Sciencemadness Discussion Board - Preparation of Succinic Acid

Preparation of Succinic Acid

Magpie - 2-10-2016 at 13:57

Attempt at the preparation of succinic acid via hydrogenation of fumaric acid, a failure

1. Introduction
This report describes an attempt to make succinic acid by the hydrogenation of fumaric acid:

The purpose of this experiment was not only to obtain succinic acid but to evaluate the apparatus and gain further hydrogenation experience using a metal catalyst.

The procedure used was based on that for preparing succinic acid in Vogel (ref 1). Although the Vogel procedure specifies maleic acid as precursor Ullmann (ref 2) indicates that it can also be made from fumaric acid, its geometric isomer. However, I could not find any procedure specifying fumaric acid as precursor. The apparatus used was essentially that in Pavia (ref 3) for the preparation of methyl stearate from methyl oleate via hydrogenation.

2. Reagents
6.9g fumaric acid
1.4g 5% Pd/C
100ml absolute ethanol
100ml 6M H2SO4
14.4g mossy Zn
10ml mineral oil
CaCl2 granules

Reagents

3. Equipment
250ml 2-neck RBF, 19/22
125ml Buchner funnel flask
50mL p-e funnel
CaCl2 guard tube
6”test tube with tublature
6mm glass tubing
¼” ID latex tubing
centrifuge w/4 test tubes
5” evaporating dish
magnetic stir bars
magnetic stirrer
magnetic stirrer-hotplate
2ea 1-hole #2 rubber stoppers
19/22 adapters w/tublature
7cm Buchner filter

4. Safety
The 5%Pd/C can catalyse a violent combustion at room temperature. Therefore, great care must be exercised when adding it in the presence of combustible vapors and air. When loading the light fluffy Pd/C it is important to get it fully submerged in the solvent, avoiding leaving any deposits on the interior walls of the reaction vessel.

During my only other hydrogenation, in a school lab, methyl oleate was dissolved in methanol in the reaction vessel. As I was loading the 10% Pd/C into the vessel there was a small but loud explosion. At that time I gained a healthy respect for metal catalysts.

5. Procedure

a. hydrogenation

The hydrogenation apparatus is shown in the picture below:

The 6” test tube bubbler was loaded with enough mineral oil to provide ~1” of submergence for the H2 outlet glass tube. CaCl2 granules were loaded into the guard tube. This was intended to insure that the hydrogen supplied to the reaction vessel was dry. An initial 5.2g of mossy Zn was placed in the Buchner flask along with a stir bar. 50mL of 6M H2SO4 was placed in the p-e funnel. The system was purged with 1.5L of argon. 100mL of absolute ethanol was added to the 250-mL reaction flask along with an oval stir bar. 6.9g of fumaric acid was added to the reaction flask. Stirring was started but not all of the fumaric acid dissolved, as was anticipated. The 6mm glass sparge tube opening was situated just above the rapidly turning stir bar. 1.4g of 5% Pd/C was carefully added to the reaction flask using a paper funnel. The oil bath was heated to 40-50°C to promote solubility of the fumaric/succinic acids.

The 6M H2SO4 was slowly dripped onto the stirring mossy Zn to effect an H2 effluent rate of 2-3 bubbles/s at the bubbler, per Pavia. The Zn and acid were replenished as necessary to provide a hydrogenation time of 3hr.

hydrogenation of fumaric acid.jpg - 157kB

At about the 2hr mark the sparge tube plugged as evidenced by a lack of bubbles at the bubbler. This resulted in a small amount of suckback of mineral oil into the reaction flask. Yes, a safety trap should always be used. The tube was removed and cleaned of a small amount of white solids.

After 3hrs the hydrogenation was stopped and the product poured into a 250mL beaker. From the beaker small test tubes were filled for use in a centrifuge.

product before centrifugation

b. catalyst removal

The product was centrifuged using 4 small test tubes allowing processing at 30mL at a time. This nicely removed the catalyst providing a clear product and a black residue. This clarity indicated that the fumaric acid was no longer in excess of saturation, hopefully having been converted to the more soluble succinic acid.

hydrogenation product centifuged.jpg - 145kB

centrifuged product

The clarified product was placed in an evaporating dish to air dry at room temperature. This took about a day. The presence of a small amount of catalyst and mineral oil was evident.

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Clarified product in evaporating dish and the catalyst in water

The catalyst was washed into a small bottle with water and capped. This will be recovered for reuse if possible.

6. Recrystallization

The dried product crystals contained some ultrawhite crystalline contaminant as can be seen more clearly in the picture below. These formed in clusters on the dish wall above the liquid level. That would have been the time to remove them. Instead I picked them out, placing them in a separate beaker as shown below. I speculate that this is unreacted fumaric acid or a by-product.

crude succinic product acid sorted.jpg - 120kB

dried product crystals sorted

The weight of the putative succinic acid was 6.33g; that of the ultrawhite crystals 0.59g.

The putative succinic acid crystals were recrystalized from 25mL of boiling water per Vogel. These were caught on a 7cm Buchner funnel as shown below.

recrystallized succinic acid product.jpg - 123kB

Recrystallized putative succinic acid

7. Results
The mp of the crystals was 235°C; the Vogel value is 184°C. Therefore the product is not succinic acid. Its composition is unknown.

8. Discussion & Conclusions
The Vogel procedure measures the volume of hydrogen consumed and specifies that the consumption will take about 2hrs. My apparatus did not allow measurement of the hydrogen generated or consumed. Also, Vogel’s precursor was maleic acid which I assumed would hydrogenate easier than my precursor, fumaric acid, due to steric factors. Therefore I hydrogenated for 3hrs as a safety factor.

Serendipitously the tramp mineral oil acted as an absorbent for the traces of Pd/C in my product. These were removed from the water surface using a small cotton swab during the recrystallization.

Chemplayer has a YouTube up that shows how to make succinic acid from Na glutamate, available OTC as Accent seasoning/meat tenderizer. This is likely a cheaper way to go considering the high cost of Pd/C even if maleic acid had been used and the synthesis had been successful.

Apparently the steric factor, cis vs trans, 1,4-butenedioic acid, is very important here and the fumaric acid double bond failed to take up the H2.

9. References
1. “A Textbook of Practical Organic Chemistry,” 3rd ed, (1956) by A. I. Vogel, pp. 473-474.
2. “Ullmann’s Encyclopedia of Industrial Chemistry,“ p. 8 under "Dicarboxylic Acids, Aliphatic."
3. “Introduction to Organic Laboratory Techniques,” (1998) by D. L. Pavia et al, pp. 121-126.

Your comments, suggestions, and recommendations are encouraged.

[Edited on 2-10-2016 by Magpie]

[Edited on 2-10-2016 by Magpie]

[Edited on 2-10-2016 by Magpie]

[Edited on 3-10-2016 by Magpie]

DJF90 - 3-10-2016 at 04:15

A couple of quick points. Its good to see you've used ethanol as solvent as its much safer around Pd/C than the commonly used methanol. Melting point of your "product" is depressed with respect to fumaric acid, suggesting some conversion has taken place (especially as the observed melting point does not correlate to any of the potential impurities you might expect to see). Ideally you'd do the hydrogenation under a balloon rather than continuous sparging - you'll get better absorption and no flammable exhaust gas. De-gas reaction mixture with vacuum and back-fill with hydrogen (x3) before heating. You can then just let it sit under balloon pressure. Make sure you have good stirring to facilitate gas transfer into solution. It may also be possible that the 5% Pd/C is just not active enough, and 10% might yield a more favourable result.

You need to have some form of IPC so that you can determine any success without having to terminate the reaction; TLC would likely be the easiest to employ if you have/can make plates. It might be that you'd see spot to spot conversion with a longer reaction period.

AvBaeyer - 3-10-2016 at 04:23

Magpie,
I suspect that the product you isolated is mostly fumaric acid - how sharp was the mp? I also suspect that the reduction of fumaric acid requires some positive H2 pressure because, as you suspected, sterics may play an adverse role.

Several alternatives are possible but may be no more successful:
1. Run the reaction in water on a salt of fumaric acid.
2. Use a transfer hydrogenation method so the entire reaction is "one pot."
It all depends on how badly you want succinct acid though I do realize that you are doing a demo experiment.

Finally, for safety reasons, methanol is one of the worst solvents for Pd/C hydrogenations. Flash fires are a constant worry using dry catalyst. If methanol is the choice then a wet (H2O) catalyst should be used. 95% ethanol is a fairly standard solvent.

AvB

Magpie - 3-10-2016 at 08:55

Thank you both for the good comments.

I mentioned my prior use of methanol only as it was the specified solvent in the experiment I did in a school lab, found in Pavia. But thanks for the information/warning.

I used absolute ethanol as that was the callout in Vogel. I assumed that any water present could cause the formation of a malic acid by-product.

