DDNP & related compounds: The über thread!

It's not due to a colour shift from changes in pH, dinitro N-nitroso acetaminophenol is an existing compound (CAS RN: 146897-61-2 ), stability and toxicity unknown. the difficulty is determining what percentage of the dark brown impurities are from remaining tablet binders versus from nitration, all I know is that the amount of impurities filtered out varies per batch of acetaminophen/nitration, usually though it represents only a minor fraction compared to the iso picramic acid obtained.

No luck yet with DDNR, an attempt to nitrate the isopicramic acid acid further to the putative trinitro nitramine compound (0 to - 20 deg C, 24 hours, AN/SA, pouring on ice) resulted in a lot of foaming and precipitation of a bright yellow compound with definite smell of p-benzoquinone. Recrystallization/hydrolyzation from refluxing in 96% ethanol for 30 minutes , followed by addition of a potassium acetate solution at pH 6 and cooling seemed to precipitate only p-DDNP. Also no luck with oxidative nitration of pDDNP at elevated temperatures, or boiling with excess nitrite. Searching for optimal reaction conditions and subsequent purification without a way to monitor tthe reaction at various stages makes it next to impossible to come to a conveniant route for DDNR IMO.

There are three experiments I would still like to perform, any thoughts on the outcomes of these reactions would be much appreciated:

1. Add 3 grams of the putative dinitro N-nitroso acetaminophenol to an acidified (equimolar or slight excess) H2O2 solution
2. Add 3 grams to 65% nitric acid letting it stir at room temperature, or 60 deg C while monitoring colour changes.
3. Adding the putative 3 nitro acetaminophen from nitrite nitration to 65% nitric acid at 0 deg C for 12-24 hours.

[Edited on 16-8-2015 by nitro-genes]

My bad, by refluxing in ethanol I meant keeping the solution at 40 deg C. (Boiling point of DCM), which is not refluxing indeed and unlike DCM a polar solvent. I did not aim for the tetranitro compound, but was hoping that possible formation of the primary aryl nitramine at very low temperatures to avoid decomposition would lead to intramoleclar rearrangement of the nitramine to produce either the trinitro diazo or lead to hydrolysis of the 3 nitro group to produce DDNR, both described and existing compounds. I recognize these routes are not the most hypothetically likely to succeed, though unlike the described non-OTC routes from literature to trinitroacetaminophen and DDNR, I'm simply reasoning from an simplicity and OTC standpoint for which either isopicramic acid or DNAc as a possible reaonably storage stable 1 or 2 step precursor to both p-DDNP and DDNR is worth investigating using small scale experiments. Another, but more complicated, OTC route would involve O-protection of acetaminophenol by reaction with benzylchloride as described by Meldola (which is OTC produced from benzylalcohol, perfume ingredient found online and concentrated HCl, (orgsynth)) and nitration using only NA.

The thing I had in mind for the first reaction is nitrating acetaminophenol to DNAc using NA, crashing the nitration mix on ice and adding a solution of one mole equivalent of nitrite to produce the bright orange putative N-nitroso dinitroacetaminophenol then try oxidation using either hydrogen peroxide or NA to obtain trinitro acetaminophenol via rearangement of the putative nitramine or lead to a decomposition leading to deacetylation, both options would be fine by me. The molybdenum catalyst seems interesting as well, saw it posted in the reference section and would be interesting to verify. As a gashead I'm thinking MoS2 + O2 --> MoO3 + NH3 --> (NH4)6Mo7O24 * 4 H20 -- > 100 deg C. --> (NH4)6Mo7O24

[Edited on 17-8-2015 by nitro-genes]

Who would have thought

It seems isopicramic acid can be conveniently and completely OTC diazotized by treating AN/SA/H2O with fine pieces of metallic copper from electricity wire. The procedure probably works to produce very pure pDDNP since nitrous gasses (NO and NO2) are formed in situ, whereas the reaction neither produces a significant amount of H2, nor is copper (unlike iron, zinc, aluminium etc) able to reduce the nitrogroups. Still needs some optimization, though it definitely works, and seems to produce better yields than heating in 65% nitric acid alone.

I used something like this:

1 gram of finely powdered isopicramic acid was suspended in 8 ml of water. Then 3 ml's of 96% SA was added and the suspension heated with stirring to produce a solution of isopicramic sulfate. When cooled to 30 deg C., 4 grams of ammonium nitrate was added and 1 gram of metallic copper. The mix was kept at 50 deg C for 1 hour and crashed on ice to precipitate 0.8 grams of pure p-DDNP.

The copper came from 2 mm thick solid eleectricity wire, cut with siccors to about 3 mm long "beads" that can be stirred with the magnetic stirrer bar without doing too much damage to the teflon coating. Be sure you strip the wire of any potential protective coatings else it will contaminate your product. The procedure is not optimized yet, it was more of a curiosity for me, so it may still need some tweaking.

Thanks, and no, I thought of it myself, reasoning that most metals are able to reduce nitric acid (wheres organic reductors tend to give a mess), I reckoned needing an OTC metal that did not react directly with H30+ such as more stronger reducing metals as zinc or iron, and did not produce any precipitate.

You bring up an interesting question though: What is the primary nitrogenoxide species that leads to formation of the diazogroup? I was under the impression that NO (being the anhydrate of nitrous acid) is. This may be important, since depending on the dilution of NA, it produces primarily NO or NO2 from the reaction with metallic copper. And you are right, the copperpowder would react much faster (maybe resulting in less by-products), on the other hand, the exotherm may be more diffult to control and it would need carefully weighed amounts to be sure no copper powder is left, whereas the beads can simply be filtered out and used again.

The really funny part is that the method described above, using metallic copper and nitrate salts/ sulfuric acid, produces the most free flowing, high density pDDNP I've seen till so far. Maybe the addition of the sulfuric, high temperatures or the presence of metallic copper or it salts seems to somehow affect crystal formation to what it seems, sort of rounded shapes.

[Edited on 25-8-2015 by nitro-genes]

You are onto something good there with the use of copper in wire form.
The fine copper wire could have its advantages by the very gradual reaction which results in a very slow diazotization which is similar to the use of nitrous fumes being bubbled from a gas dispersion tube, but is occurring in situ with the extremely fine bubbles coming off the copper wire. For finer copper wire the wires from stranded copper wire like lamp cord would be good and even finer copper wire strands are found in old vacuum cleaner cords. The copper braid that is found in coaxial cable is fine wire also but is woven into a sleeve which might need to be unraveled and teased apart into loose pieces.

The dissolved spent copper in the diluted solution could be recovered later for other uses as low soluble basic copper carbonate. A rough neutralization first done using lime to precipitate the sulfate value could leave mostly copper nitrate as an alternative material and useful byproduct itself, or which could be converted to the energetic tetraamine copper nitrate using ammonia. Waste not want not.

As to whether it is NO or NO2 that accomplishes the diazotization maybe it is both as N2O3 and it is reported that way sometimes and has been reported that NO alone can work or NO2 so it is ambiguous. It may be that exposure to the air oxidizes the NO to NO2 which then does the deed.
This could account for the use of formaldehyde being possible to cause a diazotization by its reducing effect on HNO3 which leaves no residue byproduct, as occurs for some other reducing agents like starch used with HNO3 in a gas generator.

The reaction of copper with nitric acid is probably

Cu + 4HNO3 -----> Cu(NO3)2 + 2NO2(g) + 2H2O

Anyway the use of copper wire in situ in a diazotization scheme is a new one on me and it is a very good idea.
The nascent nitrous fumes are also a highly active nitrating agent even in dilute acid solutions, where something like salicylic acid sulfonate is nitrated all the way to picric acid under mild conditions, and in quantitative yield, so this use of copper could also have other very interesting uses. Excellent.

[Edited on 8/26/2015 by Rosco Bodine]

3-diazo-picric acid (exist?) possible? precursor for iso-DDNR (exist?)

If they don't exist yet, then let us invent them here

In a couple of posts last month by nitro-genes has been provided a couple of pieces of very interesting information, regarding reaction of picric acid with hydroxylamine to form 3-amino picric acid. It is a synthesis where the lithium salt of picric acid was used for the increased solubility. I have speculated magnesium picrate may also be workable and more economical.

http://www.sciencemadness.org/talk/viewthread.php?tid=62326&...

and an easy preparation of the needed hydroxylamine

http://www.sciencemadness.org/talk/viewthread.php?tid=439&am...

In some U2U messages I have shared an idea about this on which our thinking may be parallel.

3-amino-2,4,6-trinitrophenol is isomeric with the 4-amino-2,3,6-trinitrophenol of Meldola and also Klapotke which can be diazotized to form a diazotrinitrophenol having marginal stability which has a nitro that decomposes to a hydroxyl and forms DDNR.

It may be that similarly the 3-amino picric acid will likewise be possible to diaztotize to form a marginally stable diazotrinitrophenol which likewise is subject to decomposition of one of its nitro groups to form an isomer of DDNR.

Neither of these hypothesized energetic diazo compounds have so far turned up in any search of the literature

Here is the 3-amino picric acid which would be the precursor



Attachment: US8404897 3-amino picric acid.pdf (550kB)
This file has been downloaded 796 times

[Edited on 8/27/2015 by Rosco Bodine]

The main thing I had in mind for the 3-amininopicric acid was KNDB, a mil spec approved replacement for LS, which is formed from azido reduction of 3-azido-2,4,6 trinitrophenol with K2CO3 at room temperature. I don't think it is a viable precursor to DDNR. The synthesis is listed in:

US 8748639 B1
3-azido-2,4,6-trinitrophenol, method of making, and method of transforming

"Example 1

12 mL of concentrated sulfuric acid were charged to the flask depicted in the experimental setup, and agitation was initiated. 0.897 grams (0.0037 mol) of 3-APA was then added and rinsed down with an additional 3.5 mL of concentrated sulfuric acid. The 3-APA dissolved readily and heating the reaction mixture was unnecessary. The resultant solution was cooled to 3° C. using an ice water bath, and 0.39 grams (0.0057 mol) of NaNO2 dissolved in 6 grams of concentrated sulfuric acid was added dropwise, keeping the temperature below 5° C. This addition took less than 5 minutes. The resultant solution was then stirred for 20 minutes at that temperature. 25 mL of phosphoric acid was then added at such a rate that the temperature did not exceed 5° C. This addition was somewhat exothermic and occurred over 45-50 minutes. After addition was complete, the reaction mixture was stirred at less than 5° C. for 10 minutes. During the addition and subsequent stirring, the reaction mixture became quite viscous and attained a pink-orange color. 1.18 grams (0.018 mol) of NaN3 was then added in portions, keeping the temperature below 5° C. This addition took less than 5 minutes. The reaction mixture was then stirred at less than 5° C. for 20 minutes, and was then allowed to come to room temperature by removing the ice water bath. Once the reaction mixture had reached room temperature, it was poured into 70 mL of cold (<5° C.) water with stirring. The resultant yellow precipitate was then collected by filtration, and washed with 2×20 mL of cold water. The yellow solid exhibited some water solubility, so the water washed were retained for further analysis and/or crystal growth. The remaining precipitate was then dried in a dessicator, and yielded 0.44 grams (44% yield)."

Looks like a very dangerous synthesis adding NaN3 to icecold SA, definitely not suitable for scaling up. Not sure what the phosphoric acid addition is for, presumably diluting the hN3 formed, and why no urea is added after the nitrite step. Anyway, since no precipitation is mentioned and a low temperature is used, it seems logic that the diazo derivative is presumably not very stable. My main interest was (after experimenting with the tetrazeno derivatives, which may just be an azido), that this synthesis might be performed with hydrazine sulfate instead. A two option experiment, where either the azido or tetrazeno derivative may form both of potential interest.

Another experiment I had in mind (though not very likely) is oxidative nitration of 3-aminopicric acid using 65% NA and moderate heating, which might produce the furoxan directly (can't imagine that it would have been found earlier, though very patentable if it is ). Results most likely in either picric acid or stypnic acid, though worth a shot maybe. Anyway, more ideas than time than usual...

VNS reaction of picric acid and hydroxylamine is performed at extremely high pH by addition of lithium hydroxide. Was there a particul reason you mentioned the magnesium salt? Wouldn't all magnesium picrate instaneously precipitate as magnesium hydroxide? Unlike zinc and aluminium, I'm not aware of a magnesiate being formed from dissolution in NaOH.

the N-O-diacetaminophen nitration to trinitroacetaminophen also brought me another idea. Don't know theoretical background on the most likely ring substitutions, but what if benzoxazolone was nitrated in 65% nitric acid? The N position may be more dominant in oriantating nitro groups orho para, but the alkylated O is more suscpetable to hydrolysis, which shifts the orientation during the reaction, likely very similar to the formation of trinitroacetaminophen klapotkes group described. Curious what the outcome may be.

Unlike trinitroacetaminophen, which needs Ac2O or very unhealty alkylation agents, benzoxazolone is potentially completely OTC from salicylic acid --> salicylamide --> treatment with household bleach (and maybe sulfide to prevent ring chlorination).

[Edited on 27-8-2015 by nitro-genes]

Regarding US8748639 (attached)

It looks like what they are doing is forming the soluble diazonium acid salt and then displacing the diazo with an azide to form another interesting compound.

