Author Topic: Hofmann Rearrangement Yields  (Read 3630 times)

Tsjanga

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Re: Hofmann Rearrangement Yields
« Reply #200 on: January 16, 2013, 10:41:38 AM »
Thanks, was looking back at dingbow his posts and I think the 5.6 gr of TCCA with 5 gr amide is making a bit of Chloro...
Will work on the reflux NaOH thingie ;-)

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #201 on: January 20, 2013, 07:40:47 AM »
This is infinitely strange. I'm trying to isolate the problem in my synthesis but in doing so I'm seemingly creating more.

Hydroxylamine sulfate: nitromethane/sulfuric acid, refluxed for 3 hours, crashed out with IPA.

Aldoxime: hydroxylamine sulfate freebased with NaOH and then small amounts of sodium carbonate, yielding a reddish/orange liquor. IPA alcohol is mixed into this at high stir, then the hot mix is placed into the fridge to cool. Three layers form, the clear/slightly yellow IPA layer, the red layer (of what I assume is hydroxylamine, can be slush like if I cool it too long) and a white bottom layer of salts. Alcohol and red layer decanted off leaving the salt layer behind. This salt layer is discarded. Helional mixed in to form a yellow/orange waxy aldoxime, different from the crystalline slightly green aldoxime I was getting before when I wasn't freebasing hydroxylamine before the reaction.

Pump has crapped out so I can't currently run a reflux for the beckmann, but when I do I will try toluene and a longer run time (this is what I did the first run with success) and then xylene.

I have tried to recrystallize the "amide" I had left over from a while back that was yielding the black ppt when run in the hofmann: 50g dissolved in 300ml of boiling water and run through a vacuum filter. 300ml of methanol added, causing the solution to turn snow white the second the methanol mixed in. I hope it hasn't reacted with the methanol? It's a super, super fine suspension of some very white material. I really hope its clean amide and not some reactant byproduct.

If there's any glaring errors in my description, please point them out. Thanks


java

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Re: Hofmann Rearrangement Yields
« Reply #202 on: January 20, 2013, 06:08:28 PM »
..........get some of the precipitated material, and a MP, it should be around 130+/- i have seen white amide .....it will be pure......java
¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #203 on: January 25, 2013, 10:03:00 AM »
Hey Guys,

I want to see if theres a way to skip the relatively messy aldehyde to amide steps we see in the commonly accepted method.
One of the two papers details a reaction that converts piperonal to methylenedioxybenzamide using copper sulfate 5hydrate as catalyst with hydroxylamine HCl and sodium acetate or carbonate to basify the hydroxylamine. Reaction is solventless, run at 110C for 2hrs.

With sodium acetate, it boasts a 98% yield of amide, with sodium carbonate coming in at 88%. Certainly seems very promising, especially since they use a methylenedioxy benzene compound for the tests.

I'll be looking into this. Does anyone see any glaringly obvious problems with this? I know it's going to be hard to purify my hydroxylamine, but that should be the only issue. I have the sulfate salt, so I'm thinking I'll basify and then titrate with HCl following by precipitation with alcohol and cooling(hopefully the sulfate ions won't cause an issue in the reaction?). Will use methanol so any residual will evaporate off during the reaction.

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #204 on: January 27, 2013, 01:03:13 PM »
I've run this twice now. However, I tend to suffer from excitement so I have unfortunately muddled up the first two runs. I used sodium carbonate instead of sodium acetate.

My hydroxylammonium sulfate is undoubtedly contaminated with sulfuric acid and formic acid which is a real f*cking pain because I can't get rid of those contaminants easily with the solubility of the material itself in polar liquids. Maybe basifying before the reaction, then titrating with HCl or sulfuric acid until I get the salt and crash that out with IPA?

The first run I forgot to scale down the amount of copper sulfate catalyst I was using. I scaled down the reaction to 1/10 but I forgot to apply this to the catalyst molar amounts. 5mol % was the amount required, and from what I've read, thats simply :

x/3.1 = 0.05 , x being 0.155 mol of copper sulfate, then multiplied by 0.1.
19.2g aldehyde : 3.87g copper sulfate, etc etc. Please correct me if I'm wrong there...

