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All 25 posts   Subject: from photo developer to potent hallucinogen   Please login to post   Down

(Hive Bee)
10-23-04 14:04
No 537293
      from photo developer to potent hallucinogen     

A friend of mine told me this interesting story the other night.. Apparently he accidently broke his only condenser while disconnecting one of the hoses.  Angered but not defeated he eyed the limited supply of chemicals at his disposal and here is what happenend:

In a round-bottomed flask equipped with magnetic stirring was added 250 mL of H2O, and 45 mL of 25% NaOH.  15 grams of hydroquinone was then added followed by 26mL of dimethyl sulfate.  The flask was stirred at room temperature and after 15 minutes it was obviously no longer basic judging from the light color and flakes of hydroquinone floating around.  At this point more 25% NaOH soln was added.  In fact, he admits that too much base was added at this point which really hurt the yield in this reaction by slowing it down considerably.  Anyhow, after another hour white crystals began to form out of the dark mixture and it took on the familiar smell of p-dimethoxybenzene.  Stirring was continued for another 6 hrs, after which he became impatient and proceeded to vacuum filter the crystals on a buchner funnel and wash them with H2O.  Yield: 11 grams (58%)

A solution of 10 g of potassium bromide in 250mL acetic acid was stirred on a ice/salt bath.  When the solution was sufficiently cold, 5mL of 91% sulfuric acid was added slowly and the solution took on a light brown color.  Over the course of the next 30 minutes, while maintaining the temperature at 5 degC, 8mL of 35% hydrogen peroxide was slowly added dropwise and subsequently the solution was allowed to stir for another 2 hrs.  The soln was extracted w/2x75mL toluene and the extracts were washed w/50mL 5% NaOH, and then 50mL brine.  The toluene was then removed in vacuo yielding a brown oil of presumably 1,4-dimethoxy-2-bromobenzene, which was used directly in the following reaction.  Yield was not determined but appeared to him to be very good.

To an unknown amount of 1,4-dimethoxy-2-bromobenzene was added a soln. of 5 grams of glyoxylic acid monohydrate and 12 mL H2O.  The solution was stirred vigorously on a ice/salt bath until a temperature of 5 degC was obtained and it was maintained at this temp throughout the subsequent reaction.  Over the course of the next 30 minutes, 30mL 91% sulfuric acid was added dropwise; at this point the solution took on a dark black.  The stirring was continued for the next 6 hours, the solution gradually taking on a light pink color with off-white crystals floating in the mixture.  After completion of the reaction, the mixture was so viscous it could hardly be stirred.  100mL of cold water was then added, the mixture stirred for a short time longer and the crystals were vacuum filtered.  The crystals were suspended in 100mL water and sufficent 25% aqueous NaOH was added until all of them dissolved into a dark brown solution.  The solution was then extracted w/75mL toluene.  The aqueous solution was once again cooled in an ice bath and ice-cold conc. HCl was added which cleared the solution and caused the crystals to precipitate back out and they were once again vacuum filtered and washed w/water.  Yield: 20g of 4-bromo-2,5-dimethoxymandelic acid (86% from p-dimethoxybenzene)

To a solution of 40mL distilled water, and 20mL of 31.25% HCl was added a suspension of 20 grams of 4-bromo-2,5-dimethoxymandelic acid.  The soln was cooled on an ice/salt bath to 5 degC and stirring was commenced.  Into an addition funnel was added 4mL 70% nitric acid and 10mL water.  The dilute HNO3 was added dropwise over about 15 minutes.  The flask was removed from the ice bath and placed into a water bath maintained at 50 degC.  It was heated and stirred at this temperature for about 1 hr.  The flask was cooled to room temperature and an ice-cold solution of 60mL 25% NaOH was added which caused the unreacted acid to dissolve into the mixture.  The remaining crystals were vacuum filtered and recrystallized from methanol.  Yield 12.5g (74%).

Overall yield: 12.5g 4-bromo-2,5-dimethoxybenzaldehyde from 15g hydroquinone (37.5%)

The rest of the story I will leave to your imagination since it has been told here many times before, but I will tell you that it involved nitroethane, cyclohexylamine and aluminum foil.  In the end, the experience was quite enjoyable for him as he was introduced to a new friend that goes by the name DOB.

