove the catalyst and the DCM removed in a rotovap leaving 16 g phenyl-2-nitropropane as almost colorless oil. On HPLC analysis the nitroalkane contained a just a trace of unreacted substrate, no oxime and no phenylacetone.


The same method has been applied on the following substrates:

1-(4-Fluorophenyl)-2-nitropropene, 96% yield.
1-(3,4-dimethoxyphenyl)-2-nitropropene, 99% yield.
1-(4-hydroxy-3-methoxyphenyl)-2-nitropropene, 99% yield.
1-(3,4-methylenedioxyphenyl)-2-nitropropene, 97% yield.
1-(2,4,5-trimethoxyphenyl)-2-nitropropene, 99% yield.
1-(3,4,5-trimethoxyphenyl)-2-nitropropene, 99% yield.


  • Guest
« Reply #1 on: September 26, 2004, 09:05:00 PM »
Barium......two questions , one will the agitation of the Parr Hydrogenator be sufficient agitation to make the reduction of the C=C bond, and the second question is , since amines can be reduced from nitromethane , can this also be true , if additional hydrogenation is maintained till the conversion of the nitro to the amine

edited .......the second part of the question which I failed to communicate clearly , was , since nitromethane's are reduced to the respective amine, then will additional hydrogenation convert our phenylpropene to amphetamine, perhaps with a different solvent and under different parameters for


  • Guest
methinks yes
« Reply #2 on: September 26, 2004, 09:59:00 PM »
Of course - other routes reduce the C=C bond with borohydride and replace nitro with amino via Pd/C and formate salt hydrogen donors. Only reason for this 2-step reduction is that when amination is done before saturating the double bond, it won't work.
So you should be able to get prim. amines by first reducing C=C via Barium's above catalytic hydrogenation procedure, and then reducing the nitro moiety with further hydrogenation using different conditions, like pressure or solvent. Somehow.  ;)
(but isolating the nitropropane isn't that much work either; and it can be easily&cheaply reduced with Zn/HCOOH for example)

Barium, congrats to your post N°1000! Sure about the HPLC results? If the nitro group isn't attacked under those conditions, great! But if not, it could well be that some imine or even hydroxamine is present. (take it as a compliment: I just can't believe you cracked the nut!  ;) )



  • Guest
Java, this has been discussed before.
« Reply #3 on: September 26, 2004, 11:57:00 PM »
Java, this has been discussed before. But yes a aliphatic nitro group can very well be fully reduced to the amine by catalystic hydrogenation. But this will take a very long time to achieve using Pd or Pt catalysts if drastic reaction conditions are not available. Nickel catalysts are know to do the job using less severe conditions.


  • Guest
Indole-amine, no imine could have been formed...
« Reply #4 on: September 27, 2004, 12:07:00 AM »
Indole-amine, no imine could have been formed because that would have required more hydrogen than was consumed and the imine can only be formed by reduction of either the hydroxylamine or the oxime. If the oxime would have been formed some of it would absolutely be visible in the analysis and the imine would definetly have been hydrolysed to the ketone. But any acidity leads directly to almost complete oxime formation.


  • Guest
OK, I see. As long as everything is kept ...
« Reply #5 on: September 27, 2004, 06:53:00 PM »
OK, I see. As long as everything is kept neutral, no oximation can happen. (you didn't use any buffer, did you?)

And here's some nice advanced catalyst preparation for the enthusiastic C=C bond hydrogenationist  ;) :

Activity Enhancement by the Support in the Hydrogenation of C=C Bonds over Polymer-Supported Palladium Catalysts
(Marco Zecca, Roman Fiera, Giancarlo Palma, Silvano Lora, Milan Hronec, Milan Králik)
Chemistry - A European Journal Volume 6, Issue 11, Date: June 2, 2000, Pages: 1980-1986

"Four synthetic ion-exchange resins (AH, BH, CH, DH) of different hydrophilic/hydrophobic properties were used as supports for heterogeneous palladium catalysts (A, B, C, D). The resins contained styrene (STY) and 2-(methacryloxy)ethylsulfonic acid (MESA) as the comonomers. Either divinylbenzene (DVB: CH, DH resins) or N,N-methylenebisacrylamide (MBAA: AH, BH resins) were used as the cross-linker. AH contained also N,N-dimethylacrylamide (DMAA) as the third comonomer. The catalysts (Pd 0.25-0.45 % w/w) were obtained by ion-exchanging the acidic forms of the resins with [Pd(OAc)2] and reducing palladium(II) with excess sodium borohydride. The use of NaBH4 also ensured the neutralization of the acidic sites of the supports. No effect of the hydrophilic/hydrophobic properties of the supports was observed in the hydrogenation of cyclohexene and 2-cyclohexen-1-one in methanol, at 25 °C and 0.5, 1, and 1.5 MPa, respectively. However, catalysts A and B, containing amido groups provided by either DMAA or MBAA, proved to be more active than C and D. The observed activity enhancement was directly proportional to the nitrogen/palladium molar ratio in the catalysts. This finding suggests that amido groups promote palladium through a direct interaction with the metal surface."

Interesting in particular is the following sentence: "The use of NaBH4 also ensured the neutralization of the acidic sites of the supports" - their special polymer-supported catalyst was rendered free from acidic ligands, too! And this effort in maintaining neutral conditions is done, I would guess, out of the same reason as Barium pointed out already...