However if the soluble diazonium was simply diluted, then the diazo oxide would likely precipitate. The diazo at position 3 would form a conjugate linkage with the hydroxyl at 1, and hydrogen would be displaced to form the anhydride or "diazo-oxide".

They show a chlorine there which is an interloper from somewhere that should not be there



It may be that the arrangement of the three nitro groups is stable and that there would be no decomposition during an extended digestion as may lead to an isomer of DDNR. For this possible decomposition the diazo oxide would be heated with potassium acetate solution to form the potassium salt of an iso-DDNR.

In the scheme I was contemplating there would be no displacement using azide of the diazo intermediate, but the diazo would be left intact.

What I am contemplating is a structurally analogous scenario which is possible that solves the futility of trying to introduce a third nitro at position 3 on isopicramic acid. The general reactions which involve diazotization and subsequent hydrolysis of one of the nitro groups of the resulting diazotrinitrophenol (anhydride) are believed might occur the same, leading to an iso-DDNR.

Attachment: US8748639 3-azido-2,4,6 trinitrophenol.pdf (469kB)
This file has been downloaded 1033 times

In regards to the US8404897 process and use of magnesium being potentially a problem that is possible and I have not even worked out the stoichiometry to look at the molar equivalents but had expected the reaction would proceed at a pH where the magnesium would not precipitate. Anyway you had said the reaction does proceed using sodium so that already provides a cheap alternative to the lithium if magnesium is unworkable. Magnesium was just an idea that seemed like a candidate if the pH requirement is not extreme. Ammonia might be helpful along with the magnesium and I don't recall for sure but IIRC ammonia and ammonium nitrate may work together to enhance solubility the same way as works for zinc if the high pH is required. I'll have to look that one up. If lithium is required to do things right, then lithium is required.

Update: I looked at the stoichiometry and see the reaction pH is very high, really caustic conditions so the use of lithium is pretty much required for the good yields of 3-aminopicric acid reported by the patent.

Quote: Originally posted by nitro-genes

Another experiment I had in mind (though not very likely) is oxidative nitration of 3-aminopicric acid using 65% NA and moderate heating, which might produce the furoxan directly (can't imagine that it would have been found earlier, though very patentable if it is ). Results most likely in either picric acid or stypnic acid, though worth a shot maybe. Anyway, more ideas than time than usual...

I wouldn't worry about the furoxan, just dissolve the 3-aminopicric acid in HNO3 and throw in your copper wire .....ummmm, whatever works is good.

[Edited on 8/28/2015 by Rosco Bodine]

Quote: Originally posted by nitro-genes

Who would have thought It seems isopicramic acid can be conveniently and completely OTC diazotized by treating AN/SA/H2O with fine pieces of metallic copper from electricity wire. The procedure probably works to produce very pure pDDNP since nitrous gasses (NO and NO2) are formed in situ, whereas the reaction neither produces a significant amount of H2, nor is copper (unlike iron, zinc, aluminium etc) able to reduce the nitrogroups. Still needs some optimization, though it definitely works, and seems to produce better yields than heating in 65% nitric acid alone. I used something like this: 1 gram of finely powdered isopicramic acid was suspended in 8 ml of water. Then 3 ml's of 96% SA was added and the suspension heated with stirring to produce a solution of isopicramic sulfate. When cooled to 30 deg C., 4 grams of ammonium nitrate was added and 1 gram of metallic copper. The mix was kept at 50 deg C for 1 hour and crashed on ice to precipitate 0.8 grams of pure p-DDNP.

Thanks, was surprised it worked so well actually, since supposedly o-DDNP is destroyed by hot concentrated sulphuric acid, so it needs some water at (least <60%) to prevent decomposition. On the other hand, very low sulfuric acid/nitrate salt concentrations may form mostly NO instead of NO/NO2 from the reaction with metallic copper and need stonger heating for the reaction to proceed within a couple of hours. With some tweaking, an optimum can probably be found using sulfuric acid. It's pretty cool though, p-DDNP from acetaminophen, SA, ammonium nitrate and ammonia

Didn't smell any SO2, I reckoned the nitric acid oxidation would be much faster. May, at these temperatures, the SO2 even be oxidized by nitric acid back to sulfate? In that case it may act like a catalyst for nitrous gas formation.

With only nitric acid/copper the reaction may even work with something like 15 ml of 20-25% nitric acid, which would be much more economical in terms of nitric acid usage than using 65% and may even rival the use of nitrite in terms of costs. Unlike the diazonium chloride and nitrate (if it is that), the diazonium sulfate is almost completely insoluble, thus may provde better control over crystal formation.
On the other hand, the decreased solubility of p-DDNP in the SA/nitrate salt reaction mixture may actually be the reason for the higher yield than from nitric alone.

[Edited on 29-8-2015 by nitro-genes]

Quote: Originally posted by PHILOU Zrealone

posted on 20-5-2015 at 21:21 I wonder if 3-diazonium-2,4,6-trinitrophenol does exist...thus a DDNP variant with the diazo in meta of the phenol and with 3 nitros... thus based on meta-amino-phenol. I also have good synthetic ideas about 3,5-diazido-2,4,6-trinitrophenol. Depending on the stability of iodoxy group vs phenol, nitro and diazonium group...one may also invesigate 3,5-diiodoxy-DDNP and 3,5-diiodoxy-TNP.

Quote: Originally posted by nitro-genes

posted on 21-5-2015 at 11:02 @Philou: 3-diazonium, 2,4,6 trinitrophenol must exist, since it is used as an intermediate in the synthesis of KDNBF, mentioned earlier. I've only seen it used to prepare the azido compund and uses very strong diazotising conditions at low temperatures, I reckon it would't be very stable. What was your idea about the synthesis of 3,5-diazido-2,4,6-trinitrophenol, sounds interesting

So here is my synthetic pathway to diazido-trinitrophenol!
Image:
Synthetic pathway to 3,5-diazido-2,4,6-trinitrophenol and hydroxy-azido-dinitrobenzofuroxan derivatives (5-azido-4,6-dinitro-7-hydroxy-benzofuroxane (o-HADNBF - ortho-hydroxy-azido-dinitrobenzofuroxane); 7-azido-4,6-dinitro-5-hydroxy-benzofuroxane (p-HADNBF - para-hydroxy-azido-dinitrobenzofuroxane ); 7-nitro-8-hydroxy-benzo-di-furoxane (o,p-HNBDF - ortho-para-hydroxy-nitrobenzodifuroxane))



Remarks:

1°)Note that the process will also work for mono-azido-TNP via m-chlorophenol...

2°)I thought about it since the preparation of 1,3,5-triazido-2,4,6-trinitrobenzene (TAZTNB) is easy from 1,3,5-trichloro-2,4,6-trinitrobenzene (TCTNB) and NaN3 in an appropriate solvent.

3°)Interesting fact: upon heating TAZTNB turns into hexanitrosobenzene (less sensitive and less powerful but stil as good as tetryl) what is in fact a benzo-tri-furoxan...this change occurs at moderate speed at ambiant T° (few % over several years) but becomes significant at each 10°C T° increase...

4°)Also a very good finding (for Rosco Bodine) is that TAZTNB is a good way to produce both azide salts and 1,3,5-trihydroxy-2,4,6-trinitrobenzene (trinitrophloroglucidol)

1,3,5-trichlorobenzene -HNO3/Oleum-> 1,3,5-trichloro-2,4,6-trinitrobenzene
1,3,5-trichloro-2,4,6-trinitrobenzene + hydrazine --> 1,3,5-trihydrazinium-2,4,6-trinitrobenzene tri-hydrochloride
1,3,5-trihydrazinium-2,4,6-trinitrobenzene tri-hydrochloride + NaNO2 --> NaCl + 1,3,5-triazido-2,4,6-trinitrobenzene + H2O
1,3,5-triazido-2,4,6-trinitrobenzene + NaOH --> NaN3 + 1,3,5-trihydroxy-2,4,6-trinitrobenzene

5°)About 3,5-diazido-2,4,6-trinitrophenol and hydroxy-azido-dinitrobenzofuroxan derivatives exposed above: salts of heavy metals or of amines (NH3, NH2OH, N2H4, (NH2)2C=NH, (NH2-C=NH)2), NH2-Tetrazole, NH2-NH-Tetrazole) must be quite powerful

[Edited on 1-9-2015 by PHILOU Zrealone]

possible alternative synthesis for o-DDNP

Hi Philou, thanks for this synthesis scheme, some interesting compounds, some of them never described before, especially the o,p HNBDF looks like a very interesting molecule, do you think it would be able to form salts? The synthesis route described looks doable, and apart from the NaN3 (which can be made OTC though) completely OTC. Pretty cool!

Some things I wondered about :

1 How selective would the chlorination of nitrobenzene be in producing only 3,5 dichloro nitrobenzene? This can probably be found in literature, but I haven't had the time yet to get a good look.

2. How selective is the Fe/HCl reduction in only reacting with the nitro group? Is there completely no dehalogenation? Does it need a certain strenght of HCl, or are acidic conditions enough? I'm asking, because probably, mono and dichloro aniline would be hard to separate

3. What would be the best solvent for the diazotization step, since dichloroaniline is not soluble in water, though it seems to be in ethanol. Ethanol can be used in some cases, but can give some coupling products IIRC.

4. It would be really cool to see how easily the resulting 3,5 dichlorophenol would be able to nitrate further as opposed to 1,3,5 trichlorobenzene. Do you have a reference for this nitration? Curious about how stable the chloro groups would be for the phenol.

5. the 3,5 dichloro 2,4,6 dinitrophenol would be a very nice precursor to have, the reaction with ethanolic hydrazine may produce a Di N-hydroxy benzotriazole, which has never been described before I think. If it would be stable that is, N-hydroxy benzotriazoles are notorious for explosions during synthesis IIRC. Definitely a nice mad science project, nice!



@ At Rosco, haha amazing, had the same idea and wanted to try it once! I never got around to finding a proper synthesis protocol for dinitrosalicylic acid, so thanks for the references. Also wondered how much easier the dinitro salicylic acid would reduce one nitro group, as opposed to trinitrophenol. Every TNP reduction scheme, other than with either commercial or homemade hydrogensulfide, seems to result in an mess from which only small amounts of picramic acid can be isolated. But indeed, this may be worth a try, I read the first reference you provided, and it indeed seems more selective than picric acid. There can be a big difference though between umol quantities as quantitative test and a high yield synthesis. Same goes for ascorbic acid and picric acid, which seems to form some form of inseparable complex with either picric acid or picramic, I read an article on this, but can't find it again, sorry.


Another question for those who may know more about organic chemistry than me:

Benzoxazolone can be made in high yield, completely OTC. From literature it seems the 6 and 5 positions are most activated, and 6-nitro benzoxazolone can be made from just 65% HNO3 in high yield by nitration at 0 deg C. Now, could you hydrolyze the oxazolone ring using reflux conditions and dilute mineral acids, or would the nitro group decompose? If you would get 2-amino 5-nitrophenol and nitrate it further, what would be the outcome? I couldn't find anything on this, not even for 3-nitrophenol. Suggestions for followup or stability of these compounds? This could be really interesting, as most of the reactions involved are smooth sailing.



[Edited on 2-9-2015 by nitro-genes]

Quote: Originally posted by nitro-genes

@ At Rosco, haha amazing, had the same idea and wanted to try it once! I never got around to finding a proper synthesis protocol for dinitrosalicylic acid, so thanks for the references. Also wondered how much easier the dinitro salicylic acid would reduce one nitro group, as opposed to trinitrophenol. Every TNP reduction scheme, other than with either commercial or homemade hydrogensulfide, seems to result in an mess from which only small amounts of picramic acid can be isolated. But indeed, this may be worth a try, I read the first reference you provided, and it indeed seems more selective than picric acid. There can be a big difference though between umol quantities as quantitative test and a high yield synthesis. Same goes for ascorbic acid and picric acid, which seems to form some form of inseparable complex with either picric acid or picramic, I read an article on this, but can't find it again, sorry. [Edited on 2-9-2015 by nitro-genes]

It is interesting if the route to o-DDNP from aspirin could be simplified to only require a dinitration condition, and would proceed at cooler temperatures. I don't know for sure but I think the reduction using sugar is selective for the one nitro and is not prone to further reduce the dinitrosalicylic acid to a diaminosalicylic acid. Most references only describe the color change as the point of interest for colorimetry tests of sugar content determinations done by titration to color endpoint for glucose solutions, where there is no actual isolation done for the 3-amino-5-nitrosalicylic acid which is identified as responsible for that color change that is produced by the sugar reduction of the dinitrosalicylic acid sodium salt.

Similarly there is a sugar determination by colorimetry possible using picric acid or actually it is sodium picrate being reduced in alkaline condition by glucose to form picramic acid sodium salt. Likewise for those reduction methods, there is described no actual isolation of the picramic acid. The reduction occurs in dilute solutions so the colorimetry methods may not be best for workup of more concentrated reaction mixtures where the desired result is isolation of the crystallized product of the reduction. The solubilities of the materials involved will govern what are the most desirable methods for reduction. Use of sulfides can be avoided even for the reduction of sodium picrate so those are candidate reduction schemes which may be adaptable to the reduction of dinitrosalicylic acid sodium salt, if glucose proves not to be desirable for use when the product of reduction is wished to be isolated as a solid, instead of only wished to produce a color change in a solution.

