Sciencemadness Discussion Board

Oxidation of phenethylamine to (2-nitroethyl)benzene

Quantum_Dom - 7-7-2008 at 10:37

Hi everyone !

I am interested in oxidizing phenethylamine to it's corresponding nitro compound (see scheme below). So far, I have found a few references [1-4] but unfornutaly have not yet been able to read them as I can't have access to them. They basically involve the use of oxone or peroxyacids. But I think the work in these references is done on primary amines attached to tertiary carbons or aromatic primary amines. My questions are:

1- Do anybody have expericence in the oxidation of primary aliphatic amines similar as the one illustrated in the scheme?

2- If so, what are the standard reaction parameters for such a procedure ?

Any heads up would be greatly appreciated. Thank you !

QD


[img] http://img120.imageshack.us/img120/7424/96247630eo4.png[/img]



[1] J. Am. Chem. Soc., 1957, 79, 5528
[2] J. Org. Chem., 1979, 44, 659
[3] Tetrahedron Lett., 1995, 36, 2377
[4]Tetrahedron Letters,Vol.27,No.21,pp 2335-2336,1986





[Edited on 7-7-2008 by Quantum_Dom]

stoichiometric_steve - 7-7-2008 at 10:43

the oxidation that you have in mind is impossible to achieve with primary aliphatic amines on primary carbons.

edit: you could have found that out by using the FORUM SEARCH

[Edited on 7-7-2008 by stoichiometric_steve]

Quantum_Dom - 7-7-2008 at 10:45

Thanks for the reply, I did use the search engine.

Could you please link me to the thread of interest in this case ?

BTW stoichiometric_steve : "All classes of primary amine (including primary, secondary and tertiary alkyl as well as aryl) are oxidized to nitro compounds in high yields with dimethyl dioxirane [1]"- MArch's Advanced Organic Chemistry, 5 th edition, page 1540


[1] J. Org. Chem, 1989, 54, 5783
Tetrahedron Lett., 1988, 29, 4501

Also worth of looking:
http://books.google.ca/books?id=63jyyMt38-EC&pg=PA20&lpg=PA20&dq=Oxidation+of+Primary+Amines+by+Dimethyldioxirane'&source=web&ots= skQknwtbyb&sig=rFuCt7Z84jlIO0XO2ps3d8X14tU&hl=en&sa=X&oi=book_result&resnum=2&ct=result#PPA20,M1

If I were you, I would be really careful in the future before claiming that something is impossible without proper verification.





[Edited on 7-7-2008 by Quantum_Dom]

Ritter - 7-7-2008 at 12:42

Quote:
Originally posted by Quantum_Dom
Hi everyone !

I am interested in oxidizing phenethylamine to it's corresponding nitro compound (see scheme below).


The compound you have drawn is (according to the hybrid Structure > Name nomenclature tool in ChemDraw) is (2-nitroethyl)benzene, not phenylnitropropane.

Quantum_Dom - 7-7-2008 at 12:47

Thank you, I will edit the post accordingly right away.

MagicJigPipe - 7-7-2008 at 14:47

Phenylnitroethane (or 1-phenyl-2-nitroethane) would also be technically correct. The latter would be the more accurate of the two since I suppose there could be a nitro group on the 1 carbon.

In fact, I'm almost certain the IUPAC name would be the latter (1-phenyl-2-nitroethane).

I've found that learning how to do nomenclature without help of computers/programs tends to give better results.

[Edited on 7-7-2008 by MagicJigPipe]

Ritter - 7-7-2008 at 15:15

Quote:
Originally posted by MagicJigPipe
Phenylnitroethane (or 1-phenyl-2-nitroethane) would also be technically correct. The latter would be the more accurate of the two since I suppose there could be a nitro group on the 1 carbon.

In fact, I'm almost certain the IUPAC name would be the latter (1-phenyl-2-nitroethane).

I've found that learning how to do nomenclature without help of computers/programs tends to give better results.

[Edited on 7-7-2008 by MagicJigPipe]


And I've found that using a computer program to generate names helps avoid this sort of 'just how many ways can I name that compound?'-type discussion. We all know that there are a number of (correct) ways to name the same compound. The point is to be unequivocal so that everyone knows what we're talking about.

[Edited on 7-7-2008 by Ritter]

ScienceSquirrel - 7-7-2008 at 15:49

Let me think;

1) Decarboxylate phenylalanine to phenylethylamine

2) Oxidise it to phenylnitroethane

3) React it with two moles of n-BuLi to make the dianion

4) Alkylate with MeI

5) Reduce to amphetamine

6) Beam me up Scotty! :cool:

Quantum_Dom - 7-7-2008 at 16:21

Quote:
Originally posted by ScienceSquirrel
Let me think;

1) Decarboxylate phenylalanine to phenylethylamine

2) Oxidise it to phenylnitroethane

3) React it with two moles of n-BuLi to make the dianion

4) Alkylate with MeI

5) Reduce to amphetamine

6) Beam me up Scotty! :cool:


FYI, phenethylamine is widely availlable commercialy. You should also know that nitro compound reatcs with carbonyl compound to yield nitrolalkenes through a nitro-aldol condensation. (See link provided below).

