Author Topic: Hofmann Rearrangement Yields  (Read 3630 times)

Tsjanga

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Re: Hofmann Rearrangement Yields
« Reply #220 on: April 07, 2013, 02:00:34 AM »
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
.

Honey for you my friend! Very very nice!

Sneak

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Re: Hofmann Rearrangement Yields
« Reply #221 on: April 07, 2013, 01:24:09 PM »
 :)
« Last Edit: April 07, 2013, 04:33:40 PM by Sneak »
If you really want to enjoy a pure, clean product the only way... is to make it yourself...

You miss 100% of the shots you don't take...

syn

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Re: Hofmann Rearrangement Yields
« Reply #222 on: April 29, 2013, 05:20:04 AM »
Just wanted to update from my other post. I performed the hofmann rearrangement using 8% walmart brand bleach. A solution of 120g NaOH, 2L of dH2O, and 1.2L of 8% NaClO were cooled to 2-3°C and 100g of amide was added. This was kept in an ice bath and shaken every so often for 48hrs. The reaction was then placed in hot water bath. The color went from greenish to orange to a brown/red. There appears to be a lot of unreacted amide on the bottom. I'll post yields if I get any but this appears to look like others reactions that didn't go so well. May just be something added to this particular brand of bleach that's not listed on the MSDS. If this doesn't pan out I'll be trying again with the 6% clorox. Will update.

syn

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Re: Hofmann Rearrangement Yields
« Reply #223 on: May 02, 2013, 03:41:18 AM »
Extracted with xylene yesterday. All extractions were pooled and wash with dilute NaOH/dH2O. The basic solution was drained off and small amounts of HCl added. A massive amount of pinkish crystals formed. Looks like it worked out just fine=)

syn

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Re: Hofmann Rearrangement Yields
« Reply #224 on: May 05, 2013, 01:44:23 AM »
The pink crystals were dried and I gave them an acetone anhydrous wash. They completely dissolved. Not sure what could have went wrong here :-[

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #225 on: May 05, 2013, 02:01:56 AM »
This reaction can be a real bastard. I cracked it for the second time a few months ago but I've gone off MDA since and I don't believe selling it would be a good idea so not much has happened since.

Do the TCCA hoffman. Its far better.

Hmm what else... oh yeah, when making the aldoxime, basify the hydroxylammonium salt first and then extract with ethanol. (free base hydroxylamine was way more soluble in ethanol or methanol? but poorly soluble in isopropyl? Maybe the other way round. But this part is crucial and I believe it is beneficial.) Basify hydroxyl, extract it into a alcohol and leave salts behind, then use that to make the aldoxime by just mixing with the right amount He. You'll know which one is better because it will form a nice pink liquor without any layers. And he oxime is yellow wax iirc. Try ethanol and isopropyl and see which one dissolves more hydroxyl.

The amide must be needle like crystals. I didnt realize this and kept getting a brown powder that I thought was amide but only yielded black ppt on hoffman reaction. Purification of the amide... well some say its worth trying to get a whitish one but w/e its a bit of a bastard and 1-2 purifications in xylene or water work fine. I prefer water because xylene is oily and smelly.

The beckmann should be pushed as hard as possible. Chuck it in the flask, chuck in some xylene (tolly works too but not as well.) chuck in the catalyst and chuck on the condenser then chuck it on the hotplate stirrer and hopefully u remembered to chuck in the stir bar then chuck it up on high and chuck some sossies on the barbi m8

This drug is highly overrated dam I wish I had some methylpheniidate
« Last Edit: May 07, 2013, 12:24:06 AM by uchiacon »

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #226 on: May 05, 2013, 02:03:10 AM »
Extracted with xylene yesterday. All extractions were pooled and wash with dilute NaOH/dH2O. The basic solution was drained off and small amounts of HCl added. A massive amount of pinkish crystals formed. Looks like it worked out just fine=)
lol probably your he oxime or hydroxyl amine

TCCA hoffman, bleach is only for the big boys
« Last Edit: May 07, 2013, 12:24:29 AM by uchiacon »

syn

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Re: Hofmann Rearrangement Yields
« Reply #227 on: May 05, 2013, 08:49:30 PM »
The amide I got was a brown powder, it looked like others photos I've seen after cleaning it. Considering a noticeable reaction occurred during the beckmann I'm thinking that the hofmann didn't occur. I know bleach works fine as others have reported they got good results. I will be doing this again using 6% name brand bleach as others have described and post results.

uchiacon

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Re: Hofmann Rearrangement Yields
« Reply #228 on: May 07, 2013, 12:25:46 AM »
The amide I got was a brown powder, it looked like others photos I've seen after cleaning it. Considering a noticeable reaction occurred during the beckmann I'm thinking that the hofmann didn't occur. I know bleach works fine as others have reported they got good results. I will be doing this again using 6% name brand bleach as others have described and post results.

Did it form needle like crystals upon recrystallization? They need to be needle like, not like a brown opaque powder. Purify it until you get needle like crystals or throw it out and get back to the drawing board.

needle crystals, not powder