I don't have a tank of H2 so how do I fill a balloon? My gas pressure was 1" of mineral oil (0.8" H2O). I could have increased this by simply putting more mineral oil in my bubbler. The H2 generation method I used worked well for hydrogenating methyl oleate using 10%Pd/C at room temperature, no degassing, 1"mineral oil gas pressure.

The melting point was not sharp, 232-235°C. I would have tested my product for unsaturation if I would have had any bromine water handy. Also I could have used KMNO4 water but I didn't think of this at the time and now the product has been discarded.

Is there an easy way to test the "activity" of my 5%Pd/C?

[Edited on 3-10-2016 by Magpie]

Dr.Bob - 3-10-2016 at 09:16

To test the Pd/C, just put a speck of it on some filter paper and add a few drops of MeOH. If it catches fire, it is highly active. Often 5% will not catch. but 10% will catch much more easily. If you use Pd/C, you could just add ammonium formate to generate H2 in situ, as AvBaeyer suggested. It is a nice, stable, easy to use source of hydrogen. That is a nice way to do it, can often just reflux the reaction to make the H2 and react it at the same time. Maleic acid is not too hard to come by, if you want to try it, let me know.

Magpie - 3-10-2016 at 12:39

I did your test Dr Bob: no combustion.

I then passed some warm propane over the filter paper - still no combustion.

I'm going to call the vendor, ChemCenter of La Jolla, CA.

It is labeled as 5g of Palladium on Carbon, 5% (Reduced, Eggshell, wet).

cubalibre - 3-10-2016 at 13:11

Using a centrifuge for catalyst recovery sure seems nice.
Thanks for sharing with us Magpie!

I've ran some ballon reactions in the past without access to a H2 tank either.
I produced it by adding Al to an 1l Erlenmeyer filled with some aqueous NaOH solution. The ballon was connected via a three-way valve, that way you can degas the solution and setup with argon first a few times. The aluminium was added under a stream of inert to prevent intoducing O2 to the system.
The reaction needs to be cooled externally and everything should be sealed using PTFE or Parafilm.

Same goes for running the reaction.

To test your catalyst just add it to some formic acid. If it is active you should notice gas production.

[Edited on 3-10-2016 by cubalibre]

Magpie - 3-10-2016 at 13:41

Thanks cubalibre for the procedure on filling a balloon. I don't have any formic acid handy.

I got a hold of Bill at ChemCenter. He was very accommodating and is puzzled as this is the first complaint. He said my product was taken from a 3-yr old bottle of Johns-Manville (now Alfa-Aesar). He's going to refund my money and send me a gram of 10%Pd/C gratis.

edit: I wonder if he did not mean Johnson-Matthey instead of Johns-Manville.

As a nice alternative try a Moscow Mule!

[Edited on 3-10-2016 by Magpie]

DJF90 - 3-10-2016 at 14:12

Thats a good result, Magpie. I assume you'll be attempting the reaction again once the catalyst has arrived?

Magpie - 3-10-2016 at 14:30

I don't have anymore fumaric acid. I do have 2-3g of maleic acid. I might try with that. I didn't really intend to make a research project out of this

Assured Fish - 3-10-2016 at 21:11

Just out of curiosity i don't suppose succinic anhydride subliminates in the same way that phthalic anhydride does, does it?

Cheers Fish

cubalibre - 4-10-2016 at 09:27

Magpie, did you ever notice any eggy smell when producing the H2?
I've had Zn/HCl reactions smell of H2S (?) with allegedly 99%+ zinc, it's a long shot but could be the case here too.
Maybe you poisoned your poor catalyst instead of saturating it.

Magpie - 4-10-2016 at 17:06

No, no smell of H2S.

Dr.Bob - 6-10-2016 at 05:20

Maleic acid should work fine. Let me know if you need more of any of those chems.

Magpie - 6-10-2016 at 08:17

Thanks for the kind offer Dr Bob.

Vogel also says that fumaric acid should work, but again without references, or at least ones I can access. One reference here may be parroting the other.

Now that I know that my catalyst was bad I really want to see if fumaric acid would work.

I did get my money back from ChemCenter. Now I'm waiting for the 10%Pd/C.

S.C. Wack - 6-10-2016 at 15:37

Fumaric and maleic acids have given nearly identical yields in other cases, such as CrSO4 or Raney Ni+hydrazine hydrate...that mossy zinc can reduce Cr+3/+6 to chromous BTW.

Waffles SS - 6-10-2016 at 21:45

Reaxys search:

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Magpie - 7-10-2016 at 08:52

Wow, REAXYS is awesome! Would it be possible for you to post the first article in the 2nd link?

Thank you Waffles.

Waffles SS - 7-10-2016 at 10:34

Quote:

Layered double hydroxides supported nano palladium: An efficient catalyst for the chemoselective hydrogenation of olefinic bonds

Chemoselective hydrogenation of olefinic double bonds in the presence of various functional groups using layered double hydroxides supported nanopalladium (LDH-Pd0) catalyst is described. LDH-Pd0 was recovered quantitatively by simple filtration and reused several times with consistent activity and
selectivity.
Lakshmi Kantam M, , Parsharamulu T, Manorama S.V.Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India

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[Edited on 7-10-2016 by Waffles SS]

Magpie - 7-10-2016 at 11:01

Thank you. The LDH-Pd catalyst seems extremely efficient and not to difficult to make.

cubalibre - 8-10-2016 at 14:45

Not bad at all the LDH-Pd.
Even leeching seems to be less of a problem (they only tested it on one substrate though) compared to Pd/C, no coking either .
Any idea how they compare to polymer-carried cat?
Count me in if you prepare it Magpie!

UC235 - 8-10-2016 at 16:36

Quote: Originally posted by Magpie

Thank you. The LDH-Pd catalyst seems extremely efficient and not to difficult to make.

Looks like it would be nearly ideal for making zingerone, rheosmin, or other phenylbutanones.

ScienceHideout - 8-10-2016 at 17:04

Good writeup, Magpie! I regret that I didn't see it earlier.

I have been working full time lately in a carbohydrate research lab. Around the lab I have gained a reputation for being the 'hydrogenation guy'. I primarily do hydrogenation flow chemistry (look up H-Cube, I have fixed one of these and completely taught myself everything I know about it) and I am the go-to person with Parr hydrogenation, too. Might I give just a couple quick tips?

a) I find that the most frequent time that the catalyst 'dies' is as soon as it enters the flask with your starting material. It tends to burn up in the air, even if there is no 'bang.' Its strength is diminished. I found that if you just squirt some argon in before you dump in the Pd/C, it will work a lot better. I know you did a purge, but was it enough?

b) You need to take every measure to make sure there is absolutely no sulfur anywhere in or near your setup. Sulfur is crazy poisonous to palladium catalysts. Run a column. Recrystallize. Do something to be sure of it.

c) I found that the best solvent system is plain old methanol. If that doesn't work, try methanol/ethyl acetate 7:3. It honestly doesn't even need to be all that dry.

d) A shaking motion actually creates a better surface than a stirring motion.

e) If possible, try Raney Nickel. That works especially well for double bonds.

f) I know that catalysts are expensive, but I always use a 1:1 ratio of catalyst to material I'm hydrogenating. Try a smaller scale, first?

g) Hydrogenations can take a long time. Try running it for 3 hrs, and then take a TLC plate for each following hour and compare it to the Rf of your starting materials and expected product, if possible.

Just a couple things I learned! Let me know your thoughts on them!

Magpie - 8-10-2016 at 20:21

Thanks for your input! You clearly have the benefit of a lot of catalytic hydrogenation experience.

My first thought was: this can't be all that complicated. After all this is a widely used technology that's been around for a long time. Also there is a student lab manual (Pavia) that has an experiment for hydrogenating methyl oleate to methyl stearate using the exact same technology that I used for the succinic acid attempt. Then I looked in my lab notebook from 13 yrs ago to see what my yield was for the oleate: 1.3%, a terrible yield. Industry making margarine must surely do much better.

I reported the results of my "activity" testing with methanol per Dr Bob, and with propane. Do you agree that this indicates that my 5%Pd/C has low or no activity? If not, what test would you recommend?

cubalibre - 13-10-2016 at 04:19

Quote: Originally posted by ScienceHideout

Good writeup, Magpie! I regret that I didn't see it earlier.
f) I know that catalysts are expensive, but I always use a 1:1 ratio of catalyst to material I'm hydrogenating. Try a smaller scale, first?

This sounds excessive even for academia

. Your supplier must love you.

ScienceHideout - 16-10-2016 at 12:14

Quote: Originally posted by Magpie

I reported the results of my "activity" testing with methanol per Dr Bob, and with propane. Do you agree that this indicates that my 5%Pd/C has low or no activity? If not, what test would you recommend?

