Sciencemadness Discussion Board

Alternative Synthesis of Aminoguanidine - Please Help

DBX Labs - 24-12-2020 at 18:19

Hello everyone,

I figured it was time for me to make a SM account, and now especially so, given that I have a predicament on my hands.

Recently, as both a School related project and subject of a future video, I’ve been investigating the synthesis of Aminoguanidine bicarbonate outlined in US Patent US1990511A. Basically it’s a variation of the standard Glacial Acetic / Zinc route that yields about 60%.

https://patents.google.com/patent/US1990511A/en

I’ve reached a 60% yield with the standard route of synthesis in the past, but with the mentioned patent, max yield has been 5%. Clearly something is going awry in my replication of the procedure, rather than simply losing yield in the precipitation of the Bicarbonate salt.

I’ll try to explain my procedure step day step to give you guys an idea of where something could go wrong. Honestly, I’ve done this synthesis so many times with so many variations, I just need another set of eyes.

Following the patent, I have used both 50 micron granular zinc, and 2 micron flake zinc, both of >95% purity, both producing similar yields. Only clear difference is that the flake zinc, while requiring more water than provided in the patent to keep fluid, provides greater exotherm. When I’ve tried the procedure WITH the suggested amount of water and flake zinc, the temperature of the solution does rise to 45 degrees centigrade, before rapidly becoming far too thick to be stirred consistently, even manually. The nitroguanidine I use was neutralized following dehydrating GN in sulfuric and recrystallized. I can vouch for its purity, given that I successfully make Aminonitroguanidine Nitrate (ANGN) from it.
In the second solution, I used 99% Zn(ii) Acetate and 99% Cu(ii)SO4. Nothing special there, pretty standard chemicals bought from reputable suppliers.
Now everything looks cheezy with the synthesis, all the way up to the point where I add Na Bicarb to the filtrate. Procedure calls for 45 minutes, however in most of my trials, I rather run the solution at 42 degrees until I can no longer detect the presence of nitroguanidine via a test with basic Mohr’s salt. I’ve also in my own research, found a paper from the 40’s detailing a test for ketohexoses, which I used inversely to test for the presence of ANQ. Not sure if it’s new info but it came in handy for me to verify that I had made at least SOME ANQ throughout the procedure.


https://www.jbc.org/content/182/2/605.full.pdf

After nitroguanidine is no longer present, I take off heating and promptly vacuum filter. The filtrate is yellow, not colorless as said in the patent, though in all of my trials, even ones following the procedure to an absolute T, this was always the case.

The filtrate is reacted with the proper amount of Sodium bicarbonate and cooled in a fridge overnight. As previously mentioned, the yield which precipitates out never exceeds 5%.

I can’t think of any other details I’ve missed out on, but I’ll link some pictures for better context.

Any help is GREATLY APPRECIATED.

FB560F42-B0E3-41EC-BA84-DB14E4F1177F.jpeg - 2.1MB

[Edited on 25-12-2020 by DBX Labs]

[Edited on 25-12-2020 by DBX Labs]

DBX Labs - 24-12-2020 at 19:45

If and when I get this synthesis to work, I’ll be putting this SM thread in the video on the DBX Labs YouTube Channel: https://m.youtube.com/channel/UC1fWkSGe5iluVOvlWvXmJ3A

roXefeller - 25-12-2020 at 17:13

I'm interested in your progress on this. I suspected the reduction was going to be troublesome. The Engager post mentioned adding ice (instead of water) when the mixture was getting too thick/hot. It also has additions over many hours. Have you compared notes to see where you are different?

DBX Labs - 25-12-2020 at 20:11

So there's a few major differences between the synthesis outlined in the patent and the standard synthesis utilized by Engager. Here are a couple:
More water used in zinc slurry (less thick)
Higher temperatures at which reaction takes place (40-45C vs <10C)
No free acid in solution
Should take place in only 45 minutes
No need to add ice to maintain a constant temperature
A single addition of Zinc Acetate / metal catalyst solution
Many of these differences are apparent to be advantageous, assuming that the procedure works. The inventor also reports a >90% yield based on nitroguanidine, no small potatoes in comparison to the measly 60% reported in the Engager synthesis.
I should mention that going along with the patent, I always used the suggested proportion of hydrated Copper Sulfate as a catalyst.