- phenethylman -
(Über-Führer die Ironie)
10-23-04 20:38
No 537329
      third step     

Third step; 1,4-dimethoxy-2-bromobenzene --glyoxylic acid--> 4-bromo-2,5-dimethoxymandelic acid looks really interesting. Do you happen to have a litterature ref. for that step?
(Hive Bee)
10-24-04 07:50
No 537444
User Picture 

Yield: 20g of 4-bromo-2,5-dimethoxymandelic acid (86% from p-dimethoxybenzene)

Any chance you formed 6-bromo-2,5-dimethoxymandelic acid, or a combination of these two?

President of the Iraqi Chemical Weapons of Mass Destruction Development Society
(Hive Bee)
10-24-04 09:13
No 537451
      Re: Third step; 1,4-dimethoxy-2-bromobenzene...     

Third step; 1,4-dimethoxy-2-bromobenzene --glyoxylic acid--> 4-bromo-2,5-dimethoxymandelic acid looks really interesting. Do you happen to have a litterature ref. for that step?

Not with that specific substrate, but the procedure was adapted from Patent US4190583.

Any chance you formed 6-bromo-2,5-dimethoxymandelic acid, or a combination of these two?

Yes, based on the reaction mechanism, one would expect that to be a side-product.  However, the potency of the final product seems to be consistent with what one would expect, but then again, no scales that accurate were used.  Perhaps this isomer was oxidised/decarboxylated to the aldehyde as well, and then was subsequently eliminated during recrystallization of the aldehyde.

I should add that I believe it is the gradual addition of the acid catalyst that is likely to minimize formation of such side-products.  Some of the glyoxylic acid condensations out there use a weaker acid as a catalyst and combine the reactants all at once; others use no catalyst and just run the reaction at high temperature.  I don't believe such procedures would be advantageous in this case, in fact, an improvement may be to add the acid over 6 hours and stir for a day.

- phenethylman -
(Über-Führer die Ironie)
10-24-04 12:13
No 537460
      Yes, now I remember that patent...     

Yes, now I remember that patent...

If 1,2-methylenedioxybenzene is activating enough to give good yield, p-dimethoxybenzene would bee too i guess, this is a nice route to 2,5-dimeobenzaldehyde from p-dimethoxybenzene...

did you make the glyoxylic acid yourself? good work phenetylman!
(Hive Bee)
10-24-04 12:33
No 537461
      p-dimethoxybenzene, glyoxylic acid, etc ..     

If 1,2-methylenedioxybenzene is activating enough to give good yield, p-dimethoxybenzene would bee too i guess, this is a nice route to 2,5-dimeobenzaldehyde from p-dimethoxybenzene...

Actually I believe there was a discussion here a while ago where it was stated p-dimethoxybenzene would not work, maybe prevention of the di-substituted product is impossible?  This is the exact reason I chose to brominate first; to deactivate the ring somewhat.

did you make the glyoxylic acid yourself? good work phenetylman!

Nah, it was purchased quite a while ago and was from Acros Organics.  However, I don't believe synthesis would be that difficult though; nitric acid oxidation of acetaldehyde to glyoxal and then a further oxidation to glyoxylic acid may be a suitable route.  Also procedures from ethylene glycol or from the reduction of oxalic acid are out there.

- phenethylman -
(Official Hive Translator)
10-24-04 13:29
No 537467

I would say the formylation step looks very doubtful to me, considering very different reactivity of 3,4-MD and 1,4-diMeO-2-Br compounds.
(Hive Bee)
10-24-04 22:19
No 537531
      Re: I would say the formylation step looks...     

I would say the formylation step looks very doubtful to me, considering very different reactivity of 3,4-MD and 1,4-diMeO-2-Br compounds.

What formylation step?  It's a condensation w/the aldehyde functional group of glyoxylic acid to form a subst. mandelic acid and then oxidative decarboxylation to the benzaldehyde.. Do you mean the condensation step to form the acid?

It is a general reaction for aromatics; usually only applied to phenolic compounds.  However, I assume the second functional group of glyoxylic acid along with protonation by the acid catalyst makes it a strong enough electrophile to condense w/aromatic ethers as well.

I do agree some ortho-substitution could have taken place, thou I have not the resources to confirm or deny this.. then there's also the possiblility of nitration of the ring during the oxidation step..  so there are definitely disadvantages to this approach.

- phenethylman -
(Hive Bee)
10-25-04 07:00
No 537638
User Picture 

I do agree some ortho-substitution could have taken place, thou I have not the resources to confirm or deny this.. then there's also the possiblility of nitration of the ring during the oxidation step..  so there are definitely disadvantages to this approach.

