Frodo_Baggins
Harmless
Posts: 3
Registered: 7-4-2009
Member Is Offline
Mood: No Mood
|
|
Acid halides from amides
Alo, I was studying the sandmeyer reaction in which a diazonium salt is formed from an amine and nitrous acid (formed in solution of course), then
reacted with a halogen acid and copper (I) halide to form the corresponding halogen group.
I then realized that an amide can be reformed into the corresponding carboxylic acid this way, by reacting the amide with nitrous acid in aqueous
conditions. Comparing the two, I came to the realization that perhaps the amide could be instead reacted with HX/CuX like a simple amine would to form
an acid halide, perhaps in a mechanism similar to the below.
RCONH2 + HNO2 + H+ -> RCON2 + 2H2O
RCON2 + HX (CuX)-> RCOX + N2
This is obviously a modified sandmeyer reaction.
Anyways it seems to me that the N2 would be easily replaced with the halogen to yield the acid chloride and nitrogen, but I'm not entirely sure and
can't find too much information on it. Would this reaction work? And if it exists, does it have a name?
|
|
|
PHILOU Zrealone
International Hazard
Posts: 2893
Registered: 20-5-2002
Location: Brussel
Member Is Offline
Mood: Bis-diazo-dinitro-hydroquinonic
|
|
Maybe in anhydrous state (very difficult!) with all related explosive risks,
R-CO-NH2 + R'-O-NO --> R-CO-NH-N=O + R'-OH
R-CO-NH-N=O <--> R-CO-N=N-OH --> R-CO2H + N2(g)
R-CO-N=N-OH + HCl --> R-CO-N=N-Cl + H2O -(-H2O)-> R-CO-N=N-Cl --> R-CO-Cl + N2(g)
...in hydrous media you would simply end up with the hydrolysis product of the amide...
R-CO-NH2 + H3O(+) --> R-CO2H + NH4(+)
NH4(+) + NO2(-) --> N2(g) + 2 H2O
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
|
|
|
Frodo_Baggins
Harmless
Posts: 3
Registered: 7-4-2009
Member Is Offline
Mood: No Mood
|
|
Yes of course, it obviously would have to be anhydrous which would make this procedure rather tough to actually act out I suppose.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Acyl azides exist but are certainly not produced from amides. They are produced by reaction of NaN3 with an acid halide. The reverse of your
hypothetical reaction.
The Sandmeyer Reaction is a type of aryl diazonium reaction. There are also diazo reactions with aliphatic halides, that proceed differently. But your
scheme? I do not think so.
Sic gorgeamus a los subjectatus nunc.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
Quote: Originally posted by Frodo_Baggins  |
Comparing the two, I came to the realization that perhaps the amide could be instead reacted with HX/CuX like a simple amine would to form an acid
halide, perhaps in a mechanism similar to the below.
RCONH2 + HNO2 + H+ -> RCON2 + 2H2O
RCON2 + HX (CuX)-> RCOX + N2
This is obviously a modified sandmeyer reaction. |
Your equations are incorect since they do not balance by charge and RCON2 is probably not what you wanted to write since it would be a radical (you
obviously meant to write RCON<sub>2</sub><sup>+</sup> .
Of course this can not be a Sandmeyer reaction since besides the diazonium intermediate it has nothing in common - this is not about a nucleophilic
aromatic substitution as you are talking about carbonyl compounds.
First of all you should understand what the Sandmeyer reaction is. There are essentially two types of Sandmeyer reaction different in the practical
approach, conditions, catalysis and solvent(lessness). One is the SN1 aromatic substitution and due to the terrible instability of the
Ar<sup>+</sup> it only works when the nucleophile is water or fluoride (actually BF<sub>4</sub><sup>-</sup>. The second, more commonly taught in the pedagogic institutions, is the S<sub>RN</sub>1 reaction of aromatic diazonium salts which therefore requires a Cu catalyst.
Now, obviously RCON<sub>2</sub><sup>+</sup> can not react via a radical species since the RCO<sup>+</sup>
resulting from normal decomposition is so very stabilized. Therefore copper catalyst have nothing to do with what you propose. The
RCON<sub>2</sub><sup>+</sup> is already very unstable as it is, it decomposes instantaneously, and therefore needs no
catalysis to react with the nucleophile.
However, if you would want to obtain an acid chloride from the amide you must avoid the presence of any other nucleophile besides
Cl<sup>-</sup>. This means the nitrosation must be done with a reagent that will form no water or any other nucleophilic species during
the reaction. If you consider the nitrosation of an amide with NOCl you will see that one equivalent of water forms. Similarly with an alkyl
nitrite/HCl you would also get one equivalent of water and one of the alcohol. You would have to use NCl<sub>3</sub> which is however
unlikely to react with amines without troubles and since it is a hazardous explosive it would be nonsense to even bother.