I've run a total of 12 trials so far, each different, aside from the first three. Interestingly enough, every run tested positive for Aminoguanidine via the inversive test for ketohexoses mentioned previously. This test certainly isn't corroborated by anything else I could find, and honestly, it might be feeding me false positives, however, I have found that pure nitroguanidine will not deliver a false positive, and neither will copper sulfate, zinc, zinc oxide, or zinc hydroxide.
I'll try to regurgitate my available data on the first trials and jot down the rest.

roXefeller - 26-12-2020 at 09:10

First, for those following along at home, Engager's post.

I would be interested in the meat of those 12 trials. Comparing the patent, Wyler, with Engager I see a couple things, all of which seem to confound our discussion. First thing is temperature. Wyler runs between 40-45C, while Engager stays in ice bath. Have your trials looked at the role of temperature?

Second, based on the discussion of this thread, H+ donation is necessary with the salt forming as a result. But Wyler proposes use of the salt with a limit on proton activity. I'm not familiar with the activity of copper sulfate to catalyze though, so maybe some proton activity is coming from there. Otherwise protons would have to come from water ionization and the formation of zinc hydroxide. Do any of your trials use both free acid and salt? It seems that the overall zinc quantity is similar between Wyler and Engager, and Wyler uses about 50% extra acetate quantity.

Third is time, what range of times have you been using?

Fourth, also in this thread it is mentioned that the acid is maintaining an active surface of the zinc for reactivity. Maybe there is a difference between your zinc preparation and Wyler's (which is circa 1933). Is yours unknowingly passivated for safer handling? Maybe a small amount of free acid would assist there.
Can anyone give insight on the action of copper sulfate as catalyst?

DBX Labs - 26-12-2020 at 10:44

I'll answer your four points in a couple of hours, but something that I should mention that is crucial is that at the end of each of the later runs (7,8,9,10,11, and 12) I ran at 42.5 degrees C until a test with Mohr's salt would no longer yield a positive qualitative test for Nitroguanidine. This tells me that the Nitroguanidine reduction HAS to be taking place, however, it is possible that the reduction could be only partially complete. This said, the 50-micron granular zinc takes HOURS to run to this form of completion, whereas the flake zinc takes an hour and 15 minutes on average.

Another point I need to make is that in all my tests with granular 50-micron zinc (tests 1-5, and 8-9) using the EXACT procedure listed in the patent. the solution resulting from the addition of the acetate and copper catalyst will NOT proceed to rise any higher than 35 degrees. I've attempted to negate this problem by supplying heat from a hot plate to the point in which exotherm maintains a temperature of >40 degrees, something which takes place around 35 degrees.

roXefeller - 26-12-2020 at 11:17

Ok, I agree that mohr's salt finding is interesting. I left a hanging question in the reduction thread about why that image stated the need for a strong acid to attack the oxygen over the nitrogen. Could it be that you are reducing the nitro group only half way, not quite the amine.

DBX Labs - 26-12-2020 at 16:07

Do you suppose that would mean Nitrosoguanidine is being produced? Can't find any qualitative tests online right now that might help with affirming that.

[Edited on 27-12-2020 by DBX Labs]

Diachrynic - 26-12-2020 at 16:13

I have made good experience with the procedure in a related patent, US2537328, see http://www.sciencemadness.org/talk/viewthread.php?tid=155675

They are using ammonium sulfate and no copper catalyst, I obtained 60% of yield.

DBX Labs - 26-12-2020 at 18:21

Hey Diachrynic,

I saw your post on that variant synthesis a while back and have reviewed it several times since. Very interesting. I was very surprised to find that the color of nearly all my resulting solutions is near identical to yours. Of course, the aminoguanidine content of mine were all apparently minimal.

roXefeller - 26-12-2020 at 19:53

Reading the Wikipedia page for ammonium sulfate I noticed that it has an acidic solution in water due to the strong sulfate ion. This would provide active H+ for protonation but not active enough for excess exotherms like free acetic acid.
Quote:

As a salt of a strong acid (H2SO4) and weak base (NH3), its solution is acidic; pH of 0.1 M solution is 5.5. 

Also the ammonium cation isn't bound to remain in solution, but degrade/escape and provide catalyst for additional reactions. Would the zinc sludge then be zinc II sulfate?

