(Newbee)
06-13-02 14:09
No 320730
(Rated as: excellent)
18,1g (100mmol) 1-(2-fluorophenyl)-2-nitropropene was added dry in portions to 49,5g (220mmol) SnCl2x2H2O suspended in 75ml EtOAc while the reaction temperature was kept between 20-40 deg C by a cold water bath. When all nitropropene was added and the color had changed to white (5 min) the EtOAc solution was transferred to a rb flask containing 250ml water and 50 ml hydrochloric acid. The EtOAc was removed by distillation under diminished pressure and the aqueous suspension of oxime and tin salts was allowed to stir at 80 deg C for 1 hour. The water phase was now steam distilled to remove the ketone. When no more oily drops came over the distillate was extracted with DCM. The DCM extracts was dried over MgSO4 and the DCM removed by distillation leaving a quite pure ketone as a colorless oil.
Yield: 13,5g (89%) 1-(2-fluorophenyl)-2-propanone
Purity: 98% (HPLC)
Tin(II)chloride is quite non-toxic and generally very nice.
(Chief Bee)
06-13-02 14:30
No 320732
Is this the procedure from Varma & Kabalka's paper, which I wrote about in TSII?
There have been reports of it not working so good in larger batches - but apparatly you've managed to do that. What are the physical properties of 2-Fluoro-P2P, and have you made the corresponding amphetamine or methamphetamine?
(Newbee)
06-13-02 15:08
No 320736
It´s a variation of the Varma and Kabalka method, but they stopped at the oxime stage and said that it was just to extract the oxime with ether. Well the extraction of the oxime from the tin crap/sludge is a NIGHTMARE. So I thought way not render the whole thing acidic and hydrolyse the oxime to the ketone. At the same time the problem with the tin is no more, since Sn(II)chloride and Sn(IV)chloride will stay in the water phase.
I just did this two hours ago. First trial. Great success!!
The physical properties: bp 47 deg C @ 0,05mmHg, d 1,077g/ml according to Aldrich. Clear oily liquid with a aromatic smell, quite nice. I have not distilled it yet. I rarely do so with the ketones since I get them pure enough anyway. The amphetamine, N-methyl and N-ethyl will be made in a short while.
(Newbee)
06-13-02 17:02
No 320761
This is another way of getting phenylacetones from nitropropenes without affecting aromatic halogens. So if someone starts with 2,5-dimethoxy-4-iodobenzaldehyde it seems easy enough to get the nitropropene-----phenylacetone----and get DOI without doing it the shulgin way.
Why does it seem like I am talking to myself the last days.
Not many replies to my posts. Don´t you guys and girls like them?
(Chief Bee)
06-13-02 17:14
No 320769
I love them! Haven't you noticed that I have rated a large part of them as "excellent", and archived several of them at my site?
If you want some further discussion on the various topics you've brought up, then I'll try to do that - because encouraging you to post more of your ground-breaking stuff is definitely worth it.
How did the analysis go of the compound that wasn't 2C-H?
(Newbee)
06-13-02 17:37
No 320780
Sorry about that Rhodim! I haven´t visited your webpage for a couple of days now so I haven´t seen the updates you´ve made until now. I´m glad you liked them enough to archive them.
I have not had time to send the mysterious compound for a NMR yet. But it will be done.
According to the authors of the article I posted yesterday (nickel/hypophosphite), their method will reduce nitroparffins to amines. Let´s see if it reduces 1-(2,5-dimethoxyphenyl)-2-nitroethane to 2C-H as well....
It would also be nice to hear if someone else actually tries my methods.
(Hive Prodigy)
06-13-02 17:37
No 320781
rest assured I like reading your posts as well, I just haven't been able to comment on any of them with anything significant. But just to let you know, I am also reading them and liking what I read.
(Newbee)
06-13-02 17:39
No 320782
Thanks PP!!..
(Official Hive Translator)
06-13-02 18:47
No 320801
Don't worry, Barium, it happens all the time
Actually, i have two things to note:
1) In the known (Ritter's i think, no?) experiments the reduction was attempted on a nitrostyrene. As seen from those two articles posted by Yellium, they are more picky/less stable to the conditions. Maybee, that's the cause. Or maybee it's still the matter of ring-activation, or maybee both - i personally don't have a clue
2) Barium, you used SnCl2 dihydrate - and in the original articles they said 'monohydrate'. I never heard of SnCl2*H2O - only the dihydrate, but maybee i'm just uninformed - what do you think?