Many are the joys of dye chemistry! The fun just never ends!
Some of these dyes have such penetrating properties that they can stain a hole right through armor plate.

[Edited on 9/3/2015 by Rosco Bodine]

Viable route to a possible iso-DDNR? What do you guys think?

Up to the reduction of 5-nitro benzoxazolone to 5-amino benzoxazolone is described in literature, the nitration of the latter isn't, so this is somewhat of a guess that the 4,6 nitro derivative would result, same for the oxidation/diazotization.



[Edited on 7-9-2015 by nitro-genes]

70% nitric acid means 70 grams of HNO3 per 100 grams, the molecular weight of HNO3 is 63, that means 1.11 moles of HNO3 per 100 grams of 70% nitric.

The molecular weight of acetaminophen is 151.2, since we need about a 2.2 molar equivalent to obtain the dinitroacetaminophen, we need (2.2/1.11)*100= 198 grams of 70% nitric to nitrate 1 mole or 151.2 grams of acetaminophen. Density of 70% nitric acid at 20C = 1.4134 --> so we would need 198/1.4134 = 140 ml of 70% nitric.

For 20 grams of acetaminophen, we need (20/151.2)*198= 26.2 grams 70% nitric, or 26.2/1.4134 = 18.53 ml

If we rougly use the figures from patent GB24409 for the sulfuric acid, the synthesis would look something like this:

- Pour 27 grams (15 ml) of 96% sulfuric acid in a small 100 ml beaker, and slowly add 26.2 grams (18.5 ml) of 70% nitric acid, while keeping temperature below 20 deg C.
- In a seperate beaker on ice, dissolve 20 grams of finely powdered acetaminophen in 75 grams (41 ml) 96% sulfuric acid at <10 deg C.
- When all the acetaminopehn is dissolved, slowly add the sulfuric acid/nitric acid in 2 ml portions, while keeping temp around 5 deg C.
- After the last addition, keep stirring on ice for 1 or 2 hours.

Etc...

Good luck and keep us posted!


Regarding the synthesis of 3-azido 2,4,6 trinitrophenol as a precursor to the benzofuroxan posted earlier:

US 8748639 B1
3-azido-2,4,6-trinitrophenol, method of making, and method of transforming

12 mL of concentrated sulfuric acid were charged to the flask depicted in the experimental setup, and agitation was initiated. 0.897 grams (0.0037 mol) of 3-APA was then added and rinsed down with an additional 3.5 mL of concentrated sulfuric acid. The 3-APA dissolved readily and heating the reaction mixture was unnecessary. The resultant solution was cooled to 3° C. using an ice water bath, and 0.39 grams (0.0057 mol) of NaNO2 dissolved in 6 grams of concentrated sulfuric acid was added dropwise, keeping the temperature below 5° C. This addition took less than 5 minutes. The resultant solution was then stirred for 20 minutes at that temperature. 25 mL of phosphoric acid was then added at such a rate that the temperature did not exceed 5° C. This addition was somewhat exothermic and occurred over 45-50 minutes. After addition was complete, the reaction mixture was stirred at less than 5° C. for 10 minutes. During the addition and subsequent stirring, the reaction mixture became quite viscous and attained a pink-orange color. 1.18 grams (0.018 mol) of NaN3 was then added in portions, keeping the temperature below 5° C. This addition took less than 5 minutes. The reaction mixture was then stirred at less than 5° C. for 20 minutes, and was then allowed to come to room temperature by removing the ice water bath. Once the reaction mixture had reached room temperature, it was poured into 70 mL of cold (<5° C.) water with stirring. The resultant yellow precipitate was then collected by filtration, and washed with 2×20 mL of cold water. The yellow solid exhibited some water solubility, so the water washed were retained for further analysis and/or crystal growth. The remaining precipitate was then dried in a dessicator, and yielded 0.44 grams (44% yield)."

The following patent Patent US2129136 may be interesting, possibly the ethylsulfate diazonium salt of 3-diazo 2,4,6 trinitrophenol may be formed as a reasonably stable intermediate, possibly circumventing the synthesis abovem which would be unsuitable for scaling up IMO.

Instead of adding phosphoric acid and NaN3 to the sulfuric acid/diazozium mixture, ethanol may be added slowly in order to form the ethylsulfate in situ and precipitate the ethylsulfate diazonium salt, which may be reacted with 2 equivalents of hydrazine directly at low temperatures to produce the benzofuroxan. Even better would be the reaction of calcium hydroxide or carbonate and hydrazine sulfate.

[Edited on 8-9-2015 by nitro-genes]

I just tried Nitro-genes dinitration of acetaminophen but used 70% Nitric acid instead of ammonium nitrate but something weird happened at the end.

I dissolved the Acetaminophen in 41 ml 98% Sulfuric acid and made the nitrating mix without going over 20 Degrees.
Cooled the Acetaminophen/Sulfuric acid to below 5 Degrees and started to add the nitrating mix in small portions. It responded in a temp rise very quickly going up a degrees when 4 drops were added at the start and then after about 20 drops halfway through.
The mixture attained a dark brown colour when half the nitrating mix was added as was stated in the synth. The colour started to fade to orange after the halfway point.
When there was only about 10-12 ml of nitrating mix left to add, yellow precipitate started to build up almost instantly and stopped the stir bar from even being able to spin because it got so thick so fast as can be seen in second picture. After a minute the whole thing was just a mass of fine crystal soup.
As it couldn't stir automatically anymore, I stirred by hand for another 5 minutes and then added the crushed ice which can be seen in the third and fourth pictures.
It looks like what dinitroacetaminophen has been described to look like and dyes the skin yellow on contact.
Still useable even though the last bit of nitrating mix was not added?


[Edited on 11-9-2015 by greenlight]



[Edited on 11-9-2015 by greenlight]

Hi Greenlight,

The nitration is exceedingly fast, I think most of the dinitroacetaminophenol present suddenly all precipitated from the nitration mix in the form of presumably small needle shaped crystals, making the mix very hard to stir. I've seen the same happening with AN, though not to this extent, which may be a propertie of the added AN, or extra SA present. For the synthesis I posted in the prepublication section I also added the remark that with minimal sulfuric acid present, the mix becomes very viscous and difficult to stir, maybe for the next time the acetaminophen is better dissolved in slightly more sulfuric acid for the nitration using 70% nitric acid, say 100 grams instead of 75 grams. Alternatively, it may help to keep the nitration mix at 10 degrees C after half of the SA/nitric acid is added. Anyway, I would just continue, the only uncertainty is how much of the mono-nitro compound is present in the precipitate.

Dissolving the precipitate again may be very difficult, you could try dissolving at 10 deg C. again, but do it with half the precipitate you obtained. There is no amount specified, because unless recrystallized, the DNAc will slowly partly deacetylate from the remaining acid impurities, so I usually just continue anyway. The deacetylation step is not very critical regarding the amount of sulfuric acid present, 12.5 ml of 96% SA should be enough for even a 100% yield to deactylate and form the isopicramic sulfate.

@ Greenlight, how did the deactylation work out? Can you take a look at your bottle of 70% HNO3 btw? Is it w/w or v/v? Did you weigh the HNO3 or used ml? If it is v/v, it would explain why all DNAc precipitated out and no mononitro may be present at all. Should have asked in advance, just .don't know what is more standard commercially, since I usually distil it myself and add water to a density of 1.42, which translates to 70% w/w


[Edited on 13-9-2015 by nitro-genes]

Quote: Originally posted by nitro-genes

Hi Philou, thanks for this synthesis scheme, some interesting compounds, some of them never described before, especially the o,p HNBDF looks like a very interesting molecule, do you think it would be able to form salts? The synthesis route described looks doable, and apart from the NaN3 (which can be made OTC though) completely OTC. Pretty cool! Some things I wondered about : 1 How selective would the chlorination of nitrobenzene be in producing only 3,5 dichloro nitrobenzene? This can probably be found in literature, but I haven't had the time yet to get a good look. 2. How selective is the Fe/HCl reduction in only reacting with the nitro group? Is there completely no dehalogenation? Does it need a certain strenght of HCl, or are acidic conditions enough? I'm asking, because probably, mono and dichloro aniline would be hard to separate 3. What would be the best solvent for the diazotization step, since dichloroaniline is not soluble in water, though it seems to be in ethanol. Ethanol can be used in some cases, but can give some coupling products IIRC. 4. It would be really cool to see how easily the resulting 3,5 dichlorophenol would be able to nitrate further as opposed to 1,3,5 trichlorobenzene. Do you have a reference for this nitration? Curious about how stable the chloro groups would be for the phenol. 5. the 3,5 dichloro 2,4,6 dinitrophenol would be a very nice precursor to have, the reaction with ethanolic hydrazine may produce a Di N-hydroxy benzotriazole, which has never been described before I think. If it would be stable that is, N-hydroxy benzotriazoles are notorious for explosions during synthesis IIRC. Definitely a nice mad science project, nice! Another question for those who may know more about organic chemistry than me: Benzoxazolone can be made in high yield, completely OTC. From literature it seems the 6 and 5 positions are most activated, and 6-nitro benzoxazolone can be made from just 65% HNO3 in high yield by nitration at 0 deg C. Now, could you hydrolyze the oxazolone ring using reflux conditions and dilute mineral acids, or would the nitro group decompose? If you would get 2-amino 5-nitrophenol and nitrate it further, what would be the outcome? I couldn't find anything on this, not even for 3-nitrophenol. Suggestions for followup or stability of these compounds? This could be really interesting, as most of the reactions involved are smooth sailing.

1) Selectivity is high because nitrobenzene is strong meta-director. Meta-halo-nitrobenzene is obtained in good yields. Normaly 1,3,5-di-halo-nitrobenzene should be obtainable by further treatment with excess réactants, since addition of a single halo atom will not change much the meta directing effect of the nitrogroup.
Here is a synthesis of 3-chloro-nitrobenzene from isocyanuric acid trichloride and H2SO4


Alternatively one may get acces to 1,3-dihalo-5-nitrobenzene in high yields (>95%) via p-nitro-aniline halogenation --> 2,5-dihalo-4-nitro-aniline and reductive diazotation with ethanol --> 1,3-dihalo-5-nitrobenzene

2) Fe/HCl reduction needs aqueous concentrated HCl (>20%) it is very selective of the NO2 group; so halide atoms won't be hydrolysed...alternatively one could use Sn/HCl, SnCl2/HCl, Zn/HCl or even Zinin reduction with Na2S/S/NaOH. --> 3,5-dihalo-aniline

3) Water will be fine especially if you use the ability of the aniline to form water soluble salts like Ar-NH2.HCl the later could be reacted with saturated NaNO2 aqueous solution
Ar-NH2.HCl + NaNO2 --> Ar-NH2.HNO2 + NaCl
Ar-NH2.HNO2 --> Ar-NH-N=O + H2O <==> Ar-N=N-OH (diazonium)

4) 3,5-dihalo-phenol should be nitratable easily like phenol since the halide helps a little the introduction of the nitros in a sympathetic pathway of the OH. The resulting dihalo-TNP will be stable in acidic media, but prone to dehalogenation (hydrolysis) in basic media.

5) Yes hydrazine may enter the molecule at the place of the halide, just like NH3 would or other amines
--> Methylamine for a tetryl variant (3,5-di-methylnitramino-2,4,6-trinitro-phenol ).
HO-C6(NO2)3(-N(NO2)-CH3)2

Care must be taken because depending on conditions hydrazine may reduce some NO2 groups...
On another thought dihydrazino-TNP would maybe form a mono or disalt of HClO4 or HC(NO2)3...
HO-C6(NO2)3(-NH-NH2)2 . 2 HClO4
HO-C6(NO2)3(-NH-NH2)2 . 2 HC(NO2)3

Also interesting the dihydrazino compound upon action of HNO2 will form the diazo-TNP (I like the coherence of chemistry).

6) About your idea of hydrolysis of benzoxazolone, acidic media should be OK without splitting the NO2.
But the resulting o-amino-phenol must be quite oxydisable by the air...probably forming easily o-quinonic compounds.
H2N-C=C-OH -Ox-> HN=C-C=O + H2O (aromatic ring left aside for clarity)
The later may condense with the non-oxydised product forming a 3 colladed extended aromatic ring...
HN=C-C=O + H2N-C=C-OH --> cyclo(-N=C-C=N-C=C-) + 2 H2O

[Edited on 14-9-2015 by PHILOU Zrealone]

Quote: Originally posted by nitro-genes

Viable route to a possible iso-DDNR? What do you guys think? Up to the reduction of 5-nitro benzoxazolone to 5-amino benzoxazolone is described in literature, the nitration of the latter isn't, so this is somewhat of a guess that the 4,6 nitro derivative would result, same for the oxidation/diazotization.

thanks for explaining all that philou, it's a lot to think about, I need to let it all sink in before making a thorough reply. You are right about the 5,2-amino 4,6-dinitrophenol, the 5 amino group won't oxidize or form the diazo, same as for picramide probably. The resutling compound, which might be called 2 -diazo 5-amino, 4-6 dinitrophenol might still be interesting if it exist and might form nitrate salts or perchlorate salts when diazotized in the corresponding acids using nitrite or even complex with transition metal salts containing nitrates or perchlorates, although this isn't reported for trinitroaniline itself, so maybe that won't happen.

