Author Topic: Hofmann Rearrangement Yields  (Read 3631 times)

akcom

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Re: Hofmann Rearrangement Yields
« Reply #40 on: August 11, 2011, 04:55:07 AM »
Thank you, I saw this paper but did not have access to the reference.  I've finally got a hang of the new scifinder, but the results are not impressive.  More digging is required.

edit:
The important part of that article was a reference.  I'd post it myself but its splattered with my ID.

Quote
The Hydrolysis  of  Amides,  Esters,  and  Related  Compounds  in  Acid  Solution.  Part 11. Carbamates
B y  V. C. Armstrong and  R .  B. Moodie
Journal of the Chemical Society (B, Physical Organic) 1969 pg 934
« Last Edit: August 11, 2011, 05:04:55 AM by akcom »

java

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Re: Hofmann Rearrangement Yields
« Reply #41 on: August 11, 2011, 05:14:09 AM »


Quote
The Hydrolysis  of  Amides,  Esters,  and  Related  Compounds  in  Acid  Solution.  Part 11. Carbamates
B y  V. C. Armstrong and  R .  B. Moodie
Journal of the Chemical Society (B, Physical Organic) 1969 pg 934
« Last Edit: August 11, 2011, 05:16:56 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 #42 on: August 11, 2011, 05:47:57 AM »
Quote
Allyl Cyanate-to-isocyanate Rearrangement for the Synthesis of Quaternary Stereocenter with Nitrogen Substituent
Yoshiyasu Ichikawa, Eiji Yamauchi, Minoru Isobe
Biosci. Biotechnol. Biochem. 2005, 69 (5) Pg 939-943

Last step is acid hydrolysis of an aliphatic methyl carbamate using 6N HCl.  Viola.  I need to TLC my aldehyde to make sure it hasn't degraded too much.  Hopefully I'll have some results here shortly.

edit: for those of you isolating your chloroamine
Quote
Properties of N-Chloroamines. At this point, it is important to state that all N-chloroamines are thermally unstable and can explode at elevated temperature. They can also react violently with amines, strong acids and bases, and easily oxidised organic material. N-Chlorosuccinimide has been reported to react violently with alcohols and benzylamine, 1,3-dichloro-5,5-dimethylhydantoin reacts violently with xylene, and trichloroisocyanuric acid has been reported to generate explosive nitrogen trichloride in concentrated acidic aqueous solution due to the attack of formed hypochlorous acid on the imine bond.
« Last Edit: August 11, 2011, 05:56:02 AM by akcom »

Waggledance

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Re: Hofmann Rearrangement Yields
« Reply #43 on: August 11, 2011, 07:09:00 AM »
Ever Tried TCCA in methanol? As far as I know you need completely anhydrous conditions or the reaction goes to shit and becomes rather violent! A lot of heat is evolved.

Edit: @Akcom, yea i think a few people on here are neutralizing, multiple mentions of bisulfite. Personally i would shy away from bisulfite as there are far more readily available chems that you can use, specifically there is one that reacts to form O2 and H2O, removing the addition of unnecessary reactants that could take part in side reactions..assuming NaOCl is being used!   
« Last Edit: August 11, 2011, 12:08:59 PM by Waggledance »

dingbow

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Re: Hofmann Rearrangement Yields
« Reply #44 on: August 11, 2011, 12:06:02 PM »
1. Amines Related to 2,5-Dimethoxyphenethylamine, Richard Baltzly, Johannes S. Buck, ,J. Am. Chem. Soc., 1940, 62 (1), pp 164–167, DOI: 10.1021/ja01858a047.
2. New Method for Direct Conversion of Amides to Amines. ,G. Marc Loudon et. al. J. Org. Chem., Vol. 44, No. 10, 1979, DOI: 0022-3263/79/1944-1746$01.00/0.
3. A Re-examination of Limitations of the Hofmann Reaction. Ernest Magnien, Richard Baltzly, J. Org. Chem., 1958, 23 (12), pp 2029–2032, DOI: 10.1021/jo01106a630.
4. Development of the Hofmann Rearrangement of Nr-Tosylasparagine through Calorimetric and NMR Analysis. Joseph S. Amato et. al., J. Org. Chem. 1998, 63, 9533-9534, 10.1021/jo980799l CCC: $15.00.
5. Nature of N-Bromosuccinimide in Basic Media: The True Oxidizing Species in the Hofmann Rearrangement. Chris H. Senanayake et. al., J. Am. Chem. SOC. 1994, 11 6, 7947-7948, 0002-7863/941/5 16-7947$04.50/0.
6. A Versatile Modification of the Hofmann Rearrangement. Radlick and Brown, Synthesis, 290-292, April, 1974.

Could anyone post these references up please? Especially number 2..

I have read that dioxane can be a good co-solvent, problem is its not very accessible to myself.

