I haven't done the dioxane extraction of lignin. I have done the alkaline extraction of lignin, boiling sawdust (or cardboard) with KOH in a cast iron pot. This is in Post 190600 (missing)
(halfapint: "Lignin Syringaldehyde Again", Novel Discourse). The oxidation of extracted lignin with nitrobenzene in https://www.thevespiary.org/rhodium/Rhodium/chemistry/mescalyptus.txt (https://www.thevespiary.org/rhodium/Rhodium/chemistry/mescalyptus.txt)
gives the same products, as oxidation with alkaline cupric sulfate and ferric sulfate to catalyze air or oxygen oxidation: syringaldehyde and vanillin. I have discounted nitrobenzene oxidation as too costly. Lignin chemistry is introduced at http://sofserv.forestry.auburn.edu/elder/wood_chem/ch4/lignin.html (http://sofserv.forestry.auburn.edu/elder/wood_chem/ch4/lignin.html)
.
An alternate to the vacuum fractional distillation may bee more practical, or more workable. A rapid initial separation of the vanillyl compounds from the syringyl compounds, even if it's crude, would be most helpful. I've realized that the fractional vacuum distillation would be a marathon session, watching drip-drip-drip all day. Even beez equipped for vac distillation, with a good column, rarely have a "cow" to change fractions without releasing the vacuum, so at least three interruptions of the run are needed to change fractions. Tedious, slow work.
A preliminary vacuum distillation of the ketones without a column, or a short column set for minimal reflux, may separate the lower boiling vanillyl species from the higher boiling syringyl compounds. Well, I know I'm making one distillation into three distillations, but it may be simpler by not requiring changing the receiver. When about half, or a little more than half of the ketone has come over, you look for a temperature jump. Taking the fraction when that happens, you consider the ketones remaining in the flask as syringyl ketones, as you save the vanillyl ketones for redistillation.
Then you rig your more efficient (slower) column, to get your (hopefully) syringyl-2-propanone as the first fraction. It is advisable to distill the remaining syringyl ketones then, for undoubtedly there will be some crud left in the pot after they've come over. You wouldn't want that crud complicating your successive reactions.
Then in the boiling flask you place your previously distilled vanillyl ketones, take the first fraction as vanillyl-2-propanone, and stop. There is no need to redistill the previously distilled vanillyl ketones, unless you feel the crude first distillation may have mixed a bit of syringyl ketone in.
I've complicated the distillation procedure in hopes of saving a little time. Doing this may or may not be appropriate, depending on a bee's facilities and experience. Taking the trouble to note the temperatures at which fractions come over with your vacuum, will make it much easier the next time, and you'll get it down until you are churning out these ketones routinely. They're not rare, you know, and they're not that hard to get, the second time. You don't have to expose yourself by dealing with snooty or suspicious vendors, right?
Antoncho and I, among others, have found a few techniques of chemical separation of syringaldehyde from vanillin. It would be splendid if something like differential solubility in concentrated alkaline or ammoniacal solution, would precipitate all the syringyl ketones as a solid mass, while leaving the vanillyl ketones in solution. But the presence of those side-chain alcohol groups on half these ketones, gives me no confidence in precipitation techniques.
We know the desired separations can be made. As a last resort, preparative column chromotography will separate all these ketones. Very probably, fractional distillation will give us satisfactory separation, as proposed here. There must be chemical techniques to short cut these exhaustive methods, but we have to discover them by experimentation. Nobody's going to do this work for us. We have to bee the pioneers of our own science. And, by the way, Half-a-Pint isn't going to be able to do all this experimentation alone. There just isn't enough time. Can we have a bit of hands-on participation here?
