Author Topic: Beckmann Rearrangement: From Oxime To Amide  (Read 690 times)

Twilight Mom

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Beckmann Rearrangement: From Oxime To Amide
« on: May 05, 2012, 08:47:28 PM »
Pictures 01 + 02
Time 0:00
Temp 10C
The following is added to a 5000ml flask:
1200g of Aldehyde Oxime
20g Nickel Acetate
2500ml of Toluene
500ml of Xylene
Heating mantle controller turned up to 50%
Water pump turned on for condenser

03
2:00
101C
Foil added to adapters
Controller turned down to 40% because of foaming

04
3:00
106C
Controller turned back up to 50%

05
4:00
108C
Foil added to flask

06
5:30
130C
Foil removed
Controller turned up to 100%

07
5:45
135C
Controller turned off
~2200ml of Non-Polar and ~300ml of Polar solvent have been distilled off, leaving ~800ml of NP solvent left in the reaction.

08
6:20
118C
Controller turned up to 100%

09
6:30
132C
Controller turned off
At this point a very exothermic reaction begins and the temperature climbs without added heat. The condensate running down the inside of the flask dissolves the Nickel Acetate stuck to the side of the flask and sizzles when it hits the solvent.

6:45
135C

7:45
118C
Controller turned up to 100%

10
8:30
137C
An additional ~400ml of Non-Polar solvent have been distilled of leaving ~400ml left in the reaction vessel.
Controller turned off

11
9:50
108C

12
10:00
Pour contents into a bucket of cold water
« Last Edit: May 05, 2012, 09:04:50 PM by Twilight Mom »

java

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #1 on: May 05, 2012, 09:45:59 PM »
.....did you find using toluene increased your yields , also why so much time , i would say 8 hours would be sufficient at 130?C but by you adding Toluene the temp of reflux will not go above the BP of toluene which is 110?C, hence you sort of defeated the purpose .....i will be suprised if your yields are the regular using only Xylene which averages 75-80 %.....also you have a lot of volume of solvent ....the reaction can be performed with equal  volume as qeight of oxime, i.e. 100gr of oxime and 100 ml of xylene.....java



¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

Twilight Mom

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #2 on: May 05, 2012, 09:55:59 PM »
Yea I noticed that the reaction didn't really start until the temperature gets between 125C-135C so the Toluene was pointless because it's bp is 110 and Xylene is closer to 130. Better off using equal amounts of Xylene like you said. Once the reaction kicks off though it's very noticeable, the fluid turns from dark green to dark brown.

I had 20L of Toluene that is why I wanted to use it, but the first time I tried it all ended up distilling off before the reaction happened, then once the reaction began the temp climbed to 170C and basically turned the product into a red/black oil that would not solidify.

The amide is still in the bucket of water so I haven't figured out the yield. I'm sure it's a lower yield though because like I said, almost all the toluene distills off before the oxime really reacts.
« Last Edit: May 05, 2012, 10:21:10 PM by Twilight Mom »

Enkidu

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #3 on: May 06, 2012, 02:36:49 AM »
almost all the toluene distills off before the oxime really reacts.
I can't find the reference, but this procedure is known to fail if toluene alone is used. It's unsurprising that the oxime doesn't react until the xylene's higher reflux temperature.

poisoninthestain

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #4 on: May 06, 2012, 05:24:16 PM »
I found it best to just use ~150-300ml xylene per ~96g/100ml aldoxime and scale up as you please. Gentle reflux for 7 hours, distill off 1/2 of xylene, allow to cool, buchner, wash with clean xylene til filtrate drips clear using minimal amounts clean xylene for wash. Yields as java stated are 70-80%. When recrystallized from water(hot filter upon cooling otherwise brown precip. noted) amide is needle-like off white shards. Very easy workup even if you play with it.

b6baddawg

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #5 on: May 08, 2012, 04:01:08 AM »
tried toluene with zinc nitrate as catalyst and got a bright orange goo  :-\
from the same batch of aldoxime used nickel acetate and xylene no problem
substituted the nickel acetate for zinc nitrate + xylene worked fine (had to adjust catalyst amounts from paper though )
going over 132c meant dirty amide and long workup for moi + lower yields so after twice bitten shied away from it.

ended up using a procedure something like
(cant remember solvent amount) but nickel acetate was added to xylene and refluxed at @ 110c for an hour or so.
the amide added in portions at that temperature, (oops mind fizzing) add slow enough to let it dissolve completely and temperature not drop below 100c.
reflux for @ 8 hours.
during this time temperatures are raised as bubbling slows during the reaction time and kept at 125-130c.
gotta watch this one cos temps seem too creep up.
filtered hot.
cooled, crystallised in freezer. filtered, washed. pearly white amide.
the post reaction solution if refroze sometimes dropped out unreacted aldoxime separately. if yield was down thats where it was, unreacted.
filter that out, left with dark red viscous oil once xylene stripped off.(if aldoxime was impure or temps above 132c this is probably brown-black tar i might be wrong, in my case that was the case)

total including aldoxime recovery and reuse, think it was 2786g amide from 3600g aldoxime (give or take a g or two)


java

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #6 on: May 08, 2012, 02:09:30 PM »

Reference Information


Cost efficient synthesis of amides from oximes with indium or zinc catalysts
C. Liana Allen, Céline Burel, Jonathan M.J. Williams
Tetrahedron Letters
Volume 51, Issue 20, 19 May 2010, Pages 2724–2726
http://dx.doi.org/10.1016/j.tetlet.2010.03.048,
http://www.sciencedirect.com/science/article/pii/S0040403910004697



Abstract[/b]
Simple indium and zinc salts have been successfully used as catalysts for the rearrangement of oximes into primary amides. The direct synthesis of nitriles or primary amides from aldehydes has also been demonstrated using these inexpensive catalysts.

