Quote: Originally posted by Boffis  | | Hi Rosco, I am going to have another go at this reaction but my paln is to suspend the the paracetamol, sodium nitrite and sodium acetate with and
without H2O2 in a mixture of methanol and water and then slowly add slightly more acetic acid than required to liberate the nitrous acid. This should
keep the pH fairly high, close to 7 to start with. My theory is that if the reaction is too slow at 7pH then the free acids will cause the pH to fall
until reaction occurs. I am working on the quantities at present. |
I wonder if the niche condition of mild pH and dilution causes regioselectivity for nitrosation at 3, or if that is simply the preferential position
for any reaction condition that provides the first entering nitroso group at 3. If 3 is simply the preferred position for the entering nitroso, then
you can perform synthesis using harsher reaction conditions if needed so long as temperature is kept low.
I think so long as you keep the pH low but not so low as to cause deacetylation of the paracetamol, the nitrosation should proceed. It may not even be
necessary to so gently conduct the reaction that only one nitroso is introduced, since the eventual product is to later be aggressively nitrated to
the trinitro. Based upon the reactions that involve extreme conditions of low pH needed to accomplish trinitration, yet leaving the acetyl intact, it
would seem reasonable that the deacetylation vulnerability of paracetamol is not too great at low temperature, even at extremely low pH, while a
higher temperature such as even dilute HCL at the boil, will easily split off the acetyl and leave ordinary p-aminophenol which will lead to
decomposition by attack of the amino without the protective acetyl group.
Anyway it would seem to me that the nitrosation of paracetamol would show regioselectivity for the first entering nitroso at 3. I think it was
incorrectly presumed that the use of H2O2 would oxidize the 3 nitroso to a 3 nitro, but that did not occur, and what was accomplished by the synthesis
was a simple nitrosation at the 3 that went no further.
I was looking at the similar reaction for producing styphnic acid from nitration of a precursor obtained by a nitrosation of resorcinol. Resorcinol is
likewise temperature and oxidation sensitive so I thought similar conditions might apply.
US2301912
GB1278576
Attachment: US2301912 Styphnic Acid via nitrosation and nitration method.pdf (622kB)
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Attachment: GB1278576 Nitrophenols from Nitrosophenol intermediate.pdf (572kB)
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Maybe ice cold dilute HNO3 as part of the solvent system for the paracetamol could be treated with NaNO2 solution to obtain the nitroso derivative
which could be filtered, and subsequently treated with a more concentrated maybe 35-50% ice cold HNO3 to convert the nitroso to the nitro. See
attached article for the method applied to resorcinol.
Attachment: AD0399653.pdf (1.8MB)
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In your previous post linked
http://www.sciencemadness.org/talk/viewthread.php?tid=9722&a...
The imine intermediate of Matsuno could have a similar but alternative reaction involving an oxime as the result of nitrosation.
The oxime can then be oxidized by nitric acid to a nitro.
See attached file for the analogous reaction with resorcinol
Attachment: DinitrosoResorcinol JACS 1923, 45, pg 1536 to 1539.pdf (292kB)
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[Edited on 3/4/2017 by Rosco Bodine]
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