5-diazo-styphnic acid ....(exist?)

On the preceding page the 3-diazo-picric acid was documented

http://www.sciencemadness.org/talk/viewthread.php?tid=439&am...

If the hydroxylamine reaction with styphnic acid would occur similarly as with picric acid, then a 5-amino-styphnic acid would result, which could possibly be diazotized to 5-diazo-styphnic acid.

No search has yet been done to see if this contemplated compound and resorcinol derivative is known.

Even if it is unstable and one of the 3 nitro groups hydrolyzes easily, the resulting dihydroxy-diazo-dinitrophenol-(1-anhydride) compound would possibly itself be interesting.

Update: the 5-amino-styphnic acid is known CAS 128585-26-2



Formula: C6H4N4O8
Molecular Weight: 260.11800

Synonyms:

5-amino-2,4,6-trinitro-1,3-benzenediol

5-amino-2,4,6-trinitro-resorcinol

The reported synthesis circa 1928 involves 3,5-dinitroaniline being further nitrated to pentanitroaniline and presumably followed by hydrolysis, which is far more complicated than the possible reaction of hydroxylamine with styphnic acid.

So the precursor 5-amino-styphnic acid exists and upon diazotization may lead to a nitro-iso-DDNR and / or upon hydrolysis of the third nitro may provide a hydroxy-iso-DDNR.

These compounds would fit the general template for more powerful derivatives of DDNR as described by the Von Herz 1922 patent GB207563

[Edited on 9/15/2015 by Rosco Bodine]

Deacetylation finished.
Hour under reflux at 95 Degrees, solution went from yellow to dark red, cooled, transferred to beaker and Ammonia solution added in small portions until p 4.
Brick red precipitate filtered and drying. One of the fastest compounds I've ever filtered

[Edited on 16-9-2015 by greenlight]

Nice! looks like a good yield too. When it dries, you'll see it will take on a more orange colour. Filtering is very easy indeed, I suspect they are agglomerates of small crystals, like Dabney has described. Did you filter the deacteylation mix after cooling btw? Or did you see no precipitates in the dark red solution at all? Usually there is about 100-200 mg of undissolved dark brown stuff in the filter, I suspect some left over impuritities from the tablets. What solvent and by what method did you purify the paracetamol?

Are you planning the diazotization using nitrte or sulfuric acid/nitrate salt/copper? Curious if you get the same results, from the copper method I got incredibly dense and free flowing pDDNP.

[Edited on 16-9-2015 by nitro-genes]

Thanks! Yes, I cooled down and then filtered and there was a small amount of brown precipitate in with the solution. I extracted the acetaminophen using the exact method and amounts from your writeup and I used 95% Ethanol.

I was going to attempt the diazotization with Nitric acid but in your writeup it says that excessive temperatures can cause formation of sensitive sprengel explosives so I am unsure for my first time.
How bad do you think the dangers are?
Otherwise, I will go with the sulfuric acid/ copper/nitrate salt (probably using KNO3) in a fume hood as I am not keen on any NOX

Also, should i be storing the iso-picramic acid I don't use straight away under distiller water?


[Edited on 16-9-2015 by greenlight]

Wouldn't use the 65% nitric acid alone synthesis, it give fairly low yields, presumably since much of the product is oxidized, what precipitates seems very pure though. Not sure about the risks of explosion, 65% nitric acid contains a fair amount of water, if you want to do the reaction with nitric acid, you could always use a large excess, say 30 ml for 1 gram of isopicramic, but it seems a terrible waste to me.

The copper method produces very nice yield with diluted sulfuric acid and nitrate salt, I tried both ammonium nitrate and potassium nitrate once, the potassium nitrate seemed to result in slightly higher yield.

Another thing you could try is a combined nitric acid/copper method, something I haven't tried yet:

You could try to add 1 gram of isopicramic acid to 15 ml 20-30% nitric acid, add the copper beads and keep at a temperature for which gentle generation of NOx is evident. The extra dilution will eliminate explosion hazards and prevent sudden exotherm, with some tweaking, a concentration of nitric acid and temperature can probably be found that produces good yields, while releasing a slow and minimal amount of NOx to the surrounding.

Regarding storage..I must admit, I have stored it in a dry and airtight container, away from sunlight, since the stability of the compound in distilled water or in sunlight is presently unknown. Isopicramic acid doesn't appear a direct explosion hazard, upon flame it first needs to melts and then steadily burns, leaving a lot of carbon. The potassium salt and sodium salts seem somewhat more energetic and could probably explode when burned under strong confinment. The ammonium salt is much tamer, that is why the deactylation is performed preferably with ammonia.

[Edited on 16-9-2015 by nitro-genes]

It was mainly the heating of the isopicramic acid with fuming HNO3 that would possibly be a safety issue, even though that has been done industrially with picramic acid to make DDNP, as a Dehn patent process, there is an ignition hazard where the batch is covered with mineral oil to prevent the spontaneous ignition of the fumes by reaction with oxygen in the air. Igniting a vat of DDNP in fuming HNO3 could become a crater geometry exhibit where a plant used to be

The use of a lesser concentrated HNO3 would likely be much safer and okay especially something like maybe a 35-40% HNO3 would probably be no issue. Safety is a kind of compromise where a too mild condition quenches a reaction or prevents good yields, but too harsh conditions may offer no advantage either, and have disadvantages, so there is found some happy middle ground condition where a process is reasonably optimized. It will work that way for most syntheses where you develop the best process gradually from a kind of trial and error testing to find what works.

Quote: Originally posted by greenlight

Deacetylation finished. Hour under reflux at 95 Degrees, solution went from yellow to dark red, cooled, transferred to beaker and Ammonia solution added in small portions until p 4. Brick red precipitate filtered and drying. One of the fastest compounds I've ever filtered [Edited on 16-9-2015 by greenlight]

Thanks Roscoe, I will use the diluted nitric

@Dave, I was using a dropper to dispense the ammonia solution from a bottle so I am unsure of exact amount.
It was a fair bit though, about 100-150ml.

[Edited on 17-9-2015 by greenlight]

So using the dilute HNO3 is untested ground on here.

I am going to use nitro-genes method with a nitrate salts to get the feel for the reaction and see how much NO2 fumes should be evolving as well as how the reaction mixture should look while performing the diazotization. This will give me some DDNP to experiment with initiating secondaries with.
Then I will attempt the diazotization with dilute HNO3/H2O mix first using one of the amounts listed in the above post by Nitro-genes (15-20ml 20-30% HNO3) probably starting with the more dilute acid first. I'm thinking 25% to avoid that transition were more NO is formed than NO2 that you stated.
So the variables performing a 1 gram batch with isopicramic acid and dilute HNO3 would be:

* Nitric acid concentration
* Nitric acid amount used
* Temperature
* Reaction time

There will be an optimum reaction environment, the task is just finding it

Maybe dripping the final reaction mix from an addition funnel into ice water that is being agitated (safely) would afford more desirable DDNP crystals.

Only other question is will the dilute HNO3 produce a better yield than the nitrate salt method?





[Edited on 17-9-2015 by greenlight]

Can the final product be recrystallized via acetone if the proper crystal size is not obtained.

When I attempt the diazotization with dilute HNO3 instead of nitrate salt I will make sure everything is recorded and hopefully an optimum reaction condition can be found.
And yes, I have noticed that there is very little information available on DDNP anywhere else on the internet but did not know that SM has the most extensive collection

Very right...though may I add that perfect 0.5 cm long needle shaped crystals are best avoided? Crystal breakage, static, low density etc. Believe me, I've seen them for p-DDNP. It happens for very dilute solutions of the isopicramic chloride/sulfate at very low temperatures. When recrystallized from boiling dH2O/1% HCl, pDDNP formed almost hair like crystals, very thin,long and flexible, almost like wool. Recrystallization from acetone is not necessary, when boiled too long, it can even decompose part of the product and lead to less purity. On the other hand, residual sulfuric acid in the product from copper/SA is adds an unknown to long term stability. It's interesting though, one of the culprits of DDNP has been obtaining a product with high bulk density. Both times the copper method gave a bulk density that was incredibly high, first time I thought my yield was terribly low and contemplated to throw the batch away without weighing, glad I did. Tomorrow I'll see if I can reproduce it and trow in some 40x manification pictures.

The p-DDNP from the isopicramic obtained directly after deacetylation in general yields glittering p-DDNP with a silver/golden sheen, which only happens for very pure DDNP in general.

[Edited on 17-9-2015 by nitro-genes]

In reponse to a U2U from Greenlight, and after rerunning the nitrate/SA/Copper diazotization, the method outlined in the prepublication section doesn't work, I couldn't reproduce the results I posted earier. It seems the reaction needs a minimized water content to proceed using only mild heating. Most likely, I left the reaction on the heater plate for longer period of time, for which the water content may have become lower than that what was started with. I've redid the reaction and tried to replicate the results, this time monitoring the reaction.

To produce the very dense crystals is more tricky than I thought, if there is a large exotherm from the reaction with copper, there is no time for crystal growth and almost amorphous DDNP seems to be formed.

Best result (with minimized quantities of reagents) was obtained by the following method:

- While stirring, 3 ml of 96% sulfuric acid was added to 3 ml water in a 25 ml beaker and left to cool to below 50 deg C.
- Than add: 2.2 g KNO3, 1 g isopicramic acid, and 2 gram of copper ("beads" from electricity wire)
- Give it a good swirl, to break up any remaining lumps and put some clear foil over the beaker to prevent NOx from escaping
- Keep the mixture between 40 and 50 deg C. for one hour while stirring, wash with water several times, filter and wash until filtrate is not green anymore

Very dense, light orange-brown p-DDNP, yield will be determined (its not dry yet) and I'll add some 40x magnification pictures of the resulting crystals in the coming days too.

Very interesting how the reaction does not proceed at all when water content is above a certain threshold, although NO is produced (fizzing of solution) and the isopicramic just floats around, it isn't oxidized or something. Maybe the NO2 is indeed doing the work here...puzzled...

[Edited on 24-9-2015 by nitro-genes]

I just attempted Nitro-genes revised last step from isopicramic acid to DDNP.
1 gram isopicramic, 2 grams copper beads, 2.2 grams Potassium nitrate, 3 ml 96% Sulphuric acid and 3 ml distilled water were used.
Heated for an hour at about 46-47 Degrees celcius with clear foil wrapped around the beaker to prevent escape of NOX before being poured into ice cold water and filtered.
Does this look right before I get my hopes up waiting for it to dry?

[Edited on 25-9-2015 by greenlight]

Disregard the above results, the product is not DDNP at all, the colour looks wrong too.

I had another attempt today with the same procedure and even added about 1 ml of 30% HNO3 half way through to see if that improved things, but still no luck.
All my reagents are pure and the copper beads are the right size, the only things is I don't get a greenish tint to the brown solution that nitro-genes speaks of at the end of the hour heating at 50 C.
Maybe I am not heating for long enough.


[Edited on 26-9-2015 by greenlight]

textbook download links

Here are a couple of textbook download links that are for books provding some general information

The Aromatic Diazo-compounds And Their Technical Applications

by Saunders, K. H Published 1936

https://archive.org/download/aromaticdiazocom031270mbp/aroma...


The Chemistry of the Diazo-compounds

John Cannell Cain, Published 1908

https://books.google.com/books/download/The_Chemistry_of_the...

crystallization modifiers

There was earlier in this discussion a speculation that there may be a modified crystal formation possible through a cocrystallzing of the two different isomers of o-DDNP and p-DDNP and I have found an obscure reference which tends to support the idea of the one isomer operating to modify the crystallization of the other, described for the case where o-DDNP is crystallization modified by the presence of p-DDNP in small amounts. I believe it is possible the reverse scenario is also true, that the presence of the one isomer of DDNP will work to modify the crystallization of the other.

See patent US2103926 which describes this effect. Also are listed a series of other materials which can also accomplish a modifying of the crystallization.

See the screenshot from that patent, middle of line 8 "isopicramic acid" is shown as a crystallization modifier for ordinary o-DDNP, but under the reaction conditions it is a given that it is probable the effect is also from p-DDNP and the distinction is unclear.



Attachment: US2103926 DDNP manufacture.pdf (382kB)
This file has been downloaded 815 times

OK, here as promised the photos of the nitrate/SA/copper diazotization:

Left column are from nitrate/SA/copper diazotization described earlier, right column is also very dense and free flowing p-DDNP, produced by slowly adding a sodium nitrite solution (30 minutes) to a isopicramic acid/SA solution at 30 deg C. Short story, slow nitrite addition makes best rounded crystals, though the nitrate/SA/copper method produces slightly cleaner pDDNP, as was to be expected, but more agglomerates of tiny crystals (hard to see in photo).

