Phenylacetone (P2P) synthesis from 1-phenyl-2-nitropropene (P2NP) via FeCl3

[WillD]

Reagents:

• 1-Phenyl-2-nitropropene (P2NP; cas 705-60-2) 1.63 g, 10 mmol;
• Powdered iron (Fe) 3 g;
• FeCl3 0.6 g;
• Hydrochloric acid (HCl 36% aq.) conc. 4 ml;
• Toluene 15 ml;
• Water 55 ml;
• Hydrochloric acid 3N (10.45%) HCl 25 ml;
• Sodium bicarbonate (NaHCO3);
• Magnesium sulfate (MgSO4);

Equipment and glassware:

• Round bottom flask 50 ml;
• Retort stand and clamp for securing apparatus;
• Boiling chips;
• Reflux condenser;
• Glass rod and spatula;
• Separatory funnel;
• Heating plate;
• Laboratory grade thermometer;
• Laboratory scale (0.1-200 g is suitable);
• Measuring cylinder 20 mL;
• Funnel;
• Filter paper;
• Rotovap machine (optional);
• Vacuum source (optional);
• pH Indicator paper;
• Beakers 100 ml x2 and 200 ml;

Reaction scheme:

​

Synthesis:

1. A mixture of 1-phenyl-2-nitropropene (P2NP) 1.63 g, 10 mmol, powdered iron 3 g, FeCl3 0.6 g, and hydrochloric acid (HCl 36% aq.) concentrated 4 ml in toluene 5 ml and water 5 ml are stirred vigorously at 75 °C for 18 h in 50 ml flask with reflux condenser.
2. The resulting dark green suspension is cooled to room temperature and filtered. Layers are separated.
3. The aqueous layer is washed with an additional portion of toluene 10 ml, and toluene extracts are combined and washed with hydrochloric acid 3N (10.45%) HCl 25 ml, water 25 ml, saturated sodium bicarbonate (NaHCO3) aq. 25 ml, and water 25 ml successively to neutral pH 7.
4. The toluene solution is filtered and dried over anhydrous magnesium sulfate (MgSO4). Mixture is filtered from solids.
5. Toluene solvent is evaporated from the mixture. Phenyl-2-propanone (P2P; cas 103-79-7) is obtained as an orange oil. The yield is ~75%.​

 

[btcboss2022]

Hello,

I tried this synth but is practically impossible to move the magnetic stirrer, all the iron gets stuck on it not allowing to move( is normal about magnet) haahaha how do you fix that?

Thanks.

 

[G.Patton]

top stirrer

 

[KokosDreams]

What's the obtained yield in P2P from this synthesis?
@btcboss2022
@G.Patton

 

[ASheSChem]

i see a lot of size for this reagent; any importance?

i have see to sell :
300 mesh (36 µ)
75 µm
90 μm
100-300 µm

 

[G.Patton]

Hello, sorry for a long reply. ~75%

 

[KokosDreams]

Thanks for letting me know.

 

[cokemuffin]

preferably at least 80-100 mesh.

 

[ali.co]

Hi
sorry but such a detail the proportions do not match
Other proportions in reagents
Other proportions in synthesis
I'm thinking about checking this synthesis
Long synthesis

 

[G.Patton]

Hello, what do you mean about proportions?

 

[CrystalBee]

P2np to p2p



Add to a 500ml Round bottomed boiling flask (RBF) with 3 necks
central neck has an overhead stirrer - IMPORTANT has to be an overhead stirrer and has to be powerful enough to keep iron powder from settling on the bottom, cannot use magnetic stirring as it does not have enough power to keep the iron powder up in the solution and the iron messes with the magnetic stirring anyway.
side neck has a long reflux condenser with cold water supplied
2nd side neck has a pressure-equalising addition funnel filled with 0.197 mole of conc. hydrochloric acid 35.5% in the below example thats is 20.2 ml

The RBF is in a water or oil bath to keep internal reaction temperature at 85 to 95 degC.