When brominating 2,5-dimethoxybenzaldehyde, you also obtain a mixture of two isomers. You can remove the 6-bromo isomer by "recrystallization" (dilution). Something similar has been described for nitration. Read up on Rh's page.

I would expect both isomers to be present if the reaction would be possible.

President of the Iraqi Chemical Weapons of Mass Destruction Development Society
(Hive Bee)
10-25-04 18:03
No 537733
      decarboxylation / ring nitration     

"then there's also the possiblility of nitration of the ring during the oxidation step..  so there are definitely disadvantages to this approach".

That does not seem to be a problem if you run the decarboxylation at a low enough temperature and do it in a two phase mixture (aqueous/toluene). The aldehyde goes into the toluene as it is formed. This is speaking from personal experience.

Oh, and use a crystal or two of sodium nitrite to kick start the decarboxylation reaction if you need to. There is no need to use any hydrochloric acid as is suggested in one patent on the Hive.
(Hive Bee)
10-25-04 21:56
No 537781
      Re: That does not seem to be a problem if you...     

That does not seem to be a problem if you run the decarboxylation at a low enough temperature and do it in a two phase mixture (aqueous/toluene). The aldehyde goes into the toluene as it is formed. This is speaking from personal experience.

Oh, and use a crystal or two of sodium nitrite to kick start the decarboxylation reaction if you need to. There is no need to use any hydrochloric acid as is suggested in one patent on the Hive.

yeah, I noticed one patent used almost 1 mol equiv NaNO2 per mol of substrate but equal yields were obtained in another procedure which didn't utilize any..

the two-phase rxn sounds like a good idea, thou the consensus appears to be that 50 degC is the magic number i.e. as long as the temp doesn't rise above that then only the mandelic acid chain will be attacked..

too bad my friend has no more glyoxylic acid, there's a bunch of 2,5-diMeo-toluene that wants a formyl group real bad.  anyone actually tried the oxalic acid al/hg reduction referred to in this Post 427038 (foxy2: "Preparation of Glyoxylic acid", Novel Discourse)?  I imagine the post rxn workup is not too friendly..

Maybee will try that modified duff w/TFA, but damn that shit is pricey..

- phenethylman -
(Hive Bee)
10-25-04 23:50
No 537804
      attempted chloromethylation - 2,5-dimethoxytoluene     

well, since this rxn also involves a photo chemical to phenethylamine (THQ->DOM), I will consider it on topic..

A stirred solution of 4mL formalin, 20mL hydrochloric acid, and 80mL acetic acid was saturated w/HCl gas until it would absorb no more (this took about 5-10 min).  7g of 2,5-dimethoxytoluene was then added dropwise at a moderate rate.  The rxn was suprisingly exothermic as hell and HCl gas began to evolve out of the soln as it heated up.  Once breathing became difficult the addition was accelerated somewhat so SWIM could get the hell out of there.  The addition took about 15 minutes and the exotherm ceased about 5 minutes later.  At this point the soln was full of a white precipitate and quenching the reaction in 250mL dH2O caused even more precipitation.  The solids were quickly filtered and the area quickly evacuated..

I fear it is the disubstituted product but it seems as if all the 2,5-dimethoxytoluene reacted and there wasn't really enough CH2O to react twice so we will see..  coming soon: a melting point test which should tell the rest of the story..  The plan is to react it w/sodium 2-propanenitronate to give the benzaldehyde which has always given 70%+ yields in the past on alkyl-substituted benzyl halides..

- phenethylman -
(Hive Bee)
10-26-04 06:31
No 537866
User Picture 
      To activated for chlomethylation     

I would like to congratulate for your excellent formylation method first. I wish glyoxalic acid would bee more obtainable as it would save many of us from this coursed synthetic step.wink

I don't want to disappoint you to soon, but yes you got mostly the disubstitution side product. I can tell you that chloromethylating 1,4-diMeO-benzene with the same method as you did yields only about 25% of the desired benzylchloride, the rest being the damn sideproduct which is, as you will find out, quite insoluble in ethanol or toluene. I suppose that with 2,5-dimethoxytoluene the yield of the desired product goes if further down.  However, please report your own findings for the sake of future generations.tongue
I think it was Bandil who once tried another method on this substrate but he never reported the results (try UTFSE).