@Rosco, I'll try the o-DDNP/p-DDNP diazotization, any suggestions for best approach?



[Edited on 30-9-2015 by nitro-genes]

After some more experiments regarding how the synthesis conditions for p-DDNP affect crystal shape, it seems the most influential condition determining the formation of plate like structures or almost spherical crystals seems whether the starting point is a completely clear solution of pDDNP in a strong acid, or from undissolved isopicramic as a suspension, the former producing plates, the latter more rounded structures when the nitrite is added slowly. I'm guessing the crystal shape of the isopicramic itself may be very important in determing crystal shape. The isopicramic obtained after deacetylation using sulfuric acid consists of sort of spherical aggregates of tiny needle or plate like structures as described by Dabney. Purely guess work, but perhaps by careful maintaince of undissolved and dissolved isopicramic acid these spherical like structures are both diazotized and "filled up" by acting as nucleation points for the p-DDNP formed from the soluble isopicramic acid part, which in combination with strong stirring may lead to the spherical shapes.

Diazotization of the potassium salt of isopicramic was tried before, not sure if I mentioned it though. Even when kept cold, the basified isopicramic seems to produce numerous dark coloured byproducts when the acid is added slowly, I don't see a way to do this, other than perhaps a carefully choosen slighlty acidic buffer solution. Plunging in the acid instead of adding drop by drop is no problem and gives good quality p-DDNP, so most likely the first additions lead to minor HNO2 formation in an environment that still has a too high pH, leading to oxidation, as is evident from the fact that at a certain point during the additions, it turns very dark. Maybe checking pH at this point and performing the reaction in a buffer slightly more acidic could prevent this.

Some 40x photos of experimental diazotization schemes will follow.

Quote: Originally posted by Rosco Bodine

I have an idea for a possible alternative method of synthesis for o-DDNP based upon nitration of salicylic acid to 3,5-dinitrosalicylic acid, followed by reduction by sugar to 3-amino-5-nitrosalicylic acid. This would be subjected to a combined diazotization and further nitration with accompanying decarboxylation to form o-DDNP. Attachment: Dinitrosalicylic_acid_as_a_reagent_for_the_estimation_of_sugar.pdf (344kB) This file has been downloaded 24 times Attachment: Meldoa et al 5-Aminosalicylic acid and derivatives 533.pdf (326kB) This file has been downloaded 29 times Aspirin could be used I think as the starting material since it would be easily deacetylated by the nitration mixture leading to 3,5-dinitrosalicylic acid. The sodium salt would be formed and dissolved in hot water for reaction with fructose or glucose. [Edited on 9/1/2015 by Rosco Bodine]

Recently did some experiments regarding the synthesis of 3-5 dinitrosalicylic acid (DNSal), seems like an interesting compound since it may be useful for several purposes:

1. Determination of glucose concentrations by reaction under alkaline consitions to produce the bright red coloured 3-amino-5-nitrosalicylic acid
2. Conversion of the resulting 3-amino-5-nitrosalicylic acid to o-DDNP
3. Reaction with excess urea may produce 3,5 dinitro salicylamide, which after hofmann rearrangement may produce 3,7-dinitro benzoxazolone (Wasn't able to find this compound, so it may not exist or cannot be synthesized this way, hypochlorite may also interact with the benzene ring since the nitrogroups promote formation of all kinds of meissenheimer complexes under basic conditions (chloropicrin?). So not sure about this one, although supposedly m-nitro aniline can be formed by hofmann rearangement of 3-nitrobenzamide. If this would work however the 3,7-dinitro benzoxazolone may be hydrolysed under mild conditions by a strong acid to yield a soluble picramic acid salt that can be titrated with a base to yield free picramic acid (analogous to isopicramic), which would be a hydrolysis and purification step in one. This route may have some advantages over reduction of picric, since in my experience benzoxazolone is stable to further attack during the hofmann rearangement, whereas over or under reduction of picric is always a danger, as well and canbe obtained in very high yield as well as that the reduction of PA can produce difficult to filter sulphur particles. Further nitration of 3,7-dinitro benzoxazolone may also be interesting, though perhaps not possible without hydrolysis.
6. Salts of DNSal may form interesting pyrotechnic compositions with chlorates/perchlorates

Anyway, where was I? Ah yes... DNSal synthesis

The synthesis protocol for the first article is pretty limited regarding detailed information. I attempted the synthesis using 10 grams of salicylic acid from hydrolysis of aspirin, only replacing the large excess of nitric acid used by an equimolar amount of ammonium nitrate and sulfuric acid. The reaction was kept between 5 and 10 deg C during the additions (45 minutes) and was stirred at 0 deg C. for an additional hour before crashing on ice. After recrystallizaton from boiling water, there were 3 distinctly seperate colours and crystal structures present, melting point of between 120 and 140 deg C. The solution further darkened pretty fast in sunlight, which lead me to believe that the product was mostly composed of 3 and 5 mononitro salicylic acid, together with a small amount of DNSal. Obviously, the presence of the deactivating nitro and carboxyl group prevents dinitration at these temperatures. The synthesis utilized by Meldola uses a very large excess of fuming nitric acid to overcome this. During the synthesis of piric acid there seems to be however very little decarboxylation going on below 60 deg C. So I tried the synthesis again heating in increments to 50 deg C to see if DNSal may be produced at higher temperatures and without an extreme exess of fuming nitric acid. Also here the use of AN may have some benefits over NA, since the formation of some of the NOx secies responsible for the decarboxylation (nitrous acid for example) may be hindered by the presence of the ammonium. The procedure looked something like this:

70 grams of 97% sulfuric acid was poured into a 250 ml glass beaker. The beaker was added to an icebath together with a thermometer put on a magnetic stirrer plate, after which 12.5 (2.2 molar eqv) grams of completely dry ammonium nitrate was added and stirred for 5 min to dissolve. When the AN/SA solution was cooled down to 0 deg C., 10 grams of finely powdered salicylic acid was added in about 0.5 gram amounts while keeping the temperature between 5 and 10 deg C. The exotherm is a mean one and lags considerably, so the total addition took almost 45 minutes to complete. During the aditions the mixture takes on a very slight yellow colour. After the final addition the mixture was stirred in the icebath for another 30 minutes, after which the mixture had thickened considerably and looked like unwhippped cream (off white colour, slight yellow tint). The beaker was then removed from the hotplate and allowed to slowly come to room temperature while stirring and kept there for another 30 minutes. Then the mixture was slightly heated to 40 deg C. for another hour, no decarboxylation was observed yet, viscosity was much lower and stirring easy. After briefly heating to 50 deg C, I thought to see some gas formation and icecold water from the ice bath was added to a total volume of 250 ml. The mixture was prety thin after adding the water and needed to be put at 4 deg C. for several hours for precipitating the product. After 1 hour the entire mixture had solidified to one mass. After stirring the suspention briefly with a thermometer to loosen things up, it was filtered, washed with 300 ml of icecold water and put in a clean 250 ml beaker again. To this was added 150 ml of boiling dH20 to dissolve completely and left to cool to 4 deg C in the fridge. As Meldola observed, the light yellow solution is prone to supersaturation, and was cooled almost completely when crystallization commenced. The crystals look much cleaner this time, sort of large spherical aggregates of cream coloured needle shaped crystals, clining together as one solid mass. Sort of resembles a heavy crowd of sea urchins. (Hehe, there is probably a more professional word for this).

Total yield after drying was 16.17 grams of DNSal from 10 grams of salicylic acid. This would represent a 97.9% yield, which seems a bit high. Maybe there is some TNP contamination explaining the high yield, or perhaps DNSal forms a hydrate. For the monohydrate, the yield would translate to 90.7%.

The dry material behave peculiar on the hotplate. When heated fast, it briefly partially melts at around 150-160, only 30 seconds later to solidify again, thereafter melting at around 180 deg C. Best bet would be DNP/MNS contamination, which probably sublimes at around 150, leaving only DNS behind. Other explanation would be it releases its hydrated water. Opinions?





[Edited on 29-10-2015 by nitro-genes]

Another random crazy idea with regard to OTC production of styphnic acid and DDNR:

Would it be possible to convert picric acid to styphnic acid using fenton chemistry? Phenol can be synthesized from benzene by ferrous sulfate and hydrogenperoxide, generating the extremely reactive hydroxyl radical, which is able to replace an aryl hydrogen. Another example is supposed dinitrocatechol intermediate in destruction of dinitrophenol using fentons reagent. Reaction with 2 ortho nitrogroups unknown, possibly replacement of nitrogroup? Since percarbonates are OTC, the idea might not be worth a try..

[Edited on 9-11-2015 by nitro-genes]

Thanks to Solo for uploading the article!

Seems Klapotke's group has done a folow up on the dinitrodiazophenols, summerized in a recently published paper (attachment). The article has some interesting features, though the exact scope of the article is not completely clear, the title suggests testing of the initiation capabilities of some of the novel diazo compounds described, whereas the most promominent feature of the article is mainly the nitration of N,N protected p-phenylendiamines using different nitration and deprotection schemes. Maybe they were looking for an efficient 1 or 2 step synthesis for the DDNR or the tetranitro derivative of the p-diamine as they claimed, though could not be realized this way. The nitration of p-chloroaniline seemed like a good candidate for the former, too bad the chlorine won't budge. An interesting features is also the first time shown existence of 3-amino DDNP, presumably from the mobile nitrogoup rerangement to the nitramine and decomposition to the diazo during the deprotection in sulfuric acid. It has expected very high density and roughly a DDNP comparable sensitivity to impact. Some flame sensitivity test video clips in the supplementary should be obligatory, I mean, isn't that why we make these things?

The HODDNP (DDNR sound better IMO, but maybe has a to SMDB'ish ring to it ) really seems a very potent initiator, not only was 10 mg was enough to initate RDX, the DDNR itself seems very stable to heat and moisture (for a diazo compound anyway), although acidity and metal compatibility may still be an issue. For that matter, it may also be nice to see properties of some salts of DDNR.

Personally would have liked it if they had also included a more thorough analysis and comparison between o-DDNP and p-DDNP, maybe using PETN for more resolution between the two and some statistics, but then again the initiating difference between the two likely is not that large anyway, so more of an academic discussion than of real practical value.

Attachment: Synthesis and Initiation Capabilities of Energetic Diazodinitrophenols.pdf (754kB)
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[Edited on 7-12-2015 by nitro-genes]

There is a conspicuous absence of original references and history regarding the DDNR and an odd avoidance of calling DDNR what it is and strangely applying a new naming to an old compound.

Anyway it seems they are going to some trouble to ignore information already presented here in our discussion and avoid questions raised also.

It just seems very odd, because we know that they are aware of our discussion here.

We have already identified simpler routes to DDNR via the original work of Benedikt and Hubl from mononitroaminoresorcinol or dinitroaminoresorcinol and other schemes from resorcinol or styphnic acid as the starting material.

We have also identified the route for DDNR via the further acetylation of paracetamol using acetic anhydride to form the diacetyl derivative which may be nitrated to the trinitro compound, and deacetylated,
and diazotized with a concurrent loss of the 3-nitro decomposed to a hydroxyl to form DDNR, similarly as reported in the earlier Klapotke article, and earlier by Meldola who is still not credted by Klapotke.

It seems they are going out of their way to not identify the actual history of DDNR.

And it is still an unresolved issue that the compound is a 6-diazo as Klapotke is identifying DDNR, which would require a diazo rearrangement from the 4-diazo as would initially form from a 4-amino precursor, and this seems unlikely. I think this follows somewhat the earlier confusion of Meldola about a supposedly "mobile" nitro group that later turned out to be not mobile at all



[Edited on 12/7/2015 by Rosco Bodine]

The naming is odd, I propose DiDiDIB or BeDiDIDI instead (dihydroxydinitrodiazobenzene), which sounds better than HODDNP.

Why the original historic references are not included is also surprising, perhaps it is as simple as that citing articles from the 1800's just doesn't seem like cutting edge science, many journals actually prefer not to include "out dated" references. The DDNR seems like a really interesting initiator though and a cheap, safe, up scalable synthesis of the DDNR is potentially very lucrative. A problem with the older described synthesis routes may be that the use of salts in combination with the DDNR may pose safety issues on an industrial synthesis scale, as the potassium salt of DDNR reportedly exploded on recrystallization. On the other hand, how valuable would the DDNR really be, except maybe in certain stab detonator type designs? Especially in a time where much more heat stable and brisant high nitrogen primaries are continuously being developed.

Regarding the formation of compound 4 from 2; mobility may not be the word here, I meant that hydrolysis of one of the two adjacent nitro groups will slowly form nitric acid with the small amount of water present in the sulfuric acid used for deprotection, which may rearrange to a more stable nitramine , upon dilution with water this would decompose further to the diazo. I observed something similar when I tried to nitrate the isopicramic further using sulfuric acid and 2 mole eqv of KNO3. Upon crashing in ice, initially a bright yellow substance formed that upon drying for a long time formed a more orange coloured substance that I was positive to be p-DDNP, the most likely explanation is that the initial bright yellow stuff was the nitramine.

