nitro-genes - 24-8-2015 at 07:44
I thought it might be nice to put all of the p-DDNP stuff in a document, still needs some work and added references, hopefully it will pass SMDB peer
review. 
Ideas, suggestions, corrections are welcome. 
Attachment: Synthesis of 4-amino-2,6-dinitrophenol (isopicramic acid) and p-DDNP from acetaminophen version 1.pdf (1.3MB)
This file has been downloaded 2709 times
[Edited on 11-9-2015 by nitro-genes]
Rosco Bodine - 24-8-2015 at 09:51
That reference about p-DDNP for which you were asking is I think Meldola and Stephens, JCS, Volume 87, part 2, (1905) pages 1199-1207, See pg
1203-1205
article attached
Attachment: Pages from Journal_Chemical_Society_London pg1203.pdf (380kB)
This file has been downloaded 1088 times
nitro-genes - 24-8-2015 at 09:59
Thanks for the reference, I'll include it together with the other references.
Since pDDNP was initially your idea and you provided most of the hard to find and sparsely available literature regarding DNAc, isopicramic acid and
pDDNP, I included your name in the document, I hope you don't mind, should have asked in advance probably
[Edited on 24-8-2015 by nitro-genes]
careysub - 24-8-2015 at 10:18
Excellent write up!
I do have a suggestion though: collect together some physical data on isopicramic acid from the literature, and provide specific guidance on storage.
I imagine that someone would likely be storing isopicramic acid as a stock material, and only prepare DDNP from that only as needed.
nitro-genes - 24-8-2015 at 11:24
Hi Careysub,
Thanks for you suggestions. Good point, it's good to know more about the stuff that you store indeed. I'll include some more physical data, like
melting point, incompatibilities, toxicity, crystal structure, use as pH indicator dye, pH colour transition points, maybe colour and solubility of
the salts etc
[Edited on 24-8-2015 by nitro-genes]
Rosco Bodine - 24-8-2015 at 23:55
Also see the dedicated DDNP and related compounds sticky thread in Energetic Materials which contains a lot of related and historical background
material. There continues a work of looking at possibilities for other interesting diazo compounds as candidate "green energetic materials" and maybe
some not so green but energetic anyway alternatives, which may have escaped due attention in the literature. There are many interesting possibilities
for decently powerful and reasonably stable energetic materials which are undiscovered art or were once identified like p-DDNP and then relegated to
obscurity without any extensive follow up study. There is a 110 year gap between p-DDNP being identified and then more recently revisited, with maybe
one or two brief mentions during the entire interim century. By itself that fact alone is interesting and raises the question why would p-DDNP not be
better documented since it seems an easily made good candidate initiator? I am still puzzled and thinking go figure on that one.
nitro-genes - 10-9-2015 at 10:06
Thanks to Rosco, Solo, Philou and Nicodem for the references and remarks, Henning brand for providing a clean o-DDNP comparison and careysub for
remarks regarding the manuscript, it turned out pretty nice if I may say so
Attached is version 2, with added references, more background information/historical data about isopicramic acid, and the nitrate salt/SA/Copper
diazotization method.
[Edited on 10-9-2015 by nitro-genes] -> Smaller file and working hyperlinks
(at Nitro-genes request, first version of the file removed- See his next post for updated & corrected version-)
[Edited on 11-9-2015 by Bert]
nitro-genes - 11-9-2015 at 04:06
Page numbers added, 1 ref changed, abstract added, hyperlinks to experimental procedures.
Attachment: Synthesis of 4-amino-2,6-dinitrophenol (isopicramic acid) and p-DDNP from acetaminophen.pdf (1.4MB)
This file has been downloaded 1803 times
I think it is ready for submission 
[Edited on 11-9-2015 by nitro-genes]
proposed final revision
Rosco Bodine - 11-9-2015 at 09:02
I resequenced a couple of sections to align with the reaction sequence and have reduced the file size. Take a look at this proposed file revision and
see if this looks right.