BTW, when chloromethylating it is highly advisable to use a fume hood if you would like to live long without feeding a deadly cancer in yourself.crazy

�The real drug-problem is that we need more and better drugs.� � J. Ott
(Hive Bee)
10-26-04 15:14
No 537922
      not the desired product     

nicodem:  I am sorry to confirm that you are entirely correct..  I was able to isolate a small amount of the desired product from the bis(chloromethyl) derivative, but yields were even less than unsatisfactory (<10%). frown  At least I didn't use a lot of material and it seems quite likely that the HMTA in TFA formylation will give satisfactory yields here.  Will know for sure in less than a week..

Appreciate the recommendation, it is true I already get enough cancerous material thru my smoking habit. crazy I didn't expect such an exothermic reaction otherwise I would have taken more precautions.  Perhaps cooling and a slower addition rate would work here but there's no way I'm wasting any more 2,5-diMeO-toluene on this.

- phenethylman -
(Hive Bee)
10-26-04 16:49
No 537929
      Alternative decarboxylation     

Nice work

I don't have any doubts about the condensation step between the arene and glyoxylic acid in your first post. It's true that benzodioxole is more activated than 2-bromo-1,4-dimethoxybenzene, but both will react in a similar manner with a good enough electrophile.

Further, I think the reaction with glyoxylic acid should work on 1,4-dimethoxybenzene to give the monosubstituted mandelic acid as it works on the more activated benzodioxole without disubstitution. To compare the reaction of the two arenes with another electrophile, bromine, it is far easier to stop the bromination of 1,4-dimethoxybenzene at 2-bromo-1,4-dimethoxybenzene than it is to stop the bromination of benzodioxole at the monobromo derivative. But I don't have time to check the discussion you mention which says it will not work.

I would be very interested to hear your results of the modified Duff formylation on any 1,4-dimethoxy ring. I take it you have seen Post 482940 (Lego: "Duff formylation of 2-chloro-1,4-dimethoxybenzene", Chemistry Discourse)? You should be able to get away with using half the amount of TFA as the authors. I know the amount of TFA can be halved when formylating indane, for example.

And I am also interested in hearing in any further work you do on chloromethylations, as I have a cunning plan for the near future which involves this reaction as the first step.wink

Below is another method for the oxidative decarboxylation of your mandelic acid. Maybe the procedure could be modified to work with sodium periodate and a catalytic amount of the quarternary ammonium salt, although it may be necessary to exclude water in the same way it is necessary in dichromate oxidations of alcohols to aldehydes, for example:

Tetrabutylammonium Periodate; A Selective and Versatile Oxidant for Organic Substrates
Enzo Santaniello, Ado Manzocchi, Carlo Farachi
, 1980, 563-565

Pentanal (4c) from 2-Hydroxyhexanoic Acid (3c); Typical Procedure:

2-Hydroxyhexanoic acid (3c; 1.32g, 0.01 mol) is added to a solution of tetrabutylammonium periodate (4.25g, 0.01 mol) in chloroform (10 ml). The mixture is refluxed and the progress of the reaction monitored by G. L. C. analysis (1% SE 30). The mixture becomes purple within 1 h. Upon completion of the reaction, the mixture is washed with 10% sodium thiosulfate solution (50 ml). The organic phase is dried with sodium sulfate and fractionally distilled; yield 0.77 g (90%); b. p. 101°C/760 torr.

(Hive Bee)
10-27-04 00:22
No 538003
      Glyoxylic Acid Via. Electrochem.
(Rated as: good read)

A Preliminary Investigation Of The Simultaneous Anodic And Anthodic Production Of Glyoxylic Acid
Elecnochimica Acta, Vol. 36, No. 9, pp. 1447-1452, 1991
Keith Scott.

A study of the preparative synthesis of glyoxylic acid by the simultaneous anodic oxidation of glyoxal and cathodic reduction of oxalic acid is described. The reactions both use a common electrode material; graphite and common electrolyte: acid chloride and are performed in divided and undivided batch cells. Yields and current efficiencies of the synthesis are quite good and in principle offer economic
advantages for the method compared with the single syntheses routes. The economics of the method are particularly affected by the cost of glyoxal relative to oxalic acid.