Alternatively, the process may involve some intramolecular redox/rearangement similar to bamberger, involving partial reduction of the nitrogroup and formation of the quinone first. When I drew the reaction equation for the diazotization of isopicramic I already wondered about this possibility, though would think that the presence of the other nitrogroups would prevent this from happening. Another possibility is that compound 4 may have originated from a reduction by the solvent used, this wouldn't happen this way though in a totally inert organic solvent.

[Edited on 8-12-2015 by nitro-genes]

I was thinking about the disputed "rearranged" 6 diazo of DDNR from the earlier Klapotke article reiterated in this present article called 6 diazo again, which I believe is more probably a 4 diazo.

It was something I brought up earlier several times as a structure disagreement and I am still of the same opinion as stated earlier
in the post linked and other posts earlier and later also. NMR notwithstanding it would seem it has to be a 4-diazo for DDNR or else there is a bizarre diazo mobility and migration from 4 to 6. Meldola has to be laughing from the great beyond, oh no not another mobile substituent group, first the magic? nitro and now the magic? diazo just migrating across the ring...you got to be kidding me.
http://www.sciencemadness.org/talk/viewthread.php?tid=439&am...

We are having too much fun to be unpaid for the good effort. Maybe a fat government defense contractor grant and suddenly all the NMR position 6 diazo library data is put in jeopardy or patent position is at risk, if the "new" compound is really an old compound DDNR already at least twice patented before and published even long before that.

Tom Klapotke et al should not throw all that government grant money away, just do a wire transfer to Rosco and Nitro and we will soon get to the bottom of this puzzling matter. Or maybe we could go on a chemical safari.

Have Beaker Will Travel Will Work for Beer and Women

Shucks too late ....Benedikt and Hubl already published in May 1881 which was 134 years ago

I would not risk being called a gender insensitive "pimp chemist"
for having too much HODDNP and CUNT in the laboratory and I would expect that some of the female persuasion coworkers might suggest a different nomenclature

[Edited on 12/8/2015 by Rosco Bodine]

Maybe we can try crowdfunding, small donations earn an on demand designed explosive molecule, a really large donation and you can build your own intercontinental missile or something (Haven't worked the details out completely yet). Would be really nice to legaly buy things like 100% nitric, instead of distilling it everytime from draincleaner.

Seriously though, these nitration schemes are pretty interesting, although seem to largely behave as expected from previous literature. The formation of compound 8 seems to resemble that as described for the dinitro o-toluidine "J. Org. Chem. 1986,51, 2572-2578: Synthesis of Polynitrodiazophenols", although the mechanism still eludes me. Seems I was wrong about the hdyrolysis, since here they used DCM and evaporation. Different for the p-chloroaniline is the presumable presence of 2 ortho nitro's (respectively to the aminogroup) after nitration, very interesting. But if this would be the case, the diazo be unlikely to form (similar to TNA or picramide). Really seems the formation of the trinitrochloroaniline or 2,6-dinitro 3-hydroxy 4-chloroaniline would be more favorable. Presumably, the 3-nitro and/or 4-chloro make that the 2-nitrogroup and aniline (or nitramine) interact to form some sort of unstable intermediate, that decomposes to leave the diazo. This would also be quite different however from the nitration of 3 nitro-aniline or hydrolysis of the resulting tetranitroaniline, which produces only 3-aminopicric and no diazophenols. ...puzzling...Maybe Philou can shed some light on this matter.

I would still be curious for the p-iodo or bromoaniline, or perhaps a carboxyl group somewhere could help.

Also interesting that compound 2a (the trinitrophenylenediamine) only forms from high water content nitric. I suspected that the protected amino might still protonate and pose deactivating and meta direction to the ring, though maybe it prevents formation of the secondary nitramine, which might also be deactivating or lead to decomposition. Apart from the better hydrolysis resistance, maybe the bulkyness of the methylsulfo protection group used also helps here? Also wondered if this is the reason why acetaminophen can't be nitrated to the trinitro, as it is simply too prone to oxidize from 65% nitric alone, maybe very low temperatures and a very specific water content could also do.

Very interesting point in the article is also that the heat test of DDNR (5 mg) didn't lead to detonation. I'm curious now if the isopicramic/65% nitric acid diazotization didn't produce some DDNR afterall, since the "explodes on heating" was the only real real differentiation point I had for distinguishing the DDNR from the DDNP. Colour means little, since it depends on many things like crystal shape and impurities formed.

[Edited on 10-12-2015 by nitro-genes]

This was briefly mentioned before in the DDNP thread, though now I’ve had the time to do some reading regarding the potential use of benzoxazolone to produce 2-diazophenols. In general, ring opening and deprotection are problematic and I doubt the nitration of benzoxazolone is able to produce di or trinitro isomers other than the described ones below.

Benzoxazolone can be prepared by numerous routes, of which some are easily in reach for the amateur, completely OTC and high yielding:

1. Reaction of 2-aminophenol and urea in a mineral acid solution (sulfuric acid monohydrate, HCl, phosphoric  US3812138)
2. Hofmann rearrangement of salicylamide under strongly basic conditions (CA 1150276 A1)

In general, the 6 (meta to the hydroxyl) and 5-positions of benzoxazolone are most activated, accordingly nitration using 65% nitric acid produces almost exclusively 6-nitrobenzoxazolone, while further nitration using fuming nitric acid gives 5,6 dinitro benzoxazolone [1].

Although nitration using nitric acid alone is well described in literature, I couldn’t find many references regarding the products using mixed acid nitration (nitric/nitrate salts+sulfuric). One option could be that concentrated sulphuric acid (being a stronger acid) leads to opening of the oxazolone ring, which could influence the orientation during nitration to produce different isomers than those already described. Then again, heating of 2-hydroxy phenylurea in sulphuric acid is mentioned to lead to ring closure and patent US3812138 describes condensation of urea with 2-aminophenol using sulphuric acid to yield benzoxazolone, which would imply that either this depends on pH /sulphuric concentration or benzoxazolone is reasonably stable in concentrated sulphuric, but not soluble enough or too activated for mixed acid nitrations.

One reference in which mixed acid nitration of benzoxazolone to 6-nitro benzoxazolone (92% yield) is mentioned is “Synthesis of 2-Amino-5-Nitrophenol by Two Step Process, Yin Zhenyan and Li Yanyun (2007)” They further describe hydrolysis the 6-nitro benzoxazolone using 96% ethanol and NaOH, which would represent a usable OTC route to 2-amino 5-nitrophenol.

Anyway, an idea that I had was that perhaps starting with 65% nitric and gradual addition of sulfuric acid (or even AN/SA and a good icebath) may produce 5,6 dinitro benzoxazolone directly. Would it be possible to hydrolyse the oxazolone ring without hydrolysis of one of the 2 nitro groups? If this would give 2-amino 4,5-dinitrophenol and diazotized would this lead to an undescribed isomer of DDNP, or would it be unstable? Reportedly, 2-diazo 5-nitrophenol is pretty stable and used in coupling reactions for dye manufacture. My hopes for the hydrolysis of the 5,6 dinitrobenzoxazolone are not too high though, due to the reported stabilizing effect of a 5-nitro group against hydrolysis of the oxazolone ring [2] in combination with likely increased susceptibility towards hydrolysis of the 2 adjacent nitro groups.

Anyway, any input on the behaviour of benzoxazolone during mixed acid nitrations or other ideas regarding the synthesis of energetic derivatives from benzoxazolone would be appreciated.

[1] Synthesis of Some Substituted Benzoxazolones
Robert L. Clark, Arsenio A. Pessolano
J. Am. Chem. Soc.
1958, 80 (7), pp 1662–1664
DOI: 10.1021/ja01540a038

[2] Benzazole, IX. Über das chemische Verhalten der Nitro-benzoxazolone
HELMUt Zinner, Herbert HERBIG
European journal of inorganic chemistry
Februar 1959,Volume 92, Issue 2 Pages 407–414
DOI: 10.1002/cber.19590920224






[Edited on 19-9-2016 by nitro-genes]

Attachment: phpLqOh08 (470kB)
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Attachment: Synthesis of Some Substituted Benzoxazolones.pdf (350kB)
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Also interesting:

This article describes the synthesis of a p-diazo-o-nitrophenol (presumably 4-diazo, 2-nitrophenol, but no detailed chemical analysis is performed), which seems chemically incredibly stable and maybe faster accelerating than diazodinitrophenols, as it reportedly exploded with a very loud bang and display of high brisance during an ignition temperature test. Should be doable from acetaminophenol, though probably much more sensitive than p-DDNP.

"Das o- N i t ro-p-d i a zo i urn p h en ol explodiert scharf bei 168 C. unter starkem Knall, wobei in der Regel das Schwefelsaurebad, in dem der Explosionspunkt bestilnnit wurde, in Triimmer ging. Ebenso tritt Explosion durch Schlag ein. Es ist in konzentrierter Schwefelsaure und sogar in konzentrierter, rauchender Salpetersaure glatt 10slich und scheidet sich, wenn auch nicht ganz quantitativ, beim Verdiinnen rnit Wasser a n v e r a n d e r t wieder ab. Konzentrierte Jodwasserstoflsaure (1.7 g) bewirkte unter starker Erwarmung Stickstoff-Entwicklung. In heissem Wasser ist das o.Nitro-1?-diazoniumphenol loslich, langeres Kochen bewirkt unter Stickstoff-Entwicklung Zersetzung. Es scheidet sich dabei eine braune, vollkolnnien amorpbe Masse ab, die beim Erhitzen am Platinblech verpufft. Von den organischen Liisungsmitteln ist das o-Nitro p,-diazoniumphenol nur in siedendem Aceton und Alkohol lijslich, vollkommen unloslich ist es in Ather und Benzol. Bei 100° l a s t es sich tagelang aufbewahren, ohne an Gewicht ahzunehmen. Gegen Licht scheinen die gelben Bliittchen etwas empfindlich zu sein, da sie sich nach einiger Zeit stark braun farben. Da von vorherein eine Verbrennung des o-Nitro-p-diazoniumphenolsw egen der ungemein starken explosiven Eigenschatt unausfiihrbar war, wurde die Substanz nur auf ihren Stickstoffgehalt hin analysiert"

[Edited on 20-9-2016 by nitro-genes]

Attachment: Uber die Bildung des o-Nitro-p-diazonium-phenols..pdf (474kB)
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Mono nitration of acetaminophen:

5 grams purified acetaminophenol was finely powdered and added to 16 grams 97% sulphuric acid at 0 deg C. until everything dissolved. In a separate beaker 2.7 grams of dry ammonium nitrate was dissolved in 8 g 97% sulphuric acid and. While keeping temperature between -10 and -5 (to favour mononitration, for as far as that is possible), the AN/SA was added dropwise to the acetaminophen/SA solution. Total addition took 1 hour, and was left to stir for an additional 15 minutes on ice. The clear yellow solution was added to 60 grams of crushed ice and stirred vigorously. Some sticky orange-yellow stuff separated and was removed from the beaker. The rest of the clear yellow solution was left in the fridge overnight upon which an estimated 2 grams of a bright yellow crystalline substance had separated (presumably 2-nitro 4-acetamidophenol). To the 2 grams of the yellow substance, 4 grams sulphuric and 4 grams water was added, and kept at reflux for 2 hours, creating a yellow solution. About 1 ml of the solution was added to a separate beaker and 5 grams of crushed ice added. This precipitated a light yellow micro crystalline substance, presumably the diazonium sulphate salt. This was diazotized at 0 deg C for 30 minutes using sodium nitrite, the light yellow solid filtered washed and dried for 24 hours. Additional drying for 30 minutes at 100 deg C improved burn rate significantly. It’s pretty energetic for something so oxygen defficient.

Further nitration in 65% nitric could possibly yield some DDNR, though, also the diazonium nitrate is likely meta directing resulting in p-DDNP again, but who knows. 2-nitro-4-diazophenol, might also form nitrate or perchlorate salts


Attachment: 2-nitro 4-diazoniumphenol - Copy.avi (4.2MB)
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I think there is no completely OTC way of producing DDNR (without O-alkylation) using only acetaminophen and nitric/sulfuric, although I would still like to try nitration of 2-nitro-4-diazoniumnitrate and 2-nitro-4-aminophenol and possibly 2-amino-5-nitro-phenol from the hydrolysis of 6-nitrobenzoxazolone.

[Edited on 24-9-2016 by nitro-genes]

I keep talking to myself, but ok, here it is anyway

Still had some benzoxazolone left from the synthesis described by Nlegaux (https://www.sciencemadness.org/whisper/viewthread.php?tid=63...), so I decided to try the nitration/reduction to 6-amino benzoxazolone. The benzoxazolone ater recrystallization from ethanol/water (cream colored needles) melts at around 140 ish deg C (literature, 138C). When together with salicylamide on the hotplate, the benzoxazolone melts sharply right before a clean sample of salicylamide melts (literature, 142 C).