First run was just a total messup. It was so strange, putting 38.7g copper sulfate into a beaker with about 40g of other reactants. How did they stir this, I thought. Yielded 8g of brown ppt from 19.2g aldehyde, but it didnt work in a hofmann. :(

Second run was better, but again I made an error by adding about 17g of sodium carbonate monohydrate(pool supply soda ash) instead of 13.6g. Reaction is going fine, transition from foaming blue with white particulate (carbonate) to green to terracotta brown.

1hr in, half way through, 100C, i started smelling ammonia. I didn't know that sodium carbonate could facilitate the hydrolysis of amides??

Dumped in toluene, filtered. Left with a terracotta filter cake with white grains in it, which when washed with water pretty much disappeared. Kept the toluene, discarded the water. Will evaporate off the toluene, see if any amide was in that. Its got a dark red/brown colour to it. Similar to the colour I was getting in my beckmann rearrangement with the xylene. I hope the perfumer's helional hasnt gone off in a few months..

This reaction is a bit of prick, but it would be so awesome if I could get it to work, even at 50% yield.

Tsjanga

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Re: Hofmann Rearrangement Yields
« Reply #205 on: January 30, 2013, 03:30:25 PM »
Hey Guys,

I want to see if theres a way to skip the relatively messy aldehyde to amide steps we see in the commonly accepted method.
One of the two papers details a reaction that converts piperonal to methylenedioxybenzamide using copper sulfate 5hydrate as catalyst with hydroxylamine HCl and sodium acetate or carbonate to basify the hydroxylamine. Reaction is solventless, run at 110C for 2hrs.

With sodium acetate, it boasts a 98% yield of amide, with sodium carbonate coming in at 88%. Certainly seems very promising, especially since they use a methylenedioxy benzene compound for the tests.

Will have a look into this when I have some free time!
Great work!

Tsjanga

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Re: Hofmann Rearrangement Yields
« Reply #206 on: February 03, 2013, 04:06:34 PM »
Hey Guys,

I want to see if theres a way to skip the relatively messy aldehyde to amide steps we see in the commonly accepted method.
One of the two papers details a reaction that converts piperonal to methylenedioxybenzamide using copper sulfate 5hydrate as catalyst with hydroxylamine HCl and sodium acetate or carbonate to basify the hydroxylamine. Reaction is solventless, run at 110C for 2hrs.

With sodium acetate, it boasts a 98% yield of amide, with sodium carbonate coming in at 88%. Certainly seems very promising, especially since they use a methylenedioxy benzene compound for the tests.

Will have a look into this when I have some free time!
Great work!

Have tried it, just getting some goo.
Have to get some work on it to tweak it.

b6baddawg

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Re: Hofmann Rearrangement Yields
« Reply #207 on: February 07, 2013, 08:25:23 PM »
theres a 'one pot' to the amide using zinc nitrate hexahydrate. i dont have the paper but its worth reading that if it can be found if someones wanting to tweak the copper sulfate.
« Last Edit: February 08, 2013, 05:50:20 AM by b6baddawg »

newbiechem

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Re: Hofmann Rearrangement Yields
« Reply #208 on: February 28, 2013, 04:16:02 PM »
after running the hoffman cold, everythinkg seemed right, extracted with xylene, but when hit the xylene with dilute 5%hcl , the water layer got very very dark redish color, ph4-5, what is wrong???? tryed A/B and doesnt work still give me black extractions..... reaction maybe didnt took place?
looking for a acid extraction like fries did on page 5, on the last pictures.....
is that the extraction as it is, or he did a A/B before got that yellowish?

i got my 30ml acid dark extraction,washed with xylene...... added a bit 5%naoh to ph8-9, the extracted with xylene...but that gave me also dark extraction....
should i add more water to my 30ml acid extraction? and then perfom the A/B wash?


any thoughts?

sry bout my english

Tsjanga

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Re: Hofmann Rearrangement Yields
« Reply #209 on: March 04, 2013, 01:49:24 PM »
theres a 'one pot' to the amide using zinc nitrate hexahydrate. i dont have the paper but its worth reading that if it can be found if someones wanting to tweak the copper sulfate.

Can you give us a hint?

Assyl Fartrate

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Re: Hofmann Rearrangement Yields
« Reply #210 on: March 04, 2013, 02:13:41 PM »
theres a 'one pot' to the amide using zinc nitrate hexahydrate. i dont have the paper but its worth reading that if it can be found if someones wanting to tweak the copper sulfate.