Edit: Another path might bee just to hydrogenate (or otherwise reduce) everything, all the ketones, most of which will form vic-diols, vicinal di-alcohols. Then treatment with concentrated sulfuric acid or lithium iodide would give 2-propanones from all the Hibbert ketones that weren't 2-propanones before. The two ketones which were 2-propanones before will have been reduced to 2-propanols (and may now be sulfonates). If the latter were only a small constituency of the original ketone mix, they might be discarded, giving you the lion's share of your lignin as 2-propanones without distillation, with only bisulfite purification. The resulting mix of syringyl-2-propanone and vanillyl-2-propanone will certainly be separable, quite easily, by differential solubility in hot base, just like syringaldehyde falls out of a cooling solution with vanillin. No still needed, OTC, you can cook your way home.
turning science fact into <<science fiction>>
I'm just going by what Prof. Elder at Auburn says in that lignin link above. Dioxane is about like THF as a cyclic ether, but much cheaper. And quite easy to make from auto antifreeze, ethylene glycol, as I mentioned. I'd consider that as OTC. My last sentence was of course exaggeration. You do need a still of sorts to make dioxane. Also you will need an alkylating agent, and you can't make that without a still. To make dimethyl sulfate or diethyl sulfate, you need vacuum with your still. Alkyl halides can bee distilled without vacuum, though. I have made lots of stills from jars, bottles and tubing: put heavy-duty foil around the bottom of the jar to distribute the heat, and/or use a bath of cooking oil, and you have an OTC still. Making the condenser calls for ingenuity, but that's the fun part. Leak proofing a jar lid to hold hot vapor is the biggest challenge. I found you can solder a short length of small copper or brass tubing into a jar lid, and fasten your plastic tubing to that. Ah, the good old days.
Reducing the ketones to the diols can be done with about any reducing agent, like a metal in acid. To get the propanone from this, though not in my experience, doesn't seem too hard in the old Hive posts. Lithium iodide isn't OTC, it's watched where I am, but photo batteries containing lithium are not, and HI gassed into a nonpolar solvent holding your lithium will produce it anhydrous. Sulfuric acid, as the alternative, is OTC. In the vanillyl propanone case, bromine is next required, and several threads on making OTC bromine are available here.
You posted a reference Post 198026 (https://www.thevespiary.org/talk/index.php?topic=11425.msg19802600#msg19802600)
(Antoncho: "Re: High-yield 3,4,5-TMB synth from vanillin (Russian)", Novel Discourse) which refers to the separation of vanillin from syringaldehyde after bromination of the vanillin, by precipitation of the brominated compound from acetic acid/glycol/water. It does seem this might prove very relevant here!
Is it indeed necessary to separate it? The reference you gave refers to bromination of vanillin in the presence of syringaldehyde. Caution, we have another shortcut coming up. We may have a path to TMA here without separation of the ketones. Heating with concentrated KOH will (1) substitute the 5-Br with 5-OH and (2) leave this 5-OH as the potassium phenolate salt and (3) leave the 4-OH on both types of ketones as the potassium phenolate salts.
Being very specific here, we now have one propanone with the ring substitution pattern 3-methoxy, 4-oxo-potassium (whatever you call it), and 5-oxo-potassium, which was our vanillyl ketone. In the same pot with it, we have a propanone with 3,5-dimethoxy and 4-oxo-potassium, the potassium salt of our syringyl ketone. What if we just methylate the hell out of the whole shebang? We get one component in our pot: 3,4,5-trimethoxy-phenyl-2-propanone. Amounting to most of the lignin originally present! Now does that sound like a winner?
3,4,5-TMA is only a reductive amination away. In my ignorance, I would suggest ammonium formate in formic acid and water, with Urushibara nickel for a catalyst. Same thing as bubbling ammonia through aqueous formic acid, right?
That last proposition has got my head spinning too. Look out world, we're working again.
Edit: In my search for your bromination-separation post, I found the iodovanillin thread foxy2 clinched up with that patent now at https://www.thevespiary.org/rhodium/Rhodium/chemistry/iodovanillin.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/iodovanillin.html)
. Now how did I miss that before? Scuse me, I got to get down to the feed'n'seed, badly wounded animal, need some strong iodine.
turning science fact into <<science fiction>>
Some bastard could methylenate this to piperonal... and we all know what the corresponding ketone is. Tell me, why not?
and
Yeah you right. Having the aldehyde, though, won't give you the ketone, without sending you on a merry chase for nitroethane.
According to Strike (in TSII), piperonal can be converted via the Grignard reaction into isosafrole. Nitroethane is merely the easiest method of converting piperonal into something more interesting, there are probably several other routes besides the one that Strike wrote of that haven't been posted on the Hive yet :)
This is really nice. Seriously, that's all swic can say, he just really likes it.
We're talking about changing over ten per cent by weight of cardboard into precursors for psychedelic drugs.