1) Oxidize phenethylamine to phenylnitroethane
2) Condense phenylnitroethane with formaldehyde to 3-phenyl-2-nitroprop-1-ene.
3) Hydrogenation to amphetamine.
4) Yawwwnnn....Scotty you still trying to make methyl iodide OTC ?
5)....
6)Cheers

:P

http://img297.imageshack.us/img297/975/proposalag1.png





[Edited on 7-7-2008 by Quantum_Dom]

ScienceSquirrel - 7-7-2008 at 16:29

Quote:
Originally posted by Quantum_Dom
Quote:
Originally posted by ScienceSquirrel
Let me think;

1) Decarboxylate phenylalanine to phenylethylamine

2) Oxidise it to phenylnitroethane

3) React it with two moles of n-BuLi to make the dianion

4) Alkylate with MeI

5) Reduce to amphetamine

6) Beam me up Scotty! :cool:


FYI, phenethylamine is widely availlable commercialy. You should also know that nitro compound reatcs with cabonyl compound to yield nitrolalkenes through a nitro-aldol condensation. (See link provided below).

1) Oxidize phenethylamine to phenylnitroethane
2) Condense phenylnitroethane with formaldehyde to 3-phenyl-2-nitroprop-1-ene.
3) Hydrogenation to amphetamine.
4) Yawwwnnn....Scotty you still trying to make methyl iodide OTC ?
5)....
6)Cheers

:P

http://img297.imageshack.us/img297/975/proposalag1.png

[Edited on 7-7-2008 by Quantum_Dom]

[Edited on 7-7-2008 by Quantum_Dom]


You really have to work on your spelling!
Let me see now, carbonyl starts with curly C not kicking K.

Quantum_Dom - 7-7-2008 at 16:34

Quote:
Originally posted by ScienceSquirrel

You really have to work on your spelling!
Let me see now, carbonyl starts with curly C not kicking K.


Thanks for you advice! :cool: .

ScienceSquirrel - 7-7-2008 at 16:55

Touche!

:cool:

ScienceSquirrel - 7-7-2008 at 17:38

By the way, do you spell 'the' as T H E or have you adopted the modern American spelling T E H?

Quantum_Dom - 7-7-2008 at 17:47

1- I am not an american nor do I intend to adopt the spelling.

2-If you are trying to hurt my feelings by correcting my grammar or spelling, you are wasting your time. You should invest it in learning basic organic chemistry of the nitro functional group. You are not in the right forum if your only arguments are linguistics-related.

ScienceSquirrel - 7-7-2008 at 17:57

Righto, I am sure that everyone is going to pile in with lots of advice on making amphetamine :P

Quantum_Dom - 7-7-2008 at 18:03

Quote:
Originally posted by ScienceSquirrel
Righto, I am sure that everyone is going to pile in with lots of advice on making amphetamine :P


This thread was never intented to brought the subject of amphetamine. Read the title of the thread.

You brought the subject, trying to make a cynical attempt at "revealing" my intentions, by providing an overlong and tedious reactional scheme. It failed and it came right back at you. I am sorry about it but don't take it personal, it happens sometimes.

[Edited on 7-7-2008 by Quantum_Dom]

Nicodem - 8-7-2008 at 03:52

Contrary to what March’s lead you to believe on the subject of R-NH2 => R-NO2, the oxidation works nice only for amines where R is aryl or a tertiary alkyl (like t-butyl and such). There are few references where R was a primary alkyl (like in your example), but the yields were either mediocre or only exceptional substrates worked.

PS: I don’t want to see anymore off topic replies. If anyone wants to discuss the synthesis of amphetamine or grammar please do so in appropriate forums other than SM.

Quantum_Dom - 8-7-2008 at 07:40

Hmmm I see nicodem, any references I should have a look to ?

Many thanks for your comment. Shame that such an authority like March can mislead people like that.

ScienceSquirrel - 8-7-2008 at 09:06

Your best option would be a full search using Chemical Abstracts.
You do face the disadvantage that you are going 'against the grain'.
Generally aliphatic amines are the target molecule as they are useful either as end products in themselves or as intermediates while nitro compounds tend to be starting materials so chemists tend to focus on that reaction.
Developing reactions that will be used in other peoples work is good as your paper will be be cited again and again, developing a reaction that is never used will doom you to an academic career teaching at Doo Hickey State College. :P

Quantum_Dom - 8-7-2008 at 09:19

Fair enough, will have a look at the abstracts, will post any information that I find (if there is any) worth of mentionning.

I have always liked working in some scientific direction that nobody else is working in.
--Linus Pauling (a great teacher and chemistry Nobel prize winner)




[Edited on 8-7-2008 by Quantum_Dom]

Panache - 8-7-2008 at 18:52

Recently i was reading that TCCA review article posted by sauron and theres a fascinating cohalogenation/oxidation of of a hydroxyl amine in there using DCCA and either a further Cl or Br source. It oxidises your hydroxyl amine as well as halogenating on the like carbon. its on page 392-393 of the article.

