Author Topic: Hofmann Rearrangement Yields  (Read 3631 times)

letters

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Re: Hofmann Rearrangement Yields
« Reply #20 on: August 05, 2011, 09:28:46 PM »
read the post above, and understand that you can not get good yields with fatty amides without a cosolvent! and yes, amides that have longish aliphatic chains and aromatic rings and what not can be considred fatty
« Last Edit: August 05, 2011, 09:32:15 PM by letters »

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #21 on: August 05, 2011, 09:33:33 PM »
At this point just plain yield would be great. Good yield can come later. I just want to see the expected result just one time. That's all I ask, one little time. I don't care if its 10 micrograms.
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Waggledance

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Re: Hofmann Rearrangement Yields
« Reply #22 on: August 05, 2011, 11:11:19 PM »
Your previous posts tend to suggest you are following the procedures of patent US7205440 by Wenzel et al. I would suggest that you follow this patent as closely as possible! Particularly example 6 on the table. However I can think of a much more suitable reagent to neutralize the OCl- ions that is readily available, in high concentrations, and reacts to form salt, water and oxygen. As a general rule it is more favorable to have as little unwanted species in solution as possible to reduce possible side reactions.

Learn as much as you can about equilibrium of chemical reactions and try and apply these principles to your reaction. I've seen letters mention it before, 80*C is too hot for the OCl- ion. Go find as many high conc NaOCl solutions as you can and try them all until you find one that works best beacuse generating it in the lab becomes tedious. If you do all of this then you should get a light orange to yellowy oil as jon described...don't drink it.

The carbamate can be fun but with the amide you are using you will find that the reaction involves a lot of experimentation and has very precise parameters, small deviations can fuck the whole thing. Not to mention that hydrolysis takes ages so unless you want your lab or house smelling like an asian takeaway shop for days I recommend you get a heating mantle.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #23 on: August 06, 2011, 02:40:14 AM »
I think the biggest problem here is me posting about a particular experiment of mine in a thread about a general reaction. It makes it seem as if I am asking a question here when in fact I am not. I am simply playing around with no real concern for any yield at this point. I would like to see my target compound, yes, but I am not concerned with yield at this point. I cannot read about things I am not doing and retain it. The only way I can retain knowledge is to put my hands on it and read about. jon has already scolded me numerous times and tried to help, but at the time I had no hands on experience, so as valuable as the advice may have been, it was hard for me to apply that advice without doing what I have already been doing which is blindly follow a procedure that someone else put together. Now that I've ran it twice on opposite ends of the spectrum I feel as if I have some baseline to measure from now. Now I can take jon's advice and the other advice found in this thread and in various papers on the subject and and actually apply them for the good of all mankind. I won't post anymore in this thread unless I somehow can contribute to improving the procedure for the substrate I believe we are discussing here.

In other words, my bad.
"Ego is a structure that is erected by a neurotic individual who is a member of a neurotic culture against the facts of the matter. And culture, which we put on like an overcoat, is the collectivized consensus about what sort of neurotic behaviors are acceptable."
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jon

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Re: Hofmann Rearrangement Yields
« Reply #24 on: August 06, 2011, 06:20:12 AM »
Quote
I've seen letters mention it before, 80*C is too hot for the OCl- ion.
yes that is true at that point in the reaction you have the n-chloramide and naoh so if your stoichiometry is spot on the OCl- ion is irrelavant at this point the need for this specific temperature is to cause the protonation of the chloramide and maintain the isocyanate in an equilibrium at such a rate it can undergo hydrolysis.
if it's too cool you get cyanates floating around which tend to polymerize to biurets.
too hot is no good either.

Enkidu

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Re: Hofmann Rearrangement Yields
« Reply #25 on: August 06, 2011, 06:38:54 AM »
Of course, I you do get those ureas, just hydrolize.

Waggledance

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Re: Hofmann Rearrangement Yields
« Reply #26 on: August 07, 2011, 12:25:54 AM »
Of course, I you do get those ureas, just hydrolize.

Only had time to have a quick look but how to you propose this? Could extract a bunch of urease from yeast and feed into a cooled, extracted reaction, now that would be cool.

Enkidu

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Re: Hofmann Rearrangement Yields
« Reply #27 on: August 07, 2011, 04:25:03 AM »
Base will work, and I'm assuming acid will too? Acid = soluble amine salt

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #28 on: August 07, 2011, 07:58:23 PM »
Looks like what I got when I tried (and failed) with OTC bleach.  Finally resorted to generating my own solution with much better results
Could you elaborate on this at all?
"Ego is a structure that is erected by a neurotic individual who is a member of a neurotic culture against the facts of the matter. And culture, which we put on like an overcoat, is the collectivized consensus about what sort of neurotic behaviors are acceptable."
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letters

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Re: Hofmann Rearrangement Yields
« Reply #29 on: August 09, 2011, 08:16:51 AM »
reDEEMed, if you read the refs ive attached, you will find examples of fresh preparations of NaOCl, by simply bubbling Cl2 gas into a cooled NaOH solution. there not much too it. you can generate the chlorine from many sources. gas obviously does not need to be dried, so its pretty straightforward.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #30 on: August 09, 2011, 01:04:14 PM »
Edit: I'm combining two posts in to one here and doing away with the first post.

The only reference I was able to find for free download was number one, Amines related to dimethyloxyphenethylamines. Even under the request thread here it doesn't seem anyone is asking for them. I use three tools for finding refs, maybe I'm not using the right ones. I use library.nu for full texts, toodoc and google for specific papers. On google I just search like "limitations of hoffman reaction filetype:pdf" I couldn't find any of them for free. I did find some interesting ones that I will read until I can get the ones you mentioned.