Nitration of benzoxazolone:

10 grams of 65% nitric and 5 grams of 96% sulfuric acid was added to a 20 ml beaker and cooled to 0 deg C. using an icebath. In small additions, 2 grams of benzoxazolone was added over about 30 minutes. This was kept stirring on ice for an hour and then allowed to stir at room temperature for 15 minutes or so, the mixture had thickened considerably at this point and was poured on ice. After drying at room temperature for a week, this gave 2.1 grams of cream coloured putative 6-nitrobenzoxazolone. When on the hotplate, it starts to blacken at around 200C, melting at 240C. With the hotplate at 250C a sample melts instantly (literature 240C). Both melting point and yield of the 6-nitrobenzoxazolone is much higher using the nitric/sulfuric acid nitration instead of using 65% nitric at 50C, suggesting that either less oxidation is occuring this way, or this nitration scheme is more selective towards 6-nitro instead of the much lower melting 5-nitro isomer.

Reduction of 6-benzoxazolone to 6-amino benzoxazolone:

The reduction of 6-nitro benzoxazolone was performed as described in some article I found. To 70 ml water was added 2 ml of 8% HCl and brought to 90C. Then 6 grams of steelwool was added in slightly compacted chunks. Over the course of 30 minutes, 2.1 grams of 6-nitrobenzoxazolone was added in small portions. The dissapearance of yellow colour is a good indication that complete reduction has occured, which only took about 45 minutes. Then 2.5 grams of NaOH in 10 ml water were added, everything heated to 50 deg and the iron oxides filtered off. The basified filtrate containing the sodium salt of 6-aminobenzoxazolone turned slighly reddish over the course of several hours. The filtrate was neutralized with dilute HCl to precipitate the 6-amino benzoxaolone. This needs to be done carfully with good lighting to precipitate most of the product. If the pH is lowered little too much, everything goes immediately in solution again. Final yield was 1.2 grams of brownish/white glittering crystals that melted sharply at around 200C (literature 202C), brownish colour probably from sligth oxidation or iron contamination. Product was not recrystallized.


Nitration of 6-aminobenzoxazolone:

Expecting that 6-aminobenzoxazolone is very susceptible to oxidation, the nitration was attempted on a very small scale.

Using 65% nitric:

3 ml's of nitric acid was added to a 10 ml beaker and cooled on ice, about 100 mg of's of 6-amino benzoxazolone was added in small portions. Upon contacting the nitric, the crystals seemed to blacken but no gas was evolved and slowly started to dissolve. After stirring for about 15 minutes the solution had turned a dark red but nothing further seemed to happen and the temperature was raised to 20 deg C upon wich the solution turned a dark violet colour in a about 30 minutes with no evolution of gas, then the temperature was raised further to 50 deg C, which produced a darker solution, but still no evolution of gas. Out of curiosity, a small crum of sodium nitrite was added, some NOx was evolved and kept slowly evolving until the mixture had taken on a light orange colour. Ice was added, but nothing precipitated, neutralization and salting out produced no precipitate either. suggesting that most of the product was likely destroyed.

Using AN/SA:

4 grams of AN was added to 16 grams of 96% SA and cooled to 0C using an icebath. Small additions of the putative 6-aminobenzoxazolone (500 mg) were made over the course of about 30 minutes. Upon contacting the mixed acids, there was no gas evolution. Most of the crystals dissolved very quickly after a small delay (with some dark specks remaing, maybe iron contaminants), turning the solution an orange to a dark reddish/orange after all additions had been made. No gas was evolved at this point. About 15 minutes after the final addition the mixture was still a dark reddish/orange, though very suddenly gas evolution became evident with many small bubbles being visible in the mix. Stirring was continued for several hours, during which gas evolution remained evident and constant. When no gas formation could be observed anymore (5 hours), the mixture was drowned in ice, no precipitate resulted.

It seems that the 6-amino group of 6-aminobenzoxazolone is very susceptible to oxidation, probably due to the stabilization of the imine intermediate due to the lactam-lactim resonance of the oxazolone group. Would still be interesting to try and acetylate the 3 and 6 amino groups, but this needs acetic anhydride again. It is still strange how this could happen under very acidic conditions using mixed acids though, since I would have guessed this would deactive both amines and introduce a 5-nitro, leading to further nitration. Maybe I should have recrystallized the 6-amino benzoxazolone futher, the purple colour is likely some iron complex.

[Edited on 16-11-2016 by nitro-genes]

Not speaking to yourself...speaking to all of us ;-)

"Reduction of 6-nitro-benzoxazolone to 6-amino benzoxazolone:"
The red part is missing.

I also have 1000 ideas involving diazoniums but no personal time or space to work for it (ex-girlfriend stil living at home while she should have left in march 2016 ).
When she had left, I will be able to experiment more and repeat some of your experiments and eventually pay you a visit (or you come to my place).

Thanks Philou, would be interesting to hear some of your ideas regarding the synthesis of novel diazophenols.. For me personally, trying to synthesize some of the diazophenols from relatively unstudied and OTC starting materials gives me some spare time relief. I'm not necessarily looking for a specific product, just enjoying the chemistry and lessons learned from them. So much possibilities regarding these nitrations, hydrolysable nitro groups, internal rearrangments of all kinds, mobile halogens and potentially explosive compounds...chemistry at it's best. Benzoxazolone seemed interesting, one of the things I would still like to do is the NA/SA mediated nitration of 6-chlorobenzoxazolone, whether nitration would stop at 5-nitro-6-chloro, or perhaps a second nitro group may be introduced due to the less deactivating chloro group. Kind of worried this may also produce some dioxin like structures though.

[Edited on 17-11-2016 by nitro-genes]

This may be interesting for you...6-carbamido-benzoxazolone from 6-amino-benzoxazolone and K cyanate.US Patent 2806853 A (downloadable into pdf format from there by clicking "téléchargez le pdf")

So
H2N-C6H3(-O-CO-NH-)_cyclo turns into H2N-CO-NH-C6H3(-O-CO-NH-)_cyclo

This may help prevent oxydation when nitrating.

To help a bit (by fixing the idea) I have made a synthetic pathway of your reaction...a drawing speaks more than a text...at least it helps me to have a visualization to refer to.



[Edited on 18-11-2016 by PHILOU Zrealone]

Quote: Originally posted by nitro-genes

Nitration of 6-aminobenzoxazolone: Expecting that 6-aminobenzoxazolone is very susceptible to oxidation, the nitration was attempted on a very small scale. Using 65% nitric: 3 ml's of nitric acid was added to a 10 ml beaker and cooled on ice, about 100 mg of's of 6-amino benzoxazolone was added in small portions. Upon contacting the nitric, the crystals seemed to blacken but no gas was evolved and slowly started to dissolve. After stirring for about 15 minutes the solution had turned a dark red but nothing further seemed to happen and the temperature was raised to 20 deg C upon wich the solution turned a dark violet colour in a about 30 minutes with no evolution of gas, then the temperature was raised further to 50 deg C, which produced a darker solution, but still no evolution of gas. Out of curiosity, a small crum of sodium nitrite was added, some NOx was evolved and kept slowly evolving until the mixture had taken on a light orange colour. Ice was added, but nothing precipitated, neutralization and salting out produced no precipitate either. suggesting that most of the product was likely destroyed. Using AN/SA: 4 grams of AN was added to 16 grams of 96% SA and cooled to 0C using an icebath. Small additions of the putative 6-aminobenzoxazolone (500 mg) were made over the course of about 30 minutes. Upon contacting the mixed acids, there was no gas evolution. Most of the crystals dissolved very quickly after a small delay (with some dark specks remaing, maybe iron contaminants), turning the solution an orange to a dark reddish/orange after all additions had been made. No gas was evolved at this point. About 15 minutes after the final addition the mixture was still a dark reddish/orange, though very suddenly gas evolution became evident with many small bubbles being visible in the mix. Stirring was continued for several hours, during which gas evolution remained evident and constant. When no gas formation could be observed anymore (5 hours), the mixture was drowned in ice, no precipitate resulted.

Quote: Originally posted by nitro-genes

Nitration of benzoxazolone: 10 grams of 65% nitric and 5 grams of 96% sulfuric acid was added to a 20 ml beaker and cooled to 0 deg C. using an icebath. In small additions, 2 grams of benzoxazolone was added over about 30 minutes. This was kept stirring on ice for an hour and then allowed to stir at room temperature for 15 minutes or so, the mixture had thickened considerably at this point and was poured on ice. After drying at room temperature for a week, this gave 2.1 grams of cream coloured putative 6-nitrobenzoxazolone. When on the hotplate, it starts to blacken at around 200C, melting at 240C. With the hotplate at 250C a sample melts instantly (literature 240C). Both melting point and yield of the 6-nitrobenzoxazolone is much higher using the nitric/sulfuric acid nitration instead of using 65% nitric at 50C, suggesting that either less oxidation is occuring this way, or this nitration scheme is more selective towards 6-nitro instead of the much lower melting 5-nitro isomer. Reduction of 6-benzoxazolone to 6-amino benzoxazolone: The reduction of 6-nitro benzoxazolone was performed as described in some article I found. To 70 ml water was added 2 ml of 8% HCl and brought to 90C. Then 6 grams of steelwool was added in slightly compacted chunks. Over the course of 30 minutes, 2.1 grams of 6-nitrobenzoxazolone was added in small portions. The dissapearance of yellow colour is a good indication that complete reduction has occured, which only took about 45 minutes. Then 2.5 grams of NaOH in 10 ml water were added, everything heated to 50 deg and the iron oxides filtered off. The basified filtrate containing the sodium salt of 6-aminobenzoxazolone turned slighly reddish over the course of several hours. The filtrate was neutralized with dilute HCl to precipitate the 6-amino benzoxaolone. This needs to be done carfully with good lighting to precipitate most of the product. If the pH is lowered little too much, everything goes immediately in solution again. Final yield was 1.2 grams of brownish/white glittering crystals that melted sharply at around 200C (literature 202C), brownish colour probably from sligth oxidation or iron contamination. Product was not recrystallized.

Thanks for that drawing, it does make things more clearly. There is indeed something funny about the melting points mentioned in the various nitration schemes of benzoxazolone in literature. Maybe using high temperature 65% nitric, partial hydrolysis happens during the reaction, producing more of the 5-isomer, leading to melting point depression, or maybe has to do with the reasonance of the oxazolone group and acidity during reaction otherwise. I do know that the melting point of 6-nitrobenzoxazolone from commercial providers is given as 244-249 C, and 6-aminobenzoxazolone as 202 C, so these are more trustworthy probably.

I don't think there was much left after the nitration of 6-amino benzoxazolone, even very small amounts of some residual nitrophenols could produce the orange colour and if there would have been anything left, even it's possible ammonium, sodium and potassium salts must have also been extremely soluble. I lack any good extraction solvents like ether or DCM, so wouldn't have been an option anyway.

Your right, o-aminophenols (and m-aminophenols) are quite easily destroyed (even in the presence of deactivating groups), so probably nitration of 2-aminophenols even when partly nitrated wont work. Quite surprising that this is very different from p-aminophenols indeed. In fact, p-aminophenol itself can actually be nitrated using mixed acids in reasonable yields, in which case a sulfonic acid and nitro group are added ortho to the hydroxy group [1]. In contrast to acetaminophenol, benzoxazolone does not seem to react with N2O3 or N2O4 at ordinary condidions to produce an N,N acetylnitroso and rearrangments to the diazoacetate, leading to deactylation/deprotection. [2]. So at least for benzoxazolone itself, the o-aminophenol groups seem well protected during nitration. The question is what happens when an amino group is added, which can be oxidized and may be stabilized by the lactim form. I was hoping that using 65% nitric this would favor formation of a 6-quinone. The position and order of the nitrogroups introduced would also matter and I'm not into organic chemistry enough to make any acurate predictions. A nitro in 7 position would likely lead to ring opening [3], and the possible resulting formamido group may react with HNO2, maybe leading to deamination with evolotion of N2 and CO2, or other side reactions. For that matter nitration of 6-chloro benzoxazolone might be interesting, perhaps leading to a diazooxide or 3-chloro 2,4,6 trinitrophenol directly. Then again, maybe I'm missing something and the nitration would stop at the 5-nitro 6-chloro benzoxazolone or would be destroyed completely again. Chlorination of benzoxazolone itself should be pretty straightforward, with the most prominent danger being over-chlorination. I noticed some russian patent that got 80-90% yields using bleach and HCl directly, though sulfuric acid/TCCA may also be an option. I'm not overly fond of chlorinating and nitrating chlorinated benzoxazolones though and not sure I will actually do these experiments, due to toxicity reasons. Maybe I tried nitrating the wrong amino-benzoxazolone isomer and maybe the 5-amino benzoxazolone would behave different during nitration.

To come back to the DDNR and isoforms, there may be a good reason why TNR was reduced by stannous chloride instead of sulfides in the patent by von Herz. Generally solvent and reducant used can affect the position of the nitro being reduced. Sulfides may be more selective for reduction of the nitrogroup in between the OH groups, which would likely render it very sensitive to oxidation via formation of a pyrogallol intermediate. The only other isoform I've seen described for DDNR is one having a 1,2 quinone structure, it synthesis should be listed in this article [4] though seems to be missing from the available pages.