I just printed a hard copy and it looks good to me
suitable for framing
Final Revision: I noticed that I failed to resequence the Figure numbers for Figures 4, 5, and 6, to correlate with the section resequencing I did
earlier, so I have edited those Figure numbers and references to provide a correct numerical ordering of those Figures. I think this last edit should
perfect the document. I am deleting the earlier revision and substituting what is hopefully the final revision.
Edit: Sorry I just found an additional couple of Figure number corrections I missed earlier on pages 6 and 7 fixed in the latest edited attached file.
The presently attached file I think nails it. I slept on it and reviewed the document, proof read it again, and it all looks good to me.
For anybody who wonders, I made no content changes in the earlier document but was only tweaking the document sections formatting, which then resulted
in some Figure numbering revisions for the photos.....that's it. The content is all good.
I can sign off on this file if nitro-genes concurs.
Update: I made a more legible larger font and higher resolution version and corrected some small typos.
There may be some additions, revisions later from nitro-genes
Attachment: Synthesis of 4-amino-2,6-dinitrophenol (isopicramic acid) and p-DDNP from acetaminophen 9-13B revision.pdf (2.3MB)
This file has been downloaded 1685 times
[Edited on 9/14/2015 by Rosco Bodine]
nitro-genes - 13-9-2015 at 07:37
EDIT: Old file removed, and replaced with new file, containing:
- Different diazotization schemes and 40x magnification photos for obtaining p-DDNP as high bulk density product
- Modified method for nitrate salt/SA/Copper diazotization protocol
[Edited on 6-10-2015 by nitro-genes]
Attachment: Isopicramic Acid and p-DDNP from Acetaminophen.pdf (1.5MB)
This file has been downloaded 3742 times
nitro-genes - 6-10-2015 at 13:23
Modified file uploaded in post above, old file removed to safe space
[Edited on 6-10-2015 by nitro-genes]
Endo - 11-11-2015 at 15:09
I just wanted to throw in my experiences with this procedure as outlined in the downloadable .pdf file above. I followed the procedure with the same
amounts of reagents and stuck to the process as outlined.
The solvent extraction of acetaminophen from the tablets went very well. The formulation I had included carnuba wax as one of the tablet components,
I found that boiling off the alcohol just to the point where the surface of the solution became cloudy and the wax began to solidify on the surface
was the ideal point to stop the evaporation of the alcohol. After crystallization the left over solution contained quite a lot of wax which became
apparent when I tried to get a second crop of crystals and cooked off the rest of the alcohol. Per the outlined procedure it is better to not waste
time and just discard the solution after the first crop of crystals.
The nitration went very smooth with the descriptions of the color changes being very helpful to gauge the process of the nitration. I was not in a
hurry with this process so I used smaller additions, taking ~45 min instead of the 30 listed to add all of the AN+SA mixture. Upon crashing with ice
the foam took quite a long time to subside (almost an hour).
The deacylation step was where I found that I could not reproduce the process. I boiled the nitration product for an hour with 20% sulfuric acid as
detailed. Upon cooling a large amount of un-deacylated material crystallized. The clear red supernatant still precipitated a quantity of the
expected product upon partial neutralization (as detailed) with ammonia. At this point I stopped with the process.
I took the crystallized unreacted material left after filtration of the deacylation step (2,6-dinitro-4-acetaminophenol) washed the filter cake with
3% ammonia (dissolving it as the ammonium salt) and discarded the small amount of solid material that was not soluble in ammonia. I then dried down
the ammonia solution until it formed a slurry, and performed the deacylation step again. (The smell of acetic acid was a strong indicator that I had
a lot of acylated material still present.)
I suggest that the hour detailed in the procedure may not be enough time for the deacylation reaction to run to completion. Perhaps if I were to do
over I would heat with dilute sulfuric adding additional water as needed to replace that lost to boiling, until acetic acid can no longer be smelled
from the reaction mixture.
All in all I enjoyed this synthesis and although I did not run the procedure any further than isopicramic acid I appreciate the quality of the
write-up, the large amount of work that went into this writeup and detailed descriptions.