Hmmm, as far as 'activity' is concerned, I have never personally tested for catalytic activity. Usually, if we can't get our O-debenzylations to work after several attempts, we will just write "DEAD" on the bottle and buy a new one! There's a lot of ways a catalyst can go bad, but the fact that you saw some type of product in your reaction makes me think that your catalyst is probably still good despite the results of your other test.

Magpie - 16-10-2016 at 12:52

I'm ready and willing to try another synthesis of succinic acid from maleic anhydride. But I don't want to go to that considerable effort until I can feel confident about my catalyst activity.

ScienceHideout - 16-10-2016 at 16:07

Magpie- Have you tried doing different 'types' of hydrogenations with your catalyst to test it? Such as O-benzyl deprotection, or nitro-reduction?

Magpie - 16-10-2016 at 16:37

No, I have tried no other hydrogenation.

Magpie - 21-10-2016 at 15:23

Quote: Originally posted by Magpie

No, no smell of H2S.

I am going to have to eat those words.

Today when I was preparing a balloon full of H2 I got a whiff of H2S. So I tested the gas with lead acetate paper and bubbled the H2 through a lead acetate solution. The results are shown below with plain water in the middle.

I've been making my H2 by reacting mossy Zn with 6M H2SO4. My Zn is lab grade (Al-Chymist) but I have no specs (analysis) for it. My sulfuric acid is diluted Rooto drain cleaner. I can try using muriatic acid instead of the sulfuric acid and see if the H2S goes away. If not, I will try generating my H2 electrolytically.

BTW, I have been using a $10 aquarium pump to fill the balloon with H2. It works quite well.

Edit: On 2nd thought HCl would be too volatile.

[Edited on 22-10-2016 by Magpie]

Cryolite. - 21-10-2016 at 20:08

Could you try ammonium formate or sodium formate as a hydrogen source? I don't think you could have any sulfur in there!

I just noticed that the entry for chemcenter palladium on carbon on Amazon is unreduced. Might this have prevented the catalyst from igniting methanol?

[Edited on 22-10-2016 by Cryolite.]

cubalibre - 22-10-2016 at 05:57

Quote: Originally posted by Magpie

No, no smell of H2S.

I am going to have to eat those words.

Today when I was preparing a balloon full of H2 I got a whiff of H2S.
[Edited on 22-10-2016 by Magpie]

Very glad you tested it!
It's your zinc I am pretty certain. I've used very high quality zinc (allegedly 99,99+%) and still smelled it with HCl (synth qual).
Maybe QC isn't done by some suppliers.

Looking forward to see your electrolysis setup!

[Edited on 22-10-2016 by cubalibre]

Magpie - 22-10-2016 at 08:14

Quote: Originally posted by Cryolite

Could you try ammonium formate or sodium formate as a hydrogen source? I don't think you could have any sulfur in there!

My goal is to develop catalytic hydrogenation for home chemistry.

Quote: Originally posted by Cryolite.

I just noticed that the entry for chemcenter palladium on carbon on Amazon is unreduced. Might this have prevented the catalyst from igniting methanol?

I don't know that much about it. Fleaker suggested that the Pd/C should be reduced with H2. I was getting ready to do this when I discovered the H2S.

Magpie - 22-10-2016 at 13:20

Not knowing whether the H2S contamination was coming from the Rooto 6M H2SO4 or the mossy Zn, I did some test tube tests this morning. I placed some metal, ie, either mossy Zn or a part of a Zn electrical fitting, in either Rooto 6M H2SO4 or 6 M muriatic acid using 4 small test tubes. I then placed a strip of lead (II) acetate paper on top of the test tubes during gas generation. Here are the results:

H2S tests with acids and Zn types.jpg - 106kB

So, it looks like the Rooto 6M H2SO4 is the culprit. I don't know if there is sulfide in the acid or it is a reduction product of sulfate or hydrogen sulfate.

I was surprised to see some slight evidence from the electrical Zn with muriatic acid. The ASTM B86 specs I've seen for electrical casting zinc indicate no sulfur present.

AvBaeyer - 22-10-2016 at 19:13

Magpie,

I have been following your travails with the catalytic hydrogenation problem. Your tracking down of the likely source of the sulfurous catalyst poison is quite interesting. Further, I appreciate your aim to develop a hydrogenation method suitable for the home lab environment. As you more than likely appreciate, catalytic hydrogenation is one of the most useful and generally one of the cleanest reactions in organic synthesis. However, after considerable though and musing on your objective, I wonder if you will be truly successful. I do not intend to rain on your efforts or give you all kinds of bogus theoretical blather about why you will fail. The foremost problem I see is being able to develop proper and safe equipment in a home lab setting to carry out catalytic hydrogenation.

I have run and supervised hundreds of catalytic hydrogenations in my career. This goes from very small scale reactions under a balloon to pilot plant runs in a 50 gal reactor under high pressure. Safety considerations in the use of hydrogen gas are paramount. Because of sloppy or untrained/untrainable chemists frequent issues with poor technique in filtering catalysts as well as improperly stored waste catalyst there are sometimes laboratory fires. I do not know how many times a wastebasket has inflamed because some idiot dumped a filtered catalyst into it. In the industrial setting this has led to the general banning of bench top hydrogenations using balloons or other methods as well as the establishment of spaces especially designed for the handling of hydrogen, reaction work-up and the waste products from those reactions ( ie spent catalyst).

One of the main problems one has to be concerned about with the use of hydrogen gas in a home lab setting is the possibility of forming explosive mixtures. Keep in mind that hydrogen does not "burn" - it explodes. During reaction set-up and work up, the danger is ignition at the interface between catalyst, solvent vapor, air, and hydrogen. If one is running a hydrogenation and venting gas into the atmosphere (which is what you did in your initial experiment), there exists the possibility of explosion initiated by any number of ignition sources in the home lab area unless the reaction is being run out of doors. Moreover, if one is blowing hydrogen through a volatile solvent such as methanol then a mixture of highly flammable/explosive gases is being formed outside the reaction vessel.

Much of the safety concern around the use of hydrogen gas can be alleviated by using catalytic transfer hydrogenation which is a well established technique. Unfortunately, the reaction is often not as clean as a true hydrogenation. Others have already mentioned this technique above so I won't go any further.

If hydrogen is the reagent of choice then the reduction ideally needs to be run in a closed system (with pressure relief for safety, of course). Obviously, the best source of hydrogen for this is a cylinder of the gas with the proper pressure reducing valve and suitable gas handling plumbing including vacuum evacuation and inert gas lines. If self generation of hydrogen is the method of choice, the best source of hydrogen is sodium borohydride. Hydrogen is about 10% by weight of NaBH4 and which makes it a very concentrated source of the gas.

A number of years ago HC Brown and his students devised a very versatile lab scale hydrogenation apparatus which uses internally generated hydrogen. This particular apparatus essentially turned hydrogenation into a simple titration. Hydrogen was generated by adding an aqueous solution of sodium borohydride to a solution of HCl or acetic acid. One could follow the progress of the reaction by the amount of borohydride solution consumed. I have attached the references in which this apparatus is described. A somewhat more detailed step-by-step description of the set up and its operation can be found in the 5th Edition of Vogel which is available for free download at:

(https://archive.org/details/TextbookOfPracticalOrganicChemis...)

The Brown apparatus is in my opinion the most ideal set up for the home lab. Its use, however, does not preclude the acute attention to safety which is paramount in any reduction where hydrogen from any source is being used and ultimately vented.

Sodium borohydride is not often easily available and can be appear expensive on a simple weight basis. Besides its high hydrogen content, NaBH4 is one of the most versatile of chemical reducing agents and, in my opinion, should be in every chemist's cupboard. It can be induced to reduce many functional groups and replace in many cases the use of catalytic hydrogenation. The downside can be more laborious reaction work ups but the plus side is a more safe reaction system. Sodium borohydride can be handled without any special precautions with regard to moisture and air sensitivity. It is compatible with many solvents including water. It is my go-to reducing agent for most reduction reactions.

As I said at the outset, I do not want to pour water on your efforts as I always look forward to whatever you might be up to. However, I have been musing on the problem of reductions in the home lab environment for some time as it is one of the most difficult reactions to implement for the home chemist. I wish you success in finding a suitable system. If I can be of any help, please do not hesitate to ask or contact me.

AvB

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Magpie - 23-10-2016 at 10:32

AvB,

Thank you for your thoughtful letter and the benefit of your considerable practical experience with catalytic hydrogenation.

None of my chemistry is necessary - it's just a hobby. Use of catalytic hydrogenation technology has developed into a challenge - more difficult than I had imagined. I have very little experience with heterogeneous catalysis. This synthesis of making succinic acid just seemed to fit my needs at this time.

I am aware of the risks of working with hydrogen. I purge my apparatus with argon prior to hydrogen generation. In fact my balloon was not fully bouyant, likely as the gas contained too much argon. When venting H2 I have my 400cfm hood fan ON.