DBX Labs - 28-12-2020 at 10:00

Trials:

1) Followed procedure outlined in the patent word for word at 1/2 scale. Used freshly made nitroguanidine, 50-micron zinc granules. Temperature only rose independently to a max of 35 C. Supplimental heating from a hot plate was used to reach target temperature. Ran for exactly 45 minutes after the temperature of solution exceeded 40 C. Held at 43 C for most of the duration. Filtered and added bicarbonate to the yellow filtrate. 4 grams of product produced from a 1/2 scale, contributing to a less than 10% yield. Tested product later on for zinc via ammonium hydroxide; all product was in actuality zinc bicarbonate.

2) Repeat procedure from Trial 1 instead at 1/4 scale. Added 5 grams NH4Cl to filtrate to encourage the formation of soluble zinc complex. 1.5 grams of product precipitated out overnight in fridge. Tested negative for zinc and positive for bicarbonate. Later tested blue (???) in qualitative test for aminoguanidine outlined here: https://www.jbc.org/content/182/2/605.full.pdf. Pure aminoguanidine solutions test red/purple.

3) Repeat procedure from Trial 2 with greater temperature control. Yield was only 0.5 grams of non-zinc bicarbonate salt.

4) Repeat procedure from Trial 2 with zero supplimental heating applied throughout. Yellow filtrate after 45 minutes yielded zero product.

5) Repeat procedure from Trial 2 ran for 90 minutes. Resulting mixture was extremely thick - vacuum filtration took forever. Filtrate was a much paler yellow. Yield was 0.5 grams of non-zinc bicarbonate salt.

6) Repeat procedure from Trial 2 with 2 micron flake zinc used in place of previously used 50-micron zinc granules. Temperature rose to 40 degrees within 20 minutes of addition of acetate/copper solution. Very rapidly mixture became an extremely thick paste. Temperature held at 42 degrees for 45 minutes and 100 mL water was added to help stirring. Bicarbonate added to yellow filtrate as well as the standard 5 grams of NH4Cl. Yield was 1 gram of non-zinc bicarbonate salt.

7) Repeat procedure from Trial 6 done in larger beaker with 150% more water content. Solution temperature did not rise to 40 degrees independently on addition of acetate/copper solution so supplimental heating was required. Solution was not nearly as thick initially, but still became a difficult slurry to stir by the end of 45 minutes. Yellow filtrate yielded 1 gram of non-zinc bicarbonate salt. This product later tested as red/purple in the qualitative test for aminoguanidine.

8) Repeat procedure from Trial 2 using 50-micron granule zinc. Utilized test with basified Mohr's salt throughout synthesis to test for presence of Nitroguanidine. Solution never fully tested negative for Nitroguanidine over 4 hours of running at 42 degrees, however, decrease in red coloration of testing precipitate was noticable towards the end. Yield was 1.5 grams of non-zinc bicarbonate salt. Precipitate later tested as red/purple in qualitative test for aminoguanidine.

9) Repeat procedure from Trial 8 continually testing for nitroguanidine using Mohr's and aminoguanidine using inversive test for ketohexoses outlined in: https://www.jbc.org/content/182/2/605.full.pdf
To test for aminoguanidine, I surmised that given that the test for ketohexoses outlined in the paper utilized a solution of aminoguanidine of roughly 1 gram/100mL, the zinc slurry which should contain a similar concentration of aminoguanidine towards the end should also work. If no aminoguanidine, then no red/purple coloration - or so my logic goes. The monkey wrench is that for some reason this test for aminoguanidine will turn blue instead. I honestly have no clue why this may be, although I do know that given the test takes place after diluting 0.5 ml of concentrated sulfuric acid with 0.2 mL of aminoguanidine solution and again diluting with 0.8 mg sucrose dissolved in 0.2 mL water, exotherm is certainly present, and variable temperatures might be the culprit.
In this trial, I used the smaller flake zinc as well and ran at 42 degrees until nitroguanidine was no longer present. By the 1 hour 15 minute mark, Mohr's salt no longer yielded the signature reddish color for nitroguanidine complexing. At this point, my tests for aminoguanidine from the slurry tested reddish/purple, however a precipitation of zinc sulfate occured when the 0.2 mL of slurry solution mixed with the 0.5 ml sulfuric acid. As far as I know, this had no effect on the qualitative test, as the coloration was still visible through the white precipitate. The yellow filtrate yielded 2 grams of a white, non-zinc, bicarbonate salt, which tested positive for aminoguanidine in a 1g/100ml concentration.

10) Repeat procedure from Trial 9 with identical results in every way.

11) Repeat procedure from Trial 9 with 2.5 grams of white, non-zinc, bicarbonate salt, which tested positive for aminoguanidine in a 1g/100ml concentration.