Do you remember any of the specific examples used in the paper? As in, was the conversion of piperonal, helional, or anything similar performed?

Any recollection of what journal it's in and/or what time period?
Someone Who Is Me

newbiechem

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Re: Hofmann Rearrangement Yields
« Reply #211 on: March 05, 2013, 04:04:26 AM »
i DOT NOT KNOW IF THIS IS CLOSE TO WHAT YA LOOKING FOR!!!!!

http://ntur.lib.ntu.edu.tw/bitstream/246246/171046/1/105.pdf

hope it is, and if its not, sorry! i tryed hehehe

peace

Assyl Fartrate

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Re: Hofmann Rearrangement Yields
« Reply #212 on: March 05, 2013, 04:42:34 AM »
It's a different publication - no zinc nitrate hexahydrate - but that looks useful, nonetheless. Given the examples, it seems likely it would be viable with helional, and would provide good yields, too.

This was a good find, thanks for sharing. Given the possibility of nitrile synthesis as well, it could be synthetically useful for the clandestine chemist far beyond this topic alone.
Someone Who Is Me

akcom

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Re: Hofmann Rearrangement Yields
« Reply #213 on: March 06, 2013, 03:00:07 AM »
There are a number of one pot reactions, they all seem to do the trick

newbiechem

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Re: Hofmann Rearrangement Yields
« Reply #214 on: March 08, 2013, 05:20:52 PM »
would any bee with experience at this reaction wanna help out pleaseeee?!?!?!?!

here.....

50gr sparkly white amide
590ml bleach 6%
25gr Naoh in 500ml water

everything was cooled to around 2c, then mixed together....amide...bleach then Naoh solution....
shaked well and put it back in freezer....
shaked for 4 hours every 15 minutes....
let stay in frezzer for 24 hours
take it out, let it rise to room temp....
after 24 hours out the frezer, extracted with 3x times with xylene....300ml...200ml...100ml
combine extractions which were very very dark, washed with h2o
NOW i then add 5%hcl slowly.....
10ml...ph-7
20ml ph-6
24ml ph-1-2

extraction separted and very dark color, redish.

wash with xylene, let it dry to get a very readish goey thinkg that dont really dries.....


well....
the amide is recristilized snow white....
the solution stays the same colors all the way in the frezzer and around 12 hours out the frezzer, then starts to get darker
first light brown 14hr
then the solution starts to get brownish 16hr...  the amide seems to be turning to oil, first light brown oil
after maybe 20 hours the solution is a dark redish orange thing.....
lots of black brown oil all over the solution, sticks to the walls of the botle....
when rising to room temp. always gave it a shake once in a while....

the extractions came out very dark (expected from other experience),
when i add the HCL it seems that tar start to form and get all over the sep.funil.

the whole reaction acts just like stated by other member, colors etc....

could be my work up thats flawless? tryed doing A/B on the dark hcl extraction but colors stays the same...

if im using around 25ml hcl to get a acid extraction from toluene doesnt that means that i have my amine?? i though so, then i let it dry whithoud A/B to see if any crystals would come out, dirty or not, and all i get is that red goey thinkg that dont really crystalizes....

when extracting with the hcl, when ph is around 5-6 the colors is actually a lil bit lighter and creamier, more orange than red....

you guys think the amine is being formed? the work up its screwing up?  maybe take hcl extraction out when still ph of5-6 instead of ph-2?

if anyone have any idea please share!!!

ps: the room temp where i leve is acctually warmwer than more bees, around 30-32 degrees, but thats something that i believe favor the hoffman instead screwing...

well please if any thoughts.....
peace



dingbow

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Re: Hofmann Rearrangement Yields
« Reply #215 on: March 11, 2013, 04:39:41 AM »
TCCA run:
5g amide
equimolar TCCA (note I rinse my TCCA before use to get rid of some additives in this commercial product, which apparently can cause some hydrolysis to DCCA)
400ml H2o
5g NaOH

Using a lot of ice, 1L of h2o is cooled to approx 5c. 400ml is separated, NaOH added, then placed in RB. The remaining ice water is used in an ice bath, with the ice replenished as required (ice bath never went over 8c). TCCA is added and stirred vigorously until it is completely dissolved. Amide is added in one go, stirred until almost completely reacted/dissolved. The solution is now fairly clear. The ice bath is replaced with boiling water from a kettle and the hotplate is set to high, bringing the temp up to 75c as quickly as possible and holding it. Once the reaction reaches 70c, it was maintained for 20 minutes. Extracted with non polar whilst still hot. Yielded 3g impure amine.HCl, ~69% molar yield.