Of course you could also use almost anhydrous conditions at low enough temperature where acyl chlorides hydrolyse only slowly and absorb water as it
forms. This way you could use NOCl and obtain some acyl chloride in mixture with the carboxylic acid...
I did not bother checking the literature, but you are welcome to do so as you might find something interesting on the topic. I hope this helped.
Sauron: Another common method of preparing acyl azides is also by the nitrosation of hydrazides, RCONHNH<sub>2</sub> +
HNO<sub>2</sub> => RCON<sub>3</sub> + 2H<sub>2</sub>O.
[Edited on 8/4/2009 by Nicodem]
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Thanks, Nicodem.
Sic gorgeamus a los subjectatus nunc.
|
|
|
Frodo_Baggins
Harmless
Posts: 3
Registered: 7-4-2009
Member Is Offline
Mood: No Mood
|
|
Appreciate the answers. Yeah I know I need to go back to school and re-learn all the technical stuffs 
Anyways it was an idea that I had one night and I didn't see anything wrong with it personally (other than it requiring anhydrous conditions which
would be super hard in such a reaction), but I knew there was a reason it wouldn't work as listed. That's why I put it in the beginner section Thanks for explaining that to me.
From what I've taught myself I usually understand that most oxidized groups react quite differently than their reduced counterparts (ex, acids vs
alcohols, amides vs amines and acyl halides versus haloalkanes.)
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
Well, the idea was not stupid in itself. A method of "activation" of a -CONH<sub>2</sub> can be synthetically useful. The only problem is
in that activation into an acid chloride is not desirable unless it can be used in a one-pot methodology. Otherwise, it is just much simpler to
hydrolyse the amide to an acid and use a common coupling reagent (including cheap ones like CDI or DCC). Amides, and not just of the
-CONH<sub>2</sub> type but also -CONR<sub>2</sub>, can also be hydrazinolyzed to hydrazides which upon nitrosation give acyl
azides (as mentioned in the previous post) which can be considered as activated carboxylic acids (they are pretty electrophilic and react with amines
just as acid chlorides just much less rapidly so).
It might be possible that by using a combination of NaNO2/AlCl3 in diethyl ether at 0°C you could get acyl chlorides from
RCONH<sub>2</sub> type of amides since the water formed during the nitrosation would be immediately consumed by the acid used (AlCl3).
About the reactivity of the functional groups... the ones you mentioned are all very different and it is not about their oxidation state per se, it is
about electronic densities, resonance structure and reaction mechanisms. You must be at the learning stage where you look up for symbolisms in the
chemical structures, but there is no such things. Electrons just do not care about symbolisms, they only follow the rules of molecular orbitals. Don't
worry, you will grow over this stage once you read a few dozens of books, a few hundred of reviews and several thousands of papers. Enjoy your
learning process!
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
PHILOU Zrealone
International Hazard
Posts: 2893
Registered: 20-5-2002
Location: Brussel
Member Is Offline
Mood: Bis-diazo-dinitro-hydroquinonic
|
|
| Quote: Originally posted by Nicodem |
It might be possible that by using a combination of NaNO2/AlCl3 in diethyl ether at 0°C you could get acyl chlorides from
RCONH<sub>2</sub> type of amides since the water formed during the nitrosation would be immediately consumed by the acid used (AlCl3).
|
Interesting idea...do you have reference or a plausible reaction pathway?
I would have thought the AlCl3 to be unstable towards NaNO2 ...
Because Al(NO2)3 is apparently inexistant (Google only lists nomenclature school tests and a lot of confusions with AlN (aluminium nitride)), it might
be very unstable...maybe even explosive reaction...
AlCl3 +3 NaNO2 --> 3NaCl + Al(NO2)3
2Al(NO2)3 --> Al2O3 + 3 N2O3
Then maybe:
AlCl3 + N2O3 --> (AlCl3(NO2))(-) + NO(+)
This last line shows that a tiny part of the initial NO2 turns into NO(+).
[Edited on 9-4-2009 by PHILOU Zrealone]
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
No, it was not from a reference. Actually, I didn't even bother checking SciFinder or Beilstein. I just gave that as an option where the acid used is
not protic, reacts with the water formed, while at the same time it provides a source of HCl.