The ammonium molybdate mediated nitration of acetaminophenol would be another potential route [5]. The only way I could see this working is if the molybdate forms some very stable complex with the hydroxy group of acetaminophen, enough to prevent any oxidation. Though even in this case the authors would have found di and trininitro derivatives or difficulties in the workup, so I think it is bogus. Another thing is that I found multiple occasions were 2-nitro-4-acetminophenol was wrongly denoted as the 3-nitro 4-acetminophenol. I wouldn't mind someone proving me wrong though.


[1] Riegel, E. Raymond, Howard W. Post, and E. Emmet Reid. "THE NITRATION OF SUBSTITUTED ANILINES1." Journal of the American Chemical Society 51.2 (1929): 505-508.
[2] Baker, John K. "Nitrosation of benzoxazolinone." Bulletin of environmental contamination and toxicology 16.6 (1976): 743-745.
[3] Zinner, Helmut, et al. "Benzazole, IX. Über das chemische Verhalten der Nitro‐benzoxazolone." Chemische Berichte 92.2 (1959): 407-414.
[4] Heller, Gustav, and Theodor Hemmer. "Chinonbildung aus Nitroacetaminohydrochinon." Journal für Praktische Chemie 129.1 (1931): 207-210.
[5] Sana, Sariah, et al. "Mild, Efficient and Selective Nitration of Anilides, Non-Activated and Moderately Activated Aromatic Compounds with Ammonium Molybdate and Nitric Acid as a New Nitrating Agent." Chemistry Letters 1 (2000): 48-49.

[Edited on 19-11-2016 by nitro-genes]

Would still like to try the nitration of 2 nitro-4-acetaminophenol using 65% nitric, though I'm out of nitric. A while back I came across an article describing the nitration of 2-carboxy 4-acetaminophenol using 25% nitric (attachment). The author assumes the compound is a 2-nitro, though the exceedingly high melting point may suggest a 3-nitro (assuming no oxidation producs have formed).

No luck with the nitration of 6-chloro benzoxazolone, Im adding it here just for the sake of it:

6-chloro benzoxazolone:

1 gram of finely powdered benzoxazolone was added to a 50 ml erlenmeyer, containing 30 ml's of water and heated to 70 deg C. Then, 6 grams of 8% HCl was added. Stirring was continued for 5 minutes, upon which the benzoxazolone partly dissolved. The flask was lightly stoppered and over the course of about 30 minutes, 0.55 grams of finely powdered TCCA was added in small portions, directly stoppering the flask again afterwards. Good stiring is required (vortex) or the TCCA will only remain on top of the solution. The liquid turns greenish directly after the addditions, which fades to almost colourless after only 5 minutes or so. A fine precipitate will become visible after each addition (cyanuric acid and the more insoluble chloro-benzoxazolones (This may prevent large amounts of overchlorinated products ) Stirring was continued for another 30 minutes and then allowed to cool to room temperature. The contents were filtered and washed several times,. The semi-dry solid was directly transfered to a 50 ml beaker, and 20 ml of 95% ethanol were added. While keeping at around 70 deg C, water was added untill slight clouding could be observed (6-7 ml). The solution was then heated to boiling and slowly allowed to cool to room temperature. The colourless , shard like, crystals washed and collected. The melting point is estimated between 185-195 (hotplate), with some sublimation visible. Doesn't melt sharply, probably also an unknown amount of 5-chloro present. Total yield was 0.7 grams. (With stronger cooling more could have been precipiated, though I didn't want any cyanuric acid to also precipiate)

Nitration of 6-chloro benzoxazolone:

0.5 grams of 6-chlorobenzoxazolone was added to 10 ml sulfuric acid and cooled on ice. Over the course of 15 minutes, 0.71 grams of AN (dissolved in 2 grams SA) was added. Immediately, the colour changed to a beautiful golden orange. After 30 minutes or so, an off-white product started to precipitate. Raising temperature above 40 reulsted in very slight gas production and only slighly more dissolution. Melting point of precipitated product around 250C, probably 6-chloro-5-nitro benzoxazolone (couldn't find Tm in literature).




One other idea I had was to acetylate the 6-aminobenzoxazolone using heating with acetamide in closed system (possible?)

[Edited on 29-11-2016 by nitro-genes]

Quote: Originally posted by nitro-genes

Would still like to try the nitration of 2 nitro-4-acetaminophenol using 65% nitric, though I'm out of nitric. A while back I came across an article describing the nitration of 2-carboxy 4-acetaminophenol using 25% nitric (attachment). The author assumes the compound is a 2-nitro, though the exceedingly high melting point may suggest a 3-nitro (assuming no oxidation producs have formed). No luck with the nitration of 6-chloro benzoxazolone, Im adding it here just for the sake of it: 6-chloro benzoxazolone: 1 gram of finely powdered benzoxazolone was added to a 50 ml erlenmeyer, containing 30 ml's of water and heated to 70 deg C. Then, 6 grams of 8% HCl was added. Stirring was continued for 5 minutes, upon which the benzoxazolone partly dissolved. The flask was lightly stoppered and over the course of about 30 minutes, 0.55 grams of finely powdered TCCA was added in small portions, directly stoppering the flask again afterwards. Good stiring is required (vortex) or the TCCA will only remain on top of the solution. The liquid turns greenish directly after the addditions, which fades to almost colourless after only 5 minutes or so. A fine precipitate will become visible after each addition (cyanuric acid and the more insoluble chloro-benzoxazolones (This may prevent large amounts of overchlorinated products ) Stirring was continued for another 30 minutes and then allowed to cool to room temperature. The contents were filtered and washed several times,. The semi-dry solid was directly transfered to a 50 ml beaker, and 20 ml of 95% ethanol were added. While keeping at around 70 deg C, water was added untill slight clouding could be observed (6-7 ml). The solution was then heated to boiling and slowly allowed to cool to room temperature. The colourless , shard like, crystals washed and collected. The melting point is estimated between 185-195 (hotplate), with some sublimation visible. Doesn't melt sharply, probably also an unknown amount of 5-chloro present. Total yield was 0.7 grams. (With stronger cooling more could have been precipiated, though I didn't want any cyanuric acid to also precipiate) Nitration of 6-chloro benzoxazolone: 0.5 grams of 6-chlorobenzoxazolone was added to 10 ml sulfuric acid and cooled on ice. Over the course of 15 minutes, 0.71 grams of AN (dissolved in 2 grams SA) was added. Immediately, the colour changed to a beautiful golden orange. After 30 minutes or so, an off-white product started to precipitate. Raising temperature above 40 reulsted in very slight gas production and only slighly more dissolution. Melting point of precipitated product around 250C, probably 6-chloro-5-nitro benzoxazolone (couldn't find Tm in literature). One other idea I had was to acetylate the 6-aminobenzoxazolone using heating with acetamide in closed system (possible?) [Edited on 29-11-2016 by nitro-genes]

Something all right... I don't trust my chemistry instincts enough to tell what most likely formed, so I didn't fiddle with it too much. From a small burn test (outside) I would say probably 1 nitro was introduced, likely in 5 position. Then again, I'm not even sure how the oxazolone ring behaves in SA of higher percentages... inactivation, ring opening, something else? Quit complex indeed, let alone which positions are activated with other functional groups attached. Hard to tell exactly what products form only by observing the colour, taking a very rough melting point and holding a lighter to it.

[Edited on 3-12-2016 by nitro-genes]

Quote: Originally posted by nitro-genes

Possible that multiple isomers were formed, although the preference for the 5 and 6 positions are almost universal. This was sort of an untested, unsubscribed procedure indeed, something I should have mentioned. It was loosely based on 2 procedures: one describing chlorination of benzoxazolone using hypochlorite and chlorinated solvent at Ph 1-2, and patent US 4435577, describing chlorination of benzoxazolone using chlorine gas at 40-80 deg C and dioxane as solvent. I reckoned that hydrolysis at this temperature and acid concentration would not be a big issue. I was curious whether without solvent chlorination would still work, reckoning that precipitation of the chlorobenzoxazolone could prevent over chlorination. Perhaps running at a lower temperature would be better. I must say, the crystals that formed looked very good, having a very similar appearance to recrystallized picric acid from a saturated water solution, only completely colourless. Are there any examples were multiple isomers can co-crystallize like that? I always sort of assumed that if well defined crystals formed, it would be most likely an isomeric ally pure compound. [Edited on 3-12-2016 by nitro-genes]

When I was reading Merck Index to find interesting molecular structure; I fall onto this informations:

5-chlorobenzoxazolone

CAS: 95-25-0

Formula: C7H4ClNO2

Molecular weight: 169,565

Use as a drug:
Muscular relaxant under the names:
Biomioran
Chloroxazone
Chlorzoxazon
Escoflex
Mioran
Miotran
Myoflexin
Myoflexine
Neoflex
Paraflex
Pathorysin
Solaxin
5-chloro-2(3H)-Benzoxazolone
5-chloro-2-Benzoxazolinone
2-Hydroxy-5-chlorobenzoxazole
5-Chloro-2-benzoxazolinone
5-Chloro-2-benzoxazolol
5-Chloro-2-benzoxazolone
5-Chloro-2-hydroxybenzoxazole
5-Chlorobenzoxazolidone
5-Chlorobenzoxazolinone
USAF MA-10
5-Chlorbenzoxazolin-2-on
5-Chloro-3(H)-2-benzoxazolone
5-Chlorobenzoxazol-2-one
5-Chlorobenzoksazolon-2
5-Chlorobenzoksazolinon-2
Flexazone
Parafon Forte DSC
NSC 26189

Solubilities:
Weakly soluble into water;
Soluble into methanol, ethanol and isopropanol;
Soluble into NaOH or NH4OH solutions

Melting point:
191-191,5°C

Synthesis:
See US Patent 2.895.877

Chemical structure:


Here follows the patent.
Attachment: US Patent 2895877 synthesis 5-chlorobenzoxazolone.pdf (721kB)
This file has been downloaded 770 times

It discloses amongst others:
1°) the synthesis of 5-chloro compound ...
but from hydrolysis of a 5-chloro-2-aminobenzoxazole (the -N=C(OH)-O- sequence comes from a -N=C(-NH2)-O- one) --> Pretty useless for us.
or from 4-chloro-2-amino-phenol and phosgene (p-chloro-2-amino-phenol) --> nothing new under the sun but more OTC-ish if instead of toxic phosgene, urea or dimethylcarbonate ester are used.
2°) the synthesis of the 6-chloro compound from benzoxazolone and Cl2 with a mp of 196°C.
It is also a myo-relaxant.

[Edited on 13-12-2016 by PHILOU Zrealone]

Thanks Philou, it seems the melting point is in range of what I found for the chlorinated benzoxazolone. Read something about it's use as muscle relaxant, though I'm not inclined to eat anything I produce in my shed.

Ok, here is something strange... This is based on 1 rushed experiment, it would need further examination, but I'll add it here since I don't store these things on my computer.

I was bored and had a lot of purified isopicramic acid left and decided to look at what exactly forms during nitration using 97% SA and a nitrate salt. To a 20 ml beaker, 10 grams of 97% SA was added and 0.5 grams purified isopicramic acid added and stirred at 20 deg C until everything dissolved, producing an almost red/black but transparent solution. Next, it was added to an icebath and at 0 deg C, 0.25 grams of KNO3 (~1 mol eqvt) was added. The solution was allowed to stir and no gas evolution was seen. Gradually, the solution took on a much lighter red transparent colour, indicating something was happening. A small sample withdrawn at this stage dissolved in icecold water completely, not a single bubble of gas was produced. Since this could be exlained by the H2SO4 adduct with isopicramic itself, I decided to add another mole equivalent of KNO3 and very soon, gas formation became evident. It was allowed to stir overnight in the icebath, going from 0-10 degrees, with steady evolution of gas. When water was added in the morning, copious amounts of NOx were liberated and a transpararent yellow/orange solution was left. No precipitate occured when kept at 4 deg C overnight. About 3 ml's of ethyl acetate were added and briefly stirred, upon which almost all of the colour transfered to the organic phase. This was siphoned off and allowed to evaporate. A small amount of a yellow/orange crystalline precipitate formed, that burned very characteristic for a diazonium compound, very vigorous (more than p-DDNP) and with yellow flash. It dissolved very easily in water again, but adding a saturated KNO3 solution and chilling produced no precipitate. It further seems to attack metals like crazy, although this could also be due to some extracted acid by the ethylacetate.

So, what formed here? Since it is water soluble, even after extraction, it is not p-DDNP iself, since the diazonium sulfate salt dissociates very quickly upon dilution. It still contains a diazonium group, but since it does not produce a precipitate with KNO3, it likely also isn;t DDNR, since the K-salt is reported to be very insoluble (DDNR istelf as well). One of the options is that a 1,2 quinone 3,6 dinitro 4-diazo is formed due to hydrolysis of the 2-nitro of isopicramic acid, though I'm not sure this would explain the reactivity towards metals. Another option is the 2,3,6 trinitro 4-diazo phenol descirbed before, though this would be strange considering the described deactivation of the amine group in 97% SA. Other IMO, less likely options would be some sulfonic acid replacement of the nitro, or more likely maybe some azoxy compound from coupling reactions. Any guesses, anyone?


[Edited on 17-12-2016 by nitro-genes]