                     Reactions of Phenyl-2-nitropropene

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Posted by Dreamer on the Hive 98-06-02
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To 55 g (0.5mol) Benzaldehyde in a 500ml Flask were added 40 g (0.5mol)
Nitroethane and 10ml Cyclohexylamine. All was refluxed for 6h on a
waterbath. The result were 2 layers. One orange layer at the bottom with
phenyl-2-nitropropene and a clear layer at the top with cyclohexylamine and
maybe a little bit (~1ml) of H20. 50ml of H2O were added and then sucked
off with a pipette until the phenyl-2-nitro-propene crystallized (it
crystallized when it came in touch with air in presence of 15ml H2O).
I added 200ml 95% denaturated ethanol to the orange crystals. The color
of the now needle-like crystals changed from orange to white-yellow.
The crystals were filtered. Yield 65 g, 78% of theory.

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Posted by Zorohustra on the Hive 98-07-07
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The following chemicals were introduced into a 250ml RB flask in listed order:

80ml Toluene (ACS)
40ml Bensaldehyde (~99%)
30ml Nitroethane (>99%)
10ml n-Butylamine (p.a.)

Boiling stones were added and a Dean-Stark setup was rigged (10ml trap). The
goal was to boil the solution quite heavily to achieve fast dripping from
the double surface condenser, a heating mantle was used.

When the solution had boiled for an hour 2.7ml water was in the trap.
At six hours something like 7.0ml (100% of theory) had settled in the trap,
perhaps this happened some thirty minutes earlier, because the chemist took
a short nap.

The solution was dumped into a 250ml beaker, and allowed to cool to room
temperature, it was seeded with some phenylnitropropene crystals, and
slowly cooled to around -10C (freezer).
The crystals looked REALLY nice and no further purification was needed. The
filtrate was concentrated under vacuum and cooled like above. Dirty
crystals fell and they where recrystallized from 50ml MeOH.

Yield #1: 35g Yield #2: 6g Total yield 41g (64%).

Hmm, hmm the chemist thought, perhaps Benzene will increase the yield, its
lower boiling point would probably decrease destruction of formed
phenylnitropropene. Said and done:

Same procedure, setup and chemicals as above, but 80ml of nice 99.9%
Benzene as solvent.

00:00 - Boiling
01:00 - 2.0ml water in the trap
02:00 - 2.3ml
06:00 - 3.3ml
14:20 - 6.7ml
17:20 - 6.8ml
19:00 - 6.9ml Turning it off, thinking: "I will never get 7.0ml due to
              the higher solubility of water in Benzene then in Toluene,
              just killing yield now"

The solution was concentrated under vacuum, care taken never even to smell
any Benzene. Dumped the solution in a 250ml beaker, it solidified
completely and just 150ml of MeOH was added. This was enough to dissolve
the crystals when boiling.

Yield: 42g (65.6%).

All right, the yield is just above 60% with both Toluene and Benzene,
lower temperature results in a slower reaction. But there are cases when
n-Butylamine is a much faster catalyst and the temperature is even lower,
such as when using MeOH as solvent. The chemist decided to try the reaction
and setup once more but with Cyclohexane as solvent.

The setup and the chemicals was still the same, but the solvent this time
was 80ml Cyclohexane (pure). And instead of using 10ml n-Butylamine the
amount this time was 8ml (due to the usage of the wrong vol. pipette ;)

00:00 - Boiling
01:00 - 1.5ml water in the trap
03:00 - 1.8ml
13:00 - 2.7ml At this point the chemist adds another 4 ml n-Butylamine
14:00 - 3.3ml
16:00 - 4.0ml
20:30 - 4.2ml Fuck it.

The color of the solution is a very beautiful and clear yellow. Crystals
refuses to form, so the solution is concentrated under vacuum.

The yield sucks big time, less then 10g (<15%).

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Posted on the Hive by Zorohustra 980815
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(Rhodium posted this method some time ago, I am just testing it, scaled it
up 2X by the way)

In a 1000ml E-flask 32g of pure 1-phenyl-2-nitropropene was dissolved in
400ml MeOH, the MeOH had to be heated to dissolve it all, there is nothing
to do about that (the water content was less den 0.02% in this particular
MeOH).

The solution was cooled to 0C with external ice/NaCl, when the solution got
this cool, the damn crystals reprecipitated. I hoped it would be okey
anyway.