Redeemed, its not hard to get SOMETHING out of this reaction, if you follow the steps in my first post, you will get there.

Im thinking for my next run I will dissolve the amide in minimum amount EtOH and drip this into the basic NaOCl solution. What does everyone think?

I have tried 2 different bleach sources for those wondering, one was the 12% pool stuff and the other was 4.5% industrial cleaner sold at the local hardware store. They gave identical results.

Given that so much amide is coming out at the end of the reaction I assume the major problem here is generating the chloroamide.

fries

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Re: Hofmann Rearrangement Yields
« Reply #45 on: August 11, 2011, 12:40:26 PM »
Given that so much amide is coming out at the end of the reaction...

I guess that is the answer to my question about excess NaOCl and base.

Redeemed, are you taking into account that your base is possibly the mono-hydrate? If not, that could be a reason it doesnt work so well...

java

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Re: Hofmann Rearrangement Yields
« Reply #46 on: August 11, 2011, 01:12:11 PM »
1. Amines Related to 2,5-Dimethoxyphenethylamine, Richard Baltzly, Johannes S. Buck, ,J. Am. Chem. Soc., 1940, 62 (1), pp 164–167, DOI: 10.1021/ja01858a047.
2. New Method for Direct Conversion of Amides to Amines. ,G. Marc Loudon et. al. J. Org. Chem., Vol. 44, No. 10, 1979, DOI: 0022-3263/79/1944-1746$01.00/0.
3. A Re-examination of Limitations of the Hofmann Reaction. Ernest Magnien, Richard Baltzly, J. Org. Chem., 1958, 23 (12), pp 2029–2032, DOI: 10.1021/jo01106a630.
4. Development of the Hofmann Rearrangement of Nr-Tosylasparagine through Calorimetric and NMR Analysis. Joseph S. Amato et. al., J. Org. Chem. 1998, 63, 9533-9534, 10.1021/jo980799l CCC: $15.00.
5. Nature of N-Bromosuccinimide in Basic Media: The True Oxidizing Species in the Hofmann Rearrangement. Chris H. Senanayake et. al., J. Am. Chem. SOC. 1994, 11 6, 7947-7948, 0002-7863/941/5 16-7947$04.50/0.
6. A Versatile Modification of the Hofmann Rearrangement. Radlick and Brown, Synthesis, 290-292, April, 1974.

Could anyone post these references up please? Especially number 2..



.....there is a format and a place to request references.....java
« Last Edit: August 11, 2011, 01:13:45 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!.......

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #47 on: August 11, 2011, 01:26:46 PM »
Monohydrate; no, I have only been following directions on a piece of paper, something I loathe to fucking do.
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akcom

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Re: Hofmann Rearrangement Yields
« Reply #48 on: August 11, 2011, 01:37:45 PM »
Ever Tried TCCA in methanol? As far as I know you need completely anhydrous conditions or the reaction goes to shit and becomes rather violent! A lot of heat is evolved.
I flame dried my flask and used dry methanol.  Yields were quantitative.  I don't have anything in my notes about the reaction being particularly exothermic though?

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #49 on: August 11, 2011, 01:57:04 PM »
Regarding Cl generation- Can excess Cl not be scrubbed so this can be done indoors? I live in a apartment complex and my only outdoors is on the balcony by the pool. The smell would be noticed and the girls would probably notice that I was not as interested in their tits and wonder what I was doing.

It seems to me that Cl is such a promiscuous reactive little shit it shouldn't be that hard to scrub.

Btw, I had two people recommend that I read what March's said about the Hoffman but after searching last night and this morning as well as using the pdf search function there is no mention of this reaction. 

java, I have tried your cold method and some people who saw the pics said YES THATS IT!! Others say, nope you fail. So, I'm stuck as far as that goes and with under 100gms of amide left I'm not as keen on experimentation. These 80% yeilds I'm hearing about are what I want. Even if it means reading for another week and not getting a single flask dirty.
"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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reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #50 on: August 11, 2011, 02:04:38 PM »
Something that may be of some use.

Hauser,C;Renfrow,W
An Elementary Laboratory Experiment Involving the Hofmann Rearrangement. The Preparation of Methylamine Hydrochloride from Acetamide by means of Calcium Hypochlorite
J. Chem. Educ., 1937, Vol.14(11),  pp.542-543 DOI: 10.1021/ed014p542
Quote
The well-known Hoffman reaction by which an amide, in the presence of of chlorine or bromine and an alkali, is converted into a primary amine with one less carbon atom, is of considerable interest in organic chemistry. The reaction may be used in the "going down series", and it serves as a laboratory method for the preparation of a primary aliphatic amine. The reaction is of interest also because it involves a molecular rearrangement.

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« Last Edit: August 12, 2011, 09:54:24 PM by Enkidu »
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fries

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Re: Hofmann Rearrangement Yields
« Reply #51 on: August 11, 2011, 03:48:27 PM »
Monohydrate; no, I have only been following directions on a piece of paper, something I loathe to fucking do.