In a recent industry-led survey, the need for catalytic atom efficient amide ... the reaction at reflux in lower boiling solvents resulted in lower conversions into the ... Entry, Catalyst (mol %), Solvent (temp [°C]), Conversiona (%) ...
« Last Edit: May 08, 2012, 02:11:45 PM by java »
¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

jon

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #7 on: May 08, 2012, 07:06:06 PM »
it has to get to 120-130 because i thing the intermediate has to be of syn orientation (i think) which is'nt it's thermodynamically favorable isomer

ZION1

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #8 on: May 09, 2012, 06:18:12 AM »
Copper-catalyzed rearrangement of
oximes into primary amides. Tetrahedron Letters, 52 (33), pp. 4252-4255.

The  atom ­efficient  and  cost ­effective  rearrangement
of  oximes  into  primary  amides  is  catalyzed  by  simple
copper salts.  The use of homogeneous Cu(OAc)2 was
found  to  be  effective  for  this  transformation  at  80C
using  1-­2  mol%  of  this  catalyst.  The  reaction  was
successful  with  either  conventional  or  microwave
heating.  CuO  and  CuO/ZnO  on  activated  carbon
provided  a  competent  reuseable  heterogeneous
catalyst which could be used  in a batch process or  in
flow.  Copper salts are much cheaper than the precious
metals previously used for this rearrangement, and the
reaction  conditions  are  milder  than  those  previously
reported.

Representative experimental procedure;
Benzaldehyde oxime (4) and Cu(OAc)2·H2O
(12.0 mg, 3 mol%) were dissolved in toluene
(0.5 mL) in an oven­dried Schlenk tube and
heated at 80C for 24 h.  After cooling, the
solvent was removed under vacuum and the
product isolated by column chromatography
(silica, EtOAc/hexane, 3:1) to give benzamide
(5) (298 mg, 82%) as a colourless solid.

GreenD

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #9 on: May 09, 2012, 04:46:33 PM »
Just a note ;

Benzaldehyde is not a goot representation of most oximes people want on this site.

There are some benzaldehyde oxime reactions that undergo favorable transformations in good yield, but do not transfer to alkyl oximes.

ZION1

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #10 on: May 11, 2012, 01:12:07 PM »
It may serve you well to actually read the paper and take note of the substrates that were experimented on before passing judgement.

RoidRage

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #11 on: May 11, 2012, 05:12:49 PM »
Here is the full paper:

Copper-catalyzed rearrangement of oximes into primary amides
Sumeet K. Sharmaa, Simon D. Bishoppa, C. Liana Allena, Ruth Lawrencea, Mark J. Bamfordb, Alexei A. Lapkinc, Pawel Plucinskid, Robert J. Watsonb, Jonathan M.J. Williams
Tetrahedron Letters, 52 (33), pp. 4252-4255
DOI: 10.1016/j.tetlet.2011.05.129

dingbow

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #12 on: May 24, 2012, 01:02:21 PM »
My first Beckmann was run with toluene only, refluxed for 5hrs and obtained a yield around 65%.

It does work :)

If you left the reaction stirring at room temperature for 24hrs, you would still get the colour change to a deep brown/black, but the conversion has not actually taken place.

syn

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #13 on: April 22, 2013, 05:00:45 PM »
So I'm have a real problem here :-[ I completed the oximation using 1 gallon of methanol, 2kg aldehyde, 2kg hydroxylamine hydrochloride, and made neutral using sodium bicarbonate. After 12hrs of stirring no aldoxime precipitated. I was left with a giant green blob and the bottom of the flask which is not unusual from what I've read. The consistency had changed to almost slime, viscous. I figured the reaction is a success. I washed it a few times with water and proceeded to the beckmann rearrangement.

I used 5% molar nickel acetate (to oxime) in a solvent volume 1ml per gram of the oxime, xylene was used. This was allowed to reflux for 10hrs. At no point did it turn brown as others have mentioned nor was a reaction noticeably taking place at heavy reflux. After 10hrs .4l of xylene was distilled off and the reaction mixture was aloud to cool. No precipitate evolved. I know the hydroxylamine is good as I used it to form the oxime of MDP-2-P without any issues. I know the helional is good as well as the boiling point was spot on and it formed the bisulphite adduct readily. Any insight anyone could give me would be greatly appreciated.

lugh

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #14 on: April 23, 2013, 11:48:48 PM »
You might want to consider purifying the xylene by fractional distillation using a packed column ;)  The end results from the effort applied  8)
Chemistry is our Covalent Bond

syn

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #15 on: April 28, 2013, 01:59:43 AM »
Thanks lugh but it was distilled before use. I realized the temperature wasn't going high enough, worked out alright.