Yesterday I set up a small apparatus to flare hydrogen. It was interesting to observe a nearly colorless flame. I have also learned to fill a balloon with H2 using an aquarium pump. This is all part of learning the characteristics of a reagent relatively new to me.

I have used Na borohydride before in a school setting. I don't own any as I have not needed it. I know I can get it through Elemental Scientific.

cubalibre - 6-11-2016 at 12:06

Wow, so I was wrong too

!
Keep us updated!

Magpie - 6-11-2016 at 13:54

I haven't given up on this project. I'm in the procurement stage for building an electrolysis unit using Phillip Hurley's design. I have modified the material selection slightly to drastically cut costs. When I get this functional I'll post the results.

Dr.Bob - 7-11-2016 at 20:22

Great discussion AvBaeyer, I agree that hydrogen can be dangerous, and have heard of a few small fires myself. Any catalyst should be filters with a little celite perhaps, and the used material put in a bottle with some water to keep it wet. Keeping sulfur away is key, it might even be that the hydrogen is reducing sulfate residue. I don't know. Traces of chloride are often OK, and can actually speed up some reductions. A good hood is great for safety, as is sparging everything with argon in between steps. Small scale, and using ethanol rather than methanol will contribute to less fire risk. But I agree that sodium formate is a great hydrogen source for transfer hydrogenations. Hydrazine also can work in some cases, I have used it with Raney nickel a number of times for reducing nitros to amines.

Magpie - 8-11-2016 at 14:40

I recently prepared succinic acid from monosodium glutamate (Accent meat tenderizer/flavoring) per Chemplayer's YouTube video here: https://www.youtube.com/watch?v=kDLSRk068SU

My glutamic acid weight was 29g vs his 25g. When finished I had a translucent brown solution with no crystals. I was ready to call it a failure but set it aside for a few days. Just before throwing it out I noticed crystals were growing so let this go awhile. My first batch of crystals (washed with water) were quite discolored with the brown contaminant. So I boiled them with some activated charcoal which cleaned them up considerably, but they were still not white. I repeated the charcoal treatment. The resulting crystals are shown in the photo. The mp was 183°-184°C. The lit. value for succinic acid is 184°C. The wt of this batch is something <1g.

A 2nd batch (0.66g) of crystals was obtained but they were in worse shape after one treatment of activated charcoal than the 1st batch. I titrated this batch with 0.1N NaOH, getting a MW that was 11% high but definitely in the ballpark.

So the yield was something <2g on 29g of glutamic acid. This is a very poor yield but this synthesis did produce succinic acid.

I obtained the Dakin article referenced by Chemplayer. It uses much milder conditions. I may try that.

thrice crystallized succinic acid.jpg - 157kB

[Edited on 9-11-2016 by Magpie]

j_sum1 - 8-11-2016 at 14:44

Well done Magpie. This is something of an accomplishment.
I have learned a bit reading this thread over the past couple of days. Great to get some success!

Magpie - 8-11-2016 at 18:21

Thank you j_sum1. It is a weird synthesis.

Magpie - 16-11-2016 at 14:09

I decided to attempt preparation of succinic acid using the Dakin synthesis referenced above. This prep is indeed much milder than that presented by Chemplayer. There was no tar formed and there seems to be a considerable amount of unreacted glutamic acid, a white solid insoluble in ether and mostly insoluble in water.

Ether is used to extract the succinic acid from the aqueous phase products. Succinic acid has solubility of 8.8mg/mL in ether per Wiki. A continuous "lighter-than-water" extractor is used. Luckily I have one of these bought for another project but never used. The pictures below show it in use for this preparation. So far the extraction has been running for 4 hours. I plan to run it for another 2 hours.

The little funnel catches the dripping ether and returns it to the bottom of the column via a 6mm tube. From there the ether rises through the aqueous phase and overflows into the pot. In the pot it is vaporized and then condensed in the Allihn condenser. The succinic acid remains in the pot.

succinic acid extraction bare RBF.jpg - 137kB

succincic acid extractioin Allihn condenser.jpg - 115kB

extractor return tube & funnel.jpg - 109kB

Magpie - 17-11-2016 at 13:49

I finished up my attempt at making succinic acid via the Dakin procedure as described in my previous post. I started this with 12.6g of glutamic acid made from monosodium glutamate (Accent MSG).

The ether extract described was distilled today to recover the ether as shown in the picture. When there was only a few mLs of boiling liquid left I poured it into a crystallizing dish. When the visible liquid had evaporated I placed the product in a 103°C drying oven for 2 hours. The picture below shows the mangy, sticky, paltry product, weighing 0.2g. I made no attempt to purify it.

This sparse on detail 1908 procedure then is a failure, at least in my hands. Admittedly I only ran the extraction for 6 hours. My lab manual recommends extracting for at least 24 hrs. I don't think that would have improved the quality of the product, however.

In conclusion I think Chemplayer has the right idea by incorporating more aggressive conditions. In his hands it seemed to go well. But he never did confirm the identity of his product.

distilling off the ether from succinic acid extract.jpg - 139kB

chemplayer... - 19-11-2016 at 16:09

Thanks Magpie for writing up your findings on this. The ammonium glutamate / H2O2 method does seem to work better but in the end we found it hard to find a relatively simple qualitative test for succinic acid so we never managed to conclusively confirm the product identity. It's definitely not starting material though and seems to have the right solubility profile. We may put this on our future 'to do' list if we can find a test, and then see if we can use succinic acid for something interesting.

Magpie - 19-11-2016 at 19:09

As noted above I used mp and MW to confirm the identity of the small amount of succinic acid made with your method. Is there any reason why you can't use these methods?

chemplayer... - 20-11-2016 at 01:59

We didn't think of doing a melting point but yes, although we don't have a proper apparatus we could try to improvise.

symboom - 9-12-2016 at 06:10

What about from cream of tartar potassium bitartrate .Tartaric acid its the structure with two OH groups added
Maybe there is a potassium bitartrate to succinic acid route
It just needs t o more OH groups

CuReUS - 9-12-2016 at 07:28

why not make succinic acid from MSG using a mixture of H₂O₂ and HClO₂ ? H₂O₂ reacts with HClO₂ to make HOCl which then reacts with HClO₂ to form ClO₂ which is again converted to HClO₂ by H₂O₂,completing the cycle.Simultaneously,MSG first gets converted to CHO-CH₂-CH₂-COOH(amino acid to aldehyde reaction by HOCl) and then the CHO is oxidised to COOH by HClO₂(pinnick oxidation) to give succinic acid.https://en.wikipedia.org/wiki/Pinnick_oxidation#Side_reactio...

[Edited on 9-12-2016 by CuReUS]

Preparation of Succinic Acid using the method of Chemplayer…

Magpie - 10-12-2016 at 12:00

Introduction
I found Chemplayer’s YouTube (ref 1) video for making succinic acid (SA). This method seemed attractively simple using a cheap and readily available precursor, monosodium glutamate (MSG). H2O2 (35%) was also readily available. The ammonium bicarbonate (Baker’s ammonia), was readily obtained by mail.
Chemplayer’s method is an adaption of the 1908 procedure of HD Dakin (ref 2), as indicated in his video.

Chemplayer’s method first makes glutamic acid from MSG by adding a stoichiometric amount of HCl. 25g of the resulting glutamic acid is then used to make SA. SA is finally recovered by crystallization.

Procedure
Once the required reagents were on hand I proceeded to follow the Chemplayer procedure.

A small amount of pure white SA resulted from my 1st run. Its identity was confirmed by melting point and titration. I have since made several more runs using different MSGs in an effort to improve yield and purity.

Listed below are my observations from these several runs. The results of my last synthesis are also reported:

Observations
1. Upon addition of the HCl the formed glutamic acid quickly turned very thick and I could not continue stirring with my Corning PC-320 magnetic stirrer using a 2” stirbar. The slurry had the consistency of mayonnaise. Perhaps Chemplayer has a much more powerful stirrer than I?

2. I first used Accent MSG from my grocery store but it gave a yellow colored product. Thinking this MSG might have additives, I bought Tradewinds brand (much cheaper) at a restaurant supply store. However, it also produced a colored product. As a last effort I bought Aji-No-Moto brand MSG from an Asian grocery store (even cheaper yet at $3/lb) as this is the brand cited by Chemplayer in his video. Still there was no difference in performance or product color. In review this multi-purchase seems foolish as all the MSGs had the appearance of pure, well formed crystals.

3. The major difference (and problem) was the appearance of color which I now assume is a degradation product. It first appears about ½ way through the 30 minute addition of 30% H2O2 at 65-80°C. At this point it colors the solution a translucent canary yellow but by the end of the 90 minute heating period at 80°C the color is a translucent tea brown. I tried to remove this color using an ether extraction. However, the color is highly soluble in water and none transferred to the ether. Removal of a significant amount of this color was achieved by boiling with activated charcoal. There was some residual amount that was not removed after 2 tries, however. This is an undesirable contaminant and lowers the melting point of the SA product.