Once again - your posts are a true pleasure to read, i'm glad you joyned us
Antoncho
(Newbee)
06-14-02 16:34
No 321226
This nitroalkene --> ketoxime --> ketone was tried with two other phenyl-2-nitropropenes.
40,75g (250mmol) 1-phenyl-2-nitropropene
115g (512mmol, 2,05 eq.) SnCl2x2H2O
150ml EtOAc
140ml conc HCl
500mml water
yield; 30,82g (230mmol, 92%) 1-phenyl-2-propanone
51,75g (250mmol) 1-(3,4-methylenedioxyphenyl)-2-nitroprop
115g (512mmol, 2,05 eq.) SnCl2x2H2O
150ml EtOAC
140ml conc HCl
500ml water
yield; 41,83g (235mmol, 94%) 1-(3,4-methylenedioxyphenyl)-2-propanone
(Newbee)
06-14-02 16:50
No 321230
Hi Antoncho!
Varma and Kabalka said that SnCl2/EtOAc doesn´t work with nitroethenes but does so with nitropropenes. I belive that the aldoxime doesn´t survive the enviroment but is hydrolysed to the acetaldehyde, which readily polymerises.
No I used SnCl2 not SnCl4. I have also only heard of either the anhydrous salt or the dihydrate of SnCl2.
Thank you for those kind words...
(Chief Bee)
06-14-02 17:27
No 321251
Varma & Kabalka made a followup to that paper, using basic SnCl2, and then it worked on both nitrostyrenes and nitropropenes.
(Official Hive Translator)
06-14-02 19:29
No 321288
Rhodium, i'm not sure if we're talking of the same articles, but in Post 70459 (yellium: "Syn. Comm 18(7), 693-697 (1988)", Novel Discourse) the aldoximes were made under neutral conditions, while w/sodium stannite only Ph-nitropropenes were successfully reduced. It's not like i'm picking at you
, just for the record.So, anyway....... It's definitely a great news to hear that the same method works on, seemingly, ANY phenylnitropropene - SWIM would absolutely prefer this proc to electrolytic iron in GAA [yuck].
Saved it on my HD right away.
Antoncho
(Chief Bee)
06-14-02 19:48
No 321293
You are correct, I mixed the papers up in my head (Dave, my mind's going!). Reading the actual papers, I now saw that sodium stannite reduced phenylnitropropenes, while tin(II)chloride reduced both them and nitrostyrenes.
But I don't remember which method Ritter had problems with (getting polymers when scaling up over 2g).
(Title on BackOrder)
06-15-02 01:20
No 321410
In reply to:
Is this the procedure from Varma & Kabalka's paper, which I wrote about in TSII?
Did you write articles for Srike? Or did you just slip up?
(Chief Bee)
06-15-02 04:15
No 321478
Page 164-181 in TSII is called "Rhodium's Chapter", and has a very flattering introduction by Strike (I don't think nearly as much about myself though):
This is a chapter written entirely by a chemist named Rhodium (with guest speaker Osmium!). Rhodium is, as far as Strike is concerned, the world's leading underground scientist. Knowledgeable in nearly every aspect of drug chemistry, this chemist has been the savior for many a person that was lost. Here he has contributed some new reactions for your reading pleasure. Radical stuff that you can bet will become the next wave of synthesis protocol. The rest of the chapter is Rhodium's voice.
The chapter contains the following:
1) ../rhodium /mdp2np.
2) ../rhodium /phenyla
3) The above sodium stannite and tin(II)chloride reductions of nitropropenes to oximes
4) Some oxime cleavage reactions, to form phenylacetones from the above oximes
5) ../rhodium /peroxot
6) A discussion of using various metal salts as catalysts for the NaBH4 reduction of nitrostyrenes
7) ../rhodium /mmda.me
Today I'm almost ashamed of some of the things I wrote, I wasn't nearly as knowledgeable in chemistry in 1998 as I am now, and can directly point out oversights here and there, there are even a few spelling and grammar errors in the texts!