15g NaBH4 is SLOWLY added, I mean SLOWLY, I did it slow but not slow enough
not to rise the temperature well above 15C. I again, hoped it would be okey
anyway.

I let the mixture stir at room temperature for about 2.5 hours.

The solution was again cooled to 0C, perhaps I didn't cool it to 0C, but it
was below 5C anyway.

200ml 30% H2O2 (pure) and 60g anhydrous K2CO3 is added in portions. This is
NOT "hard for a weak mag stirrer", this results in something that reminds
about a clay - bubblegum mixture, I butched it up with a kitchen knife...
The reaction is a slow exotermic one, that goes on for hours and hours
(after about 6 hours the mag. stirrer works again). The mixture was stirred
for a total of 24 hours (there is still two small "clay-bubbelgums", but
the reaction is dead).

In a 1000ml beaker 100ml 37% hydrochloric acid is mixed with 500ml dH2O,
this solution is then slowly added to the other solution, which has been
transfered to a 2500ml beaker. The solution becomes more yellow, it was
actually not very yellow at all before the addition of the acid.

The solution is extracted with 3*(70+70)ml DCM, the DCM is removed by
destillation, the impure P2P is transfered to a 100ml RB and then destilled
to a 25ml RB. I collected between 105C and 125C with GOOD aspirator vacuum.
Yield is perhaps 70%, but I don't know, the light yellow oil is still in
the 25ml RB.

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Preparation of Phenyl-2-Propanone (P2P) by Rhodium (Also found in TS II)
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In this preparation, phenyl-2-nitropropene is reduced to
phenyl-2-nitropropane with sodium borohydride in methanol, followed by
hydrolysis of the nitro group with hydrogen peroxide and potassium
carbonate, a variety of the Nef reaction. The preparation is a one-pot
synthesis, without isolation of the intermediate. 

Efforts directed to prepare MDP2P via this method results in good yields 
of a ketone with properties completely dissimilar to MDP2P, and is 
probably the propiophenone, formed by migration of the nitro group during 
the hydrolysis.

16.3g (0.1 mole) phenyl-2-nitropropene was dissolved in 200ml methanol in 
a 250ml Erlenmeyer flask situated on a magnetic stirrer, and chilled to 
0°C with an ice/salt bath. Then, with good stirring, 7.6g (0.2 mole) of 
NaBH4 was added a little at the time, and the temperature was not allowed 
to to rise above 15°C. When the generation of heat had subsided, the 
ice/salt-bath was removed and the solution was stirred at room temperature 
for two hours. At the end of this period, the flask was once again placed 
in an ice/salt bath and the solution was allowed to cool to 0°C again. 
100 ml of 30% H2O2 was then added, together with 30 grams of anhydrous 
K2CO3, and the solution was left to stir for 18-24 hours at room temp.
During the addition of H2O2/K2CO3 a white, sticky precipitate forms, which
can be a bit too thick for a weak magnetic stirrer to handle, so the mass
can be stirred with a glass rod now and then during the first two hours,
after which the precipitate will be much looser and no match for any 
mag-stirrer. The next day, the solution is slowly acidified with 2M HCl
with good stirring, care being taken for the evolution of heat and CO2.
About 300 ml of acid is needed. When the pH of the solution turned acid,
the color became significantly more yellow, but the acidity was confirmed
with pH paper. All of the precipitate was also be gone at this point. The
solution was extracted with 3x100ml CH2Cl2, and the pooled organic extracts
washed with 100ml 2M NaOH and 200ml H2O. The organic phase was dried over
MgSO4, filtered with suction, and the solvent removed under vacuum to give
a clear yellow oil. After distillation of said oil at aspirator vacuum, the
yield was around 60-70% of phenyl-2-propanone (P2P) as a light yellow oil.

