Sciencemadness Discussion Board

problems with ring-closing of n-carbamoyl-phenylethanolamin

karlos³ - 10-1-2011 at 03:43

At first, Hello everybody!
I have tried to synthesise the title compound, but not successfull. I have made the 2-amino-1-phenylethanol via the cold nitroaldol condensation with triethylamin as catalyst, and reduced it using zinc and formic acid. Then I took the harvested free base and titrated with hcl to a ph of 6,5, added potassium cyanat and refluxed 2hours. After this time the phenylethanolamin-urea precipitated on cooling, and was filtered and recrystallised.
To this point, everything went fine, but when i tried to form the oxazoline ring, something must have went wrong, because what was precipitated upon basifying has to be another compound, probably the correspondig amide, but i am not sure.
Ive tried to find it out via melting point but that compound was above 200°C so it is definitely not that what it should be.
Could it be because I used the cold method (-10°C) with a tertiary amine in 2 1/2hours, which gaves for the 2-nitro-1-phenylpropanol only erythro isomers?
I actually started after this disappointment a try using NaOH and t.he sodium salt of nitromethan in water, using the bisulfit addukt of the aldehyde, which gave again for the nitropropanol a configuration of both erythro and threo isomers, so i think it should also work for the nitroethanol.
Can somebody see what happened? In some document of Poos work i saw they were using thionylchloride and closed the oxazolinring of the chlorourea using boiling water.
But the same document also described how the ring was opened using acid or alkalihydroxide....
Maybe thats what happened, but I dont really know. English is obviously not my motherlanguage, so it could be that I understood something wrong or such thing.



[Edited on 11-1-2011 by karlos³]

Nicodem - 10-1-2011 at 11:41

We generally do not allow the discussion on the synthesis of end compounds having a black market value or the ones which are illegal in most of the word, though we do allow the discussion on anything as long as it is kept in a scientific discourse. So, if you want to discuss the synthesis of aminorex, edit your post properly so that it will be supported by references. You will also have to show that this discussion has any scientific value, which means discussing a scientific problem, not just problems with your synthesis. If you keep the thread as it is now, it will soon end in Detritus.

PS: 2-Amino-1-phenylethanol does not have any diastereoisomers. And nobody can find the reason of your failure if you don't provide the experimental and analyses. I would guess that is obvious enough.

karlos³ - 10-1-2011 at 12:23

Ok, then this thread is better deleted, as I did not know that discussion about compounds like this are unwanted here, I just saw a lot of thread to similiar substances and thought as long the language is kept scientific it is ok to discuss this one, sorry about that, please delete it.
I am not the person interested in the value of a substance, as I am rather a science-interested person which made his job to his hobby, as i am a chemical-technical assistant, thats how the job is called here.
i know about phenyl-2-nitroethanol not having diastereoisomers, there just 2 isomers, but I wanted to compare it to the nitropropanol, where this synthesis method is enantioselective, and i do not find the reference is used... my chemistry archive is so huge and chaotic, please excuse this^^

Nicodem - 10-1-2011 at 12:49

Quote: Originally posted by karlos³  
Ok, then this thread is better deleted, as I did not know that discussion about compounds like this are unwanted here, I just saw a lot of thread to similiar substances and thought as long the language is kept scientific it is ok to discuss this one, sorry about that, please delete it.

I did not say it is unwanted to discuss about illegal compounds. I said that such discussion is unwanted if it has no added scientific value. If you would have presented the problem you have properly using scientific discourse it would be tolerable. But scientific discourse means using references and discussing specific problems to be solved (for which you need to provide the minium information required, which you obviously did not bother with). For one thing, I do see a value in this are of heterocyclic chemistry and the cyclization of N-(2-hydroxyethyl)ureas certainly is an interesting enough topic. But let me use an example. If you would have used the basic scientific method of citing references, you would have realized that "I wanted to compare it to the nitropropanol, where this synthesis method is enantioselective" is wrong (the Henry reaction using Et3N or other achiral bases can only be diastereoselective, but never enantioselective). You would also realize that it does not matter how you make 2-amino-1-phenylethanol as long as you confirm its purity and identity, because this compound only has two enantiomers, no diastereoisomers, and the cyclization of its urea derivative is a symmetric transformation, hence independent of the used enantiomer or ratio of enantiomers. In short, using scientific discourse is useful to you as well as the reader of what you write, as it allows you to verify what you claim before you do so.

karlos³ - 10-1-2011 at 13:03

Ok, well thank you for this, I will give the corresponding references tomorrow, and do some correction as it is 10 pm in germany and i have to get up in seven hours.
good night


[Edited on 11-1-2011 by karlos³]

Attachment: Poos_2-amino-5-Aryl-2-oxazolines._Potent_New_Anorectic_Agents.pdf (833kB)
This file has been downloaded 544 times

jon - 20-1-2011 at 20:18

we don't know if you did'nt characterise the supposed R-ethanolamine
but a possibilty is that maybe you formed a biuret product.
this happens when the cyanate of an amine forms a trimer.
that would correspond with an off melting point.
the reason this happens is because in order to make the urea product the cyanic acid in aqueous solution has to be under a vigorous reflux ie. directly on the hotplate at a rolling boil so there is enough energy to form isocyanic acid which is what attacks the amine and forms the urea.

karlos³ - 14-6-2011 at 06:23

well, thank you jon this was really helpfull, i finally figured out according to your post how to make the oxazolinering right :)