Quantum_Dom
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Nitroethane from alpha-alanine ?
A interesting idea came to mine the other day (see scheme below). Performing a Sandmeyer reaction on beta-alanine (widely available OTC) in an aqueous
hydrochloric acid would generate 3-chloropropanoic acid [1].
The latter could then be reacted with sodium nitrite in a nucleophilic substitution fashion, followed by a decarboxylation to yield nitroethane [2].
[1] (S)-2-CHLOROALKANOIC ACIDS OF HIGH ENANTIOMERIC PURITY FROM (S)-2-AMINO ACIDS
[2] Synthesis of nitromethane from 2-chloroacetic acid
Anyone has experience or thoughts on this ?
Thanks
[Edited on 28-12-2008 by Quantum_Dom]
[Edited on 29-12-2008 by Quantum_Dom]
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sparkgap
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The decarboxylation only succeeds for nitroacetic acid, for reasons similar to the ease of decarboxylating malonic acid and acetoacetic acid. All
three cases have only one carbon separating the nitro or carbonyl from the carboxyl group, rendering the carboxyl group easily removable.
On the other hand, in your proposal, there is now a two-carbon separation between your nitro and carboxyl group...
sparky (~_~)
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Quantum_Dom
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| Quote: | Originally posted by sparkgap
The decarboxylation only succeeds for nitroacetic acid, for reasons similar to the ease of decarboxylating malonic acid and acetoacetic acid. All
three cases have only one carbon separating the nitro or carbonyl from the carboxyl group, rendering the carboxyl group easily removable.
On the other hand, in your proposal, there is now a two-carbon separation between your nitro and carboxyl group...
sparky (~_~) |
Makes sense. Thanks ! Although harder than the cases you mentionned, I think there is still some possibility to obtain fair yields of decarboxylation
by making the carboxylate salt and heat in a high BP solvent.
According to this patent, 94.5 %nitroethane can be obtained from 3-bromopropanoic acid. :
http://www.freepatentsonline.com/4319059.html
****UPDATE***** Patent is for carboxylic acids with alpha-substitution (i.e. 2-bromopropanoic acid). Sorry for
the mistake guys.
[Edited on 29-12-2008 by Quantum_Dom]
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not_important
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That patent is for "alpha-bromoalkanoic acid", which puts the -NO2 alpha to the -CO2, as sparkgap said it is then similar to malonic acid and readily
decarboxylates. You are proposing to use a beta-nitro acid, which is another story.
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sparkgap
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I was about to rail at how positioning could be gotten so wrong, but cursory reading shows that said patent only mentions "α-bromopropanoic acid"
(i.e., "2-bromopropanoic acid"), not "3-bromopropanoic acid".
In which case, no dice decarboxylating your β-nitro acid.
If you can somehow get to α-nitropropanoic acid, well...
sparky (~_~)
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Quantum_Dom
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| Quote: | Originally posted by sparkgap
I was about to rail at how positioning could be gotten so wrong, but cursory reading shows that said patent only mentions "α-bromopropanoic acid"
(i.e., "2-bromopropanoic acid"), not "3-bromopropanoic acid".
In which case, no dice decarboxylating your β-nitro acid.
If you can somehow get to α-nitropropanoic acid, well...
sparky (~_~) |
Yup, I made a mistake all right. Many thanks ! alpha-alanine should be a more interesting candidate then.
[Edited on 29-12-2008 by Quantum_Dom]
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sparkgap
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For that proposed scheme, on the other hand, what I am not now so sure of is the ease of nucleophilic substitution of the chlorine for the nitrite
(remember that initially the nitrito product is formed first before the isomerization to nitro). You have a secondary halide there in your proposal.
It worked well with chloroacetic acid because it is a primary halide that easily undergoes S<sub>N</sub>2.
sparky (~_~)
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Quantum_Dom
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| Quote: | Originally posted by sparkgap
For that proposed scheme, on the other hand, what I am not now so sure of is the ease of nucleophilic substitution of the chlorine for the nitrite
(remember that initially the nitrito product is formed first before the isomerization to nitro). You have a secondary halide there in your proposal.
It worked well with chloroacetic acid because it is a primary halide that easily undergoes S<sub>N</sub>2.
sparky (~_~) |
Yes a secondary halide SN2 substitution with nitrite is harder to acheive and give lower yields, but the ramification is only a methyl group! So
steric hindrance is minimal.
The patent I provided above reports high yields of nitroethane from 2-bromopropanoic acid. So it seems like the nitrite substitution is feasible.
Chloride is a weaker leaving group than bromide though.
I think it is at least worth an effort to try it though.
[Edited on 29-12-2008 by Quantum_Dom]
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sparkgap
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Don't worry about me, I'm just wondering aloud. It may, it may not, so do try. I'm no Nicodem. 
sparky (~_~)
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
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Quantum_Dom
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| Quote: | Originally posted by sparkgap
Don't worry about me, I'm just wondering aloud. It may, it may not, so do try. I'm no Nicodem.
sparky (~_~) |
LOL. Do continue, your pointers are extremely valueable and at least someone is giving a damn about my thread.