This comment will forever by burned onto the right side of swic's brain.
Hit a snag.
https://www.thevespiary.org/rhodium/Rhodium/chemistry/iodovanillin.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/iodovanillin.html)
The process is not useful with substituents such as... ketone groups with an alpha hydrogen, which either react with the reagent or strongly de-activate the ring. Ketone groups are deactivating, as are aldehyde groups, but ketones containing an alpha hydrogen would react with the iodinating agent whereas the aldehydes would not... Weakly de-activating groups such as aldehyde groups do not interfere with iodination.
I bet this problem would apply to ring bromination also, as well as to attempted ring iodination. While the aldehyde as well as the isopropyl ketone are both deactivating, as regards ring halogenation, the ketone has another preferred place for that halogen to go: substituting that alpha hydrogen on the side chain. Not good at all. Times like this make me wish I had taken some organic chemistry courses.
So while you can iodinate, or brominate, vanillin (the aldehyde) in the presence of syringaldehyde, in the quest of a one pot synthesis from lignin, the same does not hold true for the corresponding isopropyl ketones. At this point, there doesn't seem to bee any way to get around separating the vanillyl-2-propanone fraction from the syringyl-2-propanone, and running separate batches.
From the looks of the above quote, I'll have a hard time figuring out what to do with the vanillyl fraction, to keep the halogen from substituting on the side chain, in the attempt to halogenate the ring. If the isopropyl ketone were derivativized, say to the oxime or even to the amine (as protected by acetylation), would its alpha hydrogen remain as labile, and subject to replacement by halogen?
help --- my experimental batch was just about ready to get halogenated...
turning science fact into <<science fiction>>
Circumstances have forced delay in the practical experimentation with syringyl-2-propanone production. In the interval, I have become convinced of the general applicability of thermal rearrangement to ketones of the Hibbert syringyl diol. I expect this to occur in reflux at ambient pressure followed by distillation at reduced pressure. (Any oxidation of the propan-2-ol, if this is used, should happen after the reflux, but before the distillation.)
I am more hopeful for vanillin-2-propanone bromination, selectively in the presence of syringyl-2-propanone, than a gloomy post above suggests. In acid medium. Using Br/HBr or possibly dioxane dibromide I think I could move ahead. Antoncho's efforts have just paid off for sodium methoxide in Post 214730 (https://www.thevespiary.org/talk/index.php?topic=11470.msg21473000#msg21473000)
(halfapint: "The Hibbert Ketones of Lignin", Novel Discourse). Some of the sequencing of this complex rxn should now bee recalculated.
Try this:
1) Dissolve lignin. Use KOH in water.
(you have polymeric lignin.)
2) Hydrolyze lignin. Use HCl in dioxane.
(you have 8 Hibbert ketones, pictured above.)
3) Reduction: The resultant Hibbert ketones are all reduced to the corresponding diol, except the mono-ketones, which are reduced to the secondary alcohol.
(your side chains have diols and alcohols.)
4) Refluxing the mixture after distilling solvents and filtering off salts, dehydrates the diols to propan-2-ones.
(your side chains are 2-ketones, with some propan-2-ol.)
5) Oxidation with dichromate gives mono-ketones from the remaining alcohol side chain.
(your side chains are all 2-ketones now.)
5a) Isolate the ketones as the bisulfite addition products.
6) Halogenation: 5-Halogenation is performed on the vanillin ring, without regard to the presence of syringyl ketone.
(5-iodo or 5-bromo vanillyl ketones now mingle in the pot with your syringyl ketone.)
7) Methoxylate: Sodium methoxide treatment now gives a single-component pot of syringyl ketone.
7a) a good place to purify by distillation at reduced pressure.
8) Alkylate: 4-alkylation provides 4-alkyl-3,5-dimethoxyphenyl-2-propanone.
9) Aminate: Condense the ketone with ammonium formate and formic acid in the Leukart-Wallach reaction. Or any of your favorite reductive aminations, though reducing an oxime or hydrazide intermediate will give better yields at normal pressure, than ammonia or ammonium acetate or even benzylamine.
Then I'll have to decide on solvents, reaction conditions and workup. This sorcery becomes like working for a living, after while.
turning science fact into <<science fiction>>