Author Topic: Another easy route to P-2-P´s  (Read 5813 times)

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Barium

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Another easy route to P-2-P´s
« on: June 13, 2002, 02:09:00 PM »
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.    :)

Rhodium

  • Guest
Varma & Kabalka?
« Reply #1 on: June 13, 2002, 02:30:00 PM »
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?

Barium

  • Guest
It´s a variation of the Varma and Kabalka method, ...
« Reply #2 on: June 13, 2002, 03:08:00 PM »
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.

Barium

  • Guest
It just hit me
« Reply #3 on: June 13, 2002, 05:02:00 PM »
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? :(

Rhodium

  • Guest
I love them! Haven't you noticed that I have ...
« Reply #4 on: June 13, 2002, 05:14:00 PM »
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?

Barium

  • Guest
Ooops didn´t see that
« Reply #5 on: June 13, 2002, 05:37:00 PM »
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.

PrimoPyro

  • Guest
rest assured I like reading your posts as well, I ...
« Reply #6 on: June 13, 2002, 05:37:00 PM »
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.  :)

Barium

  • Guest
Thanks PP!!.. :-)
« Reply #7 on: June 13, 2002, 05:39:00 PM »
Thanks PP!!.. :)

Antoncho

  • Guest
Questions
« Reply #8 on: June 13, 2002, 06:47:00 PM »
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

Barium

  • Guest
This nitroalkene --> ketoxime --> ketone ...
« Reply #9 on: June 14, 2002, 04:34:00 PM »
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-nitropropene
115g (512mmol, 2,05 eq.) SnCl2x2H2O
150ml EtOAC
140ml conc HCl
500ml water

yield; 41,83g (235mmol, 94%) 1-(3,4-methylenedioxyphenyl)-2-propanone

Barium

  • Guest
Hi Antoncho! Varma and Kabalka said that SnCl 2 ...
« Reply #10 on: June 14, 2002, 04:50:00 PM »
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... :)

Rhodium

  • Guest
Varma & Kabalka made a followup to that paper, ...
« Reply #11 on: June 14, 2002, 05:27:00 PM »
Varma & Kabalka made a followup to that paper, using basic SnCl2, and then it worked on both nitrostyrenes and nitropropenes.

Antoncho

  • Guest
Actually,....
« Reply #12 on: June 14, 2002, 07:29:00 PM »
Rhodium, i'm not sure if we're talking of the same articles, but in

Post 70459 (missing)

(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 ;D , 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

Rhodium

  • Guest
You are correct, I mixed the papers up in my head ...
« Reply #13 on: June 14, 2002, 07:48:00 PM »
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).

goiterjoe

  • Guest
huh?
« Reply #14 on: June 15, 2002, 01:20:00 AM »
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?

Rhodium

  • Guest
"Rhodium's Chapter"
« Reply #15 on: June 15, 2002, 04:15:00 AM »
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)

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2np.html


2)

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#p2np

(the reaction using NaBH4/K2CO3/H2O2)
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)

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


6) A discussion of using various metal salts as catalysts for the NaBH4 reduction of nitrostyrenes
7)

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mmda.mescaline.html

(Which was written together with Osmium)

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!

Barium

  • Guest
Now it´s even easier
« Reply #16 on: June 17, 2002, 02:49:00 PM »
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.

Barium

  • Guest
Update
« Reply #17 on: June 19, 2002, 04:07:00 PM »
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. :)

Barium

  • Guest
1-(2,4,5-trimethoxyphenyl)-2-propanone
« Reply #18 on: June 20, 2002, 04:51:00 PM »
5g (19,8mmol) 1-(2,4,5-trimethoxyphenyl)-2-nitropropene
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

Rhodium

  • Guest
No polymers?
« Reply #19 on: June 20, 2002, 05:18:00 PM »
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
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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