All preparative experiments were carried out in one of two cells, an H cell or a stirred undivided batch cell. The H cell compartments, with volumes of 150 cm’, were fitted with graphite electrodes of 20 cm2 area each. The anode and cathode compartments were separated by a glass frit. The beaker cell was of 120 cm3 capacity and the electrolyte was stirred with a magnetic stirrer. Electrodes were as in the H cell. All electrodes were cleaned in nitric acid and rinsed in deionized water before each run. Electrolyte solutions, oxalic acid and glyoxal in 1 M HCl, were made from chemicals supplied by B.D.H. and with deionized water. All xperimental runs were performed galvanostatically with power supplied from a Farnell bench dc supply. Current densities were in the range of 50-200Am-2. A constant temperature of approximately 20°C was maintained in each run by holding the cells in a thermostatically controlled water bath.

This oxidation/reduction eletrochem doesn't look too complicated. It oxidizes glyoxal and reduces oxylic acid at the same time to afford a nice glyoxylic acid.
For those who are wondering, an H-cell looks like this:

Even in an undivided cell glyoxal was converted to glyoxylic acid (with low yield).
(Hive Bee)
10-27-04 05:16
No 538042
      modified duff/chloromethylations..     

Regards kinetic,

Nice decarboxylation procedure; I do have some periodic acid lying around I've been looking to find a use for..  I believe mandelic acids can also be decarboxylated simply by heating w/cupric chloride for some time in a two-phase system and there are procedures using aqueous alkaline hypochlorite in the literature as well.

I am very interested in this modified duff formylation.. I am quite astonished at the lack of information in the literature regarding the mechanism involved here, particularly the role of the trifluoroacetic acid.  I have seen no research involving using any other acids to catalyse this reaction besides GAA and glyceroboric acid (in the original duff rxn), both of which are obviously not nearly as acidic as TFA.  Both give horrible yields even on phenols and display high ortho-regioselectivity whereas the modified duff has high para-regioselectivity and gives very acceptable yields.  No explanation has been offered for this anomalous behavior which makes me wonder if other acids w/a comparable acidity to trifluoroacetic would work.  I guess the problem would be finding an acid that would be inert to the reactants and the intermediates and products thus formed.

Your formylation of indane also makes me wonder just how much TFA is required to achieve decent yields.  I have also seen formylations using 50:50 mixtures of GAA:TFA that attain comparable yields.

My view on chloromethylations is that they are more trouble then they are worth on highly activated arenes.  I would much rather use a catalyst, higher temperatures and longer reaction times with a deactivated nuclei than have to deal w/preventing the unwanted reactions involved in the former   Although I have had some success w/alkoxy-benzenes simply by saturating hydrochloric acid/paraformaldehyde w/HCl gas at low temperature (where water can absorb a lot more HCl, 82.3g/100g H2O) and stirring at that temperature for 5 or 6 hrs in the absence of a catalyst..  I think these lower temperatures are almost required to attain decent yields in many cases.

I would love to hear about your cunning plan, but I guess then you'd have to kill me, eh? wink

- phenethylman -
(Hive Bee)
10-27-04 05:45
No 538051
      Thank Moo Very Much.     

Post 459724 (moo: "Oxidation of mandelic acid to benzaldehyde etc.", Methods Discourse)  is an excellent proceedure for making the beloved benzaldehyde.

No need to deal with the nasty nitric acid (not to mention Hazmat shipment charges.)
(Hive Bee)
10-28-04 07:56
No 538283
      re: glyoxylic acid
(Rated as: excellent)

J. Am. Chem. Soc. 76(1), 647 (1954) Experimental:
Sodium Glyoxylate Monohydrate
  Tartaric acid (11 g.) was dissolved in 10 ml. of water and 13.8 g. of periodic acid (H5IO6) in 30 ml. of water. Both solutions were chilled to 0° and the solution of periodic acid was added gradually to that of tartaric acid keeping the temperature below 5°. The glyoxylic acid was separated from the reaction mixture by continuous extraction with ether. The extracts were concentrated in vacuum to about 15 ml. of a thick sirup. An equal volume of water was added, the solution filtered and chilled to 0°. The pH was adjusted to between 5 and 6 by the slow addition of concentrated (50% by weight) sodium hydroxide solution. An equal volume of acetone was then added and the mixture was allowed to stand overnight in the cold. The crystalline sodium glyoxylate was collected by suction filtration, washed with 50% aqueous acetone, then with anhydrous acetone. The yield was 75% of theory, on the assumption that one mole of periodate gives two moles of glyoxylate. The salt was recrystallized by dissolving in 4.5 ml. of warm water per g., adding 2.5 ml. of acetone, and cooling. The product was dried in air or in vacuum with P2O5...