Quantum_Dom - 9-7-2008 at 05:20

Will search for the paper, posted by Sauron, Panache. Thanks !

Halogenation, followed by nucleophilic substitution with NaNO2, is a topic much more known, that is for sure.

[Edited on 9-7-2008 by Quantum_Dom]

Methyl.Magic - 14-7-2008 at 10:50

All amines can be oxidised with trifluoroperacetic acid. I have recently seen another method using 3,3-dimethyl-dioxacyclopropane as osidising agent.

In theory amines can be oxidisez with KMnO4 but it seems dubious.

Klute - 19-7-2008 at 08:54

Quote:
The reaction of 3-chloroperoxybenzoic acid with aliphatic primary amines (2-butylamine, 1-hexylamine, 1-propylamine, 2-phenylethylamine, and cy-clohexylamine) in dichloromethane at room temperature has been shown to give excellent yields of the dimeric nitroso compounds.185


reference cited: Gilbert KE, Borden WT. J Org Chem. 1979;44:659.

Source

sonogashira - 23-7-2008 at 07:50

Quote:
Originally posted by Klute
Quote:
The reaction of 3-chloroperoxybenzoic acid with aliphatic primary amines (2-butylamine, 1-hexylamine, 1-propylamine, 2-phenylethylamine, and cy-clohexylamine) in dichloromethane at room temperature has been shown to give excellent yields of the dimeric nitroso compounds.185


reference cited: Gilbert KE, Borden WT. J Org Chem. 1979;44:659.

Source


...and mCPBA in 1,2-dichloroethane gives 73% of 1-nitro-2-phenylethane:

Attachment: Peracid Oxidation of Amines to Nitroalkanes.pdf (390kB)
This file has been downloaded 1512 times

Nicodem - 24-7-2008 at 01:39

Excellent find, thanks Klute!
I don't know what practical use could such a reaction have, but this is the first paper I saw that describes good to excellent yields in N-oxidation of R-CH2-NH2 type of amines to nitro compounds.

sonogashira - 24-7-2008 at 01:58

The reference was actually posted by quantum_dom in the very first post of this thread, though i guess he didn't have access to the paper.

Nicodem: "this is the first paper I saw that describes good to excellent yields in N-oxidation of R-CH2-NH2 type of amines to nitro compounds."

Here's another one (also given in the first post! The others concern oxidation of aromatic amines) using isomers of butylamine:

Attachment: Nitroalkanes from Amines with DMDO.pdf (119kB)
This file has been downloaded 1248 times

Quantum_Dom - 26-7-2008 at 16:35

Many thanks sonogashira !!! :D

Finally I can take a peek at those papers :)

Cheers.

Ephoton - 27-7-2008 at 02:21

do you think this reaction will work for ethylamine.

it states butyl amine as the lowest alphatic amine in it examples.

would nitro ethane azeotrope with the acetone in the dioxane solution.

secunder2 - 31-7-2008 at 10:16

Can anyone help me if i have a serious problem?
The question is:

that can the phenyl-2-nitrostyrene change to phenyl-2-nitropropene with formaldehyde and if it reacts what kind of catalizator is needed or not needed to complete the reaction?

thanks everybody

secunder

Klute - 31-7-2008 at 15:41

That's not possible in a one step reaction, and I highly doubt it's possible.

Addition of formaldehyde to the double bond would form 2-nitro-1-phenylpropan-3-ol ("b-(hydromethy)phenyl-b-nitroethane") . You would have to dehydrate this to obtain the alcene, which would surely partially rearrange to the nitropropene, but both steps would surely give alot of byproducts, polycondensations and other tar-forming reactions.

secunder2 - 1-8-2008 at 01:39

First of all thanks again Klute

Then how can I convert my phenyl-2-nitrostyrene to phenyl-2-nitropropene?

stoichiometric_steve - 1-8-2008 at 04:28

Quote:
Originally posted by secunder2
First of all thanks again Klute

Then how can I convert my phenyl-2-nitrostyrene to phenyl-2-nitropropene?


yeast

think about other ways to make amphetamine.

arsenic - 3-8-2008 at 15:37

The nitro group in organic synthesis

read the second chapter,

[Edited on by arsenic]

Filemon - 6-8-2008 at 15:31

What does it produce a primary amine with H2O2? a nitroso?

[Edited on 6-8-2008 by Filemon]

Klute - 6-8-2008 at 15:39

An oxide, presumally. hindered secondary amines can form stable nitrosyl radicals (2,2,6,6-tetramethylpiperidine, diisopropylamine, etc..)

Filemon - 8-8-2008 at 07:48

Him little that I have found H2O2 it oxidizes a secondary amine to hydroxilamine. It compares the activity of H2O2 with a peracid.



[Edited on 8-8-2008 by Filemon]

Maja - 10-9-2008 at 10:27

What are the conditions when condensing formaldehyde with phenylnitroethane ? For catalyst using some amine or base, but what if formaldehyde is in water solution 40%? What solvent should I use ?

[Edited on 10-9-2008 by Maja]