(Newbee)
06-17-02 14:49
No 322410
(Rated as: excellent)
This has been a good weekend.
This is a very general procedure and it has so far worked with every single phenylnitropropene I´ve tried. The yields has been in the range of 85-92%. The lower yields are very likely a result of my impatience. Longer time for hydrolysis should have given higher yields.
100mmol of the phenylnitropropene
220mmol Tin(II)chloride dihydrate
200mmol HCl (as a calculated amount conc. aq HCl)
50ml toluene
200ml water
NaCl (solid)
Procedure:
Dissolve the tin(II)chloride in water mixed with the hydrochloric acid. Add the substrate to a rb flask and rinse it all down with the toluene. Now add the aqueous solution to the rb flask in one portion. With good stirring bring the mixture to a gentle reflux for 2 hours. Chill the flask to room temp and saturate the aqueous phase with NaCl, separate the two layers and transfer the top organic layer to a 1L flask containing 500ml water. Steam distill until no more oily drops comes over. This means between 500ml to 1,5L distillate is to be collected depending on the volatility of the ketone. When the steam distillation is over the distillate consits of two layers, one top layer of touene and the major part of the ketone. Separate the layers in a separatory funnel and extract the aqueous phase with 2x100ml toluene. Combine the toluene extracts, dry them with MgSO4 and remove the toluene in a rotovap. This leaves the ketone as a yellow oil ready for whatever you might have in mind for it.
The tin(II)chloride can be regenerated by electrolysis of the formed tin(IV)chloride.
(Hive Bee)
06-19-02 16:07
No 323065
When the hydrolysis (reflux) is over there is actually no need to separate the layers. Just stem distill it as it is. Toulene, ketone and water will pass over, not the tin compounds. One step less.
(Hive Bee)
06-20-02 16:51
No 323366
(Rated as: good read)
5g (19,8mmol) 1-(2,4,5-trimethoxyphenyl)-2-nitropropen
12,3g (55mmol) tin(II)chloride dihydrate
15ml conc. hydrochloric acid
20ml toluene
15ml water
100ml EtOAc
Tin(II)chloride was dissolved in 15ml water and 15ml conc hydrochloric acid and the resulting solution was added to a 200ml rb flask containing 20ml toluene and 5g substrate. The mixture was heated to 80 deg C on a water bath with good stirring for 1,5 hours. During this time the color changed from a deep yellow to dark orange and then to light yellow.
After 1,5 hours 200ml water was added and the toluene was removed by steam distillation. The now bright yellow aqueous phase containing dark yellow oily droplets was saturated with NaCl and extracted with 2x50ml EtOAc which removed all color. The ethyl acetate was washed once with 50ml saturated NaHCO3 solution, once with 50ml water, once with brine and then dried with MgSO4. The solvent was removed in a rotovap leaving 3,7g of a yellow oil which slowly partially solidified to something reminding of honey.
Yield; 3,7g (83,8%) 1-(2,4,5-trimethoxyphenyl)-2-propanone
(Chief Bee)
06-20-02 17:18
No 323373
What? The nitropropene from asarone stable in hydrochloric acid? Could you please recrystallize your product and verify the melting point of the supposed ketone? Asarylacetone should melt at:
mp(°C) Source
----------------------------------------
47-48 Gazz.Chim.Ital.; 36 I; 1906; 283
47-48 J.Chem.Soc.; 1937; 1338,1340
46-47 Helv.Chim.Acta; 47; 1964; 1996-2017
44-46 J.Med.Chem.; 23; 12; 1980; 1318-1323
(Hive Addict)
03-05-04 11:01
No 493114
I was a long time ago since I tested the procedure on Rh's page, and I am currently in the need of some phenyl-2-propanone analogues, I wanted to re-evaluate the applicability of the method.
Substances: 32.6 g 1-phenyl-2-nitropropene (recrystallized from toluene), 100 g tin(II) chloride dihydrate, water and hydrochloric acid.
I allowed hydrolysis of the ketoxime for ca 1.5 h at 85-90°C. The reaction mixture was steam distilled to yield a yellow oil. The distillate was extracted with DCM and the combined organic phases washed with water. It is claimed that this procedure yields a reasonably pure product. On this, a little bit of comment...