One of the pdf's I got ended up being gold for me. Probably way too basic for you guys, but for me it has really cleared up things about the actual mechanism. I now understand what the isocyanate is and where it fits in (something I wasn't getting before). I'm gonna chew on this for a while and I think I'll be ready to read on some specific strategies and actually understand it.

So, if anyone can get any of those refs letters mentioned, please grab and attach them, thanks!
« Last Edit: August 09, 2011, 02:24:30 PM by reDEEMed »
"Ego is a structure that is erected by a neurotic individual who is a member of a neurotic culture against the facts of the matter. And culture, which we put on like an overcoat, is the collectivized consensus about what sort of neurotic behaviors are acceptable."
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akcom

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Re: Hofmann Rearrangement Yields
« Reply #31 on: August 09, 2011, 05:28:28 PM »
March's Advanced Organic Chemistry is a good resource.  They have a lot of info on the Hoffman mechanism and should allow you to understand why you allow the chloroamine to form at low temperatures, then drip into hot base.  Sorry I didn't see the post earlier, but letters was correct.  Just bubble chlorine gas into NaOH.  Good ventilation is a must, outside if you can.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #32 on: August 10, 2011, 12:49:16 PM »
akom, I have that one. IIRC that's the text I could not stop reading, very well written and easy to follow.

Letters, which of those refs specifically would you recommend for someone in my position who would like to try this again? I don't want to throw all of those on the request thread, although I guess I could if it came down to it. I'm ready to try it again. I just need to plan an approach that I can pull off. I have been reading about bubbling Cl through the solution for a few days, the problem I see is how do I bubble .412gms of Cl for every gram of amide? How in the hell is this measured, I don't see that anywhere. Also, isn't bulk gas like that made via electrolysis? I don't have what I need to do that atm.
"Ego is a structure that is erected by a neurotic individual who is a member of a neurotic culture against the facts of the matter. And culture, which we put on like an overcoat, is the collectivized consensus about what sort of neurotic behaviors are acceptable."
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fries

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Re: Hofmann Rearrangement Yields
« Reply #33 on: August 10, 2011, 02:57:06 PM »
the hoffman rxn can't go without heat.

I've run 3 Hoffmans, about 10g amide each, 1 hot and 2 cold. I got roughly the same yield from each, about 1g.

I have a question though, the original post that we saw this reaction in recommends a ratio of 20g amide to 10g NaOH to 10.5g NaOCL, or a molar ratio of 1:2.6:1.4. Most of the literature I've read on using bleach for this seems to recommend a molar ratio of about 1:2:1.1.

Does anyone know which of these ratios gives better yield? Does anyone know why the OP that I'm talking about might have wanted to use so much excess bleach and base?

On a side note, that same post also recommends at least an order of magnitude TOO MUCH HCl to salt the resultant amine. Is this just to throw noobs off and get them to ruin their product? For a 20g amide batch, which would give say 5g amine, he recommends 100ml conc. HCl. That is sure to ruin your day!

antibody2

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Re: Hofmann Rearrangement Yields
« Reply #34 on: August 10, 2011, 04:05:28 PM »
how do I bubble .412gms of Cl for every gram of amide? How in the hell is this measured, I don't see that anywhere. Also, isn't bulk gas like that made via electrolysis? I don't have what I need to do that atm.

Try weighing your beaker of NaOH solution until it has gained enough weight after bubbling Cl2 through it. To generate Cl2, take a sidearm flask with household bleach in it and drip HCl into it. Do it outside on a windy day.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #35 on: August 10, 2011, 09:34:05 PM »
Ahhh, so the chlorine is bubbled in to prepare the solution. For some reason I was thinking this was done during the reaction. That makes things easier since I can set up outside, do my bubbling, then move shit indoors to finish after I prepare my chlorine solution.

Thanks, antibody2. That answers a couple questions I had.
"Ego is a structure that is erected by a neurotic individual who is a member of a neurotic culture against the facts of the matter. And culture, which we put on like an overcoat, is the collectivized consensus about what sort of neurotic behaviors are acceptable."
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akcom

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Re: Hofmann Rearrangement Yields
« Reply #36 on: August 11, 2011, 03:24:56 AM »
Formation of the o-methyl carbamate is affected by TCCA in methanol in good yields.  Obviously FMOC can be cleaved to yield the amine in acid.  Is acid catalyzed hydrolysis of the methyl carbamate an option?

edit: also, is anyone neutralizing their oxidant before performing the rearrangement?  residual oxidant seems like a real yield killer to me...

java

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Re: Hofmann Rearrangement Yields
« Reply #37 on: August 11, 2011, 04:00:05 AM »
Formation of the o-methyl carbamate is affected by TCCA in methanol in good yields.  Obviously FMOC can be cleaved to yield the amine in acid.  Is acid catalyzed hydrolysis of the methyl carbamate an option?

edit: also, is anyone neutralizing their oxidant before performing the rearrangement?  residual oxidant seems like a real yield killer to me...

.......no doubt, however a reference would be advice to your statement....java
« Last Edit: August 11, 2011, 04:04:11 AM 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!.......

akcom

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Re: Hofmann Rearrangement Yields
« Reply #38 on: August 11, 2011, 04:15:49 AM »
unfortunately I have no references for o-methyl carbamate hydrolysis yielding an amine, thats why I'm here.  PS does anyone else hate the new web based scifinder?

java

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Re: Hofmann Rearrangement Yields
« Reply #39 on: August 11, 2011, 04:37:17 AM »
...read this, it may provide a clue, ....java



Theoretical studies on the acid hydrolysis of methyl carbamate†
Ikchoon Lee, Chang Kon Kim,  Byung Choon Lee
Journal of Computational Chemistry
1987, Volume 8, Issue 6, pages 794–800
DOI: 10.1002/jcc.540080607





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