J. Biol. Chem. 203, 1023 (1953) Experimental:
   ...In a typical run, 0.5 gm. (3.3 mmol) of [dl-]tartaric acid in 10 cc. of water was treated with 7.8 cc. of 0.42 N sodium periodate for 10 minutes. The solution was extracted continuously with alcohol-free ether for 24 hours, and the ether solution (about 30 cc.) extracted successively with a solution of 340 mg. (4 mmol) of NaHCO3 in 20 cc of water and with 10 cc. of water. The combined aqueous extracts were neutralized carefully with NaHCO3 to pH 7, concentrated in vacuo to 1 to 2 cc., and treated with absolute alcohol until precipitation occurred. Following storage overnight in the refrigerator, 442 mg. of sodium glyoxylate hydrate were obtained by centrifugation and washing with alcohol. Working up the mother liquors yielded an additional 158 mg. Total yield 80 per cent...

A Note on the Preparation of Glyoxylic acid as a Reagent
J. Biol. Chem. 6, 51 (1909):
   ...Ten grams of powdered Mg (1) are placed in a large beaker, or preferably a large Erlenmeyer flask, and shaken up with enough distilled water to liberally cover the Mg. 250 cc. of a cold, saturated solution of oxalic acid are now added slowly. The reaction proceeds very rapidly and with the liberation of much heat, so that the flask should best be cooled under the tap during the addition of the acid. The contents of the flask are shaken after the addition of the last portion of the acid and then poured upon a filter, to remove the insoluble magnesium oxalate. A little wash water is poured through the filter, the filtrate acidified with acetic acid (2), and made up to 1 l. with dH2O. The solution gives no reaction for oxalate with Ca and contains apparently only the Mg (3) salt of glyoxylic acid. This reagent gives very beautifully the characteristic reactions for glyoxylic acid.

(1) Mg ribbon may also be employed, but in this case the reaction goes more slowly and may be accelerated by warming.
(2) The reason for the addition of the acetic acid is that the filtrate may sometimes be faintly alkaline in reaction, and in such cases the Mg would be partially precipitated upon long standing, unless the acid is added.
(3) The Mg could readily be removed, but there appears to be no objection to its presence.

[there was no analysis section, in fact this is very nearly the entire article]

Crystalline Glyoxylic Acid and its Sodium-Calcium Salt
Can. J. Chem. 38, 623 (1960) Experimental:
  Glyoxylic Acid - An aqueous solution, 300 ml, containing 15 g (0.1 mole) of L-tartaric acid and 25.1 g (0.11 mole) of paraperiodic acid (H5IO6) was kept at 23° in the dark for 10 hours, when a titration by the sodium arsenite- iodine method showed that all of the periodic acid had been reduced. The addition of 110 ml of 0.52 M lead acetate (0.114 equivalent) caused the nearly quantitative separation of lead iodate, which was removed by filtration. After residual lead ions were removed as lead sulphide, the clarified liquor was evaporated in vacuo to a syrup, by-product acetic and formic acids being incidentally eliminated. The acidity of the syrup was cautiously reduced to pH 8 by the addition of cold 0.3N. barium hydroxide, and partial evaporation of the liquor caused the crystallization of 27.8 g (86.8%) of barium glyoxylate dihydrate. Although the solubility of the salt in water was reported (3) as only 0.005% at 18° and 0.08% at 68°, the present sample could be readily recrystallized from hot water. This recrystallization did not significantly change the composition. Calc. for Ba(C2HO3)2.2H2O:Ba, 43.0%. Found: Ba, 42.8, 43.0%. Samples, 0.2580 g and 0.2577 g, reduced 32.5, 32.5 ml, respectively, of 0.104 N potassium permanganate (3), the calculated amount being 30.9 ml. An aqueous solution of 8.0 g of the above salt was freed of barium ions by passage through a column of Amberlite IR-120 cation-exchange resin, and the effluent was evaporated in vacuo to a thick syrup. This syrup was dried to nearly constant weight by storage over phosphorus pentoxide in an evacuated desiccator at room temperature. After several months the colorless product, 3.68 g or 99% yield, crystallized solidly. The melting point was 104-107°, with softening at 94°. No solvent suitable for recrystallizing the glyoxylic acid was found.