For the most amongst us, this oil indeed is pure enough. However, when washing the organic phase with aqueous NaOH instead of water, a discoloured aqueous phase is noticed. Some chromatography showed me that there was some benzyl alcohol present. Also, the "purified" oil contained some benzaldehyde (ca 5%). Depending on what the purposes are of the P2P, benzaldehydes are an interfering factor (reductive amination).
Advanced clitoris massage specialist. 32 years of experience. PM me for a "sample".
(Hive Bee)
03-06-04 20:34
No 493463
i apologize if this is reduntant, but here is a procedure using Fe/HCl to reduce 1-(o-Methoxyphenyl)-2-nitro-1-propene to o-methoxyphenylacetone.
http://www.orgsyn.org/orgsyn/prep.asp?pr
(Hive Bee)
04-22-04 14:40
No 502241
Hi Stratosphere!
The advantages of the above method (compared to iron/HCl) are:
a) magnetic stirring is made possible
b) yields are slightly higher
c) it avoids messy cleaning up afterwards (no red rust)
d) not sure 'bout that, but I think Fe/HCl needs 5 hours?
Sn/HCl only 2h...
e) iron salts cannot be "regenerated", the SnCl4-soln. from above rxn. is easily converted to SnCl2 again by
electrolysis...
There are other threads about Fe/HCl reductions, too - but I think Tin(2)chloride is the reducing agent of choice for making ketones (see a) to e))...
Greetz A
"..ein Trank von unterschiedlicher Farbe, in ihm ist Heilung für die Menschen."
(Hive Bee)
08-30-04 10:53
No 528289
To achieve less benzaldehyde contamination of final ketone, I suggest the following:
Suspend SnCl2 in EtOAc and stir to dissolve as much as possible, place in cooling bath. Dissolve nitropropene of choice in just enough EtOAc, and add that via addition funnel to the SnCl2 suspension at such a rate that the temp. doesn't exceed 30°C. When done, stir for 1 hour, then add H2O, and again stir for 1h (white oxime stannate precipitates). Remove the solvent using slight vacuum, then add HCl and reflux to hydrolyze the ketoxime to its ketone. Steam distill as usual.
(to be honest, I haven't tried this yet; but the thought behind it is to remove solvent before changing the oxime's structure - I believe the reason for the BA impurities is the presence of solvent other than water during hydrolysis. Experimental data will follow soon - promised...)
Greetz A
Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
(Heavyweight Chempion(eer))
08-30-04 15:16
No 528320
What is the reasoning behind the solvent-theory? Why would the solvent disturb the hydrolysis?
I do indeed encourage improvements and welcome any and all suggestions. I'm just curious.
Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!
(Hive Bee)
08-30-04 15:50
No 528325
The idea came to me when I thought about the hydrolysis being a reversible reaction, but the ketone (once it has formed) being rather stable towards further reduction (to benzaldehyde and nitroalkane), in contrast to the oxime.
And a substance being not in solution is not as reactive as a dissolved substance is, right? (I thought this was why solvents are used at all!)
Maybe the key lies just in keeping temp. low during nitrostyrene addition and using as little SnCl2 as possible (like 2.05 eq.) - but I have some strange feeling that the solvent plays an important role in the unwanted further reduction of oxime. Experiment will tell...
(unluckily I don't know any other possibility for removing benzylalcohol from product, besides shaking with dilute NaOH - I think this is the more annoying side product, and I don't know if a careful procedure will avoid its formation... - we'll see!
)Did I mention that despite aldehyde and OH impurities, your method still simply fuckin rocks, seen yield- and workwise?!!
Greetz A
Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
08-31-04 17:43
(Rated as: insignificant)
(Hive Bee)
08-31-04 18:14
No 528630
As stated above (the 11th post in this thread): no. Maybe you should read the whole thread?
Greetz A
Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
(Newbee)
09-22-04 04:46
No 532685
swim will try this with 115g SnCl in 150ml EtOAc and 40,75g p2np in EtOAc.
after addition of water and removal of the solvent:
WHAT IS THE RIGHT AMMOUNT OF HCL 36% ?
in the original post by barium 140ml conc. HCL was used, but in other threads the ammount was not exactly described.
Thx for help