Reaction ran VERY clean, only a tiny amount of undissolved solids were seen and it was a dark golden colour. No A/B was required before gassing, though the HCl will need to be recrystalised for sure. End to end time taken including non polar extraction: 2.5hrs.

Im sure I would have gotten a bit more HCl if I had re-gassed the non polar again, as it was completely saturated on the first run, but didnt have the time to do it. The 18c reaction temperature I previously mentioned doesnt seem to give consistent results, as it failed on one run.

The above parameters have been repeated and gave consistent outcomes on two runs.

EDIT: equimolar amounts of TCCA is a bit confusing, its actually equimolar divide by 3. If using DCCA it would be equimolar divide by 2.
« Last Edit: March 11, 2013, 05:11:03 AM by dingbow »

newbiechem

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Re: Hofmann Rearrangement Yields
« Reply #216 on: March 11, 2013, 05:47:46 AM »
hehehe nice!

dingbow yield look awesome!!! so doesnt need a co-solvent after all?!?! ???

have you ran this parameter with more amide? like the other that took 25gr amide?

also, is the xylene extraction coming out very dark? like when ran with bleach?(fries pictures)

wanna give this a try, since the cold bleach hasnt shown much love yet hehehe

peace

newbiechem

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Re: Hofmann Rearrangement Yields
« Reply #217 on: March 12, 2013, 03:30:36 PM »
done EXACTLY as ding....
yiels of 10% on 10gr amide.....

ding you said 5gr naoh..... dont you mean 5% naoh solution?
will give that a shot


dingbow

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Re: Hofmann Rearrangement Yields
« Reply #218 on: March 17, 2013, 12:52:19 PM »
Nope, 5g NaOH/400ml H2O
~0.3M

Extract varies from golden amber to red. No tar. Is your amide clean? Clean TCCA?

b6baddawg

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Re: Hofmann Rearrangement Yields
« Reply #219 on: April 06, 2013, 04:35:17 PM »
assyl, tsjanga apoligies for the late reply. I cannot get access to the paper. its title is Tetrahedron Letters 51 (2010) 2724–2726. "Cost efficient synthesis of amides from oximes with indium or zinc catalysts".
 
In the paper theres a section with a modification,    15mol% zinc nitrate, 2 mol hydroxylamine, 2 mol sodium bicarbonate, 1L toluene, 1mol aldehyde. reflux 16 hours, then cool and filter to get good yields of the amide in 1 shot (80% is common).

It may -or not- be better to reduce the zinc load to 12% it could be even less. i dont recall for sure whether it was this specific reaction what benefited. id sub toluene for xylene too.

I tried toluene in the oxime>amide procedure using zinc nitrate and got orange goo. With xylene i got the amide.
Also using the general procedure in the oxime>amide using the catalyst load suggested by the paper the amide was a sandy colour. reducing the catalyst load a few % helped and white amide was obtained but it may have extended reaction time by an hour or so.

My results take with a pinch of salt, theyre from memory not notes and id hate to mislead anyone.  The procedure and mods was suggested by someone else who preferred the one step aldehyde>amide.
I personally preferred the two step and went back to it for i could get 105% to the oxime mp @54c and 70-75% in the beckman to the amide, mp @115-118c without any bother or effort.  I figured by the time i was consistantly maxing yields id never make up the amount lost from exploring and fine tuning the parameters. But thats just me, not the brightest spark.
Hopefully the reply was worth the wait, sorry about dangling a carrot on a stick.

EDITED to add a few replies to other questions.
The helionnal kept air free cool in the dark lasted a few years until used. Once opened i heard after several months the MP of the formed oxime was depressed slightly to usual, fresh heli as starting material.
The oxime and amide kept well over a year in the freezer until used without noticeable detioration
.
« Last Edit: April 06, 2013, 05:17:01 PM by b6baddawg »