I don't think aluminium nitrite could exist as a characterizable salt. I think the Al(III) cation is too acidic to keep the nitrite in the ionic form
and prevent the decomposition to N<sub>2</sub>O<sub>3</sub>. But I mentioned no Al(NO<sub>2</sub><sub>3</sub> and don't really see why you call for it. I just proposed the
use of AlCl<sub>3</sub> ethereal solution as an acid for nitrosation with NaNO<sub>2</sub> in the sense of:
R-CONH<sub>2</sub> + NaNO<sub>2</sub> + AlCl<sub>3</sub> => R-COCl + N<sub>2</sub> + NaCl +
"Al(OH)<sub>2</sub>Cl"
... where "Al(OH)<sub>2</sub>Cl" is obviously not a compound but rather an undefined hydrated aluminium oxychloride, kind of what one gets
by quenching AlCl<sub>3</sub> with water and evaporating to dryness.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
PHILOU Zrealone
International Hazard
Posts: 2893
Registered: 20-5-2002
Location: Brussel
Member Is Offline
Mood: Bis-diazo-dinitro-hydroquinonic
|
|
| Quote: Originally posted by Nicodem |
But I mentioned no Al(NO<sub>2</sub><sub>3</sub> and don't
really see why you call for it. I just proposed the use of AlCl<sub>3</sub> ethereal solution as an acid for nitrosation with
NaNO<sub>2</sub> in the sense of:
R-CONH<sub>2</sub> + NaNO<sub>2</sub> + AlCl<sub>3</sub> => R-COCl + N<sub>2</sub> + NaCl +
"Al(OH)<sub>2</sub>Cl"
|
I fully understood your point ! 
I was just trying to imagine what could happen...assuming the electropositivity of Na(+) vs Al(3+) and the electronegativity of Cl(-) vs NO2(-), one
can imagine that Na(+) will be more attracted to Cl(-) than to the NO2(-)...also in etheral maybe precipitate NaCl and favourise the equilibrium to
produce Al(NO2)3.
Also the decomposition of the Al(NO2)3 might be a competitive reaction...so everything depends on the kinetic and nothing is better than a trial
experiment...but with the due cautions and microscale of course!
It would be, if it succeded, a very interesting alternative route to Acyl halide from cheap material or easily available reactants...
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
| Quote: Originally posted by PHILOU Zrealone |
I was just trying to imagine what could happen...assuming the electropositivity of Na(+) vs Al(3+) and the electronegativity of Cl(-) vs NO2(-), one
can imagine that Na(+) will be more attracted to Cl(-) than to the NO2(-)...also in etheral maybe precipitate NaCl and favourise the equilibrium to
produce Al(NO2)3.
|
I don't think you understand the proposed role of AlCl<sub>3</sub>. It is just a simple acid+base thing, just like the reaction of HCl
with NaNO2 that is otherwise commonly used for nitrosating amides, alcohols, anilines, amines, phenols, etc.
AlCl<sub>3</sub> just happens to be a strong acid that dissolves well in diethyl ether (ethers are just basic enough to coordinate with
such strong acids). Amides, particularly those with -CONH<sub>2</sub> groups generally have low solubility in diethyl ether, but since
they are even more basic than ethers they also coordinate with AlCl<sub>3</sub>, so the mixture of RCONH<sub>2</sub> and
AlCl<sub>3</sub> in Et<sub>2</sub>O should be homogeneous even at 0°C. Yet, NaNO<sub>2</sub> is practically
insoluble in Et<sub>2</sub>O, which is however not a problem since being basic it reacts with AlCl<sub>3</sub> (or the complex
formed from the reaction of AlCl<sub>3</sub> with the amide which is a proton acid). This way, a mixture of nitrogen oxides generally
called as N<sub>2</sub>O<sub>3</sub> is formed together with NaCl and aluminium oxychlorides (both insoluble).
N<sub>2</sub>O<sub>3</sub> (or any other nitrogen electrophilic species such as NOCl, NO+NO2, HNO2, etc.; it does not matter
which) then nitrosates the amide.AlCl<sub>3</sub> complex to either the carboxylic acid or acid chloride (I have no idea, only an
experiment can tell). All in all it is just a most common nitrosation with the only exception that a Lewis acid is used. Essentially you could use an
anhydrous ethereal solution of HCl instead of AlCl<sub>3</sub>, however HCl does not remove water by forming an insoluble oxychloride and
that is the only reason I mentioned it - to use a dehydration agent as an acid. I wish I had the time for such a simple experiment, but when at work
there is always plenty of other (paid for) work to do. It is however an experiment suitable for an amateur setting as well, so maybe someone else will
take it over (the formation of RCOCl can be demonstrated by the derivatization of its ethereal solution with an amine to form a solid product, for
example).
By the way, not really related, but AlCl<sub>3</sub> is not a really a ionic compound and you can not talk about
Al<sup>3+</sup> cations since they do not exist as such, not even as solvated Al<sup>3+</sup> cations.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