Peace !
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vulture
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I've edited this thread to remove unnecessary flaming. Keep it decent and get back on topic.
One shouldn't accept or resort to the mutilation of science to appease the mentally impaired.
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McLovin382
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wouldn't this mean that you could also decarboxylate alanine and obtain ethylamine?
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sparkgap
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I believe there is a whole body of literature on the decarboxylation of amino acids. Tryptophan and phenylalanine always seemed to be attractive. 
But you should have asked that under "Short questions".
sparky (~_~)
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Ebao-lu
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| Quote: | | (remember that initially the nitrito product is formed first before the isomerization to nitro) |
If it is realy the case, then it is possible to make a nitrite from lactic acid (a-hydroxypropanoic), and rearrange it to nitro. Lactic acid seems to
be avaliable)
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497
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Is there any reason nitromethane could not be had by an analogous reaction on glycine? I'm sure it wouldn't be cost effective under current
circumstances, but it could turn out to be useful if nitromethane gets restricted or scheduled in the future (I wouldn't put it past them).
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sparkgap
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I would actually be more optimistic that the scheme QD proposed in the OT would turn glycine to nitromethane in better yield.
sparky (~_~)
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McLovin382
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Yay for amines and nitro compounds from amino acids!
Opens up worlds if one has a proper still
Edit: One note on the sandmeyer reaction. The reaction takes place by forming a diazonium salt from the amine (N=N from NH2), which is then converted
to the corresponding halide with HX and a copper(I) salt (copper(I) chloride for instance)
for that reason, it seems necessary to add copper powder (in HCl) to the reaction to catalyze the decomposition of the diazonium salt!
Also water may cause the formation of alcohols if come in contact with the diazonium salt.
http://en.wikipedia.org/wiki/Sandmeyer_reaction
[Edited on 30-12-2008 by McLovin382]
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Quantum_Dom
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| Quote: | Originally posted by McLovin382
Yay for amines and nitro compounds from amino acids!
Opens up worlds if one has a proper still
Edit: One note on the sandmeyer reaction. The reaction takes place by forming a diazonium salt from the amine (N=N from NH2), which is then converted
to the corresponding halide with HX and a copper(I) salt (copper(I) chloride for instance)
for that reason, it seems necessary to add copper powder (in HCl) to the reaction to catalyze the decomposition of the diazonium salt!
Also water may cause the formation of alcohols if come in contact with the diazonium salt.
http://en.wikipedia.org/wiki/Sandmeyer_reaction
[Edited on 30-12-2008 by McLovin382] |
Please read the paper [1] referenced in my first post. They report fair yield of chloro compound without the use of a copper salt. The latter is
usually necessary for aromatic amines substitution.
Youre right about 2-hydroxypropanoic acid, it will surely be a byproduct of this process. Perhaps a treatment, of the post-reaction mixture, with zinc
chloride (or ferric chloride) with gentle reflux could improve the yield of 2-chloropropanoic acid obtain.
Also, the diazonium salt does not decompose because of a copper catalyst but rather because of temperature.
[Edited on 31-12-2008 by Quantum_Dom]
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sparkgap
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"Also, the diazonium salt do not decompose because of a copper catalyst but rather because of temperature."
Indeed, and additionally it is entropically favorable that one of the resulting products is nitrogen gas.
sparky (~_~)
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Ebao-lu
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| Quote: | | Also, the diazonium salt does not decompose because of a copper catalyst but rather because of temperature. |
Afaik, such diazonium salts are comperatively stable, because there is an EWG-group(COOH, NO2, CHO, C(O)R, CN, COOR, etc) in alpha-position, that
would have destabilized the carbocathion if N2 was eliminated, that's why N2 does not eliminate that easy.
[Edited on 1-1-2009 by Ebao-lu]
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Quantum_Dom
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| Quote: | Originally posted by Ebao-lu
| Quote: | | Also, the diazonium salt does not decompose because of a copper catalyst but rather because of temperature. |
Afaik, such diazonium salts are comperatively stable, because there is an EWG-group(COOH, NO2, CHO, C(O)R, CN, COOR, etc) in alpha-position, that
would have destabilized the carbocathion if N2 was eliminated, that's why N2 does not eliminate that easy.
[Edited on 1-1-2009 by Ebao-lu] |
I agree that the enthalpy of the process would not be favorable since the carbocation generated would be destabilized but since the process is highy
favorable entropically, the free energy of the overall process is favorable and makes the process spontaneous at temperature roughly higher than 5
celsius.
Also keep in mind that the solvent is protic and therefore will be able to stabilize the carbocation as well.
The only stable, and isolated, diazonium salts that I heard of are tetrafluoroborate derivatives.
[Edited on 2-1-2009 by Quantum_Dom]
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Ebao-lu
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Yes, the stability of diazonium salts varries much. Some are immediately broken into carbocathions, some are not (also, some diazonium salts from
dinitro- and trinitro aniline are stable in solid state). The salts like made form aminoacids are somewhere between stable and unstable(more likely
unstable)
[Edited on 3-1-2009 by Ebao-lu]
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