Ref: R. Ballini, Synthesis 723-726 (1994)

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Dreamer - posted at the Hive 10-12-98
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18gr of Palladium on Carbon were prepared using following methode:

- 1,7gr PdCl2 in 2ml 31% HCl and 20ml dH2O are heated for 15min at 80°
- 20gr activated carbon are heated with 450ml H2O and 15ml 31% HCl for 2h; 
  the carbon is filtered off
- the PdCl2 solution is added to 30gr sodium acetat trihydrate in 200ml 
  dH2O in a 500ml Flask
- the washed carbon is added to this solution
- hydrogenate the mixture for 3h, using drone's hydrogen generator; set 
  it up to produce 1mol of H2; don't forget to stir vigorously; iron 
  powder works nicely (only powder works, sheet's won't)
- when the hydrogenation is complete and the carbon settles down and you 
  should have a colorless mixture with the catalyst at the bottom
- filter the carbon , wash it with 4-5*100ml dH2O; dry the catalyst at 50°
- I got 18gr (my filter methode wasn't good, use only glas no plastic, 
  easier to clean) of 5% Palladium on Carbon;

- - - - -

- 22gr highly purified Phenyl-2-nitropropene
- 300ml 99% glacial acetic acid (maybe too much)
- 38gr Ammonium Formate
- 9gr 5% Palladium on Carbon ( Pd-C)

were introduced in a 500ml Flask.

22gr P2NP were dissolved in 300ml 99% glacial acetic acid and added 
to the 5% Pd-C. All was heated to 100° and vigorously stirred.
I introduced 3*~13gr Ammonium Formate; All was refluxed for 25 min;
Then everything was cooled; 100ml Chloroform were added so that it 
is easier to filter the Pd-C. I used normal coffee filter paper and 
vacuum, which worked. Then i added 1l of dH2O and the Chloroform 
separated out. The layers were separated andi "washed" again with 
additional 100ml Chloroform. But amphetamine wasn't soluble in the 
glacial acetic acid, so i extracted it with the chloroform.

The chloroform was eliminated and i got 15.5gr of a yellow oil, 
which was dissolved in 200ml 15% HCl, washed trhee time with 75ml
DCM, made basic with 25% NaOH and extracted with Ether. And again 
i failed to make the HCl salt , i tried to dry the ether with Epsom 
Salt and then to afford the salt with dry HCl. But all i got was a 
slightly yellow colored layer at the bottom of my ether mixture.
I decided then to make the salt with 99% H2SO4 in Ether and Ethanol, 
which worked perfectly. (first i made again everything basic...)
The salt was washed and i got 14gr of white! Amphetamine salt.

- - - - -

I didn't use any H2SO4 in the CTH because i don't know if it helps or if 
it destroys everything, maybe it helps and the yields would be higher. 
Maybe anhydrous ethanol works better, if anyone sends my Calcium oxide 
POWDER i will try it )

Palladium on carbon is not easy to handle, i suggest to use only glas 
filter funnels, my plastic funnel is still full with carbon.

Anyone knows a secure methode to form the HCl salt of an amphetamine ?
I dried with the Epsom Salt (~30gr) for 2h, is it not possible to dry 
with Epsom Salt (MgSO4 * 7H2O)? already too many H2O's ?
   
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beagle boy:        

Excellent post! Most informative. Did your info on this reaction come from 
Tet Lett 29(45), 5733 (1988)? Any other refs?

I don't get this bit "But amphetamine wasn't soluble in the glacial acetic 
acid, so i extracted it with the chloroform." It isn't!? And you didn't 
basify the reaction mixture B4 extraction?

You had problems forming the HCl salt because it is hard to do. Much 
harder than meth HCl. Early papers on amphetamine synth. always described 
the HCl salt as hygroscopic, if they could even obtain it as a solid at 
all. Actually, when extremely pure it is not particularly hygroscopic. 

Epsom Salts are not a good drying agent. Cook in the oven for awhile to 
dehydrate first. 

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Cherrie Baby:         

Don't skimp on the formate. Most of the dudes (below) are using 5 to 12 
mole xs. of Formate, w.r.t. main reactant, in their CTHs. This will give 
the best yield.

Was all the Pd homemade? I would have got hold of some of that Pd on 
polymer - it should last at least 50 reductions.

Catalytic Transfer Hydrogenation Reactions are considered so easy that 
J. Chem. Ed. are flogging them for new undergrad. Programs. - get your 
ticket soon. Cheap, versatile - but not perfect. Ultra-cheapskates can 
even substitute Ni for Pd as the catalyst (sometimes)!