Add to RBF:
0.1 mole of P2NP (P2NP 163.2 g/mole) = 16.23g of P2NP
0.715 mole of iron (Fe 55.85 g/mole) = 40g of iron (Fe) - cast iron turnings or ideally 40 mesh iron powder (powder 0.4 mm size)
Note: Activate a metal normally involves rinsing it with a strong mineral acid like hydrochloric acid or alkali like sodium hydroxide solution for a few minutes to remove any layer of oxidation that prevents it from reacting, after this rinse with distilled water twice and use immediately else store under non-polar liquid until ready use required.
However in this reduction of nitroalkene to ketone, hydrochloric acid is one of the reagents, therefore activation can occur in situ.

75ml of distilled water
0.1g of ferric chloride - acts as an initialization catalyst - helps reaction start faster

Acid from addition funnel is added slowly over 5 to 6 hours, so as to keep the reaction going but not explosively so, reflux should never reach over half way up the reflux condenser.
At the end the reaction mixture was then basified with 25% NaOH solution until pH 11 and then steam distill the P2P oil over to a receiver.
Yield should be 75 to 77% P2P from the P2NP ie. P2P 134.3 g/mol so 0.1 mole is 13.42g and 0.75 to 0.77 % yield = 10g (9.94ml) to 10.3g (10.24ml) (Density of P2P is 1.006 g/mL)

This reaction can be scalled up to quite a large size, the molar equivalents are:
molar ratio of Fe/alkene = 7.15
molar ratio of HCl/Alkene = 1.97
1.97 x 0.1 mole of p2NP=0.197 moles of HCl x HCl 36.458 g/mol = 7.18g HCl
if you have concentrated hydrochloric acid 35.5% that means it has 355g/L, or 35.5g/100ml so 718g / 0.355 = 20.2ml of concentrated hydrochloric acid 35.5% to be added via addition funnel

So a 1 mole reaction would use a 5L RBF with 163.2 g of P2NP, 7.15 mole of Fe (7.15 x 55.85 g/mol) = 400g of iron powder, 750ml of distilled water, 1g of Ferric Chloride and 202ml of concentrated hydrochloric acid 35.5%
Yield would be 100g (99.4ml) to 103g (102.4ml) of P2P


Note: For a cheap overhead stirrer:
From ebay you can get a cheap PTFE stirrer bearing to fit the correct size of your boiling flask central neck, you can get a steel stirrer coated in PTFE to protect it from the acid, you can get a bench supply that supplies 0-30V 0-3A for about £30, and you can get a DC motor from certain handheld blenders cheap which you can take apart and connect motor shaft to stirrer shaft, stirrer shaft goes through bearing (pre-grease internal bearing ring with vaseline to help reduce friction), connect the motor to the bench power supply, set the current high enough to supply to motor, then vary speed by increasing/decreasing voltage.

PTFE Standard Stopper Lab Stirrer Bearing Adapter Stirrer Accessory No.29
https://www.ebay.co.uk/itm/313672059695
£10.84
This will fit a 29/32 socket on a boiling flask, it uses a stirrer shaft of 8mm diameter
Findind a PTFE coated stirrer with shaft diameter 8mm tricky most on ebay 7mm so it maybe best to order both items from laborxing that's 2 weeks to arrive but they have high quality equipment.

https://www.laborxing.com/products/ptfe-stirrer-bearing-adapter-joint-stopper
https://www.laborxing.com/products/ptfe-stirring-blades-propeller-2-winged-length-250-mm-to-750-mm

Bench power supply 0-30V 0-10A - potentially this is powerful enough to run electrochemical reactions, and peltier cooling modules
https://www.amazon.co.uk/dp/B09ZQBFZ4C
£44.99
You should be able to find a cheaper one because you only need 0-3A, maybe if the motor you pick up is high torque then 0-5A

 

[Rollin88]