Pictures taken during this run are as follows:

midway through H2O2 addition.jpg - 106kB

Reactants midway through H2O2 addition

Attachment: phpH769vH (110kB)
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Product after 1.5hr at 80°C

after 1st treatment with activated charcoal.jpg - 111kB

Product after 1st treatment with activated charcoal

after 2nd treatment with activated charcoal.jpg - 121kB

Product after 2nd treatment with activated charcoal

Product after evaporation

4. Chemplayer adds 10mL of 50% sulfuric acid to the final solution. IMO this is not enough as the pH only came down to 4. To get the best precipitation I have calculated from the pKa of succinic acid using the Henderson-Hasselbalch equation that the pH should be brought down to ≤ 2.2:

pH = pKa + log ([succinate ion]/[SA]) (Henderson-Hasselbalch eqn)

Succinic acid pKa1 = 4.2

For ~100% free acid:

pH = pKa1 + log (1/100) = 4.2 -2.0 = 2.2

But I found that the pH should not be lowered below 2.2 as this can destroy filter paper. A target pH of 2 is also recommended in an article by researchers separating SA from a fermentation broth (ref 3).

5. I did not get a nice clean precipitate by simply chilling the final solution as did Chemplayer. I first chilled my solution in a freezer overnight but it froze. After thawing at room temperature I left it for a day in my 10°C lab. Crystallization then occurred as shown below:

Attachment: phpoTncSu (145kB)
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1st crop precipitation

There seemed to be a strong tendency to supersaturate based on the published solubility of SA.

2 crops of crystals were recovered during the last run. These were caught on a 7cm Buchner funnel using no wash water. Washing the crystals with ice-cold water to remove color caused excessive loss to the filtrate. A picture of the two crops of crystals, dried at room temperature, is shown below:

air-dried succinic acid 1st & 2nd crops.jpg - 121kB

1st (left) and 2nd crops of crystals

Results
The first crop retained some of the yellow of the mother liquor. The 2nd crop, surprisingly, was almost pure white and glistening. An effort is being made to recover a 3rd crop. After a few days in my cold lab crystals are just starting to form.

Yields (theoretical maximum = 20.0g):

1st crop: 4.6g
2nd crop: 4.4g

The combined yield for the two crops was 9.0g of putative SA. Based on the 25g of glutamic acid charged this is a 45.0 %yield.

Melting points (Wiki value for SA = 184°C):

1st crop was 170°C
2nd crop was >230°C

Titrated MW using 0.1N NaOH (Wiki value 118.09):

1st crop: 162
2nd crop: 583

Discussion and Conclusions
After watching Chemplayer’s video I thought that this would be an easy synthesis. To the contrary, I found that, mostly due to the color, purification of the crystals was tedious. Additionally, waiting for crystal precipitation, and air drying of the crystals (a cautionary measure), became quite time-consuming.

My conclusion has to be that I produced very little if any succinic acid. I have put a lot of time and effort into trying to get this synthesis to work. It’s time for me to “stop beating a dead horse.”

I would really like to hear from Chemplayer concerning the differences in our results. I hope he can tell us why this synthesis seemed to proceed so much smoother in his hands.

References
1. “Prepare Succinic Acid from Monosodium Glutamate,” by Chemplayer, YouTube, January 16, 2016. https://www.youtube.com/watch?v=kDLSRk068SU
2. ”Succinic Acid by Oxidation of Glutamic Acid,” HD Dakin, J. of Biol. Chemistry, 1908.
3. “One Step Recovery of Succinic Acid from Fermentation Broths,” by Li, Wang, Wu et al, Separation and Purification Technology, vol 72, issue 3, May 11, 2010, pp. 294-300.
http://www.sciencemadness.org/talk/viewthread.php?tid=62326&...

Your comments, questions, and recommendations are welcomed.

[Edited on 10-12-2016 by Magpie]

[Edited on 10-12-2016 by Magpie]

[Edited on 11-12-2016 by Magpie]

chemplayer... - 10-12-2016 at 18:17

Magpie, very interesting to read another attempt at this reaction, and frustrating to read that it's not working out.

Firstly, did you get a noticeable exotherm during the H2O2 addition (especially the first 10-15ml)? We noticed that as the bubbling occurred the temperature shot up and the mixture required cooling.

Secondly, did you get ammonia evolution occurring during the 'boiling' part of the procedure? (In our video you can see the indicator paper changing colour as this is evolved.) These seem to be reasonable indications that something useful is happening.

Love to find out what is going on here and why this doesn't seem to be reproducible. We'll be trying this out again at the first possible opportunity to see if we can do it again and to see if we can do a better analysis of the product (sort of difficult though now because the equipment is all stashed away).

Magpie - 10-12-2016 at 19:06

Quote: Originally posted by chemplayer...

Firstly, did you get a noticeable exotherm during the H2O2 addition (especially the first 10-15ml)? We noticed that as the bubbling occurred the temperature shot up and the mixture required cooling.

Yes, there was a strong exotherm when adding the H2O2. I had to cool the beaker 3-4 times during the addition of H2O2. I would cool it when the temperature reached 80°C.

Quote: Originally posted by chemplayer...

Secondly, did you get ammonia evolution occurring during the 'boiling' part of the procedure? (In our video you can see the indicator paper changing colour as this is evolved.) These seem to be reasonable indications that something useful is happening.

Yes, there were ammonia vapors continually being evolved during the addition of ammonium bicarbonate.

I didn't do any boiling of the reactants - they probably never exceeded 85°C.

Quote: Originally posted by chemplayer...

Love to find out what is going on here and why this doesn't seem to be reproducible. We'll be trying this out again at the first possible opportunity to see if we can do it again and to see if we can do a better analysis of the product (sort of difficult though now because the equipment is all stashed away).

I, too, would really love to find out the cause of the striking discrepancies between your work and mine. Making succinic acid this way would be a valuable tool for the home chemist.

[Edited on 11-12-2016 by Magpie]

AvBaeyer - 10-12-2016 at 19:25

Magpie,

Perhaps you might want to try a similar but alternate approach to succinic acid from glutamic acid. Dakin published what amounts to a 2 step oxidation-hydrolysis procedure which provides succinic acid from glutamic acid. He uses chloramine-T as the oxidant though TCCA can also be used. I have attached the Dakin paper. I have also attached a review of the Strecker degradation (published in Chemical Reviews) which may give you further insight into your synthesis challenges.

The TCCA paper has a typo in it where "glutaric acid" is used for glutamic acid.

Hope you find these useful.

AvB

Attachment: Dakin_amino acid oxidation.pdf (1.6MB)
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Attachment: THE STRECKER DEGRADATION OF -AMINO ACIDS1952[1].pdf (889kB)
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Attachment: Conversion of a-Amino Acids into Nitriles TCCA Syncomm2004-34-3449.pdf (95kB)
This file has been downloaded 668 times

Magpie - 10-12-2016 at 20:28

Thank you for those references AvB. It looks like that last synthesis using TCCA could be used to convert glutamic acid to succinic acid.

chemplayer... - 20-12-2016 at 01:16

Some very weird and interesting news to report. With food grade (>99%) MSG at hand and some reagent grade c.HCl I had a go at preparing just the glutamic acid again (no proper glassware though, but accurate weights / measures).

The MSG used was 'Ajinomoto' brand (Japanese import) from a new 500g bag and was in the form of small semi translucent 'shard' crystals, some of which were quite spiky and pine-needle-like.

50g were dissolved in 90ml of water and then 25ml of c.HCl added. After a very brief pause (1 second perhaps) a thick white precipitate was generated, and a bit of heat generated in the mixture. The precipitate was then filtered and washed with difficulty.

Observations:

1. The precipitate was much finer than the previous one we captured on video, and formed a mixture more akin to 'plaster of Paris'. It didn't settle in the mixture as the previous one did.

2. Filtration was much more difficult than before and the solid very difficult to dry substantially. It also formed a 'gel' in the filter where no water would filter off (even with vacuum) but on agitation 'wetted' and then more water could be removed. This is totally different to what we previously captured on video.

3. The crystalline appearance of the starting material is very similar to the one we previously used, but is slightly different. The previous material didn't form the 'needles' and was more cubic in nature.

4. No hard evidence, but the MSG used on this occasion seemed to be slightly less water soluble than in the previous one. Dissolution seemed to be slower.

The only possible conclusion I can come to is that what we previously used in the experiment, although labelled as 'Aginomoto >99% MSG' could not have been what it said is was! I will try to track down and see if I can find any archive footage of the original bag and labeling to see if I can find the exact same brand again! This is somewhat disturbing...

I've checked our inventory list and we did retain the sample of what we thought was succinic acid from the previous experiment that we captured on video (it is in storage). So I will make an effort to get this out when the opportunity arises (probably the next week or so as chance would have it) and see if a melting point can be obtained.