12) Repeat procedure from Trial 9; boiled down yellow filtrate after adding bicarbonate and ammonium chloride to 1/5th volume and added more bicarbonate to replace the portion that decomposed. Cooled mixture precipitated out a yellow crystalline powder that tested as blue in the qualitative test for aminoguanidine in a 1g/100mL solution.

BTW - when I say I add bicarbonate, I do mean Na Bicarbonate and at 1.25 times the amount stochiometrically required to reactive with the theoretical 100% yield of aminoguanidine.

Not really sure where to go from here. Any ideas for future tests are much appreciated.




roXefeller - 31-12-2020 at 20:20

I searched for copper sulfate as a catalyst tonight. A few general links talk about it for standard chemistry experiments where copper sulfate is added to a zinc H2SO4 reaction by playing copper onto the zinc and forming up an electrolytic cell. In some way related to activity the copper allows for a better production of hydrogen. One from wiki.
Quote:

In high school and general chemistry education, copper sulfate is used as electrolyte for galvanic cells, usually as a cathode solution. For example, in a zinc/copper cell, copper ion in copper sulfate solution absorbs electron from zinc and forms metallic copper.[17]

Cu2+ + 2e− → Cu (cathode) E°cell = 0.34V


Sounds nice but now I'm trying to fit this idea into the process where ammonium sulfate is the electrolyte instead, while the copper is only a catalyst, e.g. reforming CuSO4 again for plating, and the hydrogen is directed to the nitro group.

roXefeller - 1-1-2021 at 11:19

I was reading the Wyler patent again just now. While he favors zinc acetate, he also makes a claim to other acetate salts, including ammonium. I wonder if he disclosed the patent claims, but still hid his invention except for "those familiar in the arts". Patents give away discoveries for theft unless the author uses lawyers, or something else to protect them. I wonder if he really wanted to claim ammonium acetate. It would enable free hydrogen ions, similar to the ammonium sulfate reaction, which seems to progress very easily and controllably.

macckone - 2-1-2021 at 00:01

The wonderful thing about patents is that they don't have to work.
I suspect something critical is left out of the patent.
My first thought is a catalyst that isn't mentioned.

roXefeller - 2-1-2021 at 08:18

I ran a reduction last night with the copper sulfate pentahydrate catalyst. I had 82g of a 14.41% ammonium sulfate solution which needed 2.2 grains of copper sulfate pentahydrate. When this had dissolved, I measured out 16.63 grams of solution with 1 gram nitroguanidine. I cooled this and measured 2.06 grams zinc powder. As an observation, the first hit of zinc powder changed the solution dark immediately, probably the copper plating out onto the zinc. But eventually (fractions of a second) the copper ions deplete and all the remaining zinc reacts, adding reaction heat. Additions were made to maintain 8-11C and reaction was left for another 35 minutes after last addition. The solids were filtered while 1.07grams 10% ammonia was weighed. I pulled the liquid off the top with a transfer pipette to avoid the superfine solids. This was mixed and 1.43grams sodium bicarbonate was added, stirred and left overnight at room temperature. In the morning, the solids were filtered off and dried. 0.42 grams yield, right in the middle of the other trials. So the copper sulfate didn't seem to help. You know, right in line with the other commentary about the Wyler patent worthiness, or lack thereof.

DBX Labs - 2-1-2021 at 13:34

What I'll try next is twofold,
First, I'll try running the mixture of the flake zinc according to the procedure in Trial 9, however, I plan to keep the solution at 42-43C for a good 30 minutes after it no longer tests for NQ. I suspect that intermediates in the reduction of NQ to AQ may take some time in and of themselves to reduce in solution.
Second, I'll try holding the pH at 7 throughout the procedure. In all previous testings throughout, pH rises to about 10-11 after the addition of the acetate. Maybe this will help free up some needed hydrogen ions.

Also, I just remembered,
When the zinc powder is added to the slurry of insoluble NQ at the beginning of the procedure, the persistent yellow color appears in seconds. Not sure why...

nitro-genes - 1-2-2021 at 04:31

Any thoughts on if it would be possible somehow to use copper(II)/ascorbic acid as the reductant to produce aminoguanine? Maybe as some insoluble copper complex or a poorly soluble salt? My guess would be that only copper powder would be formed and no reduction of nitroguanidine would occur, though maybe interesting to give it a try?