Sodium - Calcium Glyoxylate Tetrahydrate
  Fifteen grams (0.1 mole) of L-tartaric acid dissolved in 300 ml of water was mixed with 200 ml of 0.515 M sodium metaperiodate (0.103 mole). The reduction of the latter was complete after the mixture had been kept in the dark and at room temperature for 36 hours. After iodate ion was removed as the lead salt, the filtrate was evaporated in vacuo to 50 ml, and was adjusted to pH 8 with 2 N sodium hydroxide. A concentrated aqueous solution of 17 g (0.1 mole) of calcium acetate monohydrate was then added, and 19.6 g (87.1%) of the sodium-calcium salt separated as white crystals. Calc. for Na2Ca(C2HO3)4.4H2O: Na, 10.2; Ca, 8.3%. Found: Na, 9.65, 9.58; Ca, 9.27, 9.21%. Samples, 0.1338 g, 0.2038 g, and 0.1024 g, reduced 24.6 ml, 37.7 ml, and 19.0 ml of 0.101 N potassium permanganate (3), the calculated volumes being 23.6 ml, 35.9 ml, and. 18.1 ml, respectively. Two recrystallizations from hot water reduced the over-all yield to about 75% but failed to alter the composition significantly. A 0.0365-g sample of the salt when treated with 2,4-dinitrophenylhydrazine yielded 0.0658 g (79%) of crystalline glyoxylic acid 2,4-dinitrophenylhydrazone with the correct (10) melting point of 191-191.5°.

(3) Trans. Roy. Soc. Canada, Sect. 3, 19, 11 (1925)
(10) J. Chem. Soc. 756 (1931)

Periodates were mentioned in previous posts as well, so this might come in handy:

The Periodates of Sodium, Potassium, and Barium
Periodic Acid

Inorg. Syn. 1, 168-175

(Hive Bee)
10-28-04 10:28
No 538297
      glyoxylic acid by nitric acid oxidation of glyoxal     

Okay, might as well add this then..

from Patent US4698441..


154 g of 45% nitric acid was added dropwise to 435 g of an aqueous solution containing 19.96% of glyoxal, 0.49% of glyoxylic acid and 10.02% of hydrochloric acid, at a temperature of C., over four hours, whereby glyoxal was oxidized at C. with an oxidizing agent composition formed in situ. After one hour, at the same temperature, from the completion of the addition of nitric acid, a reaction solution containing 16.58% of glyoxylic acid and 0.007% of nitric acid was obtained. This reaction solution also contained 0.84% of glyoxal, 7.34% of hydrochloric acid and 3.31% of oxalic acid. The conversion of glyoxal was 94.7%, the selectivity for glyoxylic acid was 84.7% and the yield was 82.1%.

Note that the minute amount of glyoxylic acid present in the original soln is just an impurity resulting from the preparation of the glyoxal soln (from the oxidation of acetaldehyde) and is of course, not a requirement but rather to demonstrate that the rxn is resistant to this impurity.

I should note that glyoxal is used in photography as well and easily obtainable (you can even buy it w/your hydroquinone!) 

I am in the process of attempting a couple of other syntheses originating from photo chems; including 2C-T and MMDA derivatives starting from hydroquinone and a couple MMDA derivatives from pyrogallol as well..  ya gotta love photography.

- phenethylman -
(Hive Bee)
10-28-04 23:53
No 538382
User Picture 
      benzoquinone->hydroquinone, 100 percent!     

Kinetics of Highly Selective Catalytic Hydrogenation of 2,3,5-Trimethylbenzoquinone on Raney Nickel Catalyst
(Sudip Mukhopadhyay, Kavita H. Chandnani, and Sampatraj B. Chandalia)
Org. Proc. Res. Dev., 4 (4), 254 -258, 2000

DOI:10.1021/op990074z S1083-6160(99)00074-2


This work focuses on the catalytic hydrogenation of 2,3,5-trimethylbenzoquinone (TMBQ) to 2,3,5-trimethylhydroquinone (TMHQ). Kinetic interpretation has been made by studying the important process parameters using Raney nickel as the catalyst. Thus, at 100% TMBQ conversion level, as high as 100% selectivity to TMHQ was accomplished. Experimentation was performed to acquire the most suitable process conditions from the viewpoint of process research and development.

I thought this could be useful for some bees...

(Hive Bee)
10-29-04 09:11
No 538495
      Another Glyoxylic Acid Synthesis.     

  A Convenient Preparation of Methyl and Ethyl Glyoxylate
KELLY, T. Ross; SCHMIDT, Thomas E.; HAGGERTY, John G.
Synthesis; 10, 1972

Esters of tartaric acid (methyl, ethyl) are converted to the glyoxylate ester.


Methyl Glyoxylate.