I'm not sure if that was a 'no, i dont have the monohydrate', but If you do have the monohydrate, then 1/3rd of the weight will be water. You will need to use 50% more by weight to get what you need. So 10g of NaOH anhydrate is +-15g of NaOH monohydrate.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #52 on: August 11, 2011, 03:54:14 PM »
I would assume that I do have the monohydrate. I'm going to try bromine I think.
"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 #53 on: August 11, 2011, 04:47:25 PM »
I would assume that I do have the monohydrate. I'm going to try bromine I think.

I'm talking about the NaOH, not the NaOCl...

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #54 on: August 12, 2011, 02:45:08 AM »
Okay, this isn't making sense. I've found a ton of good refs and am slowly clawing my way through them. The thing that keeps popping up is the phrase 'heat is required'. jon said this already to me several times, but lots of people report this reaction running to completion with no heat. Java, you are pretty much credited with pushing experimentation of this reaction towards cold. What's going on here? Many many people say the cold method not only works, but yields are very acceptable as well. Is it possible that the mechanism of this reaction is not fully understood or is it something about our substrate that makes it do what is supposed to be impossible? Reading through the examples on orgsyn under the entry for phenylethylamine it says that the Hoffman degradation has been performed successfully on hydrocinnamide. This is not our substrate, but it's kinda close. Wtf does it all mean!! AAArrggghhh!

Edit:  Essential reading found! The text is called 'Strategic Application of Named Reactions in Organic Chemistry'. Download it and hit the chapter on the Hoffman rearrangement.

http://ifile.it/qzc05h
« Last Edit: August 12, 2011, 04:54:08 AM by reDEEMed »
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Waggledance

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Re: Hofmann Rearrangement Yields
« Reply #55 on: August 12, 2011, 05:51:04 AM »
Ever Tried TCCA in methanol? As far as I know you need completely anhydrous conditions or the reaction goes to shit and becomes rather violent! A lot of heat is evolved.
I flame dried my flask and used dry methanol.  Yields were quantitative.  I don't have anything in my notes about the reaction being
particularly exothermic though?

Thats awesome man, I dried the methanol over molecular sieves and dried glass multiple times. Amide was dissolved in 200mL with heating, TCCA was added very slowly and after about half was added the reaction become extremely violent, lucky i used a 2L beaker otherwise it probably would have gone everywhere. I think the solution turned orange and smelt strongly of ammonia. My only explanation was that water had got in some how, maybe I didnt leave the methanol to dry for long enough....Didn't revisit it after that but may have to now.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #56 on: August 12, 2011, 05:26:01 PM »
Another interesting read. I think this is the route I'm gonna go. It just seems easier to me to hit each point along the way if possible rather than have all these reactions happening one after another in a single pot when I barely understand the mechanism.

====

Gene A. Hiegel, Tyrone J. Hogenauer, and Justin C. Lewis
Synthetic Communicationsw, 35: 2099–2105, 2005 DOI: 10.1081/SCC-200066703
Preparation of N-Chloroamides Using Trichloroisocyanuric Acid

Quote
Amides are efficiently converted to N-chloroamides by trichloroisocyanuric
acid in methanol.

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« Last Edit: August 12, 2011, 09:35:59 PM by Enkidu »
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Waggledance

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Re: Hofmann Rearrangement Yields
« Reply #57 on: August 12, 2011, 11:34:41 PM »

Gene A. Hiegel, Tyrone J. Hogenauer, and Justin C. Lewis
Synthetic Communicationsw, 35: 2099–2105, 2005 DOI: 10.1081/SCC-200066703
Preparation of N-Chloroamides Using Trichloroisocyanuric Acid

Quote
Amides are efficiently converted to N-chloroamides by trichloroisocyanuric
acid in methanol.

>>DOWNLOAD<<

Thats the paper me and akcom at talking about, i'm going to revisit it but just remember that you need completely anhydrous conditions. Molecular sieves are probably your best bet for drying the methanol. If its not anhydrous i've found that it can become very violent so be careful!

dingbow

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Re: Hofmann Rearrangement Yields
« Reply #58 on: August 13, 2011, 12:11:15 AM »
.....there is a format and a place to request references.....java
Apologies, will put it up on the other thread.

reDEEMed

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Re: Hofmann Rearrangement Yields
« Reply #59 on: August 13, 2011, 01:06:36 AM »
My apologies for posting a ref the wrong way and one that was already here, but I didn't see it.

Okay, the formation of my N-Chloramide is almost complete. Up until now I had planned to evaporate the methanol and dry the chloramide so I could get an exact yield. But, now I'm wondering if I can put the methanol/chloramide solution into my addition funnel and drip it into hot base.

What do you guys think?
"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."
— Terence McKenna