Open to any other thoughts or suggestions!

Magpie - 20-12-2016 at 09:40

Thank you chemplayer for pursuing this discrepancy!

Your observations on making glutamic acid are consistent with what I observed with 3 different OTC sources of MSG. The last was the Aji-No-Moto, a Japanese company brand, but made in the US. I presume the manufacturing process was Japanese.

You liken the paste to Plaster-of-Paris. I agree. To get a good wash I slurried the 20g or so of the paste in 1000mL of distilled water, then sucked it damp on a 15cm Buchner filter. The acid was then air dried and ground to a powder with a mortar & pestle.

So, it seems we have some evidence that the MSG you used in making your video may be different in some important way(s) to what is available on the US OTC market.

It may be worth the effort to obtain some Aji-No-Moto MSG directly from Japan.

Cryolite. - 20-12-2016 at 13:05

When I attempted to prepare glutamic acid from MSG, I had much the same experience. I don't recall the brand used, but the branding and text was in Thai. I dissolved this in water and added excess hydrochloric acid with stirring, and almost immediately a large crop of micocrystalline white product fell out of solution, jamming the stir bar. To get a product, I ended up having to transfer the thick paste into a larger beaker, adding water, and pouring the resulting slurry into a fritted funnel.

As far as a test for glutamic acid goes, according to https://www.google.com/patents/US2849468 zinc glutamate is extremely insoluble in water. Maybe adding some zinc chloride solution to the presumed MSG, and filtering the obtained product would provide a qualitative test for the amount of actual MSG in the obtained material?

chemplayer... - 20-12-2016 at 17:16

Yes I trust the Japanese made brand to be what it says it is. I looked through the complete video footage archive and I can't find a shot of the previous bag of MSG that we used for the video, however I did find separate footage of another experiment (never turned into a video) using the same starting material (but a different reagent grade HCl source) where we dissolved it and acidified and the result was the same as in the published video - again, suggesting that it's the startiong material that is the anomaly.

I am intrigued now and might go and buy a few different 'local' brands of MSG powder and see if the results are consistent and if any of them reproduce the previous results.

Here are some quick photos / screenshots showing the 'mystery MSG' and the acidification product, and the Japanese one (where we are getting consistent results).

1. mystery msg acidification prod.jpg - 87kB

2. japanese msg acidification prod.jpg - 148kB

AvBaeyer - 20-12-2016 at 18:21

Here is some information which may help with the conundrum you currently face.

According to Greenstein and Dunitz in "Chemistry of the Amino Acids" V3, pp1929ff, the HYDROCHLORIDE salt of glutamic acid is formed in HCl solution and its insolubility "far exceeds" that of any other amino acid hydrochloride. It then stands to reason that what you isolate on acidification of MSG with a large excess of hydrochloric acid is the hydrochloride salt of glutamic acid. In fact the preferred method of isolating glutamic acid from protein hydolysates is to precipitate the HCl salt with excess hydrochloric acid. The above authors then go on to discuss the instability of glutamic acid (and glutamine) in aqueous solution as it readily cyclizes to pyroglutamic acid.

The melting point of pure, dry glutamic acid hydrochloride is reported as 208-9 C (dec).

The above authors give the following procedure for isolation of pure glutamic acid from the precipitated hydrchloride:

"36.7 g of the pure hydrochloride are dissolved in 200 ml of hot water, adding 20 g redistilled aniline, and quickly cooling to room temperature. Ethanol is added to 80% with stirring and the mixture allowed to stand at 5 C for 20 hr. The crystals of pure glutamic acid are filtered over suction, washed with 95% ethanol until chloride free, and finally with ether. When dry, the yield amounts to about 27 g; mp 211-213 C (dec)."

But wait, there's more:

For the isolation of glutamic acid from commercial Ajinomoto/MSG (also from the above reference, p 1938):

"the salt is brought into suspension in about 4 times its weight in hot water. Norit is added and the mixture filtered. To the clear solutuion, now brought to the boiling temperature, 4N hydroBROMIC acid [my emphasis] is added to pH of 3.0and the solution allowed to stand for several hours at 5 C. The crystalline glutamic acid is filtered and washed successively with ice water, ethanol and ether and should be halogen-free. The yield from 100 g Ajinomoto containing some 85 g of sodium L-glutamate may be about 50 g."

I gather from the above that some commercial MSG is less than 100% MSG, perhaps containing anti-caking material or just junk.

Clearly, the simple addition of hydrochloric acid to MSG is not giving you what you think it does thereby leading to a messed up synthesis of succinic acid. The isolation of glutamic acid is a bit more complicated than simple precipitation.

At this point I would simply buy succinic acid and , at the risk of snarkiness, suggest doing a bit more literature work before dragging out the test tubes (apologies in advance).

AvB

chemplayer... - 20-12-2016 at 18:43

That is useful information, but doesn't explain the difference in using like-for-like quantities of MSG powders and approximately equimolar acid. Another possibility is that some companies are selling 'disodium glutamate' as MSG (reading around there are problems out there with 'fake MSG' believe it or not), but this still doesn't fit the observations. I will report back as and when I can test some other sources and also check the mp of the product from the first reaction.

Cryolite. - 20-12-2016 at 20:39

Maybe a more reproducible precursor for succinic acid would be GABA? It is sold as the free acid at most vitamin stores, and it is glutamic acid minus a carbonyl.

AvBaeyer - 20-12-2016 at 21:50

chemplayer,

The explanation lies in the details, details that are so far missing. I am unaware that the mass balance of your glutamic acid precipitation step has been reported. What was the yield of your purported glutamic acid from the MSG? Did you ever dry and weigh the precipitated product? So far the only data I have seen in this discussion are qualitative. Photos do not allow conclusions. My guess is that you are isolating glutamic acid hydrochloride to the extent that you are adding hydrochloric acid. That is to say, for each mole of hydrochloric acid added you are precipitating 0.5 mole of glutamic acid hydrochloride. The remainder of the glutamic acid remains in solution as unconverted MSG. Disparate behavior observed between brands of MSG may be due to purity. However, until I see data to the contrary, I am quite sure you are getting the hydrochloride salt in a yield related to the amount of hydrochloric acid employed.

AvB

Cryolite. - 13-3-2017 at 02:59

Has there been any update on this thread? If obtaining the maleic acid is a problem, I recently purchased 500 grams of it and would be more than willing to supply Magpie some to further these experiments.

Also, is anyone aware of a good procedure for catalytic transfer hydrogenation? I am interested in making succinic acid as well (for succinimide), but I do not want to deal with the hassles of making pure hydrogen gas. My presumptive donor will be ammonium formate.

clearly_not_atara - 13-3-2017 at 12:45

If you want succinimide, I'm 99% sure that you can oxidize glutamate to succinic mono-nitrile using TCCA, as the reaction proceeds for other amino acids and glutamate is not particularly sensitive. The mononitrile is easily converted to the mono-amide with catalytic hydrogen peroxide:

http://pubs.acs.org/doi/abs/10.1021/jo00819a034

This might even be achieved by adding the sodium salt of succinonitrilic acid to 3% H2O2 disinfectant.

And the succinic monoamide is dehydrated to succinimide by heating, of course.

What I don't know about is how to extract succinonitrilic acid from the rxn mixture with TCCA. I don't think it's that hard, though.

Cryolite. - 13-3-2017 at 13:12

I am aware that I could use glutamic acid as an alternate precursor, but I already have more maleic acid than I know what to do with, and buying another reagent for this purpose seems wasteful.

BlackDragon2712 - 13-3-2017 at 13:18

Indeed, and it is done apparently in yields of 90% and the procedure looks quite simple.
When I came up with the same question I thought of reducing the nitrile to the amine but this is quite hard... I think it's better to go with a stephen aldehyde synthesis and reduce the nitrile to the aldehyde with SnCl2 and then oxidize the aldehyde to succinic acid.

I never actually tried it but is surely worth a shot

Alpha aminoacids to nitriles with TCCA:

www.sciencemadness.org/talk/files.php?pid=69963&aid=1539

BlackDragon2712 - 13-3-2017 at 13:33

Btw... I found a few years ago this paper talking about an easier, safer and reliable protocol for in situ hydrogenations and hydrogenolysis... The nice thing is that this method allows you to work at room temperature and at atmospheric pressure over methanol as a solvent... The catalyst is a mix of palladium II acetate and 90% by weight charcoal

Again... I've never actually tried it... but it looks interesting at least...