To a solution of dimethyl d-tartrate (89g, 0.5mol) in dry ether (900ml) cooled in a cold water bath was added paraperoidic acid (114g, 0.5mol) in portions over 1hr under nitrogen with stirring. The miltry reaction minxture is then stirred for a few minutes until the ether has become almost clear and a white solid seperated. The ether phase was decanted, dried and evaporated to give a clear methyl glyoxalate which is sufficetly pure for most uses. yield 71g. (Material contained 5% water but was pure.)

I'm sure this synth would work for plain tartaric acid. What is nice is that it doesn't require any continous extraction and the Sodium Iodate seperates easily from the ether phase.  (The Sodium Iodate can be recovered and used to synth more oxidant (paraperoidic acid)) 
Either than the minor differences this example is very similar to Post 538283 (gsus: "re: glyoxylic acid", Methods Discourse). This method seems more suitable for the  OTC-oriented chemist.
(Hive Bee)
11-04-04 17:12
No 539680
      modified duff formylation of 2,5-diMeO-toluene     

well, at least we know now that the modified duff works on 2,5-dimethoxytoluene..

A solution of 45mL trifluoroacetic acid, 10g (66mmol) of impure 2,5-dimethoxytoluene, and 9.25g (66mmol) hexamethylenetetramine was held under a light reflux for 12 hours.  After it had cooled somewhat, 300mL of distilled water was added and it was stirred magnetically at room temperature for a hour.  Then, anhydrous sodium carbonate was added until strongly basic which caused the precipitation of a dark oil.  This was extracted w/2x100mL toluene and the toluene was washed w/2x75mL 5% aqueous NaOH.  The washings caused some discoloration of the organic layer but it was still almost black.  Thus, it was dried w/MgSO4, and the toluene removed under vacuum, leaving a viscous brown/red oil of crude 2,5-dimethoxy-4-methylbenzaldehyde.

The aldehyde was purified by adding a saturated aqueous solution of sodium bisulfite to the oil, precipitation of the bisulfite addition product being almost immediate.  The solution was stirred for a short while, solids were filtered off and they were washed w/a few small portions of IPA and water until almost white. 

The adduct was suspended in a solution of 50mL water and 75mL toluene, and subsequently decomposed by the addition of a saturated solution of Na2CO3.  The layers were seperated and the aqueous layer was back-extracted w/50mL toluene.  The obtained organic extracts (yellow in color this time) were combined, dried, and the solvent was removed.  This time around the aldehyde was a yellow/orange solid which was pure enough to be recrystallized.  Thus, recrystallization from MeOH/H2O gave 4.5g of 2,5-dimethoxy-4-methylbenzaldehyde (38%), in the form of glistening light yellow needles.

yes, yield were low, but really only because everything was done half-assed, especially in the work-up.  However, SWIM wasn't really going for a spectacular yield considering the potency of DOM.  He just wanted a pure product, which he got.  The melting point is spot on.  As for the low yield, just a few of the contributing factors..

.. the amount of TFAA used was even less than kinetic used in his formylation of indane (less than half of the amount specified in the original article.).  Being w/out a condenser still (outer joint on top broke off), the starting 2,5-dimethoxytoluene (which should be white) was an impure brown oil resulting from the dimethylation of toluhydroquinone w/dimethyl sulfate.  I think I prob would have had to go thru the bisulfite adduct regardless.  Toluene was a terrible solvent for this but it was all that was available.

I would expect yields to be in the 50-70% range for this substrate if rxn/workup were performed as described in the original article.  I don't think the amount of acid used hurt the yield that bad, which makes me wonder just how low we can go w/the TFAA since it's somewhat expensive..

the condensation w/nitroethane and the subsequent reduction have already been performed, will do a write-up if anyone really cares but I'm too lazy to type any more so I'll just end this post here.

- phenethylman -
(Hive Addict)
11-04-04 22:19
No 539721
User Picture 

condensation w/nitroethane and the subsequent reduction have already been performed, will do a write-up if anyone really cares

You damn well bet I do laugh


(Hive Bee)
11-06-04 18:47
No 540048
      Nice synth.     

The yeild as you said is low, but it is understandable, Swim seem to have problems working with small volumes of chems, mainly due to mechanical loss, and a bisulfite adduct at such dose ranges are bound to result in losss, but excellent synth.
You definitely need a "Pioneer" rating if not an "Excellent"
keep up the research, you've motived swim and a lot of other bees.


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