Alkenes -> alkanes
ketones -> alkanes
nitroalkanes -> amines
azides -> amines
chloro-cpds -> hydrocarbons (psssst halo-ephedrine -> meth)
deprotection of peptides
deprotection of benzylic ether (to alcohol)
nitro-alkene -> oxime

Catalytic Transfer Hydrogenation Reactions for Undergraduate Practical 
Programs, R Hanson, J. Chem. Ed. 74(4), p 430-1 (1997).

Catalytic Transfer Hydrogenation of Benzaldehyde in a Microwave Oven, 
Gordon et al. Organometallics 12, 5020-2 (1993).

Microwave-Induced Organic Reaction Enhancement Chemistry. 2. Simplified 
Techniques. Bose et al., J. Org. Chem. 56, p 6968-70 (1991). [page 6969]

Transfer Hydrogenation: A stereospecific method for the conversion of 
nitro alkanes to amines, Barrett, Tetr. Lett. 29(45) p 5733-4 (1988).

Ammonium Formate in Organic Synthesis: A Versatile Agent in Catalytic 
Hydrogen Transfer Reductions. R Ehrenkaufer, Synthesis 1988, p 91-95

Reduction of Aldehydes and Ketones to Methylene Derivatives using 
Ammonium Formate as a Catalytic Hydrogen Transfer Agent. S Ram & 
L Spicer. Tetr. Lett. 29(31), p 3741-4 (1988).

Heterogeneous Catalytic Transfer Hydrogenation and its Relation to Other 
Methods for Reduction of Organic Compounds. R Johnstone, A Wilby & 
I Entwistle. Chem. Rev. 85, p 129-170 (1985).

A General Procedure for the Mild and Rapid Reduction of Aliphatic and 
Aromatic Nitro compounds using Ammonium Formate as a Catalytic Hydrogen 
Transfer Agent. S Ram & R Ehrenkaufer, Tetr. Lett. 25(32), p 3415-8 (1984).

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Dreamer:

beagle boy, after the filtration of the Pd-C with 100ml i added 1l of 
dH2O. I separeted the two layers and "washed" again with 100ml Chloroform; 
Then i added enough 50% NaOH to the glacial acetic acid to make it basic 
and extracted it with DCM, when i evaporated the DCM i found only 1ml of 
yellow oil. When i eliminated the chloroform from the washes i got ~15gr 
of a yellow oil. This oil was then converted into the sulfuric salt.

Maybe the ammonium formate didn't let the amphetamine dissolve in the 30% 
acetic acid. When i made it basic i smelled ammonia too, maybe the ammonia 
was present and reduced the dissolve power of glacial acetic(made it basic?), 
boh, i am not a chemist, i am happy that i didn't loose my amphetamine oil. 

My information source for this reaction was the internet and vogel's book 
on practical organic chemistry...

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dreamer:
   

- 0.05mol 8gr beta nitropropene C9H9NO2 63gr/mol
- 13gr 5% Pd-C
- 100ml Methanol
- 50ml THF 
- 0.15 mol NaBH4 

- 8gr P2NP are dissolved in 50ml THF and 50ml Methanol and is stirred on 
  a magnetic stirrer
- 1.9gr NaBH4 are slowly added over a period of 30min
- the addition of nabh4 is effervscent
- after 15min of stirring 13gr 5% Pd/C in 100ml methanol is added;
- don't add the Pd/C without solvent, it will catch fire )
- the you should add slowly over a period off 1h (i did it) 4 gr NaBH4;
- reaction is continued for another 3h and 5ml of acetic acid is added 
  (to neutralize NaBH4 .. maybbe you don't this) and 20ml of 31% HCl and 
  50ml of H2O;
- the solution turns red
- Pd/c is filtered away and washed with Methanol and dH2O
- Methanol and THF is eliminated, the red color disappears
- all is washed with DCM
- make it basic with 100ml 25%NaOH and extract; you should get around 5gr 
  of the freebase (i did), yield ~70%; the salt is easily made with H2SO4 
  in ethanol, but don't add too much H2SO4 or your salt dissolves (if 
  this happens make all basic and extract)

a few days bevor i tried the same thing with ethanol, yields were much 
lower and the addition of NaBH4 was not so effervescent

I would like to try to isolate the nitroalkane which is formed by the 
reduction with NaBH4 in methanol and reduce it with Al/Hg, i need to know 
if reduction of a nitroalkane with Al/Hg is sensible to water (will it 
work in 95% ethanol?) and how much Al/Hg for 0.1mol of P2NP i should use?

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