I hope this helps somehow

A Useful, Reliable and Safer Protocol for Hydrogenation and the Hydrogenolysis of O-Benzyl Groups: The In Situ Preparation of an Active Pd0 /C Catalyst with Well-Defined Properties :

http://onlinelibrary.wiley.com/doi/10.1002/chem.201001377/ab...

clearly_not_atara - 13-3-2017 at 17:55

This paper describes a number of methods of reducing olefins using Ni(0) in 2-propanol with the solvent as hydrogen donor:

https://rua.ua.es/dspace/bitstream/10045/12847/4/proofs2.pdf

The methods in the Introduction are somewhat simpler than the subject of the paper. Fumaric acid should be an easy substrate for reduction. It may be possible to convert to maleimide first if the acidity is an issue.

Boffis - 18-1-2018 at 03:02

Is it possible /worthwhile preparing succinic acid from 1,4-butanediol or tetrahydrofuran?

I am sure I have seen a YT video of the oxidation of THF to butyrolactone. Maybe this can be followed by alkali hydrolysis and then alkaline oxidation with H2O2; NaOH+permanganate or hypochlorite? (acidic conditions tend to cause the reforming of the lactone)

Alternatively can you oxidize butanediol directly to succinic acid say with sulphuric acid and potassium dichromate to get chrome alum as a byproduct?

Chemi Pharma - 19-1-2018 at 04:48

@Boffis, here's a paper where succinic acid is obtained from 1,4 butanediol and also THF by oxidation with nitric acid.

Enjoy.

Attachment: succinic acid from Tetrahydrofuran and 1,4-Butanediol with nitric acid.pdf (28kB)
This file has been downloaded 451 times

Boffis - 19-1-2018 at 10:50

@Chemi Pharma; many thanks for the paper, that looks interesting. I hadn't thought about nitric acid although thinking about it I recall that a similar process for the preparation of malonic acid from 1,3-propanediol has been posted on this forum. The only problem is that nitric acid is getting very hard to get now. I am also looking at chromic acid since I have just been given a large jar of the stuff.

Boffis - 2-2-2018 at 12:51

Since I have a fair amount of chromium trioxide and very little nitric acid I decided to try oxidizing 1,4-butanediol with chromic acid and sulphuric acid mixture. Working on the ideal formula:

3C4H10O2 + 8CrO3 + 12H2SO4 → 3C4H6O4 + 4Cr2(SO4

3 + 18H2O

I diluted just over 21g of the diol with and equal volume of water and then added it to a mixture of 63g of chromic anhydride in 100ml of water and 60ml of conc sulphuric acid previously diluted into 60ml of water and chilled. The rate of addition was at such a rate as to maintain a temperature of about 30 C. A cold water bath was used to help control the exothermic reaction. I now have about 250ml of dark blue green slurry which I am going to leave to cool overnight and them filter of the solid and see what I get. I noticed that towards the end of diol addition there was a small amount of effervescence. If this is carbon dioxide I would have expected it to have been more prevalent at the beginning as I presume its the result of over-oxidation.

I'll keep you posted

Magpie - 2-2-2018 at 12:58

Since you have the 1,4-butanediol I would try oxidizing it with nitric acid as I did in making malonic acid from 1,3-propanediol. See Prepublication.

BTW, where did you get the butanediol?

[Edited on 3-2-2018 by Magpie]

clearly_not_atara - 2-2-2018 at 17:53

I was looking for old posts about something else, and I rediscovered the reaction of hydrochloric acid with sucrose:

http://en.wikipedia.org/wiki/Levulinic_acid

Haloform elimination of this molecule with e.g. bleach gives succinate. This might be useful if you can't buy 1,4-butanediol, because 1,4-butanediol is considered a GHB analog in the United States.

JJay - 2-2-2018 at 20:54

Quote: Originally posted by clearly_not_atara

I was looking for old posts about something else, and I rediscovered the reaction of hydrochloric acid with sucrose:

http://en.wikipedia.org/wiki/Levulinic_acid

Haloform elimination of this molecule with e.g. bleach gives succinate. This might be useful if you can't buy 1,4-butanediol, because 1,4-butanediol is considered a GHB analog in the United States.

Interesting. I have always been annoyed that 1,4-BDO is so hard to purchase since it is awfully hard to make THF without it.

LearnedAmateur - 3-2-2018 at 08:48

Since alternate syntheses are popping up and that butanediol (I was a bit wary for obvious reasons) has been mentioned, I’ll insert mine which I’m planning to try. I’ve been exploring the Sandmeyer reaction recently, and it is entirely possible to get to succinic acid from GABA, which is easy to procure and still OTC in the States as far as I’m aware.

GABA is reacted with in situ, dilute nitrous acid to form the alkyldiazonium intermediate. Allowing the temperature to rise, it subsequently reacts with water to form GBL-GHB equilibrium with evolution of nitrogen. When this is complete, the aqueous layer is extracted using DCM or similar solvent which is distilled and recovered to leave GBL. After determining yield, a solution of KMnO4 is prepared, into which the GBL is added. GBL will undergo ring opening wherein the exposed hydroxyl group will be oxidised (under gentle heating or reflux, that’s up for determination) forming the monopotassium salt of succinic acid, which can then be acidified to give succinic acid. Ether can be used to extract this if necessary, possibly DCM but I’m not sure considering that it is barely soluble in chloroform and I can’t find much more information regarding the solubility in immiscible polar solvents.

By playing with more gentle oxidising agents, which is where I’m not entirely sure about, succinic semialdehyde may be synthesised instead if anyone needs to procure any.

Edit: decided to remove the ‘censors’ since the first part of the procedure is easy to find around anyway.

[Edited on 3-2-2018 by LearnedAmateur]

Boffis - 3-2-2018 at 14:32

@Magpie; some years ago now I bought a job lot of old chemicals from a guy on ebay, when I went to pick them up he asked me if I was interested in any of his other chemicals; he had quite a collection. I took the butanediol because it was in a 2.5L winchester with the acid resistant GL45 caps which are really expensive, the bottle was about a third full so I transferred it to a smaller bottle. There was about 800ml but at the time I had no particular use for it.

My succinic acid preparation is going fairly well, chilled to 6-7 C over night, stirred up to disperse the crystals formed and then filtered using a glass frit funnel. I rinsed it with a little water to give a moderate amount of pale blue crystal. If you use enough water they become white but I was worried about loosing too much to the wash water so I used a little water and I will recrystallise them. The yield of crude succinic acid was 12.274g, which is less than 50% yield but with 300ml of chromic sulphate solution there may be significant material left in solution.

A question. What to do with the 300ml of chromic sulphate solution. It is completely reduced to Cr3+ and is a lovely deep greenish blue colour but how to recover something useful from it? I could add ammonium or potassium sulphates to precipitate much of the chromium as an alum then concentrate the liquor, the chromium tends to form a sulphato complex on boil which is slow to crystallised giving the succinic acid a chance to crystallise before the remainder of the alum?

Is say ether extraction of the liquor possible to recover more succinic acid possible?

Nitric acid looks like a cleaner route but as I said above that depends on the local availability of nitric acid.

@ learned amateur; I was writing this post while yours appeared so I'll edit to incorporate a response to your post too. I was looking for a use for my diol rather than the best method to succinic acid but your post made me think.

There are several routes to nitriles from amines etc so maybe it would be simpler to try oxidizing GABA directly with say TCCA and NaOH to see if you can get 4-nitrilobutyric acid, filter off the insoluble isocyanuric acid and the extract the nitrile with a weakly polar immiscible solvent. The nitrile can then be hydrolysis to succinic acid. Other oxidizing agents may work (N-chlorosuccinimide etc) and there are several threads on SM covering versions of this idea.

[Edited on 3-2-2018 by Boffis]

AvBaeyer - 3-2-2018 at 19:31

Boffis,

Oxidation of GABA with TCCA to give 3-cyanopropionic acid should work as you proposed - good thought. Oxidation of readily available aspartic acid will also work and is documented. See attached.

The hydrolysis of the nitrile should be facilitated by the nearby carboxylic acid function.

AvB

Attachment: An Insight of the Reactions of Amines with Trichloroisocyanuric Acid[1].pdf (160kB)
This file has been downloaded 459 times

LearnedAmateur - 4-2-2018 at 02:45

Oh yeah, whatever is easiest and most readily available would ideally be the best route so focusing on 1,4-BD oxidation would be most appropriate in your case, I just wanted to propose an alternate idea since I have all of the reagents lying around whereas TCCA isn’t something I need or am willing to spend out on right now. If I do happen to procure any then I’ll be happy to explore that route; for the sake of science it may be a good idea for us to all explore their respective syntheses and compare yields and other observations.

Boffis - 9-2-2018 at 15:12

Chromic oxidation of butanediol continued

I tried an ether extraction of the chromic sulphate solution with about 40ml of ether, removal of the ether left 0.450g of colourless moist crystals that smelled slightly of sweaty feet. I added these to original crystals and recrystallised them from water. About 25ml was the minimum workable amount, it gave me a clear deep greenish blue solution that crystallised nicely on cooling. The crystals were filtered off, washed with a little cold water and dried. The very pale blue/ white crystals of succinic acid weighed 8.193g (from 12.72g). I tried cleaning up the residue by turning it into the sodium salt with excess alkali hoping that this would precipitate the the remaining chromium as hydroxide but no precipitate formed. I may try evaporating the solution down until it crystallises and see what I get.