Tsjanga

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One pot Aldehyde -> Amide
« Reply #16 on: May 19, 2013, 07:51:55 PM »
Hi all,

Have read some refs and patent about the route with copper sulfate pentahydrate, tried it and only made a gum like substance...

Now I read this: "1.1 equiv. NaOAc, 1.05 equiv. NH2OH.HCl, 1 equiv. aldehyde, 0,05 equiv. CuSO4.5H2O
Heat NaOAc and aldehyde to 110*C with stirring. Add catalyst, slowly add NH2OH over the course of an hour or so. Keep stirring for 5-6 hours, let it cool for a little while, then dissolve in ethyl acetate, toluene or xylene. Decant or filter to get rid of insolubles and let the product crystallize out."

Has anyone ever tried this method or is working on it? 

With kind regards,
 
Tsjanga






carl_nnabis

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #17 on: May 19, 2013, 10:11:09 PM »
There is a whole lot of one-pot reactions regarding the subject aldehyde to amide, Ive looked through some reactions and it seems the metal catalysed ones are a lot less desirable over all other ones, especially when it comes to one pot reactions, and even more when it comes to one-pot reactions involving oximation and beckmann rearrangement

In my opinion those reactions which form a nitrile first then get that oxidised with hydrogen peroxide to the amide without any metal catalyst are the most good looking reactions here!
Of course iodine is very expensive, youll need also very much and its watched in some parts of the world anyway, so this long known nitrile preparation from an aldehyde is not really viable for you, and I dont like the idea anyway someone is playing with huge amounts of inital explosives...

So have a look at the first attached file, its maybe of use for you because it works with cheap and easy to get reagents and the reaction scheme is the same there, and as youve asked for practical experience, i saw someone on sciencemadness has claimed even three years ago to see his amide precipitate after the reaction is done, but couldnt filter it IIRC. 
But has also not mentioned to throw it away or that he tried extracting it, and then theres only a hint known to me hat the wanted amide should dissolve in DCM and the second attached file states like some others have too, that it has a poor solubility in hot aromatic solvents/hot aqueous alcohols, and that diethyl ether doesnt at all.
 
What i mean is you cant use the procedure theyre using for work-up, you have tweak this to got it to work... maybe extraction with a hot aromatic, filter and cool or something... theyre subjecting their product to column chromatography, which would be indeed possible with cheap materials but anyway.
You have in any case if youre doing a one-pot beckmann rearrangement to check when doing it the first time how long it actually takes for the aldehyde, the oxime and amide-spot to show up on tlc-plates, to adapt this specific synthesis to your substrate

If you and your working area are suited to work with the smell/hood is good enough, then a pretty straight forward swern type oxidation with acetic anhydride on the bisulfite adduct of your aldehyde followed by quenching with an amine to give an amide comes to mind...
But you have to request it first, can find the paper here:
hxxp://www.sciencedirect.com/science/article/pii/S0040403900848935
Remember that Dimethylsulfide can and will remain your working area completely inhabitable, one would think several days or weeks for sure, maybe just hours idk and i dont want to find out  ;D
« Last Edit: May 19, 2013, 11:19:19 PM by carl_nnabis »
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syn

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #18 on: May 22, 2013, 02:46:41 AM »
Ok got around to running this again. This time I got semi-solid oxime after washing numerous times with dH2O. Tanish in color and wax like in consistency. The beckmann rearrangement was performed using 5% nickel acetate molar to oxime and 1.5ml xylene per gram of oxime. This time as soon as the temperature hit 130C the mixture turned brown/black and an exothermic reaction occurred although no foaming was noted like others have reported occurring. It was kept at reflux for 6 hours. 550ml of xylene was then distilled off and the remaining mixture was stuck in an ice bath. A large mass precipitated. There is a change to the crystal structure. Reflects light now and looks like it is composed of very small needles. Upon trying to breaking it up it all went back into solution. Hoping that's normal. I put it from the flask into a beaker in the ice bath so it will be easy to filter without breaking it up again.

myCH3

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Re: Beckmann Rearrangement: From Oxime To Amide
« Reply #19 on: May 22, 2013, 04:02:07 PM »
Here is the full paper:

Copper-catalyzed rearrangement of oximes into primary amides
Sumeet K. Sharmaa, Simon D. Bishoppa, C. Liana Allena, Ruth Lawrencea, Mark J. Bamfordb, Alexei A. Lapkinc, Pawel Plucinskid, Robert J. Watsonb, Jonathan M.J. Williams
Tetrahedron Letters, 52 (33), pp. 4252-4255
DOI: 10.1016/j.tetlet.2011.05.129

if one were to want to use this patent would it need to still be run at 120-130 C in xylene or could the parameters given 110 C in toluene be used?  Jon mentioned earlier that something makes the stereo chemistry better at the higher temperature range could any of you wiser bees give me a push in the right direction?