Thanks
Endo
nitro-genes - 17-11-2015 at 17:19
Thanks for the appreciation, it was really fantastic to bring a 100 year old synthesis back to life and this time document it with colour photos,
using completely OTC materials.
The thing you describe about the impurities floating to the surface was also noticed in my case when I tried another brand of paracetamol. Like you
also suggest, it is most likely some sort of wax. Crystallizing at this point is interesting, how did the crystals look, how long took the cooling and
complete crystallization and what was the yield? I was reasoning that the high temperature crystallization from boiling off all ethanol while rapidly
stirring would leave a lot of impurities as an emulsion, giving the filtrate the milky appearance observed. I never tried crystallizing at this point,
fearing that some of the compounds might co precipitate on cooling (like PVP for example, present in many brands over here) and/or loose much
acetaminophen from supersaturation.
About the deacetylation: the deacetylation of the dinitroacetaminophen is reportedly much faster and easier than for acetaminophen itself. Already at
70-80 degrees C there is substantial deacetylation going on, so I don't think this is the problem. One difference is that I did not boil the solution
to drive off the acetic acid formed, but heated it under reflux, I had some indication that the residual acetic acid helps to prevent the isoicramic
from precipitating during cooling later, although never really test this further. Some photos of the results would be really helpful, are you sure
residual DNAc precipitated instead of isopicramic or other dark brown stuff?
An other option is that the amount of sulfuric acid was on the low side to keep all picramic acid into solution, I noticed under an around 25-30% acid
solution it can precipitate part of the isopicramic upon cooling, depending on conditions. I tried minimizing the amount of sulfuric acid used for
deacetylation, since keeping the amount of NH4+ on the neutralization step as low as possible may increase storage stability of the final product. I
must say, only tried these quantities once to test, it may be safer to use a larger excess of sulfuric, say 15 ml instead of the 12.5 ml stated.
There are a many unknowns still regarding this synthesis that would need to be determined to provide a really high yield and pure product synthesis,
like effect of water content during nitration (affecting oxidation and sulfonation products formed), maximizing yield of DNAc, conditions to minimize
the solubility of the DNAc in the spent nitration mixture, the solubility of DNAc and isopicramic acid during the deacetylation step, temperature
dependent solubility and stability of ammonium isopicramate etc etc.These take a lot of time though and are not my primary interest, so additions or
optimizations more than welcome.
[Edited on 18-11-2015 by nitro-genes]
Endo - 11-12-2015 at 15:13
I got an 85% yield from extraction of the acetaminophen. I checked today by adding some of my acetaminophen to distilled water, a faint cloudiness
is present once it is dissolved, it is possible I have some co-precipitated wax in there. I suppose I can recrystallize it from water and hopefully
be able to filter the wax off. I did notice that upon simmering for a while that the fine wax suspension will congeal into larger globs of wax. I
can probably dissolve in an excess of water and boil until the wax congeals, then filter and recrystallize the filtrate.
I performed the deacetylation twice, once on the material still damp from the nitration, and a second time on the large amount of material left over
in the filter after the first run through. I performed the deacetylation in an open beaker instead of reflux.
I suspect that you are correct with the need to have both the sulfuric and acetic acid present.
The first time I was left with a large amount of dark red crystals in the filter (ammonia soluble), after which I was able to precipitate 4.2g of a
cinnamon colored powder with golden colored glitter like highlights.
The ammonia soluble solids which I ran through the deacetylation step again (open beaker), left a lot of muddy dark brown material in the filter
which I should not have discarded (it was most likely product, just not dissolved because of lack of acid). I was able to recover, after partial
neutralization with ammonia, 3.2g of isopicramic acid from the clear red filtrate.
I hope that my experiences at messing up this process can help others that are trying the same thing. (use reflux and a bit more acid for the
deactylation step)
The good side is that I have plenty of good purity material to use as a pH indicator. Thanks for your feedback on this nitro-genes.