The resistance of chromium sulphate solution to hydrolysis even by alkalis once they have been boiled is well known so no surprises there. In the cold the sulphochromate complexes slowly revert to chromium sulphate hydrates so I may just let the mixture stand for a few week and see what happens.

The chromium sulphate solution was evaporated down to about 150ml and now resembles black strap molasses. After 24 hours the original viscous liquid has become a viscous slurry so it looks like crystals have formed in it but it's going to be a right b**** to filter

. The liquid is immiscible even with ethanol, only water seems to dissolve it (rapidly) so not much use for washing the crystals.

Boffis - 12-2-2018 at 12:58

Interesting observation; the blue residue from recrystallising the first crop of succinic acid was made alkaline with sodium carbonate solution and as mentioned above no precipitate formed. However, after a couple of days a precipitate is forming and the solution becoming paler so hopefully the residual chromium can be precipitated. The Original chromium III sulphate liquor has become an almost porridge like consistency.

Boffis - 15-5-2018 at 13:22

I have made some further experiements into the oxidation of butanediol to succinic acid.

Firstly I tried using sodium chlorite and hydrochloric acid. A strong solution of sodium chlorite was added dropwise to butanediol diluted with about 4 times its volume of water and to which a small amount of conc 36% HCl was added. The solution turned yellow immediately and developed the characterisitc pungent smell of chlorine dioxide but to my surprise no other reaction took place even on heating. It appears that chlorine and chlorine dioxide do not oxidize 1,4-butanediol at all. Heating simply expels and decomposes the gas.

Next I tried TCCA as per De Luca et al J.Org.Chem. 2003 pp4999-5001. This reaction uses a vast excess of TCCA in the presence of a bromide salt and catalystic amounts of TEMPO to oxidize aliphatic alcohols to acids. Unfortunately when I tried to carry out this reaction following the published procedure I ran into problems that serious question the authenticity of the origin preparation. For a start the procedure calls for 15ml of 15% sodium bicarbonate solution mixed with the substrate (5 mmol) in 50ml of acetone cooled to 0 C. The problem is that at 0 C a saturated solution of NaHCO3 is about 7% and a saturated solution of 60 C is about 15% but stars to loose CO2. Never mind I though, given that my substrate is water soluble and being a diol I only need 2.5mmol I replaced the bulk of the acetone with water. I added a little acetone about, 4-5ml, with the TEMPO and potassium bromide really to help dissolve the former. during the addition of the first 2/5 of the TCCA powder a copious precipitate of isocyanuric acid formed. This made the slurry difficult to stir so at this point I filtered the solution and continued the addition of the TCCA to the filtrate. Strangely no further precipitate formed so the reaction mixture is being left stirring over night. The reaction is not particularly exothermic and it is easy to manage the rise in temperature, foaming in the early stages is a bigger problems.

I'll let you know how I get on with the work up tomorrow.

Magpie - 15-5-2018 at 19:12

Butanediol should be convertible to succinic acid with nitric acid. Please see my conversion of propanediol to malonic acid in Prepublication.

Boffis - 16-5-2018 at 05:03

@Magpie, yes I have seen your malonic acid post and good work it is too. But if you read the thread above you will seen that I am trying to find a route that avoids the now difficult to obtain nitric acid. In the US you can probably still by conc nitric acid but in the UK the nanny state has decided that we are not to be trusted with it, after all we might hurt ourselves and that would never do!

There are many other methods of oxidizing alcohols to acids, some are very substrate specific but many are claimed to be general. As I am finding out many of the leave much to be desired or need much substrate specific customisation.

According to the Luca paper when the reaction is over the excess TCCA is "simply" neutralised with solid sodium metabisulphite. Mmmmm this is proving to be messy with clouds of chlorine evolved for some mysterious reason. I can only assume that the bisulphite is oxidised to bisulphate and that this is acidic enough to cause the TCCA to react with chloride ions to generate chlorine before the excess bisulphite can reduce it. If I try to add the bisulphite faster the mixture foams badly.

By the way, if I want succinic acid I can buy it on-line as permitted food additive and it is cheap c £40/kg including tax and delivery

Boffis - 21-5-2018 at 14:08

Well, I worked up the reaction product; lots of cyanuric acid filtered off. Then I evaporated the filtrate slowly to dryness with stirring, dried the granular mass of salt and then extracted it with hot isopropanol. Most of the isopropanol was distilled off and the remainder allowed to evaporate in a small bowl. The very small amount of residue contained little organic material and was mostly inorganic salts (as determined by heating on a spatula).

So butanediol + TCCA = failure.

Looks like I am going to have to buy my succinic acid

During the evaporation of the water from the salt rich residue there was a strong pungent cheesy small remeniscient of butyric acid. Could this be 4-hydroxybutyric acid? What does butyrolactone smell like?

steadyhand - 30-4-2022 at 17:30

I believe all the consternation regarding MSG+HCl->glutamic acid is due to the high concentrations.

My first run was done using similar proportions as chemplayer and Magpie. Mud, crud, and generally a big mess. This was done at about 3.75M. I reasoned that the problem was due to the rapid crash upon adding HCL, probably precipitating both glutamic acid and its HCL salt leaving a bunch of MSG in solution.

I tried again closer to 0.9M, and this is a totally different experience! 150g MSG in 800mL boiling water (0.889 moles). 0.893 moles HCl in 200mL H20 (85mL 10.5M HCL diluted to 200mL). I let it cool very slowly, eventually into the fridge and was afforded very nice xtals. Yields on 6 runs: 68,70,71,71,73,76%. Total 538g Glutamic acid from 1.128kg MSG (includes crappy mud yield run) I didn't bother to purify any further.

From solubility of Glutamic acid: 140g/L (100C) down to 3.4g/L (0C), I expected 96% max, leaving some behind. But I don't trust solubility numbers for pure substances anyway. Probably could have boiled it down for more crops. Perhaps making sure the pH is correct for Glutamic acid, with Na-Cl equimolar. But given that MSG is $3.50/kg from the local Asian market and only $1 worth of HCl is needed, I'd say this is a fine yield.

Also, I used 10% Ammonium hydroxide to make Ammonium glutamate and later on Ammonium succinate. Why all the trouble to use Ammonium carbonate? I used Kleanstrip denatured alcohol (60:40 EtOH:MeOH) to recrystallize the Succinimide just fine. Total yield of Succinimide was 300g from 1.125kg MSG, about 50%. Total cost was <$10. The experience, priceless.

Bromination to NBS wasn't pretty. I have ideas though for the second batch.

TinyPlanets - 31-5-2022 at 03:47

I had success preparing succinic acid and succinic anhydride in the past from MSG.
The MSG reacts with an equimolar amount of hypochlorite to form the monochloroglutamate which then decomposes spontaneously to succinic semialdehyde (if I recall correctly)
The aldehyde can then be oxidised to succinic acid. This preparation was a pain because the chloro amino acid is very unstable and you can quickly end up with a soup of side products if you're not careful to keep things freezing cold when forming the monochloro product. It needs to be decomposed and processed very fast with rapid heating after that.
Sorry I don't have my lab notes.
I think the yeild was pretty bad but I did get some of my desired product which I purified by dehydration and sublimation.

[Edited on 31-5-2022 by TinyPlanets]

[Edited on 31-5-2022 by TinyPlanets]

Triflic Acid - 1-6-2022 at 20:32

Just read over this, and would like to issue a warning to all SM members. DO NOT BUY Pd/C FROM CHEMCENTER. I noticed I'm not the only one to notice this. I paid $56 for a 10g bottle and got a bunch of powdered charcoal. If you need Pd/C, buy palladium bullion and make it yourself. You'll get a lot more Pd/C for the same cost of raw palladium, and bullion is both guaranteed pure and easily buyable.

Mateo_swe - 10-6-2022 at 10:37

I have also bought some dirt cheap Pd/C from China some time ago, i havent even opened the jar yet but i suspect its all bad.
I will try test it, but im not expecting it to be good.
If one want Pd/C, buying some Pd metal is the way to go and preferably a bullion as these usually are the real deal if buying from a known company trading in such metals.
Making the Pd/C i hear is not especially hard to do.

I also bought a supposedly platinum coated anode from a chinese seller on ebay and its not platinum coated even it says so.
I tried put some H2O2 on it and it doesnt form any bubbles, a test one can make to verify that its precious metals.
Same thing with this one, if it sounds to good to be true, it is not true.
So buy the platinum bullion and make it yourself and you are sure to get what you want.
Or maybe, if the seller is very known to sell the real deal and have a long record of happy customers one can risk a purchase.