I’ve tried this reaction with these exact ratio’s, and I just can not seem to get any p2p. I am following the procedure exactly - as hard as it is to get my addition funnel to drip that slow, I’m matching every parameter.My solution turns green. The RBF is a mess that I can hardly see in. I don’t know if I’m overstirring or not but there;’s iron pieces trapped in the ground glass fittings for the addition funnel and reflex condenser. Not sure if that’s normal…When I basify, I have gone a little past 11 one time, which seemed to produce a good bit of smoke in the flask. I added a couple more drops of Hcl to bring it back down to 11 and it seemed fine. I flood the same dirty RBF with iron still in there with water, and run a 1 flask steam distillation on the reaction mixture, which is very dark at this point, with the black iron particles staining everything. The distillate that then comes over is always clear, with a fogginess or haziness too it, but no real color. No orange. I figure this is oil and water mix but when I extract with DCM (ph is double checked here and is 11.1) it stays in the water later and the DCM just seems like crystal clear DCM, maybe with a super slight pink tinge. If the DCM is clear does that tell me there’s zero P2P? I don’t want to waste more time on it I’d rather just try again. I don’t know what parameters to change. I’m using triple re-crystallized p2np purchased from a reputable overseas verndor, I’m using ‘iron filings for synthesis’ that look legit, I bought FeCl3 from the science company.com and hcl is acs grade from alliance chemical. I am using high quality glassware, an overhead stirrer from vevor with a PFTE shaft and paddle. I was thinking of trying next with Zinc powder and ZnCl2 to start the reaction, given this is my fourth time without seeminingly getting anywhere. First 2 tries were .1M and the last was .2M, as I figured maybe a bigger vessel would be more forgiving, but all 3 fail. This last one turned a nice green color after 18h, but it has like green slime formed on the inside of the glassware that made it almost impossible to see above the waterline.

Any help is appreciated.

 

[Charlie3]

Has anyone tried this method and scaled it upwards? I tried it today, used
32.6g p2np
60g Fe
12g FeCL
88ml 33% HCI
300ml toluene
1100ml water
500ml 10.45% HCI.

Doesnt seem very practical if im trying to go 1kg p2np, i wont have glasswares big enough.
Does anyone have better proportions.
Its alot simpler this method, downside is it really stains the porcelain when pouring away the unwanted layer.

 

[Cardboard1234]

I'm a little curious on what purpose the water serves in step 3? It seems to go straight through the toluene solution and stays separated.

 

[G.Patton]

Hi, It is utilized in order to get rid of water soluble salts, which are form during this reaction.

 

[Cardboard1234]

Hello, just want to make sure I understand this correctly.

step 2: after filtering the dark green suspension, I have a slightly green solution only with a few drop of brown solution. What layers do you mean to separate?

step 3: I have to pour toluene into the aqueous layer and extract the toluene solution a few times before mixing the toluene extracts with hydrochloric acid, water, sodium bicarbonate solution, water successively.

step 4: the toluene (top) layer is separated again and added MgSO4 over an hour or so to remove any water in the solution.

step 5: boil the solution to 110 to evaporate the toluene.

is that correct?

 

[G.Patton]

It is obvious from the text that there are two layers: aqueous and organic
It worth to use vacuum distillation (rotovap). Also, I recommend you to distill P2P before following synthesis.

 

[Cardboard1234]

I was able to follow the steps until step 4, but once I start heating the solution to evaporate the toluene, the mixture turns red like this with a very dark colour. Any ideas?

 

[w2x3f5]

reaction with SnCl2 and hydrochloric acid in ethyl acetate gives a cleaner oil.
With Fe not so clear reaction

 

[Cardboard1234]

can I replace Toluene with other solvents like DCM or petroleum ether?

 

[SelfExper1menter]

1. Is Fe crucial, or can another metal be used instead (like Zn, Mg or Al)? I've heard Zn/HCl also reduces P2NP to oxime.
2. Can sulfuric acid (of properly chosen amount and concentration) be used instead of hydrochloric? And, if it can't, why?